Key articles from international medical journals Dr. Guillaume Ploussard Section editor Toulouse (FR)
g.ploussard@ gmail.com
No SARS-CoV-2 in semen specimens, abnormal sex hormone secretion In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-associated infection (coronavirus disease 2019 [COVID-19]) developed rapidly and has turned into a global pandemic. Although SARS-CoV-2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID-19 may affect male reproductive functions. In this study, investigators collected semen specimens from 12 male COVID-19 patients for virus detection and semen characteristics analysis. No SARS-CoV-2 was found in semen specimens. Eight out of 12 patients had normal semen quality. They also compared the sex-related hormone levels between 119 reproductive-aged men with SARS-CoV-2 infection and 273 age-matched control men. Higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C-reactive protein levels in COVID-19 patients.
Higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group.
“urinary tract infection”, and “D-mannose”. Only clinical studies, systematic reviews, and metaanalyses reporting efficacy or safety data on D-mannose versus placebo or other competitors were selected. Evidence was limited to human data. The selected studies were organised in two categories based on the presence or absence of a competitor to D-mannose.
Outcome measures were allograft failure from any cause including death and allograft failure censored for patient death defined by the requirement for long-term dialysis or repeat transplant.
Of 385 patients, 191 were assigned to steroid withdrawal (mean [SD] age, 46.5 [12.1] years), and 194 patients to continued corticosteroids (mean [SD] age, 46.3 [12.6] years). The median (interquartile range) Most of the studies also showed D-mannose can play follow-up time was 15.8 (12.0-16.3) years. Based on a role in the prevention of rUTI or urodynamicsintent-to-treat analysis, the adjusted hazard ratio of associated UTI and can overlap antibiotic treatment in allograft failure from any cause including death was 0.83 (95% CI, 0.62-1.10; p < 0.2) and for allograft some cases. failure censored for patient death it was 0.78 (95% CI, After exclusion of non-pertinent studies/articles, 13 0.52-1.19; p < 0.26) and did not differ between the two studies were analysed. In detail, six were randomised groups. In a per-protocol-analysis among 223 patients controlled trials (RCTs), one was a randomised who continued the trial-assigned treatment (n = 114 vs cross-over trial, five were prospective cohort studies, n = 109) for at least 5 years, the results were the and one a retrospective analysis. Seven studies same. Also, the outcomes in both groups did not compared D-mannose to placebo or other drugs/ differ from similarly treated contemporary registry dietary supplements. Six studies evaluated the patients who met trial eligibility criteria and were efficacy of D-mannose comparing follow-up data with treated with the same regimens. The authors the baseline. concluded that long-term corticosteroid medication may not be necessary in low to medium immune risk D-mannose is well tolerated, with few reported renal transplantation. adverse events (diarrhoea was reported in about Source: Early corticosteroid cessation vs 8% of patients receiving 2 g of D-mannose for at long-term corticosteroid therapy in kidney least 6 months). Most of the studies also showed transplant recipients: long-term outcomes of a D-mannose can play a role in the prevention of randomized clinical trial. Woodle ES, Gill JS, rUTI or urodynamics-associated UTI and can Clark S, Stewart D, Alloway R, First R. overlap antibiotic treatment in some cases. The JAMA Surg. 2021 Feb 3:e206929. doi: 10.1001/ possibility to combine D-mannose with polyphenols jamasurg.2020.6929. Epub ahead of print. PMID: or Lactobacillus seems another important option 33533901; PMCID: PMC7859872. for UTI prophylaxis. However, the quality of the collected studies was very low, generating, consequently, a weak grade of recommendations as suggested by international guidelines. Data on Interventions for preventing D-mannose dose, frequency, and duration of thrombosis in solid organ treatment are still lacking. The authors conclude that D-mannose alone or in combination with several dietary supplements or Lactobacillus has a potential role in the non antimicrobial prophylaxis of recurrent UTI in women. Despite its frequent prescription in real-life practice, authors believe that further well-designed studies are urgently needed to definitively support the role of D-mannose in the management of recurrent UTIs in women.
