NCI 2015 / 3

ISSN 2148 - 4902

NORTHERN CLINICS OF ISTANBUL • İSTANBUL KUZEY KLİNİKLERİ

Vol. 2 • No. 3 • Year 2015

The impact of diabetes on left ventricular diastolic function in patients with arterial hypertension • Four-year retrospective look for acute scrotal pathologies • Prognosis of patients in a medical

INDEXED IN TURKIYE CITATION INDEX.

intensive care unit • Rural surgery in Guinea Bissau: An experience of Doctors Worldwide Turkey • TORCH seroprevalence among patients attending Obstetric Care Clinic of Haydarpasa Training and Research Hospital

affiliated to Association of Istanbul Northern Anatolia Public Hospitals • Causes of asymptomatic trocar site hernia: How can it be prevented? • Relation of physical activity level with quality of life, sleep and

depression in patients with knee osteoarthritis • Neck abscess: 79 cases • Treatment of chylothorax developed after congenital heart disease surgery: a case report• Pustular eruption

induced by etanercept in ankylosing spondylitis patient: a rare side effect • Non-classified type duodenal atresia: case report • A rare cause of gastric obstruction: Lighters swallowing • Parkinsonism secondary

to duloxetine use: a case report • What is hippotherapy?

The indications and effectiveness of hippotherapy

NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ Editor-in-Chief

Vıce Editors

Bekir Durmus, M.D.

Banu Mesci, M.D. Berna Terzioglu Bebitoglu, M.D. Ender Onur, M.D. Levent Doganay, M.D. Tunc Eren, M.D.

Scientıfıc Commıttee Abdullah Aydın, M.D.

Gencer Meryem, M.D.*

Ali Ihsan Dokucu, M.D.

Gozde Kir Cınar, M.D.

Ali Rıza Odabas, M.D.

Gulendam Kocak, M.D.

Murat Tuncer, M.D.*

Aliye Yıldırım Guzelant, M.D.

H. Muammer Karakas, M.D.

Mustafa Calıskan, M.D.

Asiye Kanbay, M.D.

Hale Akbaylar, M.D.

Mutse Banzragch, M.D.*

Atakan Yesil, M.D.

Haluk Vahaboglu, M.D.

Nazmiye Altintas, M.D.*

Ates Kadioglu, M.D.

Hamit Okur, M.D.

Nusret Acikgoz, M.D.*

Atilla Karaalp, M.D.*

Hanefi Ozbek, M.D.*

Onur S. Goksel, M.D.

Ayse Banu Sarıfakioglu, M.D.*

Haydar Sur, M.D.

Orhan Alimoglu, M.D.

Ayse Cikim Sertkaya, M.D.

Hulya Apaydın, M.D.

Ayten Kadanali, M.D.

Hulya Sungurtekin, M.D.

Ozge Ecmel Onur, M.D.

Bekir Atik, M.D.

Huseyin Bayramlar, M.D.

Ozlem Guneysel, M.D.

Birsen Yurugen, M.D.

Ibrahim Akalin, M.D.

S. Tahir Eren, M.D.

Bulent Gumusel, M.D.*

Ibrahim Ikizceli, M.D.

Sabahat Aksaray, M.D.

Canan Agalar, M.D.

Ihsan Karaman, M.D.

Sait Naderi, M.D.

Derya Buyukayhan, M.D.

Ilknur Aktas, M.D.

Semra Sardas, M.D.*

Didem Korular Tez, M.D.

Kamil Ozdil, M.D.

Serhat Citak, M.D.

Dilaver Tas, M.D.

Kaya Sarıbeyoglu, M.D.

Sevki Erdem, M.D.

Duygu Geler Kulcu, M.D.*

Kazim Capaci, M.D.*

Seyhan Hidiroglu, M.D.*

Ebru Zemheri, M.D.

Kemalettin Koltka, M.D.

Suayip Birinci, M.D.

Eren Gozke, M.D.

Lutfullah Orhan, M.D.

Sukran Kose, M.D.

Eren Ozek, M.D.

Mahmut Durmus, M.D.

Tayfun Kirazlı, M.D.*

Erturk Levent, M.D.

Mehmet Ali Ozcan, M.D.

Tuba Yavuzsen, M.D.

Eyup Gumus, M.D.

Mehmet Doganay, M.D.

Umut Kefeli, M.D.

Fahri Ovali, M.D.

Mehmet Eren, M.D.

Murat Muhcu, M.D.* *

*

*

Osman Ekinci, M.D.* *

*

*

Fatih Saygili, M.D.

Murat Acar, M.D.

Veli Citisli, M.D.*

Mehmet Fatih Ayik, M.D.

Yasar Bukte, M.D.

Fatma Eti Aslan, M.D.

Mehmet Kanbay, M.D.

Yuksel Altintas, M.D.

Ferruh Isman, M.D.

Mehmet Tunca, M.D.

Yurdanur Kilinc, M.D.*

Filiz Akyuz, M.D.

Melek Celik, M.D.

Fugen Aker, M.D.

Metin Kapan, M.D.

Fusun Mayda Domac, M.D.*

Muhammet Fatih Onsuz, M.D.*

*

*

*For the third issue of NCI.

NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ YEAR 2015 VOLUME 2 NUMBER 3

p-ISSN 2148 - 4902

Ownership and Accountability for Contents on behalf of the Istanbul Northern Anatolian Association of Public Hospitals

Kemal Memisoglu, M.D.

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Northern Clinics of Istanbul (NCI) is a peer-reviewed journal published triannually by the Istanbul Northern Anatolian Association of Public Hospitals.

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CONTENTS Vol. 2 • No. 3 • Year 2015 VI IX

INSTRUCTIONS FOR THE AUTHORS EDITORIAL

ORIGINAL ARTICLES 177–181 The impact of diabetes on left ventricular diastolic function in patients with arterial hypertension

M. Araz, A. Bayrac, H. Ciftci 182–188 Four-year retrospective look for acute scrotal pathologies

O. D. Ayvaz, A. C. Celayir, S. Moralioglu, O. Bosnali, O. Z. Pektas, A. K. Pelin, S. Caman 189–195 Prognosis of patients in a medical intensive care unit

A. U. Unal, O. Kostek, M. Takir, O. Caklili, M. Uzunlulu, A. Oguz 196–202 Rural surgery in Guinea Bissau: An experience of Doctors Worldwide Turkey

O. Alimoglu, J. Sagiroglu, T. Eren, K. Kinik 203–209 TORCH seroprevalence among patients attending Obstetric Care Clinic of Haydarpasa Training and Research Hospital affiliated to Association of Istanbul Northern Anatolia Public Hospitals

O. Numan, F. Vural, N. Aka, M. Alpay, A. D. E. Coskun 210–214 Causes of asymptomatic trocar site hernia: How can it be prevented?

O. Dincel, F. Basak, M. Goksu 215–221 Relation of physical activity level with quality of life, sleep and depression in patients with knee osteoarthritis

E. Mesci, A. Icagasioglu, N. Mesci, S. Turan Turgut 222–226 Neck abscess: 79 cases

S. Bulgurcu, I. B. Arslan, E. Demirhan, S. H. Kozcu, I. Cukurova

case reports 227–230 Treatment of chylothorax developed after congenital heart disease surgery: a case report

O. Bulut, D. Gul, S. Sevuk, I. Mungan, D. Buyukkayhan 231–235 Pustular eruption induced by etanercept in ankylosing spondylitis patient: a rare side effect

A. Kara, E. T. Alatas, H. S. Celebi, G. Dogan, Y. Dere 236–238 Non-classified type duodenal atresia: case report

A. Kara, E. T. Alatas, H. S. Celebi, G. Dogan, Y. Dere 239–242 A rare cause of gastric obstruction: Lighters swallowing

U. Aday, A. Tardu, M. A. Yagci, H. Yonder 243–246 Parkinsonism secondary to duloxetine use: a case report

A. Bayrak, B. Cetin, H. Meteris, S. Kesebir

REVIEW 247–252 What is hippotherapy? The indications and effectiveness of hippotherapy

T. T. Koca, H. Ataseven 253

Index of Vol. 2

INSTRUCTIONS FOR THE AUTHORS Northern Clinics of Istanbul

- NCI is a peer-reviewed open-access international journal published by the Istanbul Northern Anatolian Association of Public Hospitals. NCI printed three times a year. Free full-text articles in English are available at (www.kuzeyklinikleri.com). The NCI is indexed in Turkiye Citation Index. The journal publishes researches, interesting case reports, letters to the editor, review articles, editorial comments, medical news, guidelines. The journal accepts manuscripts written in Turkish, and English. Opinions presented in published articles by no means represent the official endorsement of the Istanbul Northern Anatolian Association of Public Hospitals.

Manuscripts should be prepared in accordance with the Uniform Requirements for Manuscripts Submitted to Biomedical Journals regularly updated by the International Committee of Medical Journal Editors, available at http:// www.icmje. org.

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Articles in press: Roten L, Derval N, Sacher F, Pascale P, Wilton SB, Scherr D, et al.

Ajmaline attenuates electrocardiogram characteristics of inferolateral early repolarization. Heart Rhythm 2011 Sep 19 [E-pub ahead of print], doi:10.1016/j.hrthm.2011.09.013.

2. Book: Brown AM. Physiology of the liver. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2003.

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coronary syndromes: a companion to Braunwald’s Heart Disease. Philadelphia: W.B. Saunders; 2003. p. 88107.

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May 3, 2011. Available at: http:// www.theheart.org/article/1220043. do. Accessed: June 12, 2011.

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EDITORIAL

Dear readers of the Journal of Northern Clinics of Istanbul, We are completing our second year with the third issue of 2015. I would like to thank our authors, reviewers who assess our papers, and readers for the interest you have shown to our journal. We are now affiliated with EBSCO and CINAHL databases thanks to your support. I hope that we will be accepted to most of the other medical indexes in the forthcoming year.

We have eight original studies, five case reports and one review in this issue. Original studies consist of articles including the Impact of Diabetes Mellitus on Left Ventricular Diastolic Function in Patients with Arterial Hypertension, a Four-year Retrospective Look for Acute Scrotal Pathologies, Prognosis of Patients in a Medical Intensive Care Unit, Rural surgery in Guinea Bissau: An experience of Doctors Worldwide Turkey, Torch Seroprevalence among patients attending obstetric care clinic of HaydarpaĹ&#x;a Training and Research Hospital of of Istanbul Anatolia North Public Hospital Association, Causes of Asymptomatic Trocar Site Hernia: How to prevent it? Relation of Physical Activity Level with Quality of Life, Sleep and Depression in Patients with Knee Osteoarthritis, and Neck Abscess: 79 Cases. Case reports include interesting studies consisting of articles including, Treatment of Chylothorax Developing after Congenital Heart Disease Surgery: A Case Report, Pustular Eruption Induced by Etanercept in Ankylosing Spondylitis Patient: A Rare Side Effect, Non-classified Type Duodenal Atresia: Case Report, Gastric Obstruction Developing in a Case Swallowing a Lighter, and Parkinsonism by using duloxetine: A case report. The review article focuses on an intriguing topic, Hippotherapy, the indications and efficacy of hippotherapy.

We congratulate our authors contributing to the composition of the content of this issue, and as the editorial team of the journal, we also thank the reviewers for making time for the assessment of the papers.

Hope to see you again in the first issue of 2016‌ Bekir Durmus, Assoc. Prof. M.D.

Editor-in-Chief

Orıgınal Article

Internal medicine

North Clin Istanbul 2015;2(3):177–181 doi: 10.14744/nci.2015.55477

The impact of diabetes on left ventricular diastolic function in patients with arterial hypertension Murat Araz,1 Aysen Bayrac,2 Hilmi Ciftci3 Department of Medical Oncology, Malatya State Hospital, Malatya, Turkey

1

Department of Internal Medicine, Ersoy Hospital, Istanbul, Turkey

2

Department of Internal Medicine, Medeniyet University Faculty of Medicine, Istanbul, Turkey

3

ABSTRACT OBJECTIVE: The aim of this study is to analyse the impact of diabetes mellitus on the left ventricular diastolic function in patients with arterial hypertension.

METHODS: Between July 2007 and July 2008, we enrolled patients aged ≥40 years who had hypertension with or without type 2 diabetes mellitus and unknown history of coronary artery disease who applied to 7.–8. internal medicine polyclinics of Goztepe Education and Training Hospital. Transthoracic echocardiography was used to assess the diastolic function. If patients with positive treadmill exercise test and/or EF ≤%50 in transthoracic echocardiography were excluded from the study. A total of 110 patients (males, n=42 38.2%, and females, n=68; 61.8%) with a mean age of 60.78 (±10.627) years were included in the study. For statistical analysis, SPSS 12.0 program and for the comparison of data chi-square test was used.

RESULTS: Diastolic dysfunction was significantly more prevalent in diabetes (81.25%) than those without diabetes group (62.9%) (p<0.05). In men, 35.9% in the DM(+) group and 41.1% in the DM(-) group had diastolic dysfunction. In women, 64.1% in the DM(+) group and 58.29% in the DM(-) group had diastolic dysfunction. In the evaluation based on gender, the difference male and female patients was not significant (p>0.05).

CONCLUSION: Diabetes in association with hypertension has a negative effect on left ventricular diastolic function. This effect appears similar in men and women.

Keywords: Diabetes mellitus; diastolic dysfunction; hypertension.

H

eart failure is generally associated with impaired left ventricular systolic function.

However, 30–40% of all patients with typical symptoms of congestive heart failure have a nor-

mal or minimally reduced ejection fraction. In these patients, diastolic dysfunction is the most important reason if not a primary cause of congestive heart failure [1, 2, 3].

Received: May 21, 2015 Accepted: November 18, 2015 Online: December 25, 2015 Correspondence: Dr. Murat Araz. Malatya Devlet Hastanesi, Tibbi Onkoloji Klinigi, Malatya, Turkey.

Tel: +90 444 56 34 e-mail: zaratarum@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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Newly onset heart failure is related to male sex, ischemic heart disease and systolic heart failure in patients with younger than 65 years old. In contrast to this data, left ventricular ejection fraction is almost normal in patients older than 70 years with heart failure and diastolic dysfunction is the first detectable abnormality in these patients [4, 5].

Diastolic functional abnormalities occurs earlier compared with systolic dysfunction in heart disease because of left ventricular relaxation process is more dependent on energy than ventricular contraction [4].

Diastolic heart failure is a clinical syndrome in patients who had symptoms and signs of heart failure, normal or slightly reduced left ventricular ejection fraction, abnormal left ventricular filling and/ or elevated filling pressures [3, 6].

Diastolic dysfunction has a particularly high prevalence in elderly patients and it is generally associated with low mortality but high morbidity. Annual mortality rate of diastolic heart failure is approximately 8% [3] as compared with annual mortality rate of 15 to 30% [7] seen in systolic heart failure. Diastolic heart failure is especially seen in the elderly patients with hypertension, valvular heart disease, hypertrophy/restrictive cardiomyopathy, tachycardia and ischemia but it can also occur in a variety of clinical disorders.

Possible mechanisms for diastolic dysfunction include interstitial accumulation of glycoprotein, slow sarcoplasmic calcium reuptake, excessive myocardial fibrosis or altered release of mediators such as nitric oxide and endothelin from a dysfunctional coronary endothelium [8]. The pathophysiology of diastolic dysfunction involves delayed relaxation, impaired left ventricular filling and/or increased stiffness [3].

The gold standard assessment of diastolic function consists of measuring the mean pulmonary capillary wedge pressure and LV end-diastolic pressure by cardiac catheterization [9, 10]. However, routine use of an invasive procedure for the evaluation of diastolic function is not rational in the polyclinic rooms.

Doppler echocardiography is a simple, non-invasive technique that can be used for the assessment of diastolic function. Transmitral velocity pattern is composed of E wave (occurring during the rapid

North Clin Istanbul – NCI

filling phase) and lower A wave (arising from atrial contraction) [5]. Transmitral flow pattern rapidly passes through the stages of normal relaxation (E>A), delayed (impaired) relaxation (E<A), and restrictive (E>>A) filling patterns [3].

The researchers have shown that diabetes mellitus results in primary myocardial abnormalities unrelated to ischemic heart disease, hypertension or obesity [8].

Identification of patients with diastolic heart failure is important because these patients almost have a poor prognosis as patients with systolic heart failure. Even asymptomatic patients with diastolic dysfunction are under the increased risk of adverse cardiovascular events [4].

The aim of this study was to analyze the impact of diabetes mellitus (DM) on left ventricular diastolic function in hypertensive patients.

MATERIALS AND METHODS Between July 2007 and July 2008, we enrolled patients aged ≥40 years who had hypertension with or without type 2 diabetes mellitus and unknown history of coronary artery disease who applied to 7.–8. internal medicine polyclinics of Goztepe Education and Training Hospital. Blood samples and history of coronary angiography and treadmill exercise test results were recorded. Patients with positive treadmill exercise stress test (according to modified Bruce protocol) and/or EF ≤50% in transthoracic echocardiography were excluded from the study.

The other exclusion criteria were age <40 years, arrhythmias (atrial fibrillation), significant valvular disease, known history of coronary artery disease and chronic renal disease.

Transthoracic echocardiography measurements of diastolic dysfunction were performed according to the American Society of Echocardiography (ASE) guidelines [4]. All echocardiography measurements were performed at midday by the same person according to the American Society of Echocardiography recommendations. Imaging was done while the patient in the left lateral decubitus position. Parasternal short and long axis, apical five

Araz et al., The impact of diabetes on left ventricular diastolic function in patients with arterial hypertension

90

Diastolic Dysfunction (-) Diastolic Dysfunction (+)

80 70

70

DM(+)

60 50

60 50

40

40

30

30

20

20

10

10 0

DM(-)

179

DM(-)

0

DM(+)

Figure 1.

Women

Figure 2. Diastolic dysfunction in male and female pa-

Diastolic dysfunction in patients with and without DM.

chamber view was obtained using M mode, color Doppler and flow Doppler a 2.5 MHz probe of Vivid 3; G.E. pro-brand ultrasound machine. Specifically, transmitral inflow measurements (E/A) were obtained from pulse wave Doppler flow velocity profiles after placing the sample volume at the tip of the mitral valve leaflets. Impaired relaxation was defined as E/A ratio <1, and an E/A ratio between 1 and 2 indicated normal diastolic filling.

Statistical analysis was performed using SPSS (Statistical Package for Social Sciences)12.0 program. Comparisons of all data were made with chisquare test. P-values were considered significant at a level of <0:05.

The study was conducted in accordance with the Helsinki Declaration and approved by the Local Ethics Committee of Goztepe Education and Training Hospital. All participants gave a written informed consent.

Men

tients.

Results A total of 110 patients (males, n=42 38.2%, and females, n=68; 61.8%) with a mean age of 60.78 (Âą10.627) years were included in the study. Sixtytwo patients (56.4%; 25 male and 37 female) had hypertension without diabetes mellitus and 48 patients (43.6%; 17 male and 31 female) had both hypertension and diabetes mellitus. Mean age of the patients was 60.78Âą10.63 years.

Diastolic dysfunction was significantly more prevalent in patients with DM (81.3%) than in patients without DM (62.9%) (p<0.05) (Figure 1).

Among men, 35.9% of the patients with DM (14 patients) and 41.1% of the patients (16 patients) without DM had diastolic dysfunction. Additionally, 64.1% of the women with DM (25 patients) and 58.3% of the women without DM (23 patients) had diastolic dysfunction (Table 1).

Table 1. Results of diastolic function by gender in diabetic and non-diabetic groups

E/A ratio

Patients with diabetes mellitus plus hypertension E/A <1 Diastolic dysfunction (+)

E/A >1 Diastolic dysfunction (-)

Patients with only hypertension E/A <1 Diastolic dysfunction (+)

E/A >1 Diastolic dysfunction (-)

Male 14 3 16 9 Female 25 6 23 14

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The prevalence of diastolic dysfunction was not significantly different between men and wome (p>0.05) (Figure 2).

Discussion Diabetic cardiomyopathy has been defined in four patients with congestive heart failure by Rubler at al.

[11] in the year 1972. These four patients had not hypertension, coronary artery disease, valvular disease and any other reason of cardiomyopathy. Microangiopathic influence and metabolic abnormalities are accepted causes of these abnormalities. Different investigators have shown left ventricular diastolic dysfunction in diabetic patients without clinical manifestations of congestive heart failure [12].

In the absence of risk factors (such as left ventricular hypertrophy, arterial hypertension, coronary artery disease, obesity and diabetes mellitus) diastolic dysfunction and diastolic abnormalities are rare even in elderly patients. According to a study on the absence of risk factors in a group of 1274 people aged 25–75 years, diastolic abnormalities and dysfunction were seen in 4.3% and 1.1% of the patients, respectively. Diastolic abnormalities and diastolic dysfunction were observed in 4.6%, and 1.2%. of the patients over 50 years of age. In the same study, diastolic abnormalities were found to be significantly higher in men than women (13.8, and 8.6%, respectively) [13].

In the presence of risk factors, its incidence rise significantly. The rate of was found as 60% [14] Diastolic dysfunction was found in 14 (60%) out of 46 asymptomatic type 2 diabetes individuals under glycemic control with non-diabetic complications.

Recently, in a prospective study performed by Watcher et al. the authors investigated the effect of diabetes on left ventricular diastolic function in hypertensive patients. In this study, totally 439 patients were divided into two groups as 315 hypertensive and 124 hypertensive diabetic patients.

Diastolic dysfunction was detected at a higher rate in diabetics (80.6%) when compared with non-diabetic patients (69.2%). Moreover, severity of diastolic dysfunction was found to be more serious in patients with diabetes. Sex-specific analysis revealed

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effects of diabetes on diastolic function in patients with concomitant hypertension. Diastolic dysfunction was determined to be significantly higher in male (p<0.003) patients without any statistically significant difference between genders [15].

In another study, the similar negative effect of diabetes on left ventricular filling pattern had been determined in normotensive and hypertensive individuals. The more serious effect of the combination of diabetes and hypertension was seen on left ventricular relaxation [16]. Poor glycemic control was associated independently with abnormal left ventricular relaxation in this study. In addition, in another study high fasting hyperglycemia was associated with increased myocardial stiffness in hypertensive patients [17].

The impact of diabetes on cardiac function is different between men and women. As a generally accepted corollary male heart seems to be more sensitive to risk factors than female [15, 18, 19].

According to our study that investigated the effects of diabetes on hypertensive patients, left ventricular diastolic dysfunction was significantly higher in patients with diabetes consistent with the other studies. There was no statistically significant difference between men and women versus other studies which analysed gender differences.

In our study, only E/A ratio was used to determine the diastolic dysfunction. Whereas, American Society of Echocardiography suggested that the different parameters need to be evaluated. Such as the E/A ratio, E’, E/E’(ratio of early mitral flow velocity (E) to early mitral annulus velocity (E’) (E/E’), and LAVI (left atrial volume index) have been used to estimate the LV filling pressure. There is still a controversy on which parameter, such as E/E’ or LAVI, provides a better predictive value for diastolic dysfunction and which parameter is a more powerful prognostic factor for clinical outcomes [9, 10].

In our study design, treadmill exercise stress test was used to exclude coronary ischemia. However, this stress test has been limited to detect only coronary ischemia because of the sensitivity level is not very high (approximately 70%). Myocardial scintigraphy or coronary angiography can be less restric-

Araz et al., The impact of diabetes on left ventricular diastolic function in patients with arterial hypertension

tive invasive methods for further studies to assess coronary ischemia that is a well-known risk factor for diastolic dysfunction.

Good glycemic control in diabetics can help in maintaining normal systolic function. It was shown in the Strong Heart Study that the degree of glycemic control quality is associated with echocardiographic evidence of diastolic function [16]. In our study, glycemic control markers HbA1c and fasting glycemia levels were excluded from evaluation.

Based on multivariate analysis of Strong Heart Study work tasks, ACE inhibitors and AT2 receptor blockers were found to have positive effects on diastolic dysfunction but beta blockers and diuretics did not demonstrate such favourable effects [16].

Therefore, considering the effects of drugs will reduce the limitations of the studies for assessing diastolic dysfunction.

Conclusion The prevalence of diastolic dysfunction is higher in hypertensive patients with diabetes mellitus than solely hypertensive patients. Its increased prevalence did not differ between male and female patients.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management. Ann Intern Med 1992;117:502–10.

2. Cregler LL, Georgiou D, Sosa I. Left ventricular diastolic dysfunction in patients with congestive heart failure. J Natl Med Assoc 1991;83:49–52.

3. Mandinov L, Eberli FR, Seiler C, Hess OM. Diastolic heart failure. Cardiovasc Res 2000;45:813–25.

4. Christopher PA. Diastolic heart function. In: Murphy JG, Lloyd MA (eds), Mayo Clinic Cardiology Concise Textbook (third ed.)

Mayo Clinic Scientific Pres 2008:1087–8.

5. Vlahović A, Popović AD. Evaluation of left ventricular diastolic function using Doppler echocardiography. [Article in Croatian] Med Pregl 1999;52:13–8. [Abstract]

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6. Aurigemma GP, Gaasch WH. Clinical practice. Diastolic heart failure. N Engl J Med 2004;351:1097–105.

7. Brogan WC 3rd, Hillis LD, Flores ED, Lange RA. The natural history of isolated left ventricular diastolic dysfunction. Am J Med 1992;92:627–30.

8. How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J 1998;19:990–1003.

9. Han JH, Han JS, Kim EJ, Doh FM, Koo HM, Kim CH, et al.

Diastolic dysfunction is an independent predictor of cardiovascular events in incident dialysis patients with preserved systolic function. PLoS One 2015;10:e0118694.

10. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009;10:165–93.

11. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972;30:595–602.

12. Shapiro LM, Howat AP, Calter MM. Left ventricular function in diabetes mellitus. I: Methodology, and prevalence and spectrum of abnormalities. Br Heart J 1981;45:122,8.

13. Fischer M, Baessler A, Hense HW, Hengstenberg C, Muscholl M, Holmer S, et al. Prevalence of left ventricular diastolic dysfunction in the community. Results from a Doppler echocardiographic-based survey of a population sample. Eur Heart J 2003;24:320–8.

14. Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care 2001;24:5–10.

15. Wachter R, Lüers C, Kleta S, Griebel K, Herrmann-Lingen C, Binder L, et al. Impact of diabetes on left ventricular diastolic function in patients with arterial hypertension. Eur J Heart Fail 2007;9:469–76.

16. Liu JE, Palmieri V, Roman MJ, Bella JN, Fabsitz R, Howard BV, et al. The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study. J Am Coll Cardiol 2001;37:1943–9.

17. Jain A, Avendano G, Dharamsey S, Dasmahapatra A, Agarwal R, Reddi A, et al. Left ventricular diastolic function in hypertension and role of plasma glucose and insulin. Comparison with diabetic heart. Circulation 1996;93:1396–402.

18. Rutter MK, Parise H, Benjamin EJ, Levy D, Larson MG, Meigs JB, et al. Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Circulation 2003;107:448–54.

19. Du XJ, Samuel CS, Gao XM, Zhao L, Parry LJ, Tregear GW. Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype. Cardiovasc Res 2003;57:395–404.

Orıgınal Article

Pediatric Surgery

North Clin Istanbul 2015;2(3):182–188 doi: 10.14744/nci.2016.16768

Four-year retrospective look for acute scrotal pathologies Olga Devrim Ayvaz, Aysenur Cerrah Celayir, Serdar Moralioglu, Oktav Bosnali, Osman Zeki Pektas, Ahmet Koray Pelin, Sefik Caman Department of Pediatric Surgery, Zeynep Kamil Obstetrics and Children’s Training and Research Hospital, Istanbul, Turkey

ABSTRACT OBJECTIVE: A group of diseases in the scrotum setting forth by the sudden swelling and redness and pain consist of acute scrotal pathologies. The most common causes of acute scrotum in children are epididymitis, epididymo-orchitis, orchitis, testicular torsion, torsion of the appendix testis, incarcerated inguinal hernia and traumatic hydro/hematocele. In this study; we aim to evaulate patients with acute scrotal pathologies who were interned in our department.

METHODS: All hospital data of cases who were interned at our deparment due to acute scrotum in between June 2010-June 2014 were evaluated retrospectively. Cases with incarcerated inguinal herni were excluded in this study.

RESULTS: In a 4-year-period 114 cases were interned in our department with acute scrotum. Mean age of the patients was 7.6±4.577 years (min: 1m-max: 18yrs). Doppler US was performed in 112 patients to evaluate the blood flow while in 2 patients applied after normal office hours were evaluated without Doppler US and operated under emergency conditions. The patients had received diagnosis of epididymitis/ epididymo-orchitis/ orchitis (n=83 cases; 72.8%), testicular torsion (n=24; 21.1%), torsion of the appendix testis (n=2; 1.8%) with and traumatic hydrocele/ hematocele (n=5; 4.4%). While detorsion was performed in 18 (75%) cases with testicular torsion and orchiectomy in 6 (25%) cases. Histopathological evaluation of orchiectomy specimens revealed hemorrhagic necrosis and hemorrhagic infarction or ischemic changes. Normal testicular size and vascularity were detected in 11 (61.1%) cases with detorsioned testis as detected by follow-up Doppler US. Late orchiectomy was performed in 7 cases (38.9%) with complete atrophy due to lack of blood supply.

CONCLUSION: Although Doppler US is very helpful for differential diagnosis of patients with acute scrotum who applied early period, if Doppler US will lead to a waste of time, direct surgery without delay will dce the risk of testicular loss.

Keywords: Acute scrotum; Doppler ultrasound; testicular loss; testicular torsion.

Received: June 10, 2015 Accepted: January 03, 2016 Online: January 10, 2016 Correspondence: Dr. Olga Devrim Ayvaz. Zeynep Kamil Kadin ve Cocuk Hastaliklari Egitim ve Arastirma Hastanesi, Cocuk Cerrahisi Klinigi, Istanbul, Turkey.

Tel: +90 216 - 391 06 80 e-mail: olga_ozbay@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Ayvaz et al., Four-year retrospective look for acute scrotal pathologies

A

group of diseases in the scrotum setting forth by the sudden swelling and redness and pain consist of acute scrotal pathologies and acute scrotum is a common pediatric surgical emergency. Especially acute scrotum refers to signs and symptoms associated with these local inflammatory conditions [1]. The most common causes of acute scrotum in children are epididymitis, epididymo-orchitis. orchitis, testicular torsion, torsion of the appendix testis, incarcerated inguinal hernia, traumatic hydrocele and hematocele [1].

Testicular torsion was described firstly in 1776 by Hunter [2]. Testicular torsion is defined as a rotation of the testis around the longitudinal axis of the spermatic cord, resulting in obstruction of testicular blood flow, which accounts for 13–54% of acute scrotal disease [3]. Torsion of testis is exactly the most serious condition affecting the scrotum that needs urgent diagnosis and early surgical treatment to save the affected testis and avoid testicular loss and possible fertility problems and medicolegal issues [1].

This study was planned to evaulate the patients with acute scrotal pathology who were hospitalized at our department and to prove the relationship between the prevention of the testicular loss by the early surgical intervention.

MATERIALS AND METHODS This retrospective study was conducted on children with acute scrotal pain and swelling who were referred to our department between June 2010 and June 2014. Patients with incarcerated inguinal hernia were excluded from this study. All medical records of the patients with acute scrotum related to the information about age, symptoms, medical history, time of admission onset of symptoms and surgery, involved side and examination findings, ultrasound (US) and Doppler US findings, initial and definitive diagnosis, medical treatment and/or surgical therapy, fixation of the contralateral testis at the same sesion and follow-up data were analyzed. Time elapsed from the onset of symptoms to the surgery in cases with testicular torsion was determined as the sum of the actual time lost. The real lost time was separated in three groups as 0–6,

183

6–12 and 12 hours and operative findings, histopathologic results of the orchiectomomized testes and follow-up Doppler ultrasonography were compared in these three groups according to this classification of timing. Failure of normal posterior anchoring of the gubernaculum, epididymis and testis is called a bell clapper deformitty because it leaves the testis free to swing and rotate within the tunica vaginalis of the scrotum much like the clapper inside of the bell. Rotation of the testis around the axis of the spermatic cord is called spermatic cord torsion. Data were presented as the mean±standard deviation (SD). Ethics Committee approval was obtained for this study.

RESULTS During the 4-year period, 114 children were hospitalized at our department with acute scrotum. The mean age was 7.6±4.6 years (age range, 1 month to 18 years). Initial diagnoses based on findings of the physical examination and Doppler US were 83 cases as epididymitis, epididymo-orchitis and orchitis in 83 (72.8%), testicular torsion in 24 (21.1%), and traumatic hydrocele/hematocele in 5 (4.4%), and torsion of the appendix testis in 2 (1.8%) cases.

The mean ages were 8.1±4.1 years (min: 1 yr, max: 18 yrs) in children with epididymitis/epididymoorchitis/orchitis was and 7.4±4.6 years (min: 1 yr, max: 13 yrs) in children with traumatic hydrocele/ hematocele, 6 years (min: 5 yrs, max: 7 yrs) in children with torsion of the appendix testis, 6.0±5.8 years (min: 1 m, max: 16 yrs) in children with testicular torsion, 9.3±7.2 years in three newborns with testicular torsion. Etiologic distribution of patients is summarized in Table 1.

