Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (=21) or placebo (=23). The 0.5-ml/min per 1.73 m per year (95% confidence interval, -4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m; =0.31), 2-year graft survival (81% versus 96%;=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.

BackgroundMycoplasma genitalium is a common cause of non-gonococcal non-chlamydial urethritis and cervicitis. Testing of asymptomatic populations has been proposed, but prevalence in asymptomatic populations is not well established. We aimed to estimate the prevalence of M. genitalium in the general population, pregnant women, men who have sex with men (MSM), commercial sex workers (CSWs) and clinic-based samples.MethodsWe searched Embase, Medline, IndMED, African Index Medicus and LILACS from 1 January 1991 to 12 July 2016 without language restrictions. We included studies with 500 participants or more. Two reviewers independently screened and selected studies and extracted data. We examined forest plots and conducted random-effects meta-analysis to estimate prevalence, if appropriate. Between-study heterogeneity was examined using the I2 statistic and meta-regression.ResultsOf 3316 screened records, 63 were included. In randomly selected samples from the general population, the summary prevalence was 1.3% (95% CI 1.0% to 1.8%, I2 41.5%, three studies, 9091 people) in countries with higher levels of development and 3.9% (95% CI 2.2 to 6.7, I2 89.2%, three studies, 3809 people) in countries with lower levels. Prevalence was similar in women and men (P=0.47). In clinic based samples, prevalence estimates were higher, except in asymptomatic patients (0.8%, 95% CI 0.4 to 1.4, I2 0.0%, three studies, 2889 people). Summary prevalence estimates were, in the following groups: pregnant women 0.9% (95% CI 0.6% to 1.4%, I2 0%, four studies, 3472 people), MSM in the community 3.2% (95% CI 2.1 to 5.1, I2 78.3%, five studies, 3012 people) and female CSWs in the community 15.9% (95% CI 13.5 to 18.9, I2 79.9%, four studies, 4006 people).DiscussionThis systematic review can inform testing guidelines for M. genitalium. The low estimated prevalence of M. genitalium in the general population, pregnant women and asymptomatic attenders at clinics does not support expansion of testing to these groups.Registration numbersPROSPERO: CRD42015020420

PurposeThe aim of the present meta-analysis was to quantify effects of resistance exercise (RE) on physical performance and function, body composition, health-related quality of life (HRQoL), and fatigue in patients with prostate cancer.MethodsTrial data were obtained from the databases PubMed, MEDLINE, EMBASE, SCOPUS, and the Cochrane Library as of inception to 31st of December 2016. Thirty-two trials with 1199 patients were included. Results that were measured by using the same assessment method in five or more of the original studies were pooled in a meta-analysis.ResultsPooled studies showed significant improvements of muscular strength in the upper and lower body (95% CI [2.52, 7.97] kg; p < 0.001 and 95% CI [10.51, 45.88] kg; p = 0.008, respectively) after RE. Furthermore, significant improvements were seen for body composition (body fat percentage 95% CI [−0.79, −0.53] %; p < 0.001; lean body mass 95% CI [0.15, 1.84] %; p = 0.028; trunk fat mass 95% CI [−0.73, −0.08] kg; p = 0.024). Additionally, the improvement of the 400-m walk time was significant (95% CI [−21.55, −14.65] s; p < 0.001). Concerning fatigue and HRQoL, there were not sufficient data for analysis.ConclusionsRE seems to be a promising approach in order to counteract loss of muscle mass, muscle strength, and physical performance in patients suffering from prostate cancer and its treatment-related side effects. RE should play part in interdisciplinary cancer rehabilitation and care of this patient group. Nevertheless, further research should investigate RE further to determine which protocols are the most pragmatic, yet yielding best patient outcomes.

Early diagnosis of sepsis, rapid identification of the causative pathogen(s) and prompt initiation of appropriate antibiotic treatment have a combined impact on mortality due to sepsis. In this observational study, a new DNA-based system (LightCycler SeptiFast (LC-SF) test; Roche Diagnostics) allowing detection of 16 pathogens at the species level and four groups of pathogens at the genus level has been evaluated and compared with conventional blood cultures (BCs). One hundred BC and LC-SF results were obtained for 72 patients admitted to the intensive-care unit over a 6-month period for suspected sepsis. Microbiological data were compared with other biological parameters and with clinical data. The positivity rate of BCs for bacteraemia/fungaemia was 10%, whereas the LC-SF test allowed detection of DNA in 15% of cases. The LC-SF performance, based on its clinical relevance, was as follows: sensitivity, 78%; specificity, 99%; positive predictive value, 93%; and negative predictive value, 95%. Management was changed for four of eight (50%) of the patients because organisms were detected by the LC-SF test but not by BC. LC-SF results were obtained in 7-15 h, in contrast to the 24-72 h required for BC. According to the LC-SF results, initial therapy was inadequate in eight patients, and antibiotic treatment was changed. Our results suggest that the LC-SF test may be a valuable complementary tool in the management of patients with clinically suspected sepsis.

Abstract---We have measured the optical and retinal fields of goldfish eyes; the animals ranged from 6 to 20 cm in body length. Both fields are spherically symmetric, invariant with the size of the eye, and equal (retinal field = 185.3" _t 4.1', optical field = 183.6" f 2.7", means rt SD.). They are tilted with respect to one another by a few f < 10) degrees. We have also measured the retinal magnification factor, the number of p per degree on the retinal surface. It is 20.5 x lens diameter, where lens diameter is expressed in mm.

BackgroundAnastomotic leakage following colorectal resection remains one of the most significant complications with relevant morbidity and mortality. There is evidence that a higher number of stapler firings for rectal division can affect the leak rate in double stapling anastomosis. However, there are no data concerning compression anastomosis. We present our institutional experience addressing this issue.DesignThis is a retrospective review of a prospective institutional database of patients undergoing colonic and rectal resection for benign and malignant indications between January 2008 and December 2014 at the surgical department of the St. John of God Hospital, Vienna. Inclusion criteria were rectal division with linear stapling devices and construction of anastomosis to the rectal stump using a circular stapler or compression device.ResultsThree hundred eighty two (196 female; 51.3%) patients were included. Mean age was 65.8 years (range: 18–95) Indications for the operation included diverticular disease (44.8%), colorectal carcinoma (51.6%), inflammatory bowel disease (1.8%), and adenoma (1.8%). A laparoscopic approach was employed in 334 cases (87.4%); in 170 patients (44.9%), a compression anastomosis was created. One, two, and three or more stapler cartridges were used for rectal division in 58.4, 33.5, and 8.1%, respectively. Male gender, neoadjuvant therapy, rectal cancer as an underlying disease, laparoscopic surgical approach, and duration of operation longer than 200 min are leading causes for the usage of more than one stapler cartridge. Overall leak rate was 4.7% (18/382). The only factor associated with the occurrence of leakage was the use of three or more stapler cartridges for the closure of the rectal stump (p = 0.002).ConclusionOur data support that multiple stapler firings for rectal division following colorectal resection has a major impact on anastomotic leak rate. Especially in laparoscopic surgery efforts should be made to minimize the number of stapler cartridges used.

Summary Background Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non‐selective beta‐blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. Aim To assess (re‐)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. Methods (Re‐)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. Results Seven hundred and sixty‐six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log‐rank: P = 0.353) nor mortality (log‐rank: P = 0.497) as compared to EBL alone. In SP, similar re‐bleeding rates were documented in EBL + NSBB vs EBL alone (log‐rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log‐rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6‐months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). Conclusions EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.

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