The description of a so-called cytokine storm in patients with COVID-19 has prompted consideration of anti-cytokine therapies, particularly interleukin-6 antagonists. However, direct systematic comparisons of COVID-19 with other critical illnesses associated with elevated cytokine concentrations have not been reported. In this Rapid Review, we report the results of a systematic review and meta-analysis of COVID-19 studies published or posted as preprints between Nov 1, 2019, and April 14, 2020, in which interleukin-6 concentrations in patients with severe or critical disease were recorded. 25 COVID-19 studies (n=1245 patients) were ultimately included. Comparator groups included four trials each in sepsis (n=5320), cytokine release syndrome (n=72), and acute respiratory distress syndrome unrelated to COVID-19 (n=2767). In patients with severe or critical COVID-19, the pooled mean serum interleukin-6 concentration was 36•7 pg/mL (95% CI 21•6-62•3 pg/mL; I²=57•7%). Mean interleukin-6 concentrations were nearly 100 times higher in patients with cytokine release syndrome (3110•5 pg/mL, 632•3-15 302•9 pg/mL; p<0•0001), 27 times higher in patients with sepsis (983•6 pg/mL, 550•1-1758•4 pg/mL; p<0•0001), and 12 times higher in patients with acute respiratory distress syndrome unrelated to COVID-19 (460 pg/mL, 216•3-978•7 pg/mL; p<0•0001). Our findings question the role of a cytokine storm in COVID-19-induced organ dysfunction. Many questions remain about the immune features of COVID-19 and the potential role of anti-cytokine and immune-modulating treatments in patients with the disease.

This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

Background Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse, and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. Methods The checklist was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process. Results The final checklist includes 16 reporting items, each of which is detailed with exemplar reporting and rationale. Conclusions The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and therefore reproducible.

Several machine learning (ML) algorithms have been increasingly utilized for cardiovascular disease prediction. We aim to assess and summarize the overall predictive ability of ML algorithms in cardiovascular diseases. A comprehensive search strategy was designed and executed within the MEDLINE, Embase, and Scopus databases from database inception through March 15, 2019. The primary outcome was a composite of the predictive ability of ML algorithms of coronary artery disease, heart failure, stroke, and cardiac arrhythmias. Of 344 total studies identified, 103 cohorts, with a total of 3,377,318 individuals, met our inclusion criteria. For the prediction of coronary artery disease, boosting algorithms had a pooled area under the curve (AUC) of 0.88 (95% CI 0.84–0.91), and custom-built algorithms had a pooled AUC of 0.93 (95% CI 0.85–0.97). For the prediction of stroke, support vector machine (SVM) algorithms had a pooled AUC of 0.92 (95% CI 0.81–0.97), boosting algorithms had a pooled AUC of 0.91 (95% CI 0.81–0.96), and convolutional neural network (CNN) algorithms had a pooled AUC of 0.90 (95% CI 0.83–0.95). Although inadequate studies for each algorithm for meta-analytic methodology for both heart failure and cardiac arrhythmias because the confidence intervals overlap between different methods, showing no difference, SVM may outperform other algorithms in these areas. The predictive ability of ML algorithms in cardiovascular diseases is promising, particularly SVM and boosting algorithms. However, there is heterogeneity among ML algorithms in terms of multiple parameters. This information may assist clinicians in how to interpret data and implement optimal algorithms for their dataset.

BackgroundAcute kidney injury (AKI), as defined by peak increase in serum creatinine, is independently associated with increased risk of mortality and length of stay. Studies have suggested that the duration of AKI may be an important additional or independent prognostic marker of increased mortality in patients with AKI across clinical settings. We performed a systematic review and meta-analysis of published studies to assess the impact of duration of AKI on outcomes.MethodsVarious bibliographic databases (MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science) were searched through database inception to December 2015. Human, longitudinal studies with patients aged 18 or above describing outcomes of duration of AKI were included. Duration of AKI categorized as “Short” if AKI duration was ≤2 days or labeled as “transient AKI”; “Medium” for AKI durations 3–6 days and “Long” for AKI duration of ≥7 days or “non-recovered”. Various outcomes looked at were Long term mortality, cardiovascular events, chronic kidney disease (CKD).ResultsEighteen studies were deemed eligible for the systematic review. The outcome of long-term mortality with duration of AKI was reported in 8 studies. The pooled Risk Ratio (RR) for long-term mortality generally was higher for longer duration of AKI: short duration of AKI (n = 8 studies, RR 1.42, 95% CI 1.21–1.66), medium duration (n = 4 studies, RR 1.92, 95% CI 1.34–2.75), and long duration (n = 8 studies, RR 2.28, 95% CI 1.77–2.94) duration of AKI. Further, Duration of AKI was independently associated with higher risk of cardiovascular outcomes and incident CKD Stage 3 when stratified within each stage of AKI.ConclusionDuration of AKI was independently associated with long term mortality, cardiovascular(CV) events, and development of incident CKD Stage 3.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-0876-7) contains supplementary material, which is available to authorized users.