Doppler US was performed in 112 patients to evaluate the blood flow while in 2 patients Doppler US could not be performed because they applied after normal office hours. Increased blood flow of the affected testis as detected by Doppler US had been reported to be compatible with testicular orchitis, epididymitis, epididymo-orchitis in 85 cases, while 2 patients had a history of trauma and in 22 patients lack of the blood supply to the testicles was detected on Doppler US. In 5 patients with a history of

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Table 1. Etiology of cases with acute scrotum

detected during the 4 years in our department Etiology

n=114

n

%

Epididymo-orchitis Torsion of testis Torsion of testicular appendix Traumatic causes

83 72.8 24 21.1 2 1.8 5 4.4

Table 2. Pain duration between onset of symptoms and timing of the surgery in our cases with testicular torsion Time interval

≤6 hours 6–12 hours ˃12 hours

Patient numbers (n=24) n

%

8 cases 8 cases 8 cases

33.3 33.3 33.3

trauma, Doppler US results were reported as scrotal hematoma and scrotal hematoma plus varicocele and cellulitis, orchitis and epididymo-orchitis. In 2 of these 5 patients who had been reported to have normal testicular blood flow by Doppler torsion of the appendix testis was observed during the operation and three of these 5 cases had history of scrotal trauma. Testicular torsion secondary to trauma was not detected in any case. Two patients who applied to the hospital after office hours were operated under emergency conditions without prior Doppler examination.

Twenty-six suspect cases with testicular torsion were operated and intraoperative diagnosis of 24 cases were compatible with testicular torsion, while in other 2 patients torsion of the appendix testis was observed. The patients with testicular torsion were operated within the first 6 hours (n=8), between 6–12 hours (n=8), and more than 12 hours (n=8) after onset of the clinical symptoms. Time intervals after the onset of the clinical symptoms are

summarized in Table 2. Patients with epididymoorchitis or traumatic hydrocele, hematocele were not operated. Preoperative diagnosis was made as suspicious testicular torsion according to the physical examination in two cases without Doppler US examination and torsion of the appendix testis was determined during the operation.

Six (25%) testes were found clearly necrotic during the operation and orchiectomy was performed in these cases. Five of these cases were operated more than 12 hours and one case between 6 and 12 hours after onset of the symptoms. Histopathological evaluation of orchiectomy specimens revealed hemorrhagic necrosis (n=4) and hemorrhagic infarction (n=2). Detorsion was made in 18 cases (75%) torsioned testis with a good blood supply.

The bell-clapper anomaly was detected in 6 of these 18 detorsioned cases. Late orchiectomy had been indicated in 3 patients with this anomaly, which had been performed 6 and 12 hours in 2, more than 12 hours after onset of the symptoms. Contralateral orchiopexy also had been made in these 6 patients.

Normal testicular size and vascularity were detected in 18 detorsioned testes by follow-up Doppler US. Perfusion of 11 testes (61.1%) were found to be normal in late follow-ups. Late orchiectomy was performed in 7 cases (38.9%) of 18 due to complete atrophy of testes and lack of blood supply.

Detorsion was made in 18 patients during the operation; 8 cases who had normal perfusion were operated within the first 6 hours, one patient between 6–12 hours and two patients more than 12 hours after onset of symptoms. Totally 13 of 24 patients lost their one testis (63.9%). Relationships between the onset of symptoms and surgical findings are summarized in Table 3.

The final postoperative diagnoses were epididymitis, epididymo-orchitis and orchitis in 83 (72.8%) testicular torsion in 24 (21.1%), torsion of the appendix testis in 2 (1.8%), and traumatic hydrocele/ hematocele in 5 (4.4%) cases.

DISCUSSION Acute scrotum is a common urologic emergency.

The primary objective of management of the acute

Ayvaz et al., Four-year retrospective look for acute scrotal pathologies

185

Table 3. Time intervals between onset of the symptoms and surgery Surgical threrapy

Cases (n=24) Early Orchiectomy (n=6) Detorsioned Testis (n=18) *Normal follow-up with Doppler US (n=11) *Late orchiectomy (n=7)

Time intervals between onset of the symptoms and surgery ≤6h

6–12h

>12h

0 8 8 0

1 7 1 6

5 3 2 1

*Follow-up findings of detorsioned testis; US: Ultrasound.

scrotum is to avoid testiculer loss. This requires a high index of clinical suspicion and prompt surgical intervention of the testicular torsion [4].

In a study with 620 patients who had presented with acute scrotum, 68 of these 620 patients had been underwent surgical exploration. Mean age of patients was 21.9±16.6 years (range, 2 month-95 years) [5]. Our study which was carried out only in the pediatric age group is different from the above research, and patients without symptoms of acute scrotum were excluded from this study (namely patients with hydrocele, undescended testis, varicocele or tumors). Average age of the cases with epididymo-orchitis was found as 7.8 years (1–14 years) in another study [6]. In our study, the mean age of these patients was similar. Torsion of testicular appendage showed a peak incidence between 10 and 12 years of age [7]. But in our study, the mean age of children with torsion of the appendix testis was 6 years (min: 5 yrs, max: 7 yrs). In an another study, mean age of the patients with testis torsion was 10.9 years (newborn-14 years). If 9 newborn patients were excluded, mean age was found to be 7.5 years (ranged 2 months to 14 years old) in 50 children with acute scrotum during the 5-year period [6]. In another study, 18 of the patients had been hospitalized due to testicular torsion whose ages changed between 3 days to 168 months, and the mean age was found as 104.1±73.2 months in that study [8].

In our study, the mean age of the children with testicular torsion was 6.0±5.8 years (min: 1 m -max:

16 yrs). The mean age was 9.3±7.2 days in three newborns with testicular torsion.

Acute scrotum in children has several different etiologies and each etiologic entity shows different symptoms and pathology [7]. The symptoms of epididymitis and orchitis generally arise more slowly than those of testicular torsion. There may be dysuria, indicating a concomitant urinary tract infection.

In these patients with epididymo-orchitis, scrotal ultrasonography reveals hyperemia with increased vascularization, along with enlargement of the epididymis or testis [9]. Another study which analyzed the clinical presentation and physical examination parameters together with the results of imaging studies in order to find out predictors for the differential diagnosis of acute scrotum with special emphasize on testicular torsion had been carried [10].

Although symptoms are very similar, ultrasonographic (especially Doppler US) findings of the epididymo-orchitis and testicular torsion are different.

The clinical approach to the acute scrotum must begin with a standardized and rapidly performed diagnostic evaluation. Doppler ultrasonography currently plays a main role [9]. The ultrasonographic evaluation of testicular perfusion includes both the arterial and the venous flow signals. Demonstration of the central vessels in the testicular parenchyma is important, as perfusion may be preserved in the periphery and the outer coverings of the testis even in the presence of testicular torsion. In a case series including 61 cases of testicular torsion, the criterion

186

of demonstrable central perfusion found could be identified by Doppler US [9].

Doppler US in the initial triage of patients with acute scrotum presenting to the emergency department have been suggested as a routine procedure because it is a highly sensitive preoperative diagnostic tool [5]. Testicular torsion was suspected in 20 patients and confirmed in 18 by preoperative ultrasonography. Doppler ultrasonography had 94% sensitivity, 96% specificity, 95.5% accuracy, 89.4% positive predictive value, and 98% negative predictive value for the diagnosis of testicular torsion in that study [5]. Postoperative diagnoses of 68 cases were testicular malignancy (n=11), hydrocele (n=8), ingunal hernia (n=8), testiculer hematoma (n=5), testicular mass (hematoma or malignancy (n=3), scrotal abscess (n=3), extratesticular tumor (n=3), undescended testis (n=3), orchiepididymitis (n=1), and Fournier gangrene (n=1), scrotal hematoma (n=1), funiculocele (n=1), and testicular torsion (n=20) [5]. In our study, any cases of orchiepididymitis or travmatic acute scrotum did not undergo surgery and in addition all cases with incarcerated inguinal hernia were excluded from this study. Results of the preoperative Doppler US were found to be compatible with peroperative findings in all patients. Only two patients were operated after normal office hours without prior Doppler US examination, because Doppler US is not at our hospital under overtime circumstances.

Doppler ultrasonography for the diagnosis of acute scrotum had been requested from our pediatric surgery departments. But theoretically, testicular perfusion could also be evaluated with magnetic resonance imaging (MRI) or scintigraphy, but these imaging modalities are of little value for the diagnostic assessment of the acute scrotum in routine clinical practice because they are time-consuming, expensive and hard to obtain [7]. In general, these auxiliary methods are not valuable as Doppler ultrasonography in the urgent clinical practice so these are secondary important methods. Besides, there are no facilities like MRI and/or scintigraphy in some hospitals too.

In a study, the diagnosis of orchiepididymitis was confirmed with Doppler US in 22 patients with or-

North Clin Istanbul â&#x20AC;&#x201C; NCI

chiepididymitis and all were treated conservatively [6]. Rates of orchiepididymitis among our patients were found more than some similar studies. Most reseachers have chosen their patients among those who were highly suspected of torsion [1, 2, 6]. Most of the patients (34%) were in the first year of their lives so that the number of their patients with testicular torsion were higher than patients with epididimoorchitis [1]. In another study, epididimoorchitis was detected during scrotal exploration [4]. Diagnosis of orchiepididymitis was confirmed with Doppler US in our patients with orchiepididymitis, and all of them were treated conservatively during that period.

In hydatid torsion, small appendages of testis and epididymis undergo torsion and become ischemic. These appendages are embryologic remnants of the Mullerian and Wolffian ducts [11]. The clinical manifestations in hydatid torsion resemble those of testicular torsion. Hydatid torsion generally treated when symptomatic, with bed rest and application of local cold compress, and if necessery with anti inflammatory drugs [11]. Torsion of appendix testis is rarely diagnosed during the operation. In a study by YapanoÄ&#x;lu et al., one of cases with torsion of appendix testis was diagnosed intraoperatively [8]. Two cases were diagnosed as hydatid torsion peroperatively, because Doppler US examination is not performed on call circumstances at our hospital.

Blunt trauma can cause a hematocele or edema of the scrotum. US and Doppler US are needed to rule out posttraumatic torsion or capsule rupture of the testes [9]. In our cases with traumatic acute scrotum, USâ&#x20AC;&#x2122;s were found to be compatible with hematocele but testicular blood supply was normal in Doppler US. Any surgery was required like rupture of the tunica albuginea of testes in our cases.

In the neonatal period sometimes scrotal hematoma, as a rare complication of adrenal hemorrhage, may mimic testicular torsion and an emergency surgical approach may be required [12]. Seventy percent of neonatal testicular torsions were diagnosed before the birth in the literature, the rest was diagnosed within the first month of life [13].

Anatomical variants such as the bell-clapper anomaly, in which the gubernaculum, testis and

Ayvaz et al., Four-year retrospective look for acute scrotal pathologies

epididymis are not anchored as they normally, predispose to testicular torsion. Failure of normal posterior anchoring of the gubernaculum is called a bell clapper deformitty because it leaves the testis free to swing and rotate within the tunica vaginalis of the scrotum much like the gong (clapper) inside of a bell. Twisting of the testis around the axis of the spermatic cord is called spermatic cord torsion.

Supravaginal torsion is more common in infants, while intravaginal torsion of spermatic cord is the usual variant occurring in adolescence and is much more common overall [9]. In our study, bell-clapper anomaly was detected in 6 patiens during the operation. Contralateral orchiopexy was performed at the same session in these patients. Fixation of the contralateral testis to the scrotum should be scheduled in the same session for the possibilty of the contralateral testis torsion [9]. Our cases of intrauterine testicular torsion were extravaginal torsion, which were similar with the literature [14]. Unfortunately, in most cases the testicles can not be recovered even with appropriate surgical exploration. Testicular salvage rate of 8.96% has been reported in the neonatal testicular torsion. This rate would been increased up to 21.7% in emergency operations [13]. In the early exploration of three cases with intrauterine testis torsion, two of them went to orchiectomy in our study. In follow-ups of one case, testicular blood suply was determined in late Doppler US after the detorsion procedure.

Experimental studies have shown that testicular hemorrhagic infarction begins to appear within 2 hours of onset of testicular torsion, irreversible damage occurs after 6 hours, and complete infarction is established by 24 hours [3]. The apply six hours after pain onset was considered as lateness in presentation. It is known that early presentation and diagnosis and prompt surgical intervention may reverse testiculer ischemia and avert unneccesary orchidectomies. This early diagnosis may involve using Doppler US where diagnosis of testicular torsion is in doubt and facilities are avaible. The diagnosis of using Doppler ultrasound is based on the finding of decreased or absent blood flow on the affected side. On the other hand, delay may lead to progressive, time dependent testiculer damage because

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twisting of the testicle causes venous occlusion and engorgement as well as arterial ischemia, leading to infarction of the testicle. How tightly the testicle is twisted appears to correlate with how quickly the testicle becomes rudimentary from ischemia [15].

Primary orchiectomy should be performed only if the testis is clearly necrotic; in all other cases, the testis should be anchored to the scrotum with two sutures. Having been left in place, the testis can later be reassessed ultrasonographically for reperfusion and potential secondary parenchymal changes [9].

Testicular salvage rates in testicular torsion are 85–97% if operated within 6 hours of onset of symptoms [7]. In a study by Yapanoğlu et al., the authors had applied manual detorsion in 3 of 4 patients with testicular torsion, surgical detorsion in one of them (5.6%) and fixated all of the testes of all patients who came within 12 hours after onset of the symptoms. If the patients came to the hospital 24 hours after onset of symptoms, they proposed orchiectomy and fixation of the other testis. Eigth patients accepted surgery among the 14 (77.8%) children in that sudy [8]. When patients were assessed according to the presence or absence of intermittent testicular torsion symptoms, the ones that had significantly longer times from the onset of symptoms to emergency admission and significantly higher rates of orchiectomy (63% versus 44%) in a study of 6 years’ [16]. Surgical detorsion and salvage were performed in two of those cases who were operated at 36th hours due to incomplete torsion [16].

Orchiectomy was performed in 6 patients and detorsion and orchiopexy was performed in 5 patients; testicular atrophy was detected in 2 of the patients in late follow up in this study [6]. Manuel detorsion were not implemented before the operation in our patients, most pediatric surgeons’s opinion that manual detorsion without surgery may be preferred in adults. In our study, 6 testes were found clearly necrotic during the surgery and orchiectomy was performed in these cases. Five of these cases have been operated in over the 12 hours, and one case had been operated in between 6 and 12 hours. It supports time-depedent testicular damage. Detorsion was made in 18 cases with testicular torsion that was a good blood supply. Normal testicular size

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and vascularity were detected in 18 detorsioned testes by follow-up Doppler US. Perfusion of 11 testes were found normal in late follow-ups. In these 11 cases, 8 of had been operated in first 6 hours, and two patients had been operated in between 6–12 hours, and one patient was operated after 12 hours.

Late orchiectomy was performed in 7 cases of 18 due to complete atrophy of testes and lack of blood supply. The ratio of our patients with late orchiectomy was quite high, we think some came late still had viable testes in the operation findings. Totally 13 of 24 patients were losed their one testes. Our orchiectomy rates were found 54% slightly higher but 16 of 24 patients (66%) had late presentation. Our testicular salvage rates in testicular torsion are 100% if operated within 6 hours of onset of symptoms.

In conclusion, Doppler US is very helpful for differential diagnosis of patients with acute scrotum who applied to the hospital at an early period. Although accuracy of imaging studies is higher for the differential diagnosis of testis torsion and epididmo-orchitis, there is a considerable risk of misdiagnosis. If performing Doppler US will lead to a waste of time, emergency surgery may decrease the risk of testicular loss. Therefore, differential diagnosis of acute scrotum, particularly testicular torsion, still remains a clinical diagnosis and clinical parameters deserve more importance in surgical decision making. Patients with acute scrotum must be evaluated urgently and surgeons should have been performed an urgent testicular exploration when the slightest suspicion arises in terms of a testicular torsion.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Khaleghnejad-Tabari A, Mirshermirani A, Rouzrokh M, Mahmudi M, Baghaiepour MR, Ghaffari P, et al. Early explo-

North Clin Istanbul – NCI ration in the management of acute scrotum in children. Iran J Pediatr 2010;20:466–70.

2. Moslemi MK, Kamalimotlagh S. Evaluation of acute scrotum in our consecutive operated cases: a one-center study. Int J Gen Med 2014;7:75–8.

3. Yang C, Song B, Tan J, Liu X, Wei GH. Testicular torsion in children: a 20-year retrospective study in a single institution. ScientificWorldJournal 2011;11:362–8.

4. Tajchner L, Larkin JO, Bourke MG, Waldron R, Barry K, Eustace PW. Management of the acute scrotum in a district general hospital: 10-year experience. ScientificWorldJournal 2009;9:281–6.

5. Yagil Y, Naroditsky I, Milhem J, Leiba R, Leiderman M, Badaan S, et al. Role of Doppler ultrasonography in the triage of acute scrotum in the emergency department. J Ultrasound Med 2010;29:11–21.

6. Erikci VS, Hoşgör M, Aksoy N, Okur O, Yıldız M, Dursun A, et al. Treatment of acute scrotum in children: 5 years’ experience.

Ulus Travma Acil Cerrahi Derg 2013;19:333–6.

7. Kocaaslan R, Ünlüer SE, Toktaş GM, Erkan E, Küçükpolat S, Demiray M, et al. Torsion of the Testicular Appendix: Case Report. İstanbul Med J 2012;13:36–8.

8. Yapanoglu T, Aydın HR, Adanur Ş, Polat Ö, Demirel A, Okyar G. Our Thirteenth-year Experience with Testicular Torsion in Children. EAJM 2007;39:164–8.

9. Gunther P, Rübben I. The acute scrotum in childhood and adolescence. Dtsch Arztebl Int 2012;109:449–58.

10. Ciftci AO, Senocak ME, Tanyel FC, Büyükpamukçu N. Clinical predictors for differential diagnosis of acute scrotum. Eur J Pediatr Surg 2004;14:333–8.

11. Vasdev N, Chadwick D, Thomas D. The acute pediatric scrotum: presentation, differential diagnosis and management. Curr Urol 2012;6:57,61.

12. Demirel G, Yılmaz Y, Özkan Ulu H, Fitöz S, Erdeve Ö, Dilmen U. A rare presentation of neonatal adrenal hemorrhage: acute scrotum. Çocuk Sağlığı ve Hastalıkları Dergisi 2012;55;32–4.

13. Celik FÇ, Aygün C, Ayçiçek T, Aykanat MA, Ayyıldız S. A newborn with antenatal testis tortion. Turk Pediatri Ars 2014;49:254–6.

14. Serdaroglu E, Takcı Ş, User R, Güçer Ş, Yiğit Ş, Yurdakök M. Intrauterine torsion of testis: a case report. Çocuk Sağlığı ve Hastalıkları Dergisi 2011;54:223–6.

15. Njeze GE. Testicular torsion: needless testicular loss can be prevented. Niger J Clin Pract 2012;15:182–4.

16. Onol FF, Sağlam H, Erdem MR, Köse O, Önol ŞY. Problems In The Diagnosis and Management of Testis Torsion: The Importance of Preoperative Intermittent Testicular Pain. The New Journal of Urology 2011;6:26–30.

Orıgınal Article

Internal medicine

North Clin Istanbul 2015;2(3):189–195 doi: 10.14744/nci.2015.79188

Prognosis of patients in a medical intensive care unit Ali Ugur Unal,1 Osman Kostek,1 Mumtaz Takir,2 Ozge Caklili,1 Mehmet Uzunlulu,1 Aytekin Oguz1 Department of Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey

1

Division of Endocrinology and Department of Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Research

2

Hospital, Istanbul, Turkey

ABSTRACT OBJECTIVE: The aim of this study is to evaluate the demographic characteristics of critically ill patients and to determine intensive care unit (ICU) mortality and its predictors.

METHODS: This study was undertaken in the Istanbul Medeniyet University Göztepe Training and Research Hospital Medical ICU. Between May 2012 and January 2013, 111 patients (53 female, 58 male; mean age, 73.79±14.73, mean length of ICU length stay, 9.1±10.7; prevalence of geriatric patients, 77.5%) were admitted to the ICU. The common indications for ICU admission, prevalence of mechanical ventilation support, hematological and biochemical parameters and their effects on mortality were assessed.

RESULTS: The common indications for ICU admission were hemodynamic instability (48.6%), respiratory failure (27.9%) and sepsis (15.3%). Hypertension (46.8%) was the most common comorbidity. Prevalance rates of heart failure and diabetes mellitus were 32.4% and 25.2% respectively. Mortality rate was 52.3% in all patients. Approximately 80% of all deaths was observed within the first fifteen-day. In additon, mortality rate (85.7%) was prominent within patients in need of the mechanical ventilation support. Mechanical ventilation requirement, increased ferritin and vitamin B12 levels were independent risk factors for mortality in critically ill patients (p<0.01, for all).

CONCLUSION: Mortality rate was higher in medical ICU. Herein, increased prevalence of geriatric population, concomitant comorbidities and mechanical ventilation requirements may play role.

Keywords: Comorbidity; mechanical ventilation; medical intensive care unit; morbidity.

I

ntensive care units (ICUs) are special treatment units managed by specially trained health personnel, and designed for the monitorization, and treatment of life-threatening organ failures which can be seen during the course of acute, and chronic diseases [1]. Most of the patients are monitored while intu-

bated, or in some cases after extubation. Some neurological diseases (Alzheimer, stroke, cerebral palsy etc.), and life-threatening complications of respiratory tract infections, intoxications, and sepsis are frequently monitored in intensive care units [2, 3].

In intensive care units all-cause mortality rates are

Received: January 30, 2015 Accepted: December 29, 2015 Online: December 31, 2015 Correspondence: Dr. Mumtaz Takır. Istanbul Medeniyet Universitesi Goztepe Egitim ve Arastirma Hastanesi, Endokrinoloji ve Metabolizma Klinigi, 34710 Istanbul, Turkey.

Tel: +90 216 - 5709195 e-mail: mumtaztakir@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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higher relative to other services. Age, primary disease, the severity of disease-related complications. can be among causative factors [4]. In addition to these factors the association of mortality with acute phase reactants as C-reactive protein, albumin, and ferritin has been reported [5, 6, 7].

Our aim in this study was to determine demographic characteristics of patients hospitalized in intensive care unit of the department of internal medicine, and also mortality rates, and prognostic parametres on mortality.

MATERIALS AND METHODS Medical files of a total of 111 patients aged >18 years who were hospitalized in intensive care unit of Department of Internal Medicine of Göztepe Training and Research Hospital from the May 2nd, 2012 (inauguration date of ICU) up to January 1st, 2013 were retrospectively examined, and evaluated.

Approval of the ethics committee of our hospital was obtained (decree no: 29/H, date: 12.28. 2012).

Study design: From patient registration forms, information about age, gender, diagnosis at admission to the intensive care unit, length of ICU stay, requirement for, and duration of mechanical ventilation, clinical, and laboratory data, and outcomes of the patients (discharge rate of the patients, and ratio of exited patients) were recorded. Diagnoses of admission were retrieved from patient files, and examined based on their ICD codes. Epicrises were scrutinized in detail, and associated comorbidities (chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, hypertension, chronic renal failure) were recorded. Admision diagnoses of the patients were investigated in consideration of their ICD codes indicated in their medical files. Associated comorbidities indicated in their detailed epicrises (chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, hypertension, chronic renal failure) were recorded. Admission diagnoses were categorized as hemodynamic instability (systolic blood pressure <90 mmHg, heart rate >120/min due to any cause apart from sepsis, acute or chronic respiratory failure. sepsis, and respiratory failure.

North Clin Istanbul – NCI

Laboratory parametres: Data related to whole blood counts, biochemical test results (urea, creatinine, uric acid, sodium, potassium, calcium, phosphorus, AST, ALT, total protein, albumin, CRP, BNP, sedimentation rate, vitamin B12, folat, ferritin, iron, total iron binding capacity, transferrin saturation, INR, procalcitonin) were recorded. In all patients, all-cause mortality rates, diagnosis at admission, length of hospital stay, incidence of comorbidities, number (%) of patients who received invasive mechanical ventilation, hematological, and biochemical data, and their correlations with mortality were evaluated. The patients were categorized as those with duration of hospitalization shorter or longer than 15 days, and compared based on age, indication for hospitalization, presence of comorbidities, requirement for mechanic ventilation, and mortality rates.

Statistical analysis: Statistical analysis was performed using SPSS for Windows V.21.0 program.

Normality of distribution of variables was checked by using Kolmogorov Smirnov test. Continuous variables were expressed as mean±SD. Classifiable data were analyzed using chi-square test, numerical data with Mann-Whitney U test. Independent factors predicting mortality were demonstrated using logistic regression (backward stepwise, LR) test, level of significance, estimated relative risk (odds ratio-OR), and 95% confidence CI) interval. Statistical significance was set at a level of p<0.05 within 95% confidence interval.

RESULTS Mean age of the study participants was 73.79±14.73 years (min-max: 21–93) with a similar gender distribution (p>0.05). Geriatric patients (>65 yaş) consisted 77.5% (n=86) of ICU population. The associated comorbidities in order of decreasing frequency were as follows: hypertension, congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, and chronic renal failure. (Table 1). The patients were most frequently hospitalized in ICU with indications of hemodynamic disorder (48.6%), respiratory failure (27.9%), and sepsis (15.3%). The patients were mostly referred to ICU from inpatient services (79.3%) followed by direct referrals from the emer-

Unal et al., Prognosis of patients in a medical intensive care unit

Table 1. Demographic characteristics, and comorbidities

Age, years (mean±SD) Gender Female Male Comorbidities Hypertension Congestive heart failure Diabetes mellitus Chronic obstructive pulmonary disease Chronic renal failure

n

%

73.79±14.73 53 47.7 58 52.3 52 36 28 17 16

46.8 32.4 25.2 15.3 14.4

191

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

HD instability

IMV (-) IMV (+)

Respiratory failure

Sepsis

45 2 6 9

29

11

Figure 1. Frequency of invasive mechanical ventilation (IMV) use among intensive care unit patients based on their diagnoses of admission.

SD: Standard deviation.

gency service (18.9%), and an external center (1.8%).

All-cause mortality rate among patients hospitalized in ICU was 52.3%, and 79.3% of deaths occurred within the first 15 days of hospitalization.

All-cause mortality rate among patients receiving IMV support was 85.7 percent.

Less than half of the ICU patients (44.1%) required mechanical ventilation. Distribution of these patients according to their indications for hospitalization is given in Figure 1. Most (93.5%) of the patients

with respiratory distress, 64.7% of those with sepsis, and 16.6% of the individuals with hemodynamic instability required invasive mechanical ventilation.

Median duration of hospitalization was 9.1 (min-max: 1–49) days. Some (15.3%) patients were hospitalized for more than 15 days. Hemodynamic instability was more frequently seen in patients hospitalized for more than 15 days (p=0.003), while respiratory failure, and requirement for mechanical ventilation were more often encountered in these patients (p=0.01, and p=0.002, respectively) (Table 2).

Table 2. Factors effective on the length of intensive care unit stay ≤15 days (n=85) >15 days (n=17)

n

Age, year (mean±SD) Hemodynamic instability Respiratory failure Sepsis Chronic obstructive pulmonary disease Diabetes mellitus Congestive heart failure Chronic renal failure Invasive mechanical ventilation Mortality

72.3±14.9 77.3±15.7 0.21 49 57.6 3 17.6 0.003 19 22.4 12 70.6 0.01 14 16.5 2 11.8 0.62 13 15.3 4 23.5 0.4 26 30.6 2 11.8 0.11 32 37.6 4 23.5 0.26 13 15.3 3 17.6 0.8 35 41.2 14 82.4 0.002 46 54.1 12 70.6 0.21

SD: Standard deviation.

%

n

p

%

Mdian length of hospital stay (days)

192

North Clin Istanbul – NCI

p=0.002 6.00 4.00 2.00 0.00

IMV +

IMV IMV support

Figure 2.

Comparison of median lengths of hospital stays in patients who received, and did not receive invasive mechanic ventilation support.

The correlation between IMV, and length of ICU stay is presented in Figure 2. Median duration of hospitalization among patients who received, and did not receive IMV support was 7 (IQR 2–18), and 4 (IQR 2–8) days, respectively. As is seen, IMV support prolonged hospital stay of the patients (p=0.002).

Biochemical, and hematological data of the study participants are given in Table 3. When compared with exited patients, higher serum urea, creatinine, total bilirubin, ferritin, vitamin B12 levels (for all p<0.05), and lower total protein, and albumin levels (for both p<0.05) were detected in survived patients.

Table 3. Biochemical parametres among patients hospitalized in the intensive care unit

Total

Exited patients

Survivors

Mean±SD

Mean±SD

Mean±SD

9.74±1.85 30.2±5.6 203.8±147.7 10.3±2.0 12.6±8.0

9.44±1.7 29.23±5.3 187.39±159.5 10.63±2.5 13.45±9.3

9.98±1.9 30.99±6.0 219.52±114.5 9.93±1.2 11.54±6

>0.05 >0.05 >0.05 >0.05 >0.05

238 95–655 55.32±32.2 12.27±12.7 6.36±4.4

494 116–903 55.95±33.8 14.35±15 6.05±4.7

143 85–259 54.36±29.8 10.26±9.8 7.08±4.4

<0.05

345 182–719 152.9±101.3 102.8±64.7 8.1±11.6 2.1±1.7 139.4±8.8 4.1±0.9 11.1±17.9 61.8±70.9 5.78±30 2.90±0.98 6.35±1.5

505 241–1094 148.08±114 120.47±73 7.47±8.3 2.38±1.8 139.59±10 4.06±0.9 14.26±20 76.38±82.9 5.49±1.03 2.58±0.74 6.06±1

198 139–364 155.90±88.4 77.95±45.9 8.87±15.4 1.56±1.32 139.52±7.5 4.21±0.92 8.27±14.8 49.59±56.5 6.08±0.9 3.20±0.68 6.77±2.06

<0.05

Hemoglobin (n=102) Hemotocrit (n=102) Platelet (n=102) MPV (n=102) Leukocyte (n=102) Ferritin (n=102) Median IQR Sedimentation rate (n=95) CRP (n=111) Folic acid (n=101) Vitamin B12 (n=102) Median IQR Glucose (n=102) Urea (n=110) Uric acid (n=110) Creatinine (n=110) Sodium (n=110) Potassium (n=110) T. bilirubin (n=104) GGT (n=103) Protein (n=98) Albumin (n=99) HbA1c (n=45)

SD: Standard deviation; CRP: C- reactive protein; GGT: Gamma glutamyl transferase.

p

>0.05 >0.05 >0.05

>0.05 <0.05 >0.05 <0.05 >0.05 >0.05 <0.05 >0.05 <0.05 <0.05 >0.05

Unal et al., Prognosis of patients in a medical intensive care unit

193

ROC Curve

Table 4. Factors effecting mortality rates of the ICU

1.0

inpatients

Age Invasive mechanical ventilation Ferritin Vitamin B12

B

OR (95% CI)

p

1.048

1.000–1.098

0.052

18.462 1.002 1.002

4.750–71.760 <0.001 1.000–1.004 0.028 1.001–1.004 0.007

ICU: Intensive care units; OR: Odds ratio.

0.8

Sensitivity

0.6

0.4

Source of the Curve Vitamin B12 Ferritin

Table 5. Vitamin B12, and Ferritin values based on

0.2

Reference line

the

area under ROC curve analysis

0.0

AUC

SE

Vitamin B12 Ferritin

0.732 0.712

0.053 0.053

95% CI

p

0.0

0.2

0.4

0.6

0.8

1.0

Diagonal segments are produced by ties

0.629–0.835 <0.001 0.608–0.815 <0.001

1 - Specificity

Figure 3. Factors effecting mortality rates in the inten-

AUC: Area under the curve.

sive care unit.

Table 6. Cut-off values of vitamin B12, and

Vitamin B12 (≥282 mg/dL) Ferritin (212 mg/dL)

ferritin levels for the prediction of mortality rates

Sensitivity (%)

Specificity (%)

PPD (%)

NPD (%)

Accuracy (%)

74 70.3

70.7 63.4

76.9 71.6

67.4 60.4

72.6 67.3

PPD: Positive cut-off value; NPD: Negative cut-off value.

Independent predictors of mortality were requirement for IMV, higher ferritin, and vitamin B12 levels (Tables 4, 5; Figure 3). The best cut-off value of vitamin B12 was 282 mg/dL which predicted mortality with 74% sensitivity, and 70.7% specificity. On the other hand, the best cut-off value of ferritin was 212 mg/dL which predicted mortality with 70.3% sensitivity, and 63.4% specificity (Table 6).

