Travma 2016 / 3

ISSN 1306 - 696X

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi

Volume 22 | Number 3 | May 2016

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Recep Güloğlu Editors Kaya Sarıbeyoğlu (Managing Editor) M. Mahir Özmen Hakan Yanar Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu Section Editors Anaesthesiology & ICU Güniz Meyancı Köksal, Mert Şentürk Cardiac Surgery Münacettin Ceviz, Murat Güvener Neurosurgery Ahmet Deniz Belen, Mehmet Yaşar Kaynar Ophtalmology Cem Mocan, Halil Ateş Ortopedics and Traumatology Mahmut Nedim Doral, Mehmet Can Ünlü Plastic and Reconstructive Surgery Ufuk Emekli, Figen Özgür Pediatric Surgery Aydın Yagmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu

www.tjtes.org

THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ President (Başkan) Vice President (2. Başkan) Secretary General (Genel Sekreter) Treasurer (Sayman) Members (Yönetim Kurulu Üyeleri)

Kaya Sarıbeyoğlu M. Mahir Özmen Hakan Yanar Ali Fuat Kaan Gök Gürhan Çelik Osman Şimşek Orhan Alimoğlu

CORRESPONDENCE İLETİŞİM Ulusal Travma ve Acil Cerrahi Derneği Şehremini Mah., Köprülü Mehmet Paşa Sok. Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul, Turkey

Tel: +90 212 - 588 62 46 Fax (Faks): +90 212 - 586 18 04 e-mail (e-posta): travma@travma.org.tr Web: www.travma.org.tr

ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI Owner (Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi) Editorial Director (Yazı İşleri Müdürü) Managing Editor (Yayın Koordinatörü) Amblem Correspondence address (Yazışma adresi)

Tel Fax (Faks)

Kaya Sarıbeyoğlu Kaya Sarıbeyoğlu M. Mahir Özmen Metin Ertem Ulusal Travma ve Acil Cerrahi Dergisi Sekreterliği Şehremini Mah., Köprülü Mehmet Paşa Sok., Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul +90 212 - 531 12 46 - 588 62 46 +90 212 - 586 18 04

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.)

Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Merve Şenol • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): May (Mayıs) 2016 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

www.tjtes.org

INFORMATION FOR THE AUTHORS The Turkish Journal of Trauma and Emergency Surgery (TJTES) is an official publication of the Turkish Association of Trauma and Emergency Surgery. It is a peer-reviewed periodical that considers for publication clinical and experimental studies, case reports, technical contributions, and letters to the editor. Six issues are published annually.

tion, called “Upload Your Files”.

As from 2001, the journal is indexed in Index Medicus and Medline, as from 2005 in Excerpta Medica and EMBASE, as from 2007 in Science Citation Index Expanded (SCI-E) and Journal Citation Reports / Science Edition, and as from 2008 in Index Copernicus. For the five-year term of 2001-2006, our impact factor in SCI-E indexed journals is 0.5.

It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PUBMED.

Figures, illustrations and tables: All figures and tables should be numbered in the order of appearance in the text. The desired position of figures and tables should be indicated in the text. Legends should be included in the relevant part of the main text and those for photomicrographs and slide preparations should indicate the magnification and the stain used. Color pictures and figures will be published if they are definitely required and with the understanding that the authors are prepared to bear the costs. Line drawings should be professionally prepared. For recognizable photographs, signed releases of the patient or of his/her legal representatives should be enclosed; otherwise, patient names or eyes must be blocked out to prevent identification.

Submission of a manuscript by electronic means implies: that the work has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; and that its publication in the Turkish Journal of Trauma and Emergency Surgery is approved by all co-authors. The author(s) transfer(s) the copyright to the Turkish Association of Trauma and Emergency Surgery to be effective if and when the manuscript is accepted for publication. The author(s) guarantee(s) that the manuscript will not be published elsewhere in any other language without the consent of the Association. If the manuscript has been presented at a meeting, this should be stated together with the name of the meeting, date, and the place.

Manuscripts may be submitted in Turkish or in English. All submissions are initially reviewed by the editor, and then are sent to reviewers. All manuscripts are subject to editing and, if necessary, will be returned to the authors for answered responses to outstanding questions or for addition of any missing information to be added. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication. Final galley proofs are sent to the authors for approval.

Unless specifically indicated otherwise at the time of submission, rejected manuscripts will not be returned to the authors, including accompanying materials.

TJTES is indexed in Science Citation Index-Expanded (SCI-E), Index Medicus, Medline, EMBASE, Excerpta Medica, and the Turkish Medical Index of TUBITAK-ULAKBIM. Priority of publications is given to original studies; therefore, selection criteria are more refined for reviews and case reports.

Open Access Policy: Full text access is free. There is no charge for publication or downloading the full text of printed material.

Manuscript submission: TJTES accepts only on-line submission via the official web site (please click, www.travma.org.tr/en) and refuses printed manuscript submissions by mail. All submissions are made by the on-line submission system called Journal Agent, by clicking the icon “Online manuscript submission” at the above mentioned web site homepage. The system includes directions at each step but for further information you may visit the web site (http://www.travma.org/en/ journal/).

Manuscript preparation: Manuscripts should have double-line spacing, leaving sufficient margin on both sides. The font size (12 points) and style (Times New Roman) of the main text should be uniformly taken into account. All pages of the main text should be numbered consecutively. Cover letter, manuscript title, author names and institutions and correspondence address, abstract in Turkish (for Turkish authors only), and title and abstract in English are uploaded to the Journal Agent system in the relevant steps. The main text includes Introduction, Materials and Methods, Results, Discussion, Acknowledgments, References, Tables and Figure Legends.

The cover letter must contain a brief statement that the manuscript has been read and approved by all authors, that it has not been submitted to, or is not under consideration for publication in, another journal.

It should contain the names and signatures of all authors. The cover letter is uploaded at the 10th step of the “Submit New Manuscript” sec-

Abstract: The abstract should be structured and serve as an informative guide for the methods and results sections of the study. It must be prepared with the following subtitles: Background, Methods, Results and Conclusions. Abstracts should not exceed 200 words.

References: All references should be numbered in the order of mention in the text. All reference figures in the text should be given in brackets without changing the font size. References should only include articles that have been published or accepted for publication. Reference format should conform to the “Uniform requirements for manuscripts submitted to biomedical journals” (http://www.icmje.org) and its updated versions (February 2006). Journal titles should be abbreviated according to Index Medicus. Journal references should provide inclusive page numbers. All authors, if six or fewer, should be listed; otherwise the first six should be listed, followed by “et al.” should be written. The style and punctuation of the references should follow the formats below: Journal article: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5.

Chapter in book: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62.

Our journal has succeeded in being included in several indexes, in this context, we have included a search engine in our web site (www. travma.org.tr) so that you can access full-text articles of the previous issues and cite the published articles in your studies.

Review articles: Only reviews written by distinguished authors based on the editor’s invitation will be considered and evaluated. Review articles must include the title, summary, text, and references sections.

Any accompanying tables, graphics, and figures should be prepared as mentioned above.

Case reports: A limited number of case reports are published in each issue of the journal. The presented case(s) should be educative and of interest to the readers, and should reflect an exclusive rarity. Case reports should contain the title, summary, and the case, discussion, and references sections. These reports may consist of maximum five authors.

Letters to the Editor: “Letters to the Editor” are only published electronically and they do not appear in the printed version of TJTES and PUBMED. The editors do not issue an acceptance document as an original article for the ‘’letters to the editor. The letters should not exceed 500 words. The letter must clearly list the title, authors, publication date, issue number, and inclusive page numbers of the publication for which opinions are released.

Informed consent - Ethics: Manuscripts reporting the results of experimental studies on human subjects must include a statement that informed consent was obtained after the nature of the procedure(s) had been fully explained. Manuscripts describing investigations in animals must clearly indicate the steps taken to eliminate pain and suffering. Authors are advised to comply with internationally accepted guidelines, stating such compliance in their manuscripts and to include the approval by the local institutional human research committee.

YAZARLARA BİLGİ Ulusal Travma ve Acil Cerrahi Dergisi, Ulusal Travma ve Acil Cerrahi Derneği’nin yayın organıdır. Travma ve acil cerrahi hastalıklar konularında bilimsel birikime katkısı olan klinik ve deneysel çalışmaları, editöryel yazıları, klinik olgu sunumlarını ve bu konulardaki teknik katkılar ile son gelişmeleri yayınlar. Dergi iki ayda bir yayınlanır.

Ulusal Travma ve Acil Cerrahi Dergisi, 2001 yılından itibaren Index Medicus ve Medline’da, 2005 yılından itibaren Excerpta Medica / EMBASE indekslerinde, 2007 yılından itibaren Science Citation Index-Expanded (SCI-E) ile Journal Citation Reports / Science Edition uluslararası indekslerinde ve 2008 yılından itibaren Index Copernicus indeksinde yer almaktadır. 2001-2006 yılları arasındaki 5 yıllık dönemde SCI-E kapsamındaki dergilerdeki İmpakt faktörümüz 0,5 olmuştur. Dergide araştırma yazılarına öncelik verilmekte, bu nedenle derleme veya olgu sunumu türündeki yazılarda seçim ölçütleri daha dar tutulmaktadır. PUBMED’de dergi “Ulus Travma Acil Cerrahi Derg” kısaltması ile yer almaktadır.

Dergiye yazı teslimi, çalışmanın daha önce yayınlanmadığı (özet ya da bir sunu, inceleme, ya da tezin bir parçası şeklinde yayınlanması dışında), başka bir yerde yayınlanmasının düşünülmediği ve Ulusal Travma ve Acil Cerrahi Dergisi’nde yayınlanmasının tüm yazarlar tarafından uygun bulunduğu anlamına gelmektedir. Yazar(lar), çalışmanın yayınlanmasının kabulünden başlayarak, yazıya ait her hakkı Ulusal Travma ve Acil Cerrahi Derneği’ne devretmektedir(ler). Yazar(lar), izin almaksızın çalışmayı başka bir dilde ya da yerde yayınlamayacaklarını kabul eder(ler). Gönderilen yazı daha önce herhangi bir toplantıda sunulmuş ise, toplantı adı, tarihi ve düzenlendiği şehir belirtilmelidir.

Dergide Türkçe ve İngilizce yazılmış makaleler yayınlanabilir. Tüm yazılar önce editör tarafından ön değerlendirmeye alınır; daha sonra incelenmesi için danışma kurulu üyelerine gönderilir.

Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur. Editörün, kabul edilmeyen yazıların bütününü ya da bir bölümünü (tablo, resim, vs.) iade etme zorunluluğu yoktur.

Açık Erişim İlkesi: Tam metinlere erişim ücretsizdir. Yayınlanan basılı materyali tam metni indirmek için herhangi bir ücret alınmaz.

Yazıların hazırlanması: Tüm yazılı metinler 12 punto büyüklükte “Times New Roman” yazı karakterinde iki satır aralıklı olarak yazılmalıdır. Sayfada her iki tarafta uygun miktarda boşluk bırakılmalı ve ana metindeki sayfalar numaralandırılmalıdır. Journal Agent sisteminde, başvuru mektubu, başlık, yazarlar ve kurumları, iletişim adresi, Türkçe özet ve yazının İngilizce başlığı ve özeti ilgili aşamalarda yüklenecektir. İngilizce yazılan çalışmalara da Türkçe özet eklenmesi gerekmektedir. Yazının ana metnindeyse şu sıra kullanılacaktır: Giriş, Gereç ve Yöntem, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekiller.

Başvuru mektubu: Bu mektupta yazının tüm yazarlar tarafından okunduğu, onaylandığı ve orijinal bir çalışma ürünü olduğu ifade edilmeli ve yazar isimlerinin yanında imzaları bulunmalıdır. Başvuru mektubu ayrı bir dosya olarak, Journal Agent sisteminin “Yeni Makale Gönder” bölümünde, 10. aşamada yer alan dosya yükleme aşamasında yollanmalıdır.

Başlık sayfası: Yazının başlığı, yazarların adı, soyadı ve ünvanları, çalışmanın yapıldığı kurumun adı ve şehri, eğer varsa çalışmayı destekleyen fon ve kuruluşların açık adları bu sayfada yer almalıdır. Bu sayfaya ayrıca “yazışmadan sorumlu” yazarın isim, açık adres, telefon, faks, mobil telefon ve e-posta bilgileri eklenmelidir. Özet: Çalışmanın gereç ve yöntemini ve bulgularını tanıtıcı olmalıdır.

Türkçe özet, Amaç, Gereç ve Yöntem, Bulgular, Sonuç ve Anahtar Sözcükler başlıklarını; İngilizce özet Background, Methods, Results, Conclusion ve Key words başlıklarını içermelidir. İngilizce olarak hazırlanan çalışmalarda da Türkçe özet yer almalıdır. Özetler başlıklar hariç 190210 sözcük olmalıdır.

Tablo, şekil, grafik ve resimler: Şekillere ait numara ve açıklayıcı bilgiler ana metinde ilgili bölüme yazılmalıdır. Mikroskobik şekillerde resmi açıklayıcı bilgilere ek olarak, büyütme oranı ve kullanılan boyama tekniği de belirtilmelidir. Yazarlara ait olmayan, başka kaynaklarca daha önce yayınlanmış tüm resim, şekil ve tablolar için yayın hakkına sahip kişiler-

den izin alınmalı ve izin belgesi dergi editörlüğüne ayrıca açıklamasıyla birlikte gönderilmelidir. Hastaların görüntülendiği fotoğraflara, hastanın ve/veya velisinin imzaladığı bir izin belgesi eşlik etmeli veya fotoğrafta hastanın yüzü tanınmayacak şekilde kapatılmış olmalıdır. Renkli resim ve şekillerin basımı için karar hakemler ve editöre aittir. Yazarlar renkli baskının hazırlık aşamasındaki tutarını ödemeyi kabul etmelidirler.

Kaynaklar: Metin içindeki kullanım sırasına göre düzenlenmelidir. Makale içinde geçen kaynak numaraları köşeli parantezle ve küçültülmeden belirtilmelidir. Kaynak listesinde yalnızca yayınlanmış ya da yayınlanması kabul edilmiş çalışmalar yer almalıdır. Kaynak bildirme “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http:// www.icmje.org) adlı kılavuzun en son güncellenmiş şekline (Şubat 2006) uymalıdır. Dergi adları Index Medicus’a uygun şekilde kısaltılmalıdır. Altı ya da daha az sayıda olduğunda tüm yazar adları verilmeli, daha çok yazar durumunda altıncı yazarın arkasından “et al.” ya da “ve ark.” eklenmelidir. Kaynakların dizilme şekli ve noktalamalar aşağıdaki örneklere uygun olmalıdır: Dergi metni için örnek: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5.

Kitaptan bölüm için örnek: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62.

Sizlerin çalışmalarınızda kaynak olarak yararlanabilmeniz için www.travma.org.tr adresli web sayfamızda eski yayınlara tam metin olarak ulaşabileceğiniz bir arama motoru vardır.

Derleme yazıları: Bu tür makaleler editörler kurulu tarafından gerek olduğunda, konu hakkında birikimi olan ve bu birikimi literatüre de yansımış kişilerden talep edilecek ve dergi yazım kurallarına uygunluğu saptandıktan sonra değerlendirmeye alınacaktır. Derleme makaleleri; başlık, Türkçe özet, İngilizce başlık ve özet, alt başlıklarla bölümlendirilmiş metin ile kaynakları içermelidir. Tablo, şekil, grafik veya resim varsa yukarıda belirtildiği şekilde gönderilmelidir.

Olgu sunumları: Derginin her sayısında sınırlı sayıda olgu sunumuna yer verilmektedir. Olgu bildirilerinin kabulünde, az görülürlük, eğitici olma, ilginç olma önemli ölçüt değerlerdir. Ayrıca bu tür yazıların olabildiğince kısa hazırlanması gerekir. Olgu sunumları başlık, Türkçe özet, İngilizce başlık ve özet, olgu sunumu, tartışma ve kaynaklar bölümlerinden oluşmalıdır. Bu tür çalışmalarda en fazla 5 yazara yer verilmesine özen gösterilmelidir.

Editöre mektuplar: Editöre mektuplar basılı dergide ve PUBMED’de yer almamakta, ancak derginin web sitesinde yayınlanmaktadır. Bu mektuplar için dergi yönetimi tarafından yayın belgesi verilmemektedir.

Daha önce basılmış yazılarla ilgili görüş, katkı, eleştiriler ya da farklı bir konu üzerindeki deneyim ve düşünceler için editöre mektup yazılabilir.

Bu tür yazılar 500 sözcüğü geçmemeli ve tıbbi etik kurallara uygun olarak kaleme alınmış olmalıdır. Mektup basılmış bir yazı hakkında ise, söz konusu yayına ait yıl, sayı, sayfa numaraları, yazı başlığı ve yazarların adları belirtilmelidir. Mektup bir konuda deneyim, düşünce hakkında ise verilen bilgiler doğrultusunda dergi kurallarına uyumlu olarak kaynaklar da belirtilmelidir.

Bilgilendirerek onay alma - Etik: Deneysel çalışmaların sonuçlarını bildiren yazılarda, çalışmanın yapıldığı gönüllü ya da hastalara uygulanacak prosedür(lerin) özelliği tümüyle anlatıldıktan sonra, onaylarının alındığını gösterir bir cümle bulunmalıdır. Yazarlar, bu tür bir çalışma söz konusu olduğunda, uluslararası alanda kabul edilen kılavuzlara ve T.C. Sağlık Bakanlığı tarafından getirilen yönetmelik ve yazılarda belirtilen hükümlere uyulduğunu belirtmeli ve kurumdan aldıkları Etik Komitesi onayını göndermelidir. Hayvanlar üzerinde yapılan çalışmalarda ağrı, acı ve rahatsızlık verilmemesi için neler yapıldığı açık bir şekilde belirtilmelidir.

Yazı gönderme - Yazıların gönderilmesi: Ulusal Travma ve Acil Cerrahi Dergisi yalnızca www.travma.org.tr adresindeki internet sitesinden on-line olarak gönderilen yazıları kabul etmekte, posta yoluyla yollanan yazıları değerlendirmeye almamaktadır. Tüm yazılar ilgili adresteki “Online Makale Gönderme” ikonuna tıklandığında ulaşılan Journal Agent sisteminden yollanmaktadır. Sistem her aşamada kullanıcıyı bilgilendiren özelliktedir.

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 22

Number - Sayı 3 May - Mayıs 2016

Contents - İçindekiler Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 205-214 Effects of transpositional muscle flaps transfected with vascular endothelial growth factor gene in the treatment of experimental osteomyelitis

Deneysel osteomyelit tedavisinde vasküler endotelial büyüme faktörü geni ile transfekte edilmiş transpozisyonel kas flebinin etkinliği Aliyev M, Aykan A, Eski M, Arslan N, Kurt B, Şengezer M 215-223 Hemostatic efficacy of local chitosan linear polymer granule in an experimental sheep model with severe bleeding of arteria and vena femoralis

Ciddi femoral arter ve ven kanaması olan deneysel koyun modelinde, lokal “chitosan linear polymer” granül uygulamanın, hemostatik etkinliği Ersoy G, Rodoplu Ü, Yılmaz O, Gökmen N, Doğan A, Dikme Ö, Aydınoğlu A, Orhon O 224-232 Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

Yanık sıçanlarda mikrodizi analiziyle ortaya çıkartıldığı gibi erken akış fazında iskelet kaslarındaki IncRNA’ların ekspresyon imzaları Haijun Z, Yonghui Y, Jiake C

Original Articles - Orijinal Çalışma 233-241 Internal fixation vs conservative treatment for displaced distal radius fractures: a meta-analysis of randomized controlled trials

Deplase distal radius kırıklarında internal fiksasyona karşın konservatif tedavi: Randomize kontrollü çalışmaların metaanalizi Yu GS, Lin YB, Le LS, Zhan MF, Jiang XX 242-246 Impact of ATLS guidelines, trauma team introduction, and 24-hour mortality due to severe trauma in a busy, metropolitan Italian hospital: A case control study

Yoğun bir metropol hastanesinde ağır travmada 24 saat içindeki ölüm oranlarına ATLS kılavuzlarının ve travma ekibinin etkisi: Bir olgu kontrollü çalışma Magnone S, Allegri A, Belotti E, Castelli CC, Ceresoli M, Coccolini F, Manfredi R, Merli C, Palamara F, Piazzalunga D, Valetti TM, Ansaloni L 247-252 Evaluating incorrect management of transferred pediatric burn patients

Transfer edilen çocuk yanık hastalarındaki yanlış uygulamaların değerlendirilmesi Şenaylı A, Öztürk F, Azılı MN, Demir S, Demir R, Şenel E 253-258 Relationship of biological factors to survival in spinal gunshot injuries

Spinal ateşli silah yaralanmasında biyolojik faktörlerin survey ile ilişkisi Seçer M, Ulutaş M, Alagöz F, Uçkun ÖM, Çınar K, Yel C, Gökçe EC, Dalgıç A 259-264 A review of intussusception cases involving failed pneumatic reduction and re-intussusception

İnvajinasyonda başarısız pnömatik redüksiyon ve reinvajinasyon olgularının incelenmesi Özcan R, Hüseynov M, Emre Ş, Tütüncü Ç, Ertem Vehid H, Dervişoğlu S, Adaletli İ, Celayir S, G Tekant 265-268 A hidden household danger: Television

Evdeki gizli tehlike: Televizyon Bol O, Cebiçci H, Koyuncu S, Şarlı B, Günay N Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 22

Number - Sayı 3 May - Mayıs 2016

Contents - İçindekiler

269-272 Ingested intraabdominal foreign bodies that require surgical intervention

Yutulan ve cerrahi müdahale gerektiren intraabdominal yabancı cisim olgularımız Kızıltan R, Yılmaz Ö, Aras A, Toktaş O, Batur A, Ağar F, Ölmez Ş, Kotan Ç 273-277 Where should the damage control surgery be performed, at the nearest health center or at a fully equipped hospital?

Hasar kontrol cerrahisi nerede yapılmalı? Yapılabilecek en yakın yerde mi, tam donanımlı hastanede mi?

Uğur M, Akküçük S, Koca YS, Oruç C, Aydoğan A, Kılıç E, Yetim İ, Temiz M 278-282 Electrical burns: Highlights from a 5-year retrospective analysis

Elektrik yanıkları: Beş yıllık geriye dönük değerlendirme Kurt A, Yıldırım K, Yağmur Ç, Kelahmetoğlu O, Aslan O, Gümüş M, Güneren E 283-289 Evaluation of outcomes in aseptic non-unions of the forearm bones in adults treated with LCP and autograft

Erişkin ön kol kemiklerinin aseptik kaynamama tedavisinde LCP ve otogreft Lapcin O, Arıkan Y, Yavuz U, Akman YE, Çetinkaya E, Gür V, Demir B

Case Reports - Olgu Sunumu 290-292 A rare cause of acute abdominal disease: two reports of caecal diverticulum perforation

Nadir akut karın nedeni: Çekum divertikül perforasyonu (İki olgu) Çiftci F, Abdurrahman İ, Eren A 293-296 Traumatic rupture of gastric pull-up after apparent mild thoracic trauma: a case report and literature review

Belirgin bir toraks travması ardından gastrik pull-up’ın travmatik rüptürü: Bir olgu raporu ve literatürün gözden geçirilmesi Valle J, Srinivasrao H, Snow D, Asbitt M 297-300 Challenging management of obturator hernia: a report of three cases and literature review

Obturator fıtıkların zorlu yönetimi: Üç olgu sunumu ve literatürün gözden geçirilmesi Şenol K, Bayam ME, Duman U, Dilektaşlı E, Doğangün M, İnal A, Tihan DN 301-303 Air gun pellet: cardiac penetration and peripheral embolization

Havalı tüfek saçması kardiyak penetrasyon ve periferal embolizasyonu Işık O, Engin Ç, Daylan A, Şahutoğlu C

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EXPERIMENTAL STUDY

Effects of transpositional muscle flaps transfected with vascular endothelial growth factor gene in the treatment of experimental osteomyelitis Mahir Aliyev, M.D.,1 Andaç Aykan, M.D.,2 Muhitdin Eski, M.D.,2 Nuri Arslan, M.D.,3 Bülent Kurt, M.D.,4 Mustafa Şengezer, M.D.2 1

Department of Plastic and Reconstructive Surgery, Military Hospital, Baku-Azerbaijan

2

Department of Plastic and Reconstructive Surgery, Gülhane Military Medical Academy, Ankara-Turkey

3

Department of Nuclear Medicine, Gülhane Military Medical Academy, Ankara-Turkey

4

Department of Pathology, Gülhane Military Medical Academy, Ankara-Turkey

ABSTRACT BACKGROUND: Based on the angiogenetic and stimulating effects of bone healing and formation of vascular endothelial growth factor (VEGF), the present study was designed to assess the efficacy of VEGF gene application in the management of experimentally induced osteomyelitis.

METHODS: Thirty-two male Sprague Dawley rats were divided into 4 groups, and osteomyelitis was induced in the left tibial bones.

Group 1 (n=8) was designated as a control group, and, after the induction of osteomyelitis, no treatment was applied for a period of 4 weeks. Group 2 (n=8) received only antibiotic treatment for 4 weeks following induction of osteomyelitis. In Group 3 (n=8), proximally pedicled gastrocnemius muscle flap was transposed over the osteomyelitic region following induction of osteomyelitis and antibiotic treatment applied for a 4-week period. In Group 4 (n=8), VEGF gene-transfected gastrocnemius muscle flap was transposed over the osteomyelitic region following identical antibiotic regimen applied for a 4-week period. For each group, body temperature, white blood cell (WBC) count, and radiological and histological parameters were evaluated.

RESULTS: Body temperature and WBC count remained high in the control group, but returned to normal in Groups 2, 3, and 4 after the third week of treatment. Statistical analysis of the total scores of radiological and histological results revealed significant differences between Groups 1 and 3, Groups 1 and 4, Groups 2 and 3, and Groups 2 and 4 (p<0.05). Regarding radiological parameters of abscess and sequester, and histological parameter of abscess, statistically significant differences were found between Group 4 and the other groups (p<0.05).

CONCLUSION: The efficacy of the VEGF gene-transfected muscle flap in the management of experimental osteomyelitis was proven by the results of the present study.

Keywords: Gastrocnemius; muscle flap; osteomyelitis; transfection; VEGF gene.

INTRODUCTION Osteomyelitis is an inflammatory process accompanied by bone destruction and necrosis caused by infection.[1,2] The Address for correspondence: Andaç Aykan, M.D. Gülhane Askeri Tıp Akademisi, Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, 06010 Etlik, Ankara, Turkey Tel: +90 312 - 304 54 07 E-mail: andac_aykan@gata.edu.tr Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):205–214 doi: 10.5505/tjtes.2015.37888 Copyright 2016 TJTES

Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

most commonly isolated pathogen is Staphylococcus aureus (S. aureus).[1] Bacterial toxin production and host inflammation frequently damage the blood supply and result in bone necrosis.[3] The devitalized bone acts as a foreign body, with sustained infection in spite of long-term antimicrobial therapy. The high rates of antimicrobial therapy success in the treatment of most infectious diseases have yet to be achieved in the treatment of osteomyelitis.

Osteomyelitis tends to be chronic, causing persistent morbidity and major financial burden, and substantially affecting quality of life. Current management of osteomyelitis includes a combination of long-term antibiotic therapy, and recurrent surgical debridement of necrotic bone and infected tissue.

[1] However, these methods are not satisfactory and may re205

Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

sult in failure in 31% of patients.[4] Therefore, more effective treatment modalities are needed.

Local or free muscle flaps are commonly used in the treatment of osteomyelitis with soft tissue defect due to trauma or vascular insufficiency localized on the lower extremity.[5–8] Muscle flaps have long been considered very useful for filling defects, revascularizing tissue, and controlling chronic infection.[9] It is shown that experimental flaps that include the muscle have a greater resistance to bacterial inoculation than random-pattern skin flaps.[10] Alternative treatment modalities that can provide neo-vascularization may be considered to treat diminished vascular supply to the bone caused by osteomyelitis. It is known that vascular endothelial growth factor (VEGF) plays an important role in new bone formation and neo-vascularization.

[11–13] Several experimental studies have indicated that administration of exogenous VEGF can induce angiogenesis and improve the survival of flaps.[14,15] However, the low half-life, enzymatic inactivation, and the need to carrier molecules are the most important factors challenging the use of exogenous growth factors. Recently, gene therapy has been utilized to avoid the need for daily injections and overcome these disadvantages.[16,17] Based on the angiogenetic and stimulating effects of bone healing, and the formation of VEGF, the present study was designed to assess the efficacy of VEGF gene application to the muscle flap in the management of experimentally induced osteomyelitis.

MATERIALS AND METHODS Animals Thirty-two adult, male Sprague Dawley rats weighing 320-360 g each were used. Prior to surgery, rats were acclimated to their new environment and fed a standard laboratory diet.

The animals were housed in single room, with a consistent room temperature. The Ethics Committee approved the study protocol (KS-06/31), (Scientific Research Board and Ethics Board of Animal Experiments, protocol number: KS06/31). All experiments were performed in accordance with the approved protocol.

Study Design Animals were divided into 4 groups, and osteomyelitis was induced in the left tibial bones. Group 1 (n=8) was designated as a control group. After 2 weeks that followed the induction of osteomyelitis in the left tibia, no treatment was applied for a period of 4 weeks. Cortical bone defects of equal size had been drilled in the right tibias of control group animals, but no bacterial inoculum was injected. Group 2 (n=8) received only antibiotic treatment (intramuscular gentamicin, 4 mg/kg) for 4 weeks following 2 weeks of induction. In Group 3 (n=8), 206

after 2 weeks of induction, a proximally pedicled gastrocnemius muscle flap was transposed over the osteomyelitic region, and antibiotic treatment (intramuscular gentamicin, 4 mg/kg) was administered for a period of 4 weeks. In Group 4 (n=8), after 2 weeks of induction, a VEGF gene-transfected gastrocnemius muscle flap was transposed over the osteomyelitic region, and the same antibiotic regimen was applied for a period of 4 weeks (Fig. 1).

Bacterial Suspension S. aureus (strain 25923; American Type Culture Collection, Manassas, VA, USA) was used as the pathogen. Preparation of bacterial suspension was achieved in accordance with reported procedure.[18] Briefly summarized, the strain was cultured for 24 hours at 37ºC on a blood agar plate. Bacterial cells were suspended in sterile saline until final optical density of 0.18 was achieved, as indicated by absorbance measurement of 600 nm by spectrophotometer (Novaspec II; Amersham Pharmacia Biotech, Inc., Piscataway, NJ, USA). Based on optical density, a suspension containing approximately 3×108 colony-forming units (CFU)/mL of S. aureus was used as inoculum.

Surgical Procedure Anesthesia was induced with a mixture of 10% ketamine hydrochloride (90 mg/kg) and 2% xylazine (10 mg/kg) via intramuscular injection. Skin preparation involved shaving and disinfection with 10% povidone-iodine solution.

Induction of Osteomyelitis After 1-cm skin incision was made, the left proximal tibia was exposed. Two holes with 1-mm diameters were drilled at distance of 7 mm on the cortical bone, and the medullar cavity was exposed. Immediately afterward, bacterial inoculum (3×108 CFU/mL of S. aureus) of 20-µL volume was injected into the medullar cavity. The drilled hole was sealed with bone wax (Braun; Aesculap AG & Co., Tuttlingen, Germany). Skin edges were reapproximated with non-absorbable suture, and the wound was cleaned with 10% povidone-iodine solution.

In control animals, cortical defects of equal size were drilled into the right tibia, but no bacterial inoculum was injected.

The drilled holes were sealed with bone wax in all animals.

Skin edges were reapproximated with non-absorbable suture, and the wound was cleaned with 10% povidone-iodine solution.

Pedicled Gastrocnemius Muscle Flap Two weeks after induction of osteomyelitis, animals were placed in the supine position, and the same incision was used for tibia exposure. The medial gastrocnemius muscle flap was raised, as described in previous studies.[19] The sural artery branch from the popliteal artery was protected, and the flap was transposed to the proximal tibia (Fig. 2).

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Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

n=32

Induction of osteomyelitis 2 weeks

Group 1 (n=8)

No treatment (control)

Group 2 (n=8)

Group 3 (n=8)

Antibiotic

Group 4 (n=8)

Gastrocnemius muscle flap VEGF-gene transfacted gastrocnemius muscle flap + + Antibiotic Antibiotic 4 weeks

Assessment

Figure 1. Experimental design.

VEGF gene Preparation and Application Plasmids including VEGF [pPI-hVEGF (165)-NEO-DHFR] were obtained from the Ecole Polytechnique FĂŠdĂŠrale de Lausanne, as represented by Prof. Patrick Aebischer. The Escherichia coli strain was transfected with this plasmid for proliferation using a TransformAid Bacterial Transformation Kit (ThermoFisher Scientific, Inc., Waltham, MA, USA). Plasmid extraction from transformed E. coli was performed using the Plasmid Giga Kit (Qiagen, Inc., Valencia, CA, USA). Plasmid amount was determined using ultraviolet spectrophotometer.

Concentration of plasmid suspended in saline was 1 mg/mL, and it was ready for injection into muscle flaps.

3 and 4 on the 3rd, 7th, and 10th postoperative days. Biopsies were obtained from the gastrocnemius muscle. MRNA-pPIhVEGF (165) was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). For each RNA specimen, dNTP (ThermoFisher Scientific, Inc., Waltham, MA, USA), reverse transcriptase enzyme (ThermoFisher Scientific, Inc.,

After the muscle flap was elevated, total dose of 0.3 mL VEGF-DNA-carrying plasmid was injected into the muscle at 3 points in Group 4 animals. The same amount of saline was injected into Group 3 animals.

Detecting Gene Expression In order to demonstrate the efficiency of VEGF gene therapy, muscle biopsies were performed on the animals in Groups Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Figure 2. Medial gastrocnemius muscle flap elevation and transposition.

207

Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

Waltham, MA, USA), 5XRT buffer (ThermoFisher Scientific, Inc., Waltham, MA, USA), and primer 1-containing reaction were used to prepare cDNA. The reaction was incubated at 42°C for 60 min and again at 95°C for 5 min, before being terminated. Polymerase chain reaction (PCR) amplification was performed as follows: 35 cycles with 20 seconds at 94°C, 20 seconds at 55°C, 20 seconds at 72°C, and 5 min of incubation at 72°C. Primers used were 5’-GAGGGCAGAATCATCACGAAGT-3’ (from EXON 2, SENSE) and 5’-TGAGAGATCTGGTTCCCGAAAC-3’ (from EXON 8, ANTISENSE).

Positive controls were used for PCR products. PCR products were analyzed by electrophoresis on 2% agarose gel (100 V, 60 minutes) and visualized by ethidium bromide staining.

Assessment Scintigraphy With Tc-99m MDP For confirmation of osteomyelitis, Group 1 animals were imaged with triple-phase bone scintigraphy (GE Optima, Milwaukee, WI, USA) 2 weeks after induction. Triple-phase examination of the tibia— consisting of radionuclide angiography (2 sec/frame), blood pool (5 min), and (2-hour) delayed images— were obtained following injection of 1 mCi (37 MBq) Tc-99m methylene di-phosphonate (MDP) in the tail vein. Images of Tc-99m MDP were evaluated by an experienced nuclear medicine physician. A focal area of increased blood flow and osteoblastic activity was considered positive evidence of osteomyelitis.

the left tibia was dissected from the surrounding tissue. After decalcification (5% formic acid in distilled water for 24 hours), specimens were embedded in paraffin, and multiple 4-µm sections were cut. Sections were stained with hematoxylin-eosin and examined under light microscope. Inflammation and fibrosis were observed. Abscess formation, presence of sequestrum, cortical expansion, and destruction of cortex were used as histological parameters to evaluate samples.[20] Using these criteria, a numerical score was assigned from an answer of “yes” or “no” (1 for yes, 0 for no), and the 4 scores were added to make an overall ranking (total histologic score; tHS) for histological assessment.

Statistical Analysis Statistical analysis was performed using SPSS software (version 16.0; SPSS Inc., Chicago, IL, USA). All data are presented as mean and SD. Kruskal–Wallis test was used to analyze differences among the experiment groups. Mann-Whitney U test was performed to test the significance of pairwise differences using Bonferroni correction to adjust for multiple comparisons. A value of p<0.05 was considered significant.

In a second step, by drawing regions of interest (ROI; diameter 3.0 mm) on the osteomyelitis-induced left tibia, as well as on the right tibia, which had been drilled only, a ratio between the number of counts per pixel (cpp) in each region was calculated using transaxial slices. Results were expressed as a tumor: background (T:BG) ratio.

Body Temperature and White Blood Cell Count Rectal body temperature of all animals was manually measured at Day 0, 7, 14, 28, 35, and 42. For assessment of white blood cell (WBC) response, 1 mL of blood was obtained from the tail vein prior to all surgical procedures, and at 2 and 6 weeks after induction.

Figure 3. Two-hour delayed images following injection of Tc-99m MDP showed markedly increased activity within the left tibia, compatible with osteomyelitis on posterior planar imaging.

Radiology Radiographs were taken at 6 weeks after induction. Development and progression of infection was assessed using 5 criteria;[20] periosteal reaction, intraosseous abscess formation, bone deformity, spontaneous fracture, and sequestrum formation. A numerical score was assigned (0—3 for the first 3 criteria, 0—1 for the last 2) and the 5 scores were added to make an overall total radiographic score (tRS) for radiological assessment.

Histology At 6 weeks after induction, the animals were euthanized, and 208

500 bp 400 bp 300 bp 200 bp 100 bp

164 kDa

(+) Control

(+) Muscle

(–) Muscle

(–) Saline

Figure 4. Polymerase chain reaction products were analyzed by electrophoresis on 2% agarose gel (100V, 60 minutes) and visualized by ethidium bromide staining. SM: Leader; 1: Positive control; 2: Positive muscle; 3: Negative muscle, 4: Negative saline. Bp: Base pair.

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Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

RESULTS

45

Scintigraphy With Tc-99m MDP

40

Quantitative analysis of scintigraphic data showed values of 10142.8±16.64 and 6004.96±19.54 for blood pool phase and delayed phase in osteomyelitis-induced left tibias, respectively. Control tibias showed values of 6013.44±18.48 and 3187.72±20.46 for blood pool phase and delayed phase, respectively. Scintigraphic data revealed significant differences between the left and right tibias in the control animals (p<0.05; Fig. 3).

35

*

38.9±0.2

*

38.4±0.3

37.4±0.2

37.1±0.4

30 25

*

20

19.48±1.86

15 10

8.82±2.42

7.68±3.40

7.8±2.64

5 0

Efficacy of Gene Therapy

The mRNA-pPI-hVEGF (165) was determined at the end of electrophoresis by RT-PCR from muscle samples at 3, 7, and 10 postoperative days in the gene therapy group (Group 4; Fig. 4). No band formation was seen in the samples containing negative muscle and serum saline (Group 3). These findings indicate that the gene had been incorporated into the muscle cell in the gene therapy group, and had begun to secrete VEGF.

Group 1

Group 2

Group 3

Body Temperature (°C)

Group 4

WBC (x1000)

Figure 5. Values (mean±SD) of body temperature and white blood cell count on the 42nd postoperative day. *p<0.05.

At the 6th postoperative week, no differences were found in body temperature between Groups 1 and 2, and Groups 3 and 4. Significant differences were found between Groups 1 and 3, and Groups 2 and 3 (p<0.05). Statistically significant differences were also found between Groups 1 and 4, and Groups 2 and 4 (p<0.05).

Body Temperature and White Blood Cell Count Preoperatively, mean body temperature and WBC count of all animals were 37.3±0.4ºC and 5.43±1.62x103, respectively.

Body temperatures and WBC levels prominently increased after 2 weeks from induction. At the 14th day, mean body temperature and WBC count of all animals were 39.1±0.2ºC and 18.24±2.74x103, respectively. Mean values of body temperature and WBC count of groups are shown in Figure 5.

Regarding WBC count, statistically significant differences were found between Group 1 and the other groups (p<0.05).

Radiology TRSs for radiological severity are shown in Table 1. Regarding tRS, no differences were found between Groups 1 and 2,

Table 1. Radiographic criteria and calculated total radiographic scores (mean±standard deviation)

Group 1

Group 2

Group 3

Group 4

Periosteal reaction

2.63±0.52 2.13±0.64 1.38±0.74 1.13±0.64

Intraosseous abscess formation

2.75±0.46

Bone deformity

2.75±0.46 2.62±0.52 1.75±0.46 1.63±0.52

Spontaneous fracture

0.50±0.54

Sequestrum formation

0.75±0.46 0.75±0.46 0.25±0.46 0.13±0.35

Total radiographic scores

9.38±1.19

2.75±0.46

1.50±0.89

0.38±0.52

0.38±0.52

0.00

8.63±1.19

0.00

4.84±0.92

3.25±1.28

Table 2. Histological parameters and calculated Total histological scores (mean±standard deviation)

Group 1

Group 2

Group 3

Group 4

Abscess formation

1.00±0.0

1.00±0.0

0.54±0.52

0.25±0.46

Presence of sequestrum

0.75±0.46

0.63±0.52

0.25±0.46

0.13±0.35

Cortical expansion

1.00±0.0

1.00±0.0

0.63±0.52

0.63±0.52

Destruction of cortex

0.88±0.35

Total radiographic scores

3.63±0.52

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0.63±0.52

3.25±0.71

0.25±0.46

1.58±0.76

0.13±0.35

1.13±0.84

209

Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

4

*

*

*

3.5 3 tRS

tRS

Radiographic Severity 10 9 8 7 6 5 4 3 2 1 0

2.5 2 1.5 1 0.5

Group 1

Group 2

Group 3

0

Group 4

Figure 6. Evaluation of total radiographic scores showed statistically significant differences between the muscle flap (Group 3 and 4) and other groups (Groups 1 and 2). tRS: Total radiographic score; *p<0.05.

Group 1

Group 2

Group 3

Group 1

Group 2

Group 4

Figure 9. Evaluation of total histologic scores showed statistically significant differences between the muscle flap (Groups 3 and 4) and other groups (Groups 1 and 2). tHS: Total histologic score; *p<0.05.

Group 4

3

Group 1 Group 2 Group 3 Group 4

Histological Score

2.5 2 weeks

Group 3

2

*

1.5 1 0.5

4 weeks

0

Periosteal reaction

Intraosseous abscess formation

Bone deformity

Spontaneous fracture Sequestrum formation

Figure 10. Histologic criteria of intraosseous abscess formation was significantly higher in Group 3, compared to Group 4. *p<0.05.

Figure 7. Radiologic images of each group taken at the 2nd and 4th weeks after induction of osteomyelitis (upper and lower rows, respectively).

3 Group 1 Group 2 Group 3 Group 4

Radiographic Score

2.5 2

*

1.5 1 0.5 0

* Periosteal reaction

Intraosseous abscess formation

Bone deformity

Spontaneous fracture Sequestrum formation

Radiographic Criteria

Figure 8. Comparison of radiographic criteria. Regarding intraosseous abscess and sequestrum formation, significant differences were found between Groups 3 and 4. *p<0.05.

and Groups 3 and 4. In addition, significant differences were found between Groups 1 and 3, Groups 1 and 4, Groups 2 and 3, and Groups 2 and 4 (p<0.05; Figs. 6, 7). Regarding intraosseous abscess and sequestrum formation, statistically significant differences were found between Group 4 and the other groups (p<0.05; Fig. 8).

210

Histology tHSs are shown in Table 2. Regarding tHS, no differences were found between Groups 1 and 2, and Groups 3 and 4. Significant differences were found between Groups 1 and 3, Groups 1 and 4, Groups 2 and 3, and Groups 2 and 4 (p<0.05; Fig. 9).

Less inflammation and more fibrosis was found in Group 4, compared to Group 3. In terms of abscess formation, statistically significant differences were found between Group 4 and the other groups (p<0.05; Figs. 10, 11).

DISCUSSION Understanding of the underlying mechanism of a disease is crucial for development of new treatment modalities. The process of osteomyelitis is initiated by the causative microorganism and inflammation, and continues with vascular insufficiency. The resulting ischemia contributes to bone necrosis.

[1,2] Current treatment modalities for osteomyelitis include combined antimicrobial therapy, and surgical approach for causative pathogen and devitalized tissue. However, it can be persistent for years, with frequent therapeutic failure. In spite of advances in both antibiotics and surgical treatment, the long-term recurrence rate remains approximately 20-30%.[21] Due to dissatisfaction with actual treatment modalities, many Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

Figure 11. Histologic examination with hematoxylin-eosin stain (x40, x100). Marked polymorphonuclear leukocyte infiltration was observed in Groups 1 and 2 (upper left and right, respectively). Compared to Group 3, less inflammation and more fibrosis were observed in Group 4 (lower left and right, respectively).

experimental and clinical approaches to osteomyelitis therapy have been described in the literature.[22â&#x20AC;&#x201C;25]

verify that muscle flaps are effective reconstructive tools for controlling infection and the progress of osteomyelitis.

Coverage of the defect with well-vascularized tissue, providing sufficient blood supply to the devitalized bone, is another important modality for the treatment of osteomyelitis. In addition to appropriate antimicrobial therapy, defect reconstruction and optimization of local microcirculation is essential in the preservation of limbs and attainment of functional results. Damage to the periosteum results in impaired blood supply to the bone, and eventually, larger bone areas become necrotic as the disease advances. Therefore, in addition to antimicrobial therapy, a more comprehensive approach to treatment of osteomyelitis should include improvement of circulation.

Due to the several drawbacks of use of growth factor in the therapeutic purposes (enzymatic inactivation, low bio-availability, the need for an exogenous carrying molecule), gene therapy has been adopted to achieve lasting effects.[26] The idea to use VEGF for gene therapy of osteomyelitis was first put forth by Jon Mader.[3] However, no research regarding the effects this treatment have yet been published. VEGF gene therapy has been used to improve flap viability with promising results in experimental settings.[27,28] In the present study, VEGF gene therapy was administered by intramuscular injection to the muscle flap in order to create a VEGF-enriched microenvironment in osteomyelitis-induced bone. In histological examination, less inflammation and more fibrosis was found in the VEGF gene-transfected muscle flap group (Group 4), compared to the group that received muscle flap without VEGF gene-transfection (Group 3). In addition, intraosseous abscess formation was found to be significantly lower in Group 4, compared to other groups in both radiological and histological analysis. According to these findings, it is believed that ideal blood supply to the damaged area was achieved with VEGF-transfected muscle flap.

VEGF gene-transfected muscle flap was used in the present experimental management of osteomyelitis. In terms of radiographic and histological scores, no differences were found between Group 1 (no treatment) and Group 2 (antibiotic treatment). These findings confirm that antimicrobial therapy alone is not effective management of osteomyelitis in an experimental setting. Moreover, significant differences were found between the groups in which muscle flaps were used (Groups 3 and 4) and not used (Groups 1 and 2). In terms of body temperature, the same results were observed. These findings Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Different methods for the administration of VEGF gene ther211

Aliyev et al. Muscle flaps transfected with VEGF gene in the treatment of experimental osteomyelitis

apy have been described. Studies have shown that adenovirus vector inserted with VEGF or liposome-mediated VEGF gene are effectively transferred and expressed via direct intramuscular injection or arterial access.[29,30] However, in addition to gene delivery techniques, the simplest method of gene delivery is the direct injection of naked plasmid DNA into tissues. Advantages of this method are local delivery to the target organ and the ability to act on non-dividing cells. The skeletal muscle has been shown to be suitable for taking up and expressing foreign genes transferred in the form of naked plasmid DNA.[31] In order to show transfection efficacy, muscle biopsies were presently performed in the postoperative period, and VEGF mRNA expression was detected by reverse transcriptase-PCR in Group 4.

For the diagnosis of osteomyelitis, clinical examination and imaging studies are used.[1] Plain x-rays, nuclear scintigraphy, and magnetic resonance imaging (MRI) are common imaging tools for diagnosis. However, because of the high cost of MRI, nuclear scintigraphy and plain x-rays were used in the present study for diagnosis and follow-up. For confirmation of osteomyelitis, scintigraphy with Tc-99m MDP was applied to the Group 1 animals 14 days after the induction of osteomyelitis.

Quantitative analysis of the scintigraphic data showed the differences between osteomyelitis-induced left and drilled-only right (control) tibias. Plain films were easily applied to the animals and used as a screening and assessment tool.

A number of parameters for monitoring the activity of osteomyelitis exist in the literature.[1,32] In general, they can be divided into 4 subgroup: hematologic, clinical, radiological and histological. Although radiological in combination with histological parameters were of primary use, clinical and hematological parameters were also used. Several systemic hematological parameters, such as erythrocyte sedimentation rate, C-reactive protein, and procalcitonin, are available to monitor response to therapy. In spite of some differences in specificity and sensitivity, all adequately contribute to assessment and follow-up of osteomyelitis.[32] In the present study, the activity of the osteomyelitis was monitored with WBC counts and rectal body temperature as hematological and clinical parameters, respectively. However, the more detailed parameters for assessment of treatment may be used in future studies.

Well-known scoring systems were utilized for radiological and histological evaluation in the present study.[20] Although in terms of tRS and tHS, no differences were found between Group 3 (without VEGF gene transfection) and Group 4 (administered VEGF gene-transfected muscle flap), some important parameters of each scoring systems were found to be statistically different. According to radiological evaluation, intraosseous abscess and sequestrum formation were found to be significantly lower in Group 4, compared to the other groups. In terms of intraosseous abscess formation, the same result was achieved in histological evaluation. This is 212

an important finding for the treatment of osteomyelitis and prevention of its progression.

In the pathogenesis of the disease, intraosseous abscess and sequestrum formation occur in the later stages.[33] Initially, bacterial toxin production and host response result in the release of lytic enzymes. This, in turn, damages the medullar cavity and the bone cortex.[3] Ensuing damage of the periosteum impairs the blood supply to the cortical and medullar bone, and larger areas of ischemic bone tissue become necrotic. Eventually, purulent material and impaired blood supply contribute to the formation of abscess and sequestrum, respectively. In addition, sequestrum is the best stimulant for proper involucrum formation, which can be seen in more advanced stages.[33] Compared to the other groups, decreased formation of abscess and sequestrum in Group 4 indicates that the treatment of VEGF gene-transfected muscle flap prevents the progression of the disease. The differences found in Group 4 can most likely be attributed to the effect of VEGF gene therapy. Accordingly, it is presently suggested that VEGF gene-transfected muscle flap could provide ideal local microcirculation, allowing for proper antibiotic delivery and a desired healing process in experimental settings.

It is known that antibiotic therapy is a critical component of osteomyelitis treatment protocol. However, systemically administered antibiotics cannot reach the osteomyelitis sites in sufficient concentration, due to lack of appropriate circulation. For that reason, various studies of appropriate antimicrobial therapy have been conducted. Photodynamic therapy was used by dos Reis JA et al.,[22] who found that photodynamic antimicrobial therapy was effective in reducing the number of S. Aureus in both in vitro and in vivo studies. In vitro antibacterial activity of the bioglass (BAG S53P4) against multiresistant microorganisms commonly involved in osteomyelitis was studied by Drago L. et al.[23] In addition, the authors evaluated its use in surgical adjunctive treatment of osteomyelitis in a prospective study of 27 patients with clinically and radiologically diagnosed osteomyelitis. In vitro tests regarding the antibacterial activity of BAG S53P4 revealed marked bactericidal activity and clinically no signs of infection were observed in 24 patients during follow-up, while infection recurrence was observed in 2 subjects. Similarly, a drug delivery system has been developed by Bhattacharya R. et al. in an effort to combat the causative agent.[24] After inducing osteomyelitis, hydroxyapatite scaffolds impregnated with antibiotic ceftriaxoneâ&#x20AC;&#x201C;sulbactam sodium were utilized in rabbit tibia. Efficient drug release of up to 42 days and infection eradication were observed. In terms of antibacterial efficiency and disease control, promising results were reported in all of these studies. Achievement of ideal antimicrobial agent delivery is one of the important contributions of VEGF gene therapy.