In this meta-analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin. Predicting those at high risk of disease extension from diagnosis could lead to personalised therapeutic strategies.

BACKGROUND Numerous studies have reported declines in semen quality and other markers of male reproductive health. Our previous meta-analysis reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America–Europe–Australia (NEA) based on studies published during 1981–2013. At that time, there were too few studies with data from South/Central America–Asia–Africa (SAA) to reliably estimate trends among men from these continents. OBJECTIVE AND RATIONALE The aim of this study was to examine trends in sperm count among men from all continents. The broader implications of a global decline in sperm count, the knowledge gaps left unfilled by our prior analysis and the controversies surrounding this issue warranted an up-to-date meta-analysis. SEARCH METHODS We searched PubMed/MEDLINE and EMBASE to identify studies of human SC and TSC published during 2014–2019. After review of 2936 abstracts and 868 full articles, 44 estimates of SC and TSC from 38 studies met the protocol criteria. Data were extracted on semen parameters (SC, TSC, semen volume), collection year and covariates. Combining these new data with data from our previous meta-analysis, the current meta-analysis includes results from 223 studies, yielding 288 estimates based on semen samples collected 1973–2018. Slopes of SC and TSC were estimated as functions of sample collection year using simple linear regression as well as weighted meta-regression. The latter models were adjusted for predetermined covariates and examined for modification by fertility status (unselected by fertility versus fertile), and by two groups of continents: NEA and SAA. These analyses were repeated for data collected post-2000. Multiple sensitivity analyses were conducted to examine assumptions, including linearity. OUTCOMES Overall, SC declined appreciably between 1973 and 2018 (slope in the simple linear model: –0.87 million/ml/year, 95% CI: –0.89 to –0.86; P &lt; 0.001). In an adjusted meta-regression model, which included two interaction terms [time × fertility group (P = 0.012) and time × continents (P = 0.058)], declines were seen among unselected men from NEA (–1.27; –1.78 to –0.77; P &lt; 0.001) and unselected men from SAA (–0.65; –1.29 to –0.01; P = 0.045) and fertile men from NEA (–0.50; –1.00 to –0.01; P = 0.046). Among unselected men from all continents, the mean SC declined by 51.6% between 1973 and 2018 (–1.17: –1.66 to –0.68; P &lt; 0.001). The slope for SC among unselected men was steeper in a model restricted to post-2000 data (–1.73: –3.23 to –0.24; P = 0.024) and the percent decline per year doubled, increasing from 1.16% post-1972 to 2.64% post-2000. Results were similar for TSC, with a 62.3% overall decline among unselected men (–4.70 million/year; –6.56 to –2.83; P &lt; 0.001) in the adjusted meta-regression model. All results changed only minimally in multiple sensitivity analyses. WIDER IMPLICATIONS This analysis is the first to report a decline in sperm count among unselected men from South/Central America–Asia–Africa, in contrast to our previous meta-analysis that was underpowered to examine those continents. Furthermore, data suggest that this world-wide decline is continuing in the 21st century at an accelerated pace. Research on the causes of this continuing decline and actions to prevent further disruption of male reproductive health are urgently needed.

Background: Cisplatin-based combination chemotherapy is standard treatment for metastatic urothelial carcinoma; however, the vast majority of patients experience disease progression. As systemic therapy alone is rarely curative for the treatment of metastatic urothelial cancer, not only are new therapies needed but also refinement of general treatment principles. Herein, we conducted a systematic review and meta-analysis to explore the role of metastasectomy in metastatic urothelial carcinoma.Methods: We conducted a systematic review of the literature regarding local treatment for metastatic urothelial carcinoma. An online electronic search of the PubMed/MEDLINE and EMBASE databases was performed to identify peer-reviewed articles. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information was then extracted including number of patients, gender, the site of the primary urothelial tumor, site of metastasis, chemotherapy before or after metastasectomy, overall survival (OS), and disease specific survival (DSS) after metastasectomy. A meta-analysis was performed with those studies with sufficient survival data to obtain pooled overall survival. The article quality was assessed using the Cochrane Handbook “risk of bias” tool.Results: Seventeen out of 3963 articles were eligible for review between 1990–2015, including a total of 412 patients. The mean time to recurrence after metastasectomy was 14.25 months. The overall survival from time of metastasectomy ranged from 2 to 60 months. Pooled analyses of studies reported survival data revealed an improved overall survival for patients treated with metastasectomy compared with non-surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49–0.81). All, except for three studies, were retrospective and non-randomized, leading to a high risk of bias associated with patient selection, patient attrition, and reporting. Such high potential of selection bias may lead to higher OS than expected. Additionally, treatment and outcome details reported across studies was highly variable.Conclusions: Limited conclusions can be drawn from the available literature exploring the role of metastasectomy in the management of metastatic urothelial cancer due to lack of uniform reporting elements and multiple sources of bias particularly related to a lack of prospective randomized trials. As a subset of patients treated with metastasectomy achieve durable disease control, this approach may be considered for select patients.