DISCUSSION In this study, higher all-cause mortality rates in patients hospitalized in intensive care unit were observed which might be attributed to increased

number of geriatric patients consulting to ICUs, associated comorbidities, and frequent need for IMV. Elder patients hospitalized in the intensive care unit constitute privileged, and very complex patient group. Generally elder patients are hospitalized because of acute exacerbations of underlying chronic health problems or multiorgan disorders. As reported in many literature studies 46% of the patients hospitalized in ICUs are elder people [4]. In patients hospitalized in ICU a significant increase in all-cause mortality rates have been observed [8, 9, 10, 11]. In our study, mean age of the patients hospitalized in ICU was 73.9±14.7 years, and 77.5% of all patients were in the geriatric age (>65) group.

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Uysal et al. reported an overall ICU mortality rate of 43 percent [1]. However in our study overall ICU mortality rate was 52.3 percent. In an international multi-centered prospective study (n=15.757) mechanical ventilator had been used in 33% of the cases with a mean duration of 5.9±7.2 days. Besides average ICU mortality rate was reported as 31% among patients who had received mechanical ventilation therapy for more than 12 hours [12]. In our study, mechanical ventilator was used in 44.1% of the patients for a mean period of 12.7±13.5 days, ICU mortality rate among mechanical ventilator users was 85.7 percent.

Altıay et al. performed a study to determine factors related to mortality rates in ICU patients, and observed that presence of arrhytmia, requirement for cardiotonic drugs, need for mechanical ventilation, and its duration had independent effects on all-cause mortality [13]. In our study, we also determined the impact of mechanical ventilation on mortality per se.

Higher ferritin levels may stem from acute phase reactions regulated by cytokines [14]. In a study by Rogers et al. the authors had demonstrated that interleukin-1 (IL-1) accelerates transcription process of ferritin [15]. In our study, higher ferritin values were detected as one of the independent factors which had an impact on mortality rates. Higher ferritin levels may be associated with significant clinical conditions, and from this perspective it can be accepted as a marker of a nonspecific disease Very scarce number of studies have been performed on higher vitamin B12 values. In a study performed by Andrès E et al. the authors indicated that higher vitamin B levels can be paradoxically seen in cases with functional cobalamine insufficiency, and added that its elevated levels can be detected in cases with severe disease states as a diagnostic marker of prognosis at an early stage of the disease [16]. In our study, the patients did not receive vitamin B12 treatment during their ICU stay or previously as disclosed from patient files. Statistically significantly higher vitamin B12 levels were detected in exited patients who had not received vitamin B12 replacement when compared with those survived.

North Clin Istanbul – NCI

While evaluating the outcomes of our study, some limitations should be considered. Relatively lower number of our patient population because of recent inauguration of our intensive care unit, inability to apply prognostic scoring systems as APACHE (Acute Physiology and Chronic Health Evaluation), Glaskow coma, retrospective retrieval of patient data from hospital registration system, and missing information in patient data charts are limitations of our study In conclusion, increased number of geriatric patients, and frequent requirement of IMV might have a role in higher all-cause mortality rates detected in the intensive care unit of the department of internal medicine. In addition, among predictors of mortality, higher vitamin B12, and ferritin levels are remarkable. Therefore, larger-scale studies which will demonstrate the correlation between vitamin B12, and ferritin levels and mortality in critically ill patients should be performed.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Brilli RJ, Spevetz A, Branson RD, Campbell GM, Cohen H, Dasta JF, et al. Critical care delivery in the intensive care unit: defining clinical roles and the best practice model. Crit Care Med 2001;29:2007–19.

2. Tran DD, Groeneveld AB, van der Meulen J, Nauta JJ, Strack van Schijndel RJ, Thijs LG. Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit. Crit Care Med. 1990;18:474–9.

3. Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care 2013;17:R81.

4. Uysal N, Gündoğdu N, Börekçi Ş, Dikensoy Ö, Bayram N, Uyar M, et al. Prognosis of Patients in a Medical Intensive Care Unit of a Tertiary Care Centre. Yoğun Bakım Derg 2010;1:1–5.

5. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000;102:2165–8.

6. Nicholson JP, Wolmarans MR, Park GR. The role of albumin in critical illness. Br J Anaesth 2000;85:599–610.

7. Jehn ML, Guallar E, Clark JM, Couper D, Duncan BB, Ballantyne CM, et al. A prospective study of plasma ferritin level

Unal et al., Prognosis of patients in a medical intensive care unit

and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 2007;165:1047–54.

8. Trivedi TH, Shejale SB, Yeolekar ME. Nosocomial pneumonia in medical intensive care unit. J Assoc Physicians India 2000;48:1070–3.

9. Seferian EG, Afessa B. Adult intensive care unit use at the end of life: a population-based study. Mayo Clin Proc 2006;81:896– 901.

10. Scott BH, Seifert FC, Grimson R, Glass PS. Octogenarians undergoing coronary artery bypass graft surgery: resource utilization, postoperative mortality, and morbidity. J Cardiothorac Vasc Anesth 2005;19:583–8.

11. Ray DC, Drummond GB, Wilkinson E, Beckett GJ. Relationship of admission thyroid function tests to outcome in critical illness. Anaesthesia 1995;50:1022–5.

12. Esteban A, Anzueto A, Frutos F, Alía I, Brochard L, Stewart

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TE,et al. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 2002;287:345–55.

13. Altıay G, Tabakoğlu E., Özdemir L, Tokuç B, Çevirme L, Hatipoğlu ON, et al. Mortality Rates and Related Factors in Respiratory Intensive Care Unit Patients. Toraks Dergisi 2007;8:79–84.

14. Lee MH, Means RT Jr. Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance. Am J Med 1995;98:566–71.

15. Rogers J, Durnowicz G, Kasschau K, Lacroix L, Bridges K. A motif within tha 5’ non-coding regions of acute phase mRna mediates control of ferritin translation by IL-1B and may contribute to the anemia of chronic disease. Blood 1991;78:361.

16. Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM 2013;106:505–15.

Orıgınal Article

General Surgery

North Clin Istanbul 2015;2(3):196–202 doi: 10.14744/nci.2015.10327

Rural surgery in Guinea Bissau: an experience of Doctors Worldwide Turkey Orhan Alimoglu,1 Julide Sagiroglu,1 Tunc Eren,1 Kerem Kinik2 Department of General Surgery, Istanbul Medeniyet University School of Medicine, Istanbul, Turkey

1

Department of Disaster Medicine, Bezm-i Alem University School of Medicine, Vakif Gureba Hospital, Istanbul, Turkey

2

ABSTRACT OBJECTIVE: In Africa, there is critical shortage of surgeons. Majority of the surgeons work in urban centers, and almost none of them is working in the rural areas. This study documents surgical interventions performed in Guinea-Bissau by Doctors Worldwide Turkey.

METHODS: A group of surgeons from the Doctors Worldwide Turkey performed various surgical interventions in the Simao Mendes, Gabu and Bafata community hospitals. Demographics, surgical methods, anesthesia techniques and complications were recorded.

RESULTS: Sixty- four procedures were undertaken between 5–16 February 2010 and 6–11 May 2011. The patient population consisted of 47 male (82.5%) and 10 female (17.5%) patients with a mean age of 44.5 (range: 6–81) years. Five emergency cases were observed. Hartmann’s procedure for rectal carcinoma; modified radical mastectomy for breast carcinoma; 2 right total thyroidectomies, 1 bilateral subtotal thyroidectomy; 2 incisional hernia repairs with mesh, 1 breast lumpectomy, 3 mass excisions, 2 keloidectomies, and various techniques of hernia repair for 35 inguinal hernias (4 bilateral, 3 strangulated and 2 coexisting with hydrocele), Winkelmann’s procedure for 5 hydroceles (1 bilateral), and unilateral orchiectomy for 1 bilateral hydrocele were recorded. Sixteen patients received general (23.5%), 23 spinal (33.8%), 7 epidural (10.3%), 15 local (22.1%), and 7 ketamine (10.3%) anesthesia. There was no mortality.

CONCLUSION: Surgical diseases, majority of which are hernias threaten public health in underdeveloped regions of Africa. Blitz surgery may be an efficient temporary solution.

Keywords: Doctors Worldwide Turkey; Guinea-Bissau; rural surgery.

G

uinea-Bissau is a West African country with a population of 1.7 million and 36.125 km2 surface area where life expectancy is about 50 years (52 for females, 48 for males). Public health act traditionally focuses on disease prevention and major-

ity of financial sources are spent for research and treatment of infectious diseases. During the recent years, public health services have shown remarkable tendency towards improving the quality of services in surgical diseases [1, 2].

Received: August 31, 2015 Accepted: November 22, 2015 Online: December 25, 2015 Correspondence: Dr. Orhan Alimoglu. Istanbul Medeniyet Universitesi Tip Fakultesi, Genel Cerrahi Anabilim Dali, Istanbul, Turkey.

Tel: +90 216 - 280 33 33 e-mail: orhanalimoglu@gmail.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Alimoglu et al., Rural surgery in Guinea Bissau

Trauma, labor and labor-related bleeding are the major causes of mortality as well as chronic diseases. Recent survey in these countries revealed that surgery is an efficient and cost effective way of treatment with the help of collaboration between international organizations, academic institutions, professional societies, humanitarian aid foundations and non-governmental organizations, surgical associations and public health organizations started to co-act on this issue. Thus, surgical diseases are being evaluated as public health problems.

Global Burden of Surgical Disease Working Group was established in 2008 and started to work in order to approach global surgical diseases within the conventional public health perspective [3]. Education of the local medical staff is apparently within these proceedings.

Doctors Worldwide (DWW) Turkey is a nongovernmental organization which was established in 2004 by a group of doctors in Turkey in order to help and medically support people who are deprived of health care services because of war, famine, asylum and natural disasters all around the world.

Doctors Worldwide Turkey expanded their team and domain in time and also started to provide preventive health services, education and help to sustain health systems in rural areas.

Since they were first established, DWW Turkey has brought medical as well as humanitarian aid to suffering communities of more than 40 countries in 4 continents.

Sub-Saharan African countries possess only 2% of the medical aid sources of the world, while suffering from 25% of the disease load of the globe. In the East Africa, there is only 1 surgeon per 400.000 population [4].

Doctors Worldwide (DWW), Republic of Turkey Ministry of Health, Turkish Collaboration and Development Department carried a collaborative act in Guinea Bissau within health screening project in African countries during 2010 and 2011.

This study discusses the impacts of surgical interventions on public health besides suggestions for non-governmental organizations and volunteers supporting rural surgery.

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MATERIALS AND METHODS Surgical interventions performed by a volunteer group of surgeons from the DWW Turkey in Simao Mendes, Gabu and Bafata community hospitals of Guinea-Bissau from 5 to 16 February 2010, and 6 to 11 May 2011 were included in this study.

Demographic features of the patients such as age and gender were recorded. Patients were grouped according to their status as candidates for emergency or elective surgery. Type and status of hernias (recurrent, bilateral, reducible, strangulated, obstructed), localization of masses, preferred surgical and anesthesia techniques as well as postoperative complications were documented.

Results Twenty four patients underwent 27 surgical procedures between 5–16 February 2010 (Table 1).

Variety of surgical interventions with different diagnoses were undertaken on 18 (75%) male and 6 (25%) female patients. Mean age was 43.8 years (range: 7–81 yrs). Two patients were considered for emergency operations. Hartmann’s procedure for locally advanced rectal cancer, modified radical mastectomy for breast cancer, right total thyroidectomy for nodular goitre, and mesh repair for an incisionel hernia were performed. Inguinal hernias of the patients, were bilateral (n=1), and strangulated (n=2) or coexisted with hydrocele. One bilateral Liechtenstein and one left Liechtenstein procedure with right inguinal darn repair were performed for the cases with bilateral inguinal hernia. Two strangulated hernia patients underwent Liechtenstein hernioplasty. Eight hernia patients underwent darn repair, for other hernia patients Liechtenstein hernioplasty (n=1), high ligation (n=1), Bassini repair (n=1), and herniectomy (n=1) were performed.

Synchronous Winkelmann’s procedure was performed for 1 patient who also had darn repair. Also, local excision of a breast mass (n=1), Winkelmann’s hydrocelectomy excision (n=1) of a local cutaneous mass (n=1), and keloid excision (n=1) were carried out. The patients received general (n=12; 17.6%), spinal (n=4; 5.9%), epidural (n=7; 10.3), ketamine (n=1; 1.5%), and local (n=8; 11.8%) anesthesia.

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Table 1. Surgical procedures between 5–16 February 2010 in Guinea-Bissau Date

Gender Age

Diagnosis

Operation

Anesthesia

February 5 M 45 Bilateral inguinal hernia L Liechtenstein Spinal

R darn repair February 5 M 42 L strangulated inguinal Liechtenstein General

hernia (no necrosis) February 8 M 7 R indirect inguinal hernia High ligation General February 8 F 27 R goitre R total thyroidectomy General February 8 M 30 R indirect strangulated hernia Liechtenstein General February 9 M 81 R indirect inguinal hernia Darn repair Spinal February 9 F 26 R submandibular mass Excision Local February 9 F 56 Rectal carcinoma with invasion Hartmann’s procedure General

of vagina and anus February 11 M 19 R inguinal hernia Darn repair Spinal February 11 M 21 Umbilical keloid Excision Local February 11 F 22 Incisionel hernia Mesh repair General February 12 M 45 Bilateral direct inguinal hernia Bilateral Liechtenstein Spinal February 12 F 23 R lateral breast mass Mass excision (benign) Local February 13 M 75 L scrotal hernia Liechtenstein Ilioinguinal blockade,

superficial general February 13 M 67 R hydrocele Winkelmann’s procedure Ilioinguinal blockade,

superficial general February 13 M 60 R direct hernia, L hydrocele Darn repair, Winkelmann’s procedure, Single dose epidural February 15 M 58 R recurrent scrotal hernia Primary repair, Bassini Single dose epidural,

sedation February 15 M 55 R sliding hernia Partial herniectomy, reduction to Ilioinguinal blockade,

abdomen, plication, darn repair superficial general February 15 M 58 L direct hernia Reduction, plication, darn repair Single dose epidural February 15 M 26 R direct hernia Herniectomy, plication, Ilioinguinal blockade,

darn repair superficial general,

epidural February 15 M 73 L indirect scrotal hernia Herniectomy, plication, Epidural, ketamine,

darn repair morphin, superficial

general February 16 M 21 R indirect inguinal hernia Herniectomy, plication, darn repair Epidural, sedation, local February 16 M 70 L indirect inguinal hernia Herniectomy, plication, darn repair Single dose epidural February 16 F 45 Left breast carcinoma MRM General M: Male; F: Female; R: Right; L: Left; MRM: Modified radical mastectomy.

Thirty three patients underwent 37 surgical procedures between 6–11 May 2011 (Table 2). Mean age was 45.1 years (range: 6–80) and there were 29 male (87.9%) and 4 female (12.1%) patients. Three patients underwent emergency operations. Of 19 inguinal hernias, 2 were bilateral and recurrent, 1

was strangulated, and 2 were recurrent. Cases with inguinal hernia (n=15) underwent Liechtenstein procedure (n=1), darn repair (n=1), while pediatric hernia patients underwent high ligation (n=2), and one case with recurrent hernia underwent mesh plug repair. One of the 6 cases with hydrocele was

Alimoglu et al., Rural surgery in Guinea Bissau

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Table 2. Surgical procedures between 6–11 May 2011 in Guinea-Bissau Date

Age (yrs)

Gender

Diagnosis

Operation

May 6, 2011 72 M Bilateral recurrent inguinal hernia Liechtenstein

(R Amyand’s hernia) May 6, 2011 24 M Bilateral recurrent inguinal hernia Darn repair

May 6, 2011 22 M L inguinal hernia Liechtenstein May 7, 2011 68 M R inguinal hernia Liechtenstein May 7, 2011 26 M R inguinal hernia (strangulated) Liechtenstein May 7, 2011 60 M Grynfeltt hernia Mesh repair May 7, 2011 13 M Plastron appendicitis Drainage May 7, 2011 29 M Nodular goitre R lobectomy May 7, 2011 32 F Incisionel hernia+umbilical hernia Mesh repair+primary repair

(Post cesarian section) May 8, 2011 60 M R inguinal hernia Liechtenstein May 8, 2011 60 M R inguinal hernia Liechtenstein May 8, 2011 43 M RLQ cyst Total excision May 8, 2011 14 M Acute appendicitis Appendectomy (Pararectal incision) May 8, 2011 35 F Multi noduler goitre Bilateral subtotal thyroidectomy May 8, 2011 20 M L recurrent inguinal hernia Liechtenstein May 9, 2011 80 M L inguinal hernia Liechtenstein May 9, 2011 60 M L inguinal hernia Liechtenstein May 9, 2011 65 M L inguinal hernia Liechtenstein May 9, 2011 58 M L inguinal hernia Liechtenstein

L hydrocele Winkelmann’s procedure May 9, 2011 70 M R hydrocele R orchiectomy May 10, 2011 30 M L inguinal hernia Liechtenstein May 10, 2011 30 M R recurrent inguinal hernia Mesh plug repair

May 10, 2011 57 M R hydrocele Winkelmann’s procedure

May 10, 2011 70 M R inguinal hernia Liechtenstein May 10, 2011 59 M L hydrocele Winkelmann’s May 10, 2011 80 M Bilateral hydrocele R orchiectomy

L Winkelmann’s procedure May 10, 2011 65 M R inguinal hernia (HIV +) Liechtenstein May 10, 2011 62 F Lipoma Local excision May 10, 2011 65 M R hydrocele Winkelmann’s procedure May 11, 2011 16 F Lower extremity keloid Excision (corticosteroid topical therapy) May 11, 2011 6 M R inguinal hernia High ligation May 11, 2011 9 M R inguinal hernia High ligation

Anesthesia

Spinal Spinal Ketalar Spinal Spinal Spinal Spinal General General Spinal Spinal Spinal Local General General Spinal Spinal Spinal Local Spinal Ketalar Spinal Local Local Ketalar Local Ketalar Spinal Spinal Spinal Spinal Local Spinal Local Ketalar Ketalar

M: Male; F: Female; R: Right; L: Left; RLQ: Right lower quadrant; IM: Intramuscular.

bilateral (underwent unilateral orchiectomy), and 1 coexisted with ipsilateral inguinal hernia (all underwent Winkelmann’s procedure). Multinodular goi-

ter was recorded in 2 patients (bilateral subtotal and unilateral) who underwent total thyroidectomy. Patients received spinal (n=19; 27.9%), general (n=4;

200

5.9%), ketamine (n=6; 8.8%), and local anesthesia (n=7; 10.3%) during the procedures. There was no mortality due to either surgery, or anesthesia.

Discussion People are not born to the same and equal circumstances and opportunities in the world. In some regions of the world, people live well in prosperity using ultimate technology, while in other regions they struggle in poverty. For instance, still today, more than 2 million people are unable to receive surgical treatment. Guinea-Bissau is one of the most underdeveloped and poverty-stricken 25 countries of the world in Africa, with an approximate population of 1.7 million.

Majority of the deaths in Guinea-Bissau are related with surgical diseases where surgical facilities are inaccessible. In order to overcome the handicaps against effective surgical care, strategies which focus on reassuring financial sources and timely surgical interventions should be established [5].

Anesthesiology is provided by advanced technological facilities as well as specialized professional teams in the developed countries. Sophisticated anesthesiology equipments are obviously safer, however, they are costly and their technical maintenance and repair cause additional expenses. Without any doubt, in low income countries such as GuineaBissau, financial sources dedicated for health care are very limited. Managing surgical interventions under local anesthesia when feasible (i. e. hernia, hydrocele), would definitely decrease the expenses for anesthesia [6]. Our surgical operations within these series have been performed under general anesthesia (n=16 patients; 28.1%), spinal anesthesia (n=24; 42.1%), epidural anesthesia (n=5; 8.8%), local anesthesia (n=10; 17.5%), and IM ketalar anesthesia (n=2; 3.5%) without complications.

Sub-Saharan countries of Africa possess only 2% of the medical aid sources of the world, while suffering from 25% of the disease load of the globe.

In East Africa, there is only 1 surgeon per 400.000 population. In some African countries, there is only 1 anesthesiologist per 1 million population. Obviously, in such circumstances, prompt training of

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new nurse anesthesia specialists is mandatory. In addition, in order to promote the suboptimal working environment, health care strategies which allow easy procurement of technical equipments and storage of essential agents such as oxygen, anesthetics and other essential pharmaceutical products must be reinforced by several maneuvers.

Traumatic injuries and obstetric emergencies are major causes of morbidity and mortality which in fact can be readily prevented by surgical interventions. Several lines of evidence documented that surgical circumstances such as injuries, obstetric emergencies and congenital anomalies are serious public health issues [7]. In addition, as it was observed, basic surgical services could be provided at a reasonable margin in countries with low and middle income. In 2004, various subgroups of World Health Organization (WHO) started working on surgical diseases and since 2008 surgical diseases have been considered as a prerequisite for the primary health care services [8]. Majority of the patients in our series had the most commonly seen surgical diseases such as hernia and hydrocele (61.4%: inguinal hernias, 8.7%: hydroceles).

According to WHO 25 physicians per 10.000 of population would be sufficient [9]. World Health Organization suggests 1 general surgeon per 13.250 individuals [10]. This rate is 1:400.000 in Uganda, and 1:2 million in North Somalia. Again, WHO suggests that sufficient primary health care can be provided by 23 health care workers per 100.000 individuals (physician, nurse and delivery nurse), however, this ratio is far lower in most African countries [11, 12]. Moreover, mortality due to anesthesia in some of the African countries is as high as 1:150 [13].

Although, many diseases can be curable and deaths preventable by surgical treatment, surgical diseases have long been considered on an individual basis separate from the global public health issues [14]. This may be due to the fact that surgical diseases are not contagious. Another argument could be that surgeons were often indifferent to public health issues. Finally, surgery comprises of more sophisticated context compared to other medical specialties. Apart from the surgeon, pursuing a surgical procedure necessitates an anesthesiology specialist,

Alimoglu et al., Rural surgery in Guinea Bissau

an operating room, sterilization facilities, surgical instruments, postoperative care and blood bank for selected cases. Moreover, traffic accidents, work-related accidents (agriculture workers), peritonitis, fractures and blindness are other remarkable surgical challenges and in fact, they are often curable. In the underdeveloped countries, surgical services are mostly accessible only in the urban areas and in contrast to the infectious diseases, achieving surgical services is even easier when the patient meets the expenses.

Blitz surgery focuses on specific fields and it is an efficient model for aid campaigns. Usual duration of this service is less than 3 weeks. Blitz surgery is an efficient service mostly brought by non-governmental organizations from wealthy to underdeveloped countries and predominantly deals with the patients of reconstructive surgery [12]. The focus is often on the treatment of particular group of diseases (cleft lip-palate) instead of training local surgeons.

This results with the continuing dependency of the mentioned countries on developed ones as well as unsolved difficulties in preoperative and especially postoperative patient care. Tendency towards completing multiple operations within a limited period may obviously downscale the surgical quality. Furthermore, surgeons may have to operate the patients with diseases unrelated to their specialty fields and assistant surgeons may have to operate by themselves. However, in spite of all limitations, blitz surgery is an efficient temporary solution. Inviting the local African surgeons to the developed countries for training for certain periods will improve the quality of surgical services when they return home.

Another solution might be supporting the reverse brain drain of the African surgeons who had immigrated to developed countries [15].

Establishing long-term collaboration between hospitals of developed and underdeveloped countries would lead to gradual and permanent improvement of the health care services. Experience share by periodical physician exchange not only provides a â&#x20AC;&#x2DC;boot campâ&#x20AC;&#x2122; for the less trained, but offers an occasion for the more sophisticated surgeons to selfcriticize and also deliver qualified surgical services to the communities in poverty as well [16]. In addition, this also helps to improve constitutional problems of

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the hospitals. Operating rooms, sterilization units, postoperative care units, blood banks, anesthesia equipments and laboratories should be promoted.

Working in rural areas where all facilities are limited or even sometimes completely absent, ironically brings acquirements in multiple aspects, both to the visiting surgeon(s) and the local team, as well as the rural community. Visiting surgeon develops new skills in order to work in restricted circumstances, while the local surgeon learns new techniques and procedures; finally, the most important achievement will be delivering solutions for the diseases of the local community [17]. Even a single complication which is not well-managed can overshade thousands of masterpiece operations. In order to prevent complications, surgical cases must be well planned in terms of procedures, teams and instrumentation and strenuous cases should not be rushed. Good communication with the local physicians must be maintained and they must be encouraged to take part in the operations.

During the patient follow-up, local physicians must be taught to take full responsibility. Visiting surgeons must be aware of the skills of the medical team and prefer surgical techniques suitable for the rural area. Minimally invasive procedures, which would require relatively shorter follow-up periods must be preferred if possible, and emphasis must be placed on the quality of the surgeries rather than their quantity. Pursuing any commercial competition with other relief organizations must be avoided during such services. Commitment to a continuous mission with preferably same workforce has a paramount importance. Ongoing collaboration with the local team, periodic calibration of all equipment and supplies, regular patient follow-ups also have utmost importance in restoring sustainable health care in the rural areas.

To sum up, surgical services in underdeveloped regions of the world can be improved with continuous and committed collaboration of the workforces.

Blitz surgery is an efficient way to start with.

Acknowledgements We thank all the health workers in Simao Mendes,

202

Gabu and Bafata community hospitals for their great effort and hospitality in this team work.

Conflict of Interest: No conflict of interest was declared by the authors.

Funding Resources: Doctors Worldwide (DWW), Republic of Turkey Ministry of Health, Turkish Collaboration and Development Department carried a collaborative act in the financial support of this project.

REFERENCES 1. Farmer PE, Kim JY. Surgery and global health: a view from beyond the OR. World J Surg 2008;32:533–6.

2. Assessment of medicines regulatory systems in sub-Saharan African countries: An overview of findings from 26 assessment reports. World Health Organization 11.12.2010.

3. Perkins RS, Casey KM, McQueen KA. Addressing the global burden of surgical disease: proceedings from the 2nd annual symposium at the American College of Surgeons World J Surg 2010;34:371–3.

4. Ozgediz D, Riviello R. The “other” neglected diseases in global public health: surgical conditions in sub-Saharan Africa. PLoS Med 2008;5:e121.

5. Grimes CE, Law RS, Borgstein ES, Mkandawire NC, Lavy CB. Systematic review of met and unmet need of surgical disease in rural sub-Saharan Africa. World J Surg 2012;36:8–23.

6. Irabor DO. Hernia repair under local or intravenous Ketamine in a tropical low socio-economic population. West Afr J Med 2005;24:143–6.

7. Chu K, Maine R, Trelles M. Cesarean section surgical site infec-

North Clin Istanbul – NCI tions in sub-Saharan Africa: a multi-country study from Medecins Sans Frontieres. World J Surg 2015;39:350–5.

8. Chirdan LB, Ameh EA. Untreated surgical conditions: time for global action. Lancet 2012;380:1040–1.

9. Drain PK, Primack A, Hunt DD, Fawzi WW, Holmes KK, Gardner P. Global health in medical education: a call for more training and opportunities. Acad Med 2007;82:226–30.

10. Global Initiative for Emergency and Essential Surgical Care (GIEESC). World Health Organization (2012) http://www. who.int/surgery/globalinitiative/en/.

11. Luboga S, Macfarlane SB, von Schreeb J, Kruk ME, Cherian MN, Bergström S, et al. Increasing access to surgical services in sub-saharan Africa: priorities for national and international agencies recommended by the Bellagio Essential Surgery Group.

PLoS Med 2009;6:e1000200.

12. Nthumba PM. “Blitz surgery”: redefining surgical needs, training, and practice in sub-Saharan Africa. World J Surg 2010;34:433–7.

13. Pollach G. Anaesthetic-related mortality in sub-Saharan Africa.

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14. Tomlinson J, Haac B, Kadyaudzu C, Samuel JC, Campbell EL, Lee CN, et al. The burden of surgical diseases on critical care services at a tertiary hospital in sub-Saharan Africa. Trop Doct 2013;43:27–9.

15. Ncayiyana D. Doctor migration is a universal phenomenon. S Afr Med J 1999;89:1107.

16. Chen L, Evans T, Anand S, Boufford JI, Brown H, Chowdhury M, et al. Human resources for health: overcoming the crisis. Lancet 2004;364:1984–90.

17. Pollock JD, Love TP, Steffes BC, Thompson DC, Mellinger J, Haisch C. Is it possible to train surgeons for rural Africa?

A report of a successful international program. World J Surg 2011;35:493–9.

Orıgınal Article

Gynecology&Obstetrics

North Clin Istanbul 2015;2(3):203–209 doi: 10.14744/nci.2015.55376

TORCH seroprevalence among patients attending Obstetric Care Clinic of Haydarpasa Training and Research Hospital affiliated to Association of Istanbul Northern Anatolia Public Hospitals Onur Numan, Fisun Vural, Nurettin Aka, Murat Alpay, Ayse Deniz Erturk Coskun Department of Obstetrics and Gynaecology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey

ABSTRACT OBJECTIVE: Toxoplasma gondii, Rubella, Cytomegalovirus and Herpes simplex viruses are microorganisms that cause congenital infections and they are called briefly as TORCH. There is an ongoing argument for the screening of reproductive age women due to the high cost of tests. For a test to be used in screening, prevalence of disease in this population should be known. The aim of this study was to investigate TORCH seroprevalence among women attending a teaching hospital in Istanbul.

METHODS: A total of 1101 patients attending outpatient clinic of Obstetric Care Clinic of Haydarpasa Training and Research Hospital affiliated to Association of Istanbul Northern Anatolia Public Hospitals between September 2013 to January 2015 and their laboratory data were evaluated retrospectively. We investigated Ig G and M seropositivity rates against TORCH. RESULTS: The age of the patients ranged between 17–47 years with a mean age of 30.3±5.8 years. Pregnant population had 99.5% anti-CMV Ig G (+), 94.2% anti-Rubella Ig G (+), 31% anti-Toxoplasma Ig G (+). Seroprevalence for Anti IgM was 0.5% for CMV, 0.2% for rubella.

CONCLUSION: The screening for Toxoplasma gondii may be suggested since the prevalence is not high in our population. The screening of CMV is not meaningful, due to high seroprevalence. Although seroprevalence of rubella is also high, it may be suggested for preconception vaccination especially in women above 20 years of age born prior to National Vaccination Programme.

Keywords: CMV; pregnancy; rubella; screening tests; TORCH; toxoplasma.

P

redominantly members of the TORCH complex microorganisms including Toxoplasma gondii, Rubella and Cytomegalovirus (CMV) many

infectious agents lead to the development of a maternal infection and may enter into intrauterine circulation at any gestational age. They sometimes

Received: March 23, 2015 Accepted: December 08, 2015 Online: December 25, 2015 Correspondence: Dr. Fisun Vural. Haydarpasa Numune Egitim ve Arastirma Hastanesi, Kadin Hastalikları ve Dogum Klinigi, Istanbul, Turkey.

Tel: +90 216 - 542 32 32 e-mail: fisunvural@yahoo.com.tr © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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lead an asymptomatic course, on the other hand they may encounter us with bad prognosis including miscarriages, sterility, congenital malformations and intrauterine fetal loss [1]. When all the cases were evaluated incidence of intrauterine growth retardation secondary to infectious agents was reported as nearly 5 percent. Prenatal infections have been held responsible from generally 2–3% of all congenital anomalies [1, 2].

Toxoplasma gondii is an intracellular protozoa an agent of parasitic infection known as toxoplasmosis.

The spectrum of congenital infection extends from asymptomatic findings up to intrauterine fetal loss and may include chorioretinitis, hearing sequelae, hydrocephalus, mental and psychomotor disorders [3]. As gestational weeks progress, risk of vertical transfer increases and the risk of infection leading to more serious malformations decreases [4]. CMV, is a member of the Herpes viridae species, having deoxyribonucleic acid encased in a nuclear envelope and may remain as a latent microorganism inside host cells. It can affect 0.5–1% of all live births and it is the most frequently seen agent of congenital viral infections which may lead to sensorineural deafness and mental retardation [5]. Rubella virus is a single-strand RNA virus and it is the infectious agent of rubella (German measles). In 20–50% of the patients who have this infection, it leads an asymptomatic course. In adults and children the disease manifests itself with adenopathy and severe febrile rashes [6]. The risk of fetal infection is at its highest level during the first 11 week and after the 36. week of gestation [2]. If primary infection is contracted within the first three months, probability of onset of “Congenital Rubella Syndrome (CRS)” is increased [6].

The importance of prenatal care is undebatable in fetal life and neonatal development Detection of TORCH group of infections which cause a very wide spectrum of damages and gestational complications carries importance. However, necessity of screening of these infectious agents during pregnancy is a debatable issue. The decision to include TORCH group of microorganisms in antenatal screening programs in a certain geographic region may be based on seroprevalence studies conducted

North Clin Istanbul – NCI

at this region. Possible use of a test as a screening test can be decided after regional prevalence studies and evaluations of cost analysis performed by health policy makers, public health specialists and perinatologists [7]. For example, in the United Kingdom surveys are not performed in many regions [8]. In France, screening for Toxoplasma gondii is a must [9, 10]. However, in our country a complete consensus does not exist on this issue [1, 7, 11]. In this study, the seroprevalence of TORCH group of infectious agents among patients who attended to the Obstetric Care Clinic of Haydarpasa Training and Research Hospital affiliated to Association of Istanbul Northern Anatolia Public Hospitals was evaluated and its use as a screening test was evaluated in the light of the literature.