Source: Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives. Cosimo De Nunzio, Riccardo Bartoletti, Andrea Tubaro, Alchiede Simonato and Vincenzo Ficarra.
transplant recipients Graft thrombosis is one of the leading causes of kidney graft failure. Currently there are no standardised protocols for thromboprophylaxis. Many transplant units use unfractionated heparin (UFH) and fractionated heparins (low molecular weight heparin; LMWH). Antiplatelet agents such as aspirin might have a role in preventing graft thrombosis. However, any pharmacological thromboprophylaxis comes with the risk of major blood loss following transplantation. This systematic review looked at benefits and harms of thromboprophylaxis in patients undergoing solid organ transplantation.
Prof. Serdar Tekgül Section Editor Ankara (TR)
serdartekgul@ gmail.com
control, any heparin (including LMWH) may make little or no difference to the number of major bleeding events (3 studies, 180 participants: RR 2.70, 95% CI 0.89 to 8.19; I² = 0%; low certainty evidence). The effect of heparin on other outcomes (including death, patient and graft survival, transfusion requirements) remains unclear (very low certainty evidence). Three studies (n = 144) investigated antiplatelet interventions in kidney transplantation: aspirin versus dipyridamole, and Lipo-PGE1 plus low-dose heparin to ’control’ in patients who had a diagnosis of acute rejection. None of these reported on early graft thromboses. The effect of aspirin, dipyridamole and Lipo PGE1 plus low-dose heparin on any outcomes is unclear (very low certainty evidence). The authors concluded that UFH may increase the risk of major bleeding in kidney transplant recipients, however, this is based on low certainty evidence, and that currently there is no good evidence to guide antithrombotic prophylaxis in renal transplantation.
Source: Interventions for preventing thrombosis in solid organ transplant recipients. Surianarayanan V, Hoather TJ, Tingle SJ, Thompson ER, Hanley J, Wilson CH. Cochrane Database Syst Rev. 2021 Mar 15;3:CD011557. doi: 10.1002/14651858.CD011557.pub2. PMID: 33720396.
The quest for an intermediate surrogate for overall survival in localised prostate cancer
Overall survival is considered the gold standard endpoint for cancer trials. However, the natural history of localised prostate cancer poses challenges in clinical trials design. Follow-up needs to be long This is the first report about semen assessment and before achieving a significant number of events. Thus, sex hormone evaluation in reproductive-aged male Antibiotics 2021, 10(4), 373; https://doi.org/10.3390/ The authors searched the Cochrane Kidney and there is a growing interest in validating intermediate COVID-19 patients. Although further studies are antibiotics10040373 Transplant Register of Studies up to November 2020. endpoints which could be correlated with overall needed to clarify the reasons and underlying Studies in the Register are identified through searches survival. Previously, the international Intermediate mechanisms, the present study presents an abnormal of CENTRAL, MEDLINE, and EMBASE, conference Clinical Endpoints in Cancer of the Prostate (ICECaP) sex hormone secretion among COVID-19 patients, proceedings, the International Clinical Trials Register working group established metastasis-free survival as Early corticosteroid cessation (ICTRP) Search Portal and ClinicalTrials.gov. suggesting that attention should be paid to a surrogate endpoint for overall survival for men with vs. long-term corticosteroid reproductive function evaluation in the follow-up. localised prostate cancer. However, patients included Only randomised controlled trials (RCTs) and in this analysis have been treated by radiotherapy in therapy after kidney Source: Evaluation of sex-related hormones and quasi-RCTs designed to examine interventions to 90% of cases. The diffusion of this model in a surgery transplant semen characteristics in reproductive-aged prevent thrombosis in solid organ transplant setting may be questioned. No surgical trials were male COVID-19 patients. Ma L, Xie W, Li D, Shi L, recipients were included for all donor types without included in the event-free survival analysis. Ye G, Mao Y, Xiong Y, Sun H, Zheng F, Chen Z, Long-term corticosteroid treatment after renal any age limit for recipients. Nine studies (712 Qin J, Lyu J, Zhang Y, Zhang M. transplantation has well known side-effects. However, participants) were identified. Seven studies (544 In the present article, the authors performed a second Journal of medical virology, 