Debridement is an approach commonly used in the clinic to treat existing osteomyelitis. The surgical removal of necrotic bone and infected tissue improve healing potential. Due to Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

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the size limitations of our experimental model (small bone dimensions), debridement was not included in the experiment design. However, it is important to point out that VEGF genetransfected muscle flap could provide effective control of the disease even without debridement. Debridement should be included in large animal models, as well in further studies.

In conclusion, it has been shown that VEGF gene-transfected muscle flap is an effective means of preventing progression of osteomyelitis to advanced stages, and is also an efficient component of treatment, due to its promotion of circulation.

Financial Interest None Conflict of interest: None declared.

REFERENCES 1. Lew DP, Waldvogel FA. Osteomyelitis. Lancet 2004;364:369–79.

2. Rao N, Ziran BH, Lipsky BA. Treating osteomyelitis: antibiotics and surgery. Plast Reconstr Surg 2011;127 Suppl 1:177–87.

3. Ross JJ. Angiogenic gene therapy as a potential therapeutic agent in chronic osteomyelitis. Med Hypotheses 2006;67:161–3.

4. Tice AD, Hoaglund PA, Shoultz DA. Risk factors and treatment outcomes in osteomyelitis. J Antimicrob Chemother 2003;51:1261–8.

5. Anthony JP, Mathes SJ, Alpert BS. The muscle flap in the treatment of chronic lower extremity osteomyelitis: results in patients over 5 years after treatment. Plast Reconstr Surg 1991;88:311–8.

6. Fitzgerald RH Jr, Ruttle PE, Arnold PG, Kelly PJ, Irons GB. Local muscle flaps in the treatment of chronic osteomyelitis. J Bone Joint Surg Am 1985;67:175–85.

7. Mathes SJ. The muscle flap for management of osteomyelitis. N Engl J Med 1982;306:294–5.

8. Zumiotti AV, Teng HW, Ferreira MC. Treatment of post-traumatic tibial osteomyelitis using microsurgical flaps. J Reconstr Microsurg 2003;19:163–71.

9. Costa H, Malheiro E, Silva A, Fidalgo R, Trigo J. The distally based posterior tibial myofasciocutaneous island flap in foot reconstruction. Br J Plast Surg 1996;49:111–4.

10. Murphy RC, Robson MC, Heggers JP, Kadowaki M. The effect of microbial contamination on musculocutaneous and random flaps. J Surg Res 1986;41:75–80.

11. Hiltunen MO, Ruuskanen M, Huuskonen J, Mähönen AJ, Ahonen M, Rutanen J, et al. Adenovirus-mediated VEGF-A gene transfer induces bone formation in vivo. FASEB J 2003;17:1147–9.

12. Peng H, Wright V, Usas A, Gearhart B, Shen HC, Cummins J, Huard J. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest 2002;110:751–9.

13. Street J, Bao M, deGuzman L, Bunting S, Peale FV Jr, Ferrara N, et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A 2002;99:9656–61.

14. Pang Y, Lineaweaver WC, Lei MP, Oswald T, Shamburger S, Cai Z, et al. Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic flap survival in rats. Plast Reconstr Surg 2003;112:556–64.

15. Machens HG, Salehi J, Weich H, Münch S, Siemers F, Krapohl BD, et al.

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Angiogenic effects of injected VEGF165 and sVEGFR-1 (sFLT-1) in a rat flap model. J Surg Res 2003;111:136–42.

16. Shenaq SM, Rabinovsky ED. Gene therapy for plastic and reconstructive surgery. Clin Plast Surg 1996;23:157–71.

17. Takeshita S, Isshiki T, Ochiai M, Eto K, Mori H, Tanaka E, et al. Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia. Circulation 1998;98:1261–3.

18. Mäkinen TJ, Lankinen P, Pöyhönen T, Jalava J, Aro HT, Roivainen A. Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus. Eur J Nucl Med Mol Imaging 2005;32:1259–68.

19. Tonken HP, Zhang F, Sudekum AE, Siko PP, Newlin L, Partington MT, et al. Microvascular transplant of the gastrocnemius muscle in rats. Microsurgery 1993;14:120–4.

20. An YH, Friedman RJ. Animal models of orthopedic implant infection. J Invest Surg 1998;11:139–46.

21. Conterno LO, da Silva Filho CR. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev 2009;3:CD004439.

22. dos Reis JA Jr, de Carvalho FB, Trindade RF, de Assis PN, de Almeida PF, Pinheiro AL. A new preclinical approach for treating chronic osteomyelitis induced by Staphylococcus aureus: in vitro and in vivo study on photodynamic antimicrobial therapy (PAmT). Lasers Med Sci 2014;29:789–95.

23. Drago L, Romanò D, De Vecchi E, Vassena C, Logoluso N, Mattina R, et al. Bioactive glass BAG-S53P4 for the adjunctive treatment of chronic osteomyelitis of the long bones: an in vitro and prospective clinical study.

BMC Infect Dis 2013;13:584.

24. Bhattacharya R, Kundu B, Nandi SK, Basu D. Systematic approach to treat chronic osteomyelitis through localized drug delivery system: bench to bed side. Mater Sci Eng C Mater Biol Appl 2013;33:3986–93.

25. Uskoković V, Desai TA. Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. II. Antibacterial and osteoblastic response. J Biomed Mater Res A 2013;101:1427–36.

26. Tepper OM, Mehrara BJ. Gene therapy in plastic surgery. Plast Reconstr Surg 2002;109:716–34.

27. Zhang F, Yang F, Hu EC, Sones W, Lei M, Lineaweaver WC. Vascular endothelial growth factor gene therapy in improvement of skin paddle survival in a rat TRAM flap model. J Reconstr Microsurg 2005;21:391– 6.

28. de Freitas AL, Gomes HC, Lisboa BC, Arias V, Han SW, Ferreira LM. Effect of gene therapy with vascular endothelial growth factor after abdominoplasty on TRAM flap viability in a rat model. Plast Reconstr Surg 2010;125:1343–51.

29. Lubiatowski P, Gurunluoglu R, Goldman CK, Skugor B, Carnevale K, Siemionow M. Gene therapy by adenovirus-mediated vascular endothelial growth factor and angiopoietin-1 promotes perfusion of muscle flaps.

Plast Reconstr Surg 2002;110:149–59.

30. Neumeister MW, Song YH, Mowlavi A, Suchy H, Mathur A. Effects of liposome-mediated gene transfer of VEGF in ischemic rat gracilis muscle.

Microsurgery 2001;21:58–62.

31. Yang LW, Zhang JX, Zeng L, Xu JJ, Du FT, Luo W, et al. Vascular endothelial growth factor gene therapy with intramuscular injections of plasmid DNA enhances the survival of random pattern flaps in a rat model.

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32. Michail M, Jude E, Liaskos C, Karamagiolis S, Makrilakis K, Dimitroulis D, et al. The performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. Int J Low Extrem Wounds 2013;12:94–9.

33. Vinod Kumar BP. Osteomyelitis; an overview. Kerala Journal of Orthopaedics 2013;26:70–6.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel osteomyelit tedavisinde vasküler endotelial büyüme faktörü geni ile transfekte edilmiş transpozisyonel kas flebinin etkinliği Dr. Mahir Aliyev,1 Dr. Andaç Aykan,2 Dr. Muhitdin Eski,2 Dr. Nuri Arslan,3 Dr. Bülent Kurt,4 Dr. Mustafa Şengezer2 Asker Hastanesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, Bakü, Azerbaycan Gülhane Askeri Tıp Akademisi, Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, Ankara 3 Gülhane Askeri Tıp Akademisi, Nükleer Tıp Anabilim Dalı, Ankara 4 Gülhane Askeri Tıp Akademisi, Patoloji Anabilim Dalı, Ankara 1 2

AMAÇ: Bu çalışma, vasküler endotelyal büyüme faktörünün (VEGF) kemik iyileşmesi ve formasyonu üzerine anjiyogenetik ve indükleyici etkisine dayanarak, deneysel olarak oluşturulmuş osteomyelitte VEGF gen uygulamasının etkinliğini araştırmak için dizayn edildi.

GEREÇ VE YÖNTEM: Bu amaçla 32 adet erkek Sprague-Dawley cinsi sıçanın sol tibiasında osteomyelit oluşturuldu ve denekler dört eşit gruba ayrıldı. Birinci grupta (kontrol grubu, n=8) dört hafta süre ile hiçbir tedavi uygulanmadı. İkinci grupta (n=8) dört hafta antibiyotik tedavisi uygulandı. Üçüncü grupta (n=8) proksimal pediküllü medial gastroknemius kas flebi osteomyelit alanına transpoze edildi ve dört hafta antibiyotik tedavisi uygulandı. Dördüncü grupta (n=8) ise proksimal pediküllü medial gastroknemius kas flebi osteomyelit alanına transpoze edildikten sonra plazmid içinde VEGF DNA’sı kas içine enjekte edildi ve dört hafta antibiyotik tedavisi uygulandı. Tüm gruplarda vücut ısısı, kan beyaz küre sayısı incelendi, osteomyelit oluşturulan kemikler radyolojik ve histolojik açıdan değerlendirildi.

BULGULAR: Vücut ısısı ve lökositoz değerleri kontrol grubunda sürekli yüksekken, ikinci, üçüncü ve dördüncü gruplarda ise tedavinin üçüncü haftasında normal seviyelere döndüğü bulundu. Radyolojik ve histolojik değerlerin toplam skorlarının istatistiksel analizinde 1-3, 1-4, 2-3, ve 2 ile 4. gruplar arasında anlamlı fark tespit edildi (p<0.05). Radyolojik parametrelerden sadece apse ve sekestrum, histolojik parametrelerden ise sadece apse oluşumu açısından dördüncü grup ve diğer gruplar arasında anlamlı fark saptandı (p<0.05).

TARTIŞMA: Elde edilen bulgular, VEGF geni ile transfekte edilmiş kas flebinin, deneysel olarak, osteomyelit tedavisinde etkin olduğunu göstermiştir.

Anahtar sözcükler: Gastrokinemius; kas flebi; osteomyelit; transfeksiyon; VEGF; VEGF geni.

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doi: 10.5505/tjtes.2015.37888

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EXPERIMENTAL STUDY

Hemostatic efficacy of local chitosan linear polymer granule in an experimental sheep model with severe bleeding of arteria and vena femoralis Gürkan Ersoy, M.D.,1 Ülkümen Rodoplu, M.D.,2 Osman Yılmaz, M.D.,3 Necati Gökmen, M.D.,4 Alper Doğan, M.D.,5 Özgür Dikme, M.D.,6 Aslı Aydınoğlu, M.D.,7 Okyanus Orhon, M.D.8 1

Department of Emergency Medicine, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

2

Family Physician (Private Doctor), İzmir-Turkey

3

Department of Laboratory Animals Science, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

4

Department of Anesthesiology and Reanimation, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

5

Department of Anesthesiology, Denizli State Hospital, Denizli-Turkey

6

Department of Emergency Medicine, İstanbul Training and Research Hospital, İstanbul-Turkey

7

Department of Emergency Medicine, Medical Park Hospital, İzmir-Turkey

Maritime Management, Salvage Master (Vessel Recovery, Wreck Removal for Ship) and Oil Spill Specialist, Oceangoing Watchkeeper, İstanbul-Turkey

8

ABSTRACT BACKGROUND: The aim of the present study was to evaluate the hemostatic effect of chitosan linear polymer in a sheep model with femoral bleeding.

METHODS: Following induction of anesthesia and intubation of sheep, groin injury was induced to initiate hemorrhage. Animals were randomly assigned to study and control groups. In the control group, absorbent pads were packed on the wound, and pressure was supplied by a weight placed over the dressing. In the study group, chitosan linear polymer was poured onto the bleeding site; absorbent pads and pressure were applied in the same manner. At 5-min intervals, bleeding was evaluated. Primary endpoint was time to hemostasis.

RESULTS: Bleeding had stopped by the 1st interval in 5 members of the study group, and by the 2nd interval in 1 member. One sheep was excluded. The bleeding stopped after the 1st interval in 1 member of the control group and after the 2nd interval in 4 members.

Bleeding stopped in 2 cases following ligation of the bleeding vessel. Hemostasis was achieved earlier in the study group, compared to the control group, and the difference was statistically significant.

CONCLUSION: Hemostasis was achieved earlier following application of chitosan linear polymer.

Keywords: Chitosan linear polymer; external bleeding; trauma; uncontrolled hemorrhage.

INTRODUCTION Uncontrolled hemorrhage continues to be the leading cause of death due to military trauma, and the second leading cause of death in a civilian setting. Bleeding treated with blood Address for correspondence: Gürkan Ersoy, M.D. Yeni Kale Mah., Dilmaç Sok., No: 10/5, Narlıdere 35330 İzmir, Turkey Tel: +90 505 - 525 14 14 E-mail: gurkan.ersoy@ymail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):215–223 doi: 10.5505/tjtes.2015.16689 Copyright 2016 TJTES

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transfusion comes with inherent risk of complication, as well as significant expense. Rapid and immediate intervention provided by the victim or an on-scene first-responder is one of the most effective means of reducing morbidity and mortality.

Even if bleeding is eventually controlled, sufficient blood loss leaves victims vulnerable to hypothermia, coagulopathy, infection, and multiple organ failure. Rapid hemostasis is essential as a strategy, not only for initial survival, but also for optimal recovery.[1–16] A recent review of autopsies of 982 combat deaths from Iraq and Afghanistan revealed that nearly 24% could have been prevented with effective treatment. Of those potentially preventable deaths, 85% occurred as a result of hemorrhage, 1/3 of which were compressible, 2/3 of which were not, em215

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phasizing the need for improvement in hemorrhage control therapy in the field and in combat hospitals.[17–20] In the past 1–15 years, significant research has been invested in developing new hemostatic agents to rapidly and securely stop severe incompressible bleeding that cannot be controlled with standard gauze dressing or tourniquet placement. Although tourniquets are vital in control of certain extremity injuries, efficacy in treating wounds in areas such as the neck, abdomen, or groin is limited or nil. When the source of bleeding is in any such area, very little can be done on the battlefield or in the street to control the hemorrhage.

In contrast, bleeding from an extremity can potentially be controlled by direct compression and application of dressing by the soldier or first-responder. In response, hemostasis research has been a major emphasis of cooperative efforts by military and civilian trauma researchers of different countries.

[1,6,7] The need for hemostatic agents is greater in the event of large-scale disaster such as terrorist attack, bombing, or devastating earthquake, though in such austere conditions, proper hemostasis of all those wounded is often impossible to achieve.[1–5,8–11,14–16,18,20] The aim of the present study was to test the hemostatic effect of chitosan linear polymer and compression, compared with standard gauze dressing and compression in an experimental young sheep model with severe bleeding of femoral artery and vein. The hypothesis was that chitosan linear polymer would stop the bleeding more quickly and effectively than the standard treatment.

MATERIALS AND METHODS The University of Dokuz Eylül, institutional review board for the care and use of animals approved the present study. Research was conducted in compliance with the Animal Welfare Act and other national statutes and regulations relating to animals and experiments involving animals. The study adhered to the principles stated in the Guide for the Care and Use of Laboratory Animals.

Study design The present study was performed in the Laboratory of Animal Sciences of the University of Dokuz Eylül, School of Medicine, İzmir, Turkey with the collaboration of the departments of emergency medicine, anesthesiology, and intensive care.

As no universally accepted animal model to observe the hemostatic effects of a new promising local hemostatic agent presently exists, the following references were used with a few modifications.[1,10,15] The design implemented was unblinded and randomized, with an accepted swine groin injury model (though juvenile sheep were used). The efficacy of 2 treatments for surgically created, lethal, groin arterial and venous bleeding injury were tested. Treatment consisted of chitosan 216

linear polymer (Celox™; MedTrade Products Ltd., Crewe, UK) granule and compression. The control group was treated only with standard gauze and compression to the site of injury.

Animal Subjects Fourteen young Kıvırcık sheep of both genders were purchased from the Bulut sheep farm in Kemalpaşa, İzmir. Mean weight was 31.8±1.9 kg (range 30–34 kg). No pilot study was conducted. All were fed on a standard diet and observed for at least 1 week to ensure good state of health. Food was withheld the night before the experiment, though free access to water was permitted. Animals were maintained on a 12-h light/dark cycle at a room temperature of 20–22°C. Regarding the modifications presently implemented, young sheep were utilized instead of swine, as swine are quite difficult to procure, due to religious reasons and recent cases of trichinosis. Sheep are docile and large, facilitating surgical manipulation, and physiology is similar to that of humans. Sheep have been well-established as models of choice in the field of heart pathology, owing to similarities to humans in heart size and hemodynamic flow parameters.[21–23]

Study Protocol The present study was carried out in the Therapy Pet Hospital in İzmir, as the physical and architectural facilities of the present research center were inadequate.

Anesthesia was induced with intramuscular injection of ketamine hydrochloride (10 mg/kg), xylazine (0.15 mg/kg), and inhaled isoflurane (4–5%). After intubation, isoflurane concentration was reduced to 0.5–1% for the remainder of the experiment. Each animal was placed in the supine position on the operating table and allowed to breathe spontaneously using a mixture of 21% oxygen and air administered through an anesthesia ventilator (Model 84, M1166A; Hewlett Packard, Palo Alto, CA, USA). The right carotid artery and a branch of the external jugular vein were cannulated with 16-gauge intravenous catheter and 9-F introducer sheath, respectively, using a cut-down technique. Catheters were attached to a Viridia CMS hemodynamic monitoring system (Hewlett Packard, Palo Alto, CA, USA) for continuous monitoring of carotid artery pressure and heart rate. Each intravenous catheter was continuously flushed with 0.9% saline solution (5 mL/h) to maintain patency (Figures 1a–c).

Measurements Mean arterial pressure, heart rate, pH, PaCO2, PaO2, serum lactate, glucose, sodium, base deficit, hematocrit, hemoglobin, and rectal core temperature were measured every 5 minutes for the first 15 minutes, and every 15 minutes thereafter.

Arterial blood samples, (except lactate levels) were analyzed with Irma Trupoint Blood Analysis System (ITC Medical Supplies, Inc., San Francisco, CA, USA). Whole blood lactate levUlus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

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(a)

(a)

(b)

(b)

(c)

(c)

Figure 1. (a) Cannulation of intubated sheep. (b) Intubated and cannulated sheep. (c) Sheep under anesthesia.

Figure 2. (a, b) Incised and active bleeding in the groin site of sheep. (c) Chitosan linear polymer on cut area, with no active bleeding.

els were analyzed using YSI Sport 1500 lactate analyzer (YSI, Inc., Yellow Springs, OH, USA) with a cell lysing agent added to the buffer. Prior to blood analysis, the analyzer was calibrated with standard solutions.

induced to produce uncontrolled hemorrhage, as described by Alam et al.[15,16] Injury included dissection of proximal thigh soft tissues (skin, quadriceps, and adductor muscles) and later, complete division of dissected femoral artery and vein just below the inguinal ligament. This was achieved by incising the vessels with a sharp no. 22 scalpel. After 30 seconds of free bleeding (simulating the response time of the helper), the animals were randomized into 2 groups (Figure 2a, b).

Induction of Uncontrolled Hemorrhagic Shock A large area of the groin was shaved with an electric razor and cleansed with povidone-iodine. Complex right groin injury was Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

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Group 1. Control group (compression only) (n=7) Group 2. Study group (chitosan linear polymer+compression) (n=7) In both groups, excess blood was evacuated from the wound with gauze, without dislodging the clot at the vascular injury site after the cut. In the study group, 15 g of chitosan linear polymer (1 package), was poured over the vascular injury site so as to completely cover the transected femoral vessels (Figure 2c), after which the wound was packed with 8x8-cm absorbent gauze (code EES110; Kuteks Sanayii, İzmir, Turkey).

Following this, a 5-kg scale weight was attached to achieve a standard level of compression. As application of circumferential compressive dressing would not have been appropriate to the type of injury, gauze was used to cover the wound, like a blanket (Figure 3a, b). At 5-min intervals, the bleeding from the site was evaluated by an unaffiliated and unblinded emergency physician with a stopwatch, who reported whether or not it had stopped. Every 5 minutes, scale weight and gauze were removed, and hemostasis was assessed (Figure 4). If the bleeding had stopped, the test was scored as “passed at 5th minute.” If the bleeding continued, the same quantity of chito-

(a)

san linear polymer granule and the same amount of compression were similarly applied for an additional 5 minutes. If the bleeding stopped after the second application, the test was scored as “passed at 10th minute.” If the bleeding continued after the second application, a third trial of the same procedure was repeated for a final 5 minutes. If the bleeding had stopped by the final assessment, the test was scored as “passed at 15th minute.” If hemostasis had not been achieved by the third application, the test was scored as “failed,” and the bleeding was stopped by ligation of the vessel. Failure of hemostasis was defined as blood pooling outside of the wound.

In the control group, the same procedures were performed, with the exception of chitosan linear polymer application.

Hemostasis was similarly assessed at the 5th, 10th, and 15th minutes after removal of compression.

Primary outcome was time to hemostasis. At the end of the 15th minute, the study was finalized, but intubation was maintained for an additional 3 hours in order to observe the hemostatic status of the cut area. Following this, the sheep were extubated and transported back to the farm at which they had been purchased. Fifteen days later, the animals were revisited.

All were alive, and no complications were observed. After all were sacrificed, 5x5-cm samples of skin were excised to aid in future studies of local histopathological effects of chitosan linear polymer, prior to the animals being sold to butchers.

Resuscitation Protocols To simulate the austere battlefield environment, the volume of resuscitation fluid was limited to 500 mL of Haemaccel™ (Polygeline 17.5 g/500 mL, Dem İlaç, İstanbul, Turkey), which was intravenously administered. The infusion was initiated 15 minutes after the induction of injury (simulating delay in establishing intravenous access).

Data Analysis Physiologic variables were analyzed using SPSS software for

(b)

Figure 3. (a, b) Application of scale weight over bleeding groin area.

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Figure 4. Formation of clot (chitosan linear polymer and blood).

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Table 2. Timetable for the hemostasis

Study group

Control group

Bleeding stopped Bleeding stopped The vessel needed Bleeding stopped Bleeding stopped The vessel needed in the first trial in the second trial to be sutured in the first trial in the second trial to be sutured

+ + 1st sheep 2nd sheep executed + 3rd sheep

+

4 sheep th

+

+ +

5th sheep + + 6th sheep

+

+

7th sheep

+

+

Windows (version 10.0; SPSS Inc., Chicago, IL, USA). Hemodynamic data, and blood gas and temperature results were expressed as means±SD. Mann-Whitney U test was used for group comparison, and p<0.05 was considered significant.

RESULTS No complications were observed in the execution of study protocol. No mortality was observed in the 14 juvenile sheep at the end of the study (180th minute). In 1 sheep in the control group, tracheotomy was successfully performed after intubation attempts were unsuccessful. One sheep from the treatment group was excluded after severe bleeding could not be induced.

Achievement of Hemostasis While hemostasis was achieved in the first interval in 5 of 7 sheep in the treatment group, it was achieved in only 1 sheep in the first interval in the control group. Hemostasis was achieved in the second interval in 4 sheep in the control group (Table 1). Difference in time to hemostasis between groups was statistically significant (p<0.05).

Monitorized Physiological Parameters Difference between variables (MAP, heart rate, hemoglobin, hematocrit, pH, PaCO2, PaO2, blood lactate levels, oxygen saturation, and rectal temperature) between the groups was not statistically significant (p>0.05) (Table 2).

DISCUSSION Results of the present study demonstrate that application of chitosan linear polymer granule and compression of the bleeding femoral artery and vein significantly reduced time to hemostasis, compared to the control group.

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so when applied by non-medical personnel. When additional circumstances are present, such as wounds in places not amenable to tourniquet application and inability to hold pressure for extended periods of time, challenges to hemostatic agent application are daunting. The aim of the present study was to develop a safe and effective treatment that would address a number of unique challenges experienced on the battlefield and in major civilian traumas, as the use of tourniquet, not always effective, may cause complications and is not without controversy.[2,3,7,18–20] While many local hemostatic agents have been tested, no clear consensus exists regarding optimal hemorrhage control strategy for external bleeding.[1,4,8,9,13–17,20,24–30] However, Pusateri and Grissom[10,19] outlined ideal qualities of hemostatic agents for prehospital and battlefield use.

The focus of the present study was on a granular hemostatic agent heavy enough to be poured into the wound without being rapidly flushed away by ongoing bleeding or easily blown away in adverse weather conditions. Product contact with site of bleeding and conformance to the wound were important priorities. Recognizing the potential limited access to additional product in emergency evacuation situations, it was likewise important that the product could be re-applied if bleeding recurred.[1,3,13,15,16, 21–28,31–33] While some reports on human use have been published, live tissue studies and animal trials have been highly encouraging.

Chitosan linear polymer has a long shelf life and requires no special assembly (or mixing of components) at the time of application. It has reportedly been effectively used to control major arterial bleeding, is non-allergenic, can be used effectively at temperature extremes, doesn’t generate heat, is lightweight, portable, and easy to administer without specialized training, and is low in cost. Chitosan linear polymer is available in granular form that gels to conform to the wound once poured over the bleeding site, and can be easily removed. It is heavy enough to be poured into the wound without being rap219

Ersoy et al. Hemostatic efficacy of “chitosan linear polymer” (CeloxTM)

Table 2. The list of the monitorized physiological parameters Parameters

Time (min)

Mean arterial pressure (mmHg)

Baseline value

Following dissection

Experimental groups Control group

Study group

95±28

95±17

189±259

82±35

5 minutes

90±13

78±37

10th minutes

91±17

89±15

15 minutes

90±17

62±44

30th minutes

95±14

48±46

45 minutes

th

th

28±50

11±29

Heart rate (beat/minutes)

Baseline value

92±24

86±21

Following dissection

th

94±14

81±40

5th minutes

92±21

89±15

10 minutes

88±17

80±15

15 minutes

90±16

56±39

30th minutes

80±14

40±38

th th

24±42

14±37

Hemoglobin (g/dL)

45 minutes Baseline value

7.3±1.7

6.0±2.8

Following dissection

th

6.9±2.2

4.9±3.9

5th minutes

4.5±3.3

4.1±2.9

10 minutes

4.5±2.0

10.6±6.8

15th minutes

4.1±2.9

4.9±2.4

30 minutes

3.5±3.4

2.9±3.8

45th minutes

13.9±37.0

0.7±1.9

Hematocrit (%)

Baseline value

21.7±4.5

16.9±6.4

Following dissection

th

th

20.6±6.5

16.3±8.8

5th minutes

16.2±5.7

15.2±4.0

10 minutes

14.6±2.58

31.1±20.2

15th minutes

25.1±24.5

14.5±7.2

30 minutes

14.8±5.2

10.2±10.6

45th minutes

2.7±7.2

2.1±5.7

th

th

pH

Baseline value

6.35±2.80

7.39±0.07

Following dissection

7.38±0.11

4.21±3.93

5 minutes

7.37±0.10

7.42±0.10

10 minutes

7.42±0.09

7.43±0.09

15th minutes

7.40±0.06

6.34±2.80

30 minutes

7.39±0.04

4.26±3.99

45th minutes

1.06±2.82

1.06±2.80

th

th

th

Partial carbon dioxide pressure(mmHg)

Baseline value

38±18

43±6

Following dissection

47±12

27±26

5th minutes

42±7

36±5

10th minutes

40±10

40±13

15th minutes

44±7

39±19

30th minutes

42±7

23±25

45 minutes

5±14

6±17

th

220

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Ersoy et al. Hemostatic efficacy of “chitosan linear polymer” (CeloxTM)

Table 2. The list of the monitorized physiological parameters (Cont) Parameters

Time (min)

Partial oxygen pressure (mmHg)

Baseline value

Following dissection

Experimental groups Control group

Study group

285±200

258±227

214±141

215±169

5th minutes

299±149

238±181

10th minutes

287±191

215±154

15th minutes

330±209

237±207

30 minutes

142±146

134±175

45th minutes

14±38

58±154

th

Blood lactat levels

Baseline value

1.49±1.60

0.85±0.62

Following dissection

1.05±1.23

0.73±0.55

5 minutes

1.80±1.48

0.76±0.33

10th minutes

1.49±1.28

0.77±0.45

15 minutes

1.37±1.60

0.31±0.32

30th minutes

1.32±1.25

0.34±0.35

45 minutes

th

th

0.04±0.12

0.24±0.44

Saturation (%)

Baseline value

83±37

83.72±37.18

Following dissection

th

96±4

96.88±4.39

5th minutes

98±2

98.48±2.60

10 minutes

98±2

98.05±2.13

15th minutes

98±2

98.52±2.17

th

30 minutes

95±3

95.61±3.97

45th minutes

13±37

13.98±37.00

th

idly flushed away by ongoing bleeding or easily blown away in adverse weather conditions.[6,13,14,17,19,24,25,27,28,31,32] These properties approximate ideal qualities of hemostatic agents for prehospital and battlefield use.[10–19] Various hemostatic products have been tested in a number of animal models, ranging from liver to complex groin injuries, with disparate results, depending on the model and the standard of cost-effectiveness. It can be argued that no agent has met all ideal criteria, though chitosan linear polymer may be a candidate.[6,7,10,13,17,19,24,25,27,28,31,32] The groin injury model presently utilized took into account realities of modern combat injuries, and has previously been tested.[1–3,13,15,16,27] Salient features include lethal but potentially salvageable injury, anatomic location unsuitable for application of tourniquet, combined arterial and venous injuries with uncontrolled hemorrhage, large soft tissue injury, realistic delays in application of dressing and start of resuscitation, and resuscitation approach consistent with new recommendations for the military. However, it should be emphasized that certain modifications were made. First, although similar studies used swine, the present was only the second to be conducted on young sheep.[21,24,25,27,28,31] In the majority of Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

studies, compression over the bleeding site was performed with finger pressure. In an effort to determine how a standard level of pressure could be achieved by use of manual compression, the technique was presently modified by placing a scale weight (weighing 5 kg) over the gauze on the bleeding site, a modification used for the second time.[1–3] In a recent paper by Ward et al.[26] a similar method of achieving standard pressure was reported. To standardize the amount of pressure applied on the wound, a pediatric blood pressure cuff was used. The aim in both studies was to maintain a standard amount of pressure over the bleeding site. It is presently believed that the method described may be more efficient than that used in the present study, as more diffuse and stable pressure could be transferred to the bleeding site.[8,15] Few studies concerning hemostatic effect of chitosan have been reported. Hamid et al.[21] conducted a study with Persian Gulf Chitosan (PGC) in a carotid puncture hole sheep model, and the results suggested that PGC was safe and effective means of achieving hemostasis. This was the 1st such study conducted with sheep, and the present was the 2nd.

Kozen et al.[28] compared Celox™ with HemCon and QuickClot in a lethal hemorrhagic groin injury porcine model. Celox™ improved hemorrhage control and survival, and has 221

Ersoy et al. Hemostatic efficacy of “chitosan linear polymer” (CeloxTM)

been accepted as a viable alternative for the treatment of severe hemorrhage. Also reported was the lifesaving use of Celox™ in 2 patients undergoing cardiothoracic surgery during which conventional techniques failed. This was the first reported surgical use.[34] However, it is difficult to understand how Celox™ was used internally, as it is indicated for external use only, though the authors may have been urged to use it due to force major.

Though use is not frequently described, it may be wise to keep local hemostatic agents, such as chitosan linear polymer, on hand, to be used in the event of emergencies including mass casualty events, such as those caused by terrorism, natural disasters, devastating earthquakes, and industrial accidents.

Hemostatic agents may also aid in patient triage, temporizing otherwise lethal hemorrhage.[24] After more human studies have been conducted, these agents may be used as a first aid agent in homes, as well.[33] However, more studies are needed before these agents can be recommended for general use.

Limitations It must be noted that the study design precluded the need for blinded investigation. The present study was also limited by the lack of universally accepted optimal model for comparison of hemostatic effects produced by wound dressings. It should be emphasized, however, that the model used was not intended to precisely mimic a clinical situation, but was meant to serve as a platform for the evaluation of dressings used to control high-pressure arterial and venous profuse bleeding.

The bleeding source was directly visible and accessible, unlike those likely to occur in the field. Finally, a scale weight was used for compression, though manual compression is generally provided in real-life situations. Complete transection of the femoral vessel could have caused retraction of the artery with resultant vasospasm that artificially contributed to improved hemostasis. Removal of a portion of the anterior arterial wall would eliminate the effect of arterial retraction.

However, patients with penetrating injuries to large vessels more commonly have complete transection of vascular structures, not glancing injures that blow out only 1 side of the vessel wall. Study protocol and parameters may be improved by the investigation of clot formation over the artery and vein. Markedly decreased fibrinolytic activity, and increased platelet number and adhesiveness in sheep may affect the hemostatic system. These factors could increase the tendency toward hypercoagulability.[22,23]

Conclusion In the present experimental young sheep model with severe bleeding of arteria/vena femoralis, application of chitosan linear polymer granule and compression over the bleeding site significantly reduced time to hemostasis, compared to the control group.

While further translational research is required, one can 222

imagine this intervention providing a prehospital hemostatic bridge for severely bleeding casualties, who would otherwise bleed to death in the field, allowing for arrival to a surgical treatment facility.

Acknowledgement We would kindly like to thank Mr. Burhan YILMAZ (owner of the Therapy Pet Hospital), who enabled us to use all hospital facilities. We would also like to thank Professor Dr. Cem BEDİZ, M.D., et al. (Dokuz Eylül University Faculty of Medicine, Department of Physiology) for measuring serum lactate levels.

Conflict of interest: None declared.

REFERENCES 1. Ersoy G, Kaynak MF, Yilmaz O, Rodoplu U, Maltepe F, Gokmen N. Hemostatic effects of microporous polysaccharide hemosphere in a rat model with severe femoral artery bleeding. Adv Ther 2007;24:485–92.

2. Ozgur D, Gurkan E, Osman Y, Ozlem D, Necati G. The Effect of Application of Local Oxidised Cellulose Powder on Hemostasis Time in a Rat Model With Femoral Artery Bleeding. Acta Medica Mediterranea 2015,31:179–82.

3. Aydinoglu A, Ersoy G, Dogan A, Akay H, Yilmaz O, Gokmen N. Hemostatic effect of microporous polysaccharide hemosphere in a heparinized rat model with femoral artery bleeding. European Journal of Emergency Medicine 2008;15:286–306.

4. Eryilmaz M, Ozer T, Menteş O, Torer N, Durusu M, Günal A, et al. Is the zeolite hemostatic agent beneficial in reducing blood loss during arterial injury? Ulus Travma Acil Cerrahi Derg 2009;15:7–11.

5. Eryilmaz M, Mentes O, Ozer MT, Ersoy G, Durusu M, Rodoplu U, et al. Current principles of use of topical hemostatic agents in trauma cases.

Turkish Journal of Emergency Medicine 2007;7:136–43.

6. Bulger EM, Snyder D, Schoelles K, Gotschall C, Dawson D, Lang E, et al. An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma. Prehosp Emerg Care 2014;18:163–73.

7. Taillac PP. Stop the bleeding. New external hemorrhage control evidencebased guideline. JEMS 2014;Suppl:18–21.

8. Velmahos GC, Tabbara M, Spaniolas K, Duggan M, Alam HB, Serra M, et al. Self-expanding hemostatic polymer for control of exsanguinating extremity bleeding. J Trauma 2009;66:984–8.

9. Kilbourne M, Keledjian K, Hess JR, Scalea T, Bochicchio GV. Hemostatic efficacy of modified amylopectin powder in a lethal porcine model of extremity arterial injury. Ann Emerg Med 2009;53:804–10.

10. Pusateri AE, Holcomb JB, Kheirabadi BS, Alam HB, Wade CE, Ryan KL. Making sense of the preclinical literature on advanced hemostatic products. J Trauma 2006;60:674–82.

11. Brown MA, Daya MR, Worley JA. Experience with chitosan dressings in a civilian EMS system. J Emerg Med 2009;37:1–7.

12. Recinos G, Inaba K, Dubose J, Demetriades D, Rhee P. Local and systemic hemostatics in trauma: a review. Ulus Travma Acil Cerrahi Derg 2008;14:175–81.

13. Özlem K, Fatma Ö, Betül ÇE, Naciye İB, Deniz S. Hemostatic effect of a chitosan linear polymer (Celox®) in a severe femoral artery bleeding rat model under hypothermia or warfarin therapy. Ulus Travma Acil Cerrahi Derg 2011;17:199–204.

14. Kheirabadi BS, Edens JW, Terrazas IB, Estep JS, Klemcke HG, Dubick MA, et al. Comparison of new hemostatic granules/powders with cur-

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15. Alam HB, Chen Z, Jaskille A, Querol RI, Koustova E, Inocencio R, et al.

Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin injury in Swine. J Trauma 2004;56:974–83.

16. Alam HB, Uy GB, Miller D, Koustova E, Hancock T, Inocencio R, et al. Comparative analysis of hemostatic agents in a swine model of lethal groin injury. J Trauma 2003;54:1077–82.

17. Bennett BL, Littlejohn L. Review of new topical hemostatic dressings for combat casualty care. Mil Med 2014;179:497–514.

18. Kragh JF Jr, Nam JJ, Berry KA, Mase VJ Jr, Aden JK 3rd, Walters TJ5, et al. Transfusion for shock in US military war casualties with and without tourniquet use. Ann Emerg Med 2015;65:290–6.

19. Grissom TE, Fang R. Topical hemostatic agents and dressings in the prehospital setting. Curr Opin Anaesthesiol 2015;28:210–6.

20. Pekcan M, Eryilmaz M. New hemostatic agents to be used in trauma cases. Scientific literature of GESDAV 2006;1:3–55.

21. Hamid M, Nakisa AM, Ali M, Farzin H. Preparation of chitosan derived from shrimp’s shell of Persian Gulf as a blood hemostasis agent. Iranian Polymer Journal 2002;11:63–8.

22. Gajewski J, Povar ML. Blood coagulation values of sheep. Am J Vet Res 1971;32:405–9.

23. Scheerlinck JP, Snibson KJ, Bowles VM, Sutton P. Biomedical applications of sheep models: from asthma to vaccines. Trends Biotechnol 2008;26:259–66.

24. Sohn VY, Eckert MJ, Martin MJ, Arthurs ZM, Perry JR, Beekley A, et al. Efficacy of three topical hemostatic agents applied by medics in a lethal groin injury model. J Surg Res 2009;154:258–61.

25. Burgert J, Gegel B, Neal AR, Kammer KE, Paul ME, Schwartz DJ, et al.

The effects of arterial blood pressure on rebleeding when BleedArrest, Celox and TraumaDex are used in a porcine model of lethal femoral in-

jury. Mil Med 2012;177:340–4.

26. Ward KR, Tiba MH, Holbert WH, Blocher CR, Draucker GT, Proffitt EK, et al. Comparison of a new hemostatic agent to current combat hemostatic agents in a swine model of lethal extremity arterial hemorrhage.

J Trauma 2007;63:276–84.

27. Littlejohn LF, Devlin JJ, Kircher SS, Lueken R, Melia MR, Johnson AS. Comparison of Celox-A, ChitoFlex, WoundStat, and combat gauze hemostatic agents versus standard gauze dressing in control of hemorrhage in a swine model of penetrating trauma. Acad Emerg Med 2011;18:340– 50.

28. Kozen BG, Kircher SJ, Henao J, Godinez FS, Johnson AS. An alternative hemostatic dressing: comparison of CELOX, HemCon, and QuikClot.

Acad Emerg Med 2008;15:74–81.

29. Shanmugam V, Robinson MH. Case report of uncontrollable pelvic bleeding-managed by a previously unreported method (QuikClot).

Colorectal Dis 2009;11:221–2.

30. Yüce S, Çandirli C, Yenidünya S, Muslu B. New hemostatic agent: the effect of Ankaferd Blood Stopper on healing wounds in experimental skin incision model. Turk J Med Sci 2014;44:288–94.

31. Burgert JM, Gegel BT, Austin R 3rd, Davila A, Deeds J, Hodges L, et al.

Effects of arterial blood pressure on rebleeding using Celox and TraumaDEX in a porcine model of lethal femoral injury. AANA J 2010;78:230–6.

32. Official web site for CeloxTM. http://www.celoxmedical.com. (Accessed March 08, 2015).

33. Markenson D, Ferguson JD, Chameides L, Cassan P, Chung KL, Epstein J, et al. Part 17: first aid: 2010 American Heart Association and American Red Cross Guidelines for First Aid. Circulation 2010;122(18 Suppl 3):934–46.

34. Millner RW, Lockhart AS, Bird H, Alexiou C. A new hemostatic agent: initial life-saving experience with Celox (chitosan) in cardiothoracic surgery. Ann Thorac Surg 2009;87:13–4.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Ciddi femoral arter ve ven kanaması olan deneysel koyun modelinde, lokal “chitosan linear polymer” granül uygulamanın, hemostatik etkinliği Dr. Gürkan Ersoy,1 Dr. Ülkümen Rodoplu,2 Dr. Osman Yılmaz,3 Dr. Necati Gökmen,4 Dr. Alper Doğan,5 Dr. Özgür Dikme,6 Dr. Aslı Aydınoğlu,7 Dr. Okyanus Orhon8 Dokuz Eylül Üniversitesi Tıp Fakültesi Hastanesi, Acil Tıp Anabilim Dalı, İzmir Aile Hekimliği Uzmanı, İzmir Dokuz Eylül Üniversitesi Tıp Fakültesi Hastanesi, Deney Hayvanları Bilimi Anabilim Dalı, İzmir 4 Dokuz Eylül Üniversitesi Tıp Fakültesi Hastanesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İzmir 5 Denizli Devlet Hastanesi, Anestezi Kliniği, Denizli 6 İstanbul Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul 7 Medikal Park Hastanesi, Acil Tıp Anabilim Dalı, İzmir 8 Denizcilik Yöneticiliği, Gemi Kurtarma Uzmanı, Uzakyol Vardiya Zabiti (3. Kaptan), İstanbul 1 2 3

AMAÇ: Femoral kanamalı, deneysel koyun modelinde, “chitosan linear polymer” uygulamasının, hemostatik etkinliğini araştırmayı amaçladık.

GEREÇ VE YÖNTEM: Koyunların anestezi ve entübasyonunu takiben, kanamayı başlatmak için kasık yaralanması oluşturuldu. Denekler, çalışma ve kontrol grupları şeklinde randomize edildiler. Kontrol grubunda, kanama alanı üstüne absorban pedler yerleştirildi ve üstüne ağırlık konarak bası oluşturuldu. Çalışma grubunda ise kanama alanına “chitosan linear polymer” döküldü, absorban pedler ve ağırlık aynı şekilde yerleştirildi. Her beş dakikada bir kanama değerlendirildi. Ana çıktı kanama duruncaya kadar geçen zamandı.

BULGULAR: Çalışma grubunda kanama, beş denekte ilk, diğer denekte ise ikinci girişimde durdu. Bir denek çalışmadan çıkarıldı. Kontrol grubunda, kanama bir denekte ilk girişimde, dört denekte ikinci girişimde, iki denekte ise, yerin dikilmesinden sonra durdu. Hemostaz çalışma grubunda, kontrol grubuna oranla, daha erken dönemde sağlandı ve her iki grup arasındaki fark, istatistiksel olarak anlamlı idi.

TARTIŞMA: Bu koyun modelinde “chitosan linear polymer” uygulaması hemostazı kontrol grubuna göre daha kısa sürede sağladı.

Anahtar sözcükler: Eksternal kanama; kitosan lineer polimer; kontrolsüz kanama; travma.

Ulus Travma Acil Cerrahi Derg 2016;22(3):215–223

doi: 10.5505/tjtes.2015.16689

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223

EXPERIMENTAL STUDY

Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats Zhang Haijun, M.D., Yu Yonghui, M.D., Chai Jiake, M.D. Department of Burn and Plastic Surgery, First Affiliated Hospital of PLA General Hospital, Beijing, China

ABSTRACT BACKGROUND: Severe thermal trauma covering more than 30% of the total body surface area (TBSA) triggers a sustained pathophysiological response, which includes, but is not limited to, hypermetabolism, chronic inflammation, and severe skeletal muscle wasting. Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the functions of lncRNAs in the regulation of responses of skeletal muscle wasting after severe burn have remained untested.

METHODS: Presently examined were the expression profiles of lncRNAs and messenger RNAs (mRNAs) in skeletal muscle tissues of 3 pairs of burned rats at the early flow phase, compared with sham rats, using microarray. Each potential lncRNA-mRNA pair identified is a strong candidate in the definitive confirmation of the presence of specific lncRNA-mRNA interactions, thus providing a detailed picture of the pathogenesis of skeletal muscle wasting in burned rats.

RESULTS: LncRNA expression levels were compared among 3 injured tissues and matched normal tissues from microarray data. An average of 117 significantly differentially expressed lncRNAs (1.5-fold) were identified. Only 202 mRNAs were significantly upregulated or downregulated, an average of 92 mRNAs were upregulated in injured, compared to matched normal, tissues, while an average of 110 mRNAs) were downregulated.

CONCLUSION: Presently identified were lncRNAs differentially expressed in skeletal muscles of burned rats, compared to normal tissues. Regulatory pathways may be involved in the pathogenesis of skeletal muscle wasting. Each lncRNA-mRNA pair identified is a strong candidate for a future study to definitively confirm the presence of specific lncRNA-mRNA interactions, thus providing a more detailed picture of the pathogenesis of skeletal muscle wasting in burned rats.

Keywords: Burn; expression; LncRNAs; microarray; muscle wasting.

INTRODUCTION Injuries represent one of the most important public health problems in economically developing and developed countries.

Of the major types of injuries, burns contribute to more than 1% of the global burden of disease.[1–3] Burn injury is a primary cause of disability and mortality, with severe economic and social consequences. It can also lead to pain, as well as somatic and psychological complications.[1] Severe thermal trauma covering more than 30% of total body surface area (TBSA) triggers a sustained pathophysiological response, which includes, Address for correspondence: Chai Jiake, M.D. 51 Fucheng Road Beijing - China Tel: +86-10-6686-7972 E-mail: cjk304@126.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):224–232 doi: 10.5505/tjtes.2015.04831 Copyright 2016 TJTES

224

but is not limited to, hypermetabolism, chronic inflammation, marked elevations in peripheral catecholamines and cortisol levels, and severe skeletal muscle wasting.[2–4] Severe burn injuries lead to a prolonged hypercatabolic state resulting in dramatic loss of skeletal muscle mass.[5] As skeletal muscle accounts for over 50% of the dry weight of the body’s cells, its catabolism exerts a profound effect on the body’s metabolism as a whole.[6] The primary mechanisms underlying skeletal muscle wasting induced by severe burn include activation of ubiquitin-proteasome pathway,[7,8] myonuclear apoptosis,[9] mitochondrial dysfunction,[10] autophagy,[11] signaling pathways driving muscle inflammation, and protein metabolism.[5] Although the mechanisms of skeletal muscle wasting following severe burn are becoming increasingly clear, the mechanisms of transcriptional and/or post-transcriptional gene regulation remain unknown.

Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation.[12] LncRNAs have been implicated Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

in a wide range of developmental processes and diseases.[13] LncRNAs have emerged as key components of the address code, allowing protein complexes, genes, and chromosomes to be trafficked to appropriate locations, and subjected to proper activation and deactivation. LncRNA-based mechanisms control the fate of cells during development, and their dysregulation underlies some human disorders caused by chromosomal deletions and translocations.[14,15] LncRNAs are generally longer than 200 nucleotides. Recent studies have shown that lncRNAs may act as important cis- or trans-regulators in various biological processes.[16] Mutations in lncRNAs are associated with a wide range of diseases, including stress, and particularly cancers and neurodegenerative diseases.[17] However, the profiles of burn-related lncRNAs have yet to be documented. Recent studies have shown that transcription of the mammalian genome is not only pervasive, but also enormously complex. It is estimated that an average of 10 transcription units, the vast majority of which make lncRNAs, may overlap with each traditional coding gene. These lncRNAs include antisense, and intronic and intergenic transcripts, as well as pseudogenes and retrotransposons.[18] Presently examined are the expression profiles of lncRNAs and mRNAs in skeletal muscle tissues of 3 pairs of burned rats at the end of the shock phase, compared with sham rats, using microarray. Differentially expressed lncRNAs were then selected for target prediction with bioinformatics analyses.

To improve the accuracy of target prediction, differentially expressed mRNAs were combined with target prediction of differentially expressed lncRNAs. The predicted target genes from the above analyses were subjected to bioinformatics analyses,[19] including gene ontology analysis, pathway analysis, and network analysis. Analyzing potential molecular markers and the possible relationship between differentially expressed lncRNAs and protein-coding genes in skeletal muscles at the early flow phase in burned rats will provide further insights into the pathogenesis of skeletal muscle wasting in thermal trauma.

MATERIALS AND METHODS Sample Preparation The present study was approved by the Committee of Science and Technology of the First Affiliated Hospital of PLA General Hospital, in accordance with the protocol outlined in the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication no. 85-23, revised 1996).

Six adult male Wistar rats weighing 200–220 g each were purchased from the Chinese Medical Scientific Institute (Beijing, China). Rats were kept in controlled standard housing conditions with free access to standard laboratory food and water for a 7-day adaptation period before being randomly assigned to groups.

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After fur was clipped, a full thickness thermal injury of 30% of TBSA was inflicted by immersing the back of the trunk in 94°C water for 12 seconds. A weight- and time-matched sham-burn group (n=3) was treated in the same manner as the trauma group (n=3), with the exception of the immersion of the sham-burn animals in room temperature water.

During the post-burn period and following immersion, all rats were immediately dried, administered fluid (40 ml/kg of Ringer’s lactate solution, calculated by the Parkland formula), and housed in individual cages with free access to food and water.[9] On the third day following burn or sham injury, the animals were euthanized. Tibialis anterior muscles were harvested and stored at -80°C for RNA extraction.

LncRNA and mRNA Microarray Rat lncRNA array was designed for profiling lncRNA and protein-coding genes. Approximately 9,000 lncRNAs were selected from the NCBI Reference Sequence Database: all UCSC mRNA records and orthologs of rat lncRNAs. While probes for coding genes were printed once, probes for lncRNAs were printed 3 times. Probes for housekeeping genes and negative probes were printed multiple times to ensure hybridization quality.

RNA Labeling and Array Hybridization Sample labeling and array hybridization were performed according to Agilent One-Color Microarray-Based Gene Expression Analysis Protocol (Agilent Technologies, Inc., Santa Clara, CA, USA). Briefly, total RNA from each sample was linearly amplified and labeled with Cy3-UTP. Labeled cRNAs were purified using the RNeasy Mini Kit (Qiagen, Inc., Hilden, Germany). Concentration and specific activity of labeled cRNAs (pmol Cy3/μg cRNA) were measured using the NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, Inc., Waltham, MA, USA). One μg of each labeled cRNA was fragmented by adding 11 μl of 10×blocking agent and 2.2 μl of 25×fragmentation buffer. The mixture was then heated at 60°C for 30 min, and finally, 55 μl of 2×GE hybridization buffer was added to dilute the labeled cRNA. A total of 100 μl of hybridization solution was dispensed into the gasket slide and assembled onto the gene expression microarray slide. The slides were incubated at 65°C for 17 hours in an Agilent hybridization oven (Agilent Technologies, Inc., Santa Clara, CA, USA). The hybridized arrays were washed, fixed, and scanned using an Agilent DNA microarray scanner (part no. G2505C; Agilent Technologies, Inc., Santa Clara, CA, USA).

Data Analysis Agilent Feature Extraction software (version 11.0.1.1; Agilent Technologies, Inc., Santa Clara, CA, USA) was used to analyze the acquired array images. Quantile normalization and subsequent data processing were performed using GeneSpring GX version 12.0 software package (Agilent Technologies, Inc., Santa Clara, CA, USA). Following quantile normalization of the raw data, lncRNAs and mRNAs for which at least 3 out 225

Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

of 6 samples had flags in “Present” or “Marginal” (“All Targets Value”) were chosen for further data analysis.