MATERIALS AND METHODS This study was performed on 1101 ambulatory patients who consulted to the Obstetric Care Clinic of Haydarpasa Training and Research Hospital affiliated to Association of Istanbul Northern Anatolia Public Hospitals between September 2013 and January 2015. Hospital files of the patients were retrospectively reviewed, from computer database serologic data of TORCH group of infections were retrieved. Toxoplasma gondii, CMV, Rubella Ig G and Ig M antibodies were analyzed using ELISA method.

RESULTS Ages of the patients included in the study ranged between 17 and 47 years and mean age of the pregnants was 30.3±5.8 years.

Seroprevalence of TORCH In the study, population Ig G positivities for CMV Ig G (99.5%), rubella (94.2%) and Toxo (31%) were detected in respective percentages of patients. The corresponding Ig M positivities for CMV and rubella were 0.5, and 0.2%, respectively. Toxoplasma Ig M positivity was not detected in any patient. A total of 749 (69%) patients were seronegative for toxoplasma. A total of 64 patients were rubella Ig

Numan et al., TORCH seroprevalence among pregnant women

205

120 100

14

99.5

10

80

8.4%

8

60

6

40

31

4

20 0

12%

12

94.2

3.2%

2 CMV

Rubella

0

Toxo

Figure 1.

17–25 years

Figure 2.

TORCH prevalence rates of the pregnants.

(The percentage of seropositivity of pregnant women)

26–35 years

36–47 years

Rubella IgG seronegativity in various age

groups.

G seronegative, while 2 of them were also IgM positive. Serologic analysis of these two patients were performed during the last trimester without causing any problems to the pregnant women and their babies. Serologic tests of 4 patients with CMV Ig M positivity were performed during the second trimester without causing any problem among babies born. Accordingly in 5.8% of our study population rubella seronegativity was detected. Details are given in Figure 1, and Table 1. Figure 1 presents TORCH IgG seropositivity among pregnant women.

Distribution of rubella seronegativities In our country within the context of national vacination program, rubella vaccines are administered.

Therefore, seropositivities were evaluated based on age groups of the patients. The patients were divided into 17–25, 26–35 and 36–44 age brackets, and re-evaluated as for Rubella Ig G according to these

age groups. Accordingly, rubella Ig G seronegativities differed among age groups of 17–25 (3.2%), 26–35 (8.4%) and 36–47 (12%) as indicated. Figure 2 presents the seronegativity of Rubella IgG in various age groups. Prevalence of seronegativity increased with age without any statistically significant difference between age groups (p>0.05). National vaccination program was started in the year 1995.

Seronegativity was not detected in cases younger than 20 years of age.

Discussion Serologic screening tests directed at agents of maternal Rubella, CMV and Toxoplasma gondii infections carry importance so as to prevent related malformations and other worse neonatal outcomes.

Prevalence rates obtained as a result of screening tests aimed to detect infectious agents of the dis-

Table 1. Seroprevalence rates for TORCH Ig G, and IgM in pregnant women

Positive (n) Negative (n) Total Positive (%) Negative (%)

CMV Ig M

CMV Ig G

Rubella Ig G

4 899 881 5 885 904 0.5 99.5 99.5 0.5

CMV: Cytomegalovirus; TOXO: Toxoplasma.

Rubella Ig M

TOXO Ig G

TOXO Ig M

1037 2 336 0 64 891 749 1068 1101 893 1085 1068 94.2 0.2 31 0 5.8 99.7 69 100

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Table 2. The summary of the some TORCH studies in Turkey City

Authors

Denizli Karabulut et al. [11] Kocaeli Tamer et al. [16] Edirne Varol et al. [18] Artvin Inci et al. [17] Hatay Ocak et al. [14] Malatya Dogan et al. [12] Afyon Yilmazer et al. [19] Mardin Tekin et al. [28] Van Karakas et al. [27] Samsun Uyar et al. [26] Sanliurfa Tekay et al. [13] Ankara Oruc et al. [32] Istanbul Polat et al. [24] Istanbul Selek et al. [25] Istanbul Our study

Toksoplazma (%) Rubella (%) IgM + 1.4 0.4 0.9 1.3 0.54 – – 4.6 – – 3 – 0.7 0.7 0

IgG +

IgM +

IgG +

CMV (%) IgM +

IgG +

37 0 95.1 1.2 98.7 48.3 0.2 96.1 0.7 96.4 31.9 0.7 76.6 1.3 80.3 30.3 0.3 95.2 1.6 98.6 52 0.54 95 0.4 94.9 37.5 – – – – 30.7 – 95.1 – 92.6 17.5 0.95 76.5 – – – 4.8 95.2 – – – 1.7 94.3 1 97.3 69.5 – – – – – – – 0.3 98.5 48 24 – – – – 31 0.2 94.2 0.5 99.5

CMV: Cytomegalovirus.

eases included in the TORCH group can change from region to region based on geographical, socioeconomic and cultural values [7, 11]. In this study, TORCH seroprevalence rates of the patients who consulted to Obstetric Care Clinic of Haydarpasa Training and Research Hospital affiliated to Association of Istanbul Northern Anatolia Public Hospitals were investigated.

Considering the applicability of screening tests in every pregnant woman, its potential cost and necessity of performing these tests are evaluated in combination. Every country can plan its antibody screening test to be performed against infection agent(s) based on national prevalence values [7]. For instance, in a study performed in the United Kingdom which lasted for 10 years, because of fetal findings detected with detailed investigations, the health authorities have concluded that all TORCH screening tests in maternal serum should not be performed in every case. Thus in UK, based on expert comments this screening test can be limited for the investigation of only CMV seropositivity [8]. In a similar study in

Japan, it was reported that serologic screening tests for TORCH have not any significance apart from CMV screening in cases with fetal growth retardation [2]. In France and Austria, toxoplasma screening test is a legal necessity. In France, prevalence of congenital toxoplasmosis is 3.3 for every 10,000 live births, while prevalence of symptomatic infection is 0.34 for every 10.000 live births [9, 10].

Clinical manifestations of mild disease emerging after Toxoplasma gondii infection are generally characterized by fever, lassitude and lymphadenopathy.

However, congenital infections can lead to pregnancy losses and serious diseases in the newborn as mental retardation, blindness and epilepsy [10]. Infection contracted during early stage of pregnancy has a risk of transmittance to the fetus less than 6%, while during the third trimester this risk ranges between 60, and 81 percent. On the other hand, during embryogenesis vertical transfer of Toxoplasma gondii is rarely seen, an infection contracted during this period exerts more serious effects on fetus. On the contrary, babies born to mothers who contracted an infection during

Numan et al., TORCH seroprevalence among pregnant women

the third trimester are usually asymptomatic [9, 10].

In parallel with cultural eating habits and socioeconomic status of the countries, the results of the seroprevalence studies for Toxoplasma gondii demonstrate variations in the world. In France where consumption of underdone red meat is prevalent 71% seropositivity rates were detected. However in UK seropositivity rates are lower ranging between 7.7, and 9.1 percent [8, 9, 10]. When other studies on TORCH seroprevalence are taken into consideration, seroprevalence rates for Toxoplasma gondii vary between 30 and 69.5 percent [11, 12]. Table 2 presents the summary of TORCH studies in Turkey. In our study, anti-toxoplasma Ig G seropositivity was detected as 31% which is consistent with most of the studies performed in Turkey [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28]. Cultural differences between regions, rich and variable cuisine culture in Turkey also reflect on this type of studies. In studies conducted in Southeastern Anatolia Region and neighbouring provincences Toxoplasma gondii seropositivity were higher and ranged between 48.4 and 69.5 percent [7, 13, 14, 15, 16, 17]. In studies conducted in Turkey, higher toxoplasmosis seroprevalence rates were detected in Urfa (69.5%; Tekay et al.), Sivas (52.2%; Duran et al.), Hatay (52.1%; Ocak et al.), AdÄąyaman (48.4%; Kogeliler et al.), and Kocaeli (48.3%, Tamer et al. [7, 13, 14, 15, 16]. Lower seropositivity rates were detected in studies performed in other provinces. Toxoplasma Ig G positivity rates in different provinces were observed as follows: Artvin (30.3%; Inci et al.), Edirne (30%; Varol et al.), Afyon (30.7%; Yilmazer et al.)

Denizli (37%; Karabulut et al.), Erzurum (24%; Yigit et al.), Diyarbakir (32.9%; Gul et al.), Elazig (41%; Asci et al.), and Van (41%; Efe et al.) [11, 17, 18, 19, 20, 21, 22, 23]. Previous seroprevalence studies performed in Metropolitan City of Istanbul, toxoplasma Ig G seropositivities were detected as 43% by Polat et al. and 21% by Selek et al. in a more recent study [24, 25]. Excluding provinces of Southeastern Anatolia, seroprevalence of toxoplasma changes between 30 and 43 percent. However, in pilot studies performed in various times in the same province, different results have been obtained. It is important to detect seronegative women especially in regions

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with higher seroprevalence rates, training people so as to ensure consumption of vegetables and fruits after vigorous washing, popularization of the habit of hand washing and refraining from intake of raw or rare cooked meat carry importance as for prevention of maternal and fetal infections. Our study results are consistent with those of the studies performed in our country excluding Southeastern Anatolia region where the toxoplasma seropositivity ranges between 30 and 43 percent. Because of lower seropositivity rates, especially during pregnancy screening for toxoplasma can be recommended. However, studies concerning its cost-effectiveness should be conducted.

Rubella courses with mild degree of rashes and fever in childhood, when it is experienced in the first months of pregnancy, it can lead to pregnancy losses and stillbirths and during the neonatal period it may result in â&#x20AC;&#x153;Congenital Rubella Syndromeâ&#x20AC;? (CRS) [1, 2, 3]. For the possible prevention of vertical transmittance from mother to the fetus, seronegative women should be detected during preconceptional period, and their pregnancies should be planned, and postponed after immunization. In Turkey rubella vaccination program was implemented firstly in the year 1995, and in the year 2006 it was introduced into National Vaccination Calender [1, 7]. National Vaccination Calender determined by Public Health Agency of Turkey, TR Ministry of Health and Social Welfare in the year 2014 Measles-Rubella-Mumps (MMR) vaccine is administered as a single dose within the first 12 month of life, and booster dose is injected in the first grade of the primary school.

When other seroprevalence studies performed in the world are taken into consideration seropositivity rates for rubella virus were reported as 87% in The United States of America (USA), 98% in Spain and 96.3% in Iran [10, 11]. In our study, seropositivity rates for rubella was detected as 94.2% which demonstrates similarities with the results of other relevant studies. Higher seropositivity rates were detected in Denizli (95.1%; Karabulut et al.)

[11], Samsun (94.3%) [26], Hatay (95%) [15], Van (99.5%) [27], and Kocaeli (96.1%) [16]. Besides, similar rubella seropositivity rates were observed in other regions. Rubella Ig G seropositivity rates were 76.5%, and 76.6% in Mardin [28], and Edirne

208

[18], respectively. These data are important in that they give an idea about whether national vaccination programs have achieved their goals and implemented all over the population, their acceptability by every section of the community and tracking the success of vaccination programs. In our study, we detected that none of 62 patients had ever encountered rubella virus and hadn’t developed immunity against the disease. Besides, in our study population, after implementation of our national vaccination program in pregnants aged 20 years and younger, rubella seronegativity was not detected. When national data obtained were evaluated globally, higher prevalence of rubella seropositivity was detected.

These data have suggested us that even though lower rubella seronegativity rates were noted, it will be appropriate to screen and immunize women over 20 years of age during preconceptional period.

CMV is the most frequently encountered congenital infection agent and apart from Toxoplasma gondii and Rubella it may emerge as a primary infection or demonstrate recurrences [29]. Therefore, maternal serologic tests may not rule out a new strain of CMV or reactivation of latent maternal infection and congenital infection. Risk of vertical transmittance after primary infection ranges between 30, and 40%, and it emerges after a secondary infection at a rate of 1 percent [29, 30, 31]. Therefore, in pregnant women routine screening tests for CMV is debatable and American College of Obstetrician and Gynecologists (ACOG) does not recommend screening tests for CMV infection [31]. CMV infections are frequently seen in communal life conditions and populations with lower socioeconomic level. In populations with higher seropositivity rates routine screening tests for CMV may not be recommended. Indeed, an effective treatment modality for congenital CMV infection has not been definitively established yet and this test is costly, and clinically useless. In developed countries, CMV seroprevalence is lower, while in developing countries it has a higher seroprevalence. Seropositivity rates were 46.8% in France, 56.8% in Australia, 56.3% in Finland, 78% in Russia, 92.1% in Saudi Arabia and 100% in Thailand [29, 30]. In studies performed in Turkey CMV seropositivity rates were detected as

North Clin Istanbul – NCI

92.6% in Afyon [19], 98.5% in Ankara [32], 97.3% in Samsun [26], 98.6% in Artvin [17], 96.4% in Kocaeli [16], and 98.7% in Denizli [1, 9, 11]. However, in our study CMV seroprevalence was detected as 99.5% which is one of the highest seropositivity rates. This CMV seroprevalence rates demonstrate parallelism with the relevant results of developed and developing countries. When these findings and seroprevalence rates of our country are taken into consideration, we think that CMV screening during pregnancy is not a necessary application.

In conclusion, seroprevalence of TORCH demonstrates changes among countries or even between regions in the same geographic location. When data of our study and relevant available studies performed in our country are investigated, increased CMV and seropositivity is detected. Because of its higher seropositivity, screening for CMV is not cost-effective and so it should not be recommended.

If national vaccination program can be applied fully, then rubella screening tests during pregnancies of women born after the year 1995 will be useless.

However, for the time being, if possible it will be appropriate to perform rubella screening tests during preconceptional period and in women over 20 years of age in addition to vaccination of women against rubella before becoming pregnant. Although seroprevalence of toxoplasmaosis changes among regions, since its treatment is possible at the time of diagnosis and its higher seroprevalence (30–43%) outside the risky regions, it may be presumably included in antenatal screening programs. We think that perinatologists, public health specialists and health policy makers should work in collaboration and cost-effectiveness of the screening for TORCH group of diseases (if any) should be reviewed.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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12. Dogan K, Kafkaslı A, Karaman U, Atambay M, Karaoğlu L, Colak C. The rates of seropositivity and seroconversion of toxoplasma infection in pregnant women. Mikrobiyol Bul 2012;46:290–4.

13. Tekay F, Ozbek E. The seroprevalence of Toxoplasma gondii in women from Sanliurfa, a province with a high raw meatball consumption. Turkiye Parazitol Derg 2007;31:176–9.

14. Ocak S, Zeteroglu S, Ozer C, Dolapcioglu K, Gungoren A. Seroprevalence of Toxoplasma gondii, rubella and cytomegalovirus among pregnant women in southern Turkey. Scand J Infect Dis 2007;39:231–4.

15. Kolgelier S, Demiraslan H, Kataş B, Guler D. Seroprevalence of Toxoplasma gondii in Pregnant Women. Dicle Tıp Derg 2009;36:170–2.

16. Tamer GS, Dundar D, Caliskan E. Seroprevalence of Toxoplasma gondii, rubella and cytomegalovirus among pregnant women in western region of Turkey. Clin Invest Med 2009;32:43–7.

17. Inci A, Yener C, Güven D. The investigation of toxoplasma, rubella and cytomegalovirus seroprevalancies in pregnant women in a state hospital. Pam Med J 2014;7:143–6.

209 18. Varol FG, Sayin NC, Soysuren S. Seroprevalance of toxoplasma gondii antibodies in antenatal population of Trakya region. J Turk Soc Obstet Gynecol 2011;8:93–9.

19. Yilmazer M, Altindis M, Cevrioglu S, Fenkci V, Aktepe O, Sirthan E. Toxoplasma, Cytomegalovirus, Rubella, Hepatitis B and Hepatitis C Seropositivity Rates in Pregnant Women Who Live in Afyon Region. Kocatepe Tıp Derg 2004;2:49–53.

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23. Efe S, Kurdoğlu Z, Korkmaz G. Van yöresindeki gebelerde Sitomegalovirüs, Rubella ve Toksoplazma antikorlarının seroprevalansı.

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Gebe kadınlarda toxoplasma gondii Ig M ve Ig G antikorlarının ELISA yöntemi ile araştırılması. T Parazitol Derg 2002; 26:350– 1.

25. Selek MB, Bektöre B, Baylan O, Özyurt M. Serological Investigation of Toxoplasma gondii on Pregnant Women and Toxoplasmosis Suspected Patients Between 2012-2014 Years on a Tertiary Training Hospital. Turkiye Parazitol Derg 2015;39:200–4.

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28. Tekin A, Deveci Ö, Yula E. The seroprevalence of antibodies against Toxoplasma gondii and Rubella virus among childbearing age women in Mardin province. J Clin Exp Invest 2010;1:81–5.

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Orıgınal Article

General Surgery

North Clin Istanbul 2015;2(3):210–214 doi: 10.14744/nci.2015.50479

Causes of asymptomatic trocar site hernia: How can it be prevented?

Oguzhan Dincel,1 Fatih Basak,2 Mustafa Goksu1 Department of General Surgery, Adiyaman University Faculty of Medicine, Adiyaman, Turkey

1

Department of General Surgery, Umraniye Training and Research Hospital, Istanbul, Turkey

2

ABSTRACT OBJECTIVE: The aim of this study is to evalute risk factors which trigger the development of trocar site hernia after elective laparoscopic cholecystectomy operation and to discuss what needs to be done to prevent it.

METHODS: Patients operated with laparoscopic cholecystectomy between 2011 and 2013 were evaluated. Patients were called back for follow-up visit at 12 month after operation. Physical and ultrasonographic examinations were performed at follow-up. Factors that facilitate development of trocar site hernia were investigated.

RESULTS: One hundred and ninty patients were operated during the study period. One hundred and thirty-two patients who had been examined at follow-up period were included in the study. Mean age of the patients was 50.64±11.86 (18–76) years and female /male ratio was five. Trocar site hernia was detected in four patients at umblical trocar site. One of these patients had chronic obstructive lung disease, two of them had diabetes and three of them had obesity. Advanced age and obesity were found to be statistically significant in patients having trocar site hernia (p value: 0.007, and 0.008, respectively).

CONCLUSION: Development of trocar site hernia after laparoscopic surgery may be prevented by repair of trocar site in patients taken into consideration risk factors such as advanced age and obesity.

Keywords: Hernia; laparoscopic cholecystectomy; trocar site.

L

aparoscopic cholecystectomy has been firstly done by Mouret in 1987. Use of laparoscopy did not remain limited to gallbladder operations and it has been dramatically increased for the last two decades [1]. Although the frequent use of laparoscopy decreased the risk for the development of large incisional hernia, which is likely to develop after an open surgery, laparoscopic trocar site hernias may be seen, even if rarely. Trocar site hernia

(TSH) is the hernia that develops in the laparoscopic entry site and this complication may result in severe morbidity and mortality in case of intestinal strangulation within hernia [2].

A case of TSH who developed small intestinal obstruction following laparoscopic cholecystectomy was firstly reported by Maio et al. in 1991 [3]. Although this complication potentially results in important problems, it may be missed due to indistinct

Received: July 10, 2015 Accepted: November 11, 2015 Online: December 25, 2015 Correspondence: Dr. Oguzhan Dincel. Adiyaman Universitesi Tip Fakultesi, Genel Cerrahi Anabilim Dali, Adiyaman, Turkey.

Tel: +90 416 - 781 61 31 e-mail: droguzhandincel@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Dincel et al., Causes of asymptomatic trocar site hernia

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clinical signs. The incidence of TSH ranges between 0.18% and 2.8% in the studies performed with large series. As a widely accepted condition, many cases cannot be diagnosed due to the lack of long-term follow-ups and thereby, the actual incidence is expected to be higher [4, 5].

In this study, we aimed to present our asymptomatic cases of TSH, which developed in the early period after laparoscopic cholecystectomy and to evaluate the relevant risk factors. Furthermore, we targeted to discuss the issue in the light of the existing literature.

statistics (mean, standard deviation, frequency, rate) whereas intergroup comparisons of the parameters that show normal distribution and the evaluation of the mean values of two groups were performed using Student’s t test. Qualitative data were compared using chi-square test and Fisher’s Exact Test. Results were evaluated within 95% confidence interval and p<0.05 was considered as the level of significance.

MATERIALS AND METHODS

During the course of the study, 190 patients underwent laparoscopic cholecystectomy. Fifty-eight patients who did not attend to their scheduled followup visits were excluded and 132 patients who were followed-up were enrolled to the study. Of these patients, 110 were female and 22 were male (female/ male=5). Mean age was 50.64±11.86 years (age range 18–76 years). Fourteen (10.6%) patients had also diabetes and eight (6%) patients had chronic obstructive pulmonary disease (COPD). Eighteen (13.6%) patients were obese.

In our study, we detected TSH in four patients, all being localized in the umbilical region. During the study and the follow-up periods, none of the patients were re-admitted with TSH symptoms.

Patients in whom hernia was detected were diagnosed based on physical examination and ultrasound findings. Patient characteristics are given in Table 1. Gender of the patients was not found to be a significant factor for the development of TSH (p=1.000). It was seen that advanced age was significantly correlated with the development of TSH (p=0.007). Comorbid diseases, diabetes and COPD were evaluated and any effect of these diseases on the development of TSH was not seen (p=0.055 and p=0.223, respectively). However, presence of obesity had a statistically significant effect on the development of TSH (p=0.008).

Written informed consent was obtained from patients who participated in this study. We enrolled the patients who had unergone elective laparoscopic cholecystectomy with the indication of cholecystolithiasis between 2011 and 2013 in the study. Priorly an abdominal transverse incision under the umblicus was made. Then the abdomen was inflated using aVeress needle and 10-mm trocar was introduced into abdomen. Patients who underwent trocar incision using open surgery and those whose incisions were enlarged to extract the gallbladder were excluded from the study. Trocars with a caliber of 10-mm were introduced through the epigastric area and 5-mm trocars were inserted through the right upper and lower quadrants. Gallbladder was removed through epigastric port and trocar sites were not closed with suture.

All patients received prophylactic antibiotic.

Skin sutures were removed at day 10.

Body mass index above 30 kg/m2 was considered as obesity. Age, gender and comorbidity status of the patients and the presence of obesity were recorded.

Patients were called for a control visit at postoperative 12th month. The presence of TSH was evaluated on physical examination. The presence of hernia was confirmed ultrasonographically. The study protocol was approved by the Local Ethics Committee.

Statistical analysis For statistical analyses, GraphPad Prism (v6.0, GraphPad Software, Inc., USA) Software was used. Study data were evaluated using descriptive

Results

Discussion Tonouchi classified the types of TSH in three groups in 2004 as follows:. Early-onset type: It results from the rupture of the anterior and posterior

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Table 1. Patients’ characteristics Total (n=132)

Number of patients Mean age (Mean±SD) Female/Male Diabetes Chronic obstructive pulmonary disease Obesity

TSH negative n

TSH positive %

n

p* %

128 97 4 3 50.16±11.70 66.25±2.98 0.007** 106/22 4/0 1.000 12 9.3 2 50 0.055 7 5.4 1 25 0.223 15 11.7 3 75 0.008**

TSH: Trocar site hernia; SD: Standard deviation; *t test, Fisher’s Exact test; **p<0.05.

fascial planes in the early post-operative period.

Small intestinal obstruction is commonly seen.

Late-onset type: It results from the rupture of the anterior and posterior fascial planes several months after the operation. Small intestinal obstruction is not seen and it manifests as an asymptomatic swelling. Special type: It results from the rupture of whole abdominal wall immediately after the operation and there is no hernia sac [6]. All of our cases were asymptomatic and were thought to represent the late-onset type.

Some risk factors that promote the development of TSHs have been demonstrated. These factors include advanced age, diabetes, smoking, increased body mass index, infection at the trocar site, enlargement of the trocar site, trocar diameter and type, the localization area of the trocar and the defects greater than the diameter of the trocar. It was found that especially lower quadrant incisions made for insertion of the trocar which does not contain rectal sheath increase the predisposition to hernia development [1, 5, 6, 7, 8].

In many studies, it has been demonstrated that more than 80% of the TSHs originate from the site resulting from the location 10 mm above the trocar entry site. However, in a substantial number of studies, the investigators also detected hernias resulting from the defects of the trocars with calibers smaller than 5 mm in the presence of risk factors. Therefore, many authors recommend that

entry sites resulting from the trocars sized 10 mm or above should be closed [5, 7, 8]. In some studies, it was recommended that the trocar defects with a size of 10 mm or below should be repaired in the presence of some risk factors such as advanced age, obesity, diabetes and long lasting interventions [9, 10]. All hernias observed in our study originated from the 10 mm-long trocar sites in the umbilical region, while no hernia was observed in 5-mm trocar entry sites.

Literature reviews demonstrated that the obesity is a predisposing factor for TSH but no evidence exists to prove the effect of the body mass index on the incidence of hernia [5, 6, 11]. In a previous study, 50% of the patients who developed TSH had morbid obesity (body mass index >40 kg/m2) and 83% had obesity (body mass index >30 kg/m2) [12]. Obesity was an important risk factor in some uni- and multivariate studies and, as suggested as a hypothesis in the publications supported by some studies, increased intra-abdominal pressure which creates difficulties for complete closure of the defect play an important role in the development of TSH [11]. Among four TSH cases presented in the present study, three were obese and the presence of obesity was statistically significant in the subjects who developed TSH (p=0.008).

In some previously published multivariate analyses, the correlation between TSH and the age, which is among the risk factors, was not found to

Dincel et al., Causes of asymptomatic trocar site hernia

be significant. Although age of 70 years or more was not significantly relevant, as a hypothesis, weak fascia and decreased volume of abdominal muscles were reported to be potential risk factors in the elderly [13]. In the study presented herein, evaluation of the age of the patients with TSH yielded significant results and the incidence of TSH was more commonly seen in the advanced age group (p=0.007).

There are some conflicting insights about the potential role of the gender of the patients in the development of TSH. While some reports suggested that the incidence was higher in male patients, another study demonstrated a higher incidence rate in female patients. Although the role of the gender in TSH is conflicting in the literature, the factors that account for TSH appear to be multifactorial rather than being limited to the gender. The fact that the majority of the cases are female may explain the prejudice about the female gender [14]. In our study, the patients with TSH were all female but any statistically significant difference was not detected between genders (p=1.000).

Although the effect of pre-existing diabetes on wound healing is well known, it is difficult to explain this correlation. A similar correlation was detected between incisional hernia and diabetes. In this study, two of four patients with TSH had diabetes but this did not reach statistical significance (p=0.055). It was demonstrated that COPD and abdominal wall infections increased the predisposition to the development of incisional hernia [15].

We think that COPD leads to the development of hernia by delaying the wound healing and by causing cough episodes that increase the intra-abdominal pressure. In one of the TSH cases presented in the study, COPD was present but the effect of COPD on TSH development was not statistically significant (p=0.223).

In the literature, some studies reported pre-existing umbilical hernia as a risk factor. Nassar et al. reported the pre-operative presence of umbilical or paraumbilical hernia in 12% of the patients (84% of them were asymptomatic) who had undergone laparoscopic cholecystectomy. It was reported that, despite primary closure of these defects, 1.8% of

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them had developed TSH [14]. Again, Azurin et al. reported similar results in their study. In nine of their ten patients with TSH, umbilical hernia had been detected and repaired during the operation [5]. Our cases did not show any symptoms suggestive of preoperative hernia.

Conclusion Trocar site hernia may emerge as an important problem following laparoscopic surgery. Therefore, the trocar entry site defects greater than 10 mm should be routinely closed and the defects with a size of 10 mm that cannot be enlarged should be absolutely closed in the presence of any risk factor, such as age and obesity.

The present study does not allow for any comment on the closure of the trocar defects with a size of 5 mm, but some studies recommend their closures. Especially the people with risk factors should be informed about the likelihood of hernia development and an earlier diagnosis should be ensured.

Development of trocar site hernia after laparoscopic surgery may be prevented by repair of the trocar site in patients who have risk factors such as advanced age and obesity.

Ethics Committee Approval: Since this was a retrospective study we didn’t apply to the ethics committee for approval.

Informed Consent: Written informed consent was obtained from the patients who participated in this study.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Coda A, Bossotti M, Ferri F, Mattio R, Ramellini G, Poma A, et al. Incisional hernia and fascial defect following laparoscopic surgery. Surg Laparosc Endosc Percutan Tech 2000;10:34–8.

2. Lee JH, Kim W. Strangulated small bowel hernia through the port site: a case report. World J Gastroenterol 2008;14:6881–3.

3. Maio A, Ruchman RB. CT diagnosis of postlaparoscopic hernia.

J Comput Assist Tomogr 1991;15:1054–5.

4. Swank HA, Mulder IM, la Chapelle CF, Reitsma JB, Lange JF, Bemelman WA. Systematic review of trocar-site hernia. Br J Surg 2012;99:315–23.

214 5. Azurin DJ, Go LS, Arroyo LR, Kirkland ML. Trocar site herniation following laparoscopic cholecystectomy and the significance of an incidental preexisting umbilical hernia. Am Surg 1995;61:718–20.

6. Tonouchi H, Ohmori Y, Kobayashi M, Kusunoki M. Trocar site hernia. Arch Surg 2004;139:1248–56.

7. Ahmad SA, Schuricht AL, Azurin DJ, Arroyo LR, Paskin DL, Bar AH, et al. Complications of laparoscopic cholecystectomy: the experience of a university-affiliated teaching hospital. J Laparoendosc Adv Surg Tech A 1997;7:29–35.

8. Freedman AN, Sigman HH. Incarcerated paraumbilical incisional hernia and abscess--complications of a spilled gallstone. J Laparoendosc Surg 1995;5:189–91.

9. Reardon PR, Preciado A, Scarborough T, Matthews B, Marti JL. Hernia at 5-mm laparoscopic port site presenting as early postoperative small bowel obstruction. J Laparoendosc Adv Surg Tech A 1999;9:523–5.

10. Paya K, Wurm J, Fakhari M, Felder-Puig R, Puig S. Trocarsite hernia as a typical postoperative complication of mini-

North Clin Istanbul – NCI mally invasive surgery among preschool children. Surg Endosc 2008;22:2724–7.

11. Hussain A, Mahmood H, Singhal T, Balakrishnan S, Nicholls J, El-Hasani S. Long-term study of port-site incisional hernia after laparoscopic procedures. JSLS 2009;13:346–9.

12. Agaba EA, Rainville H, Ikedilo O, Vemulapali P. Incidence of port-site incisional hernia after single-incision laparoscopic surgery. JSLS 2014;18:204–10.

13. Mayol J, Garcia-Aguilar J, Ortiz-Oshiro E, De-Diego Carmona JA, Fernandez-Represa JA. Risks of the minimal access approach for laparoscopic surgery: multivariate analysis of morbidity related to umbilical trocar insertion. World J Surg 1997;21:529–33.

14. Nassar AH, Ashkar KA, Rashed AA, Abdulmoneum MG. Laparoscopic cholecystectomy and the umbilicus. Br J Surg 1997;84:630–3.

15. Beltrán MA, Cruces KS. Incisional hernia after McBurney incision: retrospective case-control study of risk factors and surgical treatment. World J Surg 2008;32:596–603.

Orıgınal Article

PM&R

North Clin Istanbul 2015;2(3):215–221 doi: 10.14744/nci.2015.95867

Relation of physical activity level with quality of life, sleep and depression in patients with knee osteoarthritis Erkan Mesci,1 Afitap Icagasioglu,1 Nilgun Mesci,2 Selin Turan Turgut3 Department of Physical Therapy and Rehabilitation, Istanbul Medeniyet University Goztepe Training and Research Hospital,

1

Istanbul, Turkey Department of Physical Therapy and Rehabilitation, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey

2

Department of Physical Therapy and Rehabilitation, Karaman State Hospital, Karaman, Turkey

3

ABSTRACT OBJECTIVE: In the present study, we aimed to investigate the effects of physical activity level on the quality of life, depression, sleep quality and functional capacity in elderly patients with knee osteoarthritis (OA).

METHODS: Fifty-five patients over 65 years of age (age range: 65–84 years) with knee osteoarthritis were enrolled in the study. Patients were divided into two groups including Insufficient Activity Group (IAG) and Physically Active Group (PAG) according to their responses to the International Physical Activity Questionnaire. Radiological OA grading was performed using Kellgren-Lawrence classification system. Patients were evaluated using ShortForm 36 (SF-36) questionnaire, Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

RESULTS: Mean age, body mass indices, mean pain scores and gender distribution were comparable between the two groups. WOMAC physical function scores were lower in the Physically Active Group (p=0.01). Mean PSQI scores did not differ statistically significantly between the two groups (p=0.242). Mean BDI score of PAG was significantly lower compared to that of IAG (p=0.015). Mean SF-36 physical function (p=0.044), physical role (p=0.008) and physical component (p=0.016) scores of the Physically Active Group were significantly higher vs Insufficient Activity Group.