2021-01, Vol.93 (1), cessation of corticosteroids is associated with a higher participants) included kidney transplant recipients. two-stage meta-analytical approach to p.456-462. DOI: 10.1002/jmv.26259 PMID: 32621617 risk of short-term rejection. The long-term outcomes Selection bias was high or unclear in eight of the nine comprehensively assess intermediate clinical of patients who withdraw from corticosteroids remain studies; five studies were at high risk of bias for endpoints across the most common treatments in uncertain. The aim of this prospective, randomised, performance and/or detection bias; while attrition localised prostate cancer (radical radiotherapy, radical double-blind and placebo-controlled trial was to prostatectomy, and hormone therapy). Published and reporting biases were in general low or unclear. Recurrent UTI in women: compare long-term renal transplant outcomes of randomised trials investigating a therapeutic option D-mannose may play a role patients randomised to early steroid withdrawal or for localised or biochemically recurrent prostate …currently there is no good continued steroid treatment. cancer and reporting overall survival and at least one Urinary tract infections (UTI) are highly frequent in intermediate clinical endpoint were included. evidence to guide antithrombotic women, with a significant impact on healthcare clinical endpoints were: time to …authors concluded that long-term prophylaxis in renal transplantation. Intermediate resources. Although antibiotics still represent the biochemical failure, time to local failure, time to standard treatment to manage recurrent UTI (rUTI), distant metastases, time to biochemical failure plus corticosteroid medication may not D-mannose, an inert monosaccharide that is Three studies (n = 180 participants) primarily clinical failure, biochemical failure-free survival, be necessary in low to medium metabolised and excreted in urine and acts by investigated heparin in kidney transplantation. Only progression-free survival, and metastasis-free inhibiting bacterial adhesion to the urothelium, survival. Preplanned subgroups across treatment immune risk renal transplantation. two studies reported on graft vessel thrombosis in represents a promising non-antibiotic prevention kidney transplantation (n = 144). These small studies types were assessed. Postoperative radiotherapy was strategy. The aim of this narrative review was to were at high risk of bias in several domains and included in the surgical subgroup. Another analysis critically analyse clinical studies reporting data The trial was conducted in 28 US transplant centres reported only two graft thromboses between them. It evaluated only patients with high-risk disease and concerning the efficacy and safety of D-mannose in therefore remains unclear whether heparin decreases those with duration of follow-up > 9 years. Overall, between November 1999 and December 2002 with the management of rUTIs. linkage to a mandatory national registry with the risk of early graft thrombosis or non-graft after screening, 75 randomised trials were included validated outcome ascertainment. 386 low to thrombosis (very low certainty). UFH may make little (53,631 patients). A non-systematic literature search, using the PubMed, moderate immune risk adult recipients of a living or no difference versus placebo to the rate of major EMBASE, Scopus, Web of science, Cochrane Central or deceased donor kidney transplant without bleeding events in kidney transplantation (3 studies, Intermediate clinical endpoints evaluating Register of Controlled Trials and Cochrane Central delayed graft function or short-term rejection in the n = 155; RR 2.92, 95% CI 0.89 to 9.56; I² = 0%; low biochemical failure showed poor correlation with Database of Systematic Reviews databases, was certainty evidence). Sensitivity analysis using a first week were included. Patients were overall survival. Correlation with local failure was also performed for relevant articles published between randomised to receive tacrolimus and fixed-effect model suggested that UFH may increase poor. Correlation of progression-free survival was January 2010 and January 2021. The following Medical mycophenolate mofetil with or without the risk of haemorrhagic events compared to placebo moderate (R² 0.46). Metastasis-free survival showed Subjects Heading were used: “female/woman”, corticosteroids 7 days after transplant. (RR 3.33, 95% CI 1.04 to 10.67, p = 0.04). Compared to the strongest correlation (R² 0.78). Key articles
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