Differentially expressed lncRNAs and mRNAs with statistical significance were identified using volcano plot filtering. Hierarchical clustering was performed using GeneSpring GX software (version 12.0; Agilent Technologies, Inc., Santa Clara, CA, USA).

Construction of the Coding-Non-Coding Gene Co-Expression Network To show that the lncRNAs directly regulated the expression of target mRNAs, lncRNA target predictions were superimposed onto the lncRNA-mRNA correlation network. The resulting network was defined as an lncRNA-mRNA regulatory

network. A direct connection was placed from an lncRNA to an mRNA using either a blue line (trans-interaction) or a red line (cis-interaction).

Statistical Analysis Results were expressed as mean±SD. Statistical analysis was performed using Student’s t-test for comparison of 2 groups in the microarray, and analysis of variance was used for multiple comparisons. In both cases, differences with p<0.05 were considered to be statistically significant. Statistical significance of microarray results was analyzed by fold change and Student’s t-test. False discovery rate was calculated in order to correct p values. The threshold value used to screen differentially expressed lncRNAs and mRNAs was a fold change ≥1.5 (p<0.05).

Table 1. Upregulated lncRNA profiles Probe name

p value

Fold change and regulation Absolute fold change ([T] vs [C])

Regulation ([T] vs [C])

Probe name

p value

Fold change and regulation Absolute fold change ([T] vs [C])

Regulation ([T] vs [C])

XR_007625_P1 0.042436516 1.513741298

up

S75669_P1

0.007335414 1.939438731

up

XR_008295_P1 0.006886517 1.608696682

up

S75669_P1

0.007335414 1.939438731

up

MRAK080815_P1 0.020947862 1.520309795

up

S75669_P1

0.007335414 1.939438731

up

XR_005515_P1 0.040546402 1.626680595

up

S75669_P1

0.007335414 1.939438731

up

XR_009083_P1 0.006434708 1.617928104

up

XR_009355_P1 0.048364759 1.556603421

up

XR_006772_P1 0.038080035 1.549397303

up

XR_005513_P1 0.006641351 1.75941563

up

XR_005733_P1 0.01100545 1.551780677

up

XR_006841_P1 0.028879691 1.564961501

up

XR_007062_P1 0.003142118 1.914118172

up

AY643514_P1

0.033154207 1.503992702

up

XR_007206_P1 0.024360851 2.084225919

up

AY643514_P1

0.033154207 1.503992702

up

MRAK142335_P1 0.043959593 1.955781634

up

XR_006694_P1 0.006682623 1.691703812

up

MRuc007guc_P1 0.026266496 1.93846981

up

MRAK053201_P1 0.049504017 1.694329931

up

XR_006148_P1 0.012795552 1.640795758

up

DQ832324_P1 0.01193803 1.604519178

up

AF332363_P1

up

XR_008093_P1 0.005252984 1.622082653

up

XR_007393_P1 0.042234037 1.836920259

up

XR_005488_P1 0.049406948 1.739175513

up

MRAK040107_P1 0.034288649 1.743452026

up

XR_009151_P1 0.034915223 1.514451804

up

MRAK040107_P1 0.034288649 1.743452026

up

XR_005800_P1 0.001871706 1.715524821

up

BC098776_P1 0.005731768 1.543092558

up

uc.152-_P1

0.04315685 1.713979119

up

XR_006678_P1 0.042567859 1.708809769

up

XR_008501_P1 0.023420274 1.61734673

up

MRAK012222_P1 0.018538406 1.592452676

up

XR_007720_P1 0.014669486 1.727730824

up

XR_006337_P1 0.023330015 1.736155055

up

XR_006550_P1 0.002260132 1.531738302

up

XR_007784_P1 0.010820094 1.541399506

up

XR_005754_P1 0.006875391 1.819631944

up

XR_006785_P1 0.009177714 1.647233223

up

XR_007321_P1 0.011698519 1.673666406

up

MRAK006088_P1 0.047430249 1.535065022

up

XR_008911_P1 0.014100815 1.593491511

up

MRAK006088_P1 0.047430249 1.535065022

up

MRAK004125_P1 0.012228179 1.50735389

up

MRAK032396_P1 0.002439049 1.745553893

up

BC168236_P1 0.033712827 2.592948166

up

MRAK032396_P1 0.002439049 1.745553893

up

MRAK032113_P1 0.025968499 1.865618242

up

XR_006529_P1 0.005485356 1.651250693

up

XR_007247_P1 0.013873027 1.574192895

up

MRAK145223_P1 0.028223934 1.904590841

up

AY383698_P1

0.042209102 1.525491351

up

XR_006328_P1 0.022030979 1.550920784

up

AY383698_P1

0.042209102 1.525491351

MRAK135387_P1 0.019185074 1.501364733

up

MRAK131727_P1 0.034235162 1.513193901

up

XR_005665_P1 0.041147848 2.239151018

up

XR_005772_P1 0.035771322 1.533147498

up

S75669_P1

up

D26496_P1

up

0.009779 1.767327041

0.007335414 1.939438731

0.043220295 1.510179878

up

Fold change cut-off: 1.5; #p value cut-off: 0.05; #Condition pairs: T vs C.

#

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Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

RESULTS Overview of Expression Profiles of lncRNAs From the lncRNA expression profiles, differentially expressed lncRNAs were found from among samples of skeletal muscles obtained from thermal rats (thermal group) and sham-burn rats (control group). Expression profiles of lncRNAs in paired samples were shown by calculating logfold change of the thermal group/the control group (T/C).

Agreement was formulated as follows: fold change cut-off was 1.5, and for any fold change, positive value indicated upregulation, while negative value indicated downregulation.

Log-fold change signified log2 value of absolute fold change.

Fold change and p values were calculated from the normalized expression.

LncRNA expression levels were compared among the 3 injured tissues and their matched normal tissues from the microarray data, and an average of 117 long lncRNAs that were significantly differentially expressed (1.5-fold) were identified.

Results demonstrated that a very large number of lncRNAs could be examined in normal and injured tissues, while only 117 of these were significantly upregulated (Table 1) or downregulated (Table 2), and could be used to discriminate skeletal muscles of burned rats from matched normal tissues.

Compared to the normal tissues, MRAK080917 (log2 fold change T/C=6.777752082) was most significantly downregulated, while BC168236 (log2 fold change T/C=2.592948166) was most significantly upregulated. It was determined that downregulated lncRNAs were more common than those that were upregulated.

Overview of mRNA Profiles Results demonstrated that tens of thousands of mRNAs could be examined in normal and injured tissues, but that only 202 mRNAs were significantly upregulated or downregulated. An average of 92 mRNAs were upregulated in the injured tissues (Table 3), compared to the matched normal ones, while an average of 110 mRNAs were downregulated (Table 4).

Table 2. Downregulated lncRNA profiles Probe name

p value

Fold change and regulation Absolute fold change ([T] vs [C])

Regulation ([T] vs [C])

Probe name

p value

Fold change and regulation Absolute fold change ([T] vs [C])

Regulation ([T] vs [C])

MRAK15842

5.30947E-05 2.397271208

down

uc.414+_P1

0.035614403 1.742281172

down

MRAK05384

0.047353911 1.826165856

down

XR_008292_

0.002067679 1.683021803

down

BC088246_P1 0.010256908 1.691622866

down

BC088244_P1 0.016885746 1.559107747

down

MRAK01357

0.049684039 2.110840155

down

XR_006390_

0.03336485 1.666808775

down

XR_005853_

0.012668374 1.995183722

down

XR_007170_

0.031927225 1.504417159

down

XR_007420_

0.044076153 1.932416621

down

MRAK01401

0.047898874 1.861431079

down

MRAK13343

0.046766231 1.741470861

down

BC091431_P1 0.040444159 1.774696923

down

XR_008004_

0.049786366 1.564872337

down

MRNR_0274

0.043534745 1.520794796

down

XR_007008_

0.027827377 1.586787642

down

MRNR_0274

0.043534745 1.520794796

down

XR_009508_

0.010834758 1.621010085

down

MRAK08854

0.034608972 1.594106481

down

MRuc008lum

0.046532415 1.731525939

down

MRAK13756

0.049387275 2.266269552

down

MRBC05287

0.036183082 1.986867961

down

XR_006360_

0.031595041 1.992246736

down

MRAK01247

0.035900857 1.627108736

down

XR_005641_

0.010076191 1.875123347

down

XR_006437_

0.035308453 1.655361222

down

MRuc007lsc

0.010926997 1.779102256

down

XR_006093_

0.044244767 1.578948628

down

MRAK04093

0.033756148 2.464227295

down

L27129_P1

0.011395706 1.840498533

down

MRAK08024

0.03462557 2.578548176

down

MRuc008ras

0.043368383 1.651454361

down

uc.392+_P1

0.030557302 1.897403964

down

XR_008415_

0.009885108 3.936073061

down

XR_007260_

0.027345191 1.87398062

down

uc.292+_P1

0.033380577 1.544869528

down

BC129118_P1 0.049050374 1.795345078

down

MRAK16128

0.006865299 1.704064842

down

BC105769_P1 0.036040215 1.532308552

down

BC161881_P1 0.000525852 2.903724206

down

MRBC02501

0.02883171 1.84676539

down

MRAK17259

0.047606367 1.505013888

down

MRAK08082

0.003419968 1.688903112

down

XR_005949_

0.029279799 1.740566901

down

BC091254_P1 0.043449559 1.774148166

down

XR_006777_

0.044210245 1.586528935

down

MRAK03323

0.022282206 2.550611731

down

MRAK08091

0.018362991 6.777752082

down

MRAK08884

0.013406108 1.688892108

down

uc.414+_P1

0.035614403 1.742281172

down

MRAK03718

0.018860453 2.452178953

down

uc.414+_P1

0.035614403 1.742281172

down

#

Fold change cut-off: 1.5; #p value cut-off: 0.05; #Condition pairs: T vs C.

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Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

Construction of the Coding-Non-Coding Gene Co-Expression Network

A coding-non-coding gene co-expression network (CNC network) was constructed based on correlation analysis of

the differentially expressed lncRNAs and mRNAs (Figure 1).

LncRNAs and mRNAs with Pearson’s correlation coefficients not less than 0.99 were selected to draw the network, using the Cytoscape program (Institute of Systems Biology, Seattle,

Table 3. Upregulated mRNA profiles Probe name

p value

Fold change and regulation Absolute fold change Regulation ([T] vs [C]) ([T] vs [C])

Probe name

p value

Fold change and regulation Absolute fold change Regulation ([T] vs [C]) ([T] vs [C])

CUST_1210_PI421866198 0.045606394 1.59759874

up

CUST_11657_PI421866198 0.012815076

2.177136405

up

5.063922528

up

CUST_7560_PI421866198 0.040101847 1.65046247

up

CUST_1855_PI421866198 0.00137129 2.617241527

up

CUST_10534_PI421866198 0.01945795

1.628197076

up

CUST_2486_PI421866198 0.020719392 1.90840495

up

CUST_13435_PI421866198 0.037294419

2.018765962

up

CUST_4642_PI421866198 0.029708762 1.654661374

up

CUST_3946_PI421866198 0.00503991 2.915539092

up

CUST_6944_PI421866198 0.007240272 4.257326589

up

CUST_4654_PI421866198 0.001786365 3.507455905

up

CUST_15260_PI421866198 0.000577946

up

CUST_10867_PI421866198 0.039276132

2.023074619

up

CUST_5342_PI421866198 0.037533375 2.430356579

up

CUST_11542_PI421866198 0.001880145

3.595193945

up

CUST_11829_PI421866198 0.0100799

3.253144336

up

CUST_874_PI421866198 0.030490411 1.549625107

up

CUST_15262_PI421866198 0.00574348

2.040395513

up

CUST_6327_PI421866198 0.019006624 1.656331373

up

CUST_2300_PI421866198 0.043473392 2.041859786

up

CUST_10004_PI421866198 0.009444256

up

CUST_10432_PI421866198 0.014915171

up

CUST_2643_PI421866198 0.042958202 1.611518406

up

CUST_7003_PI421866198 0.005680592 1.966802326

up

CUST_12088_PI421866198 0.007111663

4.217454975

up

CUST_5856_PI421866198 0.00444493 1.514130444

up

CUST_11522_PI421866198 0.016947821

1.526485621

up

CUST_3262_PI421866198 0.011125493 1.626468671

up

CUST_7763_PI421866198 0.044559992 2.452112778

up

CUST_3486_PI421866198 0.026690711 1.861147332

up

CUST_9248_PI421866198 0.021534995 1.573094493

up

CUST_4557_PI421866198 0.032782771 2.377418854

up

CUST_10991_PI421866198 0.033401846

up

CUST_13837_PI421866198 0.036516598

up

CUST_654_PI421866198 0.011979725 1.904043361

up

CUST_7855_PI421866198 0.013731288 2.031357834

up

CUST_11606_PI421866198 0.035018534

2.611823367

up

CUST_9330_PI421866198 0.002192444 1.821304992

up

CUST_14500_PI421866198 0.011436587

2.178194373

up

CUST_8448_PI421866198 0.03433747 2.348021686

up

CUST_1791_PI421866198 0.012327838 1.685268466

up

CUST_7759_PI421866198 0.030562675 2.302327658

up

CUST_10895_PI421866198 0.002460083

1.803186767

up

CUST_8107_PI421866198 0.039949858 1.817725142

up

CUST_2059_PI421866198 0.016699039

4.0862396

up

CUST_13967_PI421866198 0.011714172

1.502536808

up

CUST_12802_PI421866198 0.001146504

1.959951788

up

CUST_13858_PI421866198 0.031802356

4.327122709

up

CUST_14787_PI421866198 0.021016027

1.847760579

up

CUST_3094_PI421866198 0.049342616 1.559352399

up

CUST_12797_PI421866198 0.043673356

1.626239603

up

CUST_4831_PI421866198 0.009792921 3.028942659

up

CUST_3027_PI421866198 0.038742155 2.095886609

up

CUST_9367_PI421866198 0.002270001 1.504368323

up

CUST_3860_PI421866198 0.006603383 2.072462648

up

CUST_10195_PI421866198 0.010355438

1.563042132

3.255336544

1.518998312

1.801275848

2.651287522

CUST_12576_PI421866198 0.021936529

1.530467349

up

CUST_9836_PI421866198 0.046263826 2.805332937

up

CUST_11559_PI421866198 0.037735196

1.586725757

up

CUST_6100_PI421866198 0.023983273 1.646977676

up

CUST_10215_PI421866198 0.020469822

1.987755392

up

CUST_9174_PI421866198 0.044585762 1.572939157

up

CUST_862_PI421866198 0.029139124 1.62620372

up

CUST_9559_PI421866198 0.00320455 1.85037819

up

CUST_11044_PI421866198 0.043897171

2.412127444

up

CUST_12615_PI421866198 0.044961697

5.12824374

up

CUST_11815_PI421866198 0.008441526

3.050925744

up

CUST_12694_PI421866198 0.000445438

6.028735911

up

CUST_12246_PI421866198 0.03359414

1.950991285

up

CUST_5146_PI421866198 0.029780754 3.435343433

up

CUST_13854_PI421866198 0.042522872

2.037577641

up

CUST_14214_PI421866198 0.022183257

up

CUST_8809_PI421866198 0.017832572 2.054859613

up

CUST_5814_PI421866198 0.019676952 2.119471646

up

CUST_2710_PI421866198 0.002845954 8.341076172

up

CUST_5887_PI421866198 0.04427284 1.726615686

up

CUST_3992_PI421866198 0.037372541 1.584239441

up

CUST_9879_PI421866198 0.026613386 3.480238877

up

CUST_3166_PI421866198 0.00670917 1.673006325

up

CUST_10303_PI421866198 0.030728741

up

CUST_6053_PI421866198 0.046093471 1.731258715

up

CUST_5232_PI421866198 0.019294662 1.711679983

up

CUST_11231_PI421866198 0.036003194

up

CUST_539_PI421866198 0.034040423 2.229217679

up

CUST_7773_PI421866198 0.036907358 1.608969152

up

CUST_1893_PI421866198 0.010545646 1.566298301

up

CUST_8733_PI421866198 0.015020579 1.695315831

up

CUST_2513_PI421866198 0.02086206 2.028827679

up

CUST_6940_PI421866198 0.036482366 1.644952586

up

CUST_2838_PI421866198 0.019319005 1.660433334

up

CUST_1492_PI421866198 0.037677048 1.765124567

up

CUST_370_PI421866198 0.000366622 1.907148258

up

228

1.665044421

1.906633522

4.236377053

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Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

Table 4. Downregulated mRNA profiles Probe name

p value

Fold change and regulation Absolute fold change Regulation ([T] vs [C]) ([T] vs [C])

Probe name

p value

Fold change and regulation Absolute fold change Regulation ([T] vs [C]) ([T] vs [C])

CUST_4198_PI421866198 0.0067783 1.628791683

down

CUST_7536_PI421866198 0.049372269 1.895256483

down

CUST_776_PI421866198 0.007212239 1.814502444

down

CUST_9125_PI421866198 0.012439588 2.087408269

down

3.252387526

down

CUST_11390_PI421866198 0.048161951

2.326862939

down

CUST_7779_PI421866198 0.033695322 1.75749043

down

CUST_10258_PI421866198 0.037506169

1.684580066

down

CUST_3858_PI421866198 0.003915407 1.539287448

down

CUST_11901_PI421866198 0.031870641

1.941909095

down

CUST_1082_PI421866198 0.029269283 1.585292074

down

CUST_3360_PI421866198 0.024288361 1.964775215

down

CUST_4192_PI421866198 0.013624005 1.502800985

down

CUST_3248_PI421866198 0.01717798 1.65095485

down

CUST_10318_PI421866198 0.02131578

CUST_14720_PI421866198 0.044151095

1.983600187

down

CUST_11572_PI421866198 0.042170403

1.623829696

down

CUST_10036_PI421866198 0.015626469

1.605582355

down

CUST_13054_PI421866198 0.010350555

2.672858999

down

CUST_5668_PI421866198 0.008412707 1.549091469

down

CUST_9107_PI421866198 0.039358033 2.054262673

down

CUST_11039_PI421866198 0.022341275

4.302450915

down

CUST_10023_PI421866198 0.033561008

down

CUST_12190_PI421866198 0.038150892

2.184822485

down

CUST_8571_PI421866198 0.024507169 1.931788968

down

CUST_7670_PI421866198 0.030325542 1.786994631

down

CUST_6493_PI421866198 0.016041024 1.534768436

down

CUST_6411_PI421866198 0.02170252 4.228192419

down

CUST_4967_PI421866198 0.016405071 1.732526997

down

CUST_9295_PI421866198 0.012044678 5.265246349

down

CUST_9652_PI421866198 0.038653891 1.698414312

down

CUST_333_PI421866198 0.02729877 2.068126692

down

CUST_11024_PI421866198 0.041375285

1.585211494

down

CUST_7231_PI421866198 0.045267906 1.988425486

down

CUST_11380_PI421866198 0.023145073

1.972866179

down

CUST_2560_PI421866198 0.049736128 2.029461915

down

CUST_4567_PI421866198 0.000735864 1.609649972

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CUST_33_PI421866198 0.014357628 1.634448213

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CUST_8200_PI421866198 0.015255319 1.854687725

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CUST_9028_PI421866198 0.003902698 1.500420452

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CUST_5928_PI421866198 0.034725016 1.649610019

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CUST_14935_PI421866198 0.012652676

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CUST_8516_PI421866198 0.026925455 1.545754637

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CUST_8147_PI421866198 0.047774903 2.512465466

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CUST_3482_PI421866198 0.027384736 1.56126868

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CUST_11318_PI421866198 0.024469389

1.801610366

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CUST_6919_PI421866198 0.023519185 2.867930507

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CUST_12570_PI421866198 0.0199879

6.164450222

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CUST_2509_PI421866198 0.041171198 2.197500256

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CUST_9797_PI421866198 0.018976082 2.905925735

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CUST_5357_PI421866198 0.005533369 2.464244091

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CUST_13012_PI421866198 0.044403789

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CUST_383_PI421866198 0.005899414 2.043783909

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CUST_2160_PI421866198 0.023758555 1.875550749

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CUST_6065_PI421866198 0.033150212 3.01190688

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CUST_6349_PI421866198 0.009680624 1.664260649

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1.604777926

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CUST_609_PI421866198 0.039611572 2.048383439

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CUST_5578_PI421866198 0.022595551 1.518187137

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CUST_5091_PI421866198 0.029473561 1.741826508

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CUST_101_PI421866198 0.024100642 1.732010889

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CUST_9434_PI421866198 0.016207278 1.699652485

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CUST_1302_PI421866198 0.010298785 3.640830473

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CUST_14233_PI421866198 0.025889633

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CUST_8391_PI421866198 0.019406484 1.678849454

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CUST_1862_PI421866198 0.043523032 1.989012487

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CUST_4319_PI421866198 0.018043175 1.591434007

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CUST_2828_PI421866198 0.012457514 2.296501406

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CUST_5514_PI421866198 0.021748994 2.160062964

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CUST_3303_PI421866198 0.000785041 1.634238713

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CUST_12018_PI421866198 0.043888152

2.505456518

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CUST_7885_PI421866198 0.019408921 1.61555388

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CUST_14802_PI421866198 0.047467746

2.091477871

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CUST_6904_PI421866198 0.031971115 1.687945512

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CUST_12841_PI421866198 0.015876313

2.924250563

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CUST_9084_PI421866198 0.020976626 1.633773816

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CUST_4276_PI421866198 0.037379472 1.541802423

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CUST_10372_PI421866198 0.034163437

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CUST_4886_PI421866198 0.028589317 1.645704145

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CUST_6343_PI421866198 0.02350771 1.591532443

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CUST_7724_PI421866198 0.026010169 1.700709814

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CUST_9900_PI421866198 0.009545992 1.627704149

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CUST_1736_PI421866198 0.034807531 1.527727959

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CUST_2923_PI421866198 0.01879922 1.526455819

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CUST_3184_PI421866198 0.027050956 1.67183407

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CUST_3414_PI421866198 0.045886349 1.728345527

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CUST_5601_PI421866198 0.000686672 1.52572276

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CUST_9269_PI421866198 0.030872404 1.795461851

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CUST_584_PI421866198 0.044594505 1.623093751

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CUST_1731_PI421866198 0.004534508 1.519119469

down

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CUST_14236_PI421866198 0.000522689

2.343916593

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CUST_6202_PI421866198 0.034681376 1.680710099

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CUST_14943_PI421866198 0.041784213

1.52157488

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CUST_5030_PI421866198 0.047914238 1.735625876

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CUST_9835_PI421866198 0.009566858 1.549027046

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1.793223113

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CUST_1976_PI421866198 0.037596345 1.768400442

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CUST_5098_PI421866198 0.037846355 1.676871727

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CUST_5440_PI421866198 0.003370002 1.966515649

down

CUST_14308_PI421866198 0.007826484

CUST_11240_PI421866198 0.009535117

CUST_12238_PI421866198 0.001505492

CUST_14123_PI421866198 0.00919136

1.599796943

1.510598473

1.872143645

1.777394587

1.566228458

1.830465522

1.531920752

CUST_12249_PI421866198 0.035589358

1.693185845

down

CUST_601_PI421866198 0.008108411 1.546657228

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CUST_14318_PI421866198 0.039627075

1.887104087

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CUST_596_PI421866198 0.03101802 1.518329418

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CUST_12907_PI421866198 0.030763082

1.553773667

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CUST_8394_PI421866198 0.020034374 1.596096633

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CUST_6039_PI421866198 0.047285771 1.537592638

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CUST_8563_PI421866198 0.027774993 2.714663103

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CUST_19_PI421866198 0.042225177 1.832891771

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CUST_6633_PI421866198 0.006083932 1.746328538

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Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

Figure 1. Predicted regulation network. A coding-non-coding gene co-expression network.

Node color: Upregulated lncRNAs: purple; Downregulated lncRNAs: blue; Upregulated mRNAs: red; Downregulated mRNAs: green.

Node size: Betweenness centrality (equal to the number of shortest paths from all vertices to all others that pass through that node).

Line color: Trans interaction: blue; Cis interaction: red; Cut-off: abs(correlation) >=0.95.

WA, USA); 117 lncRNAs and 202 mRNAs comprised the CNC network node. A total of 319 network nodes made 1392 associated network pairs of co-expressed lncRNAs and mRNAs. The CNC network indicated that one mRNA could correlate with 1 to several lncRNAs, and vice versa.

The CNC network presented in Table S9 could implicate the inter-regulation of lncRNAs and mRNAs in burned rats.

DISCUSSION Skeletal muscle wasting is an exacerbating factor in the prognosis of critically ill patients, including those with severe burn injury.[11] Molecular treatment mechanisms of skeletal muscle 230

wasting in burn injuries have been extensively studied. However, the pathogenesis and gene regulation involved are still unknown.

Increasing evidence has confirmed lncRNAs to be one of the most important factors controlling gene expression.

[20] Therefore, the lncRNA expression profile in the skeletal muscle tissue of burned rats was presently evaluated in an attempt to reveal the potential role of lncRNAs in the pathogenesis of skeletal muscle wasting in burn injury (Tables 1, 2). Microarray analyses revealed a set of differentially expressed lncRNAs, with 64 upregulated and 53 downregulated Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Haijun et al. Expression signatures of lncRNAs in skeletal muscles at the early flow phase revealed by microarray in burned rats

lncRNAs in skeletal muscles of burned rats, when compared to normal tissue.

Recent studies have demonstrated that lncRNAs can guide changes in gene expression in either the cis (neighboring genes) or trans (distantly located genes) manner, which is not easily predicted, based on lncRNA sequence.[21] In principle, lncRNAs can guide chromatin change in cis in a cotranscriptional manner (tethered by RNA polymerase) or as a complementary target for small regulatory RNAs. Guidance in trans can occur by an lncRNA binding to target DNA as an RNA:DNA heteroduplex, RNA:DNA:DNA triplex, or by RNA recognition of a complex surface of specific chromatin features.[22] The established role of lncRNAs in diseases creates an urgency to understand the mechanisms by which these RNAs seek their targets. A simplistic model in which the RNA remains tethered to the site of origin to regulate transcriptional changes in cis has been suggested. Perhaps the most intensely studied and best understood cis mechanism of regulation by lncRNA is the mammalian X inactivation center, a genetic locus that specifies a number of lncRNAs, including X-inactivation–specific transcript, or XIST.[21] Target genes under cis mechanism of regulation by lncRNAs were predicted via genome browser and annotation tool.

Further investigation of the lncRNA-gene network in an effort to gain insight into the functions of lncRNA targets demonstrated that MRAK080917 was predicted to target the Zbtb16 genes of the glioma pathway, which could affect total body weight, adiposity, lipid profile, insulin sensitivity of skeletal muscles, and mitochondrial function in skeletal muscles.[23,24] Uc.414+ was predicted to target THRA and Nr1d1. THRA is downregulated in skeletal muscle of patients with non-thyroidal illness syndrome secondary to non-septic shock,[25] while Nr1d1 could modulate skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy.[26] MRBC025014 was predicted to target Sucla2, which is involved in mitochondrial disorder and progressive dystonia.[27,28]

Conclusions In conclusion, lncRNAs differentially expressed in skeletal muscles of burned rats, compared to normal tissues, were identified in the present study. Regulatory pathways of lncRNAs may be involved in the pathogenesis of skeletal muscle wasting. Moreover, MRAK080917, uc.414+, and MRBC025014 could be critical in skeletal muscle wasting, via their targets, but these findings need to be confirmed, and the underlying mechanisms require further study. The present results also point to several exciting directions for future research. The CNC network presented in Table S9 implicated the inter-regulation of lncRNAs and mRNAs in burned rats. Each potential lncRNA-mRNA pair identified is a strong Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

candidate for a future study that can definitively confirm the presence of specific lncRNA-mRNA interactions,[29] thus providing a more detailed picture of the pathogenesis of skeletal muscle wasting in burned rats.

Acknowledgments This study was financially supported by the National Natural Science Foundation of China (81120108041, 81471873, 81171807) and the State Key Program of the General Logistics Department of the PLA (BWS14J048, BWS14J049). The authors wish to thank Kang Cheng Bio-tech Shanghai P.R. China for the microarray work.

Conflict of interest: None declared.

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2. Porter C, Hurren NM, Herndon DN, Børsheim E. Whole body and skeletal muscle protein turnover in recovery from burns. Int J Burns Trauma 2013;3:9–17.

3. Jeschke MG, Gauglitz GG, Kulp GA, Finnerty CC, Williams FN, Kraft R, et al. Long-term persistance of the pathophysiologic response to severe burn injury. PLoS One. 2011;6:e21245.

4. Chai J, Wu Y, Sheng ZZ. Role of ubiquitin-proteasome pathway in skeletal muscle wasting in rats with endotoxemia. Crit Care Med 2003;31:1802–7.

5. Merritt EK, Cross JM, Bamman MM. Inflammatory and protein metabolism signaling responses in human skeletal muscle after burn injury. J Burn Care Res 2012;33:291–7.

6. Chaı JK. Mechanisms of skeletal muscle wasting after severe burn and its treatment. [Article in Chinese] Zhonghua Shao Shang Za Zhi 2009;25:243–5.

7. Lagirand-Cantaloube J, Cornille K, Csibi A, Batonnet-Pichon S, Leibovitch MP, Leibovitch SA. Inhibition of atrogin-1/MAFbx mediated MyoD proteolysis prevents skeletal muscle atrophy in vivo. PLoS One 2009;4:e4973.

8. Sheriff S, Kadeer N, Joshi R, Friend LA, James JH, Balasubramaniam A. Des-acyl ghrelin exhibits pro-anabolic and anti-catabolic effects on C2C12 myotubes exposed to cytokines and reduces burn-induced muscle proteolysis in rats. Mol Cell Endocrinol 2012;351:286–95.

9. Duan H, Chai J, Sheng Z, Yao Y, Yin H, Liang L, et al. Effect of burn injury on apoptosis and expression of apoptosis-related genes/proteins in skeletal muscles of rats. Apoptosis 2009;14:52–65.

10. Tzika AA, Mintzopoulos D, Mindrinos M, Zhang J, Rahme LG, Tompkins RG. Microarray analysis suggests that burn injury results in mitochondrial dysfunction in human skeletal muscle. Int J Mol Med 2009;24:387–92.

11. Hosokawa S, Koseki H, Nagashima M, Maeyama Y, Yomogida K, Mehr C, et al. Title efficacy of phosphodiesterase 5 inhibitor on distant burninduced muscle autophagy, microcirculation, and survival rate. Am J Physiol Endocrinol Metab 2013;304:922–33.

12. Zhang J, Cui X, Shen Y, Pang L, Zhang A, Fu Z, et al. Distinct expression profiles of LncRNAs between brown adipose tissue and skeletal muscle.

Biochem Biophys Res Commun 2014;443:1028–34.

13. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell 2013;152:1298–307.

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15. Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 2013;152:1308–23.

16. Ma H, Hao Y, Dong X, Gong Q, Chen J, Zhang J, et al. Molecular mechanisms and function prediction of long noncoding RNA. ScientificWorldJournal 2012;2012:541786.

17. Mizutani R, Wakamatsu A, Tanaka N, Yoshida H, Tochigi N, Suzuki Y, et al. Identification and characterization of novel genotoxic stress-inducible nuclear long noncoding RNAs in mammalian cells. PLoS One 2012;7:e34949.

18. Lee JT. Epigenetic regulation by long noncoding RNAs. Science 2012;338:1435–9.

19. Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, et al. Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun 2013;433:200,6.

20. Khachane AN, Harrison PM. Mining mammalian transcript data for functional long non-coding RNAs. PLoS One 2010;5:e10316.

21. Hung T, Chang HY. Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol 2010;7:582–5.

22. Pauli A, Rinn JL, Schier AF. Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 2011;12:136–49.

23. Seda O, Liska F, Sedová L, Kazdová L, Krenová D, Kren V. A 14-gene

region of rat chromosome 8 in SHR-derived polydactylous congenic substrain affects muscle-specific insulin resistance, dyslipidaemia and visceral adiposity. Folia Biol (Praha) 2005;51:53–61.

24. Plaisier CL, Bennett BJ, He A, Guan B, Lusis AJ, Reue K, et al. Zbtb16 has a role in brown adipocyte bioenergetics. Nutr Diabetes 2012;2:e46.

25. Lado-Abeal J, Romero A, Castro-Piedras I, Rodriguez-Perez A, AlvarezEscudero J. Thyroid hormone receptors are down-regulated in skeletal muscle of patients with non-thyroidal illness syndrome secondary to nonseptic shock. Eur J Endocrinol 2010;163:765–73.

26. Woldt E, Sebti Y, Solt LA, Duhem C, Lancel S, Eeckhoute J, et al. Reverb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy. Nat Med 2013;19:1039–46.

27. Randolph LM, Jackson HA, Wang J, Shimada H, Sanchez-Lara PA, Wong DA, et al. Fatal infantile lactic acidosis and a novel homozygous mutation in the SUCLG1 gene: a mitochondrial DNA depletion disorder. Mol Genet Metab 2011;102:149–52.

28. Morava E, Steuerwald U, Carrozzo R, Kluijtmans LA, Joensen F, Santer R, et al. Dystonia and deafness due to SUCLA2 defect; Clinical course and biochemical markers in 16 children. Mitochondrion 2009;9:438– 42.

29. Yu H, Kim PM, Sprecher E, Trifonov V, Gerstein M. The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics. PLoS Comput Biol 2007;3:e59.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Yanık sıçanlarda mikrodizi analiziyle ortaya çıkartıldığı gibi erken akış fazında iskelet kaslarındaki IncRNA’ların ekspresyon imzaları Dr. Zhang Haijun, Dr. Yu Yonghui, Dr. Chai Jiake PLA Genel Hastanesi, Yanık ve Plastik Cerrahi Kliniği, Pekin, Çin

AMAÇ: Tüm vücut yüzeyinin (TVY) %30’dan fazlasını kaplayan ağır termal travma hipermetabolizma, kronik enflamasyon ve iskelet kaslarında güçsüzleşmeyi içermekle birlikte bu bulgularla sınırlı olmayan süregelen bir fizyopatolojik yanıtı da tetiklemektedir. Uzun zincirli proteini kodlamayan RNA’lar (lncRNA’lar) çeşitli biyolojik fonksiyonlara katılan, önemli ve yaygın bgenler sınıfıdır. Ancak ağır yanıklardan sonra iskelet kaslarının zayıflamasına ilişkin yanıtları düzenleyen RNA’ların fonksiyonları hâlâ test edilmemiştir.

GEREÇ VE YÖNTEM: Burada mikrodizi analizi kullanılarak, plasebo sıçanlarla karşılaştırmalı olarak erken akış fazında üç çift yanık sıçanın iskelet kası dokularındaki IncRNA’lar ve haberci RNA’ların (miRNA’lar) ekspresyon profilleri incelendi. Tanımlanmış her bir potansiyel lncRNA-mRNA çifti spesifik lncRNA-mRNA etkileşimlerin varlığının kesin olarak doğrulanmasında kullanılan ve yanık sıçanlarda iskelet kası zayıflamasının ayrıntılı bir patogenezini gösteren güçlü bir aday belirteçtir.

BULGULAR: Üç yaralı dokuyla eşleştirilmiş üç normal doku örneğinde mikrodizi analiz verileri kullanılarak LncRNA ekspresyon düzeyleri karşılaştırıldı. Ortalama 117 adet anlamlı derecede farklılaşmış IncRNA (1.5 katı) tanımlandı. Yalnızca 202 adet miRNA anlamlı derecede arttı veya azaldı. Eşleştirilmiş normal dokulara göre zedelenmiş dokularda ortalama 92 adet miRNA’nın düzeyleri artarken, ortalama 110 miRNA’nın düzeyleri azaldı.

TARTIŞMA: Burada, normal dokulara göre sıçanların yanık dokularında IncRNA’ların farklı düzeylerde eksprese edildiği saptanmıştır. İskelet kasları zayıflamasının patogenezinde düzenleyici yolaklar da rol oynayabilmektedir. Tanımlanmş her bir lncRNA-mRNA çifti spesifik IncRNA-miRNAA etkileşimlerinin varlığının doğrulanmasında kullanılan ve yanık sıçanlarda iskelet kası zayıflamasının ayrıntılı bir patogenezini gösteren güçlü bir aday belirteçtir.

Anahtar sözcükler: Ekspresyon; kas zayıflaması; LncRNA’lar; mikrodizi; yanık.

Ulus Travma Acil Cerrahi Derg 2016;22(3):224–232

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doi: 10.5505/tjtes.2015.04831

Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

ORIGINAL ARTICLE

Internal fixation vs conservative treatment for displaced distal radius fractures: a meta-analysis of randomized controlled trials Guang-Shu Yu, M.D.,1 Yan-Bin Lin, M.D.,1 Li-Sheng Le, M.D.,2 Mei-Feng Zhan, M.D.,3 Xiao-Xiang Jiang, M.D.4 1

Department of Orthopaedics and Traumatology, Fuzhou The 2nd Hospital of Xia Men University, Fu Zhou, Fujian-China

2

Department of Orthopaedics and Traumatology, Mawei Branch of Fuzhou The 2nd Hospital, Fu Zhou, Fujian-China

3

Department of Orthopaedics and Traumatology, Luoyuan County Hospital, Luo Yuan, Fujian-China

4

Graduate School, Fujian University of Traditional Chinese Medicine, Fu Zhou, Fujian-China

ABSTRACT BACKGROUND: The aim of the present study was to compare clinical outcomes of internal fixation and conservative approach in the treatment of displaced distal radius fractures.

METHODS: Reports of studies were retrieved from the PubMed, Cochrane Library, EMBASE, BIOSIS, Ovid, CNKI, and Wanfang Data databases, as well as other sources. Methodological quality of the trials was critically assessed, and relevant data were extracted.

Review Manager (RevMan) meta-analysis software (version 5.0; Cochrane Collaboration, London, UK) was used for data analysis.

RESULTS: A total of 10 randomized controlled trials, which included 653 patients, were eligible for inclusion in the present metaanalysis, 7 of which were in English, and 3 of which were in Chinese. The trials had medium risk of bias. Results of meta-analysis showed that patients undergoing conservative treatment for distal radius fractures had better restoration of pronation (MD=1.80, 95% confidence interval [CI]=0.18—3.42, p=0.03; heterogeneity p=0.17, I2=43%), but shorter restoration of radial length (MD=2.62, 95% CI=1.47—3.76, p<0.00001; heterogeneity p=0.02, I2=73%). Wrist range of motion other than pronation, grip strength, radiographic parameters other than radial length, and rates of complications were not significantly different between the 2 treatments.

CONCLUSION: Very few clinical differences were found between results of internal fixation and conservative treatment for displaced distal radius fractures. Best course of of treatment must be determined based on concrete conditions.

Keywords: Conservative treatment; distal radius fracture; internal fixation; meta-analysis.

INTRODUCTION Distal radius fractures are one of the most common types of fractures, and the pediatric and elderly populations are at greatest risk.[1] Most distal radius fractures can be treated by closed reduction and plaster immobilization, which often Address for correspondence: Yan-bin Lin, M.D. Department of Orthopaedics and Traumatology, Fuzhou the 2nd Hospital of Xia Men University, No: 47, Shang-Teng Road, Cang-Shan District, Fuzhou, People 350007 Fuzhou, China Tel: +86-13960743906 E-mail: 812953900@qq.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):233–241 doi: 10.5505/tjtes.2015.05995 Copyright 2016 TJTES

Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

leads to satisfactory outcome.[2] However, the elderly are increasingly likely to choose a more active and independent lifestyle, requiring increased limb function. As a result of which, comprehension of nonsurgical and surgical treatment is evolving, with recently developed methods of fixation.[3,4] Redisplacement is a risk of conservative treatment of distal radius fractures, because parking position accuracy is sometimes impossible to attain. Subsequently, the opportunity to perform early postoperative functional exercise may be lost, resulting in likelihood of wrist ankylosis and limited activity.

A trend toward selection of open reduction and internal fixation has been identified.[5] Using diverse document retrieval systems, many meta-analyses of external fixation vs internal fixation for distal radius fractures were found that identified significantly better functional outcome of internal fixation.[6–8] Only one meta-analy233

Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

sis supported the use of external fixation.[9] Choices of treatment have been compared in many randomized controlled trials (RCTs). However, these have lacked systemic evaluation.

In order to clarify whether internal fixation is superior to conservative treatment of distal radius fractures, in terms of functional outcome and on the basis of new evidence, the present meta-analysis was conducted, incorporating reports of all relevant RCTs available in Chinese or English. Sub-group analyses were presently performed on the basis of range of motion and radiological outcome.

MATERIALS AND METHODS Search Strategy Reports of studies were retrieved (from the earliest records available to those dated August 1, 2014) from the PubMed, Cochrane Library, EMBASE, BIOSIS, Ovid, CNKI, and Wanfang Data databases, as well as manually. The following search terms were used: (distal radial fractures or distal radius fractures or fracture radius or fractures radius or fractures of distal radius or Colles’ fractures or Smith’s fractures or wrist injuries) and (internal fixation or plate or plating or percutaneous pinning or percutaneous crossed-pin fixation or percutaneous pin fixation) and (conservative treatment or plaster cast or casting). The search was limited to human subjects and RCTs published in Chinese or English.

the following criteria: (1) population, patients with unstable distal radius fracture that had occurred less than 14 days previously or axial compression >2 mm or dorsal angulation >20°, (2) study design, randomized controlled trials, (3) comparison intervention, internal fixation vs conservative treatment for distal radius fractures, (4) outcome measures, clinical results, radiological outcomes, and complication.

Exclusion Criteria Trials were excluded if they (1) were abstracts, letters, or meeting proceedings, (2) used repeated data or the data could not be obtained by calculation, and (3) if original documents of experimental design were not precise.

Data Extraction and Outcome Measures Inclusion decisions were independently made by 2 authors according to eligibility criteria, and were recorded on a specially developed form. Differences in opinion between authors were resolved by discussion, and a third author was consulted if necessary. The following data were recorded for each study (1) first author’s name, methods of treatment, gender distributions, average age, duration of follow-up, year of publication, country of origin, revised Jadad score, (2) wrist range of motion (wrist flexion and extension, forearm pronation, and supination, and radial and ulnar deviation), (3) grip strength, (4) radiographic parameters of dorsal angulation, radial length, radial inclination, and ulnar variance, (5) rates of complications, etc.

Inclusion and Exclusion Inclusion Criteria

Risk-of-Bias Quality Assessment and Quality Scoring

Studies were considered acceptable for inclusion if they met

Risk-of-bias assessment was performed in accordance with

Records identified through database

Additional records identified through

searching (n=469)

other sources (n=2)

Records after duplicates removed (n=156)

Records excluded (n=112): (1) Not relevant (n=36) (2) Case report (n=62) (3) Not reporting comparisons (n=14)

Full-text articles assessed for eligibility (n=44)

Full-text articles excluded (n=34): (1) No outcomes of interest reported: 30 (2) used repeated data: 4

10 randomized trials included in meta-analysis

Figure 1. Selection process for randomized controlled trials included in meta-analysis.

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Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

Meta-Analysis Meta-Analysis of Clinical Results

Incomplete outcome data addressed?

Free of selective reporting?

Free of other bias?

Data for flexion, extension, pronation, supination, and radial and ulnar deviation were pooled among 3 studies. Analysis of

Blinding?

(1) Was the study described as randomized? Yes: +1; No: 0.

(2) Was the method of randomization appropriate? Yes +1; No: -1; Not described: 0. (3) Was the study described as blinded? Yes: +1; No: 0.

(4) Was the method of blinding appropriate? Yes: +1; No: -1; Not described: 0.

(5) Was there a description of withdrawals and dropouts?

Yes: +1; No: 0.

(6) Was there a clear description of the inclusion/exclusion criteria? Yes: +1; No: 0.

(7) Was the method used to assess adverse effects described?

Yes: +1; No: 0.

(8). Was the method of statistical analysis described? Yes: +1; No: 0.[10]

Quality was evaluated using modified Jadad score, the total score of which was 8 points. Studies that received 3 points or fewer were considered low-quality (level B), and those that received 4 points or more were considered high-quality (level A). Seven studies qualified as level A, and 3 qualified as level B. Risk-of-bias analysis revealed that all trials were of medium risk of bias (Fig. 2).

Allocation concealment?

Quality scoring for each trial was performed using modified Jadad scale, an 8-item scale designed to assess randomization, blinding, withdrawals and dropouts, inclusion and exclusion criteria, adverse effects, and statistical analysis.

the database. After browsing by title, then reading the abstract and the entire text, 10 published studies met all inclusion criteria and proved eligible for the present investigation.

These studies collectively included 653 patients (340 of whom received conservative treatment, and 313 of whom received internal fixation). In the present meta-analysis, 7 studies were reported in English and 3 were reported in Chinese,[11–20] and 9 studies included only adult patients (Fig. 1).

Adequate sequence generation?

guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.0), with the Cochrane Collaboration’s tool for assessing risk of bias. Studies were classified using 3 categories, as follows: yes (low risk of bias; all criteria met), unclear (moderate risk of bias; 1 or more criteria partly met), and no (high risk of bias; 1 or more criteria not met). Each RCT was independently assessed by 2 reviewers. Any disagreements were resolved by discussion and consensus.

Arora R 2011

?

–

+

+

+

?

Azzopardi T 2005

–

+

+

+

–

?

Diao HH 2013

–

?

+

–

+

?

Gupta R 1999

?

?

–

–

?

?

Hu YX 2012

?

?

+

?

–

?

Li JQ 2012

+

?

?

–

+

?

Miller 2005

+

+

+

–

+

?

Rodriguez-Merchan EC 1997

?

?

+

–

?

?

Stoffelen 1999

?

?

+

–

?

?

Wong TC 2010

+

+

+

+

–

?

The score of each article ranged from 0 (lowest quality) to 8 (highest quality). Scores of 4–8 denoted good to excellent quality, and 0–3 denoted poor to low quality.

Statistical Analyses Data were independently entered into the Review Manager (RevMan) meta-analysis software program (version 5.0; Cochrane Collaboration, London, UK) by 2 authors. Relative risk (RR) was used as the summary statistic for dichotomous outcomes, and weighted mean difference was used for continuous outcomes, both with 95% confidence interval (CI).

A fixed-effects model was used when there was no statistical evidence of heterogeneity; otherwise, a random-effects model was used. If presence of heterogeneity was found, it was indication that study population, treatment, outcome measures, and methodologies should be checked to determine the source of heterogeneity. If it could not be quantitatively synthesized, or event rate was too low to be measured, it was indication that this should be described in qualitative evaluation. Publication bias was assessed using funnel plots.

RESULTS Studies Included in Meta-Analysis A total of 469 potentially eligible studies were identified by Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Figure 2. Risk-of-bias summary: Author judgments regarding each risk-of-bias item for included studies.

235

Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

Internal fixation Study or Subgroup

Mean

conservative treatment

SD Total

Mean

SD

Mean Difference

Total Weight

Mean Difference

IV, Fixed, 95% CI

IV, Fixed, 95% CI

1.1.1 Flexion Arora R 2011

55

11

36

57

10

37

3.4%

Azzopardi T 2005

87

12

27

82

15

27

1.5% 5.00 [-2.25, 12.25]

Wong TC 2010 Subtotal (95% CI)

73

8.2

30 93

72

10

30 94

3.7% 8.7%

1.00 [-3.63, 5.63] 0.52 [-2.52, 3.55]

Heterogeneity: Chi– = 2.56, df = 2 (p=0.28); I– = 22%

-2.00 [-6.83, 2.83]

Test for overall effect: Z = 0.33 (p=0.74) 1.1.2 Extension Arora R 2011

59

10

36

61

7

37

5.1%

-2.00 [-5.97, 1.97]

Azzopardi T 2005

94

11

27

95

9

27

2.8%

-1.00 [-6.36, 4.36]

Wong TC 2010 Subtotal (95% CI)

72

7

30 93

71

8

30 94

Heterogeneity: Chi– = 1.18, df = 2 (p=0.56); I– = 0%

5.5% 1.00 [-2.80, 4.80] 13.4% -0.55 [-3.00, 1.89]

Test for overall effect: Z = 0.44 (p=0.66) 1.1.3 Pronation

-1.00 [-4.45, 2.45]

84

7

36

85

8

37

6.7%

Azzopardi T 2005

100

2

27

97

6

27

14.1%

3.00 [0.61, 5.39]

Wong TC 2010 Subtotal (95% CI)

77

4

30 93

75

7

30 94

9.6% 30.4%

2.00 [-0.88, 4.88] -1.80 [0.18, 3.42]

0.00 [-3.67, 3.67]

Arora R 2011

Heterogeneity: Chi– = 3.53, df = 2 (p=0.17); I– = 43%

Test for overall effect: Z = 2.17 (p=0.03) 1.1.4 Supination Arora R 2011

85

8

36

85

8

37

5.9%

Azzopardi T 2005

91

19

27

95

7

27

1.4% -4.00 [-11.64, 3.64]

Wong TC 2010 Subtotal (95% CI)

76

4

30 93

75

7

30 94

9.6% 16.9%

1.00 [-1.88, 3.88] 0.24 [-1.93, 2.42]

-1.00 [-3.99, 1.99]

Heterogeneity: Chi– = 1.47, df = 2 (p=0.48); I– = 0%

Test for overall effect: Z = 0.22 (p=0.83) 1.1.5 Radial deviation Arora R 2011

24

6

36

25

7

37

9.0%

Azzopardi T 2005

89

15

27

80

41

27

0.3% 9.00 [-7.47, 25.47]

Wong TC 2010 Subtotal (95% CI)

21

6

30 93

24

7

30 94

7.4% -3.00 [-6.30, 0.30] 16.6% -1.71 [-3.90, 0.49]

Heterogeneity: Chi– = 2.43, df = 2 (p=0.30); I– = 18%

Test for overall effect: Z = 1.52 (p=0.13) 1.1.6 Ulnar deviation Arora R 2011

35

8

36

35

8

37

5.9%

Azzopardi T 2005

93

12

27

76

26

27

0.7% 17.00 [6.20, 27.80]

Wong TC 2010 Subtotal (95% CI)

20

6

30 93

21

7

30 94

Heterogeneity: Chi– = 9.81, df = 2 (p=0.007); I – = 80%

0.00 [-3.67, 3.67]

7.4% 14.0%

-1.00 [-4.30, 2.30] 0.31 [-2.08, 2.70]

564 100.0%

0.32 [-0.58, 1.21]

Test for overall effect: Z = 0.25 (p=0.80)

558 Total (95% CI) Heterogeneity: Chi– = 27.94, df = 17 (p=0.05); I – = 39%

-50

Test for overall effect: Z = 0.70 (p=0.49) Test for subgroup differences: Chi– = 6.98, df = 5 (p=0.22); I– = 28.3%

-25 0 25 50 Internal fixation conservative treatment

Figure 3. Table and forest plot illustrating meta-analysis of range of motion.

the data revealed no significant difference in range of motion, but pronation was significantly better among patients who 236

received conservative treatment (flexion MD=0.52, 95% CI= -2.52–3.55, p=0.74; heterogeneity p=0.28, I2=22%; extenUlus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

Internal fixation Study or Subgroup

Mean

conservative treatment

SD Total

Mean

SD

Total Weight

Mean Difference

Mean Difference

IV, Random, 95% CI

IV, Random, 95% CI

2.1.2 Dorsal angulation (Latest follow-up examination)

-3

10

27

4

8

27

5.3% -7.00 [-11.83, -2.17]

Hu YX 2012

9.13

5.01

48

8.81

2.84

70

6.8%

Li JQ 2012

8.5

2.8

33

5.6

2.1

33

6.9%

2.90 [1.71, 4.09]

-4

1

30 138

3

1

30 160

7.0% 25.9%

-7.00 [-7.51, -6.49] -2.56 [-8.64, 3.51]

Azzopardi T 2005

Wong TC 2010 Subtotal (95% CI)

Heterogeneity: Tau – = 36.79; Chi – = 273.11, df = 3 (p<0.00001; I – = 99%

0.32 [-1.25, 1.89]

Test for overall effect: Z = 0.83 (p=0.41) 2.1.4 Radial length (Latest follow-up examination)

8

3

27

5

4

27

6.7%

3.00 [1.11, 4.89]

Li JQ 2012

10

1.5

33

8.2

1.3

33

6.9%

1.80 [1.12, 2.48]

Wong TC 2010 Subtotal (95% CI)

7.5

2.2

30

4.2

1.1

Azzopardi T 2005

90

Heterogeneity: Tau – = 0.70; Chi – = 7.42, df = 2 (p=0.02; I – = 73%

30

6.9%

3.30 [2.42, 4.18]

90

20.5%

2.62 [1.47, 3.76]

5.30 [2.28, 8.32]

Test for overall effect: Z = 4.49 (p<0.00001) 2.1.6 Radial inclination (Latest follow-up examination) Arora R 2011 Azzopardi T 2005 Hu YX 2012 Li JQ 2012 Wong TC 2010

21.2

2.6

36

15.9

9

37

6.2%

22

5

27

19

6

27

6.2%

3.00 [0.05, 5.95]

12.78 21.5

3.81 2.1

48 33

18.41 18.9

3.71 4.6

70 33

6.8%

-5.63 [-7.01, -4.25]

20

2

30 174

16

2

30 197

6.7% 6.9% 32.9%

2.60 [0.87, 4.33] 4.00 [2.99, 5.01] 1.79 [-2.63, 6.21]

-2.50 [-3.60, -1.40]

Subtotal (95% CI)

Heterogeneity: Tau – = 24.19; Chi– = 133.75, df = 4 (p<0.00001; I – = 97% Test for overall effect: Z = 0.79 (p=0.43) 2.1.8 Ulnar variance (Latest follow-up examination)

0.7

1.8

36

3.2

2.9

37

6.9%

3

2

27

3

2

27

6.9%

0.00 [-1.07, 1.07]

2.1

1.1

30 93

3.2

1.4

30 94

7.0%

-1.10 [-1.74, -0.46]

20.7%

-1.19 [-2.40, 0.02]

495 541 100.0% – – – Heterogeneity: Tau = 18.80; Chi = 949.07, df = 14 (p<0.00001; I = 99%

0.25 [-2.00, 2.50]

Arora R 2011 Azzopardi T 2005 Wong TC 2010 Subtotal (95% CI)

Heterogeneity: Tau – = 0.91; Chi – = 10.23, df = 2 (p=0.006; I – = 80% Test for overall effect: Z = 1.93 (p=0.05) Total (95% CI)

Test for overall effect: Z = 0.22 (p=0.83)

-20 -10 0 10 20 Internal fixation conservative treatment

Figure 4. Table and forest plot illustrating meta-analysis of radiological outcomes.

sion MD= -0.55, 95% CI= -3.00–1.89, p=0.66; heterogeneity p=0.56, I2=0%; pronation MD=1.80, 95% CI=0.18–3.42, p=0.03; heterogeneity p=0.17, I2=43%; supination MD=0.24, 95% CI= -1.93–2.42, p=0.83; heterogeneity p=0.48, I2=0%; radial deviation MD= -1.71, 95% CI= -3.90–0.49, p=0.13; heterogeneity p=0.30, I2=18%; ulnar deviation MD=2.86, 95% CI= -3.33–9.05, p=0.37; heterogeneity p=0.007, I2=80%) (Fig. 3).