CONCLUSION: Maintaining a high physical activity level reduces the possibility of depression and improves the quality of life and functional capacity in geriatric patients with knee osteoarthritis.

Keywords: Knee osteoarthritis; physical activity; quality of life.

K

nee osteoarthritis (OA) is one of the most common musculoskeletal diseases with a lifetime prevalence of 44.7 percent [1]. In addition to

pain and disability, knee OA may cause significant morbidity and even mortality as a result of secondary obesity, osteoporosis and cardiovascular risks

Received: September 30, 2015 Accepted: October 28, 2015 Online: December 25, 2015 Correspondence: Dr. Erkan Mesci. Istanbul Medeniyet Universitesi, Goztepe Egitim ve Arastirma Hastanesi, Fizik Tedavi ve Rehabilitasyon Klinigi, Istanbul, Turkey.

Tel: +90 216 - 566 40 00 e-mail: erkanmesci@hotmail.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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associated with reduced mobility. Encouraging increased physical activity (PA) level as a priority during treatment of patients with osteoarthritis has been previously reported for effective protection against cardiovascular risks and comorbidities [2].

It is known that OA patients have often depression, lower physical activity levels and diminished quality of life associated with poor physical activity which progressively worsen disability in a vicious circle [3]. Up to 49.3% of the patients with knee OA suffer from depression [4].

Several studies including systematic reviews have shown favorable effects of exercise in patients with osteoarthritis [5, 6]. Although, results of these studies have demonstrated that exercises are usually effective only for a short term, exercises are still the mainstay of conservative treatment [7]. For knee osteoarthritis, regular physical activity is known to have beneficial effects on the quality of life [8, 9] and physical functions of the affected patients [10, 11].

However, the level of activity in relation to depression and particularly sleep quality has not been investigated adequately. So far, studies on the effects of physical activity level on the aforementioned parameters have included osteoarthritis patients from all age groups. There seems to be a need to investigate the effects of regular physical activity in geriatric patients with knee osteoarthritis. On the other hand, differential data are found in the literature on the association of physical activity level with a number of factors such as age, body mass index and pain [12].

In the present study, our first aim was to explore the effects of physical activity level on the quality of life, depression, sleep quality and functional capacity in knee OA patients over 65 years of age. Secondly, we sought to determine the relation between physical activity level and age, body mass index, radiological grade of osteoarthritis and pain severity of the patients.

MATERIALS AND METHODS The study was conducted in patients over 65 years of age who were diagnosed with knee osteoarthritis at our outpatient clinics of the department of physical therapy and rehabilitation according to the

North Clin Istanbul – NCI

American College of Rheumatology (ACR) criteria. Approval for the conduct of the study was obtained from the institutional ethics committee prior to initiation of the study. Patients who agreed to participate and gave their written informed consent were enrolled in the study.

Elderly patients with chronic knee osteoarthritis were enrolled if the duration of the disease was at least six months and they had no signs suggestive of acute inflammation or acute pain and/or joint contracture that would restrict activity. Patients with any inflammatory, infectious or malignant conditions, central or peripheral nervous system disorder(s) restricting physical activity and a severe cardiac, pulmonary or psychiatric illness were excluded form the study. Fifty-five patients (33 females and 22 males) who met the inclusion criteria were enrolled in the study.

Radiological grading Kellgren-Lawrence (KL) classification system was utilized for radiological grading of the patients. In this system, KL Grade 1 is doubtful osteophyte, Grade 2 is definite osteophyte, without narrowing of joint space, Grade 3 is definite osteophyte with narrowing of joint space and Grade 4 is definite osteophyte with marked narrowing of joint space [13]. For radiological grading, standard anteroposterior radiograms of the weight-bearing knee were used. Radiological grading of knee OA was performed by the same person for all patients and those patients considered to have grade 2–4 knee OA were enrolled in the study.

Pain assessment For all patients 10-cm long visual analogue scale (VAS) was used to evaluate current pain associated with knee osteoarthritis. Left end of the 10-cm line was labeled as “no pain” and right end as “worst imaginable pain”. Patients were asked to rate the intensity of their pain at rest and during activity.

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (WOMAC-P) was used as a secondary measure for pain assessment. WOMAC pain score is obtained by summing the scores for the intensity of pain ex-

Mesci et al., Relation of physical activity level with quality of life, sleep and depression in patients with knee osteoarthritis

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perienced by the patient during five different activities marked on a Likert scale [14].

group (IAG) and those exceeding this level in the physically active group (PAG) [15].

Assessment of functional state WOMAC physical function subscale (WOMACPF) consisting of 17 questions was used to evaluate physical functions. In this subscale, the difficulty experienced during various physical activities is rated by the patient on a Likert scale and higher scores indicate increased disability [14].

Assessment of depression Current depressive state of patients was assessed using Turkish version of Beck Depression Inventory (BDI) [16]. In BDI, higher scores indicate an increased tendency for depression.

Assessment of joint stiffness WOMAC joint stiffness subscale (WOMAC-S) was used for this purpose. Patients rate their intensity of joint stiffness using a Likert scale and a score is obtained. Total score is obtained by summing the scores after first walking in the morning and later during the day [14].

Physical activity level The International Physical Activity QuestionnaireShort Form (IPAQ-SF) was used to determine physical activity level of the patients. IPAQ is a scale used to measure physical activity level of individuals which is expressed in units of metabolic equivalent of task (MET) by evaluating physical activities performed within one week. The frequency and duration of physical activities (walking, moderate activity and vigorous activity) performed within the last seven days are questioned.

MET score for walking is calculated by multiplying the time spent for walking per day by the number of walking days per week and 3.3 METs. MET score for moderate activity is calculated by multiplying the time spent for moderate activity per day by the number of moderate activity days per week and 4 METs. MET score for vigorous activity is calculated by multiplying the time spent for vigorous activity per day by the number of vigorous activity days per week and 8 METs. Total physical activity score is obtained by summing these three scores. For the present study, total physical activity scores of patients were included in the analysis. Patients with a physical activity level below 600 METs per week were included in the insufficient activity

Quality of life assessment Turkish version of Short Form-36 (SF-36) questionnaire was used for assessment of quality of life (QoL) in study patients. SF-36 is a brief questionnaire that is widely used to evaluate multiple aspects of QoL based on the subscores for eight different domains [17].

Assessment of sleep quality Sleep quality assessments were performed using Turkish version of the Pittsburgh Sleep Quality Index (PSQI) and total PSQI scores were included in the analysis. In PSQI, higher scores indicate impaired sleep quality [18].

Statistical analyses Study findings were statistically analyzed using SPSS (Statistical Package for Social Sciences) for Windows version 19.0. For analysis of study data, descriptive statistical methods (mean, median, standard deviation, minimum-maximum) were used as well as Student-t test for between-group comparisons of normally distributed quantitative data and Mann-Whitney U test for between-group comparisons of non-normally distributed quantitative data.

Correlations between physical activity level and other parameters were explored using Spearman’s correlation analysis. Results were interpreted at 95% confidence interval with significance level set at p<0.05.

Results There were 27 patients (age range: 65–81) in the physically active group and 28 patients (age range: 65–84) in the insufficient activity group who were enrolled on the basis of their physical activity levels.

Both groups did not differ in mean age (Table 1). Fe-

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North Clin Istanbul – NCI

Table 1. Characteristics of study groups Characteristics

Physically active group (n=27)

Insufficient activity group (n=28)

Age, mean (SD), years 69.8±4.6 72.7±5.9 Sex (female), n (%) 15 (56%) 18 (64%) BMI, mean (SD), kg/m2 27.2±4.1 28.8±4.3 Duration of OA, mean (SD), years 10.5±3.9 11.6±4.2 Radiological grade, Grade 2 (n) 10 12 Grade 3 (n) 9 5 Grade 4 (n) 8 11 VAS-R, mean (SD) 5.2±3.1 4.6±2.8 VAS-A, mean (SD) 6.6±2.3 7.2±1.9 WOMAC pain 11.8±4.5 12.3±3.9 WOMAC stiffness 4.4±2.1 4.9±1.9 WOMAC physical function 38.1±7.5 42.9±8.2 BDI, mean (SD) 10.2±5.0 15.6±9.8 PSQI, mean (SD) 5.5±3.5 7.0±4.5 IPAQ, mean (SD) 1091.9±403.7 276.7±171.7

p 0.076 0.509 0.155 0.294 0.410

0.472 0.338 0.793 0.453 0.010* 0.015* 0.242 0.000**

SD: Standard deviation; BMI: Body mass index; OA: Osteoarthritis; VAS-R: Visuel analog scale-rest; VAS-A: Visuel analog scale-activity; WOMAC: Western ontario and McMaster Universities osteoarthritis index; BDI: Beck depression index; PSQI: Pittsburgh sleep quality index; IPAQ: International physical activity questionary; *p<0.05; **p<0.001.

male/male ratio was comparable between the study groups (PAG: 15 females, 12 males; IAG: 18 females, 10 males) (p=0.509). Mean body mass index (BMI) and disease duration were also comparable between the two groups. VAS results for the intensity of knee pain during activity and at rest did not show any difference between the study groups (Table 1).

There was no statistically significant difference between the groups with respect to mean WOMAC-P and WOMAC-S scores (Table 1). However, WOMAC-PF scores were significantly lower in the physically active group compared to those found in the insufficient activity group (p=0.01). Statistically, there was a highly significant difference between the groups as for physical activity levels (Table 1).

PAG had a significantly lower (10.2±5.0) mean Beck Depression Inventory score versus IAG (15.6±9.8) (p=0.015). PAG also had a lower PSQI score compared to IAG but the difference was not statistically significant (p=0.242) (Table 1).

Comparison of SF-36 scores between the groups

is shown in Table 2. Physically active group had a mean physical function subscale score of 61.5±28.4 which was significantly higher versus insufficient activity group (46.6±25.0) (p=0.044). Similarly, mean physical role score of the physically active group (63.9±47.2) was higher compared to the insufficient activity group (27.7±43.8) (p=0.008).

Physically active group had a mean physical component summary score of 42.0±13.3 which was significantly higher compared to insufficient activity group (33.7±11.3) (p=0.016). However, no difference was found between study groups in bodily pain, vitality, general health, social functioning, emotional role, mental health and mental component summary scores (Table 2).

The results of correlation analyses conducted for 55 patients in aggregate without considering their physical activity levels are shown in Table 3.

These analyses did not show a correlation between physical activity levels and age, BMI, Kellgren-Lawrence radiological grades and WOMAC-pain and WOMAC-stiffness scores (Table 3).

Mesci et al., Relation of physical activity level with quality of life, sleep and depression in patients with knee osteoarthritis

Table 2. Comparison of SF-36 scores between groups SF-36 subscale

PAG

IAG

Mean±SD

Mean±SD

Physical functioning Role physical Physical component Bodily pain Vitality General health Social functioning Role emotional Mental health Mental component

61.5±28.4 63.9±47.2 42.0±13.3 54.4±30.4 57.8±21.1 62.1±20.1 82.4±23.8 75.3±42.9 60.0±9.1 48.6±7.3

46.6±25.0 27.7±43.8 33.7±11.3 41.8±25.7 47.9±22.3 53.9±21.1 76.3±26.0 66.7±45.4 55.3±12.6 47.7±9.6

p

0.044* 0.008** 0.016* 0.100 0.096 0.140 0.286 0.363 0.118 0.716

SF-36: Short form-36; PAG: Physical activity group; IAG: Insufficient activity group; SD: Standard deviation; *p<0.05; **p<0.01.

Table 3. Relations between physical activity level and other parameters

IPAQ Spearman Rho

p

Age -.245 0.071 BMI -.250 0.065 WOMAC-P -.171 0.211 WOMAC-S -.205 0.133 K-L scale -.120 0.381 BMI: body mass index; IPAQ: International Physical Activity Questionary; K-L scale: Kellgren-Lawrence scale; Spearman Rho: Correlation coefficient; WOMAC-P: WOMAC-pain; WOMAC-S: WOMAC stiffness.

Discussion Our results showed that elderly patients with knee osteoarthritis who are physically more active had better quality of life and low depression scores in comparison to their less active counterparts despite experiencing similar pain severity. However, no difference was found in sleep quality in favor of the physically active group. Greater SF-36 subscale scores found in the PAG, particularly for those associated with physical functions demonstrate beneficial effects of adequate physical activity on physical

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capacity. Systematic reviews have shown the presence of a positive correlation between regular physical activity and health-related quality of life [8, 9].

In one study, Dunlop et al. divided patients in four groups based on their physical activity levels and showed an increase in functional performance in relation to increased activity level in patients with knee OA [10]. Similarly, we also observed that functional state as measured by WOMAC physical function subscale was much better in patients with adequate physical activity. Quadriceps muscle strength was shown to be greater in patients performing regular PA in comparison to those with insufficient activity [19]. Low PA level is known to be associated with reduced functional capacity both in patients with hip and knee osteoarthritis [12]. Follow-up of the patients with different PA levels for one year showed that at the end of one year, those patients with adequate PA had better functional capacity [11].

Our results are consistent with those of White et al. who reported lower depression scores in physically more active patients [20]. Depression has been shown to be associated with higher WOMAC scores in patients with knee osteoarthritis [4]. Consistently, we found low BDI scores as well as low WOMAC-PF scores in the PAG. It is known that insufficient PA increases the risk for functional loss and healthcare costs in patients with arthritis [21]. Dunlop et al. reported a difference in functional performance between level 1 and level 2 patients although both groups had a PA level lower than the average which suggests that activity encouraged at every level will contribute to physical functioning of the patients even when it is suboptimal [10].

According to Veenhof et al., increased PA and specific exercise programs are equally effective for pain and functional capacity. In that study, increasing the level of PA was found to be more effective in preventing disability over the long-term. The same study also showed better compliance to assigned exercises among patients with enhanced PA levels [22].

De Vreede et al. found that functional task exercise programs are superior versus strengthening exercises in achieving increased functional capacity [23].

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The effectiveness of specific exercise programs was shown to decline in long-term in osteoarthritis patients. However, effectiveness is maintained over long-term when booster sessions are added into the exercise programs or exercises integrated into daily activities are assigned to patients [24]. A shift in exercise programs was seen in recent years from exercises directed at restoring impaired body functions such as muscle strength and joint range of motion (ROM) towards exercises to increase functional activity level including walking and climbing stairs [23].

A major finding of our study was that patient groups with comparable body mass index, radiological grade and pain intensity had markedly different levels of PA. In line with this finding, our correlation analyses did not show an association of PA level with age, BMI, degree of pain, severity of joint stiffness and radiological grade. Dunlop et al. failed to determine a relation between PA level and radiological grade, body mass index and pain severity [10]. Groot et al. reported that pain severity and joint stiffness did not have an impact on the level of PA but advanced age and greater BMI was associated with lower PA levels. That study was conducted in patients with end-stage knee or hip osteoarthritis who were scheduled to undergo joint replacement surgery [25]. In one study, only 30% of OA patients have been shown to perform PA at an intensity recommended by the guidelines. In the same study, radiological OA grade was not associated with the level of PA [26].

Rosemann et al. reported that PA level was affected by advanced age and greater BMI. The same authors did not find an association between radiological OA grade and activity level [27]. Contradictory results were obtained in studies on factors associated with PA level in patients with osteoarthritis. Data from a systematic review showed that limited evidence exists to suggest that age and BMI have an impact on PA level in hip OA, while no such evidence is found for knee OA [12].

Interestingly, Murphy et al. concluded that pain severity is increased with an increase in the level of physical activity. In the same study, PA level was not effected by BMI and age [28]. According to White et al., there is no difference between knee OA pa-

North Clin Istanbul â&#x20AC;&#x201C; NCI

tients with or without pain regarding the level of PA. Moreover, they failed to find a difference between patients with or without knee OA radiographically.

The same authors reported that the primary barrier to PA among patients with knee OA was not the disease itself or pain and drew attention to factors associated with lack of PA in the general population including time constraints, non-prioritization of physical activity, use of motor vehicles for transports and design-related problems of the cities [20].

Studies have shown that pain-related fear that evolves following initial exacerbation of pain with movement becomes the major cause of immobility in the later stages. Subsequently patients avoid movement due to fear of pain even if they do not experience a significant amount of pain. Inactive patients were shown to avoid some of the daily living activities because of low self-esteem although there is no real physical cause for pain [29]. Indeed, actual PA levels of the patients with end-stage knee or hip osteoarthritis measured by activity monitor were demonstrated to be better than what is expected from patientsâ&#x20AC;&#x2122; self-reported assessments of impaired physical function [25].

The major limitation of our study is the small sample size. As a second limitation, we relied on self-reports of the patients for evaluating their level of physical activity. Further studies are needed in a larger number of geriatric subjects using activity monitors.

In conclusion, increased physical activity has beneficial effects on the quality of life, depression and functional capacity in patients with knee osteoarthritis. For management of knee osteoarthritis, it is essential to employ programs directed at increasing overall physical activity through more patientfriendly exercises integrated into daily activities in addition to specific exercises directed at strengthening of muscles and improvement of ROM. In this way, improved adherence to exercise programs and sustained participation in exercises might be achieved in the long-term. When tailoring physical activity programs, fear of pain, lack of motivation, loss of self-confidence, social preferences and environmental factors that could affect an individualâ&#x20AC;&#x2122;s activity level should all be considered.

Mesci et al., Relation of physical activity level with quality of life, sleep and depression in patients with knee osteoarthritis

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, et al. Lifetime risk of symptomatic knee osteoarthritis.

Arthritis Rheum 2008;59:1207–13.

2. Nüesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Jüni P. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ 2011;342:1165.

3. Rosemann T, Grol R, Herman K, Wensing M, Szecsenyi J. Association between obesity, quality of life, physical activity and health service utilization in primary care patients with osteoarthritis. Int J Behav Nutr Phys Act 2008;5:4.

4. Küçükşen S, Yılmaz H, Karahan AY, Bağçacı S. The prevalence of depression and its relevance to clinical and radiological characteristics amog older adults with knee osteoarthritis. Clinical Medicine Research 2014;2:25–30.

5. Uthman OA, van der Windt DA, Jordan JL, Dziedzic KS, Healey EL, Peat GM, et al. Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis. BMJ 2013;347:f5555.

6. Fransen M, McConnell S. Exercise for osteoarthritis of the knee.

Cochrane Database Syst Rev 2008;4:CD004376.

7. Davis AM, MacKay C. Osteoarthritis year in review: outcome of rehabilitation. Osteoarthritis Cartilage 2013;21:1414–24.

8. Bize R, Johnson JA, Plotnikoff RC. Physical activity level and health-related quality of life in the general adult population: a systematic review. Prev Med 2007;45:401–15.

9. Klavestrand J, Vingård E. The relationship between physical activity and health-related quality of life: a systematic review of current evidence. Scand J Med Sci Sports 2009;19:300–12.

10. Dunlop DD, Song J, Semanik PA, Sharma L, Chang RW. Physical activity levels and functional performance in the osteoarthritis initiative: a graded relationship. Arthritis Rheum 2011;63:127–36.

11. Dunlop DD, Semanik P, Song J, Sharma L, Nevitt M, Jackson R, et al. Moving to maintain function in knee osteoarthritis: evidence from the osteoarthritis initiative. Arch Phys Med Rehabil 2010;91:714–21.

12. Veenhof C, Huisman PA, Barten JA, Takken T, Pisters MF. Factors associated with physical activity in patients with osteoarthritis of the hip or knee: a systematic review. Osteoarthritis Cartilage 2012;20:6–12.

13. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957;16:494–502.

14. Tüzün EH, Eker L, Aytar A, Daşkapan A, Bayramoğlu M. Acceptability, reliability, validity and responsiveness of the Turkish version of WOMAC osteoarthritis index. Osteoarthritis Carti-

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lage 2005;13:28–33.

15. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35:1381–95.

16. Hisli N. Beck Depresyon Envanteri’nin üniversite öğrencileri için geçerliği ve güvenirliği. Psikoloji Dergisi 1989;7:3–13.

17. Koçyigit H, Aydemir Ö, Ölmez N, Memiş A. Kısa Form-36’nın Türkçe versiyonunun güvenilirliği ve geçerliliği. İlaç ve Tedavi Dergisi 1999;12:102–6.

18. Ağargün MY, Kara H, Anlar O. Pittsburgh uyku kalitesi indeksinin geçerliği ve güvenirliği. Türk Psikiyatri Dergisi 1996;7:107–15.

19. Pietrosimone B, Thomas AC, Saliba SA, Ingersoll CD. Association between quadriceps strength and self-reported physical activity in people with knee osteoarthritis. The International Journal of Sports Physical Therapy 2014;9:320–8.

20. White DK, Tudor-Locke C, Felson DT, Gross KD, Niu J, Nevitt M, et al. Do radiographic disease and pain account for why people with or at high risk of knee osteoarthritis do not meet physical activity guidelines? Arthritis Rheum 2013;65:139–47.

21. Dunlop DD, Semanik P, Song J, Manheim LM, Shih V, Chang RW. Risk factors for functional decline in older adults with arthritis. Arthritis Rheum 2005;52:1274–82.

22. Veenhof C, Köke AJ, Dekker J, Oostendorp RA, Bijlsma JW, van Tulder MW, et al. Effectiveness of behavioral graded activity in patients with osteoarthritis of the hip and/or knee: A randomized clinical trial. Arthritis Rheum 2006;55:925–34.

23. de Vreede PL, Samson MM, van Meeteren NL, van der Bom JG, Duursma SA, Verhaar HJ. Functional tasks exercise versus resistance exercise to improve daily function in older women: a feasibility study. Arch Phys Med Rehabil 2004;85:1952–61.

24. Pisters MF, Veenhof C, van Meeteren NL, Ostelo RW, de Bakker DH, Schellevis FG, et al. Long-term effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a systematic review. Arthritis Rheum 2007;57:1245–53.

25. de Groot IB, Bussmann JB, Stam HJ, Verhaar JA. Actual everyday physical activity in patients with end-stage hip or knee osteoarthritis compared with healthy controls. Osteoarthritis Cartilage 2008;16:436–42.

26. Farr JN, Going SB, Lohman TG, Rankin L, Kasle S, Cornett M, et al. Physical activity levels in patients with early knee osteoarthritis measured by accelerometry. Arthritis Rheum 2008;59:1229–36.

27. Rosemann T, Kuehlein T, Laux G, Szecsenyi J. Osteoarthritis of the knee and hip: a comparison of factors associated with physical activity. Clin Rheumatol 2007;26:1811–7.

28. Murphy SL, Smith DM, Clauw DJ, Alexander NB. The impact of momentary pain and fatigue on physical activity in women with osteoarthritis. Arthritis Rheum 2008;59:849–56.

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Orıgınal Article

Otorhinolaryngology

North Clin Istanbul 2015;2(3):222–226 doi: 10.14744/nci.2015.50023

Neck abscess: 79 cases Suphi Bulgurcu, Ilker Burak Arslan, Erhan Demirhan, Sureyya Hikmet Kozcu, Ibrahim Cukurova Department of Otorhinolaryngology, Tepecik Training and Research Hospital, Izmir, Turkey

ABSTRACT OBJECTIVE: Neck abscess is a disease that might cause mortality and severe morbidity, if it is not treated urgently. In our study, patients with diagnosis of neck abscess in our clinic were analyzed retrospectively and presented in the light of the literature.

METHODS: In our clinic, age distribution, source of infection, systemic disease, imaging methods that were used in diagnosis, preferred anaesthesia during drainage, abscess sites, culture results of abscess material, complications during treatment procedure, any antibiotherapy before admission and duration of hospitalization of 79 cases with neck abscess who were treated in the hospital between January 2008 and January 2015 were assessed.

RESULTS: Cases in our study were aged between 1–79 (mean 28.3) years and 43 of them were female and 36 were male patients. Systemic diseases were determined in 19 of the cases. The most common systemic disease was diabetes mellitus. Abscesses were localized mostly at peritonsillar region and 13 of the cases were operated when abscess were in multipl localizations. In 74 of the cases, drainage was performed under local anaesthesia and in 5 cases under general anaesthesia. Four of these 5 cases, abscesses were localized within retropharyngeal region and 1 of them had multipl abscesses at various regions. Staphylococcus aereus was the most detected microorganism based on culture results. Three adult cases were followed up in the intensive care unit because of development of mediastinitis. One of these 3 cases exited because of sepsis. Hospitalization periods of 79 cases ranged between 2–21 days (mean 7.64 days). Hospitalization period of 19 cases with systemic diseases were 9.47 days (p<0.05) and statistically which were statistically significantly longer when compared with those without any systemic disease.

CONCLUSION: Neck abscess must be diagnosed early and treated with surgical drainage and parenteral therapy because it might cause severe complications.

Keywords: Abscess; complication; neck.

N

eck abscess is infection of potential spaces of throat with bacterial pathogens which may present diagnostic difficulties and lead to serious complications. Previously, they had higher mor-

tality rates, however nowadays, early diagnostic methods, broad spectrum antibiotics and surgical interventions have dropped mortality rates substantially [1].

Received: May 25, 2015 Accepted: September 01, 2015 Online: December 25, 2015 Correspondence: Dr. Suphi Bulgurcu. Tepecik Egitim ve Arastirma Hastanesi, Kulak, Burun, Bogaz ve Bas Boyun Cerrahisi Klinigi, Izmir, Turkey.

Tel: +90 232 - 444 35 60 e-mail: suphibulg@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Bulgurcu et al., Neck abscess: 79 cases

Deep neck infections which play an important role among neck abscesses have been described firstly by Galen and currently their incidence rates have ranged between 9, and 12/100.000 [2]. Prompt diagnosis and treatment are important for neck abscesses, otherwise, they lead to the development of important complications as respiratory distress, mediastinitis, pseudoaneurysm, empyema, asphyxia and jugular vein thrombosis. Anatomical structure of the neck mainly consists of superficial and deep fascia and deep fascia divides into superficial, middle (visceral), and deep layers. Knowledge about anatomical and functional interrelationships between this fascia and their layers in the neck and their association with the primary source of infection is important with respect to our treatment. Treatment of neck abscesses priorly consists of maintaining the patency of the airway, drainage of the abscess and intravenous application of appropriate antibiotherapy [3]. In this study, 79 neck abscesses were investigated retrospectively and presented in the light of the literature.

MATERIALS AND METHODS In our clinic, age distribution, source of infection, systemic disease, diagnostic imaging methods, anesthesia preferred during drainage, location of abscess, culture results of the abscess material, complications during treatment period and hospital stays were retrospectively investigated among 79 cases with abscess diagnosed in our clinic between January 2008 and January 2015. Patients with an improved general health state and those who could tolerate oral intake easily were closely followed up without hospitalization were not included in the study group.

Data obtained were organized using SPSS for Windows 20 program into a data base. Data were evaluated in SPSS 20 statistical package program.

Level of statistical significance was set at p<0.05 Results Our study population consisted of 43 female and 36 male patients aged between 1 and 79 years (median,

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20

Cases with a systemic disease

18

Cases without a systemic disease

16 14 12 10 8 6 4 2 0

0–10 11–20 21–30 31–40 41–50 51–60 61–70 71–80

Figure 1.

Total number of cases with or without systemic disease based on age groups.

28.3 years). In 19 of all cases, systemic disease was detected. Distribution of the systemic diseases and longevity of the hospital stay among cases according to age of the patients was investigated (Figur 1). Among systemic diseases, most frequently diabetes mellitus (n=10) then hypertension (n=7), and other systemic diseases (coronary artery disease, chronic obstructive pulmonary disease and asthma etc) (n=10) were detected. In more than 8 cases, systemic disease was found. Fifty-five cases reported use of antibiotherapy before admission to our clinic. Diagnostic accuracy rates for ultrasound (US) (21.5%; n=17), computed tomography (CT) (16.4%; n=13), combined US-CT use (25.3%; n=20), combined use of US, BT, and MRI (3.7%; n=3) in the diagnosis of neck abscess were determined. For twenty-nine cases which consisted of clinical diagnosis with peritonsillar abscess (n=25), submental abscess (n=2), and submandibular abscess (n=2) imaging modalities were not required.

As sources of infection, firstly upper respiratory tract infections then odontogenic infections, infected congenital neck cysts, stabs of foreign objects, skin infection, surgical site infections and cyalolithiasis were detected (Table 1). Abscess was most frequently detected on peritonsillar area and in 13 of all neck abscesses, abscesses localized on more than one area were intervened (Table 2). Abscess drainage was applied under local (n=74) or general (n=5) anesthesia. Four of these 5 cases who were

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Table 1. Number of cases based on etiologic factors

15

Duration of hospitalizations (mean)

10

Source of infection

Patients (n)

Upper respiratory tract infection 32 Odontogenic infection 24 Penetrating foreign object 3 Congenital cyst infection 3 Surgical site infection 2 Skin infection 2 Cyalolithiasis 1 Any etiologic factor could not be determined 12

Table 2. Number of cases based on the anatomical location of abscesses Location of abscess

Patients (n)

Peritonsillar 29 Submandibular 22 Submental 12 Parapharyngeal 10 Retropharyngeal 5 Masticatory 5 Parotid 2 Retromolar 1 Infrahyoid 4 Superficial 5

operated under general anesthesia had only retropharyngeal abscess, while in one case abscesses were localized on more than one location. Microbiological examination of all 79 cases revealed methicillinesensitive Staphylococcus aureus (n=7), staphylococci spp.(n=3), Streptococcus anginosus (n=3), Streptococcus pyogenes (n=3), Candida albicans (n=2), Streptococcus mitis (n=1), Pseudomonas aeruginosa (n=1), Streptococcus agalactiae (n=1), and Klebsiella pneumoniae (n=1). Bacterial growth was not detected in fifty-seven abscess materials. Forty-two out of these 57 cases were receiving antibiotherapy 2, and 10 days before consulting to our clinic (p>0.05). Upon development of mediastinitis in 3 adult cases, these

5 0

0–10 11–20 21–30 31–40 41–50 51–60 61–70 71–80

Figure 2.

Hospital stay of the cases based on age

groups.

patients were monitored under conditions of intensive care. One of these 3 cases exited because of sepsis. Because of impaired general health state one case was intubated and tracheotomy was applied in another patient and followed up under intensive care conditions because of respiratory distress and later the patient was discharged with cure. In one case with submandibular abscess, paralysis of the marginal mandibular branch of the facial nerve was observed. Until antibiotic susceptibility test results were obtained empirical treatment with broad spectrum antibiotics were initiated. After test results were acquired, treatment of the patient was reorganized after consultation with the department of infectious diseases. Hospital stay of 79 cases ranged between 2, and 21 days (median, 7.64 days). Average longevity of hospital stays based on age groups of the cases was evaluated (Figur 2). The longest hospital stay was seen among patients aged 61-70 years. Fifty-five Patients (n=55) who received and did not receive (n=24) treatment previously were hospitalized for an average of 7.81, and 6.58 days, respectively (p>0.05). Average hospital stay of 19 cases with systemic disease was 9.47 days (p<0.05) which was statistically significantly longer when compared with those without any systemic disease.

Discussion Neck abscess is infection of potential spaces of throat with bacterial pathogens which may present diagnostic difficulties and risks of mortality, if not treated prematurely. Frequently, they occur as a result of upper respiratory tract infections followed

Bulgurcu et al., Neck abscess: 79 cases

by odontogenic infections [4]. Infected neck cysts, penetrating foreign objects and surgical site infections may be considered as sources of infection. In some cases source of infection may not be detected [5]. In our study as etiologic factors most frequently upper respiratory tract infections, then odontogenic infections and other etiologies were found. In 13 cases any etiologic factor could not be detected.

Physical examination of the patient at his/her first admission is very important. Respiratory distress of the patient should be taken seriously, oropharynx and larynx should be very well evaluated as for development of complication(s) [6]. Progression and passage of the neck abscess through interconnected anatomical spaces may lead to the development of complications as empyema, pericarditis, mediastinitis, pericardial effusion, carotid artery rupture, aortopulmonary fistula, cranial nerve paralysis, cervical necrotizing fasciitis, jugular vein thrombosis, venous embolism, septic shock, disseminated intravascular coagulation, renal insufficiency, meningitis and epidural abscess [7]. In the literature complication rates were indicated to range between 12.85, and 25.5 percent [8].

Abscesses of our five cases with respiratory distress were urgently drained. Four patients whose endoscopic examinations revealed retraction of the posterior pharynx and CT s demonstrated retropharyngeal abscess, while one patient with a diffuse abscess were operated because of these indications. In 3 of 5 cases with respiratory distress, mediastinitis was detected and postoperatively 2 of them were intubated and the third one was tracheotimized under intensive care conditions. Among these monitorized cases, one intubated patient died of sepsis. Other intubated case and tracheotimized patient were discharged with cure.

In this study of ours, we detected that advanced age and concomitant systemic diseases are important predisposing factors which prolong hospital stay of these patients.