Grip strength was reported in 2 studies that were found to be statistically heterogeneous (p=0.08, I2=67%), and a random-effects model was used. Meta-analysis showed that no statistically significant between-group difference in grip strength was found (MD=1.58, 95% CI= -2.24–5.93, p=0.42).

Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Meta-Analysis of Radiological Outcomes Dorsal angulation was reported in 4 studies (heterogeneity p<0.00001, I2=99%). A random-effects model was used and suggested that there was no significant difference in dorsal angulation between the treatment groups (MD= -2.56, 95% CI= -8.64–3.51, p=0.41). Radial length was reported in 3 studies, and a random-effects model suggested that radial length of the conservative treatment group was longer than that of the internal fixation group (MD=2.62, 95% CI=1.47– 3.76, p<0.00001; heterogeneity p=0.02, I2=73%). Radial inclination was reported in 5 studies, among which there was no significant between-group difference (MD=1.79, 95% CI= -2.63–6.21, p=0.43; heterogeneity p<0.00001, I2=97%). Ulnar variance was reported in 3 studies (heterogeneity p=0.006, 237

Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

Study or Subgroup Arora R 2011

Internal fixation Events Total

conservative treatment Events Total Weight

Risk Ratio M-H, Fixed, 95% CI

13

36

5

37

13.3%

2.67 [1.06, 6.73]

Azzopardi T 2005

1

27

1

27

2.7%

1.00 [0.07, 15.18]

Diao HH 2013

1

30

3

30

8.1%

0.33 [0.04, 3.03]

Gupta R 1999 Miller BS 2005

1 6

25 16

1 9

25 18

2.7% 22.9%

1.00 [0.07, 15.12] 0.75 [0.34, 1.64]

21

48

18

50

47.6%

1.22 [0.74, 1.98]

1

30

1

30

2.7%

1.00 [0.07, 15.26]

217 100.0%

1.21 [0.85, 1.74]

Stoffelen DV 1999 Wong TC 2010 Total (95% CI) Total events

212 44

– – Heterogeneity: Chi = 5.63, df = 6 (p=0.47); I = 0%

Risk Ratio M-H, Fixed, 95% CI

38 1 10 50 0.02 0.1 Internal fixation conservative treatment

Test for overall effect: Z = 1.06 (p=0.29)

Figure 5. Table and forest plot illustrating meta-analysis of rate of complications.

Study or Subgroup

Internal fixation Events Total

conservative treatment Events Total Weight

Risk Ratio M-H, Fixed, 95% CI

Arora R 2011

2

36

5

37

58.5%

0.41 [0.09, 1.98]

Diao HH 2013

1

30

0

30

5.9%

3.00 [0.13, 70.83]

Gupta R 1999

0

25

1

25

17.8%

0.33 [0.01, 7.81]

Wong TC 2010

0

30

1

30

17.8%

0.33 [0.01, 7.87]

122 100.0%

0.54 [0.18, 1.63]

Total (95% CI) Total events

121 3

– – Heterogeneity: Chi = 1.42, df = 3 (p=0.70); I = 0% Test for overall effect: Z = 1.10 (p=0.27)

Risk Ratio M-H, Fixed, 95% CI

7 1 10 100 0.01 0.1 Internal fixation conservative treatment

Figure 6. Table and forest plot illustrating meta-analysis of complex regional pain syndrome.

Study or Subgroup

Internal fixation Events Total

conservative treatment Events Total Weight

Risk Ratio M-H, Fixed, 95% CI

Azzopardi T 2005

1

27

0

27

25.5%

3.00 [0.13, 70.53]

Miller BS 2005

2

16

0

18

24.1%

5.59 [0.29, 108.38]

Stoffelen DV 1999

2

48

0

50

25.5%

5.20 [0.26, 105.68]

Wong TC 2010

1

30

0

30

25.5%

3.00 [0.13, 70.83]

125 100.0%

4.17 [0.91, 19.13]

121

Total (95% CI) Total events

6

– – Heterogeneity: Chi = 0.14, df = 3 (p=0.99); I = 0%

Risk Ratio M-H, Fixed, 95% CI

0 1 10 100 0.01 0.1 Internal fixation conservative treatment

Test for overall effect: Z = 1.84 (p=0.07)

Figure 7. Table and forest plot illustrating meta-analysis of infection.

I2=80%). A random-effects model suggested no significant between-group difference (MD= -1.19, 95% CI=-2.40–0.02, p=0.05) (Fig. 4).

Meta-Analysis of Complications Data on rate of complications were pooled from the 10 studies found to be statistically heterogenous (p=0.47, I2=0%). A fixed-effects model suggested that there was no significant between-group difference in rate of complications (RR=1.18, 95% CI=0.82–1.70, p=0.37). Complex regional pain syndrome 238

was one of the most frequently reported complications, and no significant between-group difference was found (RR=0.54, 95% CI=0.18–1.63, p=0.27; heterogeneity p=0.70, I2=0%). Infection was one of the other most frequently reported complications, and no significant between-group difference was found (RR=4.17, 95% CI=0.91–19.13, p=0.07; heterogeneity p=0.99, I2=0%) (Figs. 5–7).

Publication Bias Some quality scoring was low, which made publication bias a Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

0

SE(MD)

2

0

SE(log[RR])

4 0.5 6 1

8

10 -50

-25

Subgroups Flexion Extension Pronation

0

25

MD 50

Supination Radial deviation Ulnar deviation

1.5

2 0.02

0.1

1

10

RR 50

Figure 8. Funnel plots analysis.

concern. However, in the process of selecting literature and extracting data, the meta-analysis was in strict accordance with relevant requirements. Funnel plot analysis revealed no evidence of publication bias (Fig. 8).

DISCUSSION Pooled results with significant heterogeneity from the present meta-analysis of 10 RCTs suggested that patients undergoing conservative treatment for distal radius fractures had better restoration of pronation, but shorter restoration of radial length. Wrist range of motion other than pronation, grip strength, radiographic parameters other than radial length, and rate of complication were not found to be significantly different between the 2 treatments.

In spite of the frequent incidence of distal radius fractures, optimal treatment remains controversial.[21] Zyluk A et al.[22] concluded that conservative treatment of distal radius fractures should be confined only to non- or minimally-displaced fractures, and that all other patients with exceeding acceptable dislocation were candidates for surgery. Some authors concluded that best treatment option is dependent on type of fracture, extent of metaphyseal comminution, quality of the bone, and the medical condition of the patient.[23] Others concluded that conservative treatment remains the safest option in most cases.[24] In the present meta-analysis, no significant difference between internal fixation and conservative treatment were found. It was presently concluded that closed reduction and plaster immobilization are the best treatment of distal radius fracture. Nonetheless, surgical treatment is recommended if fracture redisplacement has occurred.[25] At the same time, the authors believe that a scoring system is a valuable decision-making tool.[26] Distal radius fractures are the most common fracture of the upper extremity and cause variable disability.[27] Evaluation of Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

treatment options is in dispute. Some clinicians believe that ulnar variance and volar tilt are the most important radiographic parameters to be restored, in order to obtain good functional outcome, and that small variations in other radiographic parameters seem not to affect the final outcome in short-term follow-up.[28] The ability of volar locked plating to restore and maintain ulnar variance and volar tilt decreases in more complex fracture types.[29] Treatment of unstable distal radius fractures with volar locked plating and without additional bone graft leads to good fracture reduction without significant secondary displacement.[30] However, Lutz K et al. found that elderly patients with distal radius fractures who underwent surgery had higher rates of complication than those nonsurgically treated.[31] Approximately 2% of patients sustained complication within 30 days following open reduction and internal fixation.[32] Nevertheless, results of the present meta-analysis suggested that there were no significant differences in complication rates between the internal fixation groups and the conservative treatment groups. Regardless of the method of reduction and stabilization, early restoration of wrist function is the goal of distal radius fracture treatment.

Several potential limitations may have affected the present meta-analysis. Ten RCTs were included, but 3 were of low quality (Jadad score <4). The number of cases was small, with a lack of adequate data for analysis. Second, the meta-analysis did not reveal differences in effects specific to fracture type or patient age, due to the limited number of trials. Finally, the performance of activities of daily living, vocational function, and economic impact parameters were not presently discussed, due to lack of reported data.

Generally speaking, the present results are reliable, in spite of the limitations. Clinical differences among patients who received internal fixation and those who received conservative treatment were very slight, although an increase in distal ra239

Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

dius fracture incidence and number of surgeries has been reported.[33,34] Further verification in higher-quality trials is warranted. In such future studies, long-term outcomes should be more carefully considered, more detailed information regarding fracture type should be provided, and explicit concerns regarding patient age should be taken into consideration.

Conclusions Very little clinical difference was found between patients who underwent internal fixation and conservative treatment for displaced distal radius fractures. Optimal choice of treatment must depend upon concrete conditions.

Conflict of interest: None declared.

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27. Tahririan MA, Javdan M, Nouraei MH, Dehghani M. Evaluation of instability factors in distal radius fractures. J Res Med Sci 2013;18:892–6.

28. Dario P, Matteo G, Carolina C, Marco G, Cristina D, Daniele F, et al. Is it really necessary to restore radial anatomic parameters after distal radius fractures? Injury 2014;45 Suppl 6:21–6.

29. Mignemi ME, Byram IR, Wolfe CC, Fan KH, Koehler EA, Block JJ, et al.

Radiographic outcomes of volar locked plating for distal radius fractures.

J Hand Surg Am 2013;38:40–8.

30. Ayong S, Traore A, Postlethwaite D, Barbier O. Functional evaluation of unstable distal radius fractures treated with an angle-stable volar T-plate.

Acta Orthop Belg 2014;80:183–9.

31. Lutz K, Yeoh KM, MacDermid JC, Symonette C, Grewal R. Complications associated with operative versus nonsurgical treatment of distal radius fractures in patients aged 65 years and older. J Hand Surg Am 2014;39:1280–6.

32. Jiang JJ, Phillips CS, Levitz SP, Benson LS. Risk factors for complications following open reduction internal fixation of distal radius fractures.

J Hand Surg Am 2014;39:2365–72.

33. Mattila VM, Huttunen TT, Sillanpää P, Niemi S, Pihlajamäki H, Kannus P. Significant change in the surgical treatment of distal radius fractures: a nationwide study between 1998 and 2008 in Finland. J Trauma 2011;71:939–3.

34. Koo OT, Tan DM, Chong AK. Distal radius fractures: an epidemiological review. Orthop Surg 2013;5:209–13.

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Yu et al. Internal fixation vs conservative treatment for displaced distal radius fractures

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Deplase distal radius kırıklarında internal fiksasyona karşın konservatif tedavi: Randomize kontrollü çalışmaların metaanalizi Dr. Guang-Shu Yu,1 Dr. Yan-Bin Lin,1 Dr. Li-Sheng Le,2 Dr. Mei-Feng Zhan,3 Dr. Xiao-Xiang Jiang4 Xia Men Üniversitesi, Fuzhou İkinci Hastanesi, Ortopedi ve Travmatoloji Kliniği, Fu Zhou, Fujian-Çin Fuzhou İkinci Hastanesi Mawei Şubesi, Ortopedi ve Travmatoloji Kliniği, Fu Zhou, Fujian-Çin 3 Luoyuan İlçe Hastanesi, Ortopedi ve Travmatoloji Kliniği, Fujian-Çin 4 Fujian Üniversitesi, Geleneksel Çin Tıbbı Yüksek Okulu, Fujian-Çin 1 2

AMAÇ: Deplase distal radius kırıklarında internal fiksasyona karşın konservatif tedavinin klinik sonuçlarını karşılaştırmak.

GEREÇ VE YÖNTEM: Yapılan çalışma sonuçları PubMed, Cochrane Library, EMBASE, BIOSIS, Ovid veri tabanları ile CNKI ve Wanfang veri tabanından derlendi. Çalışmaların metodolojik kalitesi eleştirel açıdan değerlendirildi ve ilgili veriler çıkartıldı. Veri analizi için istatistiksel Revman 5.0 yazılımı kullanıldı.

BULGULAR: Çalışmaya katılımı uygun görülen toplam 653 hastayı kapsayan randomize kontrollü yedi İngiliz ve üç Çin çalışmasının metaanalizi yapıldı. Çalışmaların sonuçları orta derecede yanılgı payına sahipti. Metaanaliz sonuçları distal radius kırıkları için konservatif tedavi gören hastalarda pronasyonun daha iyi (MD=1.80; %95 GA: 0.18–3.42; p=0.03; heterojenite p=0.17; I2=%43) sağlandığını, ancak radius boyunun daha kısa kaldığını gösterdi (MD=2.62; %95 GA: 1.47–3.76, p<0.00001; heterojenite p=0.02; I2=%73). Pronasyon dışında el bileğinin hareket erimi, kavrama gücü, radius uzunluğu dışındaki radyografik parametreler ve komplikasyon oranları iki tedavi grubu arasında anlamlı derecede farklı değildi.

TARTIŞMA: Deplase distal radius kırıklarının tedavisinde internal fiksasyon ile konservatif tedavi arasında çok az klinik farklılık olduğu gibi en iyi tedavi seçeneğinin somut koşullara göre kararlaştırılması gerekmektedir.

Anahtar sözcükler: Distal radius kırıkları; internal fiksasyon; konservatif tedavi; metaanaliz.

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Impact of ATLS guidelines, trauma team introduction, and 24-hour mortality due to severe trauma in a busy, metropolitan Italian hospital: A case control study Stefano Magnone, M.D.,1 Andrea Allegri, M.D.,1 Eugenia Belotti, M.D.,2 Claudio Carlo Castelli, M.D.,3 Marco Ceresoli, M.D.,1 Federico Coccolini, M.D.,1 Roberto Manfredi, M.D.,1 Cecilia Merli, M.D.,2 Fabrizio Palamara, M.D.,1 Dario Piazzalunga, M.D.,1 Tino Martino Valetti, M.D.,4 Luca Ansaloni, M.D.1 1

Department of General Surgery I, Pope John XXIII Hospital, Bergamo-Italy

2

Department of Emergency Medicine, Pope John XXIII Hospital, Bergamo-Italy

3

Department of Orthopeadics, Pope John Hospital XXIII, Bergamo-Italy

4

Department of Intensive Care Unit, Pope John Hospital XXIII, Bergamo-Italy

ABSTRACT BACKGROUND: Advanced Trauma Life Support (ATLS) guidelines are widely accepted for use in initial management of trauma patients. The application of ATLS guidelines and introduction of management by means of trauma team (TT) both took place in April 2011. The aim of the present study was to evaluate related effects on mortality in the shock room (SR) and at 24 hours after admission.

METHODS: Data were retrieved by administrative software based on patient admission for trauma of at least 48 hours. Study period was from April 2011 to December 2012, and control period was from January 2007 to March 2011. All admitted patients were identified by first diagnosis (ICD 9-CM), excluding traumatic brain injuries, and only patients admitted to the general intensive care, general surgery, and orthopedics units were included.

RESULTS: The control group (CG) included 198 patients; the study group (SG) included 141. Differences were determined in patient age, which was mean 45.2 years (SD: 19.2) in the CG and mean 49.3 years (SD±18.3) in the SG (p=0.03). Differences were not found regarding gender, length of hospital stay, or Injury Severity Score (ISS). Among the patients who died, no differences were found in terms of systolic blood pressure, metabolic acidosis, or packed red blood cell consumption. Mortality was significantly higher in the CG, compared to the SG (14.1% vs 7.1%, respectively; p=0.033; confidence interval [CI]: 0.21–0.95). Mortality in the shock room was significantly lower in the SG, compared to the CG (0.7% vs 7.1%, respectively; p=0.002; CI: 0.004–0.592).

CONCLUSION: The introduction of ATLS guidelines and TT had a positive impact on mortality in the first 24 hours, both in the SR and after admission.

Keywords: Advanced trauma life support; fatal outcome; trauma centers; trauma system; trauma team.

INTRODUCTION The Advanced Trauma Life Support (ATLS) program has been a mainstay in the treatment of severe trauma for almost 30 years in the US.[1,2] It was imported to Europe in the late ‘80s Address for correspondence: Stefano Magnone, M.D. Piazza Oms 1 24128 Bergamo, Italy Tel: +00 39 035 2673477 E-mail: smagnone@hpg23.it Qucik Response Code

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and readily spread throughout the continent. The first course in Italy was held 20 years ago, and the program has gained popularity since. Moreover, the management of severe trauma by means of a team, the trauma team (TT), has recently been shown to conclusively improve outcome.[3] If correctly implemented, management by TT may have beneficial impact on functional results,[4] as well as mortality.[5] The present aim was to compare 24-hour mortality, shock room (SR) mortality and length of stay (LOS), transfusion rate, and times of first surgical maneuver before and after implementation of ATLS and TT in a busy general hospital in northern Italy.

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MATERIALS AND METHODS The present study was retrospective, with historical controls and level IV evidence.[6] Pope John XXIII is a big metropolitan hospital in Bergamo, serving a population of over 1 million.

Cases of major trauma are referred from throughout the province, as well as from local minor hospitals. Casualties in the accident and emergency department are around 90000 per year, while hospital admission, including urgent and elective admissions, is approximately 50000 per year.

In April 2011, after having drafted a series of diagnostic and therapeutic protocols in accordance with the literature, ATLS guidelines and TT management were implemented. Yearly ATLS courses have been taught since 2010 at the institution, and 60% of all physicians have attended. In late 2011, and in an effort to establish the hospital as a top high-level trauma center, a trauma system for pre-hospital triage was designed in accordance with the ATLS algorithm, to implement TT management.[7] In the present observational study, due to the lack of a trauma register, data for patients admitted to the intensive care unit, or the general surgery or orthopedics wards were retrieved from the discharge chart database using ICD9-CM codes (800–959.9, excluding 905–909.9, 910–924.9, and 930– 939.9, which account for chronic post-traumatic problems, in accordance with Resources for Optimal Care of the Injured Patient[8]). Admitted patients who experienced trauma no more than 3 hours before arrival should have had a minimum 48-hour LOS. Due to differences in triage, transferred patients and elderly patients who experienced domestic trauma were excluded.

Hence, data from the period of January 2007–March 2011 in the control group (CG) and from April 2011–December 2012 in the study group (SG) were retrospectively compiled.

Patients who were not admitted, who died in the SR, were identified as deaths due to trauma by accident and emergency software. All patients were older than 18 years. Mortality that occurred in the first 24 hours of admission was included.

The entirety of clinical charts were reviewed. Only patients with Injury Severity Score (ISS) >15 were included.

In the CG, cases of severe trauma were initially managed by an anesthesiologist, who could call for consultation from a surgeon, orthopedist, or neurosurgeon. Minor trauma could be managed in the accident and emergency department independently by an emergency physician, a surgeon, or an orthopedist, according to existing triage guidelines. In the SG, patients were managed by a team composed of a surgeon with an interest in trauma, an anesthesiologist, and an emergency physician. All decisions were made collectively, with possible referrals from neurosurgery and orthopedic specialists. All members of the team performed the primary survey, as per ATLS guidelines. Pure traumatic brain injury was not considUlus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

ered for admitted patients, as ATLS and TT impact on cases of multitrauma and/or bleeding were considered. Age, gender, LOS, and ISS were used to compare the groups. Other parameters, shown in Table 1, were considered for deceased patients. Traumatic deaths that occurred in the SR were included, even if ISS could not be estimated because computed tomography (CT) or autopsy could not be performed. It is not believed that this impacted final results, and the authors wish to stress the impact of the new guidelines on initial management of severe trauma in the first hours.

Statistical analysis was performed with SPSS software (version 20.0; SPSS Inc., Chicago, IL, USA). Continuous variables not normally distributed were expressed in median and interquartile range (IR), while normally distributed variables were expressed in mean and SD, and were compared with Student’s t-test or Mann-Whitney U test, as appropriate.

Discrete variables were analyzed with Pearson’s chi-square test and Fisher’s exact test, as appropriate. Differences in mortality rate were expressed as odds ratio (OR) with 95% confidence interval (CI). Statistical significance was defined as p<0.05.

RESULTS From the retrospective review, 345 patients were identified, 198 in the CG and 147 in the SG (Fig. 1). Demographics are reported in Table 2. No significant difference between the groups was found in gender, overall LOS, or ISS. The only statistically significant parameter was age – patients in the SG tended to be older. Patient burden increased since April 2011 due to centralization; patient-per-month mean increased from 3.9 to 6.7. At the end of the selections, median ISS of 14 (9–25) was observed in the SG, and 16 (9–25) in the CG, signifying that cases of severe trauma were included in both groups.

Ten deaths occurred in the SG and 28 in the CG (7.1% vs 14.1%, respectively; p=0.033; OR: 0.446; CI: 0.21–0.95), while all other parameters were identical, with the exception of hemoglobin (11.0 in the SG vs 7.7 in the CG, p=0.001) (Table 3). Patients were severely injured, with a median ISS Table 1. Measured parameters in deceased patients Initial systolic blood pressure First available gas analysis and hemoglobin Time spent in the shock room Time to CT (when applicable) Time to first emergency maneuver (surgery, angiography, when applicable) Packed red blood cell units Injury Severity Score (ISS)

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only occurred in the CG (4 patients). Among patients with ISS>15, 14.5% mortality occurred in the SG and 24% in the CG (p=0.14; OR: 0.538; CI: 0.23–1.24). Among mortalities that occurred in the SR, 0.7% was observed in the SG, and 7.1% was observed in the CG (p=0.002; OR: 0.08; CI 0.01– 0.62).

ICD 9 diagnosis (800-959.9 with exlusion of 905-909.9, 910-924.9, 930-939.9) 48 hrs admissions in ICU, General Surgery and Orthopedics 1/2007-12/2012

In the SG, SR LOS tended to be shorter (59 min vs 118 min in the CG), though the difference was not statistically significant (p=0.221). In addition, time to CT scan also tended to be shorter in the SG (47.5 min vs 70.3 in the CG, p=0.59).

Median time to first surgical procedure was shorter in the CG (35 min, 34–99), compared to the SG (54 min, 25–58), though the IR of the SG was narrower, due to a patient who waited more than 120 minutes at the beginning of the period of study. A trend toward more aggressive resuscitation, with a median of 12 packed red blood cell units in the SG (vs 6 in the CG) was evident, but not statistically significant (p=0.82).

Only patients admitted at least 48 hours in Orthopedics, General Surgery and ICU (exluding Neuro ICU) + All deaths before 24 hours

Control Group 1/2007-3/2011

Study Group 4/2011-12/2012

198 patients (exluding deaths

147 patients (exluding deaths

related to TBI)

related to TBI)

Figure 1. Study design.

of 30 (25–37) for deaths in the SG and 26 (25–33) in the CG. While there was no statistically significant difference between groups (p=0.42), deaths among patients with ISS<15

DISCUSSION Trauma centers are regarded as the optimal regional environment for severe trauma care and evaluation of trauma ca-

Table 2. Group demographics

Study group (4/2011–12/2012)

Patients Gender (M/F) % of male

Control group (1/2007–3/2011)

p

141 198 (113/28) 80.1%

(158/40) 75.4%

0.9

Mean age, years, Mean±SD

49.3±18.3

45.2±19.2

0.03

Length of hospital stay, days, Mean±SD

14.9±14.1

14.0±11.9

0.72

Injury Severity Score (IR)

14 (9–25)

16 (9–25)

0.59

Patient per month, mean

6.7

3.9

//

Study Group

Control group

p

90±17

88±22

0.87

SD: Standard deviation; IR: Interquartile range.

Table 3. Characteristics of deceased patients

Initial systolic blood pressure (mmHg), Mean±SD First hemoglobin (g/L)

11.0 (9.8–13.3)

7.7 (5.7–10.2)

0.001

Base excess

-9.3 (-7.5–-11.7)

10.0 (-5.0–-15.5)

0.301

pH

7.08 (7.08–7.26)

7.17 (7.06–7.33)

0.522

59 (74–159)

118 (19–121)

0.221

Time in the Shock Room (minutes) Time to CT (minutes), Mean±SD Time to first emergency maneuver (surgery, angiography) (minutes)

47.5±45

70.3±40

0.59

54 (25–58)

35 (34–99)

0.756

Red blood cell units

12 (2–14)

6 (8–16)

0.82

Injury Severity Score (ISS)

30 (25–37)

26 (25–33)

0.42

7.1 (10)

14.1 (28)

0.033

Mortality, % (n) SD: Standard deviation; IR: Interquartile range; CT: Computed tomography.

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sualty.[9] Recent opinion and studies have clearly established the advantages of ATLS guidelines and multidisciplinary TT, which include better organization, improvement of clinical and non-clinical skills, adherence to guidelines,[10] and priority approaches, if correctly implemented.[11] Strong evidence of a positive effect on mortality and morbidity is still lacking, though a trend toward improvement has been shown.[12–14]

effect of bleeding, though no differences in base excess or pH were observed. Levels are thought to have been higher in the SG due to shorter stay in the SR and faster primary evaluation.[18,19] Another explanation could be a trend toward damage control resuscitation in a prehospital setting (i.e., less crystalloid infusion used). Unfortunately, no data is available to confirm this hypothesis.

At the time, in 2010, that the present hospital administration acknowledged the need for improvement, ATLS was not yet included in local guidelines. There was no team-centered management of moderate to severe trauma, and patients could have been managed in the emergency department for hours before a physician took definitive charge, and then only after several consultations. In early 2011, surgeons, emergency physicians, and intensive care unit doctors drafted several diagnostic and therapeutic protocols, which in some cases were published.[15] Though this certainly contributed to the present results, we are confident that implementation of ATLS provided the necessary improvement. Surgeons were the first to complete the ATLS provider course, followed by emergency physicians, and intensive care and anesthesiologist teams. An extensive annual ATLS training program is ongoing, in an effort to broaden a common language among physicians.

Currently, more than 50% of TT members are ATLS-certified.

The delay in the certification of all is due to the large number of anesthesiologists who are on TT duty, a number in the emergency on-call rotation that will hopefully be reduced in the near future. In early 2015, nurses began to attend Advanced Trauma Care for Nurses certificate training.

Several limitations affected the present study, including the retrospective design. No existing registry was used, potentially complicating patient selection and impairing statistical significance of mortality. Fewer patients were included in the CG, as centralization had not yet been implemented. In early 2011, a shared protocol between the Emergency Medical System and the hospital led to a steep increase in per month patient case load (mean of 3.9 patients per month in the CG, vs 6.7 patients per month in the SG). It is believed that more pronounced centralization, accounting for more than 80% of severe trauma patients in the local area, explains the difference in mean age of groups. It is of great value that, in spite of the older age of the SG, a lower mortality rate was observed.

Time spent in the SR was significantly lower in the SG. It is believed that this is one of the main contributions of ATLS and TT implementation, with a better focus on decision-making and priority of treatment. On the contrary, some aspects, due to low numbers (namely time to CT and mortality in the SR) showed better trends in the SG without reaching statistical significance, as has been recently confirmed.[20] Further study is required to confirm these promising results, but we strongly believe that ATLS and TT implementation provided a great improvement in the treatment of severe trauma.

Presently, the TT leader is the surgeon, due to the relatively low number of attending surgeons, 10 with an interest in general, emergency, and trauma surgery. Another reason is that we believe a surgeon-led team is the best way to achieve timely decisions regarding diagnosis and course of treatment.[16] A huge effort was made to change behavior and attitude toward the course and functioning as a team, initially regarded as a source of hurdles and time-consuming on-site consultation. The present results indicate that SG mortality was significantly lower, as was time spent in the SR, even if not statistically significant. Moreover, the present data show that unstable patients no longer undergo CT scan, a critical issue prior to the introduction of the new rules. Two patients had sustained cardiac arrest and died during the scan, and 3 had worsened during radiological examination and died in the SR without receiving surgical or interventional treatment.

In the CG, 4 deaths were observed in patients with ISS<15, while no such deaths were observed in the SG. ATLS and TT introduction likely had an impact on preventable deaths, a major concern of every medical system.[17] The only statistically significant difference between groups was in hemoglobin, which is presently believed to be a later Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Conclusions Implementation of ATLS guidelines and TT had a strong impact on 24-hour mortality, and led to further expediting of initial management of multiple trauma patients. Low numbers mandate further study, to confirm these favorable trends.

Conflict of interest: None declared.

REFERENCES 1. Radvinsky DS, Yoon RS, Schmitt PJ, Prestigiacomo CJ, Swan KG, Liporace FA. Evolution and development of the Advanced Trauma Life Support (ATLS) protocol: a historical perspective. Orthopedics 2012;35:305–11.

2. Søreide K. Three decades (1978-2008) of Advanced Trauma Life Support (ATLS) practice revised and evidence revisited. Scand J Trauma Resusc Emerg Med 2008;16:19.

3. Tiel Groenestege-Kreb D, van Maarseveen O, Leenen L. Trauma team.

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4. Leung GK, Ng GK, Ho W, Hung KN, Yuen WK. Impact of a multidisciplinary trauma team on the outcome of acute subdural haematoma.

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6. Sauaia A, Moore EE, Crebs JL, Maier RV, Hoyt DB, Shackford SR. Evidence level of individual studies: a proposed framework for surgical research. J Trauma Acute Care Surg 2012;72:1484–90.

7. Advanced Trauma Life Support, 8th Edition. American College of Surgeons Committee on Trauma 2008.

8. Resources for Optimal Care of the Injured Patient. American College of Surgeons Committee on Trauma 2006.

9. MacKenzie EJ, Rivara FP, Jurkovich GJ, Nathens AB, Frey KP, Egleston BL, et al. A national evaluation of the effect of trauma-center care on mortality. N Engl J Med 2006;354:366–78.

10. Tsang B, McKee J, Engels PT, Paton-Gay D, Widder SL. Compliance to advanced trauma life support protocols in adult trauma patients in the acute setting. World J Emerg Surg 2013;8:39.

11. Kelleher DC, Jagadeesh Chandra Bose RP, Waterhouse LJ, Carter EA, Burd RS. Effect of a checklist on advanced trauma life support workflow deviations during trauma resuscitations without pre-arrival notification. J Am Coll Surg 2014;218:459–66.

12. Mohammad A, Branicki F, Abu-Zidan FM. Educational and clinical impact of Advanced Trauma Life Support (ATLS) courses: a systematic review. World J Surg 2014;38:322–9.

13. Jayaraman S, Sethi D. Advanced trauma life support training for hospital staff. Cochrane Database Syst Rev 2009.

14. Leung GK, Ng GK, Ho W, Hung KN, Yuen WK. Impact of a multidisciplinary trauma team on the outcome of acute subdural haematoma.

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15. Magnone S, Coccolini F, Manfredi R, Piazzalunga D, Agazzi R, Arici C, et al. Management of hemodynamically unstable pelvic trauma: results of the first Italian consensus conference (cooperative guidelines of the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology -Section of Vascular and Interventional Radiology- and the World Society of Emergency Surgery). World J Emerg Surg 2014;9:18.

16. Leeper WR, Leeper TJ, Vogt KN, Charyk-Stewart T, Gray DK, Parry NG. The role of trauma team leaders in missed injuries: does specialty matter? J Trauma Acute Care Surg 2013;75:387,90.

17. Navarro S, Montmany S, Rebasa P, Colilles C, Pallisera A. Impact of ATLS training on preventable and potentially preventable deaths. World J Surg 2014;38:2273–8.

18. Knottenbelt JD. Low initial hemoglobin levels in trauma patients: an important indicator of ongoing hemorrhage. J Trauma 1991;31:1396–9.

19. Richards JB, Wilcox SR. Diagnosis and management of shock in the emergency department. Emerg Med Pract 2014;16:1–23.

20. Rados A, Tiruta C, Xiao Z, Kortbeek JB, Tourigny P, Ball CG, et al. Does trauma team activation associate with the time to CT scan for those suspected of serious head injuries? World J Emerg Surg 2013;8:48.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yoğun bir metropol hastanesinde ağır travmada 24 saat içindeki ölüm oranlarına ATLS kılavuzlarının ve travma ekibinin etkisi: Bir olgu kontrollü çalışma Dr. Stefano Magnone,1 Dr. Andrea Allegri,1 Dr. Eugenia Belotti,2 Dr. Claudio Carlo Castelli,3 Dr. Marco Ceresoli,1 Dr. Federico Coccolini,1 Dr. Roberto Manfredi,1 Dr. Cecilia Merli,2 Dr. Fabrizio Palamara,1 Dr. Dario Piazzalunga,1 Dr. Tino Martino Valetti,4 Dr. Luca Ansaloni1 Papa 23. John Hastanesi, 1. Genel Cerrahi Kliniği, Bergamo, İtalya Papa 23. John Hastanesi, Acil Tıp Kliniği, Bergamo, İtalya Papa 23. John Hastanesi, Ortopedi Kliniği, Bergamo, İtalya 4 Papa 23. John Hastanesi, Yoğun Bakım Ünitesi, Bergamo, İtalya 1 2 3

AMAÇ: Travma hastalarının başlangıç tedavisinde ATLS kılavuzları geniş ölçüde kabul görmüştür. Hastanemiz Nisan 2011’de ATLS ve travma ekibi uygulamasını başlatmıştır. Bu çalışmanın amaçları şok odasında ve kabulden sonraki 24 saat içinde ölüm oranlarındaki değişiklikleri değerlendirmektir.

GEREÇ VE YÖNTEM: Travma sonrası en az 48 saat içindeki hasta kabullerinin kaydedildiği idarenin bilgisayar yazılımından hastalara ait veriler alındı. Çalışma dönemi Nisan 2011 ila Aralık 2012 ve kontrol dönemi Ocak 2007 ila Mart 2011 arası idi. Kabul edilen hastaların tümü ilk tanılarına (ICD 9-CM) göre tanımlandı, travmatik beyin travmaları dışlandı, yalnızca genel yoğun bakım ünitesi, genel cerrahi ve ortopediye kabul edilen hastalar göz önüne alındı.

BULGULAR: Kontrol grubunda (KG) 198, çalışma grubunda (ÇG) ise 141 hasta vardı. İki grup cinsiyet, hastanede yatış süresi ve Travma Şiddet Derecesi Skoru açısından benzer olmasına rağmen yaşları farklıydı (yaş ortalamaları: KG, 45.2±19.2 yıl ve ÇG 49.3±18.3 yıl [p=0.03]). İki grupta eks olan hastalarda sistolik kan basıncı, metabolik asidoz veya eritrosit süspansiyonu kullanımı açısından herhangi bir fark yoktu. Kontrol grubunda ölüm oranları anlamlı derecede daha yüksekti (KG 1 %4.1, ÇG, %7,1; p=0.033, Güven Aralığı [GA] 0.21–0.95). Şok odasında mortalite çalışma grubunda anlamlı derecede daha düşüktü (ÇG, %0.7 ve KG, %7.1 (p=0.002, GA 0.004–0.592).

TARTIŞMA: Hem şok odasında hem de hastaneye kabul sonrası ATLS kılavuzları ve travma ekibinin kullanılmaya başlanması hem şok odasında hem de hastaneye kabulden sonraki ilk 24 saat içindeki mortaliteyi azaltmıştır.

Anahtar sözcükler: Ölümcül sonuç; travma ekibi; travmada ileri yaşam desteği; travma merkezleri; travma sistemi.

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ORIG I N A L A R T IC L E

Evaluating incorrect management of transferred pediatric burn patients Atilla Şenaylı, M.D.,1 Fatma Öztürk, M.D.,2 Müjdem Nur Azılı, M.D.,2 Sabri Demir, M.D.,2 Rabia Demir, M.D.,2 Emrah Şenel, M.D.1 1

Department of Pediatric Surgery, Yildirim Beyazit University Faculty of Medicine, Ankara-Turkey

2

Department of Pediatric Surgery, Children’s Health and Disease Haemotology-Oncology Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Burns constitute one of the most important, potentially fatal types of trauma. Appropriate emergency management is essential in the avoidance of complication and the success of treatment. Emergency management and indications of transfer throughout the country were reviewed in the present study.

METHODS: Charts of 187 patients transferred to the present hospital from other cities between January 2009 and December 2013 were evaluated. Factors included demographics, referral vehicles, intravenous fluid therapy, respiratory conditions, urine drainage, and surgical complications.

RESULTS: According to transfer criteria, only 15 patients (8%) were transferred under appropriate conditions. In the transfer of 172 (92%) patients, at least 1 error was found.

CONCLUSION: Transport failure, and incorrect management and treatment causing complications such as the development of respiratory problems after unnecessary sedation, occur in developing countries such as Turkey. Referral protocols for burn patients have already been defined in the country, though training and feedback regarding effective treatment is still lacking.

Keywords: Burns; children; prevention; therapy.

INTRODUCTION Acute burn management is necessary for survival. Organ damage, infection, and pain during burn treatment are widely regarded as the primary problems.[1,2] Burn injury may occur on an individual basis, or may be sustained by multiple people in conditions such as those of an earthquake.[3] Simple procedures to treat acute injury are effective in achieving survival.[4] Assessing need for hospitalization is a component of treatment.[1] Hospitals with facilities inadequate for burn treatment should have transfer strategies. Some indications for patient transfer are 2nd-degree burns covering 10% or more of total body surface area (TBSA), 3rd-degree burns, burns in Address for correspondence: Atilla Şenaylı, M.D. Ziraat Mahallesi, İrfan Baştuğ Caddesi, Kurtdereli Sokak, No: 10, Ankara, Turkey Tel: +90 312 - 326 05 54 E-mail: atillasenayli@gmail.com Qucik Response Code

certain locations, chemical burns, electric burns, inhalation injury, associated trauma, current diseases, and unskilled staff.

[5] The error rate of non-specialist physicians has been reported as high as 75%.[4,6,7] In addition, unfortunately, 58% of burn centers have no treatment protocols.[8] Errors in management during burn patient transfer were presently evaluated in an effort to improve accountability and reform emergency care strategies.

MATERIALS AND METHODS Patients transferred from other cities were evaluated in the present retrospective study. Reports of status at arrival were recorded and compared with the standards of transfer. Parameters evaluated were: transfer status, TBSA of burn, intravenous access status, bladder catheterization, intubation, respiratory problems, infections, and surgical problems. Results were compared with those reported.

Ulus Travma Acil Cerrahi Derg 2016;22(3):247–252 doi: 10.5505/tjtes.2015.46037

RESULTS

Copyright 2016 TJTES

Between January 2009 and December 2013, 187 patients (106 males, 81 females) were admitted to the present institution from other cities. Mean patient age was 41 months. De-

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Table 1a. Patient demographics Demography Findings Male/female 106/81 Mean age (month)

41.34

Mean hospitalization (days)

22.2

Fluid Management

Table 1b. Burn types, numbers, and percentages Burn type

Findings

Scald burn

137

Flame 30 Electricity 10 Contact burn

2

Flame+inhalation 6

A total 136 (72%) patients had scald burns, 37 (19%) had flame burns, and 11 (6%) had electrical burns. Three (2%) patients had contact burns and chemical injuries (Table 5), and 5 patients had flame burns with inhalation injuries.

69

20–39% 77 41

40% and higher

Intravenous catheter had not been administered in 22 (12%) patients upon admission. In addition, no intravenous fluid had been administered in a total of 128 patients (68%), including the 22, upon admission. Hypotonic fluid had been administered to 38 (24.5%) patients; Ringer’s lactate and 0.9% NaCl solution had been administered to only 21 (12.2%) patients.

Fluid management is shown in Table 4.

Burn Area Measurements

Chemicals 2 1–19% burn area

the first 2–4 hours of admission. In total, 17 patients were extubated on the first day of admission, all of whom had been intubated due to respiratory depression of narcotic analgesics. All had scald burns, inhalation burns were not detected.

Two other patients, intubated due to concerns of sepsis, had inhalation-related problems. One patient recovered, after the development of cerebral palsy. Patient numbers and causes of intubation are shown in Table 3.

mography and burn features are described in Tables 1a and b.

The summary of evaluated parameters and their percentages were shown in Table 2.

When calculated burn area differed more than 5% at initial and final examination, the discrepancy was assumed to be based on miscalculation. According to the criteria, 38% (n=71) of burn rates had been miscalculated. In addition, 11 transferred patients had burns of less than 10%, rendering the transfer unnecessary.

Intubation and Respiratory Problems A total of 21 patients (13%) were intubated prior to arrival or in the present unit. Average burn percentage of these patients was 38%. If intubation indications were accurate, ventilation was continued. If indications were inaccurate, as in the majority of cases, patients were extubated, typically within

Burn area measurement errors were evaluated. Measurement errors of less than 5% were considered insignificant. A total of 71 (38%) patients had burns that covered less TBSA than had been originally recorded. Eleven of the 71 patients (16%) had burns covering less than 10% TBSA. A total of 116 patients (62%) had been transferred with correct burn area measurements. Burn conditions, which are important for transfer indication, are summarized in Box 1.

Urinary Bladder Catheterization Urinary catheters had been administered in only 27 patients.

Burn areas were less than 20% TBSA in 67 patients, who should have been transferred without catheterization. Among patients with burn areas greater than 20%, 93 patients had not been administered a catheter. The transfer of these patients without urinary catheterization was assumed to be an error. Rates of urinary catheterization are shown in Table 6.

Table 2. Referral parameters of burn patients. Well-maintained is defined as optimal conditions for transfer (effective fluid, right solution, urinary monitoring) Transferring conditions

Present

Absent

Wrong indication findings

% Wrong ind.

Intravenous catheter

165

22

22

11.7

Ringer’s lactate

21

166

166

88.7

Urinary catheter

27

160

93

49.7

Intubated patient

21

166

17

9

Air ambulance

18

169

Well-maintained

15 172

248

– 172

91.9

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Emergency Fasciotomy

Table 3. Intubations and related problems are shown Intubation

Number of Wrong patients indications

Respiratory depression

17

17

Septic problem

2

0

Inhalation

2 0

Total

21 17

Transfer Types

Table 4. Fluid management of patients Fluid management

Number of TBSA burn patients percentage

No intravenous fluid

128* 25

Hypotonic solutions

38

30

Ringer lactate

21

30

Total

187 –

Emergency fasciotomy is considered to be an important burn treatment, particularly of circular burns. The procedure was not performed in 5 patients, and was performed inadequately in 1. Refasciotomy was performed in 5 patients and fasciotomy was extended for 1. Three patients in this group died during follow-up.

*22 patients did not have intravenous catheter, and 106 patients had intravenous catheter without fluid. TBSA: Total body surface area.

Three types of transfer vehicles were used: vehicles belonging to the patient, land ambulance, and air ambulance. Eighteen patients (9.6%) were transferred from other cities in their own vehicles, 13 of whom had burns covering more than 10% of TBSA (mean: 23%; min: 10%; max: 50%), and who should have been transferred by ambulance. Eighteen patients (9.6%) arrived by air ambulance, 3 of whom died within 24–72 hours.

A total of 151 patients arrived by land ambulance. Although transfer indication is a burn area of 10% TBSA or greater, 10 patients transferred by land ambulance had a burn area of less than 10%. Types of transfer and information regarding indication are shown in Table 8.

DISCUSSION Infection and Other Acute Problems Infection was detected in 6 patients by specimens obtained at arrival. Candidiasis (n=3), Acinetobacter (n=2) and Enterococcus with Klebsiella (n=1) were identified. Two patients died 48 hours after arrival. Median burn area of these patients was 28%. One died of acute renal failure, the other of septicemia due to Acinetobacter. Rates of infection are shown in Table 7.

Millions of people world-wide sustain burn injuries in a single year.[1] Burns are a major problem, particularly in developing countries.[9–11] In spite of the number and scale of injuries, primary burn management has yet to be perfected.[1] Many factors may contribute to insufficient management. Lack of data feedback regarding mistakes is a major problem, usually caused by insufficient data collection training of primary care

Table 5. Burn type, mean burn total body surface area, and number of patients Burn area measurements

Scald burns

Flame burns

Electric burns

Chemical burns

Number (% patients), n (%)

136 (73)

37 (20)

11 (6)

3 (1)

34

24

9.70

15

Burn total body surface area percentage (%) Box 1: Number of patients with misidentified burn areas.

Number of patients

Diagnostic difference Incorrect burn area measurement

71

Burn area less than10%

11

Table 6. Catheterization of urinary bladder, according to burn total body surface area Urinary catheter

Number of patients

1–19%

20–39%

40–59%

60-↑

Present

27 2* 11 9 5

Absent

160 67* 65 23 5

Total

187 69* 76 32 10

*Transferring without urinary catheterization was suggested as acceptable.

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Table 7. Infections of referred patients are shown Infection

Number of patients

Candidiasis 3 Acinetobacteria 2 Other 1 Death 2

providers. It was reported that degree of burn was incorrectly defined in 75% of cases, with incorrect burn classification in the majority of patients.[6] Primary care physicians manage the majority of burn cases.[6] A primary goal of these physicians is to evaluate indications for hospital admission or outpatient care.[1] If necessary, patients should be consulted, and transfer, if appropriate, must be conducted properly.[12,13] Transfer criteria have been identified[5] as follows: Patients must be transferred if they have 2nd-degree burns covering 10% or more of TBSA, 3rd-degree burns, burns in certain locations, chemical burns, electric burns, inhalation injury, associated trauma, current disease, and/or if staff at the immediate institution are unskilled.[5] These indicators should be reported correctly, in addition to time of injury.[5] In some countries, burns are sufficiently treated in a few tertiary management centers in certain big cities.[14] Burn units and centers are distributed all over Turkey, and are collectively integrated with structured protocols. The Turkish Ministry of Health has also prepared protocols for the adequate treatment of burn patients, and related training and graduate programs exist.[15] These criteria have also been published by the Scientific Burn Council of Ministers.[16] Although a theoretically well-defined protocol is available, significant errors affecting efficiency and outcome of burn management are common, as is demonstrated by the present results. To our knowledge, the present is the first report to assess emergency burn management in Turkey. There was, surprisingly, insufficient information available in the literature in English. As a result, we prefer to individually discuss each parameter of the transfer criteria.

Children have narrower airways than adults.[8] Particularly in cases of inhalation injury, intubation may be performed when needed,[6,17] as it may be life-saving if correctly performed.

However, the present results show that intubation has often been incorrectly performed, and that a majority of patients should not be intubated. By evaluating transfer reports, it was discovered that intubation was often performed after incorrect doses of inappropriate sedative agents were administered.

Unfortunately, 1 patient with ischemic hypoxia developed cerebral palsy after an incorrectly administered intubation.

In Turkey, one of the most significant errors in burn management during transfer is failure of fluid resuscitation. Suitable organ perfusion is a protective agent against shock.[5,13,18] Crystalloid solutions are important in the protection of vital organs.[5,13,18] Timing is also important; if fluid resuscitation is not initiated within 2 hours of injury, risk of death may increase.[18,19] Standard criteria for adequate fluid resuscitation exist.[20,21] However, rates of incorrect fluid resuscitation have been reported as 23%.[22] Although this percentage was greater in the present study, results of resuscitation (11.3%) were also better. Patient transfer is a major handicap for fluid resuscitation. When transfer time is long, risk of complication increases.[14] Though the national burn management protocol includes guidelines for fluid resuscitation,[15] these guidelines have not been correctly implemented, as is regrettably demonstrated by the present results.

Burn wounds are expressed as a percentage of TBSA, and evaluation of TBSA is an important factor in appropriate burn management.[1] For children, the Lund and Browder chart is the easiest and most accurate form of measurement.[23] In addition, it is possible to calculate the appropriate amount of liquid for treatment.[24] On this issue, the present findings may contribute to decreasing the number of unnecessary referrals, as well as rates of morbidity during transfer. It was found that in 38% of cases, initial burn area measurements recorded were lower than those conducted at the present institution.

A similar rate (37%) was reported in a study in which burn percentages were compared.[25] In addition, as the burn area was less than 10% in 16 of the present patients, hospitalization was not indicated.

Organ perfusion is an important concern during burn treatment.[5,13,18] A main determinant of proper perfusion is urine output.[18] Proper fluid administration is classified as 1 mL/ kg/h.[5,13] Patients must be monitored for urine output with urinary catheterization in intensive care units. Among the 160

Table 8. Transfer types of patients Transfer types

Number

Wrong indication

Reason of wrong indication

Own vehicle

18

13*

>10 burn TBSA

Land ambulance

151

10**

<10 burn TBSA

Air ambulance

18

0

0

*Patients with more than 10% burn TBSA were not supposed to be transferred using their own vehicles. **Patients with less than 10% burn TBSA were not supposed to be transferred. TBSA: Total body surface area.

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present patients without urinary catheters, no urinary catheter had been administered in 93 patients with burns covering more than 20% of TBSA. In the present assessment, this finding was considered a failure of treatment. In fact, rates of urinary catheterization may indicate efficacy of treatment.

In the present series, 6 patients had infection upon arrival, though none were colonized. It is believed that primary causes of infection were poor wound care, poor excision of dead tissue, inadequate surgical procedure, and unnecessary use of antibiotic. All infected patients had been transferred late, suggesting that infection may spread during the transfer.

Ethical problems are also present.

Escharotomy and fasciotomy are the most important surgical procedures performed in burn patients. Indications are typically high-voltage electrical injury, and fractured bone or vascular injuries.[13] Compartment syndrome is the main reason to perform fasciotomy,[13,18] though fasciotomy is rarely necessary.[13] However, if these procedures are not performed when necessary, irreversible problems occur. In a total of 6 patients (3%), fasciotomies were performed or revised upon arrival. As a result, performance of emergency fasciotomy was found to be insufficient.

Land and air ambulances are effective tools for patient transfer.

In the present study, 151 patients arrived with land ambulance, 18 arrived with air ambulance, and 18 arrived in their own vehicle. Medial burn percentage of TBSA was 45% for patients transferred by air, all of whom were transferred with correct indications. Air ambulance transfers were found to be incorrect in nearly 50% of cases, in a study with an English population. In Turkey, air transfers are a new function, which may be the reason for the high percentage of correct transfer performance.[26] Three patients transferred by air ambulance died.

Presently revealed are significantly high rates of errors made by emergency staff during burn transfer management. Major mistakes were evident in selection of fluid (88.7%), use of urinary catheter (49.7%), intubation (9%), and fasciotomy (3%). Each may cause death. Other problems may arise during transfer, and some patients may travel to various hospitals before being admitted. This too will contribute to increased morbidity and/or mortality.[27] As mentioned above, little related information is available in the literature, constituting a limitation of the present study.

Nevertheless, the present may be a pioneering study in the evaluation of burn transfer management.

Conclusion Burn injuries are common, and fortunately, death is a rare outcome. Complications may arise when emergency management is inappropriately performed, which may occur in any care center. Transfer to a more advanced center is a logical Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

means of minimizing complications. However, rational transfer strategies are needed. If transfer policy is to be improved, training is necessary. For this purpose, as an example, the American Burn Association has published an Advanced Burn Life Support protocol. Treatment protocol for burn patients has been published in most countries. In Turkey, protocol published by the Ministry of Health was implemented in all emergency service departments. However, universal adaptation has been difficult to achieve in Turkey and in other developing countries, as the present results demonstrate. Effective management of burn patients requires appropriate transfer decisions and timing, as well as accurate recording of information. In order to ensure optimal burn management, training must be provided to all staff, and feedback is vital in the efficacy of this education.

Funding: None declared.

Conflict of interest: None declared.

REFERENCES 1. Morgan ED, Bledsoe SC, Barker J. Ambulatory management of burns.

Am Fam Physician 2000;62:2015–26, 2029–30, 2032.

2. Düzgün AP, Senel E, Ozmen MM, Kulaçoğlu H, Işik Y, Coşkun F. The evaluation of the patients admitted to a burn center in Turkey. Ulus Travma Acil Cerrahi Derg 2003;9:250–6.

3. Dursun R, Karadaş S, Görmeli G, Işık Y, Cakır C, Görmeli CA. Analysis of burn cases observed after the 2011 Van earthquake. Ulus Travma Acil Cerrahi Derg 2013;19:251–5.

4. Allison K, Porter K. Consensus on the prehospital approach to burns patient management. Emerg Med J 2004;21:112–4.

5. Mlcak RP, Buffalo MC, Jimenez CJ. Pre-hospital management transportation and emergency care. In: Hendron DN, editor. Total Burn Care, London: Elsevier Saunders; 2014. p. 93–102.

6. Spanholtz TA, Theodorou P, Amini P, Spilker G. Severe burn injuries: acute and long-term treatment. Dtsch Arztebl Int 2009;106:607–13.

7. McCormack RA, La Hei ER, Martin HC. First-aid management of minor burns in children: a prospective study of children presenting to the Children’s Hospital at Westmead, Sydney. Med J Aust 2003;178:31–3.

8. Holland AJ. Pediatric burns: the forgotten trauma of childhood. Can J Surg 2006;49:272–7.

9. Senel E, Yasti AC, Reis E, Doganay M, Karacan CD, Kama NA. Effects on mortality of changing trends in the management of burned children in Turkey: eight years’ experience. Burns 2009;35:372–7.

10. Cuenca-Pardo J, de Jesús Alvarez-Díaz C, Comprés-Pichardo TA. Related factors in burn children. Epidemiological study of the burn unit at the “Magdalena de las Salinas” Traumatology Hospital. J Burn Care Res 2008;29:468–74.

11. Razzak JA, Luby SP, Laflamme L, Chotani H. Injuries among children in Karachi, Pakistan--what, where and how. Public Health 2004;118:114– 20.

12. Mandl KD, Kohane IS, Brandt AM. Electronic patient-physician communication: problems and promise. Ann Intern Med 1998;129:495–500.

13. White CE, Renz EM. Advances in surgical care: management of severe burn injury. Crit Care Med 2008;36(7 Suppl):318–24.

14. Ahuja RB, Bhattacharya S. Burns in the developing world and burn disasters. BMJ 2004;329:447–9.

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16. Yastı AÇ, Şenel E, Saydam M, Özok G, Çoruh A, Yorgancı K. Guideline and treatment algorithm for burn injuries. Ulus Travma Acil Cerrahi Derg 2015;21:79–89.

17. Foley FD, Moncrief JA, Mason AD Jr. Pathology of the lung in fatally burned patints. Ann Surg 1968;167:251–64.

18. Latenser BA. Critical care of the burn patient: the first 48 hours. Crit Care Med 2009;37:2819–26.

19. Wolf SE, Rose JK, Desai MH, Mileski JP, Barrow RE, Herndon DN. Mortality determinants in massive pediatric burns. An analysis of 103 children with > or = 80% TBSA burns (> or = 70% full-thickness). Ann Surg 1997;225:554–69.

20. Warden GD. Burn shock resuscitation. World J Surg 1992;16:16–23.

21. Carvajal HF. Fluid therapy for the acutely burned child. Compr Ther 1977;3:17–24.

22. Hagstrom M, Wirth GA, Evans GR, Ikeda CJ. A review of emergency department fluid resuscitation of burn patients transferred to a regional, verified burn center. Ann Plast Surg 2003;51:173–6.

23. Lund CC, Browder NC. The estimation of areas of burns. Surg Gynecol Obstet 1944;79:352–8.

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26. Chipp E, Warner RM, McGill DJ, Moiemen NS. Air ambulance transfer of adult patients to a UK regional burns centre: Who needs to fly? Burns 2010;36:1201–7.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Transfer edilen çocuk yanık hastalarındaki yanlış uygulamaların değerlendirilmesi Dr. Atilla Şenaylı,1 Dr. Fatma Öztürk,2 Dr. Müjdem Nur Azılı,2 Dr. Sabri Demir,2 Dr. Rabia Demir,2 Dr. Emrah Şenel1 1 2

Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Ankara Ankara Çocuk Sağlığı ve Hastalıkları Hematoloji-Onkoloji Eğitim ve Araştırma Hastanesi, Çocuk Cerrahisi Kliniği, Ankara

AMAÇ: Yanıklar çocuklarda ölüme en çok neden olabilen travmalardan biridir. Bu yüzden, uygun acil müdahale komplikasyonları önlemek ve başarılı tedavi sağlamak için gereklidir. Bu çalışmada, yanık hastalarının acil müdahale çalışmaları değerlendirildi ve ülkemizdeki sevk endikasyonları gözden geçirildi.

GEREÇ VE YÖNTEM: Hastanemize Ocak 2009 ile Aralık 2013 tarihleri arasında diğer şehirlerden sevk edilmiş olan 187 hastanın dosyaları değerlendirildi. Demografiler, sevk araçları, intravenöz sıvı tedavileri, solunum durumları, idrar çıkışları ve cerrahi komplikasyonlar değerlendirildi.

BULGULAR: Transfer kriterlerine göre sadece 15 hasta (8%) uygun koşullarda sevk edilmiştir. Yüz yetmiş iki hasta (%92) için ise, en az bir transfer hatası ile sevk edildiği anlaşılmıştır.

TARTIŞMA: Gelişmekte olan ülkelerde; yanlış müdahaleler, hatalı tedaviler, gereksiz sedasyon ile solunum problemleri ve transport hataları mevcuttur. Ülkemizde, sevk edilecek hastaların protokolleri tanımlanmıştır ancak etkili tedavi için eğitim ve geri bildirim eksikliği vardır.

Anahtar sözcükler: Çocuklar; korunma; terapi, yanıklar.

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ORIG I N A L A R T IC L E

Relationship of biological factors to survival in spinal gunshot injuries Mehmet Seçer, M.D.,1 Murat Ulutaş, M.D.,2 Fatih Alagöz, M.D.,3 Özhan Merzuk Uçkun, M.D.,3 Kadir Çınar, M.D.,2 Cihat Yel, M.D.,4 Emre Cemal Gökçe, M.D.,5 Ali Dalgıç, M.D.3 1

Department of Neurosurgery Deva Hospital, Gaziantep-Turkey

2

Department of Neurosurgery, Sanko University Sani Konukoğlu Hospital, Gaziantep-Turkey

3

Department of Neurosurgery, Ankara Numune Training and Research Hospital, Ankara-Turkey

4

Department of Emergency, Antakya State Hospital, Hatay-Turkey

5

Department of Neurosurgery, Turgut Özal University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: Gunshot injuries are the third leading cause of spinal injuries, after falls from a significant height and traffic accidents. Severity of spinal damage from gunshot injury depends upon certain mechanical and biological factors. The aim of the present study was to investigate the effect of biological factors on survival in cases of spinal gunshot injury.

METHODS: A total of 110 cases of spinal gunshot injury admitted multiple times to emergency services between 2012 and 2014 were included. Age, sex, region of trauma, additional organ or systemic involvement, treatment modalities (conservative, surgical), and mortality rates were analyzed. Effects of biological factors on survival were evaluated.

RESULTS: Mean age of the study population was 25.51±11.74 years (min: 4; max: 55) and 95.5% of the population was male. Regions of trauma were thoracic in 50 (45.4%) subjects, cervical in 42 (38.2%), and lumbar in 18 (16.4%). Most common American Spinal Injury Association (ASIA) score was category A, as was found in 77 (70%) cases. No significant correlation was found among age, sex, ASIA score, treatment modality (conservative or surgical), and survival (p>0.05). Additional organ or systemic injury was present in 66 (60%) patients. Additional organ or systemic injury significantly affected survival, independent of the spinal region of trauma (p<0.01).

CONCLUSION: Spinal gunshot injuries are complex, with unclear treatment protocol. Irrespective of the indications of spinal surgery, additional organ injuries unfavorably affect survival in cases of spinal gunshot injury. Appropriate management of all biological factors directly affects mortality rate in cases of spinal gunshot injury.

Keywords: Biological factors; spinal gunshot injury; survival.

INTRODUCTION Spinal gunshot injuries are the third most common cause of spinal injuries after falls from a significant height and traffic accidents.[1] While incidence varies by region, involving political and ethnic factors, spinal gunshot injuries are responsible for 13–17% of all spinal injuries.[2] Although some properties

Address for correspondence: Mehmet Seçer, M.D. Batıkent Mah., 88 Nolu Cad., 167 Nolu Sok., İkizevler A Blok, D: 3227060, Şehit Kamil, 27060 Gaziantep, Turkey Tel: +90 342 - 211 99 00 E-mail: memetsecer@gmail.com Qucik Response Code

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may resemble those of other traumatic spinal injuries, certain principles of follow-up and therapy are dissimilar.

Severity of spinal gunshot injury depends upon certain mechanical and biological factors.[3] Among these, mechanical factors include gunshot type, bullet or shrapnel velocity and size, bullet trajectory, and distance between target and firearm.[3,4] Biological factors include vertebral level of injury (cervical, thoracic, or lumbar), vertebral column instability, dural tear/cerebrospinal fluid (CSF) leakage, metallic or bony fragments retained in the spinal canal, contaminated tissue within the canal, and presence of additional organ or systemic injuries.[3] While mechanical factors are non-modifiable, wellorganized management of biological factors positively contribute to survival. The aim of the present study was to explore the effects of biological factors on survival in cases of spinal gunshot injury.

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MATERIALS AND METHODS A total of 110 patients admitted multiple times to emergency services following spinal gunshot injury between 2012 and 2014 were enrolled. Effects of age, sex, region of trauma, additional systemic injury, and treatment modality on survival were analyzed. Cases of pure spinal and/or additional organ injury were included.

Airway, breathing, and circulation were initially checked by emergency services, and were followed with detailed physical and neurological examination. Clothing was removed with care, and location of foreign body entry, and if present exit, was determined. No deep manual examination was performed through the entry and/or exit holes (particularly in cases of abdominal injury). Additional systemic injuries accompanying spinal injury were evaluated by relevant consulting physicians. Appropriate radiological tests were performed once circulation and breathing were stabilized. Admission examination was scored according to the Medical Research

Council (MRC) Scale for Testing Muscle Strength, and neurological injury was scored using the American Spinal Injury Association (ASIA) scoring system.

In patients with primary injuries at cervical, thoracic, and lumbar levels (Figs. 1â&#x20AC;&#x201C;3), exploration for additional injury was conducted due to the proximity of primary injury to vital organs and systems. In the event of organ injury, the affected organ or system was primarily treated. After general stabilization, surgery was performed when 1 or more of the following conditions was present: incomplete injury, progressive neurological deficit, foreign body (bullet or shrapnel) in the spinal canal compressing the structures or with potential to migrate, biomechanically instability, or CSF leakage that did not improve with conservative therapy (Table 1).

Effects of biological factors (vertebral column instability, CSF leakage, metallic or bony fragments retained in the spinal canal, contaminated tissue inside the spinal canal, and presence of additional visceral organ injury) on survival were explored.

Figure 1. Radiological and gross appearance of shrapnel fragment with intramedullary location compressing the cord at the C7-Th1 level.

Figure 2. Scenographic and axial-section computed tomographic images of a bullet in the thoracic region of the spinal canal.

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Table 1. Criteria for surgical management in spinal gunshot injuries

Cervical Thoracic Lumbar

Decompression in incomplete injury

2

4

–

Progressive neurological deficit

2

6

1

medulla spinalis

2

5

4

CSF fistula

1

3

1

Instability

2 6 5

Total

9 24 11

Mass effect or presence of foreign material with risk of migration in the canal or

Figure 3. Shrapnel fragment in the spinal canal at the S-1 level.

Study data were analyzed using SPSS software (version 16.0; SPSS Inc., Chicago, IL, USA). Kolmogorov-Smirnov test was used to test normalcy of descriptive statistics (mean, SD).

Chi-square test was used to compare data. Factors affecting mortality and morbidity were determined by logistic regression analysis. Results were evaluated with a confidence interval of 95%, and a p value of less than 0.05 was considered statistically significant.

RESULTS Mean age was 25.51±11.74 years (min: 4; max: 55), and 95.5% of the population was male. Regions of trauma were thoracic in 50 (45.4%) subjects, cervical in 42 (38.2%), and lumbar in 18 (16.4%). ASIA score was most frequently category A, as was determined in 77 (70%) patients. Age, sex, ASIA score, and treatment modality (conservative or surgical) were not significantly correlated with survival (p>0.05) (Table 2).

Additional organ or systemic injuries were present in addition to spinal injury in 58 (52.7%) patients (Tables 2, 3). Regardless of cervical, thoracic, or lumbar region of these injuries, it was detected that additional organ or systemic injuries significantly affected survival (p<0.01). Among 66 patients who underwent conservative management, additional systemic and/or organ injury was found in 35, and 18 (51.4%) died during treatment (p<0.05). Of the 44 patients managed surgically, additional systemic and/or organ injury was found in 23 patients, and 9 (39.13%) died (Table 3).

Nine (23.8%) patients with cervical injury underwent surgery.

Two cases of vertebral artery injury were treated with embolization, 1 of whom died of cerebellar ischemia. Two of 3 patients with esophageal injury died of mediastinitis (Table 4).

Twenty-four (48%) patients with thoracic injury underwent surgery. The majority of patients with additional organ or systemic injuries (n=35, 70%) had thoracic vertebral injuries, owing to proximity of abdominal and thoracic organs. Thoracic traumas were generally managed with tube thoracostomy, while thoracotomy was used when necessary. Relevant Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Table 2. Age, sex, American Spinal Injury Association score, and treatment modality (surgery or conservative management) did not significantly affect the survival rate in the general study population (p>0.05)

n

%

105

95.5

5

4.5

42

38.2

Sex Male Female Spinal trauma region Cervical Thoracic

50

45.4

Lumbar

18

16.4

77

70

American Spinal Injury Association A C

9

8.1

D

18

16.4

E

6

5.5

Additional injury Yes

58

52.7

No

52

47.3

Surgery

44

40.0

Conservative

66

60.0

Treatment modality

Mortality Alive

75

68.2

Dead

35

31.8

organ repairs were conducted by members of the general surgery department, particularly in cases of abdominal injury (Table 5).

Eleven (61.1%) patients with lumbar injuries underwent sur255

Seçer et al. Relationship of biological factors to survival in spinal gunshot injuries

Table 3. Distribution of the patients according to the treatment modality and additional organ- system injuries. Additional organ injuries significantly increased the mortality rate in surgically and conservatively managed patient groups (p<0.01)

Additional injury in conservatively managed patients (n=66)

Additional injury in surgically managed patients (n=44)

Yes No Yes No

Cervical (n=42)

13 (died:10)

20 (died:3)

3 (died:3)

6 (died:1)

Thoracic (n=50)

17 (died:6)

9 (died:3)

18 (died:5)

6 (died:1)

Lumbar (n=18) Total

5 (died:2)

2

2 (died:1)

9

35 (died:18)

31 (died:6)

23 (died:9)

21 (died:2)

Table 4. Additional organ injuries and their outcomes in cervical injuries

n

Treatment modality

Mortality

Cause of mortality

Vertebral artery injury

2

Embolization

1

Cerebellar ischemia

Tracheal injury

1

Surgical repair

1

Pneumonia

Esophageal rupture

3

Primary Repair

2

Mediastinitis

Hemopneumothorax

10

Tube thoracostomy

6

Pneumonia and sepsis

Total 16* *

10*

Additional injury was significantly effective on mortality (p<0.01).

Table 5. Additional organ injuries and their outcomes in thoracic injuries

n

Treatment modality

Mortality

Cause of mortality

Brachial plexus injury

1

Cerebral edema + contusion

3

Antiedema therapy

3

Cerebral herniation, pneumonia

Hemopneumothorax

18

Tube thoracostomy

5

Sepsis, Pneumonia

Intraabdominal and thoracic injury

7

Surgical repair

3

Sepsis, Pneumonia

Intraabdominal organ injury

6

Primary repair

3

Sepsis, Intraabdominal infection

Conservative

Total 35* *

–

14*

Additional injury was significantly effective on mortality (p<0.01).

Table 6. Additional organ injuries and their outcomes in lumbar injuries

n

Treatment modality

Mortality

Cause of mortality

Lumbar plexus injury

1

Conservative

–

–

Intraabdominal organ injury

5

Surgical repair

2

Sepsis, intraabdominal infection

Iliac artery and vein injury

1

Surgical repair

1

Hypovolemia and DIC

7 *

*

3 *

Additional injury was significantly effective on mortality (p<0.01).

gery. Seven (38.8%) patients in this group had additional organ injury. Gastrointestinal systemic injuries were surgically managed. One patient with iliac artery and vein injury died of hypovolemia and disseminated intravascular coagulopathy, 256

in spite of surgical intervention (Table 6). Spinal infection and intraabdominal infection was detected in 6 patients with thoracic and lumbar injuries, 5 of whom died in spite of surgical drainage and wide-spectrum antibiotics.

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Seçer et al. Relationship of biological factors to survival in spinal gunshot injuries

As patients admitted to study centers were from foreign countries, and returned to their country of origin following medical care, no long-term follow-up data were available.

DISCUSSION Spinal gunshot injury is most frequently observed in the thoracic region, followed by the lumbar and cervical regions,[4,5] as a larger area of the thoracic region. This may be due to the thoracic region being a select target in military combat. Rates of mortality in cervical region injuries is reportedly higher due to concomitant vertebral artery injury and respiratory dysfunction.[6–9] Spinal injuries were presently most commonly located in the thoracic region, (45.4%) followed by the cervical region (38.2%) and the lumbar region (16.4%). Cervical injuries were associated with the highest number of deaths (n=17). Thirteen of these patients had additional organ injuries, including vertebral artery, tracheal, and esophageal injuries, which significantly affected the mortality rate. Fifteen (30%) patients with thoracic injury died, 11 of whom also had thoracic and lung injuries. Three (16.6%) patients with lumbar injury died of intraabdominal organ injury and/or diffuse infection. Additional injuries seem to have led to significantly increased mortality in injuries of all 3 regions. (p<0.01).

Infectious complications including empyema, spinal abscess, intraabdominal sepsis, psoas abscess, subcutaneous abscess, and acute infection of bullet trajectory may occur after spinal gunshot injuries.[10] Lower extremity pain syndrome or new neurological deficits may occur as a result of arachnoiditis.

[3] Septic complications of lumbar region injuries are more common than thoracic and cervical injuries, because a bullet usually crosses the gastrointestinal system.[11,12] Romanick et al. reported that early bullet removal prevented infectious complications, particularly in cases with abdominal injury.[13] Venger et al. reported a higher contamination rate in cases with bullet removal in bronchial and hollow organ injuries.[14] Spinal infections were presently particularly observed in 6 patients with thoracic and lumbar region injuries accompanying intraabdominal injuries. Five patients died from diffuse intraabdominal infection, while 1 patient was treated with abscess drainage, irrigation drains, and wide-spectrum antibiotics.

The role of surgical therapy in spinal gunshot injuries is controversial. To date, many researchers have reported that surgical therapy had no benefit for neurological recovery in cases with complete neurological deficit without instability.

However, laminectomy performed within 24–48 hours is recommended in cases with partial neurological deficit or, particularly, cauda equina syndrome, secondary to a bony or metallic fragment in the canal. Absolute indications for surgery include cutaneous or pleural CSF fistulae and progressive neurological deficit with radiologically demonstrable neural compression. The other indication for surgery is instability due to spinal fracture, which is observed in 10% of cases.

[15] These were accepted as criteria for surgical therapy in patients surgically managed.

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Spinal gunshot injuries are usually biomechanically stable.[16] Isiklar et al.[17] and le Roux et al.[18] reported instability rates of 10% and 12%, respectively. It has been reported that acute or chronic instability may develop in transverse fractures crossing the vertebral facet and pedicle in the lumbar region.[19] In the present study, Denis’ 3-column theory was used for instability evaluation.[20] One of 42 cervical injuries was managed by anterior stabilization (due to disrupted corpus integrity), and another was managed by posterior stabilization. Thoracic injuries are more stable, due to the costotransverse joint and thoracic cage, while the cervical and lumbar regions are more prone to biomechanical instability.[3,18] Six cases of 50 with thoracic vertebral injury underwent surgery due to instability.

These predominantly occurred with facet or pedicle fracture at more than 1 level of the thoracolumbar junction. Five of 18 cases with lumbar injury underwent surgery due to instability.

The present instability rate at all regions was 11.8%.

Dural injury and CSF leakage are significant risk factors for meningitis.[3] It has been reported that a lumbar subarachnoid drain after laminectomy, in addition to a primary dural repair, or repair with a dural graft, benefits dural repair in patients with persistent CSF leakage.[21] An external lumbar drainage catheter was implemented in 5 patients with persistent CSF leakage, in spite of dural repair, and in 7 patients who were conservatively followed. CSF leakage was brought under control by placement of a lumbar drainage system in all cases.

In cases of spinal gunshot injury, spinal cord injury directly occurrs as a result of bullet heat and pressure. However, low-energy injuries may also lead to neural injury, due to spinal cord or nerve root compression by metallic fragments or fractured bony parts. A retained bullet in the spinal canal may lead to delayed neurological signs and symptoms, depending on reactive changes around the bullet.[21,22] Rarely, spinal canal compression by a disc fragment may occur following bullet-induced nucleus pulposus injury.[3,23] It is presently believed that neurological injury occurred due to spinal cord compression by bullet or shrapnel, thermal effect, direct injury to spinal cord, or bony fragments in the spinal cord. Risk of bullet migration within the spinal canal was present in the lumbar region.

[24–26] Surgery was conducted on 1 patient for cauda equina syndrome, which developed 2 days after an L2 gunshot injury.

Conclusion Spinal gunshot injuries are complex, with unclear treatment protocol. Criteria for surgical intervention include incomplete neurological deficit, CSF fistula, mechanical instability, risk of foreign material migration within the canal, and bullet intoxication. Irrespective of the indications of spinal surgery, additional organ injuries unfavorably affect survival in spinal gunshot injuries. Thus, appropriate addressing and management of biological factors directly affect mortality in cases of spinal gunshot injury.

Conflict of interest: None declared.

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REFERENCES 1. Miller CA Penetrating wounds of the spine. In: Wilkins RH, Rengachary SS, editors. Neurosurgery. Vol. 2. San Francisco: McGraw-Hill; 1985. p.

1746–8.

2. Farmer JC, Vaccaro AR, Balderston RA, Albert TJ, Cotler J. The changing nature of admissions to a spinal cord injury center: violence on the rise. J Spinal Disord 1998;11:400–3.

3. Jaiswal M, Mittal RS. Concept of gunshot wound spine. Asian Spine J 2013;7:359–64.

4. Seçer M, Ulutaş M, Yayla E, Cınar K. Upper cervical spinal cord gunshot injury without bone destruction. Int J Surg Case Rep 2014;5:149–51.

5. Heiden JS, Weiss MH, Rosenberg AW, Kurze T, Apuzzo ML. Penetrating gunshot wounds of the cervical spine in civilians. Review of 38 cases.

J Neurosurg 1975;42:575–9.

6. Hopla DM, Mazur JM, Bass RM. Cervical vertebrae subluxation. Laryngoscope 1983;93:1155–9.

7. Kahraman S, Gonul E, Kayali H, Sirin S, Duz B, Beduk A, et al. Retrospective analysis of spinal missile injuries. Neurosurg Rev 2004;27:42–5.

8. Medzon R, Rothenhaus T, Bono CM, Grindlinger G, Rathlev NK. Stability of cervical spine fractures after gunshot wounds to the head and neck. Spine (Phila Pa 1976) 2005;30:2274–9.

9. Kupcha PC, An HS, Cotler JM. Gunshot wounds to the cervical spine.

Spine (Phila Pa 1976) 1990;15:1058–63.

10. Benzel EC, Hadden TA, Coleman JE. Civilian gunshot wounds to the spinal cord and cauda equina. Neurosurgery 1987;20:281–5.

11. Velmahos G, Demetriades D. Gunshot wounds of the spine: should retained bullets be removed to prevent infection? Ann R Coll Surg Engl 1994;76:85–7.

12. Miller BR, Schiller WR. Pyogenic vertebral osteomyelitis after transcolonic gunshot wound. Mil Med 1989;154:64–6.

13. Romanick PC, Smith TK, Kopaniky DR, Oldfield D. Infection about the spine associated with low-velocity-missile injury to the abdomen. J Bone

Joint Surg Am 1985;67:1195–201.

14. Venger BH, Simpson RK, Narayan RK. Neurosurgical intervention in penetrating spinal trauma with associated visceral injury. J Neurosurg 1989;70:514–8.

15. de Barros Filho TE, Cristante AF, Marcon RM, Ono A, Bilhar R. Gunshot injuries in the spine. Spinal Cord 2014;52:504–10.

16. Meyer PR, Apple DF, Bohlman HH, Ferguson RL, Stauffer ES. Symposium: management of fractures of the thoracolumbar spine. Contemp Orthop 1988;16:57–86.

17. Isiklar ZU, Lindsey RW. Low-velocity civilian gunshot wounds of the spine. Orthopedics 1997;20:967–72.

18. le Roux JC, Dunn RN. Gunshot injuries of the spine--a review of 49 cases managed at the Groote Schuur Acute Spinal Cord Injury Unit. S Afr J Surg 2005;43:165–8.

19. Yoshida GM, Garland D, Waters RL. Gunshot wounds to the spine. Orthop Clin North Am 1995;26:109–16.

20. Denis F. The three column spine and its significance in the classification of acute thoracolumbar spinal injuries. Spine (Phila Pa 1976) 1983;8:817–31.

21. Bono CM, Heary RF. Gunshot wounds to the spine. Spine J 2004;4:230– 40.

22. Linden MA, Manton WI, Stewart RM, Thal ER, Feit H. Lead poisoning from retained bullets. Pathogenesis, diagnosis, and management. Ann Surg 1982;195:305–13.

23. Mirovsky Y, Shalmon E, Blankstein A, Halperin N. Complete paraplegia following gunshot injury without direct trauma to the cord. Spine (Phila Pa 1976) 2005;30:2436–8.

24. Kafadar AM, Kemerdere R, Isler C, Hanci M. Intradural migration of a bullet following spinal gunshot injury. Spinal Cord 2006;44:326–9.

25. Oktem IS, Selçuklu A, Kurtsoy A, Kavuncu IA, Paşaoğlu A. Migration of bullet in the spinal canal: a case report. Surg Neurol 1995;44:548–50.

26. Moon E, Kondrashov D, Hannibal M, Hsu K, Zucherman J. Gunshot wounds to the spine: literature review and report on a migratory intrathecal bullet. Am J Orthop (Belle Mead NJ) 2008;37:47–51.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Spinal ateşli silah yaralanmasında biyolojik faktörlerin sağkalımla ilişkisi Dr. Mehmet Seçer,1 Dr. Murat Ulutaş,2 Dr. Fatih Alagöz,3 Dr. Özhan Merzuk Uçkun,3 Dr. Kadir Çınar,2 Dr. Cihat Yel,4 Dr. Emre Cemal Gökçe,5 Dr. Ali Dalgıç3 Deva Hastanesi, Nöroşirürji Kliniği, Gaziantep Sanko Üniversitesi Sani Konukoğlu Hastanesi, Nöroşirürji Kliniği, Gaziantep Ankara Numune Eğitim ve Araştırma Hastanesi, Nöroşirürji Kliniği, Ankara 4 Antakya Devlet Hastanesi, Acil Servis Kliniği, Hatay 5 Turgut Özal Üniversitesi Tıp Fakültesi, Nöroşirürji Anabilim Dalı, Ankara 1 2 3

AMAÇ: Ateşli silah yaralanmaları yüksekten düşme ve trafik kazasına bağlı yaralanmalardan sonra, spinal yaralanmaların en sık üçüncü nedenidir.

Ateşli silah yaralanmasına bağlı spinal hasarın şiddeti ateşli silaha bağlı mekanik faktörler ve biyolojik faktörlere bağlıdır. Bu çalışmada, omurga ve/ veya omurilik yaralanması bulunan ateşli silah yaralanmalarında biyolojik faktörlerin sağkalım üzerine etkileri değerlendirildi.

GEREÇ VE YÖNTEM: 2012–2014 yılları arasında çoklu merkez acil servislerine getirilen spinal ateşli silah yaralanması olan 110 olgu çalışmaya alındı.

Hastaların yaş, cinsiyet, travma bölgesi, ek organ ve sistem yaralanma olması, tedavi şekilleri (konservatif, cerrahi), mortalite durumları incelendi.

Biyolojik faktörlerin sağkalım üzerine olan etkileri değerlendi.

BULGULAR: Çalışmamıza alınan 110 olgunun yaş ortalaması 25.51±11.74 yıl (minimum: 4; maksimum: 55) olup, hastaların %95.5’i erkekti. Hastaların yaralanma bölgelerine göre dağılımında; torakal 50 (%45.4), servikal 42 (%38.2) ve lomber 18 (%16.4) idi. ASIA skoru 77 (%70) olgu ile en sık A kategorisinde idi. Yaş cinsiyet, ASIA skorunun ve tedavi şeklinin (konservatif veya cerrahi), survey üzerine etkili olmadığı görüldü (p>0.05).

Hastaların 58’inde (%52.7) spinal yaralanmaya ek organ ve sistem yaralanması tespit edildi. Spinal bölge ayrımına bakılmaksızın ek organ ve sistem yaralanmaların sağkalım üzerinde istatistiksel olarak anlamı etkisi olduğu saptandı (p<0.01).

TARTIŞMA: Spinal ateşli silah yaralanmaları kompleks bir yaralanmadır ve tedavi protokolleri tartışmalıdır. Spinal ateşli silah yarlanmasında spinal cerrahi endikasyonundan bağımsız olarak ek organ yaralanması sağkalımı olumsuz etkilemektedir. Bu nedenle biyolojik faktörlerin iyi yönetilmesi mortalite üzerinde doğrudan etkilidir.

Anahtar sözcükler: Biyolojik faktörler; spinal ateşli silah yaralanması; survey.

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doi: 10.5505/tjtes.2015.76228

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ORIG I N A L A R T IC L E

A review of intussusception cases involving failed pneumatic reduction and re-intussusception Rahşan Özcan, M.D.,1 Mirzaman Hüseynov, M.D.,1 Şenol Emre, M.D.,1 Çiğdem Tütüncü, M.D.,2 Hayriye Ertem Vehid, M.D.,3 Sergülen Dervişoğlu, M.D.,4 İbrahim Adaletli, M.D.,5 Sinan Celayir, M.D.,1 Gonca Tekant, M.D.1 1

Department of Pediatric Surgery, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

2

Department of Anesthesiology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

3

Department of Biostatistics, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

4

Department of Pathology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

5

Department of Radiology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to evaluate cases in which intussusception was unsuccessfully treated with pneumatic reduction (PR), and intussusception recurred following PR. METHODS: The medical records of 401 patients who presented with intussusception between 2003 and 2014 were retrospectively analyzed. Included were 61 patients, 20 of whom underwent unsuccessful PR (Group 1), and 41 of whom experienced intussusception recurrence following PR (Group 2). Treatment and outcome were summarized.

RESULTS: In Group 1 (mean age: 14.2 months; range: 2.5 months–6 years) surgery was indicated due to PR failure in 15 patients, and perforation occurred during PR in 5. In these 5 patients, age was under 1 year (range 6–9 months) and mean time to presentation was 3 days (range 2–4). During laparotomy, pathologies were noted: mesenteric lymphadenopathy (LAP) and/or Peyer’s patch hyperplasia was observed in 15 cases, Meckel’s diverticulum in 5 cases. In Group 2 (mean age: 20 months; range: 3 months–6 years), intussusception developed after successful PR in 41 patients, most frequently within the first 24 hours (21.51%). Of the 41 patients, recurrent intussusception (RI) was treated with PR in 36, and laparotomy in 5. Operative findings were mesenteric LAP in 4 and polyp in 1.

CONCLUSION: PR is effective for the treatment of intussusception and recurrences. Delayed presentation reduces the success rate. In the event of failure, a lead point is usually encountered at laparotomy.

Keywords: Intussusception; pneumatic reduction; recurrent intussusception.

INTRODUCTION Intussusception is the most common cause of bowel obstruction in children between the ages of 3 months and 3 years, and incidences in children between the ages of 5 and 9 months are on the rise. The classic triad of intussusception consists of colicky abdominal pain, palpable abdominal mass, and red Address for correspondence: Rahşan Özcan, M.D. İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 414 33 00 E-mail: rozcan1@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):259–264 doi: 10.5505/tjtes.2016.79851 Copyright 2016 TJTES

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currant jelly stools. However, this triad is encountered in only 25–50% of cases. This can result in delays in diagnosis and treatment. Ultrasonography (USG) is the method most commonly used to diagnose intussusception.[1] Treatment options include enema reduction when appropriate, and should nonoperative methods prove unsuccessful, surgical intervention. Recently, the most commonly used method of treatment has been fluoroscopic or USG-guided pneumatic reduction (PR). It is known as a reliable approach based on the high rates of success and low rates of complication reported in several case series. In spite of this, there have been cases in which PR was unsuccessful, or intussusception recurred early on, following the PR, though these cases are rare. The present objective was to evaluate cases in which intussusception was unsuccessfully treated with PR in the present institution, as well as cases in which intussusception recurred following PR treatment.

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Özcan et al. A review of intussusception cases involving failed pneumatic reduction and re-intussusception

MATERIALS AND METHODS Files of 401 patients who presented with intussusception and were treated with PR between 2003 and 2014 were retrospectively reviewed.Of the cases reviewed, 61 were included.

In 20 of which, reductions could not be completed using the pneumatic method (Group 1), and in 41 of which, intussusception recurred following successful reduction (Group 2).

Patient age and gender, duration of symptoms, seasonal distribution, failure and recurrence rates, and underlying pathologies were evaluated.

All patients underwent the same standard procedures. Diagnosis was based on physical examination, upright direct abdominal radiography, and abdominal USG. USG was used to detect the presence of intussusception, intra-abdominal fluid, mesenteric lymphadenopathy (LAP) and pathological lead point, as well as to determine the length of the intussuscepted segment. Sufficient intravenous fluid replacement and a single dose of antibiotics were administered prior to the procedure. A nasogastric tube was inserted. As soon as the families gave consent, PR was performed.

All PR procedures were performed by a pediatric surgery and anesthesiology team under standard operating conditions with fluoroscopic guidance. Blood pressure, heart rate, and oxygen saturation were monitored. Sedation was achieved by administering a 0.1 mg/kg intravenous dose of Dormicum (midazolam). An insufflator bulb, a sphygmomanometer, and an 18-F Foley catheter were used during PR. Air was insufflated to a maximum pressure of 120 mmHg via the Foley catheter, which was inserted into the rectum. When fluoroscopy demonstrated that the mass was gone and that air was passing into the small intestine, the procedure was considered successful and the operation was brought to a close. If the intussuscepted segment was not reduced, or perforation occurred during the procedure, the procedure was deemed unsuccessful and laparotomy was performed.

Re-intussusception was defined as the occurrence of colicky abdominal pain and the radiologic appearance of intussuscepted segment recurrence following an initial successful PR of the intussuscepted segment, either immediately or after a delay. In these patients, PR was repeated in the same manner as in primary intussusception cases. Laparotomy was performed if reduction could not be accomplished using the pneumatic method.

Statistical analysis was performed using chi-square test and Student’s t-test. A p value of <0.05 was considered significant.

RESULTS A total of 401 patients underwent PR during the study period.

PR was unsuccessful in 20 of these cases. In 41 cases, patients experienced at least 1 recurrent episode of intussusception.

260

Group 1 consisted of 20 cases (15 male, 5 female) for whom reduction could not be completed using the pneumatic method. Rate of failed PR was 5%. Mean age of this group was 14.2 months (range 2.5 months–6 years). Age distribution analysis demonstrated that 15 patients (75%) were aged between 0 and 1 years, and 5 patients (25%) were aged between 1 and 6 years. Mean symptom duration prior to presentation was 2.5 days (range 1–7 days). Rectal bleeding was present in 7 cases. Intussusception was detected on USG in 16 cases. Average size of intussuscepted segment detected by USG was 7 cm (range 3–10 cm). Anechoic fluid was detected in the abdomens of 9 patients (45%). Mesenteric lymphadenopathy (MLA) was observed in 7 patients. No additional pathological lead points were detected on USG (Table 1).

Fifteen of the 20 patients in Group 1 underwent laparotomy due to failure to reduce the intussuscepted bowel segment.

During laparotomy, additional pathologies were noted: mesenteric LAP and/or Peyer’s patch hyperplasia in 13 cases, and Meckel’s diverticulum in 2 cases. Five of the 20 patients underwent laparotomy after perforation occurred (Figure 1).

Of these 5, mean age was 8 months (range: 6–9 months), and mean time to presentation was 3 days (range: 2–4 days).

Rectal bleeding was present in 3 cases. In 1 case, no intussusception had been detected on USG. Average size of intussuscepted segments detected on USG was 3 cm (range 3–6 cm). Anechoic fluid was detected in the abdomen in 4 cases (80%), and mesenteric LAP was present in 3 cases.

Underlying pathologies observed during laparotomy were Meckel’s diverticulum in 3 cases and mesenteric LAP and/or Peyer’s patch hyperplasia in 2. The properties of these cases of perforation were considered, and statistical analysis was performed (Table 2). Analysis demonstrated that in the cases of perforation, only the presence of intra-abdominal fluid on USG was statistically significant (p<0.05). Anatomic location of intussusception in Group 1 was ileocolic in 18 cases, ileoileal in 1 case, and colocolic in 1 case.

Group 2 consisted of 41 patients (33 male, 8 female) who Table 1. Patient demographic specifications and radiological findings in Group 1 (n=20) Age

1.5 years

(2.5 mo-6 yrs)

Male gender

15 (75%)

Rectal bleeding

7 (35%)

Duration of symptoms

2.5 days (1–7 days)

Intussuscepted segment on USG

16 (80%)

Size of intussuscepted segment on USG

7 cm (3–10 cm)

Mesenteric lympadenopathy (MLA) on USG 7 (35%) Fluid on USG

9 (45%)

MLA: Mesenteric lymphadenopathy; USG: Ultrasonography.

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Group 1 Unsuccessful PR n=20

Failed PR n=15

Perforation n=5

Laparotomy n=15

Laparotomy n=5

Mesenteric lymphadenopathy and/or Peyer’s patch hyperplasia n=13 Meckel’s diverticulum n=2

Mesenteric lymphadenopathy and/or Peyer’s patch hyperplasia n=2 Meckel’s diverticulum n=3

Figure 1. Surgical management and operative findings in Group 1.

experienced re-intussusception. Rate of re-intussusception was 10.2%. Mean age of this group was 20 months (range: 3 months–6 years). Analysis of age distribution demonstrated that 26 patients (63%) were aged between 0 and 1 years, 11 patients (27%) were aged between 1 and 3 years, and 4 patients (10%) were aged between 3 and 6 years. Time to appearance of re-intussusception was within the first 24 hours in 21 cases (51%). Twelve of these patients (29%) were younger than 1 year. Re-intussusception occurred in spring in 20 cases (49%), in winter in 10 cases (24%), in summer in 9 cases (22%), and in autumn in 2 cases (5%).

No intussusception was detected on USG examination in 5 cases in Group 2. Mean size of intussuscepted segments detected with USG was 5 cm (range: 2–12 cm). Mesenteric LAP was present in 30 cases (73%). Anechoic fluid was detected in the abdomen in 12 cases. No additional pathological lead points were detected on USG.

of intussusception. Of the 41 Group 2 patients, recurrent intussusception (RI) was treated by PR in 36, and laparotomy and manual reduction in 5 (Figure 2). In 2 of the 5 cases, no intussuscepted segment was detected on USG examination.

Anechoic fluid was detected in the abdomen in 3 cases. No additional pathological lead points were detected on USG in these patients. Operative findings were mesenteric LAP and/or Peyer’s patch hyperplasia in 4 patients and polyp in 1.

Pathologic examination of the polyp was consistent with juvenile polyps. Anatomic location was ileocolic in 3 cases and ileoileal in 1. The patient with ileoileal intussusception was the only to undergo laparotomy twice. No statistically significant difference was found in age, gender, presence of intraabdominal fluid on ultrasound, or size of intussuscepted segment in Group 2 patients who underwent surgery (p>0.05).

Group 2 Re-intussusception n=41

Five Group 2 patients experienced more than 1 recurrence Table 2. Properties and statistical analyis of Group 1 Variable p Age

>0.05

Successful PR n=36

Laparotomy n=5

Gender =0.29 MLA on USG

=0.78

Fluid on USG** =0.00982** Size of intussuscepted segment on USG

>0.05

Statistical significance; MLA: Mesenteric lymphadenopathy; USG: Ultrasonography.

Mesenteric lymphadenopathy and/or Peyer’s pa tch hyperplasia n=4 Juvenile polyp n=1

**

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Figure 2. Management and operative findings in Group 2.

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Özcan et al. A review of intussusception cases involving failed pneumatic reduction and re-intussusception

When data of Groups 1 and 2 were statistically compared, no significant differences were found regarding age, gender, presence of intra-abdominal fluid on USG, or presence of mesenteric LAP.

DISCUSSION Intussusception is the most commonly encountered cause of bowel obstruction in childhood, with a reported incidence of 56/100000. It most frequently occurs in patients aged between 3 months and 3 years. The classic triad of intussusception symptoms, which includes colicky abdominal pain, red currant jelly stools, and palpable abdominal mass, are encountered in only 25–50% of cases. The potential variety of symptoms can lead to difficulty in identification and diagnosis, and thus delays in therapy.

The first-line treatment of intussusception, if no signs of perforation or peritonitis are present, is enema reduction, a nonoperative method. Surgical intervention is performed on patients with signs of peritonitis upon initial presentation, and in cases in which enema reduction was not successful. Enema reduction is performed in a hydrostatic or a pneumatic manner, and under guidance of fluoroscopy or USG. Various studies have reported success rates of 40–95% for nonoperative treatments. Hydrostatic and pneumatic reductions have been compared in numerous studies, and higher rates of success and lower mortality rates have been reported with the use of pneumatic reductions.[1–4] The success rate of PR was found to be 88–95%.[3,5] The pneumatic method has other advantages, as well. It may be used in the diagnosis and treatment of intussusception, and it carries a lower radiation risk, compared to hydrostatic reduction. Moreover, in the event of perforation, there will be less peritoneal spread, corresponding to a lower rate of morbidity and mortality.[5] For these reasons, many publications recommend PR as a firstline treatment.[3] The open surgery method was the former first-line treatment at the present institution, but PR has increasingly taken its place, particularly over the past decade,[6] and the PR success rate is 95%.

Two limiting factors must be discussed with regard to PR: failure to identify lead points and pseudo reductions.[5] In the present series, a total of 25 laparotomies were performed, and pathological lead points were identified in 6 of these patients (Meckel’s diverticulum in 5 cases, juvenile polyp in 1 case). Perforation was observed during the PR procedure in 3 of the 5 patients with Meckel’s diverticulum. The complications of PR are failed reduction, perforation, and in rare cases tension pneumoperitoneum and RI.[7–9] Reasons for failure of nonoperative methods have been questioned in a number of studies. Success rates may vary based on patient-related factors or factors relating to the team performing the procedure. Patient-related factors evaluated were lateness of presentation, age of patient, dehydration, 262

lethargy, the presence of bloody stools, and the length of the intussuscepted segment. It has been determined by a majority of authors that the factors increasing the probability of surgical intervention were use of hydrostatic enema, failure of the first attempt at enema reduction, bloody stools, symptoms that had lasted more than 24–48 hours, age younger than 1 year, and a long length of intussuscepted bowel.[1,10] In the present series, the rate of unsuccessful reduction was 5%, and 75% of those patients were younger than 1 year of age.

However, this was not found to be statistically significant. In contrast to these studies, Tareen found no relationship between failure in PR and length of symptoms, and reported a PR success rate of 88%, even in recurrent cases.[3] At a different center, Curtis et al. reported that patients presenting following unsuccessful reduction showed similar PR results to primary patients.[11] In the present study, the average time from onset of symptoms was 60 hours in the failed reduction group, suggesting that time alone should not be a contraindication for PR, but must be evaluated together with other factors.

The success rate of PR demonstrates a correlation with USG data in the diagnostic stage. USG indications of thinning of the intestinal walls, lead points, or fluid (either between bowel loops or free in the abdomen) increases the probability of need for surgical intervention. Presence of these findings may be associated with failed reduction and occurrence of perforation. Presence of fluid between bowel loops has been shown to result in a fourfold reduction in the success rate of PR. Nevertheless, it is recommended in the literature that USG findings be evaluated with other clinical findings. In the present study, it was particularly noteworthy that free intraabdominal fluid was found on USG in 80% of cases that included perforation.[1,5,12] No correlation of USG signs of intraabdominal fluid and perforation were presently determined.

Another factor that may affect the success of PR is the experience of the team performing the procedure and the techniques used. This procedure is generally carried out by a pediatric radiology team. A pediatric anesthesiology and surgical team must also stand by at the ready in the event of an unsuccessful reduction or the development of other complications. PR can be performed under guidance of USG or fluoroscopy. USG-guided PR is a non-invasive procedure with a high success rate. The drawback is that it requires a high level of experience with USG. The most frequent point of criticism in fluoroscopic-guided PR is the exposure to radiation. PR has been shown to possess a lower radiation risk, compared to reduction with barium enema.[3] As experience with PR increases, the rate of complications decreases, procedure time is shortened, and consequently, the exposure to radiation decreases.[5,13] PR performed by inexperienced teams is reported to have lower success rates and higher rates of complication.[5] PR procedures at the present clinic are performed under standard operating conditions with fluoroscopic guidance. An anesthesiology team performs the Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Özcan et al. A review of intussusception cases involving failed pneumatic reduction and re-intussusception

sedation, and PR is performed by a pediatric surgery team.

This eliminates the need for a pediatric radiologist to be at the clinic around the clock, and allows for fast intervention in the event of complications. Moreover, the high success rate of the present series is thought to be due to the same team performing this procedure, and the high level of experience they have obtained in doing so.

The most feared complication of PR is perforation, and consequent tension pneumoperitoneum. Perforation rates of 0.1–3% have been reported in various case series.[5,9,14,15] In the present series, that rate was 1.2%. It has been reported that intracolonic pressure can be safely maintained at 80–130 mmHg.[8,14,16] The area of perforation in PR is smaller, generally does not increase in size, and results in less fecal spread, compared to hydrostatic reduction.[16] The rate of complications such as ischemic bowel, perforation, and peritonitis particularly increases in cases involving late diagnosis, general poor health, and a history of bloody stools. Perforation is seen more often in patients younger than 1 year.[3] The presence of pathological lead points increases the probability of perforation during PR.[1] In the literature, 20% of patients undergoing open surgery demonstrated pathological lead points such as Meckel’s diverticulum, lymphoma, intestinal polyps, and adenocarcinoma. Patients older than 5 years of age were found to have a higher probability of underlying pathology.[1,15] In the present series, all 5 patients who experienced perforation were under 1 year of age, and a pathological lead point was present in 60%. Average time to presentation was 3 days.

This suggests that late presentation increases complications, which is consistent with the literature.

The use of sedation during the PR procedure remains controversial. In an experimental study by Shiels, the performance of the Valsalva maneuver during PR was reported to protect against perforation, but deep sedation prevents the patient from performing this maneuver.[16] On the other hand, Ilivitzki et al. has stated that the use of propofol provides sedation, reduces the dose of radiation exposure by shortening the procedure, and makes the entire procedure more comfortable for children and families.[17] At the present clinic, the anesthesiology team administered intravenous midazolam for sedation during PR to all patients. When the high rate of success and the low rate of perforation in the present series are considered, it does not appear that the use of sedation is associated with the development of perforation.

Incidence of RI following enema reduction has been reported between 8–15%.[7,14,15] In the present study, this rate was 10.2%. In the work of Niramis et al., it was reported that 68% of RI patients experienced the initial episode younger than 1 year of age, and 70% of recurrences occurred in the 6 months following the initial episode. In cases of RI, it was noted that patients were brought to the hospital earlier, due to earlier symptom recognition by families. Niramis et al. also reported that the rate of pathological lead point presence was 3 times Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

higher in cases of RI.[7] Of the present cases of RI, 65% were under 1 year of age, 42% occurred within the first 24 hours after PR, and they were associated with a high rate (75%) of mesenteric LAP on USG. In this group, 4 of the 5 patients (80%) who underwent laparotomy exhibited pathological lead points. Other studies have shown that PR can be safely performed, even in the presence of a pathological lead point, but that in these patients the incidence of RI was higher. The relationship between recurrence and surgical intervention is controversial. For patients older than 2 years of age at the first episode, for patients in which the first treatment method used was reduction enema, and for patients suspected of having pathological lead points, surgical intervention is recommended.[7,18]

Conclusion PR is an effective and safe method in the treatment of intussusception. Late presentation and additional underlying pathologies reduce the success of the procedure and increase the rate of complications. The presence of intra-abdominal fluid on USG should be considered a strong indication of the possibility of perforation. Nevertheless, patients should be evaluated by taking all other factors into consideration. Prior failed intervention, the existence of long-lasting symptoms, and re-intussusception should not provide any obstacle to attempting PR, particularly when an experienced pediatric radiologist, and an experienced pediatric surgery and anesthesiology team are present.