In a study by Chen et al. performed on 214 cases with deep neck infections, most frequently affected areas were reported as peritonsillar, parapharyngeal, submental and retropharyngeal regions in order of decreasing frequency. [9]. In a study by Miman et al. performed on 31 cases, peritonsillar abscess, retropharyngeal abscess and submandibular abscess were

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reported as the most frequently affected regions in order of decreasing frequency [10]. In our group of 79 neck abscesses most frequently peritonsillar, submandibular and submental regions were affected.

Mostly US and CT were requested for patients with initial diagnosis of neck abscess. However, in some cases we required evaluation using MR in cases where we could not discriminate between cellulitis and abscess [11].

In 29 cases diagnosis of abscess was made without any need for imaging modalities. Twenty-five of these cases were diagnosed as peritonsillar abscess which was treated with local drainage.

In 22 of 79 cases bacterial growth was detected on culture. In 42 of 57 patients whose culture results could not demonstrate any bacterial growth had used antibiotics before consultation to our clinic. Bacterial growth can not be seen in antibiotic susceptibility tests of the patients who used antibiotics previously. Besides, bacterial growth may not be detected on samples sent for antibiotic susceptibility tests under inappropriate conditions [12].

In cases with neck abscesses, on culture media most frequently staphylococi (S.Aureus and S.epidermidis), streptococci (S.milleri spp, and S.viridans), peptostreptococci, klebsiella, bacteroides spp. and fusobacterium spp. have been identified [13]. In our clinic, most frequently growth of Staphylococcus aureus, then other staphylococci spp., streptococci and other bacterial strains was identified.

In neck abscesses, administration of early and effective treatment is very important. Patients with impaired general health and oral intake should be also hospitalized and treatment with parenteral broad spectrum antibiotics should be initiated [14].

In our clinic, empirically, parenteral ampicillin-sulbactam treatment is administered for adult patients at daily doses of 2 g, and pediatricians organize treatment for pediatric patients. After location of the abscess, drainage is applied.

Conclusion In cases with neck abscess, priorly a safe airway patency should be maintained. Afterwards, parenteral medical treatment should be initiated and under

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appropriate conditions surgical drainage should be applied. Resorting to the imaging modalities for the determination of clinical status of the patient helps the physicians. Because of life-threatening complications, in the treatment process of neck abscess, extreme care should be instituted.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Huang TT, Liu TC, Chen PR, Tseng FY, Yeh TH, Chen YS. Deep neck infection: analysis of 185 cases. Head Neck 2004;26:854–60.

2. Vieira F, Allen SM, Stocks RM, Thompson JW. Deep neck infection. Otolaryngol Clin North Am 2008;41:459–83.

3. Freling N, Roele E, Schaefer-Prokop C, Fokkens W. Prediction of deep neck abscesses by contrast-enhanced computerized tomography in 76 clinically suspect consecutive patients. Laryngoscope 2009;119:1745–52.

4. Johnson JT. Deep neck abscesses. Operative otolaryngology:Head and Neck Surgery. 1. baskı. Philadelphia. W.B. Saunders Company 1997;667–75.

5. Guney E. Baş boyun bölgesi fasyalar arası enfeksiyonlar, IN: Topçu AW, Söyletir G, Doğanay M, İnfeksiyon Hastalıkları ve

North Clin Istanbul – NCI Mikrobiyoloji, Nobel Tıp Kitapevleri, İstanbul 2002. s. 492–504.

6. Marra S, Hotaling AJ. Deep neck infections. Am J Otolaryngol 1996;17:287–98.

7. Lee JK, Kim HD, Lim SC. Predisposing factors of complicated deep neck infection: an analysis of 158 cases. Yonsei Med J 2007;48:55–62.

8. Suehara AB, Gonçalves AJ, Alcadipani FA, Kavabata NK, Menezes MB. Deep neck infection: analysis of 80 cases. Braz J Otorhinolaryngol 2008;74:253–9.

9. Chen MK, Wen YS, Chang CC, Huang MT, Hsiao HC. Predisposing factors of life-threatening deep neck infection: logistic regression analysis of 214 cases. J Otolaryngol 1998;27:141–4.

10. Miman MC, Öncel S, Kalcıoğlu T, Kızılay A, Aktaş D, Özturan O. Derin boyun enfeksiyonlarına klinik yaklaşım. Kulak Burun Boğaz İhtisas Dergisi 2001:8:206–13.

11. Miller WD, Furst IM, Sàndor GK, Keller MA. A prospective, blinded comparison of clinical examination and computed tomography in deep neck infections. Laryngoscope 1999;109:1873–9.

12. Santos Gorjón P, Blanco Pérez P, Morales Martín AC, Del Pozo de Dios JC, Estévez Alonso S, Calle de la Cabanillas MI. Deep neck infection. Review of 286 cases. Acta Otorrinolaringol Esp 2012;63:31–41.

13. Lee YQ, Kanagalingam J. Bacteriology of deep neck abscesses: a retrospective review of 96 consecutive cases. Singapore Med J 2011;52:351–5.

14. Bottin R, Marioni G, Rinaldi R, Boninsegna M, Salvadori L, Staffieri A. Deep neck infection: a present-day complication. A retrospective review of 83 cases (1998-2001). Eur Arch Otorhinolaryngol 2003;260:576–9.

Case Report

neonatology

North Clin Istanbul 2015;2(3):227–230 doi: 10.14744/nci.2015.58569

Treatment of chylothorax developed after congenital heart disease surgery: a case report Ozgul Bulut, Doruk Gul, Sibel Sevuk, Ilke Mungan, Derya Buyukkayhan Department of Neonatology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey

ABSTRACT Chylothorax is defined as the accumulation of lymphatic fluid or chyle in the pleural space. Chylothorax treatment is composed of conservative; pleural drainage, termination of enteral feeding, total parenteral nutrition and supplementation with medium- chain triglycerides and surgical therapies; ductus thoracicus ligation, pleuroperitoneal shunts or pleuredesis. Nowadays, for cases among which conservative therapies fail, treatment with octreotide has been reported to be beneficial with promising results. A neonate who developed chylothorax after surgery performed for congenital heart disease was treated successfully with octreotide.

Keywords: Chylothorax; congenital heart disease; octreotide; surgery.

C

hylothorax which develops following cardiac surgery in pediatric patients is a prevalent complication associated with causes of serious morbidity and mortality including severe malnutrition, impairments in hematological, metabolic and immune systems, need for a longer ventilation and prolongation of hospital stay [1, 2, 3]. In single centered studies incidence of chylothorax following cardiac surgery has been reported as nearly 4–9% [3, 4, 5].

Development of chylothorax can be associated with injury of the thoracic duct, disruption of lymphatic channels, increase in venous pressure and central venous thrombosis [1].

For the diagnosis of chylothorax pleural fluid should appear like a milk, its culture should be sterile, triglyceride level should be higher than 110 mg/ dL, and total amount of cells, and the ratio of lym-

phocytes should be above 1000 cells/µL, and 80%, respectively [6].

Current treatment strategies include conservative methods as drainage of the pleural fluid, discontinuation of the enteral nutrition, total parenteral nutrition (TPN), feeding with formulas containing medium chain triglyceride (MCT), and in resistant cases, surgical methods as ligation of the thoracic duct, pleuro-peritoneal shunt or pleurodesis [6, 7].

However, surgical treatment increases morbidity rates, hospital stay and costs. In the literature, with octreotide treatment successful treatment results have been reported in unresponsive cases [8]. In this case report we presented a patient who had chylothorax developed after surgical procedure because of congenital heart disease in the neonatal period.

Received: September 08, 2015 Accepted: November 02, 2015 Online: December 25, 2015 Correspondence: Dr. Ozgul Bulut. Istanbul Medeniyet Universitesi Goztepe Egitim ve Arastirma Hastanesi, Neonatoloji Bilim Dali, Istanbul, Turkey.

Tel: +90 216 - 566 40 00 e-mail: ozgulbulut@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul – NCI

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Case Report A male baby was born via cesarean section at 38 1/7 weeks gestation and birth weight of 2970 g. On antenatal ultrasound (US) atrioventricular septal defect was detected. On physical examination, the patient with respiratory distress was intubated and hospitalized in the neonatal intensive care unit. On echocardiograms complete atrioventricular channel defect, muscular ventricular septal defect and pulmonary hypertension were detected. Diuretic and inotropic treatment were initiated. Transfontanel and abdominal US findings were unremarkable.

Pulmonary artery band operation was performed the postnatal 40th day. Twenty days after the procedure, the patient was extubated and monitored with continuous positive airway pressure (CPAP).

During monitorization, respiratory distress increased progressively and he was re-intubated. On physical examination, decreased respiratory sounds on the left hemithorax were auscultated. On telecardiogram left lung was opaque and consistent with pleural effusion (Figure 1). Pleural fluid was detected 4 cm on thoracic US. For diagnosis and treatment 50 ml milky-colored fluid was evacuated with thoracentesis (Figure 2). Biochemical analysis of the sample fluid was determined as follows: triglyceride, 161mg/dL, WBC 1300/mm3 with a 90% lymphocyte dominancy and culture negativity. One day later 50 ml fluid was drained, baby formulas containing TPN and MCT were initiated. Series pulmonary chest radiograms revealed persistence of preexisting pleural effusion, consequently, a chest tube was implanted into the left hemithorax and underwater drainage was performed. On the third day of the treatment her respiratory distress persisted, and amount of pleural fluid did not change which encouraged us to initiate three equal doses of octreotide (10 µg/kg/d/SC Sandostatin®). On the eight day of the treatment, intravenous infusion treatment with octreotide doses of 3 µg/kg/h was initiated. The dose of octreotide was increased stepwise. On the 20. day of the treatment amount of the drained fluid decreased. Control pulmonary radiogram was normal and thoracic US did not reveal any pleural effusion. (Figure 3). Chest tube was removed.

The patient was extubated because of regression of respiratory failure symptoms and he was monitored on nasal CPAP support. Any adverse effect second-

Figure 1. On telecardiogram opacified left lung consistent with pleural effusion.

Figure 2.

Milky colored pleural fluid drawn by thora-

centesis.

ary to octreotide treatment was not seen. The dose of octerotide was tapered and finally discontinued.

The baby was gradually switched to breast feeding.

Parents of our case gave their “Informed Consent” for the publication of this case report.

Bulut et al., Treatment of chylothorax developed after congenital heart disease surgery

Figure 3. Post-treatment control telecardiogram.

DISCUSSION Chylothorax which develops following cardiac surgery in pediatric patients is a prevalent complication associated with causes of serious morbidity and mortality. However, a complete consensus does not exist about the optimal treatment approach for chylothorax developed after surgery. In the literature, various algorithms have been developed dependent on the experience and preferences of the physicians [3, 4, 9]. Generally, preferred method is conservative approach including discontinuation of enteral nutrition, feeding with formula containing TPN or MCT, drainage of pleural fluid and mechanical ventilation. This treatment leads to hypoproteinemia, coagulopathy, lymphopenia, hypogammaglobulinemia, sepsis and ventilation-related pulmonary injury [10]. Firstly, in the year 1998, in the medical treatment of chyhlothorax developed following cardiac surgery the use of intravenous somotastatin was reported [11].

Octreotide is a long-acting synthetic somatostatin analogue. Though mechanism of action of somatostatin and octreotide has not been fully elucidated, its suppressive effects on lymphatic fluid formation predominantly by vasoconstriction and resultant decrease in splenic blood flow [12, 13].

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Somatostatin is administered as a continuous infusion, while octreotide can be also applied as subcutaneous injection. Recommended initial dose of somatostatin can be as high as 3.5 mg/kg/h, while in case of need use octreotide dose within the range of 0.3–10 µg /kg/hr is recommended [14, 15]. Optimal timing and dose of these two drugs have not been known so far [12]. Though duration of treatment is controversial, generally treatment should be continued for 3–5 days after cessation of the drainage of the pleural fluid [8, 16]. During treatment with octreotide and somotatin adverse effects as hyperglycemia, hypothyroidism, muscle cramps, hypertension, nausea, diarrhea, necrotizing enterocolitis, renal involvement and hepatic dysfunction can be encountered [17]. Development of anaphylaxis secondary to octreotide use has been reported [18].

In the treatment of chylothorax which develops during childhood where conservative and medical treatment modalities failed, surgical treatment alternatives should be conceived. Thoracic duct ligation described by Lampson in 1948 is used prevalently in patients who did not recover with medical treatment [19]. Obliteration of pleural space with surgical or chemical methods is another surgical method. To this end, tetracyclin, talc, bleomycin, and povidone iodure have been used [17]. In cases where lymph leakage continues despite medical, and surgical treatment modalities, pleuroperitoneal shunt can be applied [12].

In this case, intravenous octreotide was used in the treatment of chylothorax developed following cardiac surgery during neonatal period with successful outcomes. We hope that this treatment modality will take its proper place in routine clinical use after prospective controlled studies.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Zuluaga MT. Chylothorax after surgery for congenital heart disease. Curr Opin Pediatr 2012;24:291–4.

2. McCulloch MA, Conaway MR, Haizlip JA, Buck ML, Bovbjerg VE, Hoke TR. Postoperative chylothorax development is associated with increased incidence and risk profile for central venous

230 thromboses. Pediatr Cardiol 2008;29:556–61.

3. Chan EH, Russell JL, Williams WG, Van Arsdell GS, Coles JG, McCrindle BW. Postoperative chylothorax after cardiothoracic surgery in children. Ann Thorac Surg 2005;80:1864–70.

4. Biewer ES, Zürn C, Arnold R, Glöckler M, Schulte-Mönting J, Schlensak C, et al. Chylothorax after surgery on congenital heart disease in newborns and infants -risk factors and efficacy of MCT-diet. J Cardiothorac Surg 2010;5:127.

5. Cormack BE, Wilson NJ, Finucane K, West TM. Use of Monogen for pediatric postoperative chylothorax. Ann Thorac Surg 2004;77:301–5.

6. Paramés F, Freitas I, Fragata J, Trigo C, Pinto MF. Octreotide-additional conservative therapy for postoperative chylothorax in congenital heart disease. Rev Port Cardiol 2009;28:799–807.

7. Migliori C, Boroni G, Milianti S, Ekema G. Chylothorax. [Article in Italian] Minerva Pediatr 2010;62(3 Suppl 1):89–91.

[Abstract] 8. Das A, Shah PS. Octreotide for the treatment of chylothorax in neonates. Cochrane Database Syst Rev 2010;9:CD006388.

9. Panthongviriyakul C, Bines JE. Post-operative chylothorax in children: an evidence-based management algorithm. J Paediatr Child Health 2008;44:716–21.

10. Au M, Weber TR, Fleming RE. Successful use of somatostatin in a case of neonatal chylothorax. J Pediatr Surg 2003;38:1106–7.

11. Rimensberger PC, Müller-Schenker B, Kalangos A, Beghetti M.

North Clin Istanbul – NCI Treatment of a persistent postoperative chylothorax with somatostatin. Ann Thorac Surg 1998;66:253–4.

12. Soto-Martinez M, Massie J. Chylothorax: diagnosis and management in children. Paediatr Respir Rev 2009;10:199–207.

13. Kalomenidis I. Octreotide and chylothorax. Curr Opin Pulm Med 2006;12:264–7.

14. Goto M, Kawamata K, Kitano M, Watanabe K, Chiba Y. Treatment of chylothorax in a premature infant using somatostatin. J Perinatol 2003;23:563–4.

15. Helin RD, Angeles ST, Bhat R. Octreotide therapy for chylothorax in infants and children: A brief review. Pediatr Crit Care Med 2006;7:576–9.

16. Moreira-Pinto J, Rocha P, Osório A, Bonet B, Carvalho F, Duarte C, et al. Octreotide in the treatment of neonatal postoperative chylothorax: report of three cases and literature review. Pediatr Surg Int 2011;27:805–9.

17. Tutor JD. Chylothorax in infants and children. Pediatrics 2014;133:722–33.

18. Azkur D, Yoldas T, Toyran M, Kocabas CN. A pediatric case of anaphylaxis due to octreotide. Asian Pac J Allergy Immunol 2011;29:361–3.

19. Zanin A, Padalino MA, Cerutti A, Vida VL, Milanesi O, Stellin G, et al. Surgical ligation of cisterna chyli: an alternative treatment for chronic chylothorax in children. Ann Thorac Surg 2010;90:1732–4.

Case Report

Dermatology

North Clin Istanbul 2015;2(3):231–235 doi: 10.14744/nci.2015.95914

Pustular eruption induced by etanercept in a patient with ankylosing spondylitis: a rare side effect Asude Kara,1 Emine Tugba Alatas,2 Hilal Semra Celebi,2 Gursoy Dogan,2 Yelda Dere3 Department of Dermatology, Mugla Sitki Kocman University Training and Research Hospital, Mugla, Turkey

1

Department of Dermatology, Mugla Sitki Kocman University Faculty of Medicine, Mugla, Turkey

2

Department of Pathology, Mugla Sitki Kocman University Faculty of Medicine, Mugla, Turkey

3

ABSTRACT Etanercept is a tumor necrosis factor alpha (TNF-α) antagonist with anti-inflammatory effects. It is used in the treatment of dermatologic and rheumatologic diseases such as rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. However, etanercept has various cutaneous and systemic side effects. Herein, we report a case of generalized pustular eruption due to etanercept therapy in an ankylosing spondylitis patient and review pustular diseases.

Keywords: Ankylosing spondylitis; etanercept; pustular drug eruption.

E

tanercept is the first tumor necrosis factor-alfa (TNF-α) antagonist obtained from human protein. Etanercept is an FDA approved drug was firstly used in the treatment of rheumatoid arthritis (RA) in the year 1998. It has been used in the treatment of polyarticular juvenile rhematoid arthritis, psoriatic arthritis, anxylosing spondylitis (AS) and moderate-severe chronic plaque psoriasis with FDA approval [1]. Pustular eruption due to etanercept is rare. Pustular eruption commonly seen with antibiotics, corticosteroids, antiepileptic agents, anthistaminics, and nonsteroidal antiinflammatory drugs [2]. Herein, we report a case of pustular eruption developed due to etanercept therapy in an AS patient.

Case Report A 45-year-old male with the diagnosis of AS, consulted to our outpatient clinic with itching and pustular eruption on his palms, soles, trunk, and back.

His complaints had developed after the first course of etanercept treatment. The skin rash had started on the back 1.5 months ago and gradually had increased after the second and third courses of etanercept therapy, and finally had spread to the palms and soles.

The medical history was unremarkable. In the family history, mother of the patient had diabetes mellitus and hypertension, his father had coronary artery disease. The patient was generally healthy and had no fever. Laboratory tests were unremarkable. On

Received: December 26, 2014 Accepted: April 09, 2015 Online: July 24, 2015 Correspondence: Dr. Asude Kara. Mugla Sitki Kocman Universitesi Egitim ve Arastirma Hastanesi, Deri ve Zuhrevi Hastaliklar Klinigi, Mugla, Turkey.

Tel: +90 252 - 214 13 23 e-mail: asudekara@yahoo.com.tr © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul – NCI

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Figure 1.

Multiple pustular lesions on the palmoplantar areas and back.

dermatological examination, multiple erythematous pustules and papules were observed on the both palmar and plantar regions, trunk, and back (Figures 1–3). There was no bacterial growth on the culture media taken from the pustular lesion.

Histopathological examination revealed intraepidermal infiltration of neutrophils and eosinophils, and also inflammatory cells infiltration in the papillary dermis (Figure 3). We diagnosed the patient as pustular drug eruption with the histopathological and clinical findings. After withdrawal of the etanercept therapy, the skin lesions cleared within 3 weeks. Low-dose oral methylprednisolone, oral antihistaminic, and topical steroid therapies were started. We did not observe any new skin lesion during the follow-up of a year.

Discussion Pustular drug eruptions are rarely seen forms of drug reactions. In diagnosis of pustular drug

eruption, presence of suspicious drug use history, histopathological examination, and rule out of other pustular dermatoses are important. The most frequently responsible drugs are antibiotics, antifungal, antituberculostatic, and antiepileptic drugs. Pustular drug eruption due to TNF-α antagonists have been reported previously [3, 4].

TNF–α antagonists have been successfully used in the treatment of several chronic autoimmune and inflammatory diseases. Among these agents, etanercept is a recombinant TNF-α receptor (TNFR) fusion protein and constitutes of two extracellular components bound to Fc fragment of human IgG. It competitively inhibits the interaction of circulatory TNF-α with cell surface receptors [5].

It is an effective agent in the treatment of moderately severe chronic psoriasis, psoriatic arthritis, RA, juvenile rheumatoid arthritis, and AS. Although it has been safely used in many diseases, drug-induced adverse effects have been observed [6].

Etanercept has systemic adverse effects involving

Figure 2. Improvement in the skin lesions after the treatment.

Kara et al., Pustular eruption induced by etanercept in a patient with ankylosing spondylitis: a rare side effect

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Figure 3. Inflammatory cell infiltration in the epidermis and papillary dermis (H&E, x200), Neutrophils and eosinophils infiltration in the epidermis (H&E, x400).

activation of latent infections such as tuberculosis, increase the frequency of demyelinizating diseases, and development of malignancy [7]. In addition, cutaneous adverse effects of etanercept are not rare.

Cutaneous reactions have been reported in nearly 65 cases [7]. The most frequently reported cutaneous adverse effect of etanercept is injection site reaction.

This reaction is characterized by eythema, itching, pain, and edema on the injection site [7, 8]. In our case, we did not observe such a reaction during the etanercept therapy.

Etanercept induces various cutaneous symptoms that exacerbation of psoriasis symptoms is one of the adverse effects. It has been recommended that these symptoms should be treated as psoriasis and another TNF-α antagonist should be started in resistant cases [6]. However, in a case series reported in the literature, in two cases treated with antiTNF-α, upon development of psoriatic symptoms, another anti-TNF-α agent also induced psoriatic manifestations [9]. In the literature, apart from etanercept, exacerbation of psoriatic symptoms has been observed also with infliximab and adalimubab.

In a study performed by Joyau et al., pustular lesions, especially on palmoplantar regions, have been observed in the patients with AS, Crohn’s disease, RA, plaque psoriasis on anti-TNF-α therapy with the frequency of 33%. Of these patients, 1.7% had palmoplantar pustular psoriasis. In nearly half of the patients, these side effects developed secondary to infliximab. In the same study literature had been

reviewed and 42.9% of 184 cases on anti-TNF-α had pustular lesions as adverse effects [10].

Other cutaneous adverse effects due to etenarcept are eczematous eruptions, cutaneous lymphoma, herpes simplex infection, bacterial infections, lichenoid eruptions, erythema multiforme, lupus erythematosus, and acute generalized exanthematous pustulosis. Among 153 patients reported as case reports, psoriasis and its subtypes (n=38), skin infections (n=31), malignancies (n=15), lupus and related skin manifestations (n=19), and other non-specific skin diseases (n=35) have been found associated with adverse effects due to etanercept that nonspecific skin rash was the most frequently detected finding [7]. In only one case, generalized maculopapular eruption have been reported [11]. In a study, an increase in the frequency of pustular dermatitis has been reported during anti-TNF-α therapy. This study revealed that especially TNF-α blockage increased the release of interferon-alfa (IFN-α) and the frequency of pustular dermatitis and psoriasis [12].

In our case, we observed erythematous pustules and papules on both palmar and plantar regions, ventral side of trunk, and back as adverse effects of etanercept treatment.

In the differential diagnosis of pustular eruption, generalized pustular psoriasis, Reiter syndrome, subcorneal pustular dermatosis, acute generalized exanthematous pustulosis (AGEP), acneiform drug eruptions, folliculitis, eosinophilic folliculitis,

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Table 1. Clinical and histopathological features of pustular diseases Disease

Clinic

Histopathology

Generalized pustular psoriasis

Sterile pustules with erythematous surface on the back, extremities, and palmoplantar region

Spongioform neutrophilic pustules, parakeratosis, elongation of rete, and mononuclear cell infiltration in the dermis

Acute generalized exanthematous pustulosus

Fever, leukocytosis, nonfollicular sterile fistulas, involvement of skin folds, intact palmoplantar region

Spongioform pustules, massive edema in the superficial dermis, perivascular eosinophilic infiltration, and keratinocytic necrosis

Reiter syndrome

Urethritis, oligoarthritis, conjunctivitis, onset of vesicular and pustulous formation on the palmoplantar region, and then transform into hyperkeratotic lesions (keratoderma blennorrhagica)

Psoriasiform changes; epidermal hyperkeratosis and parakeratosis, acanthosis, elongation of retes and infiltration of mixed inflammatory cells

Subcorneal pustular dermatosis Loose sterile annular and serpinginous pustules with erythematous surface on the inguinal, axillary regions, flexor side of extremities, under breast, and abdomen

Subcorneal pustules containing neutrophils

Acneiform drug eruption

Follicular sterile pustules without comedones on the back, shoulders and upper arm

T-cell infiltration in follicular infundibulum, in suppurative folliculitis in hair follicle at late stage

Folliculitis

Follicular pustules on the scalp, axilla, inguinal region, and extremities

Follicular fistula

Eosinophilic folliculitis

In HIV patients sterile papules and pustules on the chest, scalp, and face; higher serum IgE levels

Follicular and perifollicular abscesses mainly with eosinopilic content

Palmoplantar pustulosis

Pustules on the palmoplantar region developing in a short time

Sterile intraepidermal pustules infiltrated with polymorphonuclear leukocytes

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis)

Various dermatological manifestations such as palmoplantar pustulosis, pustular psoriasis, and acne conglobata

Parakeratosis, hyperkeratosis, psoriasiform hyperplasia, and acanthosis

Hand, foot, and mouth disease

Vesiculopustules on the palmoplantar

Vacuolar and reticular degeneration in the epidermis

region and oral mucosa surrounded by an erythematous halo

Varicella

Polymorphous lesions consisting of papules, vesicles, and pustules on the scalp, back, face and extremities

palmoplantar pustulosis, SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis), handfoot-and-mouth disease, and viral diseases such as

Intracellular edema in the epidermis (balloon degeneration) and nuclear changes

varicella should be considered [3, 13, 14, 15, 16].

Clinical and histopathological examinations are helpful in the differential diagnosis (Table 1).

Kara et al., Pustular eruption induced by etanercept in a patient with ankylosing spondylitis: a rare side effect

Histopathologically, acanthosis and psoriatic changes at dermoepidermal junction are seen in pustular psoriasis, whereas massive edema in the superficial dermis, perivascular eosinophilic infiltration, and keratinocytic necrosis are seen in AGEP [8]. Histopathological examination of our patient revealed intraepidermal cells infiltration involving neutrophils and eosinophils and also inflammatory cells infiltration in the papillary dermis. We diagnosed the patient as pustular drug eruption with these clinical and histopathological findings.

In conclusion, cutaneous side effects can be seen with etanercept therapy and the therapy should be discontinued if these adverse effects develop.

Adverse effects regress with cessation of etanercept therapy in most cases, however, cutaneous symptoms should be treated in some cases [7, 8]. We observed marked improvement in the skin lesions after cessation of etanercept therapy. In addition, we also started therapies for cutaneous symptoms.

Informed consent of the patient was obtained: Received.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Akdeniz N, Çalka Ö, Bilgili SG. Biyolojik ajanlar. In: Tüzün Y, Serdaroğlu S, Erdem C, Özpoyraz M, Önder M, Öztürkcan S, editor. Dermatolojide tedavi. İstanbul: Nobel Tıp Kitapevleri 2010. p. 927–41.

2. Adams BB, Mutasim DF. Pustular eruption induced by olanzapine, a novel antipsychotic agent. J Am Acad Dermatol 1999;41(5 Pt 2):851–3.

3. Mengesha YM, Bennett ML. Pustular skin disorders: diagnosis and treatment. Am J Clin Dermatol 2002;3:389–400.

4. Vasconcelos LMF, Teixeira FM, Francelino EV, Almeida TLP,

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Chagas LB, Valença JT, et al. Acute generalized exanthematous pustulosis in a 51-year- old patient under etanercept treatment for psoriasis. J Pharmacovigilance 2014;2:120.

5. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253–9.

6. Collamer AN, Guerrero KT, Henning JS, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action.

Arthritis Rheum 2008;59:996–1001.

7. Kavala M, Zindancı I, Türkoglu Z, Can B, Kocatürk E, Senol S, et al. Acute generalized exanthematous pustulosis induced by etanercept: another dermatologic adverse effect. Case Rep Dermatol Med 2013;2013:601412.

8. Revuz J, Valeyrie-Allanore L. Drug Reactions. In: Bolognia JL, editor. Dermatology 2012;21:335–56.

9. Cohen JD, Bournerias I, Buffard V, Paufler A, Chevalier X, Bagot M, et al. Psoriasis induced by tumor necrosis factor-alpha antagonist therapy: a case series. J Rheumatol 2007;34:380–5.

10. Joyau C, Veyrac G, Dixneuf V, Jolliet P. Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect? Clin Exp Rheumatol 2012;30:700–6.

11. Lai-Cheong J, Warren R, Bucknall R, Parslew R. Etanerceptinduced dermatitis in a patient with rheumatoid arthritis. J Eur Acad Dermatol Venereol 2006;20:614–5.

12. de Gannes GC, Ghoreishi M, Pope J, Russell A, Bell D, Adams S, et al. Psoriasis and pustular dermatitis triggered by TNF{alpha} inhibitors in patients with rheumatologic conditions. Arch Dermatol 2007;143:223–31.

13. Dimitrova V, Yordanova I, Pavlova V, Valtchev V, Gospodinov D, Parashkevova B, et al. Keratoderma blenorrhagicum in a patient with Reiter syndrome. J of IMAB 2008;14:68–71.

14. İlaç ve diğer tedavi reaksiyonları. In: Baykal C, editör. Dermatoloji atlası. 3. baskı. İstanbul: Nobel Tıp Kitapevleri 2012. p. 344–69.

15. Zhao Z, Li Y, Li Y, Zhao H, Li H. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with review of the relevant published work. J Dermatol 2011;38:155–9.

16. Öztürkcan S. Derinin viral hastalıkları. In: Tüzün Y, Serdaroğlu S, Erdem C, Özpoyraz M, Önder M, Öztürkcan S, editor.

Dermatolojide tedavi. İstanbul: Nobel Tıp Kitapevleri 2010. p.

554–650.

Case Report

Pediatric Surgery

North Clin Istanbul 2015;2(3):236–238 doi: 10.14744/nci.2015.86548

Non-classified type duodenal atresia: case report Emrah Aydin Department of Pediatric Surgery, Bahcelievler State Hospital, Istanbul, Turkey

ABSTRACT Our aim is to present a case with initial diagnosis of non-classified type duodenal atresia operated in our clinic.

A patient with prenatally suspected to be duodenal atresia was explored. At laparotomy type 3 duodenal atresia was found between 2nd and 3rd parts of duodenum. In addition, a web was detected distal to the atresic part. Duodenoduodenostomy together with web excision was performed. He had not any additional pathology. Although duodenal atresia is a very well known pathology by pediatric surgeons, though rarely a non-classified type duodenal atresia can be encountered. Possible presence of a second atresia should be kept in mind, proximal and distal segments of the duodenum and intestinal passage must be explored carefully for the presence of second atresic segment before performing duodenoduodenostomy.

Keywords: Duodenal atresia.

D

uodenal atresia is seen in an average of every 5000–10000 live births which is more frequent in baby girls rather than baby boys [1]. Atresia usually occurs at the second part of the duodenum [1, 2]. In more than 50% of the cases associated congenital anomalies are seen [2].

The classification of duodenal atresia encompass a spectrum from duodenal stenosis to complete separation of proximal and distal parts of the duodenum. Besides, it is classified as pre- and postampullar based on its location relative to ampulla vateri. Rarely, through a “Y” shaped biliary ductuli, bile flow can be provided for both atresic parts [3,

4]. With our case, Type 3 duodenal atresia associated with udodenal web which is not included in the classical classification is presented.

Case Report A baby boy weighing 2930 g delivered via cesarean section at 36. gestational week to a G2P2 mother was admitted to our intensive care unit with initial diagnosis of duodenal atresia. His prenatal ultrasound obtained at 29. gestational week revealed suspect polyhydramnios and duodenal atresia. The first evaluation of his postnatal radiogram which

Received: January 30, 2015 Accepted: July 09, 2015 Online: December 25, 2015 Correspondence: Dr. Emrah Aydin. Bahcelievler Devlet Hastanesi, Kocasinan Merkez Mahallesi, Karadeniz Caddesi, No: 48, Bahcelievler, Istanbul, Turkey.

Tel: +90 212 - 496 70 00 e-mail: dremrahaydin@yahoo.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Aydin, Non-classified type duodenal atresia

demonstrated a double-bubble image could not disclose any additional pathology (Figure 1). Nasogastric drainage was devoid of any evidence of bile. On postnatal 3. day he was operated. During laparotomy dilated stomach and first part of the duodenum were seen. Between the proximal and distal parts of the duodenum luminal integrity was not found (Figure 2). Exploration of the proximal part of the duodenum could not detect any secretion of bile. Distal part was tried to be catheterized vith 10 F Foley catheter and a 5 F Fogarthy balloon catheter so as to detect a second atresic segment and a distal duodenal web 1.5 cm away from atresic part was disclosed. Following excision of the web, Foley catheter could be hardly advanced up to the distal part. Air and isotonic serum delivered from duodenum up to the distal part of the bowel passed freely up to the most distal part of the duodenum. Then bilious secretion was seen to flow from the distal duodenum. Choleduct was

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retrogradely catheterized with 3 F ureteral stent (Figure 3). Proximal duodenum was catheterized using Foley catheter and any additional pathology could not be detected. Diamond shaped duodenoduodenostomy was performed. Postoperative 5. day, oral nutrition was started, he could receive full dose nutrition. On postoperative 7. day, he was discharged from the hospital with cure. He is currently at his postoperative 7. month without any medical problem.