Conflict of interest: None declared.

REFERENCES 1. Fallon SC, Lopez ME, Zhang W, Brandt ML, Wesson DE, Lee TC, et al.

Risk factors for sur-gery in pediatric intussusception in the era of pneumatic reduction. J Pediatr Surg 2013;48:1032–6.

2. Beres AL, Baird R. An institutional analysis and systematic review with meta-analysis of pneumatic versus hydrostatic reduction for pediatric intussusception. Surgery 2013;154:328–34.

3. Tareen F, Ryan S, Avanzini S, Pena V, Mc Laughlin D, Puri P. Does the length of the history influence the outcome of pneumatic reduction of intussusception in children? Pediatr Surg Int. 2011;27:587–9.

4. Sonmez K, Turkyilmaz Z, Demirogullari B, Karabulut R, Kale N, Basaklar AC. Intussuscep-tion in children: experience with 105 patients in a department of paediatric surgery, Turkey. S Afr J Surg 2012;50:37–9.

5. Mensah YB, Glover-Addy H, Etwire V, Twum MB, Asiamah S, Appeadu-Mensah W, et al. Pneumatic reduction of intussusception in children at Korle Bu Teaching Hospital: an initial ex-perience. Afr J Paediatr Surg 2011;8:176–81.

6. Eliçevik M, Özcan R, Emre Ş, İlçe Z, Tekant GT, Sarımurat N, et al. A rapid review of a very well known: Intussusception. Cerrahpasa J Med 2006;37:41–4.

7. Niramis R, Watanatittan S, Kruatrachue A, Anuntkosol M, Buranakitjaroen V, Rattanasuwan T, et al. Management of recurrent intussusception: nonoperative or operative reduction? J Pediatr Surg 2010;45:2175–80.

8. Ryan ML, Fields JM, Sola JE, Neville HL. Portal venous gas and cardiopulmonary arrest dur-ing pneumatic reduction of an ileocolic intussus-

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ception. J Pediatr Surg 2011;46:5–8.

9. Fallon SC, Kim ES, Naik-Mathuria BJ, Nuchtern JG, Cassady CI, Rodriguez JR. Needle de-compression to avoid tension pneumoperitoneum and hemodynamic compromise after pneumat-ic reduction of pediatric intussusception. Pediatr Radiol 2013;43:662–7.

10. Fike FB, Mortellaro VE, Holcomb GW 3rd, St Peter SD. Predictors of failed enema reduc-tion in childhood intussusception. J Pediatr Surg 2012;47:925–7.

11. Curtis JL, Gutierrez IM, Kirk SR, Gollin G. Failure of enema reduction for ileocolic intus-susception at a referring hospital does not preclude repeat attempts at a children’s hospital. J Pe-diatr Surg 2010;45(6):1178–81.

12. Gartner RD, Levin TL, Borenstein SH, Han BK, Blumfield E, Murphy R, et al. Interloop fluid in intussusception: what is its significance? Pediatr Radiol 2011;41:727–31.

13. Cullmann JL, Heverhagen JT, Puig S. Radiation dose in pneumatic reduction of ileo-colic intussusceptions--results from a single-institution

14. Cankorkmaz L, Köylüoğlu G, Arslan MS, Güney C. Our childhood cases with intussuscep-tion and pneumatic reduction. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2010;16:363–6.

15. Feltis AB, Schmeling DJ. Intussusception. In: Ziegler M, Azizkhan RG, Von Allmen D, We-ber TR, editors. Operative Pediatric Surgery, 2th ed.

McGraw-Hill; 2014. p. 592–6.

16. Shiels WE 2nd1, Kirks DR, Keller GL, Ryckman FR, Daugherty CC, Specker BL, et al. John Caffey Award. Colonic perforation by air and liquid enemas: comparison study in young pigs. AJR Am J Roentgenol 1993;160:931–5.

17. Ilivitzki A, Shtark LG, Arish K, Engel A. Deep sedation during pneumatic reduction of in-tussusception. Pediatr Radiol 2012;42:562–5.

18. Kaiser AD, Applegate KE, Ladd HP. Current success in the treatment of intussusception in children. Surgery 2007;142:469–77.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İnvajinasyonda başarısız pnömatik redüksiyon ve reinvajinasyon olgularının incelenmesi Dr. Rahşan Özcan,1 Dr. Mirzaman Hüseynov,1 Dr. Şenol Emre,1 Dr. Çiğdem Tütüncü,2 Dr. Hayriye Ertem Vehid,3 Dr. Sergülen Dervişoğlu,4 Dr. İbrahim Adaletli,5 Dr. Sinan Celayir,1 Dr. Gonca Tekant1 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, İ̇stanbul İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Anesteziyoloji Anabilim Dalı, İ̇stanbul 3 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Biyoistatistik Anabilim Dalı, İstanbul 4 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Patoloji Anabilim Dalı, İstanbul 5 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul 1 2

AMAÇ: İnvajinasyon tedavisinde pnömatik redüksiyon (PR) ile başarısız olunan olgular ve PR ile tedavi sonrası tekrar invajinasyon gelişen olguların değerlendirilmesidir.

GEREÇ VE YÖNTEM: 2003–2014 yılları arasında invajinasyon nedeni ile tedavi edilen 401 olgunun kayıtları geriye dönük olarak incelendi. Bu çalışmaya alınan 61 olgunun 20’si (Grup 1) başarısız PR ve 41’i (Grup 2) başarılı redüksiyon sonrası tekrar invajinasyon gelişen olgulardı. Uygulanan tedavi ve sonuçları incelendi.

BULGULAR: Grup 1’de (yaş ortalaması: 14.2 ay) operasyon endikasyonu 15’inde başarısız PR ve beşinde PR sırasında perforasyondu. Bu beş olgunun tamamı bir yaş altındaydı ve ortalama başvuru zamanı üç gün (2–4 gün) idi. Laparatomide ek patoloji olarak; olguların 15’inde mezenterik lenfadenopati ve/veya peyer plak hiperplazisi, beşinde meckel divertikülü saptandı. Grup 2’de (yaş ortalaması: 20 ay) reinvajinasyon en sık ilk 24 saatte (n=21) görüldü. Kırk bir olgunun 36’sında reinvajinasyon PR ile tedavi edildi, beşine laparotomi yapıldı. Operasyon bulguları dördünde mezenterik lenfadenopati ve birinde polip idi.

TARTIŞMA: Pnömatik redüksiyon invajinasyonu ve nüksetme tedavisinde etkili ve güvenilir bir yöntemdir. Geç başvuru pnömatik redüksiyon başarısını azaltmaktadır. Başarısız PR’de laparotomide genellikle lead point ile karşılaşılır.

Anahtar sözcükler: İnvajinasyon; pnömatik redüksiyon; rekürren invajinasyon.

Ulus Travma Acil Cerrahi Derg 2016;22(3):259–264

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doi: 10.5505/tjtes.2016.79851

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ORIG I N A L A R T IC L E

A hidden household danger: Television Oğuzhan Bol, M.D.,1 Hüseyin Cebiçci, M.D.,1 Serhat Koyuncu, M.D.,3 Bahadır Şarlı, M.D.,4 Nurullah Günay, M.D.2 1

Department of Emergency Medicine, Kayseri Training and Research Hospital, Kayseri-Turkey

2

Department of Emergency Medicine, Erciyes University Faculty of Medicine, Kayseri-Turkey

3

Department of Emergency Medicine, Karabük University Faculty of Medicine, Karabük-Turkey

4

Department of Cardiology, Kayseri Training and Research Hospital, Kayseri-Turkey

ABSTRACT BACKGROUND: Today, at least 1 television (TV) is owned in most households, and watching TV has become a significant part of daily life. Time spent in front of the TV has increased as its popularity has grown, which may pose a danger to children. The aim of the present study was to draw attention to cases of TV tip-over-related pediatric injuries.

METHODS: Cases of TV tip-over injuries of pediatric patients admitted to the Emergency Department of Kayseri Training and Research Hospital recorded between June 1, 2011 and December 31, 2013 were included. Data were prospectively collected, including age and gender of patient, part(s) of the body affected, Glasgow Coma Scale score, TV screen size and brand, and whether the patient was hospitalized in the general ward or the intensive care unit (ICU).

RESULTS: There were 53 pediatric patients enrolled in the study, including 30 males (56.6%) and 23 females (43.4%). Eight patients (17%) had a fracture somewhere in the body, whereas 45 patients (83%) had no fracture. Of patients with a fracture, 3 (2 males, 1 female) were treated in the general ward and 3 (male) in the intensive care unit. One male patient died.

CONCLUSION: An increasing number of individuals present to emergency services with injuries sustained by TV toppling. Cases of injury, permanent disability, and even death associated with falling TVs suggest that awareness of the danger should be increased, as it may affect children in particular.

Keywords: Child; toppling; TV.

INTRODUCTION Deaths related to trauma, and domestic accidents in particular, account for significant incidence of childhood mortality.[1] Childhood trauma primarily affects toddlers and preschoolaged children.[2] In the US, the Consumer Product Safety Commission released the top 5 hidden household hazards in 2007 and listed tip-overs as the third leading cause of morbidity and mortality.[3] Today, almost every family owns at least 1 television (TV), and the majority of time at home is spent watching TV.[4] Decreased cost and widespread availability of TVs have led to an increase in both screen size and weight.[5] Address for correspondence: Oğuzhan Bol, M.D. Bahçelievler Mah., Bahçelievler Caddesi, Yamaç Apt., No: 45 8/24, Talas, Kayseri, Turkey Tel: +90 352 - 336 88 88 E-mail: mariachiozi@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):265–268 doi: 10.5505/tjtes.2015.42078 Copyright 2016 TJTES

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Bulkier TVs manufactured using older technology, namely the cathode ray tube (CRT), are still marketed and can be found in many households, though flat screen alternatives, including TVs with liquid crystal display (LCD) are preferred. Outmoded, large-screen CRT TVs have a high risk of falling, as their center of gravity is at the front, and most of the weight is in the screen. In addition, they are usually placed on unsecured stands, often with wheels.[6] An increasing number of patients present with injuries caused by falling TVs.[7] According to a report published in the US, 169 children (69%) died from injuries caused by falling TVs between 2000 and 2010, and a rise in the number of patients rushed to emergency departments due to such injuries was observed during the decade.[8] The present authors were surprised by the high number of patients presenting to emergency services with injuries caused by falling TVs. The present results indicate that these injuries are far more common that had been imagined. The preventable nature of these accidents and the fact that children are primarily affected contributed to the decision to conduct a comprehensive investigation. The present aim was to draw attention to incidence of accidents involving toppling TVs. 265

Bol et al. A hidden household danger: TV

MATERIALS AND METHODS Cases of TV tip-over injuries sustained by pediatric patients admitted to the Emergency Department of Kayseri Training and Research Hospital recorded between June 1, 2011 and December 31, 2013 were included. Conduct approval was obtained from the institutional ethics committee. Data including patient age and gender, part(s) of the body affected (divided into 3 regions including head-neck, upper extremities, and lower extremities), Glasgow Coma Scale score at presentation, TV dimension and brand, and hospitalization in the general ward or intensive care unit (ICU) were included. TV brand names are not published in the present study. Patients were evaluated by emergency care specialists and their assistants.

Consultation was sought from pediatric surgery, orthopedics, and brain surgery departments when necessary. Data were analyzed using SPSS software (version 21.0; SPSS Inc., Chicago, IL, USA). Quantitative and qualitative values were expressed as mean±SD, median (min–max) and percentage. Qualitative data were additionally analyzed using the chi-square test, and p values below 0.05 were considered statistically significant.

RESULTS A total of 53 pediatric patients were enrolled, including 30 boys (56.6%) and 23 girls (43.4%). Mean age of boys was 4 years (range 1–10), and that of girls was 3.7 years (range 2–8).

Three patients (2 boys, 1 girl; 5.7%) sustained an injury to the head-neck region, 39 patients (20 boys, 19 girls; 73.6%) sustained an injury to an upper extremity, and 11 patients (8 boys, 3 girls, 20.8%) sustained an injury to a lower extremity.

No significant difference in gender and injury site was found (p=0.419) (Table 1).

Eight patients (17%) had sustained a fracture, while 45 (83%) had not. Two of the fractures were to the skull, and 6 affected the upper extremities. A statistically significant difference was observed with regard to the absence of fractures in the lower extremities, compared to other sites of injury (p=0.001). Of the patients with fractures, 7 were boys, and 1 was a girl. Incidence of trauma-related fractures among boys was statistically significant (p=0.032) (Table 2).

Size and number of TVs involved were as follows: 3 37-inch TVs (5.7%), 14 55-inch TVs (26.4%), 33 72-inch TVs (62.3%), and 3 82-inch TVs (5.7%). No significant difference was found between screen size and patient gender (p=0.302) (Table 3).

There were 5 cases of fracture associated with 72-inch TVs, 2 with 55-inch TVs, and 1 with an 82-inch TV. No statistically significant association was found between screen size and presence of fracture (p=0.692).

Of patients with fracture, 3 (2 boys, 1 girl) were treated in the general ward, and 3 were treated in the ICU. One male

Table 1. Injuries due to falling TVs according to gender, age groups, presence of fracture, hospitalization and Glasgow Coma Scale scores

Males

Number

Females p

30 (56.6%)

23 (43.4%)

Age (years)

4 (1–10)

3.7 (2–8)

Fracture (n)

7

1

=0.032

General ward: 2

General ward: 1

=0.178

Hospitalization (n)

Intensive care unit: 3

Glasgow Coma Scale scores Death

14.27 (3–15)

=0.190

15

1 –

Table 2. Injuries due to falling TVs according to site of injury and presence of fracture

Injury area Gender (n)

Head-neck region

3 (5.6%)

Gender (n)

2

Male (1)

Female (1)

Upper extremities

Male (20)

39 (73.5%)

Lower extremities

11 (20.7%)

266

Male (2)

Presence of fractures at the site of injury

6

Female (1) Male (6)

Female (19) Male (8)

0

Female (3)

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Bol et al. A hidden household danger: TV

Table 3. Size and number of TVs causing trauma and fracture Size

37-inch 55-inch 72-inch 82-inch p

Number

3 (5.7%)

14 (26.4%)

Fracture 0

33 (62.3%)

2

5

3 (5.7%) 1 =0.692

Table 4. Presence of fracture according to TV brand Brand

Brand A

Brand B

Brand C

Brand D

Brand E

Brand F

Brand G

Number 37 8 3 2 1 1 1 Fracture 5 2 – 1 – – –

patient died. Another patient was discharged and asked to return for follow-up visits. Remaining patients were discharged from the emergency department following completion of overall assessment. While all patients treated in the ICU were boys, no statistically significant difference in gender was found, based on the total number of patients (p=0.190). Likewise, no statistically significant difference in gender was found with regard to admission to the general ward (p=0.178).

Mean Glasgow Coma Scale score was 14.27 (range 3–15) among boys and 15 (15–15) among girls.

Seven TV brands were found to be associated with tip-overs.

Brand A was the most common, with 37 TVs (69.8%), followed by Brand B (n=8, 15.1%), Brand C (n=3, 5.7%), Brand D (n=2, 3.8%) and Brands E, F, and G (n=1 each, 1.9%) Five fractures were associated with Brand A, 2 with Brand B, and 1 with Brand D (Table 4). No statistically significant association between fractures and TV brands was found (p=0.228).

DISCUSSION TV toppling mainly affects small children and carries a high risk of injury and mortality among household accidents. Data of pediatric patients admitted to the emergency department over a period of 18 months were reviewed. Fifty-three patients were admitted with injuries sustained due to falling TVs during the study period. The authors of the present study believe that such a high number of patients presenting to a single hospital underscores the significance of these accidents among pediatric patients. DiScala et al. identified 183 such cases in a retrospective review of a 10-year period, and Dotchin et al. identified 102 such cases that had presented over a period of 12 years.[9,10] Authors of a report published in the US identified 12,800 emergency room visits due to such injuries in 2011 in patients aged 19 and under.[8] Unfortunately, TV has become an inseparable part of life.

Family members spend their free time, which could be spent engaging socially, watching TV. A study conducted in Turkey found that the total percentage of people spending 2 to more Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

than 4 hours watching TV was 90% in 1994, while the number reportedly fell to 76.4% in 2014.[11,12] Although a decline was observed, it is obvious that families still spend their valuable free time watching TV. Due to the long hours spent watching TV, the area around the set is increasingly used for play, and it is unfortunate that the set sometimes becomes part of the game. As a result, accidents caused by these dangerous “toys” are increasing, and studies show that accidents related to falling TVs are on the rise.[13–15] The present male:female ratio and mean age were comparable, with most patients aged between 1–4 years. However, the number fractures was higher among boys, possibly due to them being more physically active. Rutkoski et al. reported a male:female ratio of 1:1, with a mean age of 36 months,[3] while Gokhan et al. reported a mean age of 39 months, with a predominance of male patients (70.4%).[2] In a retrospective review spanning 10 years, Murray et al. found that the population affected was primarily male, and included children aged between 1–4 years.[6] In recent years, large-screen LCD and light-emitting diode (LED) TVs have become more common. In spite of their availability, outmoded CRT TVs are still found in many households. Several physical properties of these sets increase the risk of injury from toppling. The heaviest part of a standard CRT TV is the screen. Thus, weight increases dramatically with larger screen sizes (a 72-inch CRT TV can weigh up to 50 kg), and the center of gravity of the sets is based in the screen.[16] Each of the present patients was a small child, and 55-inch and 72-inch screens were more commonly associated with injury. Güloğlu et al. and De Roo et al. reported similar findings regarding screen size,[1,13] which may be due to the popularity of these sizes.

Given the mechanism of injury associated with falling TVs and the anatomy of children, injuries to the head and upper extremities can be expected. High placement of TVs can 267

Bol et al. A hidden household danger: TV

pose significantly greater risk. Although isolated head traumas were presently found to be less common than those to the upper and lower extremities, it was striking that 2 of 3 patients with head injuries had skull fractures that led to hospitalization. The head was the most common site of injury reported by DiScala et al., and Güloğlu et al. reported similar results.[1,10] In the present study, 3 patients were treated in the general ward and 3 in the ICU. One patient treated in the ICU survived with neurologic sequelae and is still dependent. Another died in the emergency room. These figures may not be statistically significant, but real-life consequences are substantial. It is clear that we should be more aware of such preventable traumas.

Conclusion TV has become an essential part of our daily lives, and is one of the most popular household commodities. Many families own more than 1, and children spend most of their time watching TV, rather than playing games. The inclusion of the TV set in a game can have undesired consequences. It is presently recommended that TVs should be placed on more secure stands, affixed with securing tools, or, preferably, mounted on a wall.

Care should be taken not to leave children in front of the TV unattended. It may be advisable to allow children to spend as little time as possible in front of the TV. Conflict of interest: None declared.

REFERENCES 1. Güloğlu R, Sarıcı IS, Bademler S, Emirikçi S, Işsever H, Yanar H, et al.

Falling television related child injuries in Turkey: 10-year experience.

Ulus Travma Acil Cerrahi Derg 2012;18:61–4.

2. Gokhan S, Kose O, Ozhasenekler A, Orak M, Ustundag M, Guloglu C. Mortality and morbidity in children caused by falling televisions: a retrospective analysis of 71 cases. Int J Emerg Med 2010;3:305–8.

3. Rutkoski JD, Sippey M, Gaines BA. Traumatic television tip-overs in the pediatric patient population. J Surg Res 2011;166:199–204.

4. Suresh N, Harini G, Radhika R, Chidambaram B. Head injuries in children resulting from the fall of television. Indian J Pediatr 2010;77:459–60.

5. Jea A, Ragheb J, Morrison G. Television tipovers as a significant source of pediatric head injury. Pediatr Neurosurg 2003;38:191–4.

6. Murray KJ, Griffin R, Rue LW 3rd, McGwin G Jr. Recent trends in television tip over-related injuries among children aged 0-9 years. Inj Prev 2009;15:240–3.

7. Mills J, Grushka J, Butterworth S. Television-related injuries in children-the British Columbia experience. J Pediatr Surg 2012;47:991–5.

8. USA Facts: Television and Furniture Tip-Over Safety 2012 [Internet].

Available from: http://www.preventionworks-nj.org/ pdfs/2012FactSheetTVFurniture.pdf.

9. Dotchin SA, Gordon KE. The terrible truth about toppling televisions.

Paediatr Child Health 2007;12:221–4.

10. DiScala C, Barthel M, Sege R. Outcomes from television sets toppling onto toddlers. Arch Pediatr Adolesc Med 2001;155:145–8.

11. T.C. Başbakanlık Aile Araştırma Kurumu Türkiye’de Televizyon Ve Aile. [Internet]. Available from: http://ailetoplum.aile.gov.tr/ data/54293ea2369dc32.

12. Türkiye Aile Yapısı Araştırması Tespitler, Öneriler. [Internet]. Available from: http://ailetoplum.aile.gov.tr/data/54292ce0369dc32358ee2a46/ taya2013trk.pdf.

13. De Roo AC, Chounthirath T, Smith GA. Television-related injuries to children in the United States, 1990-2011. Pediatrics 2013;132:267–74.

14. Scheidler MG, Shultz BL, Schall L, Vyas A, Barksdale EM Jr. Falling televisions: The hidden danger for children. J Pediatr Surg 2002;37:572– 5.

15. Sikron F, Glasser S, Peleg K. Children injured following TV tipovers in Israel, 1997-2003. Child Care Health Dev 2007;33:45–51.

16. Yapısal Olmayan Tehlikelerin Azaltılması. Available at: http://www.koeri.boun.edu.tr/aheb/pdf%20dokumanlar.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Evdeki gizli tehlike: Televizyon Dr. Oğuzhan Bol,1 Dr. Hüseyin Cebiçci,1 Dr. Serhat Koyuncu,3 Dr. Bahadır Şarlı,4 Dr. Nurullah Günay2 Kayseri Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Kayseri Erciyes Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Kayseri Karabük Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Karabük 4 Kayseri Eğitim ve Araştırma Hastanesi, Kardiyoloji Kliniği, Kayseri 1 2 3

AMAÇ: Her evde en az bir tane bulunan televizyonlar günlük hayatın önemli bir parçası olmuştur. Televizyon karşısında geçirilen vakit artmıştır.

Televizyon boyutları ve ağırlıkları artmıştır. Bu durum ise evlerde çocuklar için başka bir tehlikeyi ortaya çıkarmıştır. Amacımız üzerine televizyon düşmesi olgularına dikkat çekmektir.

GEREÇ VE YÖNTEM: 01.06.2011 ile 31.12.2013 yılları arasında Kayseri Eğitim ve Araştırma Hastanesi Acil Servisi’ne gelen üzerine televizyon düşme olguları kayıt altına alındı. Hastaların yaş, cinsiyet, travmadan etkilenen bölgeleri, Glaskow koma skala değerleri, düşen televizyon boyutu, markası, servis veya yoğun bakım yatışlarının olup olmadığı ve yatış oldu ise kaç gün olduğu kayıt altına alındı.

BULGULAR: Çalışmaya alınan 53 olgunun 30’u erkek (%56.6) ve 23’ü kadındı (%43.4). Sekiz hastanın vücudun herhangi bir yerinde kırık var idi. Bu hastaların üçü (erkek) yoğun bakımda, üçü (iki erkek, bir kadın) ise genel serviste takip edilmişlerdir.

TARTIŞMA: Acil servislere başvuran üzerine televizyon düşme sayıları son zamanlarda giderek artmaktadır. Yaralanmaların yanı sıra sakatlanma hatta ölümlerin görülmesi çocuklarımızın evde karşılaşabilecekleri tehlikeler konusunda dikkatli olmamızı gerektirmektedir.

Anahtar sözcükler: Çocuk; düşme; televizyon.

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ORIG I N A L A R T IC L E

Ingested intraabdominal foreign bodies that require surgical intervention Remzi Kızıltan, M.D.,1 Özkan Yılmaz, M.D.,1 Abbas Aras, M.D.,1 Osman Toktaş, M.D.,1 Abdulsamet Batur, M.D.,2 Fatma Ağar, M.D.,1 Şehmus Ölmez, M.D.,3 Çetin Kotan, M.D.1 1

Department of General Surgery, Yüzüncü Yıl University Faculty of Medicine, Van-Turkey

2

Department of Radiology, Yüzüncü Yıl University Faculty of Medicine, Van-Turkey

3

Department of Gastroenterology, Yüzüncü Yıl University Faculty of Medicine, Van-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to review cases that required surgical intervention to remove ingested foreign bodies.

METHODS: Medical records of 7 patients who underwent surgical intervention at the Yüzüncü Yıl University Department of General Surgery between 2009 and 2014 after ingesting foreign bodies were reviewed.

RESULTS: Female:male ratio was 5:2; mean age was 25 (16–35). Four patients had swallowed pins, 1 patient had swallowed a sewing pin, 1 patient had swallowed a safety pin, and 1 patient had swallowed a wristwatch. The patient who had swallowed the wristwatch had psychiatric disorders. All other patients stated that they had swallowed the objects by accident.

CONCLUSION: Most ingested foreign bodies pass smoothly through the gastrointestinal (GI) tract within a week, but those that migrate out of the lumen require surgical intervention due to complications including perforation, abscess, fistula, and peritonitis.

Early diagnosis and intervention is crucial to reduce morbidity and mortality. It is believed that sharp and pointed objects that migrate outside of the lumen ought to be removed, lest they cause complications.

Keywords: Foreign body; ingested; laparoscopy; laparotomy; surgical intervention.

INTRODUCTION Incidences of foreign body ingestion are globally observed.

While foreign bodies often exit the body by gastrointestinal (GI) transit, surgical intervention is required in some cases.

Though foreign body ingestion is observed among all age groups, it is most commonly encountered in children and early adolescents. Healthy adults may accidentally swallow objects such as needles, toothpicks, dentures, fish bones, and chicken bones. In addition, various foreign bodies are ingested by individuals with psychiatric disorders. Most ingested foreign bodies pass through the GI tract without inducing comAddress for correspondence: Remzi Kızıltan, M.D. Yüzüncü Yıl Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 65100 Van, Turkey Tel: +90 432 - 215 04 72 / 6835 E-mail: bergamalidr@mynet.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):269–272 doi: 10.5505/tjtes.2015.87400 Copyright 2016 TJTES

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plication.[1,2] Otherwise, bleeding caused by mucosal erosion and abrasion may occur, and can be very serious, or even life-threatening. Massive gastrointestinal system (GIS) bleeding associated with aortoduodenal fistula, which occurred following needle ingestion, was described in a report by Kotan C. from the present clinic.[3] In addition, migration out of the lumen, GIS perforation, abscess, and peritonitis may be observed. The rate of such complications arising from the ingestion of foreign bodies is estimated to be less than 1%.[4] Presently described are clinical presentations of various ingested objects and the treatments applied.

MATERIALS AND METHODS The Ethics Committee of the Yüzüncü Yıl University Medical Faculty approved the present study in decision no. 1 made on June 18, 2015. Medical records of 7 patients who underwent surgical retrieval of ingested foreign bodies at Yüzüncü Yıl University Department of General Surgery between 2009 and 2014 were retrospectively reviewed. The foreign bodies were pins in 4 patients, a sewing pin in 1 patient, a safety pin in 1 patient, and a wristwatch in 1 patient (Figs. 1, 2).

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showed that it was adjacent to the stomach wall, outside the stomach. The object was not visible on gastroscopy. Gastroscopy was performed on another patient, who had ingested a wristwatch, but surgical procedure was deemed necessary due to failure of the extraction process.

RESULTS Five female and 2 male patients were included, with an average age of 25 (16â&#x20AC;&#x201C;35). The patient who swallowed the wristwatch had psychiatric disorders; the others stated that they had swallowed the foreign bodies by accident.

Figure 1. Safety pin in the abdomen.

Figure 2. The wristwatch was removed from the stomach.

Physical examinations were performed, plain abdominal radiographs were taken, and high-fiber diet was recommended during weekly follow-ups. Comparison of the localization of the foreign body with that shown on previous radiography served as evaluation of radiography during follow-up. Abdominal tomography was planned when localization of the foreign body was constant. On abdominal computed tomography (CT) scans, it was observed that foreign bodies were extraluminal in 6 cases, 2 of which were in the liver, 2 of which were in the omentum majus, and 1 of which was in the omentum minus. In the case in which the patient ingested a safety pin, localization of the foreign body appeared constant on plain abdominal radiography follow-up. CT scan of the abdomen 270

Common symptoms were non-specific abdominal pain in the right upper quadrant or the epigastric region. Surgical intervention was scheduled because the patients were symptomatic, and because foreign bodies were extraluminal on abdominal CT scans. In 2 patients, pins were laparoscopically removed from the omentum majus and omentum minus. Two foreign bodies were extracted from the liver segment, and 5 were extracted from the omentum minus via direct laparotomy in 2 patients. In the other 3 patients, decision to perform laparotomy was made because it was not possible to detect the foreign bodies via laparoscopic exploration. Location of the foreign bodies was determined with the aid of fluoroscopy. In 1 patient, a pin was removed from the liver parenchyma.

In another, laparoscopic exploration was performed to extract a safety pin localized adjacent to the stomach, though it proved impossible to detect the foreign body via laparotomy.

A safety pin was located in the lumen of the cecum on CT scan of the abdomen obtained on the first postoperative day.

This was interpreted as a probable translocation of the safety pin due to surgical manipulation of the intestinal lumen that superposed with the stomach. During follow-up, the safety pin was safely discarded by defecation. Subsequent to laparoscopic exploration, the patient who ingested the wristwatch underwent gastrotomy. The wristwatch was located in the gastric fundus and was removed from the abdomen by slightly expanding the port site and gastrostomy line (Table 1).

DISCUSSION Incidence of foreign body ingestion is not known. The most common cause is ingestion by accident. Perforation most commonly occurs in the duodenal, ileocecal, and rectosigmoid regions.[4] Most foreign bodies transmigrate uneventfully from the stomach to the duodenum and transverse from the colon to the liver.[5] Of those included in the present study, 2 foreign bodies were extracted from the right lobe of the liver, 1 was extracted from the omentum minus, and 2 were extracted from the omentum majus. For this reason, the starting point of transmigration is thought to be the duodenum.

Average follow-up period was 2.5 months. The psychiatric patient who ingested the wristwatch attended the shortest follow-up period (1 month), while the longest (6 months) was Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Kızıltan et al. Ingested intraabdominal foreign bodies that require surgical intervention

Table 1. Summary of cases No Name- Age Gender

Surname

1

F.G

22

Female

Duration of the pre-operative Follow-up (month) 2

Type and localization of the foreign body

Performed surgical procedure

A pin in the liver segment seven

The foreign body was removed via

open surgery which started with

laparoscopy

2

Y.T

26

Female

2

A pin in the omentum majus

The foreign body was removed via

laparotomy

3

A sewing needle in the liver

The foreign body was removed via

segment five

laparotomy

4

A pin in the omentum majus

The foreign body was removed via

A.A M.C.Ö

16 34

Female Male

2 2

laparoscopy

5

The foreign body was removed via

A.A

35

Female

2

A pin in the omentum minus

6

A.A

25

Female

6

A safety pin in the abdomen

laparoscopy Started with laparoscopy and

continued with laparotomy but the

foreign body could not be found

7

Started with laparoscopy, then

E.Ö

22

Male

1

A wristwatch in the stomach

foreign body removed via

laparotomy

attended by the patient who ingested the safety pin. Most ingested foreign bodies pass harmlessly through the GI tract within 1 week.[6–8] If this does not occur, clinicians must seriously consider the possibility of complications.

Plain radiography is sufficient for the determination of the localization of most radio-opaque foreign bodies;[9] CT and magnetic resonance imaging are rarely necessary. In the present study, follow-up involved plain radiography of the abdomen. Biochemical hemogram and CT scan of the abdomen were obtained in symptomatic patients with unchanging foreign body localization observed on plain radiography of the abdomen.

As foreign bodies migrate out of the lumen, they may cause very small perforation and minimal leakage. Therefore, peritonitis occurrence is thought to be very rare. Foreign bodies that migrate to the extraluminal region may remain unnoticed for long periods of time, and are thus more likely to cause infection and abscess. Occurrence of abscess was not observed in the present cases. Çekirdekçi reported cardiac tamponade in 2 cases in which sewing pins migrated from the esophagus.[10] Localization in the vertebrae resulting from migration was reported by Özsunar.[11] In a study by Chen, thyroid abscess that occurred following ingestion of a fish bone by a 50-year-old female Chinese patient was reported.[12] Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Gurjit Singh reported an increase in the frequency of children aged between 6 months and 6 years swallowing button batteries from toys, which can cause corrosive injuries.

Therefore, if detected in the esophagus, batteries should be removed immediately via endoscopic intervention.[13] Urgent intervention is indicated if any of the following warning signs are present:[14] - Localization of battery in the esophagus - Patient showing signs of airway compromise - Evidence of near-complete esophageal obstruction - When the ingested object is sharp, long (>5 cm), and localized in the esophagus or stomach - When the ingested object is a high-powered magnet or magnets - When signs or symptoms suggesting inflammation or intestinal obstruction are present (fever, abdominal pain, or vomiting).[15] Surgical removal should be considered for blunt objects beyond the stomach that remain in the same location for longer than 1 week.[16]

Conclusion Ingested foreign bodies should be strictly followed until they are naturally expelled from the body. Furthermore, early diagnosis and intervention is crucial in the reduction of morbidity and mortality. Sharp and pointed objects that migrate 271

Kızıltan et al. Ingested intraabdominal foreign bodies that require surgical intervention

outside the lumen should be removed before they cause complications.

8. Lotfi M. Foreign body in the liver. Int Surg 1976;61:228.

Conflict of interest: None declared.

10. Cekirdekci A, Ayan E, Ilkay E, Yildirim H. Cardiac tamponade caused by an ingested sewing needle. A case report. J Cardiovasc Surg (Torino) 2003;44:745–6.

REFERENCES 1. Crankson SJ. Hepatic foreign body in a child. Pediatr Surg Int 1997;12:426–7.

2. Lee KF, Chu W, Wong SW, Lai PB. Hepatic abscess secondary to foreign body perforation of the stomach. Asian J Surg 2005;28:297–300.

3. Başer M, Arslantürk H, Kisli E, Arslan M, Oztürk T, Uygan I, et al.

Primary aortoduodenal fistula due to a swallowed sewing needle: a rare cause of gastrointestinal bleeding. Ulus Travma Acil Cerrahi Derg 2007;13:154–7.

4. Santos SA, Alberto SC, Cruz E, Pires E, Figueira T, Coimbra E, et al. Hepatic abscess induced by foreign body: case report and literature review.

World J Gastroenterol 2007;13:1466,70.

5. Nishimoto Y, Suita S, Taguchi T, Noguchi S, Ieiri S. Hepatic foreign body - a sewing needle - in a child. Asian J Surg 2003;26:231–3.

6. Abel RM, Fischer JE, Hendren WH. Penetration of the alimentary tract by a foreign body with migration to the liver. Arch Surg 1971;102:227–8.

7. Crankson SJ. Hepatic foreign body in a child. Pediatr Surg Int 1997;12:426–7.

9. Suita S, Ohgami H, Nagasaki A, Yakabe S. Management of pediatric patients who have swallowed foreign objects. Am Surg 1989;55:585–90.

11. Ozsunar Y, Tali ET, Kilic K. Unusual migration of a foreign body from the gut to a vertebral body. Neuroradiology 1998;40:673–4.

12. Chen CY, Peng JP. Esophageal fish bone migration induced thyroid abscess: case report and review of the literature. Am J Otolaryngol 2011;32:253–5.

13. Singh G, Sharma S, Khurade S, Gooptu S. Ingested foreign bodies in children: a report of two cases. J Family Med Prim Care 2014;3:452–5.

14. Gilger MA, Jain AK, McOmber ME. Foreign bodies of the esophagus and gastrointestinal tract in children. Literature review current through.

2013. Aug, [Last cited on 2013 Aug 23]. Available at: http://www.uptodate.com/contents/foreignbodies of the esophagus and gastrointestinal tract in children.

15. Uyemura MC. Foreign body ingestion in children. Am Fam Physician 2005;72:287–91.

16. Ikenberry SO, Jue TL, Anderson MA, Appalaneni V, Banerjee S, BenMenachem T, et al. Management of ingested foreign bodies and food impactions. Gastrointest Endosc 2011;73:1085–91.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yutulan ve cerrahi müdahale gerektiren intraabdominal yabancı cisim olgularımız Dr. Remzi Kızıltan,1 Dr. Özkan Yılmaz,1 Dr. Abbas Aras,1 Dr. Osman Toktaş,1 Dr. Abdulsamet Batur,2 Dr. Fatma Ağar,1 Dr. Şehmus Ölmez,3 Dr. Çetin Kotan1 1 2 3

Yüzüncü Yıl Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Van Yüzüncü Yıl Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Van Yüzüncü Yıl Üniversitesi Tıp Fakültesi, Gastroenteroloji Anabilim Dalı, Van

AMAÇ: Bu çalışmada yutulan yabancı cismin vücut dışına çıkarılması için cerrahi müdahale yapılan olgular analiz edildi.

GEREÇ VE YÖNTEM: Van Yüzüncü Yıl Üniversitesi Tıp Fakültesi Genel Cerrahi Anabilim Dalı’nda 2009 ile 2014 yılları arasında yabancı cisim yutulması sonrasında cerrahi müdahale yapılmış yedi olgunun tıbbi kayıtları geriye dönük olarak incelendi.

BULGULAR: Erkek/kadın oranı 2/5, ortalama yaş 25 (16–35), dört olgu toplu iğne, bir olgu dikiş iğnesi, bir olgu çengelli iğne ve bir olgu da kol saati yutmuştu. Kol saati yutan olgunun psikyatrik hastalığı bulunmaktaydı. Diğer bütün olgular yabancı cisimleri kazara yuttuklarını ifade ediyorlardı.

TARTIŞMA: Yutulan yabancı cisimlerin çoğu bir hafta içinde gastrointestinal tarktusu sorunsuzca geçmekte ancak lümen dışına migrasyon yapan bir kısmı perforasyon, apse, fistül ve peritonit gibi komplikasyonlar nedeni ile cerrahi tedavi gerektirmektedir. Morbidite ve mortalitenin azaltılması için erken tanı ve müdahale önemlidir. Lümen dışına çıkan keskin ve sivri cisimlerin, herhangi bir komplikasyon meydana getirmeden cerrahi müdahale ile çıkarılması gerektiğini düşünmekteyiz.

Anahtar sözcükler: Cerrahi müdahale; laparoskopi; laparotomi; yabancı cisim; yutma.

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ORIG I N A L A R T IC L E

Where should the damage control surgery be performed, at the nearest health center or at a fully equipped hospital?

Mustafa Uğur, M.D.,1 Seçkin Akküçük, M.D.,1 Yavuz Savaş Koca, M.D.,2 Cem Oruç, M.D.,1 Akın Aydoğan, M.D.,1 Erol Kılıç, M.D.,1 İbrahim Yetim, M.D.,1 Muhyittin Temiz, M.D.1 1

Department of General Surgery, Mustafa Kemal University Faculty of Medicine, Hatay-Turkey

2

Department of General Surgery, Süleyman Demirel University Faculty of Medicine, Isparta-Turkey

ABSTRACT BACKGROUND: Transport of casualties from a combat area to a fully equipped hospital where all techniques of damage control surgery (DCS) can be performed requires a great deal of time. Therefore, prior to transport, prompt control of hemorrhage and contamination should be achieved, and resuscitative procedures should be performed at the nearest health center. The aim of the present study was to investigate the effect of the location at which DCS was performed on rates of mortality.

METHODS: The present retrospective study included 51 combat casualties who underwent DCS at the present clinic or at hospitals nearest the combat area due to high kinetic energy gunshot injuries to the abdomen between 2010 and 2015. Patients were evaluated in terms of acidosis, hypothermia, coagulopathy, and mortality.

RESULTS: Patients were divided into 2 groups depending on the location where the first step of DCS was performed: (1) at the present hospital or (2) at other hospitals. Group 1 comprised 26 patients (51%), and Group 2 comprised 25 (49%). Total mortality occurred in 23 (45.1%) patients, including 15 (57.7%) patients in Group 1 and 8 (32%) in Group 2. In Group 1, mean time from injury to hospital admission was longer, and deep acidosis, hypothermia, and coagulopathy were more marked.

CONCLUSION: Initial surgical control of hemorrhage and contamination in patients injured by high kinetic gunshots should be promptly achieved at the nearest health center. In this way, acidosis, hypothermia, and coagulopathy can be prevented, and the risk of mortality can be reduced.

Keywords: Damage control surgery; locality of surgery; mortality.

INTRODUCTION Damage control surgery (DCS) has been used as a life-saving procedure in patients with severe trauma since its first description in 1983. The primary aim in the performance of DCS is to increase likelihood of patient survival by maintaining tolerable levels of the lethal triad of acidosis, hypothermia, and coagulopathy.[1] Complete performance of DCS requires experienced staff and fully equipped hospitals that can provide technical equipAddress for correspondence: Mustafa Uğur, M.D. Mustafa Kemal Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Hatay, Turkey Tel: +90 505 - 346 32 09 E-mail: drmustafaugur@gmail.com Qucik Response Code

ment needed in order to reverse acidosis, hypothermia, and coagulopathy.[2] However, as combat and riots are irregular in war zones, experienced staff and fully equipped hospitals are difficult to find.[3] Therefore, combat casualties are transported either long distances to fully equipped hospitals or a short distance to the nearest hospital, where the first step of DCS is performed.

The aim of the present study was to investigate the effect of DCS administration location on the mortality rate of combat casualties due to high kinetic energy gunshot injuries to the abdomen. DCS was either performed in entirety at the Mustafa Kemal University Medical School General Surgery Department or the first step was performed at hospitals close to the combat area before the patients were transported, between 2010 and 2015.

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MATERIALS AND METHODS

Copyright 2016 TJTES

The present retrospective study included 51 combat casualties . All casualties were transported to the Turkish border, either by vehicle or by unidentified method, before being

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transported to the clinic by ambulance. Patients were divided into 2 groups depending on the location at which the first step of DCS was performed: (1) at the present hospital or (2) at other hospitals. Age, gender, time from injury to hospital admission, body temperature at hospital admission, pH level, systolic blood pressure, international normalized ratio (INR) level, associated organ injury, amount of blood transfused, and mortality were recorded. Other information included exact time of injury, admission time to other hospital, laboratory parameters, amount of erythrocyte suspension transfused, and body temperature, obtained via clinical records sent from Syrian hospitals, accompanying ambulance personnel, or immediate accounts of escorts. Following admission, physical examination was performed, and both groups underwent the same resuscitation procedure. Axillary body temperature was measured, and blood samples were obtained for whole blood count, arterial blood gas, and biochemical and coagulation tests. Following initial evaluation, the patients were transferred either directly to the operating room or to the intensive care unit (ICU). Four patients whose preoperative cardiopulmonary resuscitation took more than 5 minutes were excluded, as were 3 patients who died during DCS procedure performed at the present hospital, 2 of whom presented with aortic injury, and 1 of whom presented with inferior vena cava injury. Also excluded were 5 patients with incomplete preoperative data.

ries were primarily repaired and tube thoracostomy was performed in injuries preoperatively diagnosed. Selective ligation of hepatic and biliary leakages was achieved using finger fracture technique or packing procedure. Finger fracture technique was performed following the Pringle maneuver, which was performed with an overall median time of 20 min. Packing procedure was performed with the insertion of 2–4 packs around the liver. Splenectomy was performed for splenic injuries. For major intestinal injuries, primary closure was performed with intestinal staplers or 2-0 silk suture. No intestinal resection was performed, and no anastomosis, feeding tubes, or ostomy were used.

Damage Control Surgery

Statistical Analysis

Each initial examination was performed in the emergency service unit. Patients who had not undergone surgery in Syria were promptly transferred to the operating room. Following the infusion of 2000-cc lactated Ringer’s solution, systolic blood pressure was considered (1) as stable in patients with systolic blood pressure >90 mmHg, (2) as temporarily stable in patients with >90 mmHg that lowered to <90 mmHg as a result of cessation of infusion, requiring transfusion of blood and blood products, and (3) as unstable in patients with systolic blood pressure <90 mmHg. Decision to perform DCS was based on following sings: pre- or intraoperative arterial pH <7.20, body temperature <35.5 °C, INR level >1.9, and presence of hemodynamic instability.

Data were analyzed using SPSS software for Windows (version 20.0; SPSS Inc., Chicago, IL, USA). Student’s t-test was used to analyze demographic data. Two-way analysis of variance for repeated measures was used to analyze changes over time. Mann-Whitney U test and χ2 test were used with appropriate corrections to analyze ordinal data. Continuous variables were presented as mean±SD or median (range). A p value of <0.05 was considered significant.

Patients were evaluated by an infectious diseases specialist, and antibiotic therapy was initiated. Central venous catheter was inserted for fluid and electrolyte replacement. In patients who underwent the first step of DCS in Syria, central venous catheter was inserted in the ICU. Warmed blankets and heaters were used to prevent temperature loss in patients.

In addition, fluids were heated to body temperature before transfusion.

In Group 1, laparotomy was performed via midline incision.

Initial step included hemostatic control via abdominal packing in all 4 abdominal quadrants. Vascular injuries were treated using vascular clamp or suture ligation. Diaphragmatic inju274

In order to avoid acute abdominal compartment syndrome, and to achieve rapid transfer of the patient to ICU, the skin was simply closed with skin-only closure or sterile serum physiologic bag (Bogota bag). Following DCS procedure, all patients were transferred to the ICU, and fluid resuscitation was performed, with intravenous fluid, blood, plasma, and volume expanders. Following correction of physiological and biochemical abnormalities, definitive surgery was performed 24–48 h after initial surgery.

Associated organ injuries were treated during definitive surgery. Intestinal injuries were treated using primary repair, ileostomy-colostomy, or anastomotic techniques.

RESULTS Patients were divided into 2 groups depending on the location where the first step of DCS was performed: (1) at the present hospital or (2) at other hospitals. Group 1 included 26 (51%) patients, and Group 2 included 25 (49%). All 51 patients were male (100%), with a mean age of 27.92±8.51 years in Group 1 and 34.84±12.10 years in Group 2. No significant difference in mean age was found (p=0.02). Mean time from injury to hospital admission was 188.07±52 minutes in Group 1 and 85.20±29.59 minutes in Group 2, and a significant difference was observed (p=0.001). Mean pH level was 7.14±0.13 in Group 1 and 7.24±0.08 in Group 2, and a significant difference was found (p=0.002). Mean body temperature was 35.89±0.50°C in Group 1 and 36.08±0.65°C in Group 2 (p=0.234). Mean INR level was 1.95±0.64 in Group 1 and 1.86±0.45 in Group 2 (p=0.602). No significant difference was observed between the groups regarding amount of Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

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Table 1. Clinical profiles of the patients at admission Parameter

Group I (n=26; 51%)

Group II (n=25; 49%)

p

Age

27.92±8.51

34.84 ±12.10

=0.02

Gender

Male (100%)

Male (100%)

n=17; 54.8%

n=14; 45.2%

Mechanism of Injury

Gunshot

Shrapnel

Time from injury to hospital admission (min)

=0.493

n=9; 45.0%

n=11; 55.0%

188.07±52.00

85.20±29.59

=0.001

pH

7.14±0.13

7.24±0.08

=0.002

Body temperature (°C)

35.89±0.50

36.08±0.65

=0.234

INR

1.95±0.64

1.86±0.45

=0.602

ES

3.61±1.57

3.72±1.62

=0.816

Stable

n=3; 11.5%

n=8; 32.0%

=0.68

Temporarily stable

n=15; 57.6%

n=7; 28.0%

Unstable

n=8; 30.7%

n=10; 40.0%

n=5; 19.2%

n=6; 24.0%

Systolic blood pressure

Associated organ injury

Liver

Liver and other abdominal organs

n=11; 42.3%

n=10; 40.0%

Abdominal organs other than liver

n=10; 38.4%

n=9; 36.0%

n=15; 57.7%

n=8; 32.0%

Mortality

=0.918

=0.65

Group I: The patients who underwent damage control surgery at our hospital; Group II: The patients who underwent the first steps of damage control surgery at other hospitals; ES: Erythrocyte suspension transfused; p<0.05.

erythrocyte transfusion, hemodynamic stability, mechanism of injury, or associated organ injury. Total mortality occurred in 23 (45.1%) patients, including 15 (57.7%) patients in Group 1 and 8 (32.0%) patients in Group 2. No significant difference regarding total mortality was found (p=0.65) (Table 1).

DISCUSSION DCS consists of 3 steps when used to treat patients with hypothermic, coagulopathic, and acidotic abdominal trauma.

The first and most important step includes prompt surgical control of hemorrhage and contamination.[4,5] Decision to perform DCS should be made in the first 15 minutes and be based on indications including hypothermia (body temperature <35.5°C), severe acidosis (arterial pH <7.20), and coagulation disorder (INR >1.9).[6,7] However, the decision should be made before the onset of all 3 indications, which may mark the “point of no return” and may indicate DCS failure. Systolic blood pressure can be used as an indication of hemodynamic instability.[8] The second step of DCS includes core rewarming and completion of acute resuscitation. The primary goal of this step is to reverse hypothermia, acidosis, and coagulopathy.[9,10] In major trauma patients with acidosis, hypothermia, and hypotension, the presence of coagulopathy is characterized by Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

INR >1.9 and/or activated partial thromboplastin time level >60 seconds. In such patients, administration of fresh frozen plasma and cryoprecipitate, in addition to transfusion of crystalloid fluids and erythrocyte suspension, has been reported to decrease risk of mortality.[11–13] For the reversal of hyperthermia, core rewarming should be performed in the operating room and the ICU, and the blood and the intravenous fluids should be rewarmed. The third step of DCS includes definitive surgery for all associated organ injuries following metabolic normalization.[14–16] Performance of all 3 steps of DCS requires an ICU supplied with technical equipment, available blood stock, mechanical ventilator, advanced monitorization systems, and trained medical personnel. Decision to perform DCS may be controversial in war zones, and can also be controversial during hospital admission, depending on the availability of equipment required for DCS performance. In addition, the decision can be dependent on other factors, including the number and frequency of admitted combat casualties, the number of casualties anticipated, the availability and qualifications of medical personnel, and the availability of blood supply.[17] In times of war, unexpected scenarios may occur regarding treatment and evacuation of combat casualties. Accounts of 275

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casualties and their clinical and surgical features indicate that combatants in the Syrian civil war have established health centers near the combat area where laparotomy can be performed. It has also been revealed that initial triage for combat casualties is performed at these centers, where the decision regarding whether surgery should be performed in Syria or Turkey is made. Patients transported from these centers include those who have undergone surgery in Syria before being transported to Turkey for ICU support, as well as those who have been directly transported to Turkey for surgery.

Health facilities in combat areas are generally inoperative or inadequate.[17] Given the clinical and surgical features of patients who underwent the first step of DCS in Syria and were then transported (Group 2), it is presently believed that the health centers at which those procedures were performed have equipment and personnel adequate for the performance of the first step of DCS. However, clinical records reveal that the hospitals have inadequate ICUs. Prolonged administration time also leads to delayed DCS and resuscitation. Hence, poor prognosis in the management of patients with penetrating abdominal trauma is caused by the lethal triad.[7] In patients who underwent DCS at the present hospital, deep acidosis, hypothermia, and coagulopathy were more noticeable. It is presently believed that this was associated with the higher mortality rate in this group. It is also believed that more noticeable presence of the lethal triad in this group resulted from prolonged mean time from injury to hospital admission. On the other hand, the most important problem for the patients who underwent the 1st step of DCS in Syria was the delay in administration of the 2nd step, which includes the prompt reversal of acidosis, hypothermia, and coagulopathy.

In combat casualties who require DCS due to severe abdominal trauma, the 1st step should be performed at the health center nearest the combat area, after which the transport of the patient for the administration of the 2nd and 3rd steps may prevent occurrence of the lethal triad, and may decrease risk of mortality. Vehicles used for patient transport should be supplied with equipment required to reverse hypothermia, acidosis, and coagulopathy. The employment of trained medical personnel may also contribute to the successful treatment of combat casualties.

Conflict of interest: None declared.

276

REFERENCES 1. Stagnitti F. Uncontrolled bleeding in patients with major abdominal trauma. Ann Ital Chir 2013;84:365.

2. Eiseman B, Moore EE, Meldrum DR, Raeburn C. Feasibility of damage control surgery in the management of military combat casualties. Arch Surg 2000;135:1323–7.

3. Giannou C, Baldan M. First aid in armed conflict. In: Giannou C, BaldanM, eds. War surgery: working with limited resources in armed conflict and other situations of violence. Vol. 1. Geneva: International Committee of the Red Cross 2010:153–61.

4. Nicol AJ, Hommes M, Primrose R, Navsaria PH, Krige JE. Packing for control of hemorrhage in major liver trauma. World J Surg 2007;31:569– 74.

5. Aydin U, Yazici P, Zeytunlu M, Coker A. Is it more dangerous to perform inadequate packing? World J Emerg Surg 2008;3:1.

6. Kouraklis G, Spirakos S, Glinavou A. Damage control surgery: an alternative approach for the management of critically injured patients. Surg Today 2002;32:195–202.

7. Rotondo MF, Zonies DH. The damage control sequence and underlying logic. Surg Clin North Am. 1997;77:761–77.

8. Matsumoto H, Mashiko K, Sakamoto Y, Kutsukata N, Hara Y, Yokota H. A new look at criteria for damage control surgery. J Nippon Med Sch 2010;77:13–20.

9. Hoey BA, Schwab CW. Damage control surgery. Scand J Surg 2002;91:92–103.

10. Rotondo MF, Schwab CW, McGonigal MD, Phillips GR 3rd, Fruchterman TM, Kauder DR, et al. ‘Damage control’: an approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma 1993;35:375–83.

11. Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007;63:805–13.

12. Byers R. An upshot of war - damage control resuscitation. Int Emerg Nurs 2010;18:221–5.

13. Sirieix D, Delayance S, Paris M, Massonnet-Castel S, Carpentier A, Baron JF. Tris-hydroxymethyl aminomethane and sodium bicarbonate to buffer metabolic acidosis in an isolated heart model. Am J Respir Crit Care Med 1997;155:957–63.

14. Kapan M, Onder A, Oguz A, Taskesen F, Aliosmanoglu I, Gul M, et al.

The effective risk factors on mortality in patients undergoing damage control surgery. Eur Rev Med Pharmacol Sci 2013;17:1681–7.

15. Moore EE, Cogbill TH, Malangoni MA, Jurkovich GJ, Shackford SR, Champion HR, et al. Organ injury scaling. Surg Clin North Am 1995;75:293–303.

16. Sharp KW, Locicero RJ. Abdominal packing for surgically uncontrollable hemorrhage. Ann Surg 1992;215:467–75.

17. Giannou C, Baldan M, Molde Å. Injuries to the abdomen. In: Giannou C, BaldanM, Molde Å eds. War surgery: working with limited resources in armed conflict and other situations of violence. Vol. 2. Geneva: International Committee of the Red Cross 2013:442–5.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Hasar kontrol cerrahisi nerede yapılmalı? Yapılabilecek en yakın yerde mi, tam donanımlı hastanede mi?

Dr. Mustafa Uğur,1 Dr. Seckin Akküçük,1 Dr. Yavuz Savaş Koca,2 Dr. Cem Oruç,1 Dr. Akın Aydoğan,1 Dr. Erol Kılıç,1 Dr. İbrahim Yetim,1 Muhyittin Temiz1 1 2

Mustafa Kemal Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Hatay Süleyman Demirel Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı- Isparta

AMAÇ: Savaş koşullarında ciddi şekilde yaralanmış hastaları hasar kontrol cerrahisinin tüm aşamalarını başarıyla yapabilecek tam donanımlı hastanelere nakletmek için uzun süreye ihtiyaç vardır. Bu nedenle savaşta yaralananlar ya yaralanma alanına yakın birimlerde kanama ve kontaminasyon kontrolü sağlanarak yada sadece resusitatif işlemler yapılarak tam donanımlı hastanelere sevk edilmektedir. Bu çalışmanın amacı hasar kontrol cerrahisinin yapıldığı yer ile mortalite arasındaki ilişkiyi belirlemektir.

GEREÇ VE YÖNTEM: Bu çalışmaya 2010–2015 yılları arasında abdominal bölgeden yüksek kinetik enerjili ateşli silahlarla yaralandıktan sonra hastanemizde ya da yaralanma yerine daha yakın diğer hastanelerde hasar kontrol cerrahisi yapılan 51 hasta dahil edildi. Hastalar hasar kontrol cerrahisinin ilk aşamasını oldukları yere göre gruplandırılarak asidoz, hipotermi, koagülopati ve mortalilte açısından değerlendirildi.

BULGULAR: İlk ameliyatı hastanemizde olanların sayısı 26’idi (%51). Diğer hastanelerde ameliyat olanların sayısı 25’di (%49). Tüm hastaların %45.1’i (n=23) kaybedildi. İlk ameliyatı hastanemizde yapılanların %57.7’si (n=15); diğer hastanelerde yapılanların %32.0’si (n=8) kaybedildi. Hastanemizde ameliyat olanlarda başvuru zamanı daha uzundu. Asidoz, hipotermi ve koagülopati daha belirgindi.

TARTIŞMA: Abdominal bölgeden yüksek kinetik enerjili silahlarla yaralananlarda kanama ve kontaminasyonun erken kontrolü yapılabilecek en yakın yerde gerçekleştirilmelidir. Bu uygulama asidoz, hipotermi ve koagülopati gelişmesini önleyebilir ve böylece mortalite oranının düşürülmesinde etkili olabilir.

Anahtar sözcükler: Ameliyatın yapıldığı yer; hasar kontrol cerrahisi; mortalite.

Ulus Travma Acil Cerrahi Derg 2016;22(3):273–277

doi: 10.5505/tjtes.2016.63833

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ORIG I N A L A R T IC L E

Electrical burns: Highlights from a 5-year retrospective analysis Alper Kurt, M.D.,1 Kamil Yıldırım, M.D.,1 Çağlayan Yağmur, M.D.,3 Osman Kelahmetoğlu, M.D.,2 Ozan Aslan, M.D.,1 Murat Gümüş, M.D.,1 Ethem Güneren, M.D.,2 1

Department of Plastic Reconstructive and Aesthetic Surgery, Samsun Training and Research Hospital, Samsun-Turkey

2

Department of Plastic Reconstructive and Aesthetic Surgery, Bezm-i Alem Vakif Foundation University Faculty of Medicine, İstanbul-Turkey

3

Department of Plastic Reconstructive and Aesthetic Surgery, Ondokuz Mayıs University Faculty of Medicine, Samsun-Turkey

ABSTRACT BACKGROUND: Electrical burns are the third most common cause of burn injuries, after scald and flame burns. In spite of decreasing mortality rates as advancements are made in treatment modalities and medical equipment, significant complications and socioeconomic consequences still accompany electrical burns. Analyzed in the present study were data from patients hospitalized for electrical burns between 2008 and 2012 in the Samsun Training and Research Hospital, the only burn care center in the Black Sea region of Turkey.

METHODS: Data from 94 patients (84 males, 10 females) hospitalized for electrical burns between 2008 and 2012 were retrospectively evaluated. Patient age, gender, occupation, presence of coexisting trauma, burn degree, burned percentage of total body surface area (TBSA), voltage of the electric current (low or high), medical cost (per day and total), and infection rates were analyzed.

RESULTS: Mean patient age was 26.4±13.2 years. Ten patients were female (10.6%) and 84 were male (89.4%). High-voltage burns were sustained by 47 patients (50%) and low-voltage burns by 42 (44.7%); the remaining 5 were flash burns. Mean burned TBSA was 21.8±19.8% in high-voltage injuries and 11.9±6.9% in low-voltage injuries. Seven patients had accompanying soft tissue lacerations, major bone fractures, or epidural hematomas. Findings of infection were encountered in 31 patients (32.9%), and appropriate treatments were initiated according to culture results. Mean duration of hospitalization was 21.3±19.8 days in patients with high-voltage burns and 8.6±6.2 days in patients with low-voltage burns. Mean hospital stay was 2.5-fold longer, and total medical costs were 4-fold higher in patients with high-voltage burns.

CONCLUSION: Young adult males who were injured in industrial accidents constituted the majority of high-voltage burn patients.

Incidence of these injuries may be reduced by improvements in training regarding the safe use of electrical devices, and correct installation and safe maintenance of power grids, as well as by a review of occupational safety regulations.

Keywords: Electrical burns; retrospective analysis.

INTRODUCTION Electrical injuries are the third most common cause of burns after scald and flame burns. In spite of advances in treatment modalities and the resulting decrease in mortality rates, electrical burns may lead to socioeconomic burden, as well as Address for correspondence: Çağlayan Yağmur, M.D. Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, Samsun, Turkey Tel: +90 363 - 312 19 19 E-mail: caglayanyagmur@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(3):278–282 doi: 10.5505/tjtes.2015.55491 Copyright 2016 TJTES

278

significant functional and cosmetic problems.[1–5] An electric current can reach deep tissues, and cause deep and extensive injuries. Depending on voltage magnitude, injury may be sustained in nerve, bone, and tendon tissue, as well as that of the skin.[3,6–8] The primary mechanism of tissue injury is the direct effect of the electric current. However, electrical injury can arise from both thermal and non-thermal mechanisms, and other injuries can accompany electrical burns. Tissue injury is determined by the magnitude of the electric current, the duration of exposure, and by tissue resistance. Electrical burns are traditionally classified as high-voltage (>1000V) or low-voltage (<1000V).[1,9] Flash arc and lightning burns remain outside the traditional classification scheme, and are usually considered high-voltage burns.

These injuries are most prevalent in young adult males, and cause loss of working hours.[1,3,6,7,10] Importantly, these injuries Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Kurt et al. Electrical burns

20 15 10 5

Burn degree and total body surface area (TBSA) were assessed prior to admission. Each patient was examined for cardiac rhythm and renal function (fluid intake/output, myoglobinuria, blood urea nitrogen, and serum creatinine levels).

Accompanying trauma or coexisting disease were also evaluated during initial management. Proper fluid resuscitation was administered according to the Parkland formula (via 2 venous routes in patients with burned TBSA <30%, and via central venous line in patients with burned TBSA >30%; an arterial line was provided to monitor need for endotracheal intubation). Urine output of >30 cc/hour indicated sufficient fluid replacement. Relevant cultures were obtained, and intravenous antibiotics were empirically initiated when signs of infection (hypotension, hypo- or hyperglycemia, alterations in mental state, or fever) were observed. Non-steroidal antiinflammatory drugs were orally or intravenously administered for routine pain relief, and opioids were used as second-line drugs. Wound dressing changes were made daily. Wound debridement, tangential excision, and grafting were performed when necessary. Patients were closely observed for signs of compartment syndrome, and escharotomy or fasciotomy was performed as needed.

Demographics, length of hospital stay, injury mechanism, accompanying trauma, coexisting illnesses, voltage classification of the exposed electrical current (low or high), site of inlet and outlet current, burned TBSA, culture results of burn wounds, surgical interventions, and medical costs per patient were evaluated.

RESULTS Data from 94 patients (84 males and 10 females) were evaluated retrospectively. Patient age ranged from 47 months to 72 years. Mean age was 18.8±8.7 years for female patients and 27.4±12.8 years for male patients. Age and gender data are shown in Figure 1.

Causes of electrical injuries were industrial accidents (n=47), contact with unattended open electrical wires (n=21), accidents related to climbing utility poles (n=13), lightning (n=4), Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

e ag

e

–↑ 60

–5

9

ag

e 50

9

ag

e –4 40

–3

9

ag

e 30

20

–2

9

ag 9 –1

ag

e

e

0

10

Data from patients admitted to the center for electrical burn injuries between 2008 and 2012 were retrospectively analyzed. All patients were admitted upon sustaining the injury, though those referred from other centers were also included.

25

ag

MATERIALS AND METHODS

Male Female

9

The aim of the present study was to retrospectively analyze cases of electrical injury treated within a 5-year period at the Samsun Training and Research Hospital, the only burn care center in the Black Sea region of Turkey.

30

0–

can be avoided with proper education, safety regulations, and a safe, effective electricity delivery network.

Figure 1. Gender and age distribution of patients with electrical burns.

18 16 14 12 10

Persons Electric supply workers Buildig workers Painters Farmers Roof maintenance workers Junk dealers

17 13 7 4 3 3

8 6 4 2 0

Figure 2. Occupational distribution of patients with electrical injuries sustained in industrial accidents.

attempted suicide (n=1), and others (n=8). Patients who sustained industrial injuries were electricity supply workers (n=17), construction workers (n=13), painters (n=7), farmers (n=4), roof maintenance workers (n=3), and junk dealers (n=3) (Figure 2). Four patients (4.2%) died during the study period. Of these patients, 3 died of acute renal failure, and 1 died of sepsis and multiple organ failure.

Injuries were classified as low-voltage burns (n=42; 44.7%), high-voltage burns (n=47; 50%), or flash burns caused by lightning (n=5; 5.3%). Minimum burned TBSA was 2% for low-voltage burns, 7% for high-voltage burns, and 5% for flash burns. Maximum burned TBSA was 20% for low-voltage burns, 80% for high-voltage burns, and 70% for flash burns. Mean burned TBSA was 11.9±6.9%, 21.8±19.8%, and 23.4±26.3% per classification, respectively.

Length of hospital stay was 2–30 days (with a mean of 8.6±6.2 days) for low-voltage burns. Patients with high-voltage burns were admitted for 3–116 days (with a mean of 21.3±19.8 days). Patients with flash burns were admitted for 4–20 days (with a mean 13.2±14.6 days).

279

Kurt et al. Electrical burns

Two patients had coexisting epilepsy, 1 of whom had mental retardation and made contact with an electrical wire with the intention of committing suicide. This patient had seconddegree skin burn over 12% of TBSA and spent 8 days in admission. Following treatment he was discharged, without the need for surgical intervention. The other epileptic patient was an 11-year-old male with 2nd- and 3rd-degree burns over 15% of TBSA. The patient required debridement and grafting before being discharged on the 16th day of admission. Two patients had gastric ulcer, only 1 of whom had undergone surgical treatment. A female patient in the sixth month of pregnancy was hospitalized for 2 days and discharged after an uneventful course of treatment. During the follow-up period, no complication was observed in the mother or fetus. Two patients had coronary artery disease, and treatment was uneventfully completed.

Enterobacter spp., 2 Esherichia Coli, 3

Pseudomonas, 11

Upper extremities were found to be more frequently injured than lower extremities. Injury sites were: the right upper extremity (in 58 patients), left upper extremity (in 47), right lower extremity (in 39), left lower extremity (in 28), thoracic wall (in 22), posterior trunk (in 18), abdomen (in 15), face (in 12), neck (in 7), and the genital region (in 4) (Figure 4).

During the early phase of management, 35 patients (37%) required surgical wound debridement, 24 of whom required 2 or more additional debridements. Reconstruction with skin graft was performed in 32 patients, while 9 patients required the use of various flaps to cover wounds. Eight patients underwent amputation during the early phase. Fasciotomy was performed in 3 cases of suspected compartment syndrome.

Z-plasty was performed in 3 patients, all of whom required surgical revision due to skin graft complication. Tenolysis was performed in 1 patient, and surgical revision was performed to treat scar formation in 1 patient.

280

Acinobacter spp., 11

Figure 3. Isolated microorganisms.

Seven patients (7.4%) presented with trauma accompanying the electrical injury, all of which were caused by falls from height. These patients had sustained high-voltage electrical injury. Accompanying trauma was intracranial injury in 2 patients, soft tissue injury in 2, bone fracture in 2, and intraabdominal injury in 1 patient.

Findings suggestive of infection (fever, hypotension, hypo- or hyperglycemia, or alterations in mental state) were observed in 31 patients (32.9%). Culture results identified 10 bacterial types, with 19 subtypes. Empirical antimicrobial treatment was initiated immediately, followed by drug replacement based on culture results, as necessary. Positive cultures grew mainly gram-negative cocci, primarily enterobacteriaceae, followed by gram-positive cocci, predominantly staphylococci and enterococci. Microorganisms identified were Staphylococcus spp. (n=16), Acinetobacter spp. (n=11), Pseudomonas spp. (n=11), Enterococcus spp. (n=5), Escherichia coli (n=3), Enterobacter spp. (n=2), Klebsiella spp. (n=2), Pantoea spp. (n=2), Proteus spp. (n=1), and Serratia spp. (n=1) (Figure 3).

Staphlococus spp., 16

Enterococus spp., 5

12

12

7

22 58

18 47

47

58

15 4

39

28

28

39

Figure 4. Regional distribution of electrical burns.

Average cost per patient was 1,208.55 TL in cases of lowvoltage electrical burns, and average cost per hospital day was 139.23 TL. Average cost per patient with high-voltage burn injury was 4,765.13 TL, and per day cost was 224.44 TL.

DISCUSSION Electrical burns, the result of exposure to supraphysiologic electric currents, are among the most devastating tissue injuries. Electrical burns occur less frequently than scald or flame burns, but have higher associated rates of mortality and morbidity, particularly in cases of high voltage. The mechanism of tissue damage is generally related to puncture Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Kurt et al. Electrical burns

and denaturation of cell membranes caused by the direct electrical forces.

Electrical burns are more frequently sustained in Turkey, compared to the global average.[11] They are most frequently sustained by young male adults in industrial accidents. Al et al. reported that 76.4 % of electric burns are sustained by adult males, 23.6 % by females.[11] Haberal et al. similarly reported that 82% of electric burns are sustained by adult males and 18% by females.[12] In the present study, 89% of patients were male, 11% female, and results were comparable with the literature with a plethora of male subjects.

In a study performed in Turkey, the authors reported that rates of the high- and low-voltage electricity burns were 54.5% and 45.5%, respectively.[13] Similarly, the rate of highvoltage burns in the present study was 50%, and the rate of low-voltage burns 44.7% (while the rate of flash burns was 5.3%). High-voltage electricity burns cause more serious tissue damage due to the high amounts of energy exerted.[14,15] Mean patient age was reported as 30.2 or 25 years in a majority of studies.[13,16,17] Mean age in the present study was 18.8 years in females and 27.4 years in males. It was presently determined that mean TBSA was 11.9% in cases of low-voltage burns, and 21.8% in those of high voltage. It was also found that these burns are most commonly sustained by young male adults, and can lead to significant loss in employment.[1,3,6,7,10] Hospitalization was longer for patients with high-voltage burns. Duration of hospital stay for patients with low-voltage and high-voltage burns was presently determined as 8.6±6.2 days and 21.3±19.8 days, respectively. Greater energy is expended in high-voltage burns, and tissues are more deeply penetrated, creating wider burn surface areas, and resulting in longer periods of hospitalization and higher treatment costs.

Cancio et al. reported that 25% of electricity burns accompanied by traumas were caused by falls from heights.[18] In the present study, 7 patients (7.4%) sustained concomitant trauma in this way, a rate lower than that reported. Patients may have been primarily treated for their otherwise lifethreatening conditions elsewhere before they were referred to the present burn center, accounting for the low rate.

Hammond et al. reported that 3% of electricity burns caused death.[19] The rate in Turkey has been reported as 4.7%. The present rate of mortality was 4.25%. While the most frequently reported cause of electrical burn-related mortality was sepsis, 3 patients in the present study died from acute renal failure, and 1 patient died from sepsis.[20] This discrepancy may be attributed to either inadequate hydration at the early stages prior to referral or delay in referral to emergency services. Attempted suicide is a rare cause of electricity burn.

[21,22] However, in the present study, 1 patient with epilepsy and mental retardation attempted suicide by electric shock.

Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

Wound infections and complications frequently accompany electrical burns. Estahbanati et al. reported that the agents that most commonly caused these infections were Pseudomonas aeruginosa (57%), Acinetobacter spp. (17%), Escherichia coli (12%) and Staphylococcus aureus (8%).[23] In the present study, Staphylococcus spp. (n=16), Acinetobacter spp. (n=11), Pseudomonas spp. (n=11), Enterococcus spp. (n=5), Escherichia coli (n=3), Enterobacter spp. (n=2), Klebsiella spp. (n=2), Pantoea spp. (n=2), Proteus spp. (n=1), and Serratia spp. (n=1) were grown from cultures. It has been emphasized that local and intravenous antibiotics designed to target a specific agent are essential in the treatment of wound infection and sepsis. The most common cause of death in the present study was acute renal failure, though sepsis is the most frequently reported cause of electrical burn-related mortality. Consequently, it should be noted that intravenous fluid resuscitation and close observation of patients is essential in the treatment of burn injury.

Cost is another factor in the treatment of electrical burn injuries. Cases of high-voltage injury were found to incur costs more than twice as high as those of low-voltage injury. Average total cost per patient was 1,208.55 TL in cases of lowvoltage electrical burns, and average cost per hospital day was 139.23 TL. Medical costs of the 46 patients with high-voltage electrical burns ranged from 120.89 TL to 15,033.00 TL. Total medical cost per high-voltage burn patient averaged 4,765.13 TL, and average cost per day was 224.44 TL. It is believed that these high costs can be attributed to longer hospital stays, higher number of surgical procedures, and more extensive surgeries required by patients with high-voltage electrical injuries.

In conclusion, although treatment modalities have evolved and awareness among the public has increased, electrical burn injuries still cause significant mid- and long-term morbidity.

Increasing awareness of electrical safety, the construction of safer electrical distribution networks, and the implementation of more effective means of occupational safety may serve to reduce the number of these devastating and occasionally fatal injuries.

Acknowledgement: This study was presented as a poster at the 34th National Congress of Turkish Society of Plastic Reconstructive and Aesthetic Surgeons. The authors would thank Dr. Umut Tuncel for his assistance in preparing this manuscript.

Conflict of interest: None declared.

REFERENCES 1. Haddad SY. Electrical burn - a four-year study. Ann Burns Fire Disasters 2008;21:78–80.

2. Iqbal T, Saaiq M, Ali Z. Epidemiology and outcome of burns: early experience at the country’s first national burns centre. Burns 2013;39:358–62.

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4. Liu Y, Cen Y, Chen JJ, Xu XW, Liu XX. Characteristics of paediatric burns in Sichuan province: epidemiology and prevention. Burns 2012;38:26–31.

5. Liu Y, Chen JJ, Crook N, Yu R, Xu XW, Cen Y. Epidemiologic investigation of burns in the elderly in Sichuan Province. Burns 2013;39:389–94.

6. Luz DP, Millan LS, Alessi MS, Uguetto WF, Paggiaro A, Gomez DS, et al. Electrical burns: a retrospective analysis across a 5-year period. Burns 2009;35:1015–9.

7. Sun CF, Lv XX, Li YJ, Li WZ, Jiang L, Li J, et al. Epidemiological studies of electrical injuries in Shaanxi province of China: a retrospective report of 383 cases. Burns 2012;38:568–72.

8. Kim HD, Hwang SM, Lim KR, Jung YH, Ahn SM, Song JK. Toe Tissue Transfer for Reconstruction of Damaged Digits due to Electrical Burns.

Arch Plast Surg 2012;39:138–42.

9. Singerman J, Gomez M, Fish JS. Long-term sequelae of low-voltage electrical injury. J Burn Care Res 2008;29:773–7.

10. Vierhapper MF, Lumenta DB, Beck H, Keck M, Kamolz LP, Frey M. Electrical injury: a long-term analysis with review of regional differences.

Ann Plast Surg 2011;66:43–6.

11. Al B, Aldemir M, Güloğlu C, Kara IH, Girgin S. Epidemiological characteristics of electrical injuries of patients applied to the emergency department. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2006;12:135– 42.

12. Haberal M, Uçar N, Bilgin N. Epidemiological survey of burns treated in Ankara, Turkey and desirable burn-prevention strategies. Burns 1995;21:601–6.

13. Karadaş S, Gönüllü H, Oncü MR, Işık D, Canbaz Y. The effects on complications and myopathy of different voltages in electrical injuries. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2011;17:349–53.

14. ten Duis HJ. Acute electrical burns. Semin Neurol 1995;15:381–6.

15. Cooper MA. Emergent care of lightning and electrical injuries. Semin Neurol 1995;15:268–78.

16. Kopp J, Loos B, Spilker G, Horch RE. Correlation between serum creatinine kinase levels and extent of muscle damage in electrical burns. Burns 2004;30:680–3.

17. Blackwell N, Hayllar J. A three year prospective audit of 212 presentations to the emergency department after electrical injury with a management protocol. Postgrad Med J 2002;78:283–5.

18. Cancio LC, Jimenez-Reyna JF, Barillo DJ, Walker SC, McManus AT, Vaughan GM. One hundred ninety-five cases of high-voltage electric injury. J Burn Care Rehabil 2005;26:331–40.

19. Hammond JS, Ward CG. High-voltage electrical injuries: management and outcome of 60 cases. South Med J 1988;81:1351–2.

20. Kurtoğlu M, Alimoğlu O, Ertekin C, Güloğlu R, Taviloğlu K. Evaluation of severe burns managed in intensive care unit. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2003;9:34–6.

21. İnce CH, Fincancı ŞK, Arıcan M, Akkay E. Elektrikle intihar: bir olgu bildirisi. 1. Adli Bilimler Kongresi (12-15 Nisan) Kongre Kitabı. Adana 1994. p. 342–3.

22. Byard RW, Hanson KA, Gilbert JD, James RA, Nadeau J, Blackbourne B, et al. Death due to electrocution in childhood and early adolescence. J Paediatr Child Health 2003;39:46–8.

23. Estahbanati HK, Kashani PP, Ghanaatpisheh F. Frequency of Pseudomonas aeruginosa serotypes in burn wound infections and their resistance to antibiotics. Burns 2002;28:340–8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Elektrik yanıkları: Beş yıllık geriye dönük değerlendirme Dr. Alper Kurt,1 Dr. Kamil Yıldırım,1 Dr. Çağlayan Yağmur,3 Dr. Osman Kelahmetoğlu,2 Dr. Ozan Aslan,1 Dr. Murat Gümüş,1 Dr. Ethem Güneren2 Samsun Eğitim ve Araştırma Hastanesi, Plastik Rekonstrüktif ve Estetik Cerrahi Kliniği, Samsun Bezm-i Alem Vakıf Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, İstanbul 3 Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif ve Estetik Cerrahi, Samsun 1 2

AMAÇ: Elektrik yanığı; haşlanma ve alev yanıklarından sonraki en sık üçüncü yanık şeklidir. Tedavi olanaklarındaki gelişmeler sayesinde düşme görülen mortalite oranlarına rağmen elektrik yanıkları halen ciddi komplikasyonlara ve sosyoekonomik sonuçlara neden olan yaralanmalardır. Bu çalışmada 2008–2012 yılları arasında Samsun Eğitim Araştırma Hastanesi Yanık Merkezi’nde yatarak tedavi gören hastalara ait verilerin geriye dönük analizi sunuldu.

GEREÇ VE YÖNTEM: 2008–2012 yılları arasında elektrik yanığı ile yatırılan ve gerekli tedaviler uygulanan toplam 94 (84 erkek, 10 kadın) hasta incelendi. Hasta demografik bilgileri, yanık derecesi, toplam alanı, voltaj türü (yüksek/alçak), tedavi maliyeti, tedavi yöntemleri, enfeksiyon oranları ve eşlik eden travmalar açısından değerlendirildi.

BULGULAR: Hastalarda ortalama yaş 26.4±13.2 olarak bulundu, 47 hastada (%50) yüksek voltaj yanığı, 42 hasta düşük voltaj yanığı ve beş hasta ark yanığı mevcuttu. Toplam yanık alanı yüksek voltajda %21.8 (±19.8), düşük voltajda %11.9 (±6.9) olarak bulundu. Yedi hastada eşlik eden travma mevcuttu. Otuz bir hastada (%32.9) enfeksiyon bulguları gelişti ve uygun tedavi başlandı. Yüksek voltaj ve düşük voltaj yaralanmalarının toplam hastanede kalma ve tedavi maliyetleri arasında anlamlı fark mevcuttu.

TARTIŞMA: Yaptığımız geriye dönük araştırmada yüksek voltaj yaralanmalarının büyük çoğunluğunu sanayi yaralanmaları olduğunu ve olguların tümünün genç erkek yetişkinlerden oluştuğunu gözlemledik. Çalışanların iş güvenliklerinin artırılmasını sağlayan önlemlerin yanı sıra elektrik dağıtım şebekelerinin güvenliğinin pekiştirilmesi ve elektrik kullanımı konusundaki güvenlik bilincinin artırılması bu önemli yaralanmaların sıklığını ve şiddetini azaltacaktır.

Anahtar sözcükler: Analiz; elektrik yanıkları, geriye dönük.

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doi: 10.5505/tjtes.2015.55491

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ORIG I N A L A R T IC L E

Evaluation of outcomes in aseptic non-unions of the forearm bones in adults treated with LCP and autograft Osman Lapcin, M.D., Yavuz Arıkan, M.D., Umut Yavuz, M.D., Yunus Emre Akman, M.D., Engin Çetinkaya, M.D., Volkan Gür, M.D., Bilal Demir, M.D. Deparment of Orthopaedics and Traumatology, Metin Sabancı Baltalimani Bone Diseases Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to evaluate the effect of locking compression plate (LCP) and autografting application in patients with nonunion of forearm fractures on radiologic and clinical outcome.

METHODS: A total of 26 patients (16 males, 10 females; mean age: 45.7 years) with nonunion after surgical treatment of forearm fractures were included. Nonunion was located in the ulna in 14 patients, in the radius in 5 patients, and in both in 7 patients (21 ulna, 12 radius).Infection markers were checked prior to surgery. Samples for microbiologic cultures were peroperatively obtained in 7 patients with a history of open fractures. Autografting from the iliac crest and 3.5-mm LCP were applied. Type of nonunion, time to unification, range of motion in the wrist and elbow joints, and complications were analyzed. Functional evaluation was performedusing the scoring system described by Anderson et al.

RESULTS: Mean follow-up period was 49.3 months (range 24–73 months). Unification was achieved in a mean 5.7 months (range 3–14 months). Additional surgical process was not required. No bacterial proliferation was observed in cultures. Superficial infection was observed in 3 patients and deep infection in 1. Results were scored as excellent in 10 (38.4%) patients, satisfactory in 13 (50%), and unsatisfactory in 3 (11.6%).

CONCLUSION: Treatment of aseptic forearm nonunion in adults with autografting from the iliac crest and 3.5-mmLCP fixation increases unification rate and aids in function recovery.

Keywords: Aseptic; autograft; forearm; nonunion; plate.

INTRODUCTION Surgical treatment of ulnar and radial fractures with compression plates has been widely performed for many years. Low complication rates and successful results in large series have been reported.[1–5] The most commonly reported conclusion is that fixation with plate provides anatomical, reliable reduction that makes early mobilization possible.[5,6–15] However, infection, neurovascular injury, non-union, malunion, compartment syndrome, and radioulnar synostosis are potential complications.[16] Address for correspondence: Umut Yavuz, M.D. Baltalimanı Kemik Hastalıkları Eğitim ve Araştırma Hastanesi, Rumelihisarı Cad., No: 62, Sarıyer, İstanbul, Turkey Tel: +90 212 - 323 70 75 E-mail: umut78@yahoo.com Qucik Response Code

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In spite of the number of studies in which successful results have been reported after use of dynamic compression plate (DCP), locking compression plate (LCP), anatomical plate, or locking nail applications, rates of non-union still vary between 2–10%.[1,5–7] Factors related to the fracture, patients, or customization of the initial treatment have been held responsible for the development of non-union, as is the case with fractures in all long bones. The aim of surgical treatment of forearm non-union is to restore proper bone length, anatomy, and functionality. In spite of recently developed surgical techniques and use of modern implants, the results are not fully satisfactory, and debates regarding the necessity of grafting and type of implant to be used continues.[15–21] In the present study, efficacy of LCP application and autografting in the treatment of aseptic non-union of the adult forearm was retrospectively evaluated from a radiological and clinical perspective.

MATERIALS AND METHODS Presently included were 26 adult patients (16 male, 10 female) who presented between 2005 and 2012 with com283

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plaints of non-union in the forearm (20 dominant arm, 6 non-dominant arm). They were treated with LCP and autografts harvested from the iliac wing. Mean age at time of surgery was 45.7 (range: 19â&#x20AC;&#x201C;73) years (Table 1). Reasons for surgical intervention included radiological non-union, clinical pain, and loss of range of motion (ROM) and strength.

Patients who underwent follow-up of less than 2 years, and those who received conservative treatment or had active infection were excluded.

The mechanism of fracture was a fall in 16 patients, motor vehicle accident in 6, and assault or occupational accident in 4. Thirteen patients had ulnar, 7 had radial, and 6 had both ulnar and radial non-unions. Three patients had type 22-A1 fracture, 3 had type 22-A2, 3 had type 22-A3, 11 had type 22-B1, 2 had type 22-B2, 3 had type 22-B3 and 1 had type 22-C2 fracture according to MĂźller AO Classification. Seven (26.9%) patients had open fractures according to the Gustilo open fracture classification system;[22] 6 were type 1, and 1

was type 2. One patient had an injured radial artery, another had an injured radial nerve (Table 1).

Eight (30.7%) patients were smokers, and 4 (15.3%) had accompanying diabetes mellitus. All patients had undergone at least 1 surgical intervention (with plate-screw in 21 patients, with intramedullary k wire in 3 patients, and with tension band [secondary to proximal metaphyseal fracture] in 2 patients). Complete blood count, sedimentation, and C-reactive protein (CRP) were analyzed for preoperative assessment of infection. When lab results were within normal range, and when clinical symptoms of infection were not observed, patients were considered to have aseptic non-union.

Type of non-union was radiologically evaluated prior to surgery. Patients with no callus formation on fracture ends, and those with atrophic presentation or bone defects were considered to have atrophic non-union. Absence of obvious cal-

Table 1. Preoperative demographic characteristics and radiological findings of the patients n Age Follow-up Bone Type of fracture Type of nonunion Smoking Diabetus (M) (AO-22) mellitus 1

60

73

Ulna

B1

Atrophic

+

2 50 69 Ulna+Radius

B3

Oligotrophic

3 41 64 Ulna+Radius

A3

Oligotrophic

4

Ulna

A1

Oligotrophic

Ulna

B1

Oligotrophic

6 23 58

Ulna

B1

Oligotrophic

+

7 58 58

Ulna

B1

Oligotrophic

+

45

63

A3

Oligotrophic

9 40 54

Ulna

B1

Oligotrophic

10 37

53

Ulna

A1

Oligotrophic

11 19

52

Ulna

B1

Oligotrophic

12 69

50

Radius

A2

Oligotrophic

13

50

Radius

B2

53

55

Ulna+Radius

+

49

Ulna+Radius

A3

Oligotrophic

15 31

49

Ulna+Radius

B3

Oligotrophic

16

48

Ulna

B1

Atrophic

47

Radius

A2

Oligotrophic

18 64

45

Radius

A2

Oligotrophic

19

42

Ulna

A1

Atrophic

+

20 40

41

Ulna+Radius

C2

Oligotrophic

21 31

40

Ulna

B1

Oligotrophic

22 41

37

Ulna

B1

Oligotrophic

23

37

B3

Oligotrophic

45

Ulna+Radius

Type 1

Type 2

Type 1

+

24 63

33

Radius

B2

Oligotrophic

+

25 73

31

Ulna

B1

Oligotrophic

+

26 42

24

Ulna

B1

Oligotrophic

284

Type 1

+

17 52 58

Type 1

+

Atrophic

14 55 37

Type 1

+

5 28 60

8

33

Open fracture

Type 1

+

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lus formation and atrophy on bone ends were accepted as oligotrophic non-union.[17] All devitalized tissue and foreign matter were removed during surgery. Both sides of the medullar cavity were drilled, and cultures were taken from various spots during debridement in 7 patients with open fractures. After restoration of anatomical parameters in bone alignment, size and rotation were confirmed with radiological and clinical assessments during surgery. Fixation was performed with LCP, allowing for use with both locking and non-locking screws. In order to enhance reduction and stability on at least 1 side of the nonunion site, compression was performed with a single nonlocking screw, and fixation was achieved with either locking screws (engaged on a minimum of 6 cortices on both sides of the fracture), or with bicortical non-locking screws (Fig. 1). Autografts harvested from the iliac wing were used in an attempt to cover the defect and support the biological environment. Postoperatively, patients used long-arm splints until formation of a callus, indicating a union, was observed.

Sutures were removed at the end of the 2nd week, and rehabilitation was begun by the end of the 3rd week. Patients were allowed to perform controlled mobilization after callus formation was observed, and were advised to avoid heavy activities for a period of 3–4 months.

(a)

(b)

(c)

Preoperative radiographs of patients were retrieved from archives, and anteroposterior and lateral radiographs of the forearms, including the wrist and elbow, were obtained at final follow-up. Radiological evidence of a bridging callus in the non-union site on 3 or 4 planes was considered a union.

Clinically, absence of pain with palpation over the fracture line or during daily activities was accepted as union. In addition, the scoring system based on the evaluation of joint ROMs, as used by Anderson et al.,[1] was utilized at final follow-up for functional evaluation. Results were recorded as excellent, good (satisfactory), fair (unsatisfactory), or poor.

RESULTS Mean follow-up was 49.3 months (range: 24–73), mean time to union was 5.7 months (range: 3–14), and mean time to return to work was 7.1 months (range: 3–18). No bacterial growth was observed in cultures obtained during surgery. Radial nerve palsy developed in 1 patient in the postoperative period, and the patient recovered by the fourth month. Superficial infection was observed in 3 patients in the early postoperative period.

The infection was treated with antibiotics; no surgical intervention was required. One patient had deep infection, and Staphylococcus aureus grew on the culture. Serial debridements and parenteral antibiotic treatment were successful. No patient developed chronic osteomyelitis or radioulnar synostosis.

(d)

Figure 1. A 33-year-old male patient who had previously undergone both conservative and surgical treatment. (a, b) Oligotrophic nonunion. (b, c) Follow-up radiographs taken at the 52nd month following rigid fixation with long plates and grafting.

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Mean ROM was 55.4° (range: 30°–80°) in flexion of the wrist, 56.2° (range: 20°–80°) in extension of the wrist, 66.2° (range: 30°–80°) in pronation of the wrist, 69.2° (range: 45°–80°) in supination of the wrist, and 120.7° (range: 80°–130°) in flexion of the elbow. Mean loss of extension in the wrist was 4.2° (range: 0°–30°). Details regarding time to union, ROM, and functional evaluation are summarized in Table 2.

According to the functional scoring system used by Anderson et al., 10 (38.4%) patients had excellent, 13 (50%) had good (satisfactory), and 3 (11.6%) had fair (unsatisfactory) results.

No patient received a poor score. All patients with fair (unsatisfactory) results had limited ROM and a stiff elbow, and 1 had a substantive loss of motion in the wrist. When previous clinical findings were analyzed, it was determined that ROM slightly increased and pain at movement significantly decreased over time.

Material removal was performed in 6 (23.1%) patients due to

skin irritation after union was observed. Removal was performed from the ulna in 5 patients and from both bones in 1.

Fracture during removal did not occur.

DISCUSSION Prevalence of non-union in the forearm bones is reportedly 2–10%.[1,5–7,17–20] Factors related to fracture (comminution, open fracture, location of the fracture, state of soft tissue), patient (age, smoking, additional diseases), and initial treatment (implant used, surgical technique) have been held responsible for forearm non-union. Debridement of devitalized tissue, removal of failed implant, proper alignment during surgery, and achievement of rotation are the stages to be followed during non-union surgery. Use of grafts should be avoided to ensure a biological environment for the union.

Stable fixation and early rehabilitation are essential in obtaining successful results.[23] All patients presently reported had an unstable fixation; 7 had an open fracture, 8 had a

Table 2. Functional outcomes of the patients during the final follow-up No Union time Extension of Flexion of Supination of Pronation of Flexion of Ekstension of Anderson (M) elbow elbow forearm forearm wrist wrist Scoring 1 6

-10

120

70

60

50

50 Good

2 7 0 130 60 50 50 50 Good 6 0 140 80 70 60 60 Excellent 3 4 3 0 130 80 70 30 20 Good 5 6

-10

110

60

30

50

60 Good

6 4 -20 90 50 80 30 30 Fair 7 3

0

120

80

0

50

50 Good

8 8

-20

110

45

30

50

60 Good

7 0 110 45 30 50 50 Good 9 10 5 0 130 80 80 50 60 Excellent 11 6 -20 90 50 50 60 60 Fair 12 5 0 130 80 80 60 60 Excellent 13 4 0 120 80 80 80 70 Good 14 7 0 130 50 70 80 70 Good 15 11 0 130 80 80 50 60 Excellent 16 5

-10

130

70

60

50

50

Good

17 4 0 130 80 80 60 60 Excellent 18 3 0 120 80 70 20 40 Good 19 3 -30 80 50 60 50 40 Fair 20 14 0 130 80 80 60 60 Excellent 21 5 0 120 80 80 80 70 Excellent 22 6 0 130 70 70 60 60 Good 23 5 0 130 80 80 70 60 Excellent 24 7 0 130 70 60 60 50 Good 25 3 0 130 80 80 80 80 Excellent 26 5 0 130 70 60 70 70 Excellent

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history of smoking, and 4 had diabetes mellitus. It is believed that presence of any of these factors may have led to nonunion.

In accordance with those of previous studies,[6,8,16,24,25] oligotrophic non-union was the prevailing finding. The majority of the present patients underwent surgery at another clinic and were referred upon development of non-union. The most common cause of non-union, again in accordance with other studies, was inadequate surgical fixation. In addition, the implants most frequently encountered were plates with insufficient number of screws and intramedullary k wires. Today, the fixation material most commonly preferred for recent fractures in the region is the 3.5-mm compression plate. Although bilateral passing through 4 cortices has been shown to be biomechanically sufficient,[11] most authors advocate passing through 6 cortices on each side of the fracture.[15â&#x20AC;&#x201C;21,26] In each patient, 3.5-mm LCP was used, and fixation was performed by passing through at least 6 cortices on both sides of the fracture. The high rate of union observed following this application suggests that preoperative planning and more stable fixation with the use of locking plates contribute to successful outcome.

Fixation of acute fracture of adult forearm with plate is a widely accepted treatment, and success rates of over 90% have been reported.[1,2,4,5,8,21] Until recently, DCP has been used with success rates of 92% and over.[1,4,27] However, the possibility that DCP use may lead to osteoporosis of the bone or refracture are disadvantages.[28] Today, LCP is more frequently used in treatment of long bone fracture. LCPs allow for stronger stabilization than conventional plates and more reliable stability on the osteoporotic bone.[29â&#x20AC;&#x201C;31] Gardner et al. biomechanically proved that hybrid and locking systems can bear axial and torsional forces better than non-locking systems.[31] The decision was presently made to use LCPs that could be used with non-locking and locking screws. The present patients had been treated with conventional plates and various implants, with unsatisfactory results. Either a nonlocking screw at a proximity of at least 1 fracture line, a locking screw in the distal, or bicortical non-locking screws were presently used. It was concluded that application of a plate enabling hybrid screwing and the presently employed reduction technique were essential in the achievement of high rates of union.

Use of autografts in the treatment of non-union of the long bones is still a matter of debate. Absence of immunological response and risk of disease transfer are the main advantages.

Nicoll et al. used corticocancellous grafts for the first time in non-union of the forearm bones, and several other authors have reported results of graft application.[19,24] Ring et al. reported successful results with the use of non-vascularized autogenous corticocancellous grafts on defects up to 6 cm in size with atrophic non-union.[32] dos Reis et al. reported Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

excellent radiological and clinical results with application of corticocancellous grafts and plates in cases with atrophic and hypertrophic non-union.[33] In a study by Kumar et al., a union rate of 96% following LCP and autograft treatment was reported in patients with atrophic and hypertrophic nonunion of the humerus.[23] Saka et al. also reported high rates of union and functional recovery using nails and autografts in cases of forearm non-union.[21] When coverage of the surrounding soft tissue was taken into account, it was presently preferred to harvest autografts from the iliac wing, as donor site morbidity was lower in this region.[34] Based on the present outcomes, it is believed that when soft tissues have adequate blood supply, use of corticocancellous grafts increase the rate of union, and have a positive impact on functional recovery.

Although debridement is a routine procedure during nonunion surgery, it is unusual to obtain cultures from patients who do not present with findings of infection. In spite of a lack of accepted procedure to detect subclinical infection, clinical evaluation and CRP measurement are other commonly used markers.[35,36] With a series of 87 patients, Amorosa et al. performed single-stage treatment and follow-up of aseptic non-union of the long bones, and 28% of cultures obtained during surgery yielded positive results.[37] The authors reported the need for repeat surgery in 28% of the culture-positive group, and in 6% of the culture-negative group. It was also reported that 60% of culture-positive patients had an open fracture. Cultures were also obtained from the present patients with open fractures, though no bacterial growth was observed. Nevertheless, debridement was performed in 1 patient with deep infection. Thus, even if lab results do not indicate findings of infection, it is believed that repeating the surgery can be prevented by obtaining cultures from patients with non-union who have undergone at least 1 surgery.

Limitations of the present study were retrospective design and lack of a control group. However, the adequate follow-up period included, the type of implants used, and the homogenous use of autografts are strengths.

Sufficient debridement of dead tissues and stable fixation of the bone with LCP in aseptic treatment of adult forearm fracture have a positive impact on recovery. In addition, use of autografts to cover the defect area and/or to support the biological environment will increase the rate of union and eliminate the risk of infection that may be caused by allograft.

Although use of implants such as DCP or intramedullary nail may yield successful results, use of LCP and autografts is also an efficient method of single-stage treatment of non-unions.

In spite of the retrospective design, the present study may be a valuable reference for future comparative, prospective studies.

Conflict of interest: None declared.

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REFERENCES 1. Anderson LD, Sisk D, Tooms RE, Park WI 3rd. Compression-plate fixation in acute diaphyseal fractures of the radius and ulna. J Bone Joint Surg Am 1975;57:287–97.

2. Chapman MW, Gordon JE, Zissimos AG. Compression-plate fixation of acute fractures of the diaphyses of the radius and ulna. J Bone Joint Surg Am 1989;71:159–69.

3. Droll KP, Perna P, Potter J, Harniman E, Schemitsch EH, McKee MD. Outcomes following plate fixation of fractures of both bones of the forearm in adults. J Bone Joint Surg Am 2007;89:2619–24.

4. Hertel R, Pisan M, Lambert S, Ballmer FT. Plate osteosynthesis of diaphyseal fractures of the radius and ulna. Injury 1996;27:545–8.

5. Ross ER, Gourevitch D, Hastings GW, Wynn-Jones CE, Ali S. Retrospective analysis of plate fixation of diaphyseal fractures of the forearm bones. Injury 1989;20:211–4.

6. Wei SY, Born CT, Abene A, Ong A, Hayda R, DeLong WG Jr. Diaphyseal forearm fractures treated with and without bone graft. J Trauma 1999;46:1045–8.

7. Wright RR, Schmeling GJ, Schwab JP. The necessity of acute bone grafting in diaphyseal forearm fractures: a retrospective review. J Orthop Trauma 1997;11:288–94.

8. Mikek M, Vidmar G, Tonin M, Pavlovcic V. Fracture-related and implant-specific factors influencing treatment results of comminuted diaphyseal forearm fractures without bone grafting. Arch Orthop Trauma Surg 2004;124:393–400.

9. Ring D, Rhim R, Carpenter C, Jupiter JB. Comminuted diaphyseal fractures of the radius and ulna: does bone grafting affect nonunion rate? J Trauma 2005;59:438–42.

10. Leung F, Chow SP. A prospective, randomized trial comparing the limited contact dynamic compression plate with the point contact fixator for forearm fractures. J Bone Joint Surg Am 2003;85-A:2343–8.

11. Sanders R, Haidukewych GJ, Milne T, Dennis J, Latta LL. Minimal versus maximal plate fixation techniques of the ulna: the biomechanical effect of number of screws and plate length. J Orthop Trauma 2002;16:166–71.

12. Deluca PA, Lindsey RW, Ruwe PA. Refracture of bones of the forearm after the removal of compression plates. J Bone Joint Surg Am 1988;70:1372–6.

13. Hidaka S, Gustilo RB. Refracture of bones of the forearm after plate removal. J Bone Joint Surg Am 1984;66:1241–3.

14. Labosky DA, Cermak MB, Waggy CA. Forearm fracture plates: to remove or not to remove. J Hand Surg Am 1990;15:294–301.

15. Rosson JW, Shearer JR. Refracture after the removal of plates from the forearm. An avoidable complication. J Bone Joint Surg Br 1991;73:415– 7.

16. Stern PJ, Drury WJ. Complications of plate fixation of forearm fractures.

Clin Orthop Relat Res 1983;175:25–9.

17. Weber BG, Bech O. Pseudarthrosis: pathophysiology, biomechanics, therapy, results. Grune & Stratton, Philadelphia, 1976.

18. Langkamer VG, Ackroyd CE. Internal fixation of forearm fractures in the 1980s: lessons to be learnt. Injury 1991;22:97–102.

19. Faldini C, Pagkrati S, Nanni M, Menachem S, Giannini S. Aseptic forearm nonunions treated by plate and opposite fibular autograft strut. Clin

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Orthop Relat Res 2009;467:2125–34.

20. Hadden WA, Reschauer R, Seggl W. Results of AO plate fixation of forearm shaft fractures in adults. Injury 1983;15:44–52.

21. Saka G, Sağlam N, Kurtulmuş T, Avcı CC, Akpınar F. Treatment of diaphyseal forearm atrophic nonunions with intramedullary nails and modified Nicoll’s technique in adults. Acta Orthop Traumatol Turc 2014;48:262–70.

22. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg Am 1976;58(4):453–8.

23. Kumar MN, Ravindranath VP, Ravishankar M. Outcome of locking compression plates in humeral shaft nonunions. Indian J Orthop 2013;47:150–5.

24. Cai RB. Analysis of 81 cases of nonunion of forearm fracture. Chin Med J (Engl) 1983;96:29–32.

25. Nıcoll EA. The treatment of gaps in long bones by cancellous insert grafts. J Bone Joint Surg Br 1956;38-B:70–82.

26. Ozkaya U, Kiliç A, Ozdoğan U, Beng K, Kabukçuoğlu Y. Comparison between locked intramedullary nailing and plate osteosynthesis in the management of adult forearm fractures. [Article in Turkish] Acta Orthop Traumatol Turc 2009;43:14–20.

27. Schulte LM, Meals CG, Neviaser RJ. Management of adult diaphyseal both-bone forearm fractures. J Am Acad Orthop Surg 2014;22:437–46.

28. Perren SM, Cordey J, Rahn BA, Gautier E, Schneider E. Early temporary porosis of bone induced by internal fixation implants. A reaction to necrosis, not to stress protection? Clin Orthop Relat Res 1988;232:139– 51.

29. Egol KA, Kubiak EN, Fulkerson E, Kummer FJ, Koval KJ. Biomechanics of locked plates and screws. J Orthop Trauma 2004;18:488–93.

30. Azboy I, Demirtas A, Uçar BY, Bulut M, Alemdar C, Ozkul E. Effectiveness of locking versus dynamic compression plates for diaphyseal forearm fractures. Orthopedics 2013;36:917–22.

31. Gardner MJ, Griffith MH, Demetrakopoulos D, Brophy RH, Grose A, Helfet DL, et al. Hybrid locked plating of osteoporotic fractures of the humerus. J Bone Joint Surg Am 2006;88:1962–7.

32. Ring D, Allende C, Jafarnia K, Allende BT, Jupiter JB. Ununited diaphyseal forearm fractures with segmental defects: plate fixation and autogenous cancellous bone-grafting. J Bone Joint Surg Am 2004;86-A:2440–5.