Figure 2. Proximal and distal parts of the duodenum.

Figure 1. Double-bubble appearance on abdominal radiogram.

Figure 3. Choleduct was catheterized retrogradely using a 3 F ureteral stent.

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Discussion Duodenal atresia can be diagnosed beginning from the early stages of pregnancy in line with developments in diagnostic methods [4]. Gastroduodenal dilation seen in ultrasound during prenatal period is diagnostic for duodenal atresia or stenosis. Upright plain abdominal radiograms of the newborns which demonstrate double air levels and distal bowel devoid of intestinal gas have diagnostic values [3, 4]. Also in our case, ultrasonographic examination performed at prenatal 29. week revealed dilated stomach and duodenum in the upper abdominal quadrant. Upright abdominal radiogram obtained with suspect duodenal atresia disclosed a “double-bubble” image.

When literature series are reviewed, in more than 50% of the cases association of duodenal atresia with down syndrome, esophageal atresia, anal atresia and cardiac problems can be seen [2]. In our case, preoperative examinations could not detect any additional anomaly. However, during laparotomy, distal to the Type 3 duodenal atresia a duodenal web was detected. In a study by Escobar et al. the authors reported that all of their 137 cases with duodenal atresia were amenable to classical classification [5]. However, Lin et al. shared 20 years of their experience concerning gastrointestinal system webs, reported only presence of a duodenal atresia in only one of their 37 cases [6]. Grosfeld et al. reported duodenal web in only 1–3% of their cases with duodenal atresia [7]. In our clinic, previously two cases with double duodenal web were detected, however Type 3 duodenal atresia associated with duodenal web has not been encountered so far.

In cases with duodenal atresia surgery is the treatment modality and in technically suitable cases most frequently diamond shaped duodenoduodenostomy is preferred. Ruangtrakool et al. reported that in cases with duodenal web, web excision and duodenoplasty were performed with outcomes comparable to duodenoduodenostomy [8]. In our clinic, in both conditions we prefer duodenoduo-

North Clin Istanbul – NCI

denostomy. In our case also diamond shaped duodenoduodenostomy was performed and at postoperative 7. month any complication has not been encountered so far.

Duodenal atresia is a well known pathology by pediatric surgeons, though rarely one can encounter non-classified cases. Therefore, before proceeding with duodenotomy, possibilities of concomitant second atresia or web should be kept in mind and during the procedure, presence of any atresic distal and/or proximal segment should be investigated.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Kimura K, Loening-Baucke V. Bilious vomiting in the newborn: rapid diagnosis of intestinal obstruction. Am Fam Physician 2000;61:2791–8.

2. Hajivassiliou CA. Intestinal obstruction in neonatal/pediatric surgery. Semin Pediatr Surg 2003;12:241–53.

3. Miller AJW, Rode H, Cywes S. Intestinal atresia and stenosis.

In: Ashkraft KW, Holcomb III GW, Murphy JP, eds. Pediatric surgery 2005. p. 416–34.

4. Rode H, Numanoglu A. Congenital atresia and stenosis of the small intestine. In: Spitz L, Coran AG, eds. Operative pediatric surgery 2006. p. 393-404.

5. Escobar MA, Ladd AP, Grosfeld JL, West KW, Rescorla FJ, Scherer LR 3rd, et al. Duodenal atresia and stenosis: long-term follow-up over 30 years. J Pediatr Surg 2004;39:867–71.

6. Lin HH, Lee HC, Yeung CY, Chan WT, Jiang CB, Sheu JC, et al. Congenital webs of the gastrointestinal tract: 20 years of experience from a pediatric care teaching hospital in taiwan. Pediatr Neonatol 2012;53:12–7.

7. Grosfeld JL, Rescorla FJ. Duodenal atresia and stenosis: reassessment of treatment and outcome based on antenatal diagnosis, pathologic variance, and long-term follow-up. World J Surg 1993;17:301–9.

8. Ruangtrakool R, Mungnirandr A, Laohapensang M, Sathornkich C. Surgical treatment for congenital duodenal obstruction. J Med Assoc Thai 2001;84:842–9.

Case Report

General Surgery

North Clin Istanbul 2015;2(3):239â&#x20AC;&#x201C;242 doi: 10.14744/nci.2015.97268

A rare cause of gastric obstruction: Lighters swallowing Ulas Aday, Ali Tardu, Mehmet Ali Yagci, Huseyin Yonder Department of General Surgery, Inonu University Faculty of Medicine, Malatya, Turkey

ABSTRACT The majority of swallowed foreign bodies are thrown spontaneously without causing complications in the digestive system. Multiple number of foreign bodies may be swallowed by psychiatric patients which delay diagnosis and increase the complication rate. Long and hard objects cannot pass through the pylorus, and may cause obstruction, ulceration, bleeding and perforation. Endoscopy is used as an effective method in such cases. An exploratory laparatomy was performed after unsuccessful endoscopic foreign object removal in a 28-year-old schizophrenic patient with gastric outlet obstruction due to multiple cigarette lighter swallowing. Ten lighters were removed from the stomach through gastrotomy and one more lighter was removed from the descending colon by milking through the anus. The aim of this paper is to discuss encountered difficulties in psychiatric patients who underwent surgery due to intake of foreign bodies.

Keywords: Foreign body; schizophrenia; stomach.

T

hough swallowing foreign objects is seen in children, it is more frequently observed in elder people, mentally retarded group, prisoners, and patients with psychiatric disorder. Surgical treatment is applied in 1% of the patient group when endoscopic interventions remain adequate or complications develop [1]. Patients with psychosis like schizophrenia tend to swallow usually multiple foreign objects repetitively. Since the patients do not give history of swallowing foreign objects, diagnosis is delayed, and risk of complications increases [2].

In our study in a 28-year-old patient with the diagnosis of schizophrenia who developed gastric outlet obstruction has been presented in the light of current literature.

Case report A 28-year-old male patient consulted to the emergency service with complaints of abdominal pain, nausea, and vomiting persisting for two days. His physical examination did not reveal any finding except for tenderness over epigastrium. He was diagnosed as schizophrenia, but he was not receiving antipsychotic drugs. His whole blood cell counts, and biochemical parameters were not remarkable.

Multiple radiopaque images of foreign objects were seen in the stomach on his upright abdominal radiograms (Figure 1). His mother said that two years ago he swallowed a metal coin which was extracted using endoscopic intervention. The patient under-

Received: March 27, 2015 Accepted: June 06, 2015 Online: December 25, 2015 Correspondence: Dr. Ali Tardu. Inonu Universitesi Tip Fakultesi, Genel Cerrahi Klinigi, Malatya, Turkey.

Tel: +90 422 - 341 06 60 e-mail: tarduali@gmail.com Š Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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Figure 1. Multiple number of lighters in the stomach. went gastrointestinal endoscopy on an emergency basis with the initial diagnosis of foreign object which caused pyloric obstruction Since the stomach was full of food remnants the ingested foreign objects could not be identified, and examination was repeated after 12 hours of fasting. During the second endoscopic procedure multiple number of lighters which filled the stomach almost completely were observed. Endoscopic removal of the lighters was attempted, however injury of the distal part of the esophagus necessitated termination of the procedure, and urgently open surgery was planned.

Preoperatively, plain abdominal radiograms were obtained, and one lighter which had previously passed through the stomach, and engaged in the descending colon was detected (Figure 2). During laparotomy an induration caused by multiple number of lighters were detected on palpation. A dilated stomach was observed. A nearly 2 cm-long gastrotomy incision was made on the anterior surface of the antrum, and 10 lighters each measuring 8x2 cm were extracted through this incision (Figure 3). Small bowel, and colon were explored in detail.

One lighter in the descending colon was manually milked away from the anal canal. After confirmation of absence of any foreign object by using intraoperative fluoroscopy, gastrotomy defect was closed in two layers. On the postoperative second day oral

Figure 2. One lighter in the descending colon.

Figure 3. Ten lighters extracted from inside the stomach. intake was started, and the patient was discharged with cure on the postoperative 5. day.

Discussion Ingestion of foreign object frequently occurs accidentally during intake of oral food. In most of the cases, ingredients of food, and bony particles are detected. In elder people, dental prostheses, and in mentally retarded people, and psychiatric patients frequently multiple number of atypical objects are observed [1, 3].

Aday et al., A rare cause of gastric obstruction: Lighters swallowing

In psychiatric patient group, self-inflicting behaviours are observed. In this condition with potential recurrences, patient does not either intend to commit suicide or consciously try to injure him/ herself. Since most of the patients do not mention swallowing a foreign object, diagnosis is usually delayed, and complications increase. Generally multiple number of various kinds of foreign objects are swallowed [2, 4]. Mother of this patient said that her son had swallowed a metal coin two years ago. Besides he had swallowed more than two foreign objects.

Clinical picture, and treatment approach change according to the shape, size, number, and level of the foreign object. Since most of the foreign objects are radiopaque, plain abdominal radiography is priorly resorted imaging modality which provides information about the number, size, and location of the foreign object. Still endoscopy can be used at the same time for diagnostic purposes. However computed tomography is used in the presence of complications, and in the identification of radiolucent foreign objects which can not be visualized using plain radiograms [5]. In our case, for initial diagnosis plain radiogram was used, then endoscopy was applied to make a definitive diagnosis.

In 80–90% of the cases, swallowed foreign objects are eliminated naturally through gastrointestinal tract without any complication [3]. Twelve percent of the swallowed foreign objects can not pass through pylorus, and stuck in the stomach. In cases with obstruction, and intake of sharp objects which cause penetrating-stab injuries, and also large objects (width >2 cm, and length >6 cm) which presumably can not be eliminated through gastrointestinal tract, endoscopic intervention should be preferred as the first-line treatment with its higher success, and lower complication rates [6, 7, 8]. Long, solid, and rigid objects can cause gastric outlet obstruction, and by adhering to the gastrointestinal mucosa can induce ulcerations, bleeding, and perforation. Since liquid in the lighters contains toxic chemicals as benzene, butane, hexamine, and propane, and lighters are rigid objects measuring generally more than 6 cm in length, their extraction is recommended [3, 6]. Especially, in children, and patients with psychiatric disorders, longer duration of endoscopic intervention, and incompliance of the

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patient require an effective sedation, and intubation is recommended in case of need. In experienced hands, and in the presence of adequate equipment, endoscopic extraction procedures have a 95% success rate [7, 8, 9].

Scarce number of foreign objects require surgical treatment. In cases with perforation, obstruction, internal fistulas, abscess, and failed endoscopic interventions, surgical treatment is performed. Type of the surgical procedure differs according to potential complication, and location of the foreign objects [5, 10]. In our case multiple number of lighters which obstructed gastric outlet were tried to be removed using endoscopic interventions. However because of injury of the esophageal mucosa, and multiple number of lighters swallowed, endoscopic procedures failed, and the patient underwent open gastrotomy so as to extract 10 lighters.

In conclusion, in cases evaluated because of swallowing multiple number of foreign objects, before surgical operation, radiograms should be obtained if radiopaque objects are identified. Intraoperative exploration should be performed, if the foreign object is radiopaque, in case of need, fluoroscopic examination should be carried out to confirm that all foreign objects are removed completely. Especially, as was the case in our patient, in patients with psychiatric disorders, it should not be forgotten that multiple number of foreign objects might be swallowed at various time points.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Erbil B, Karaca MA, Aslaner MA, Ibrahimov Z, Kunt MM, Akpinar E, et al. Emergency admissions due to swallowed foreign bodies in adults. World J Gastroenterol 2013;19:6447–52.

2. Mutlu H, Aydın B: Ölüm nedeni 41 lira, 32 kuruş: Bir olgu. Anadolu Psikiyatri Derg 2014;15:89.

3. Trgo G, Tonkic A, Simunic M, Puljiz Z. Successful endoscopic removal of a lighter swallowed 17 months before. Case Rep Gastroenterol 2012;6:238–42.

4. Petrea S, Brezean I. Self-ingested intraduodenal foreign bodies-expectancy or surgical sanction? J Med Life 2014;7:421–7.

5. Ricci S, Massoni F, Schiffino L, Pelosi M, Salesi M. Foreign

242 bodies ingestion: what responsibility? J Forensic Leg Med 2014;23:5–8.

6. Bektaş A, Bahar K, Özkan H, Yurdaydın C, Özşahin T, Karayalçın S. Foreign bodies in gastrointestinal tract: A case report. Turk J Gastroenterology 1998;1: 81-4.

7. Sugawa C, Ono H, Taleb M, Lucas CE. Endoscopic management of foreign bodies in the upper gastrointestinal tract: A review. World J Gastrointest Endosc 2014;6:475–81.

8. Emara MH, Darwiesh EM, Refaey MM, Galal SM. Endoscopic

North Clin Istanbul – NCI removal of foreign bodies from the upper gastrointestinal tract: 5-year experience. Clin Exp Gastroenterol 2014;7:249–53.

9. Katsinelos P, Kountouras J, Paroutoglou G, Zavos C, Mimidis K, Chatzimavroudis G. Endoscopic techniques and management of foreign body ingestion and food bolus impaction in the upper gastrointestinal tract: a retrospective analysis of 139 cases. J Clin Gastroenterol 2006;40:784–9.

10. Petrea S, Brezean I. Self harm through foreign bodies ingestion rare cause of digestive perforation. J Med Life 2014;7:246–53.

Case Report

Psychiatry

North Clin Istanbul 2015;2(3):243–246 doi: 10.14744/nci.2015.63634

Parkinsonism secondary to duloxetine use: a case report Arzu Bayrak, Bugra Cetin, Handan Meteris, Sermin Kesebir Department of Psychiatry, Erenkoy Training and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey

ABSTRACT In literature, there are more than hundred cases of extrapyramidal symptoms (EPS) associated with selective serotonin reuptake intibitors (SSRI) whereas EPS case reports associated with serotonin noradrenaline reuptake inhibitors (SNRI) are in a relatively small number. A SNRI group drug duloxetine that is used for indication of major depression since 2004 is a double acting antidepressant that acts by blocking serotonin and noradrenaline reuptake. Side effects of duloxetine on extrapyramidal system are not expected due to low affinity to D2 receptors. In this case report manifestations of parkinsonism developed in a patient who used duloxetine for major depression are presented. Since any duloxetine induced EPS case has not reported so far, we have thought that this case can contribute to the literature.

Keywords: Duloxetine; extrapyramidal symptoms; parkinsonism.

D

epression therapy can be defined as a process that was started with tricyclic antidepressants (TCA) and goes on with many kind of antidepressants like SSRIs, SNRIs and it continuously renews itself. It has been relatively 23 years since first antidepressant fluoxetine from SSRI group was started to be used in the treatment of depression [1]. Meanwhile, SSRI group are used widely so that side effects of this group of drugs have been oberved. These side effects include nausea, diarrhea and gastric irritation when the SSRIs were taken on an empty stomach due to their effects on gastrointestinal system, sexual dysfunction due to inhibition of serotonin reuptake and headache, vertigo, weight gain and weight loss during the early period of treatment. Also insomnia, irritability, agitation,

tremor and extrapyramidal system symptoms are observed due to SSRI’s effects on central nervous system [2]. Their extrapyramidal system symptoms can be sorted in decreasing order of frequency as akathisia, dystonia, parkinsonism and tardive dystonia [3]. Side effects of drugs on extrapyramidal system are rare relative to other side effects [4].

In some studies, drugs in the SNRI group were found to be more effective than those in the SSRI group [5]. An SNRI group drug duloxetine that is used for the indication of major depression since 2004 is a double acting antidepressant that acts as serotonin and noradrenaline inhibitor [1, 6]. It inhibits dopamine reabsorption weakly and has a low affinity to histamine 1, alfa 1, beta 1, 5HT1, cholinergic, histaminergic, D2, opioid and glutama-

Received: November 16, 2014 Accepted: September 08, 2015 Online: December 25, 2015 Correspondence: Dr. Bugra Cetin. Erenkoy Ruh ve Sinir Hastaliklari Egitim ve Arastirma Hastanesi, Istanbul, Turkey.

Tel: +90 216 - 302 59 59 e-mail: cetinbugra@gmail.com © Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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tergic receptors [6]. SNRI group drugs have similar side effects with drugs in the SSRI group. Minimal increase in heart rate, increase in blood pressure, nausea, vomiting, tiredness, somnolence or insomnia, headache, vertigo, sweating and dry mouth have been reported as side effects of duloxetine due to inhibition of noradrenaline reuptake [6]. Side effects on extrapyramidal system are not expected due to low affinity to D2 receptors.

In the literature there are more than a hundred cases of EPS associated with SSRIs whereas case reports concerning EPS induced by SNRIs are in a relatively small number [3]. There is not any case report of parkinsonism associated with venlafaxine.

However, three cases of akathisia has been reported with venlafaxine [7, 8, 9].

One case that developed dyskinesia with duloxetine is reported [10].

In a review of duloxetine induced 59 cases with EPS, extrapyramidal symptoms including tremor (34%), akathisia (14%), dyskinesia (13%), tardive dystonia and dystonia (8%) were detected in respective percentage of patients [11].

There are two cases of milnacipran induced parkinsonism [12, 13].

In this case report a patient using duloxetine for major depression who developed parkinsonism symptoms was presented. Since any duloxetine induced EPS case hasn’t been reported before, this case can contribute to the literature.

Case Report S. A. was a 45-year- old, secondary school graduate, married housewife. She was admitted to outpatient service with complaints of social isolation, insomnia, reluctance and occasional cryings that started one year ago with increasing frequency. Her complaints intensified with her daughter’s marriage which happened 6 months previously. She attempted suicide for 4 times within the last four months and she was complaining basically about the problems in her family. She did not receive regular treatment in the past and she had not suffered from a medical illness in the past.

In the psychiatric assessment, she was appearing at her chronological age. Her psychomotor activity was normal and she had depressed mood and

affect. Any psychotic symptom was not detected.

Deficiency in her voluntary and involuntary attention was observed. She was entertaining suicidal thoughts. Her judgement and insight were intact.

After anamnesis and psychiatric assessment, depression and cluster B personality disorder were diagnosed and the patient was admitted to mood disorder clinic. Olanzapine (10 mg 1x1) and mirtazapine (30 mg 1x1) treatment was started. With this treatment partial remission was obtained. Any side effects were not observed. After 23 days of hospitalization she was discharged to be followed up on an ambulatory basis. After 15 days in the outpatient clinic, based on her anamnesis, her symptoms of reluctance, social isolation, cries and anhedonia aggravated. Duloxetine 60 mg/day was added to the treatment. In this examination, she did not define any physical complaint. Fifteen days later, in the second visit, she was having difficulty in walking with rigidity, restlessness and tremor in her hands. In the examination, cogwheel rigidity, increase in muscle tone, bradikynesia, rigidity and tremor at rest were determined. Patient’s symptoms could not be explained with the use of any drug other than duloxetine. Duloxetine and the other drugs were ceased due to patient’s disturbance and then biperiden (2 mg bid) treatment was started. At the third visit 15 days later her complaints decreased markedly. At the following visits biperiden treatment was ceased and any extrapyramidal system symptoms were not seen. Cranial MR imaging was not remarkable.

Discussion Pathophysiology of parkinsonism resulting from SSRI and SNRI group drugs is still not clearly understood. It is reported that it can be derived from the interaction between serotonin and norepinephrine in the cortex and basal ganglia and might be related with dopamine function [4]. The inhibitory effect of increase in serotonin transmission on dopamine pathway is another proposed [14].

It has been suggested that drugs may cause EPS with a change in postsynaptic transmission of dopamine receptors resulting in pathophysiological changes in basal ganglions [15].

Another proposed vision of developing parkinsonism with drugs is that it might be associated

Bayrak et al., Parkinsonism secondary to duloxetine use

with a predisposition to Parkinson’s disease [16].

Drug interactions are another mechanism that is related with the etiology of EPS associated with SSRIs and SNRIs. Duloxetine is metabolized by the enzymes cytochrome 1A2 and 2D6 and especially inhibition of CYP 1A2 increases duloxetine level markedly. Duloxetine causes drug interactions by inhibiting the enzymes CYP 1A2 mildly and CYP 2D6 moderately [17]. In our case, the patient was receiving duloxetine and olanzapine. Olanzapine is the molecule that is, metabolized mostly by CYP 1A2 and then by CYP 2D6 [18] . Due to mild inhibition of CYP 1A2 by duloxetine, we think that EPS in our patient is not related with the drug interactions but with the molecule itself. Although case reports of EPS secondary to duloxetine are rare, according to FDA Adverse Event Reporting System (AERS) incidence of EPS induced by duloxetine is higher than that induced by sertraline, escitalopram, fluoxetine and bupropion [11].

When we have reviewed the cases of EPS caused by antidepressants, we have seen that EPS were observed more often when there were predisposing factors such as psychomotor disorder, extrapyramidal symptoms that developed secondary to another drug use in the past, different kinds of drug applications at the same time, insufficiency of cytochrome enzymes, simultaneous Parkinson’s disease, recent cessation of monoamine oxidase inhibitors [19].

Some studies have demonstrated that the presence of A1 allele in the polymorphism of D2 dopamine receptor gene taq 1a is a risk factor for EPS [20].

Ageing and female sex are also risk factors for antidepressant- induced EPS [11]. No family history for Parkinson’s disease, simultaneous onset of movement disorder and duloxetine treatment did not provide supportive evidence about drug induced parkinsonism in this 45-year-old women.

In cases of antidepressant induced EPS, dose of drug can be reduced or it can be ceased or replaced by another antidepressant [3]. In some cases underlying concealed Parkinson’s disease can emerge by using antidepressants. At that time levodopa can be added to treatment [12]. In our case EPS emerged by adding duloxetine to the patient’s current antipsychotic treatment and due to her complaints’ severity treatment was ceased. Then biperiden (4 mg/ day) was started. After her complaints disappeared

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another antidepressant ie.fluoxetine is started.

Recently SNRIs are being used commonly just like SSRIs. It should be remembered that antidepressant associated EPS can occur at any time of the treatment. Monitorization of these side effects are important for both clinicians and patients.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Schatzberg AF, Cole JO, DeBattista C. Klinik Psikofarmakoloji.

Bozkurt A (Çeviri editörü) 6. Baskı, Ankara: Ayrıntı Basımevi 2010:35–157.

2. Hariri AG, Ceylan ME. Depresyonda İlaç Tedavisi:Özgül Serotonin Gerialım Engelleyicileri. Duygudurum Dizisi 2003;7:339– 45.

3. Gerber PE, Lynd LD. Selective serotonin-reuptake inhibitor-induced movement disorders. Ann Pharmacother 1998;32:692–8.

4. Gill HS, DeVane CL, Risch SC. Extrapyramidal symptoms associated with cyclic antidepressant treatment: a review of the literature and consolidating hypotheses. J Clin Psychopharmacol 1997;17:377–89.

5. Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biol Psychiatry 2007;62:1217–27.

6. Yüksel N. Duloksetin: Farmakolojisi. Klinik Psikiyatri 2009;12(Ek 1):3–8.

7. Ng J, Sansone RA, McDonald S. Akathisia and abnormal movements of the upper extremities with venlafaxine and methimazole. Gen Hosp Psychiatry 2009;31:388–90.

8. George M, Campbell JJ 3RD. Venlafaxine causing akathisia: a case report. J Neuropsychiatry Clin Neurosci 2012;24:3–4.

9. Lai CH. Venlafaxine-related akathisia side-effects and management in a depressed patient. Psychiatry Clin Neurosci 2013;67:127–8.

10. Deuschle M, Mase E, Zink M. Dyskinesia during treatment with duloxetine. Pharmacopsychiatry 2006;39:237–8.

11. Madhusoodanan S, Alexeenko L, Sanders R, Brenner R. Extrapyramidal symptoms associated with antidepressants--a review of the literature and an analysis of spontaneous reports. Ann Clin Psychiatry 2010;22:148–56.

12. Arai M. Parkinsonism associated with a serotonin and noradrenaline reuptake inhibitor, milnacipran. J Neurol Neurosurg Psychiatry 2003;74:137–8.

246 13. Muraoka T, Oku E, Sugataka K, Yamada S. A case of severe parkinsonism associated with short-term treatment with milnacipran. Clin Neuropharmacol 2008;31:299–300.

14. Damsa C, Bumb A, Bianchi-Demicheli F, Vidailhet P, Sterck R, Andreoli A, et al. “Dopamine-dependent” side effects of selective serotonin reuptake inhibitors: a clinical review. J Clin Psychiatry 2004;65:1064–8.

15. Dixit S, Khan SA, Azad S. A Case of SSRI Induced Irreversible Parkinsonism. J Clin Diagn Res 2015;9:VD01-VD02.

16. Gönül AS, Aksu M. SSRI-induced parkinsonism may be an early sign of future Parkinson’s disease. J Clin Psychiatry 1999;60:410.

17. Knadler MP, Lobo E, Chappell J, Bergstrom R. Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmaco-

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18. Urichuk L, Prior TI, Dursun S, Baker G. Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab 2008;9:410–8.

19. Lane RM. SSRI-induced extrapyramidal side-effects and akathisia: implications for treatment. J Psychopharmacol 1998;12:192– 214.

20. Hedenmalm K, Güzey C, Dahl ML, Yue QY, Spigset O. Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms. J Clin Psychopharmacol 2006;26:192,7.

REVIEW

PM&R

North Clin Istanbul 2015;2(3):247â&#x20AC;&#x201C;252 doi: 10.14744/nci.2016.71601

What is hippotherapy? The indications and effectiveness of hippotherapy Tuba Tulay Koca,1 Hilmi Ataseven2 Department of Physical Medicine and Rehabilitation, Malatya State Hospital, Malatya, Turkey

1

Public Hospitals Union, Malatya, Turkey

2

ABSTRACT Hippotherapy is a form of physical, occupational and speech therapy in which a therapist uses the characteristic movements of a horse to provide carefully graded motor and sensory input. A foundation is established to improve neurological function and sensory processing, which can be generalized to a wide range of daily activities. Unlike therapeutic horseback riding (where specific riding skills are taught), the movement of the horse is a means to a treatment goal when utilizing hippotherapy as a treatment strategy. Hippotherapy has been used to treat patients with neurological or other disabilities, such as autism, cerebral palsy, arthritis, multiple sclerosis, head injury, stroke, spinal cord injury, behavioral disorders and psychiatric disorders. The effectiveness of hippotherapy for many of these indications is unclear, and more research has been needed. Here, we purpose to give information about hippotherapy which is not known adequately by many clinicians and health workers.

Key words: Equine-assisted therapy; hippotherapy; therapeutic horse back riding.

H

ippotherapy is a physical, occupational, and speech therapy that utilizes the natural gait and movement of a horse to provide motor, and sensory input. It is based on improvement of neurologic functions, and sensory processes, and used for patients with physical, and mental disorders.

Especially in paralyzed individuals it contributes to physical rehabilitation programs [1, 2].

Herein, we wanted to provide information about hippotherapy whose effectiveness has been demonstrated in scientific studies, and so prevalently used in many countries in the fields of physical, and

mental disabilities. In our study, recognition of the importance of this new method for our country will provide benefit for many patient groups.

Diagnosis Hippotherapy means treatment with the aid of a horse. Despite long-term use in history, only a few studies have been performed on its theoretical basis.

Only scarce information are available on its psychological, physical, social, and educational effects in specially trained children. Hippotherapy is a treatment method with concurrently favourable psy-

Received: November 27, 2015 Accepted: January 09, 2016 Online: January 15, 2016 Correspondence: Dr. Tuba Tulay Koca. Malatya Devlet Hastanesi, Fiziksel Tip ve Rehabilitasyon Klinigi, Malatya, Turkey.

Tel: +90 416 - 228 28 00 e-mail: tuba_baglan@yahoo.com Š Copyright 2015 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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chological, social, and educational effects on many organ systems including sensory, musculoskeletal, limbic, vestibular, and ocular systems [3, 4, 5].

History, and hippotherapy in the world Hippotherapy consists of the words meaning horse” hippos”, and treatment” therapy” in ancient Greek. It is defined as equine-assisted treatment. Firstly it was mentioned in the works of Hippocrates. However, it has not become a discipline with an established protocol up to 1960s. During 1960s, it is used as an adjunct to traditional physical therapy in Germany, Austria, and Sweeden. In countries as Germany, Austria, and Sweeden which used the horse in physical therapy the term “hippotherapy” was introduced into medical literature. During 1970s in the United States of America (USA ) hippotherapy was started to be standardized [1, 2, 3, 6].

It was standardized by a group of Canadian, and American therapists who traveled to Germany in order to learn hippotherapy near the end of 1980s.

American Hippotherapy Association (AHA) was founded in the year 1992, and established an official, and international protocol. In the year 1994 certification document, and standards for certified hippotherapy clinical specialist (HPSC) were established, and in 1999 the first certification examination was realized. This certification program consists of three steps, and encompasses a training period of 3 years [1, 6].

With certification program bestowed by American Hippotherapy Association hippotherapist assumes the title of hippotherapy clinical specialist (HPSC). These specialists have knowledge, and experience about hippotherapy. The physiotherapist who received 6000 hours of training, and 100 hours of practical application for at least 3 years, occupational therapist, speech and language specialist deserve to be in this team [1].

In the world, many states in the USA, Seul province in Southern Korea are providing their services in colloboration with AHA. In many European countries as Germany, Belgium, Netherlands, Greece, and Sweeden hippotherapy is covered by general health insurance [1, 6, 7].

In our country, scarce number of centers provide only limited service. Besides, these patients receive a nonstandardized, and uncontrolled treatment

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procedure. In our country, hippotherapy is not covered by general health insurance. Every year many hippotherapy centers are inaugurated by The Ministry of Health, Agriculture and Livestock. With increasing number of the centers which provide certified hippotherapy training, and coverage of hippotherapy sessions with general health insurance, it will be possible to offer effective, safe, and reliable services to patients.

Why are horses are used?

1. During ambulation the horse provides a rhytmic movement which stimulates anterior, and posterior swinging movements 2. Movements of the horse encourage the rider to achieve a proper balance, and posture 3. The horse, and those around provide the rider a large spectrum of sensory, and motor input [5, 6, 7].

Horseback riding provide effective, and sensory stimulation for its rider through variable, rhytmic, and repetitive movements of the horse. The movement of the horse mimics the normal movements of the human pelvis during walking. Variations in horse gait enable therapist to measure sensory stimulation, and integrate these measurements with clinical therapies so as to arrive at desired outcomes [7].

Hippotherapy shortens recovery times, and improves balance and muscle control of the patient.

Slow, and rhytmic movements of the horse’s body have therapeutic values, and ensure development of paraspinal muscles. Multifaceted swinging rhythm of a horse gait effects the bones of patient’s pelvic girdle twice more strongly than the gait of a patient.

The patients are responding to this entertaining treatment modality with greater compliance, and enthusiasm. Thus, hippotherapy improves balance, mobility, and posture [7, 4].

Mechanism of action of hippotherapy Physical, and educational therapists have used the movements of the horse for the cure of the patient, while psychologists, and mental health therapists benefit from the horse’s mobility so as to achieve or increase compliance of the patients [1, 3, 5].

Horse pelvis, just like the human pelvis displays a 3-axial movement pattern while walking. Horse

Koca et al., What is hippotherapy? The indications and effectiveness of hippotherapy

gait has been carefully graded at every step of the patientâ&#x20AC;&#x2122;s treatment. These variable rhytmic, and repetitive movements provides physical, and sensory feedback to the patient. Favourable physical effects of equine-assisted therapy on coordintion, muscle tonus, postural balance, stiffness, flexibility, endurance, strength, correction of abnormal movement pattern, and improvement of gait, and balance have been demonstrated in many studies [7, 4, 8, 9, 3].

Mechanism of action of hypotherapy can be divided into four main groups. The first one is core connection.As we know, during daily living performance, balance, lying supine, and walking, postural control, and core connection are very important.

Besides, one of the many beneficial effects of hippotherapy is its favourable effect on postural control, and core body connection. During hippotherapy sessions, during horse riding direct contact with patientâ&#x20AC;&#x2122;s pelvis, and spine is ensured. Movements of the horse provide sensory input, and induce motor responses in pelvis, and trunk. Other mechanisms of action of hippotherapy can be enumerated as sensory connection, communication connection, and neuroconnection [1, 10, 11, 8, 9].

Hippotherapy has favourable effects on different domains as physical, social, cognitive, psychologic fields, learning, and adaptive behaviours.