33. dos Reis FB, Faloppa F, Fernandes HJ, Albertoni WM, Stahel PF. Outcome of diaphyseal forearm fracture-nonunions treated by autologous bone grafting and compression plating. Ann Surg Innov Res 2009;3:5.

34. Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma 1989;3:192–5.

35. Wright EH, Khan U. Serum complement-reactive protein (CRP) trends following local and free-tissue reconstructions for traumatic injuries or chronic wounds of the lower limb. J Plast Reconstr Aesthet Surg 2010;63:1519–22.

36. Bourguignat A, Férard G, Jenny JY, Gaudias J, Kempf I. Diagnostic value of C-reactive protein and transthyretin in bone infections of the lower limb. Clin Chim Acta 1996;255:27–38.

37. Amorosa LF, Buirs LD, Bexkens R, Wellman DS, Kloen P, Lorich DG, et al. A single-stage treatment protocol for presumptive aseptic diaphyseal nonunions: a review of outcomes. J Orthop Trauma 2013;27:582–6.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Erişkin ön kol kemiklerinin aseptik kaynamama tedavisinde LCP ve otogreft Dr. Osman Lapcin, Dr. Yavuz Arıkan, Dr. Umut Yavuz, Dr. Yunus Emre Akman, Dr. Engin Çetinkaya, Dr. Volkan Gür, Dr. Bilal Demir Metin Sabancı Baltalimanı Kemik Hastalıkları Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul

AMAÇ: Bu çalışmanın amacı erişkin ön kol kemiklerinde aseptik kaynamama gelişen hastalarda kilitli kompresyon plağı (LCP) ve otogreft kullanımının radyolojik ve klinik iyileşme üzerine etkinliğini değerlendirmektir.

GEREÇ VE YÖNTEM: Ön kol cisim kırıkları sonrası kaynamama gelişen ve cerrahi yöntemle tedavi edilen 26 hasta (16 erkek, 10 kadın; ortalama yaş 45.7 yıl) çalışmaya alındı. On dört hastada ulna, beş hastada radius ve yedi hastada her iki kemikte (21 ulna, 12 radius) kaynamama mevcuttu.

Cerrahi öncesinde enfeksiyonu değerlendirmek için enfeksiyon belirteçleri bakıldı. Açık kırık öyküsü olan yedi hastadan cerrahi sırasında kültür alındı. Hastalar 3.5 mm kilitli kompresyon plağı ve iliak kanattan alınan otogreft ile tedavi edildi. Hastaların kaynamama tipi, kaynama süreleri, cerrahi sırasında greft kullanımı, el bileği ve dirsek hareketleri, gelişen komplikasyonlar sorgulandı. Fonksiyonel değerlendirme Anderson ve ark.nın tanımladığı sisteme göre yapıldı.

BULGULAR: Takip süresi ortalama 49.3 aydı (dağılım 24–73 ay). Tüm hastalarda ortalama 5.7 ayda (dağılım 3–14 ay) kaynama sağlandı. İlave cerrahi gereken hasta olmadı. Cerrahi sırasında alınan kültürlerde bakteri üremesi gözlenmedi. Üç hastada yüzeysel, bir hastada derin enfeksiyon gelişti.

Anderson ve ark.nın değerlendirme sistemine göre 10 hastada (%38.4) mükemmel sonuç, 13 hastada (%50) yeterli sonuç ve üç hastada (%11.6) yetersiz sonuç elde edildi.

TARTIŞMA: Aseptik önkol kaynamamalarının tedavisinde 3.5 mm LCP ile tespit ve beraberinde iliak kanattan alınan otogreft kullanımı kaynama oranını artırmakla beraber fonksiyonel iyileşmeye yardımcı olmaktadır.

Anahtar sözcükler: Aseptik; kaynamama; otogreft; ön kol; plak.

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CA S E REP OR T

A rare cause of acute abdominal disease: two reports of caecal diverticulum perforation Fatih Çiftci, M.D.,1 İbrahim Abdurrahman, M.D.,2 Abdülkadir Eren, M.D.3 1

Department of General Surgery, İstanbul Gelişim University Vocational High School of Health Services, İstanbul-Turkey

2

Department of Emergency, İstanbul Safa Hospital, İstanbul-Turkey

3

Department of Radiology, İstanbul University Cerrahpasa Faculty of Medicine, İstanbul-Turkey

ABSTRACT Diverticulum of the caecum is a rare lesion. From a clinical point of view, the inflammation it causes can mimic symptoms of acute appendicitis, causing difficulties in diagnosis and thus prescription of appropriate treatment. It is almost impossible to differentiate this disease from acute appendicitis through physical examination alone, and radiological imaging may also prove insufficient. For this reason, it is common to perioperatively diagnose diverticula of the caecum.Two cases of patients who underwent surgery for perforated caecal diverticula are presently described.

Keywords: Acute abdomen; caecum; diverticulum perforation.

INTRODUCTION Diverticula of colonic origin are most frequently located on the antimesenteric surface of the sigmoid colon. Incidence of colonic diverticula among the general population is very high. However, diverticula of the right colon and the caecum are comparatively rare. Inflammation of right colon diverticulum generally presents with fever, right lower quadrant pain with evidence of peritoneal irritation, and increase in white blood cell count. Such a presentation would call to mind acute appendicitis. For this reason, definitive diagnosis of the pathology is typically made during surgery. Since 1912, when Potier[1] first described the disease, many cases of solitary caecal diverticula have been reported. However, a consensus has yet to be reached regarding correct approaches to diagnosis and treatment. Therefore, cases of caecal diverticula must be carefully handled.

Address for correspondence: Fatih Çiftci, M.D. Başakşehir Mahallesi, 2. Etap, Erciyes Sok., No: 15/24, 34063 İstanbul, Turkey Tel: +90 212 - 444 72 32 E-mail: oprdrfatihciftci@gmail.com Qucik Response Code

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Diverticula of the appendix vermiformis are extremely rare and remain asymptomatic until inflammation occurs. Inflamed caecum diverticulum presents with clinical symptoms similar to those of acute appendicitis. Presently described are 2 cases of clinically diagnosed acute appendicitis that were found, during surgery, to be perforated caecal diverticula.

CASE REPORT Case 1– A 45-year-old woman presented to emergency services complaining of abdominal pain that had begun 2 days prior. On examination, tenderness was present in the right lower quadrant. The patient had experienced neither nausea nor vomiting. White blood cell count was 13400/mm3, and minimal collection was present in the pericecal region on ultrasonography. Computed tomography (CT) scan of the abdomen showed heterogeneity at a site conforming to the lodge of the appendix. The patient was taken to surgery following clinical diagnosis of acute appendicitis. On exploration, however, the appendix vermiformis was found to be intact and the epiploic appendices were found to be oedematous and inflamed. After dissection of the epiploic appendices, perforated diverticulum of the caecum was revealed.

Right hemicolectomy and ileocolic anastomosis were then performed. A drain was placed in the lodge and removed on the fourth postoperative day. No complications were observed and the patient was discharged on the seventh day with a prescription for oral ciprofloxacin 7mg/kg twice daily.

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of the right colon. Within the first postoperative year the patient developed incisional hernia and underwent a herniorrhaphy. No further complaints were reported during the 3-year follow-up period.

Case 2– A 48-year-old man presented to emergency services complaining of abdominal pain and nausea. White blood cell count was 14700/mm3. Physical examination revealed abdominal wall defense and rebound tenderness in the right lower quadrant. Body temperature was 37.9°C, and no abnormal findings were detected following biochemical examination.

Ultrasonography showed increased intensity of the mesenteric tissue in the right lower quadrant. CT scans of the abdomen are shown in Fig. 1.

The patient was taken for laparoscopic exploration with a clinical diagnosis of acute appendicitis or perforated caecal diverticulum. On examination, the appendix vermiformis was found to be intact. However, the caecum and right colon were oedematous and covered with perforated epiploic appendices. Right colon resection and anastomosis were performed. A drain was inserted and removed on the third postoperative day. On the sixth postoperative day, the patient was discharged from the hospital with a prescription for oral cefuroxime axetil 7mg/kg twice daily. Histopathological examination of the tissues showed results similar to those of the previous case. Multiple inflamed diverticula were found, the walls of which included all layers of the colon, and the edges of which included ischemically necrotic areas. The patient reported no complaints associated with the surgery during the 2-year follow-up period.

DISCUSSION Solitary caecal diverticula are rare lesions that are generally asymptomatic and located on the anterior wall of the caecum.[2] Contrary to colonic diverticula, caecal diverticula are generally congenital, and their walls include all layers of the colon. Actual prevalence of caecal diverticula is unknown.

However, studies have shown that prevalence is higher in Eastern (Asian) populations.[2,3] Presentation of diverticulitis, a result of occlusion of the diverticular orifice by objects such as fecaloma, mimics that of acute appendicitis. Therefore,

Figure 1. Tomographic view of caecum diverticulum perforation.

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clinical differential diagnosis is difficult. Rates of incidence in the literature are based on diagnosis through surgery, and it has been shown that 1 in every 300 cases of acute appendicitis scheduled for surgery is found to be caecal diverticula.

Prevalence of caecal diverticula in the general population is thus estimated to be 1/1,000,000.[3,4] It has been shown in retrospective studies that, in comparison to sigmoid colon diverticulitis, caecal diverticulitis occurs in relatively young patients (average age: 44 years) and is slightly more common in females.[3,5,6] One patient presently reported was female, the other male. Attention has been drawn to symptomatic caecal diverticulitis because clinical and laboratory manifestations include leukocytosis in complete blood count, and fever and pain in the right lower quadrant (frequently with defense and rebound tenderness). This presentation, as is to be expected, leads many clinicians to the diagnosis of acute appendicitis. Moreover, imaging techniques are not sufficient for definitive diagnosis. Therefore, patients are frequently taken for surgery with clinical diagnosis of acute appendicitis, as was the case in the present report. In spite of close resemblance to acute appendicitis in clinical, laboratory, and imaging findings, absence of profound anorexia, vomiting, and septic manifestations even 24 hours after abdominal pain onset should lead to the consideration of isolated caecal diverticulitis.[4,5,7] If latent perforation due to diverticulitis does develop, the patient may present with a paucity of symptoms and a palpable mass, and postoperatively develop an “onion skin-like” appearance of the region visible on histological examination, which may be limited by fibrin deposits.[5] In such cases, diseases such as Crohn’s disease, ameboma, tumor of the caecum, gastrointestinal tuberculosis, and pelvic inflammatory disorder, which may present with a palpable mass in the right lower quadrant, should also be considered.[4,6] In a study by Chou et al., which included 934 patients who presented with right lower quadrant pain, 91% sensitivity and 99% specificity of ultrasonography for diagnosis was reported.[8] In another study of right colon diverticular disease, conducted by Sardi et al. and including 881 patients, sensitivity and specificity ratios from CT were reportedly similar to those of ultrasonography.[9] In the 2 cases presently described, specificity and sensitivity of imaging techniques can be explained by the fact that these cases were not definitively diagnosed as acute appendicitis, as diagnosis of perforations was not possible prior to surgery.

That the 2 large studies mentioned above included all manifestations of right colon diverticula should not be overlooked.[8,9] However, ultrasonography and CT scanning may not be successful in differentiating caecal diverticular disease, due to the close proximity of the appendix vermiformis, particularly in cases of complicated diverticulitis, which can alter the anatomy of the region. It has been reported that diagnosis 291

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of 65–85% of solitary caecal diverticulitis cases are confirmed during surgery.[1,4,5,6] This has also been confirmed by the results of the present report.

Conclusion Acute appendicitis is the most common cause of acute abdominal disease in surgical practice. However, the possibility of caecal diverticulitis and its complications should also be considered in patients presenting with clinical manifestations of acute appendicitis, particularly in patients aged outside the common range for acute appendicitis.

It is suggested that surgeons scheduling patients for acute appendicitis surgery bear in mind the possibility of caecal diverticulitis and are thus prepared for such a finding, in an effort to reduce occurrence of postoperative complication.

Conflict of interest: None declared.

This report was presented as an electronic paper at the 19th National Surgery Congress of Turkey (April 16–20, 2014, Antalya, Turkey).

REFERENCES 1. Connolly D, McGookin RR, Gidwani A, Brown MG. Inflamed solitary caecal diverticulum - it is not appendicitis, what should I do? Ann R Coll Surg Engl 2006;88:672–4.

2. Karatepe O, Gulcicek OB, Adas G, Battal M, Ozdenkaya Y, Kurtulus I, et al. Cecal diverticulitis mimicking acute Appendicitis: a report of 4 cases.

World J Emerg Surg 2008;3:16.

3. Cole M, Ayantunde AA, Payne J. Caecal diverticulitis presenting as acute appendicitis: a case report. World J Emerg Surg 2009;4:29.

4. Ruiz-Tovar J, Reguero-Callejas ME, González Palacios F. Inflammation and perforation of a solitary diverticulum of the cecum. A report of 5 cases and literature review. Rev Esp Enferm Dig 2006;98:875–80.

5. Kumar S, Fitzmaurice GJ, O’Donnell ME, Brown R. Acute right iliac fossa pain: not always appendicitis or a caecal tumour: two case reports.

Cases J 2009;2:88.

6. Tihan DN, Küçükyılmaz M, Hepgül G, Öztürk O, Binboğa S. Cecum Diverticulum Perforation Mimicking an Acute Appendicitis: A Report of Two Cases. Kolon Rektum Hast Derg 2011;21:126–9.

7. Abogunrin FA, Arya N, Somerville JE, Refsum S. Solitary caecal diverticulitis-a rare cause of right iliac fossa pain. Ulster Med J 2005;74:132– 3.

8. Chou YH, Chiou HJ, Tiu CM, Chen JD, Hsu CC, Lee CH, et al. Sonography of acute right side colonic diverticulitis. Am J Surg 2001;181:122– 7.

9. Sardi A, Gokli A, Singer JA. Diverticular disease of the cecum and ascending colon. A review of 881 cases. Am Surg 1987;53:41–5.

OLGU SUNUMU - ÖZET

Nadir akut karın nedeni: Çekum divertikül perforasyonu (İki olgu) Dr. Fatih Çiftci,1 Dr. İbrahim Abdurrahman,2 Dr. Abdülkadir Eren3 1 2 3

İstanbul Gelişim Üniversitesi, Sağlık Hizmetleri Meslek Yüksekokulu, Genel Cerrahi Anabilim Dalı, İstanbul, Türkiye İstanbul Safa Hastanesi, Acil Tıp Kliniği, İstanbul İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Radioloji Anabilim Dalı, İstanbul

Çekum divertikülü nadir görülen bir lezyon olmakla birlikte, klinik semptomları akut apandisit ile benzerlik gösterdiğinden dolayı tanı ve tedavi açısından zorluklar sergiler. Fiziksel inceleme ile akut apandisitten hemen hemen hiçbir zaman ayırt edilemez. Radyolojik görüntülemede yetersiz kalabilir.

Bu nedenle tanının ameliyat esnasında konulduğu durumlar olur. Bu yazıda, perfore çekum divertikülü saptanıp ameliyat edilen iki olgu sunuldu.

Anahtar sözcükler: Akut karın; çekum; divertikül perforasyonu.

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CAS E R EP O RT

Traumatic rupture of gastric pull-up after apparent mild thoracic trauma: a case report and literature review Joaquin Valle, M.D., Hanumantha Srinivasrao, M.D., David Snow, M.D., Mike Asbitt, M.D. Department of Emergency Medicine, Southport and Omskirk Hospital, Southport-United Kingdom

ABSTRACT While elderly patients account for only 10â&#x20AC;&#x201C;12% of all trauma victims, they consume 25% of trauma-related health care resources, with higher rates of mortality and complication. Presently described is the case of an elderly patient who presented to the emergency department (ED) following mild thoracic trauma, with previous history of gastric pull-up surgery. The patient had consulted another facility 48 hours earlier and was prescribed analgesia and x-ray follow-up for a mechanical fall and pain in the lower rib cage. At arrival, the patient complained of increasing dyspnea and pain at the right hemithorax. X-ray showed right hemithorax effusion, and contrast computed tomography (CT) demonstrated a large amount of contrast filling the pleural space and a relatively small point of gastric pull-up rupture in the stomach. The patient was referred to the cardiothoracic unit, but was unresponsive upon arrival and died. The aim of the present report was to raise the index of clinical suspicion of traumatic rupture of the gastric pull-up following traumatic chest injury, and to affirm that contrast CT should be the gold standard for diagnosis.

Keywords: Elderly; gastric pull-up; trauma.

INTRODUCTION

CASE REPORT

Elderly patients with minor injuries and pre-existing medical conditions have increased risk of death, compared to their younger counterparts, and are more likely to die of medical complications late in hospital admission. Overall, 38% of all injury-related deaths occur in individuals aged 75 years and older among the ageing population, and these figures are likely to increase. Data from Western countries suggest an increase from 19% in 2010 to 23% in 2035 in the UK.[1] Esophagectomy with gastric pull-up is a surgical procedure in which the stomach is used to replace the esophagus, and quality of life in patients who survive 10 or more years after esophagectomy and gastric pull-up is excellent. However, the number of patients presenting to emergency departments (EDs) with related complications will increase.

An 85-year-old man presented to the ED 2 days after sustaining a fall with blunt trauma to the lower right rib cage. The patient had been seen at a primary care facility after missing a step in the kitchen, falling backwards, and striking his chest against the corner of a chair. Tenderness at the eighth rib was elicited, and probable rib fracture was diagnosed. The patient was discharged under the care of his family and given a prescription for paracetamol with codeine (co-dydramol), with chest x-ray scheduled for 48 hours later. History included gastric pull-up for the treatment of esophageal adenocarcinoma 13 years prior, in addition to hypertension and transient ischemic attack. Treatment included aspirin 75 mg, omeprazole 40 mg, and bendroflumethiazide 2.5 mg. After 48 hours, the patient was transferred by ambulance to the accident and emergency department, with main complaint of severe stabbing right hemithorax pain and gradually worsening dyspnea; the pain was worse on inspiration. Upon arrival, the patient had dyspnea with use of accessory muscles, palpable regular pulses with a rate of 130 bpm, and arterial pressure of 110/60 mmHg. On pulse oximetry, saturation was 88% in room air.

Glasgow Coma Scale score was 15.

Address for correspondence: Joaquin Valle, M.D. Gordon Street 14450 Southport, United Kingdom Tel: 673916576 E-mail: joa51274@hotmail.com Qucik Response Code

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Complete physical examination revealed tenderness over the right posterolateral chest wall with ecchymotic bruises.

Breath sounds were absent in the right hemithorax. Abdominal and neurological examinations were unremarkable.

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Thoracic bedside ultrasound was consistent with pleural effusion, and Focused Assessment with Sonography for Trauma (FAST) scan was negative. Complete blood count, serum electrolytes, glucose, urea, and creatinine were normal, while electrocardiogram showed sinus tachycardia. Portable chest x-ray showed right hemithorax effusion (Fig. 1). Arterial blood gases on admission were: pH 7.246; partial pressure of carbon dioxide: 49.3 mmHg; partial pressure of oxygen: 47 mmHg; bicarbonate: 21.9 mEq/L; oxygen saturation: 89.9%; lactate: 2.1 mmol/L. Further work-up included non-contrast thorax computed tomography (CT; Fig. 1), which revealed a mixture of primarily fluid with some air in the pleural space, and with right lung compression. No rib fracture was present, though possible rupture in the gastric pull-up was indicated.

Contrast CT was used assess the integrity of the esophagus and stomach (Fig. 2). It showed a large amount of contrast filling the pleural space, and a relatively small point of rupture in the stomach, posterolaterally. The patient was immediately referred to the cardiothoracic unit. Upon arrival, he went into respiratory distress (saturation: 75% on 15L of oxygen), and became hypotensive (blood pressure: 54 over 40 mmHg) and tachypneic (respiratory frequency: 24 breaths/minute).

The patient became pulseless and asystolic, with fixed, dilated pupils. Resuscitation attempts failed, and the patient was pronounced dead. Ultimate diagnosis was traumatic rupture

of the gastric pull-up with significant hydrothorax of gastric content.

DISCUSSION As the elderly population within the UK continues to grow,[1] more elderly patients will suffer trauma. While this growing number of elderly patients form a small percentage of overall trauma patients, they consume a disproportionate amount of medical resources[2] and are more likely to require hospital admission.[3] There has been an associated increase in the number of elderly major trauma patients presenting to EDs, without clear guidelines for the optimization of management of this vulnerable group. Aggressive early management of such patients results in increased survival rate, and of those who survive, the majority return home.[4] Mortality due to trauma continues to fall, but the highest rates are seen in patients older than 65 years. The majority of traumas are secondary to falls.[5] Elderly patients with minor injuries have increased risk of death, compared to their younger counterparts, and are more likely to die of medical complications late in hospital admission. The elderly undergo significant physiologic changes that disguise the normal stress response, such as arteriosclerotic arteries, reduced response

Figure 1. Chest x-ray showing right hemithorax effusion, and non-contrast thorax computed tomography showing a mixture of primarily fluid with some air in the pleural space, and with right lung compression.

Figure 2. Traumatic rupture of the gastric pull-up with significant hydrothorax of gastric content, and, posterolaterally, a relatively small point of rupture in the stomach.

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to catecholamines, decreased cardiac output and myocardial contractility, muscular atrophy, decreased bone mass, and decreased lung compliance. Other influencing factors are preexisting illnesses, current medications, and the mechanism of injury. Injuries in older patients are more likely to have fatal outcome.[6–8] In one study, Shorr et al.[9] reported a mortality rate that was 2.76 times higher in older victims of blunt chest trauma.

There is a significant association between severe preexisting medical disease and death during admission for trauma. A UK study analyzed the cases of 100 consecutive trauma patients 65 years of age and over that had been prospectively entered into the UK Trauma Network database from a single center.

Of the 100 patients, 16 died and 84 survived. Eleven of the 16 who died and 12 of the survivors had preexisting medical disease and social dependency, suggesting poor outcome, as these factors are significantly associated with mortality.[10] Elderly patients with isolated chest injuries have more than twice the mortality rate of younger patients with the same injuries.[11] Esophagectomy with gastric pull-up is a surgical procedure in which the stomach is used to replace the esophagus. It is an integral part of the curative treatment of esophageal cancer, either as initial therapy or following preoperative chemoradiotherapy, and is also performed to treat end-stage benign conditions in some patients. Mortality and morbidity of esophagectomy and gastric pull-up for carcinoma of the esophagus is high.[12] Patients who present with blunt thoracic trauma and previous gastric pull-up are rarely encountered in ED practice. However, it has recently been reported that quality of life in patients who survived 10 or more years following esophagectomy and gastric pull-up was excellent, matching or exceeding population normal values.[13] Complications after gastric pull-up include anastomotic leak, pneumonitis, pleural effusion, wound infection, heart failure, anastomosis stricture, chylous fistula, hemothorax, hemoperitoneum, and burst abdomen.

Presently described was a geriatric patient with minor chest trauma seen at a primary care facility and treated for suspected rib fracture. Nevertheless, one of the most important aspects of this case was the history of gastric pull-up. No previous cases of traumatic pull-up rupture have been reported.

One point of consideration is that patients with pull-up do not commonly present to the ED, though it has been demonstrated that patients who survive have a normal quality of life.

[13] Therefore, in the future, more patients will be presenting to the ED with several conditions, including trauma. That a rupture of the gastric pull-up may occur should be taken into consideration, and contrast CT should be requested.

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In the management of trauma in elderly patients, it is essential that clinicians compile an improved base of evidence to further inform our approach in this vulnerable group of patients. There are many barriers to the research and gathering of good evidence that will support clinical decision-making in the resuscitation environment. A diversity of approaches should be developed to treat trauma in elderly patients, even when minor, as pre-injury health status, management goals, treatment paradigms, and likely outcomes are very different.

[14] The present case serves as a useful reminder that there is less room for error when examining and treating older patients with blunt injuries to the chest.

Conflict of interest: None declared.

REFERENCES 1. Office for National Statistics, United Kingdom. Topic guide to Population estimates. Available at: http://www.statistics.gov.uk/hub/population/population-change/population-estimates/index.html.

2. MacKenzie EJ, Morris JA Jr, Smith GS, Fahey M. Acute hospital costs of trauma in the United States: implications for regionalized systems of care.

J Trauma 1990;30:1096–103.

3. Court-Brown CM, Clement N. Four score years and ten: an analysis of the epidemiology of fractures in the very elderly. Injury 2009;40:1111–4.

4. Broos PL, D’Hoore A, Vanderschot P, Rommens PM, Stappaerts KH. Multiple trauma in elderly patients. Factors influencing outcome: importance of aggressive care. Injury 1993;24:365–8.

5. Griffiths C, Wright O, Rooney C. Trends in injury and poisoning mortality using the ICE on injury statistics matrix, England and Wales, 19792004. Health Stat Q 2006;32:5–18.

6. Evans R. Trauma and falls. In: Sanders AB, editor. Emergency care of the elder person. Philadelphia: Society for Academic Emergency Medicine, Beverly Cracom Publications; 1996. p. 153–70.

7. Levy DB, Hanlon DP, Townsend RN. Geriatric trauma. Clin Geriatr Med 1993;9:601–20.

8. Oreskovich MR, Howard JD, Copass MK, Carrico CJ. Geriatric trauma: injury patterns and outcome. J Trauma 1984;24:565–72.

9. Shorr RM, Rodriguez A, Indeck MC, Crittenden MD, Hartunian S, Cowley RA. Blunt chest trauma in the elderly. J Trauma 1989;29:234–7.

10. Pickering SA, Esberger D, Moran CG. The outcome following major trauma in the elderly. Predictors of survival. Injury 1999;30:703–6.

11. Taylor MD, Tracy JK, Meyer W, Pasquale M, Napolitano LM. Trauma in the elderly: intensive care unit resource use and outcome. J Trauma 2002;53:407–14.

12. Leers JM, DeMeester SR, Chan N, Ayazi S, Oezcelik A, Abate E, et al.

Clinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus. J Thorac Cardiovasc Surg 2009;138:594–602.

13. Greene CL, DeMeester SR, Worrell SG, Oh DS, Hagen JA, DeMeester TR. Alimentary satisfaction, gastrointestinal symptoms, and quality of life 10 or more years after esophagectomy with gastric pull-up. J Thorac Cardiovasc Surg 2014;147:909–14.

14. Mitra B, Cameron PA. Optimising management of the elderly trauma patient. Injury 2012;43:973–5.

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OLGU SUNUMU - ÖZET

Belirgin bir toraks travması ardından gastrik pull-up’ın travmatik rüptürü: Bir olgu raporu ve literatürün gözden geçirilmesi Dr. Joaquin Valle, Dr. Hanumantha Srinivasrao, Dr. David Snow, Dr. Mike Asbitt Southport ve Omskirk Hastanesi, Acil Tıp Kliniği, Southport, İngiltere

Yaşlı hastalar tüm travmaya uğrayanların yalnızca %10–12’sini oluşturmasına rağmen göreceli yüksek mortalite ve komplikasyon oranlarıyla sağlık kaynaklarının %25’ini tüketmektedirler. Bu yazıda, daha önce gastrik pull-up cerrahisi geçirmiş, hafif bir göğüs travması ardından acil servise (AS) başvuran yaşlı bir hasta sunuldu. Hasta 48 saat önce başka bir merkeze başvurmuş, düşme ve göğüs kafesi alt kısmındaki ağrısı için ağrı kesici reçetelendirilmiş ve radyolojik takip önerilmiş. Hasta acil servise vardığında giderek artan nefes darlığı ve sağ hemitoraksta ağrıdan yakınmıştır. Röntgende sağ hemitoraksta efüzyon, kontrastlı bilgisayarlı tomografide (BT) plevra boşluğunu dolduran büyük miktarda kontrast madde ve midede gastrik pull-up operasyon yerinde oldukça ufak bir rüptür görülmüştür. Hasta kardiyotorasik birime sevk edilmiş olmasına rağmen vardığında bilinç kaybı vardı ve yaşamını yitirmişti. Bu olgu sunumunun amacı, toraks travmasından sonra gastrik pull-up yerinde travmatik rüptürden yüksek derecede klinik kuşku duyulmasını sağlamak ve tanıda altın standardın mutlaka kontrastlı BT olduğunu doğrulamaktı.

Anahtar sözcükler: Gastrik pull-up; travma; yaşlılar.

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Challenging management of obturator hernia: a report of three cases and literature review Kazım Şenol, M.D., Mehmet Emrah Bayam, M.D., Uğur Duman, M.D., Evren Dilektaşlı, M.D., Muhammed Doğangün, M.D., Abdullah İnal, M.D., Deniz Necdet Tihan, M.D. Depatment of General Surgery, Şevket Yılmaz Training and Research Hospital, Bursa-Turkey

ABSTRACT Obturator hernia (OH) is a rare condition with high rates of morbidity and mortality.While diagnosis is difficult, surgery is the definitive treatment. Intestinal obstruction is the most common symptom upon admission. In addition, small-bowel obstruction is documented in more than half of OH patients.Advanced age, intestinal obstruction, bowel perforation, comorbid diseases, and clinical deterioration are risk factors for higher rates of mortality. The aim of the present report was to document clinical and surgical management of 3 female patients, each over 80 years of age, admitted to the emergency surgery department with intestinal obstruction and OH. Keywords: Computed tomography; mortality; obturator hernia; small-bowel obstruction.

INTRODUCTION Obturator hernia (OH) is a rare clinical entity with an incidence between 0.05–1.4% of all hernias.[1] Excessive weight loss and multi-parity in women, chronic obstructive pulmonary disease, increased intraabdominal pressure associated with chronic constipation, and ascites are risk factors for obturator canal enlargement leading to the development of peritoneal dimple and invagination of a peritoneal sac into the obturator canal.[2] Clinical characteristics of OH are obscure. Lack of significant examination findings and clinical symptoms usually increase rates of morbidity and mortality. Although Howship–Romberg sign (HR) is the pathognomonic finding of a compressed obturator nerve by internal rotation of the hip, only 15–50% of patients present with pain in the medial part of the thigh.

[3] Hannington-Kiff (HK) sign, characterized by the absence of adductor thigh reflex, is another specific finding of OH.[4] In addition to obturator neuralgia and lower abdominal pain, intestinal obstruction is the most significant clinical manifestation.

Address for correspondence: Kazım Şenol, M.D. Bursa Şevket Yılmaz Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Yıldırım, Bursa, Turkey Tel: +90 224 - 295 50 00 E-mail: kazimsenol@outlook.com Qucik Response Code

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The aim of the present report was to provide a review of clinical presentations of 3 patients with OH, as well as a clinical perspective, even in challenging diagnosis with complicated clinical courses.

CASE REPORT Case 1– An 83-year-old woman was admitted to the department of emergency surgery with vomiting, nausea, and obstipation that had lasted 4 consecutive days. Medical history was unremarkable. On physical examination, she had tenderness throughout the abdomen without defense or rebound.

HR sign, HK sign, and related obturator neuralgia was not observed. Laboratory parameters were within normal range.

Direct abdominal x-ray graphs showed small-bowel obstruction, and initial computed tomography (CT) scan aided in diagnosis of right-sided, incarcerated OH (Fig. 1). The patient underwent emergency surgery with midline laparotomy. Exploration of the abdomen revealed a 5-cm ileal segment 60 cm above the ileocecal valve, incarcerated through the obturator canal. Gentle traction of the hernia sac and incarcerated bowel was performed to avoid iatrogenic perforation of the ileal segment. The strangulated ileal segment was gangrenous (Fig. 1). Following segmentectomy and anastomoses, obturator defect was repaired with interrupted sutures. Postoperative follow-up was uneventful, and the patient was discharged on the tenth postoperative day.

Case 2– An 89-year-old woman was admitted to the department of emergency surgery with lower abdominal pain and obstipation that had begun 2 days prior. The patient had a 297

Ĺ&#x17E;enol et al. Challenging management of obturator hernia

(a)

(b)

(c)

Figure 2. (a) Peroperative exploration of enlarged obturator canal and illustration of anatomical indexes. (b) Strangulated and gangrenous small-bowel segment with complete detachment form mesentery. (c) Computed tomography scan showing incarcerated intestinal loop through the right obturator canal. CL: Cooper ligament; CM: Corona mortis; FR: Femoral ring; IEA: Inferior epigastric artery; IL: Inguinal ligament; P: Surgical clamp; SP: Symphysis pubis.

history of appendectomy and left inguinal hernia repair. Physical examination revealed tenderness in the lower quadrants of the abdomen and mild abdominal distention. Rectal examination was normal. Laboratory tests showed leukocytosis, hyponatremia, and hypokalemia. Direct x-ray graphs and abdominal ultrasonography showed unperistaltic dilated intestines. Oral intake was stopped, and initial therapy with serial physical examination check-ups was planned. On the second day, direct x-ray graphs showed increased obstruction of the small intestine with findings of severe peritonitis. Exploratory laparotomy revealed incarcerated ileal segment 100 cm above the terminal ileum, through a large obturator canal.

Strangulated ileal segment was gangrenous, and perforation was limited to the obturator canal. Hence, resection anastomosis was performed. Necrotic tissue and bowel contents in the obturator canal were removed with radical debridement.

Obturator canal was closed with interrupted sutures, and a sump drain was placed in the rectovesical space. Postoperative follow-up was uneventful. On the fifth postoperative day, oral intake was resumed, and abdominal drain was removed.

The patient was discharged on the tenth postoperative day with favorable outcome.

Case 3â&#x20AC;&#x201C; An 81-year-old woman was admitted with fecaloid vomiting and recurrent lower abdominal pain. Abdominal distention had begun 3 months prior, and slight amounts of watery defecation had occurred 2 or 3 times per week. Medical history included 2 caesarian sections and appendectomy operations. Physical examination revealed tenderness with findings of peritonitis, distention, and hyperactive bowel sounds.

Rectal palpation demonstrated a painful mass externally compressing the rectal mucosa into the anal canal. White blood cell count was 14500 cells/ÂľL, and serum amylase level was 2 times higher than normal limits. Direct abdominal x-ray graphs showed dilated small-bowel loops and multiple air298

fluid levels. Medical therapy was planned and initial decompression was maintained by nasogastric tube insertion. Further investigation with oral and rectal contrast-enhanced CT demonstrated a right-sided OH with small-bowel strangulation. Midline laparotomy confirmed the diagnosis. Strangulated intestines were firmly adherent, and careful traction did not reduce the hernia sac. Adhesions between the peritoneum and the obturator membrane were dissected with careful cauterization. A nelaton catheter was inserted through the obturator foramen along the obturator canal, and hydrostatic pressure was maintained using slight infusion of isotonic saline solution with 50-cc syringe. Hence, hernia sac and intestines were reduced by gentle means, without perforation or ischemia. Consequently, obturator defect was repaired with interrupted sutures. Postoperative follow-up was uneventful.

Nasogastric tube was removed on the second day, and oral intake was initiated. The patient was discharged on the eighth day, with full recovery.

DISCUSSION OH commonly occurs in elderly, emaciated, multiparous women, with a female:male ratio of 9:1.[5,6] Acute intestinal obstruction is the most significant clinical presentation, present in over 90% of OH patients.[2] Approximately half present with small-bowel strangulation.[7] In addition, OH may contain the large bowels, omentum, appendix, or fallopian tubes.[8,9] Other clinical symptoms include lower abdominal pain, abdominal distention, nausea, vomiting, and obturator neuralgia, associated with intestinal ischemia, all of which are non-specific findings ranging from mild to severe.[2] Unfortunately, these symptoms in isolation are not sufficient for differential diagnosis.

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proximately 10% of patients are diagnosed prior to surgery.

[10] Better diagnostic performance with higher sensitivity and specificity rates are demonstrated by CT, as opposed to ultrasonography, direct abdominal x-ray radiographs, or magnetic resonance imaging.[11] CT is relatively non-invasive, a fast and reliable tool, with a preoperative diagnosis rate of 90%.

[12] CT is thus defined as a gold standard, first-line imaging modality, particularly in cases of acute intestinal obstruction when supported with direct abdominal x-ray radiographs and subtle clinical presentation of OH.[13] However, it has been noted in recent studies that preoperative CT plays a controversial role in postoperative outcomes.

Kammori et al. have suggested that preoperative CT reduced both intestinal resection rates and surgical mortality,[14] whereas Yokoyoma et al. reported insignificant impact on patient outcome.[15] In the cases presently described, initial CT evaluation revealed intestines incarcerated into the obturator canal in all cases. Compared to examination findings, CT provided a definitive diagnosis, allowing for the performance of prompt and accurate treatment. Therefore, preoperative CT should be used as a primary screening tool for differential diagnosis of intestinal obstruction, particularly in elderly, emaciated, and multiparous women with high suspicion of OH. In routine practice, clinical efforts to identify the underlying causes of acute intestinal obstruction usually delay the timing of initial surgical intervention and complicate the clinical course.

It has been argued that prolonged diagnosis of incarcerated OH leads to an increase of up to 70% in rates of morbidity and mortality.[7] High morbidity rates are also associated with advanced age, bowel perforation, comorbid diseases, and deterioration or disability.[16] Several algorithms have been described for management of suspected OH to reduce morbidity and mortality.[6,11] Above all, clinicians should specify admission signs and symptoms of possible OH presentation with history and physical examination. The next step is to determine peritonitis findings and small-bowel obstruction with direct abdominal x-ray graphs and CT scan. Whether or not diagnosis is clear, urgent laparotomy must be performed if intestinal obstruction symptoms persist and/or manifest with peritonitis.

Even with challenging diagnosis in emergent or recurrent OH, surgery is stated as the main treatment. Several surgical procedures have been described, including abdominal, inguinal, retropubic, and obturator approaches.[2] Inguinal, retropubic and obturator approaches are preferred when preoperative diagnosis is clear, and intestinal strangulation is excluded. The aims of surgical intervention should be to evaluate viability of incarcerated organs or intestines for adequate resection and to repair the corrupted obturator canal. The abdominal approach was preferred in the present cases. The patients were examined for intestinal ischemia, and the anatomy of Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 3

the obturator canal was more properly observed by lower midline laparotomy. In all cases, midline laparotomy and primary repair of the defect resulted in satisfactory postoperative outcomes.

In recent reports, surgeons have been encouraged to perform laparoscopy in cases of OH.[17] Laparoscopic surgery has been recently described as an elective treatment modality in cases of accurate preoperative diagnosis subsequent to CT. Disadvantages of laparoscopic surgery are inability to assess viability or resection of intestines, and inability to perform as an emergency procedure. Some authors have suggested that even in emergent settings with abdominal distention, formal diagnostic laparoscopy should be performed to visualize intestinal viability, and that transabdominal preperitoneal approach should be performed to repair obturator defects.[3] In conclusion, OH is a clinical entity that an experienced surgeon may rarely identify in routine clinical practice. Clinical signs and symptoms are not specific enough for immediate diagnosis. Obturator neuralgia presenting with intestinal obstruction is the most significant finding upon examination that can lead clinicians with high clinical suspicion to an accurate diagnosis. Among all abdominal wall hernias, OH has the highest rates of morbidity and mortality. Therefore, fast and accurate diagnosis plays an important role in improving postoperative outcomes. Assessment of elderly, emaciated, multiparous women with lower abdominal pain and abdominal distention should be performed more cautiously, and CT should be promptly performed in cases of potential OH. Whether or not diagnosis is clear, urgent laparotomy must be performed if symptoms of intestinal obstruction persist and/or manifest with peritonitis.

Conflict of interest: None declared.

REFERENCES 1. Lo CY, Lorentz TG, Lau PW. Obturator hernia presenting as small bowel obstruction. Am J Surg 1994;167:396–8.

2. Petrie A, Tubbs RS, Matusz P, Shaffer K, Loukas M. Obturator hernia: anatomy, embryology, diagnosis, and treatment. Clin Anat 2011;24:562–9.

3. Nasir BS, Zendejas B, Ali SM, Groenewald CB, Heller SF, Farley DR. Obturator hernia: the Mayo Clinic experience. Hernia 2012;16:315–9.

4. Hannington-Kiff JG. Absent thigh adductor reflex in obturator hernia.

Lancet 1980;1:180.

5. Ziegler DW, Rhoads JE Jr. Obturator hernia needs a laparotomy, not a diagnosis. Am J Surg 1995;170:67–8.

6. Chang SS, Shan YS, Lin YJ, Tai YS, Lin PW. A review of obturator hernia and a proposed algorithm for its diagnosis and treatment. World J Surg 2005;29:450–4.

7. Gray SW, Skandalakis JE, Soria RE, Rowe JS Jr. Strangulated obturator hernia. Surgery 1974;75:20–7.

8. Hartley BE, Davies MS, Bowyer RC. Strangulated appendix in an obturator hernia presenting as gas gangrene of the thigh. Br J Surg 1994;81:1135.

9. Karasaki T, Nakagawa T, Tanaka N. Obturator hernia of the fallopian tube. Abdom Imaging 2013;38:619–21.

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Şenol et al. Challenging management of obturator hernia 10. Bjork KJ, Mucha P Jr, Cahill DR. Obturator hernia. Surg Gynecol Obstet 1988;167:217–22.

11. Rodríguez-Hermosa JI, Codina-Cazador A, Maroto-Genover A, PuigAlcántara J, Sirvent-Calvera JM, Garsot-Savall E, et al. Obturator hernia: clinical analysis of 16 cases and algorithm for its diagnosis and treatment.

Hernia 2008;12:289–97.

12. Terada R, Ito S, Kidogawa H, Kashima K, Ooe H. Obturator hernia: the usefulness of emergent computed tomography for early diagnosis. J Emerg Med 1999;17:883–6.

13. Mandarry MT, Zeng SB, Wei ZQ, Zhang C, Wang ZW. Obturator hernia-a condition seldom thought of and hence seldom sought. Int J Colorectal Dis 2012;27:133–41.

14. Kammori M, Mafune K, Hirashima T, Kawahara M, Hashimoto M, Ogawa T, et al. Forty-three cases of obturator hernia. Am J Surg 2004;187:549–52.

15. Yokoyama Y, Yamaguchi A, Isogai M, Hori A, Kaneoka Y. Thirty-six cases of obturator hernia: does computed tomography contribute to postoperative outcome? World J Surg 1999;23:214–7.

16. Hennekinne-Mucci S, Pessaux P, Du Plessis R, Regenet N, Lermite E, Arnaud JP. Strangulated obturator hernia: a report of 17 cases. [Article in French] Ann Chir 2003;128:159–62. [Abstract] 17. Hunt L, Morrison C, Lengyel J, Sagar P. Laparoscopic management of an obstructed obturator hernia: should laparoscopic assessment be the default option? Hernia 2009;13:313–5.

OLGU SUNUMU - ÖZET

Obturator fıtıkların zorlu yönetimi: Üç olgu sunumu ve literatürün gözden geçirilmesi Dr. Kazım Şenol, Dr. Mehmet Emrah Bayam, Dr. Uğur Duman, Dr. Evren Dilektaşlı, Dr. Muhammed Doğangün, Dr. Abdullah İnal, Deniz Necdet Tihan Şevket Yılmaz Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Bursa

Obturator herni yüksek mortalite ve morbidite yüzdeleri ile seyreden nadir görülen bir sağlık sorunudur. Tanı koymak güç olmakla birlikte kesin tedavisi cerrahidir. Bağırsak tıkanıklığı en sık başvuru semptomudur. Bununla birlikte hastaların yarısından fazlasında ince bağırsak tıkanıklığı izlenmektedir. İleri yaş, kadın cinsiyet, eşlik eden kronik hastalıklar, bağırsak tıkanıklığı, bağırsak perforasyonu ve hastanın klinik olarak kötü durumda olması yüksek mortalite için risk faktörleridir. Bu olgu sunumunda, acil cerrahi servise intestinal obstrüksiyon ve obturator herni ile kabul edilmiş 80 yaş üzeri, üç kadın hastanın klinik ve cerrahi yönetimini sunmayı amaçladık.

Anahtar sözcükler: Bilgisayarlı tomografi; ince bağırsak tıkanıklığı; mortalite; obturator herni.

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CAS E R EP O RT

Air gun pellet: cardiac penetration and peripheral embolization Onur Işık, M.D.,1 Çağatay Engin, M.D.,1 Ahmet Daylan, M.D.,1 Cengiz Şahutoğlu, M.D.2 1

Department of Cardiovascular Surgery, Ege University Faculty of Medicine, İzmir-Turkey

2

Department of Anesthesia and Reanimation, Ege University Faculty of Medicine, İzmir-Turkey

ABSTRACT Use of high-velocity air guns can to lead to serious injuries. Management options of cardiac pellet gun injuries are based on patient stability, and course and location of the pellet. Presently reported is the case of a boy who was shot with an air gun pellet. Following right ventricular entry, the pellet lodged in the left atrium and embolized to the right iliac and femoral artery. Following pellet localization, right ventricular injury was repaired, and the pellet was removed successfully.

Keywords: Air gun pellet; heart; penetrating trauma.

INTRODUCTION Air gun injuries to the extremities are common, though a penetrating injury to the heart is very rare. In addition, pellet embolization occurs infrequently in cases of penetrating trauma.

Lack of adequate experience at any single institution contributes to controversy regarding diagnostic and therapeutic approaches to management. Presently described is a case of pellet embolization from the left atrium to the right femoral artery.

CASE REPORT An 11-year-old boy presented to another hospital with single air gunshot wound to the chest. Cardiac computed tomography (CT) was performed, and the pellet was localized in the left atrium cavity (Fig. 1). The patient was transferred to the present institution for further evaluation and management. Upon arrival, the boy was sedated but conscious, with complaint of pain over the anterior chest wall. He had no significant medical or surgical history.

Address for correspondence: Onur Işık, M.D. Ege Üniversitesi Tıp Fakültesi, Kalp Damar Cerrahisi Anabilim Dalı, 35100 İzmir, Turkey Tel: +90 312 - 305 61 59 E-mail: dr.onur.aras@gmail.com Qucik Response Code

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On initial assessment he was fully conscious and alert, with patent airway and normal respiration. He was hemodynamically stable with no evidence of external bleeding or cardiac tamponade. No jugular venous distention was observed. Lung examination showed decreased breath sounds in the right lung base. A 0.5-cm entry wound was localized over the right fifth intercostal space, between the sternum and nipple. The wound was not bleeding, and no exit wound was found.

Secondary physical examination revealed weakened right femoral pulse with weakened popliteal and pedal pulses.

Handheld Doppler insonation revealed monophasic signals over the pedal arteries. No motor or sensory deficits were present. Electrocardiogram showed sinus rhythm with no alterations. Chest radiography showed widened mediastinum and right-sided hemothorax. No foreign body was found.

CT of chest, abdomen, pelvis, and upper thigh showed retrosternal hematoma, pericardial effusion, right-sided hemothorax and foreign body (pellet) in the right common iliac artery (Fig. 2). Decision to operate on an emergency basis was made. Conventional median sternotomy approach was selected. On opening the pericardium, hemopericardium was present. Tract of the missile could be made out from a small wound in the right side of the pericardium and in the adjacent right ventricular anterior wall. The ventricular wound had apparently sealed on its own. The wound was repaired using 5-0 polypropylene stitches with Teflon pledgets. No other wound was found on anterior or posterior walls of the heart. Intraoperative transesophageal echocardiography revealed a 2-mm atrial septal defect, intact ventricular septum, and normal valvular structures. Atrial septal defect shunt was unremarkable. Chest was closed after mediastinum and chest wall homeostasis.

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Figure 1. Chest radiograph with radiopacity (pellet) in the mediastinum. Computed tomography indicated the location of the radiopacity (pellet) in the left atrium.

Figure 2. Chest radiograph with radiopacity (pellet) in the abdomen. Computed tomography showed migration of the pellet in the likely location of the right common iliac artery.

A right vertical groin incision was made, and the pellet was palpated in the common femoral artery. After preparing for incision, the pellet was removed from the femoral artery. The patient did well after surgery and was discharged on the fifth postoperative day.

DISCUSSION Air guns, though perceived as toys, can cause life-threatening injuries. Muzzle velocities range from 290 to 940 ft/s, and some are comparable to 0.22 long or short conventional rifles, or 0.38 revolvers.[1] Though these guns are not legally considered firearms, such high velocities exceed the speed needed to penetrate the eye (39 m/s) and bone (106 m/s).

[2,3] Few cases of cardiac injury caused by air gun pellets in the pediatric age group have been reported.[4] Air gun pellet cardiac injuries differ from other penetrating cardiac injuries in clinical presentation, outcome, and management. Low incidence of air gun injuries makes management strategy more difficult. Clinical presentation may vary from adequate vital signs to hemodynamic instability. Such penetrating injuries to the heart may be mortal due to hemorrhagic shock and pericardial tamponade. Presence of missile in the heart or great vessels may be caused by penetrating injury or embolism. Important variables for missile embolism are force and direction of blood flow, arterial lumen (including size and take-off angle), missile size and weight, body 302

position immediately after injury, and point of entry to the cardiovascular system.[5] Strategies for the management of air gunshot injuries include observation, pericardial drainage, and cardiac exploration.

Cardiac injuries were described as plugged, with a blood clot or without active bleeding, in most reported cases in which full cardiac exploration was undertaken.[6] Emergency surgery was presently selected due to location of the pellet wound on the anterior chest wall and location of the pellet in the left atrium cavity. A pellet may cause multiple injuries to the heart, and repair must be performed, even in the absence of signs of cardiac tamponade. Preoperative or intraoperative echocardiography is crucial when deciding whether or not to perform intracardiac exploration. In addition, peripheral pulse examination is a useful tool in cases of pellet embolization/migration. When peripheral pulses are absent or weakened, reimaging of the pellet must be performed. Embolization was suspected after the second physical exam, and CT was repeated. No foreign body was found in the thoracic cavity during the second exam, and the pellet was located in the femoral artery. The present authors conclude that cardiac exploration is necessary in all cases of cardiac or pericardial penetration by missile.

Conflict of interest: None declared.

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REFERENCES 1. Harris W, Luterman A, Curreri PW. BB and pellet guns-toys or deadly weapons? J Trauma 1983;23:566–9.

2. Di Maio VJM. Penetration of the skin by bullets and missiles. Forensic Sci Gaz 1980;11:1–2.

3. Bowen DI, Magauran DM. Ocular injuries caused by airgun pellets: an analysis of 105 cases. Br Med J 1973;1:333–7.

4. Alejandro KV, Acosta JA, Rodríguez PA. Air gun pellet cardiac injuries: case report and review of the literature. J Trauma 2003;54:1242–4.

5. Massad M, Slim MS. Intravascular missile embolization in childhood: report of a case, literature review, and recommendations for management.

J Pediatr Surg 1990;25:1292–4.

6. DeCou JM, Abrams RS, Miller RS, Touloukian RJ, Gauderer MW. Lifethreatening air rifle injuries to the heart in three boys. J Pediatr Surg 2000;35:785–7.

OLGU SUNUMU - ÖZET

Havalı tüfek saçması kardiyak penetrasyon ve periferal embolizasyonu Dr. Onur Işık,1 Dr. Çağatay Engin,1 Dr. Ahmet Daylan,1 Dr. Cengiz Şahutoğlu2 1 2

Ege Üniversitesi Tıp Fakültesi, Kalp ve Damar Cerrahisi Anabilim Dalı, İzmir Ege Üniversitesi Tıp Fakültesi, Anestezi ve Reanimasyon Anabilim Dalı, İzmir

Havalı tabancalar atıldıktarı doğrultuda yüksek hızlara çıkabilir ve ciddi yaralanmalara neden olabirler. Kardiyak havalı tüfek saçması yaralanmalarında yönetim hastanın stabilitesine; saçmanın izlediği yola ve yerine göre planlanmaktadır. Biz havalı tüfek saçmasıyla sağ ventrikülden yaralandıktan sonra saçmanın sol atriyuma ilerleyip sağ iliyak ve femoral artere embolize olduğu erkek hastamızı sunuyoruz. Saçmanın lokalizasyonunun ardından sağ ventrikül yaralanması tamir edildi ve saçma başarıyla çıkartıldı.

Anahtar sözcükler: Havalı tüfek saçması; kalp; penetre travma.

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doi: 10.5505/tjtes.2015.76570

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