Hippotherapy team Hippotherapy team consists of a therapist, horse trainer, and riding instructors walking on both sides of the horse. Hippotherapy is applied in the presence of an experienced physiotherapist, horse, and horse carer. Physiotherapist controls the horse gait, gait velocity, and orients the horse into various directions, and all these movements induce neuromuscular, and sensory reactions in the patient. [7, 10, 8, 9].

Indications of hippotherapy Hippotherapy can be used in different indications as cerebral palsy [12, 13, 14, 15, 16], traumatic brain damage [2, 3], Down syndrome, autistic behavioural disorders [17, 18], muscular dystrophy, amputated patients, cerebrovascular disease (SVD) [19, 20], multiple sclerosis [3, 21], psychiatric diseases [14, 15, 16], spinal cord diseases, and rheumatismal joint diseases etc.

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Hippotherapy as a physical therapy In physical therapy, multidirectional movements of the horse are utilized in gait training, balance, postural control, strengthening, and increasing range of motion. In many studies, improvements in gross motor skills, and functional activities have been reported in disabled children [4, 6, 7, 22, 10].

Hippotherapy as ocupational therapy In occupational therapy, movements of the horse are utilized with the intention to improve motor control, coordination, balance, attention, sensory processes, and performance in daily activities. Sensory processes, vestibular, proprioceptive, tactile, visual, and auditory systems are targeted simultaneously [4, 6, 7].

Hippotherapy as speech, and language therapy Hippotherapy also targets improvements in speech, language, cognitive, and masticatory functions [4, 6, 7].

Scientific clinical studies performed concerning hippotherapy Hippotherapy provides sensory feedback by utilizing movements of the horse, and thanks to this characteristic its used in diverse neurological conditions. Multiple sclerosis (MS) affects multiple number of neurological processes leading to to disorders of postural balance [21]. Munoz-Lasa et al. compared hippotherapy, traditional physical therapy on 27 patients with MS, and observed marked improvements in performance-oriented mobility assessment scores, and two gait parametres (jump time, and ground reaction force) [21]. They concluded that in ambulatory MS patients hippotherapy can improve postural balance, and gait. In their Internet-based home-training program, Frevel D et al. [23] investigated the effect of hippotherapy on the postural balance of MS patients, and applied twice weekly hippotherapy sessions (n=9) or Internet-based home therapy (n=9) for 12 weeks, and investigated static, and dynamic balance capacity in both groups. They observed comparable effects of both methods on postural balance, while in the hippotherapy group they noted marked improvement in fatigueness, and quality of life [23].

In a study by Lee CW et al. [19] on 36 patients

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with CVO, the patients were subjected to a program lasting for 8 weeks. The first group received hippotherapy, while the second group practiced treadmill exercises. In the first group, significant improvements of gait parametres as pace, and length of stride, asymmetry rate, while Berg balance scores were not significantly different [19]. In a similar study performed by Kim SG et al. [20] on elder patient population, the patients were also divided into hippotherapy, and ytreadmill groups. At the end of the study, increase in stride length, and decrease in stride time, and period of swinging (shorter in the hippotherapy group) were seen in both groups. The authors concluded that hippotherapy can improve static balance, and gait in elder population [20].

Parents of many autistic children included in the hippotherapy program observe marked improvements in physical, social, and sensory functions of their children. Hippotherapy effects behaviours of autistic children favourably [17]. Aizenman F et al. applied twice weekly hippotherapy sessions on 6 autistic children aged between 5–12 years for 12 weeks, and evaluated Vineland adaptive behaviour scale II, and Activity Card Measurements before, and after treatment [18]. At the end of the study marked decrease in postural swing, and increases in all adaptive behaviours (communication, copying), self-care, light activities, and social interaction were observed. At the end of the study, favourable effects of hippotherapy on these pediatric population were seen. Hippotherapy can be one of the complementary treatment strategies in autistic children.

In children with cerebral palsy (SP) exercisebased therapies aimed at improving postural control have been used more frequently during the last decade [22, 10]. In many studies, the authors have concluded that hippotherapy improved balance, and postural control. Park ES et al. [24] investigated the effect of hippotherapy on gross motor functions, and functional performance in children with SP (15 male, and 19 female children, aged 3–12 years), and applied twice weekly hippotherapy programs for 8 weeks each session lasting for 45 minutes, and measurements were based on gross Motor Function Measurement Scale -66, And 88 (GMFM), and Pediatric Functional Skill Scale (PEDİ-FSS) [24].

Parametres before hippotherapy were comparable between groups, while at the end of the study mean

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GMFM-66, and 88 scores improved markedly (being more prominent in the hippotherapy group).

When compared with the control group, PEDIFSS scores improved predominantly in the hippotherapy group.

In conclusion, hippotherapy can be beneficial in maximizing functional performance in children with SP. Kwon JY [25] randomized 96 patients with SP aged 4–10 years into 2 groups, and the first group received twice weekly hippotherapy sessions each lasting for 30 minutes for a period of 8 weeks, and the results were evaluated based on Gross Motor Function Classification System -66, and 88, and Pediatric Postural Balance Scale [25]. At the end of the study marked improvement was detected in the hippotherapy group as evaluated using GMFCS-88 scale. We can say that hippotherapy exerts favourable effects on gross motor functions, and postural balance of children with SP at various functional levels [24, 25, 26]. In a literature screening performed by Sterba JA’nın [12] on the effectiveness of hippotherapy on gross motor functions in children with SP, the authors had found 11 articles published on effectiveness of hippotherapy in SP: Hippotherapy is efcfective in the treatment of trunk, and hip asymmetry, and it also improves gross motor functions when compared with classical treatment modalities [26, 12]. Şık B et al. performed a study on a total of 20 patients with SP, and observed a statistically significant favourable effect of hippotherapy on gross motor functions, and balance coordination when compared with the control group [13].

Animal-assisted psychotherapy used in childhood has attracted attention for years. In cases with chronic diseases, favourable effect of small pet animals on these children is already known. In recent years, in pediatric, and adolescent psychiatry horse or pony-assisted therapy has been an interesting phenomenon which is also encouraged by health professionals [14, 15]. Guerino et al. investigated the effectiveness of hippotherapy in two young women (18, and 21 years of age, respectively) who were exposed to sexual assault during childhood [16]. They observed serious motor limitation, coordination disorders, conspicuous muscle spasms, and postural disorders as thoracic, and cervical kyphosis, and cervical protrusion in these girls. These two patients had undergone 20 sessions of hippother-

Koca et al., What is hippotherapy? The indications and effectiveness of hippotherapy

apy each lasting for 30 minutes. At the end of the therapy, they observed improvements in the posture (30%), coordination (80%), body balance, sociality, and self-confidence (50%) at indicated rates.

Among mental diseases, most frequently the patients with eating disorders require multidisciplinary treatment. In these patients effectiveness of equine-assisted psychotherapy has been observed in various studies [27, 28].

Conclusion Hippotherapy is a treatment modality whose effectivenes has been confirmed in a large patient group with physical or mental disabilities when applied by an experienced therapist with the aid of a horse.

Equine-asisted therapy is being used widely in many countries of the world. We think that as the importance of hippotherapy is acknowledged more deeply by physicians, and therapists in our country, greater number of patients, and their families will benefit from this form of treatment.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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7. Meregillano G. Hippotherapy. Phys Med Rehabil Clin N Am

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8. Shurtleff TL, Engsberg JR. Changes in trunk and head stability in children with cerebral palsy after hippotherapy: a pilot study.

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9. Shurtleff TL, Standeven JW, Engsberg JR. Changes in dynamic trunk/head stability and functional reach after hippotherapy.

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10. Zadnikar M, Kastrin A. Effects of hippotherapy and therapeutic horseback riding on postural control or balance in children with cerebral palsy: a meta-analysis. Dev Med Child Neurol 2011;53:684–91.

11. Rigby BR, Grandjean PW. The Efficacy of Equine-Assisted Activities and Therapies on Improving Physical Function. J Altern Complement Med 2016;22:9–24.

12. Sterba JA. Does horseback riding therapy or therapist-directed hippotherapy rehabilitate children with cerebral palsy? Dev Med Child Neurol 2007;49:68–73.

13. Yıldırım Şık B, Çekmece C, Dursun N, Dursun E, Balıkçı E, Altunkanat Z, et al. Is Hyppotherapy Beneficial for Rehabilitation of Children with Cerebral Palsy? Türk Klin J Med Sci 2012;32:601–8.

14. Masini A. Equine-assisted psychotherapy in clinical practice. J Psychosoc Nurs Ment Health Serv 2010;48:30–4.

15. Quint C, Toomey M. Powered saddle and pelvic mobility: an investigation into the effects on pelvic mobility of children with CP of a powered saddle which imitates the movements of a walkinghorse. Physiother 1998;84:376–84.

16. Guerino MR, Briel AF, Araújo Md. Hippotherapy as a treatment for socialization after sexual abuse and emotional stress. J Phys Ther Sci 2015;27:959–62.

17. Muslu GK, Conk H. Animal-Assisted Interventions and Their Practice in Children. Duehyo ED 2011;4:83–8.

18. Ajzenman HF, Standeven JW, Shurtleff TL. Effect of hippotherapy on motor control, adaptive behaviors, and participation in children with autism spectrum disorder: a pilot study. Am J Occup Ther 2013;67:653–63.

19. Lee CW, Kim SG, Yong MS. Effects of hippotherapy on recovery of gait and balance ability in patients with stroke. J Phys Ther Sci 2014;26(2):309–11.

20. Kim SG, Lee CW. The effects of hippotherapy on elderly persons’ static balance and gait. J Phys Ther Sci 2014;26:25–7.

21. Muñoz-Lasa S, Ferriero G, Valero R, Gomez-Muñiz F, Rabini A, Varela E. Effect of therapeutic horseback riding on balance and gait of people with multiple sclerosis. G Ital Med Lav Ergon 2011;33:462–7.

22. Snider L, Korner-Bitensky N, Kammann C, Warner S, Saleh M. Horseback riding as therapy for children with cerebral palsy: is there evidence of its effectiveness? Phys Occup Ther Pediatr 2007;27:5–23.

23. Frevel D, Mäurer M. Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial. Eur J Phys Rehabil Med 2015;51:23–30.

24. Park ES, Rha DW, Shin JS, Kim S, Jung S. Effects of hippo-

252 therapy on gross motor function and functional performance of children with cerebral palsy. Yonsei Med J 2014;55:1736–42.

25. Kwon JY, Chang HJ, Yi SH, Lee JY, Shin HY, Kim YH. Effect of hippotherapy on gross motor function in children with cerebral palsy: a randomized controlled trial. J Altern Complement Med 2015;21:15–21.

26. Benda W, McGibbon NH, Grant KL. Improvements in muscle symmetry in children with cerebral palsy after equine-

North Clin Istanbul – NCI assisted therapy (hippotherapy). J Altern Complement Med 2003;9:817–25.

27. Granados AC, Agís IF. Why children with special needs feel better with hippotherapy sessions: a conceptual review. J Altern Complement Med 2011;17:191–7.

28. Casady RL, Nichols-Larsen DS. The effect of hippotherapy on ten children with cerebral palsy. Pediatr Phys Ther 2004;16:165– 72.

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NORTHERN CLINICS OF ISTANBUL SUBJECT INDEX FOR VOLUME 2 (2015) Abdominal hernia see 2015;2(1):26-32 Abdominal wall see 2015;2(2):152–154 Abscess see 2015;2(3):222-226 Acute scrotum see 2015;2(3):182-188 Adenocarcinoma see 2015;2(2):162–164 Adolescent pregnancy see 2015;2(2):122-127 Adult onset Still’s disease see 2015;2(2):155–158 Ageing see 2015;2(1):73-80 Amyotrophy see 2015;2(2):165–170 Ankylosing spondylitis see 2015;2(3):231-235 Anti DNase B see 2015;2(2):136-141 Antibiotic use see 2015;2(2):107-114 Aspiration pneumonia see 2015;2(1):41-47 Astigmatism see 2015;2(1):1-6 Atrial fibrillation see 2015;2(1):7-12 Atrophy see 2015;2(2):165–170 Attitude see 2015;2(1):19-25 Autism see 2015;2(1):13-18 Awareness see 2015;2(1):13-18 Biopsy see 2015;2(1):48-54 Birth see 2015;2(2):142-150 Breast see 2015;2(1):59-61 Cachexia see 2015;2(2):165–170 Cancer incidence see 2015;2(1):73-80 Cancer see 2015;2(1):73-80 Catheter see 2015;2(1):55-58 Cesarean ratio see 2015;2(2):122-127 Childhood dermatoses see 2015;2(1):48-54 Childhood obesity see 2015;2(2):87-91 Chronic subdural hematoma see 2015;2(2):115-121 Chylothorax see 2015;2(3):227-230 CMV see 2015;2(3):203-209 Colon see 2015;2(2):171–174 Comorbidity see 2015;2(1):41-47 Complication see 2015;2(3):222-226 Congenital heart disease see 2015;2(3):227230 Contact lens see 2015;2(1):1-6 Corneal aberrations see 2015;2(1):1-6 Cyst hydatid see 2015;2(2):152–154 Dementia see 2015;2(1):66-68 Diabetes mellitus see 2015;2(3):177-181 Diabetic neuropathy see 2015;2(2):165–170 Diagnosis see 2015;2(1):81-86 Diastolic dysfunction see 2015;2(3):177-181

Doctors Worldwide Turkey see 2015;2(3):196-202 Doppler ultrasound see 2015;2(3):182-188 Duloxetine see 2015;2(3):243-246 Duodenal atresia see 2015;2(3):236-238 Ebola virus disease see 2015;2(1):81-86 Echocardiography see 2015;2(1):7-12 Education see 2015;2(1):13-18 Emergency medicine see 2015;2(2):107-114 Emergency treatment see 2015;2(1):26-32 Epidemiology see 2015;2(1):33-40 see 2015;2(1):48-54 see 2015;2(1):81-86 Epiploic appendicitis see 2015;2(2):171–174 Epiploic appendix see 2015;2(2):171–174 Equine-assisted therapy see 2015;2(3):247252 Eskisehir see 2015;2(1):33-40 Etanercept see 2015;2(3):231-235 External approach see 2015;2(1):62-65 Extrapyramidal symptoms see 2015;2(3):243-246

Knowledge level see 2015;2(1):19-25 Knowledge see 2015;2(1):13-18 Laparoscopic cholecystectomy see 2015;2(3):210-214 Left atrial dilatation see 2015;2(1):7-12 Leukemia see 2015;2(1):55-58 Maternal complication see 2015;2(2):122-127 Maternal see 2015;2(2):128-135 Mechanical ventilation see 2015;2(3):189-195 Medical intensive care unit see 2015;2(3):189-195 Methotrexate see 2015;2(2):159–161 Morbidity see 2015;2(3):189-195 Mortality see 2015;2(1):41-47 Mucocele see 2015;2(1):62-65 Mucopyocele see 2015;2(1):62-65 Myopia see 2015;2(1):1-6 Neck see 2015;2(3):222-226 Neonatal see 2015;2(2):128-135 Neurofibromatosis see 2015;2(2):162–164 Neurosyphilis see 2015;2(1):66-68 Neutrophil /lymphocyte ratio see 2015;2(2):87-91 Nuchal translucency see 2015;2(2):92-100

Ferritin see 2015;2(2):155–158 Fetal outcomes see 2015;2(2):122-127 Field research see 2015;2(1):33-40 First-trimester screening see 2015;2(2):92-100 Obturator hernia strangulation Foreign body see 2015;2(3):239-242 see 2015;2(1):69-72 Fronto-orbital mucocele see 2015;2(1):62-65 Octreotide; surgery see 2015;2(3):227-230 Organ donation see 2015;2(1):19-25 Gastric cancer see 2015;2(2):101-106 General paresis see 2015;2(1):66-68 Papillovesicular rash see 2015;2(1):55-58 Guinea-Bissau see 2015;2(3):196-202 Parkinsonism see 2015;2(3):243-246 Perinatal see 2015;2(2):128-135 Health care see 2015;2(2):128-135 Physical activity see 2015;2(3):215-221 Hernia see 2015;2(3):210-214 Pleural effusion see 2015;2(2):155–158 Hippotherapy see 2015;2(3):247-252 Postnatal care see 2015;2(2):128-135 Hypertension see 2015;2(3):177-181 Postpartum see 2015;2(2):128-135 Pregnancy see 2015;2(3):203-209 Inflammation see 2015;2(2):87-91 Prolapsus see 2015;2(1):59-61 Inguinal hernia see 2015;2(1):26-32 Psoriasis see 2015;2(2):159–161 Internal medicine clinic see 2015;2(1):41-47 Psychiatric manifestations Interobserver reliability see 2015;2(2):92-100 see 2015;2(1):66-68 Intestinal obstruction see 2015;2(1):69-72 Pulmonary fibrosis see 2015;2(2):159–161 Intraductal papilloma see 2015;2(1):59-61 Pustular drug eruption see 2015;2(3):231-235 Ischemic stroke see 2015;2(1):7-12 Quality of life see 2015;2(3):215-221 Knee osteoarthritis see 2015;2(3):215-221 Questionnaire see 2015;2(1):33-40

North Clin Istanbul – NCI

254 Reliability see 2015;2(2):142-150 Rubella see 2015;2(3):203-209 Rural area see 2015;2(1):33-40 Rural surgery see 2015;2(3):196-202 Satisfaction see 2015;2(2):142-150 Schizophrenia see 2015;2(3):239-242 Screening tests see 2015;2(3):203-209 Serological tests see 2015;2(2):136-141 Serratia see 2015;2(1):55-58 Stomach see 2015;2(2):162–164 see 2015;2(3):239-242 Streptococcus pyogenes see 2015;2(2):136-141

Subcutaneous see 2015;2(2):152–154 Subdural drainage see 2015;2(2):115-121 Subgaleal drainage see 2015;2(2):115-121 Surgery see 2015;2(2):101-106 Symptomatic medications see 2015;2(2):107-114 Testicular loss see 2015;2(3):182-188 Testicular torsion see 2015;2(3):182-188 Therapeutic horse back riding see 2015;2(3):247-252 TORCH see 2015;2(3):203-209 Toxoplasma see 2015;2(3):203-209 Transplantation see 2015;2(1):19-25 Treatment see 2015;2(1):81-86

Trisomy 21 see 2015;2(2):92-100 Trocar site see 2015;2(3):210-214 Turkey see 2015;2(2):101-106 University students see 2015;2(1):19-25 Upper respiratory tract infections see 2015;2(2):107-114 Validity see 2015;2(2):142-150 Varicella see 2015;2(1):55-58 Visual quality see 2015;2(1):1-6

NORTHERN CLINICS OF ISTANBUL AUTHOR INDEX FOR VOLUME 2 (2015) Acar A (see Ozbagriacik M et al.) 2015;2(1):26-32 Acmaz G (see Aksoy H et al.) 2015;2(2):92-100 Adaleti R (see Delice S et al.) 2015;2(2):136-141 Aday U, et al. see 2015;2(3):239-242 Ak R (see Ozdemir S et al.) 2015;2(2):107-114 Aka N, (see Numan O et al.) 2015;2(3):203-209 Akar E (see Berkman MZ et al.) 2015;2(1):62-65 Akdeniz N (see Karadag AS et al.) 2015;2(2):159–161 Aker SS (see Yuce T et al.) 2015;2(2):122-127 Akinci OF (see Atalay T et al.) 2015;2(1):59-61 Akkilic EC (see Misirli HC et al.) 2015;2(1):7-12 Akmil MF (see Berkman MZ et al.) 2015;2(1):62-65 Aksaray S (see Delice S et al.) 2015;2(2):136-141 Aksoy H, et al. see 2015;2(2):92-100 Aksoy U (see Aksoy H et al.) 2015;2(2):92-100 Aktas S (see Alimoglu O et al.) 2015;2(2):101-106 Akyer E (see Ozer MN et al.) 2015;2(1):41-47 Alagoz P (see Delice S et al.) 2015;2(2):136-141 Alatas ET (see Kara A et al.) 2015;2(3):231-235 Alimoglu O (see Burcu B et al.) 2015;2(2):171–174 Alimoglu O (see Ozbagriacik M et al.) 2015;2(1):26-32 Alimoglu O, et al. see 2015;2(2):101-106 Alimoglu O, et al. see 2015;2(3):196-202 Alkan S (see Gulmez M et al.) 2015;2(2):152–154 Alp A see 2015;2(2):175–176 Alpay M (see Numan O et al.) 2015;2(3):203-209 Araz M, et al. see 2015;2(3):177-181 Araz O (see Misirli HC et al.) 2015;2(1):7-12 Arslan IB (see Bulgurcu S et al.) 2015;2(3):222-226 Atakan TG (see Demir M et al.) 2015;2(1):1-6 Atalay T, et al. 2015;2(1):59-61 Ataseven H (see Koca TT et al.) 2015;2(3):247-252 Awiwi M (see Surmen A et al.) 2015;2(1):13-18

Aydın M, et al. see 2015;2(2):87-91 Aydin E, et al. see 2015;2(3):236-238 Ayhan İ (see Ozay O et al.) 2015;2(1):33-40 Ayvaz OD, et al. see 2015;2(3):182-188 Babayigit MA (see Aksoy H et al.) 2015;2(2):92-100 Bahadir A, et al. 2015;2(1):55-58 Barut B, et al. see 2015;2(2):162–164 Bas G (see Alimoglu O et al.) 2015;2(2):101-106 Bas G (see Ozbagriacik M et al.) 2015;2(1):26-32 Basak F (see Alimoglu O et al.) 2015;2(2):101-106 Basak F (see Dincel O et al.)2015;2(3):210-214 Basak F (see Ozbagriacik M et al.) 2015;2(1):26-32 Bayrac A (see Araz M et al.) 2015;2(3):177-181 Bayrak A, et al. see 2015;2(3):243-246 Bayram T (see Misirli HC et al.) 2015;2(1):7-12 Bedel A (see Delice S et al.) 2015;2(2):136-141 Berkman MZ, et al. 2015;2(1):62-65 Borklu BE (see Oral S et al.) 2015;2(2):115-121 Bosnali O (see Ayvaz OD et al.) 2015;2(3):182-188 Bulgurcu S, et al. see 2015;2(3):222-226 Bulut O, et al. see 2015;2(3):227-230 Burcu B, et al. see 2015;2(2):171–174 Buyukkayhan D (see Bulut 0 et al.) 2015;2(3):227-230 Caklili O (see Unal AU et al.) 2015;2(3):189-195 Caliskan E (see Kaya A et al.) 2015;2(2):151 Caman S (see Ayvaz OD et al.) 2015;2(3):182-188 Celebi HS (see Kara A et al.) 2015;2(3):231-235 Cerrah Celayir A (see Ayvaz OD et al.) 2015;2(3):182-188 Cetin B (see Bayrak A et al.) 2015;2(3):243-246 Cetin FC, et al. see 2015;2(2):142-150 Cevan S (see Delice S et al.) 2015;2(2):136-141

NCI Index of Vol. 2

Ciftci H (see Araz M et al.) 2015;2(3):177-181 Cinar D, et al. 2015;2(1):73-80 Cukurova I (see Bulgurcu S et al.) 2015;2(3):222-226 Delice S, et al. see 2015;2(2):136-141 Demir M, et al. see 2015;2(1):1-6 Demirbas S, et al. see 2015;2(2):155–158 Demirhan E (see Bulgurcu S et al.) 2015;2(3):222-226 Demirkol M (see Aydın M et al.) 2015;2(2):87-91 Dere Y (see Kara A et al.) 2015;2(3):231-235 Dincel O, et al. see 2015;2(3):210-214 Dogan G (see Kara A et al.) 2015;2(3):231-235 Dogan Merih Y (see Cetin FC et al.) 2015;2(2):142-150 Domac FM (see Toptan T et al.) 2015;2(1):66-68 Donma MM (see Aydın M et al.) 2015;2(2):87-91 Ekinci O (see Burcu B et al.) 2015;2(2):171–174 Erdogan D, et al. 2015;2(1):69-72 Erdogan SN (see Misirli HC et al.) 2015;2(1):7-12 Erdoğan M (see Aydın M et al.) 2015;2(2):87-91 Erduran E (see Bahadir A et al.) 2015;2(1):55-58 Eren T (see Alimoglu et al.) 2015;2(3):196-202 Eren T (see Alimoglu O et al.) 2015;2(2):101-106 Eren TT (see Burcu B et al.) 2015;2(2):171–174 Erturk Coskun AD(see Numan O et al.) 2015;2(3):203-209 Gedik C (see Karadag AS et al.) 2015;2(2):159–161 Gok S (see Berkman MZ et al.) 2015;2(1):62-65 Goksu1 M (see Dincel O et al.)2015;2(3):210-214 Gul D (see Bulut 0 et al.) 2015;2(3):227-230 Gulmez M (see Erdogan D et al.) 2015;2(1):69-72 Gulmez M, et al. see 2015;2(2):152–154 Gürel A (see Aydın M et al.) 2015;2(2):87-91 Harputluoglu M (see Barut B et al.) 2015;2(2):162–164 Hidiroglu S (see Surmen A et al.) 2015;2(1):13-18 Hikmet Kozcu S (see Bulgurcu S et al.) 2015;2(3):222-226 Icagasioglu A (see Mesci E et al.) 2015;2(3):215-221 Inan I (see Burcu B et al.) 2015;2(2):171–174 Ince V (see Barut B et al.) 2015;2(2):162–164 Isik B (see Barut B et al.) 2015;2(2):162–164 Isikli B (see Ozay O et al.) 2015;2(1):33-40 Kadanali A, et al. 2015;2(1):81-86 Kalafat E (see Yuce T et al.) 2015;2(2):122-127 Kanbay A (see Karadag AS et al.) 2015;2(2):159–161 Kandemir B (see Demirbas S et al.) 2015;2(2):155–158 Kara A,et al. see 2015;2(3):231-235 Kara VM (see Erdogan D et al.) 2015;2(1):69-72 Karadag AS (see Ozkanli S et al.) 2015;2(1):48-54 Karadag AS, et al. see 2015;2(2):159–161 Karadag OI (see Aksoy H et al.) 2015;2(2):92-100

255 Karagoz G (see Kadanali A et al.) 2015;2(1):81-86 Karavus A (see Surmen A et al.) 2015;2(1):13-18 Karavus M (see Surmen A et al.) 2015;2(1):13-18 Kaya A, et al. see 2015;2(2):151 Kenangil G (see Toptan T et al.) 2015;2(1):66-68 Kesebir S (see Bayrak A et al.) 2015;2(3):243-246 Keskin M (see Kaya A et al.) 2015;2(2):151 Kinik K (see Alimoglu et al.) 2015;2(3):196-202 Koban BU (see Gulmez M et al.) 2015;2(2):152–154 Koca TT see 2015;2(2):165–170 Koca TT, et al. see 2015;2(3):247-252 Kose OO, et al. see 2015;2(1):19-25 Kostek O (see Ozer MN et al.) 2015;2(1):41-47 Kostek O (see Unal AU et al.) 2015;2(3):189-195 Kucuk A (see Oral S et al.) 2015;2(2):115-121 Kudas I (see Ozbagriacik M et al.) 2015;2(1):26-32 Kurna SA (see Demir M et al.) 2015;2(1):1-6 Kuru B (see Ozkanli S et al.) 2015;2(1):48-54 Kutlu O (see Demirbas S et al.) 2015;2(2):155–158 Leblebici M (see Alimoglu O et al.) 2015;2(2):101-106 Mesci E, et al. see 2015;2(3):215-221 Mesci N (see Mesci E et al.) 2015;2(3):215-221 Meteris H (see Bayrak A et al.) 2015;2(3):243-246 Metiner Y (see Ozdemir S et al.) 2015;2(2):107-114 Metintas S (see Ozay O et al.) 2015;2(1):33-40 Misirli HC, et al. see 2015;2(1):7-12 Moralioglu S (see Ayvaz OD et al.) 2015;2(3):182-188 Mungan I (see Bulut 0 et al.) 2015;2(3):227-230 Mutlu E (see Aksoy H et al.) 2015;2(2):92-100 Nuhoglu C (see Delice S et al.) 2015;2(2):136-141 Numan O, et al. see 2015;2(3):203-209 Ocal O (see Ozdemir S et al.) 2015;2(2):107-114 Oguz A (see Ozer MN et al.) 2015;2(1):41-47 Oguz A (see Unal AU et al.) 2015;2(3):189-195 Oguz AS (see Surmen A et al.) 2015;2(1):13-18 Onal RS (see Gulmez M et al.) 2015;2(2):152–154 Onsuz MF (see Kose OO et al.) 2015;2(1):19-25 Onsuz MF (see Ozay O et al.) 2015;2(1):33-40 Oral S, et al. see 2015;2(2):115-121 Oz A (see Kaya A et al.) 2015;2(2):151 Ozay O, et al. 2015;2(1):33-40 Ozbagriacik M, et al. 2015;2(1):26-32 Ozdemir F (see Barut B et al.) 2015;2(2):162–164 Ozdemir S, et al. see 2015;2(2):107-114 Ozdilek B (see Toptan T et al.) 2015;2(1):66-68 Ozer MN, et al. 2015;2(1):41-47 Ozkan D (see Misirli HC et al.) 2015;2(1):7-12 Ozkanli S, et al. 2015;2(1):48-54 Ozlu E (see Karadag AS et al.) 2015;2(2):159–161

256 Ozpek A (see Ozbagriacik M et al.) 2015;2(1):26-32 Ozturk A (see Atalay T et al.) 2015;2(1):59-61 Ozturk TC (see Ozdemir S et al.) 2015;2(2):107-114 Ozyalvac FT (see Burcu B et al.) 2015;2(2):171–174 Ozyurt S (see Aksoy H et al.) 2015;2(2):92-100 Pektas OZ (see Ayvaz OD et al.) 2015;2(3):182-188 Pelin AK (see Ayvaz OD et al.) 2015;2(3):182-188 Sagiroglu J (see Alimoglu et al.) 2015;2(3):196-202 Sahin T (see Demir M et al.) 2015;2(1):1-6 Sakin A (see Demirbas S et al.) 2015;2(2):155–158 Selcuklu A (see Oral S et al.) 2015;2(2):115-121 Sengor T (see Demir M et al.) 2015;2(1):1-6 Seval MM (see Yuce T et al.) 2015;2(2):122-127 Sevuk S (see Bulut 0 et al.) 2015;2(3):227-230 Sezer A (see Cetin FC et al.) 2015;2(2):142-150 Simsek Celik A (see Gulmez M et al.) 2015;2(2):152–154 Sisik A (see Alimoglu O et al.) 2015;2(2):101-106 Sisik A (see Ozbagriacik M et al.) 2015;2(1):26-32 Soylemez F (see Yuce T et al.) 2015;2(2):122-127 Surmen A, et al. see 2015;2(1):13-18 Takir M (see Ozer MN et al.) 2015;2(1):41-47 Takir M (see Unal AU et al.) 2015;2(3):189-195 Tardu A (see Aday U et al.) 2015;2(3):239-242 Tas D (see Cinar D et al.) 2015;2(1):73-80 Toptan T, et al. 2015;2(1):66-68 Topuzoglu A (see Kose OO et al.) 2015;2(1):19-25 Tulubas F (see Aydın M et al.) 2015;2(2):87-91 Turan Turgut S (see Mesci E et al.) 2015;2(3):215-221 Tutus S (see Aksoy H et al.) 2015;2(2):92-100

North Clin Istanbul – NCI Ulker M (see Toptan T et al.) 2015;2(1):66-68 Ulutabanca H (see Oral S et al.) 2015;2(2):115-121 Unal AU, et al. see 2015;2(3):189-195 Usta HH (see Surmen A et al.) 2015;2(1):13-18 Uzun MA (see Erdogan D et al.) 2015;2(1):69-72 Uzun MA (see Gulmez M et al.) 2015;2(2):152–154 Uzuncakmak TK (see Karadag AS et al.) 2015;2(2):159–161 Uzunlulu M (see Ozer MN et al.) 2015;2(1):41-47 Uzunlulu M (see Unal AU et al.) 2015;2(3):189-195 Vural B (see Vural F et al.) 2015;2(2):128-135 Vural F (see Numan O et al.) 2015;2(3):203-209 Vural F, et al. see 2015;2(2):128-135 Yagci MA (see Aday U et al.) 2015;2(3):239-242 Yananli Z (see Atalay T et al.) 2015;2(1):59-61 Yanar HT (see Misirli HC et al.) 2015;2(1):7-12 Yılmaz A (see Aydın M et al.) 2015;2(2):87-91 Yildirim F (see Vural F et al.) 2015;2(2):128-135 Yonder H (see Aday U et al.) 2015;2(3):239-242 Yuce T, et al. see 2015;2(2):122-127 Yucel B (see Aksoy H et al.) 2015;2(2):92-100 Yucel M (see Ozbagriacik M et al.) 2015;2(1):26-32 Yucel O (see Erdogan D et al.) 2015;2(1):69-72 Zemheri E (see Ozkanli S et al.) 2015;2(1):48-54 Zenginkinet T (see Ozkanli S et al.) 2015;2(1):48-54 Zindanci I (see Ozkanli S et al.) 2015;2(1):48-54