Hasan, Bashar

Background and objectives AKI is classified as prerenal, intrinsic, and postrenal. Prerenal AKI and intrinsic AKI represent the most common causes for AKI in hospitalized patients. This study aimed to examine the accuracy of the fractional excretion of sodium for distinguishing intrinsic from prerenal AKI. Design, setting, participants, & measurements We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, the Cochrane Library, and Scopus for all available studies that met the criteria until December 31, 2021. We included studies that evaluated fractional excretion of sodium in differentiating AKI etiologies in adults, whereas studies that did not have sufficient data to extract a 2×2 table were excluded. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and extracted the diagnostic accuracy data for all included studies. We conducted a meta-analysis using the bivariate random effects model. We performed subgroup analysis to investigate sources of heterogeneity and the effect of the relevant confounders on fractional excretion of sodium accuracy. Results We included 19 studies with 1287 patients. In a subset of 15 studies (872 patients) that used a threshold of 1%, the pooled sensitivity and specificity for differentiating intrinsic from prerenal AKI were 90% (95% confidence interval, 81% to 95%) and 82% (95% confidence interval, 70% to 90%), respectively. In a subgroup of six studies (511 patients) that included CKD or patients on diuretics, the pooled sensitivity and specificity were 83% (95% confidence interval, 64% to 93%) and 66% (95% confidence interval, 51% to 78%), respectively. In five studies with 238 patients on diuretics, the pooled sensitivity and specificity were 80% (95% confidence interval, 69% to 87%) and 54% (95% confidence interval, 31% to 75%), respectively. In eight studies with 264 oliguric patients with no history of CKD or diuretic therapy, the pooled sensitivity and specificity were 95% (95% confidence interval, 82% to 99%) and 91% (95% confidence interval, 83% to 95%), respectively. Conclusions Fractional excretion of sodium has a limited role for AKI differentiation in patients with a history of CKD or those on diuretic therapy. It is most valuable when oliguria is present.

There is no clear consensus regarding the optimal approach for secondary prophylaxis of gastric variceal bleeding (GVB) in patients with cirrhosis. We conducted a systematic review and network meta‐analysis (NMA) to compare the efficacy of available treatments. A comprehensive search of several databases from each database's inception to March 23, 2021, was conducted to identify relevant randomized controlled trials (RCTs). Outcomes of interest were rebleeding and mortality. Results were expressed as relative risk (RR) and 95% confidence interval (CI). We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to rate the certainty of evidence. We included 9 RCTs with 647 patients who had histories of GVB and follow‐ups >6 weeks. A total of 9 interventions were included in the NMA. Balloon‐occluded retrograde transvenous obliteration (BRTO) was associated with a lower risk of rebleeding when compared with β‐blockers (RR, 0.04; 95% CI, 0.01‐0.26; low certainty), and endoscopic injection sclerotherapy (EIS)–cyanoacrylate (CYA) (RR, 0.18; 95% CI, 0.04‐0.77; low certainty). β‐blockers were associated with a higher risk of rebleeding compared with most interventions and with increased mortality compared with EIS‐CYA (RR, 4.12, 95% CI, 1.50‐11.36; low certainty), and EIS‐CYA + nonselective β‐blockers (RR, 5.61; 95% CI, 1.91‐16.43; low certainty). Analysis based on indirect comparisons suggests that BRTO may be the best intervention in preventing rebleeding, whereas β‐blocker monotherapy is likely the worst in preventing rebleeding and mortality. Head‐to‐head RCTs are needed to validate these results.

An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton, and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targeting Ezh2 through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated by Ezh2 for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss of Ezh2 in the tendon cells did not disrupt overall tendon structure or collagen organization suggesting that tendon differentiation and maturation are independent of Ezh2 signaling.

Abstract Background Excess adipose tissue is associated with an abnormal lipid profile that may improve with weight reduction. In this meta-analysis, we aimed to estimate the magnitude of change in lipid parameters associated with weight loss in adults who are overweight or obese. Methods We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus from 2013 to September, 2018. We included randomized controlled trials (RCTs) that evaluated interventions to treat adult obesity (lifestyle, pharmacologic and surgical) with follow-up of 6 months or more. Results We included 73 RCTs with moderate-to-low risk of bias, enrolling 32 496 patients (mean age, 48.1 years; weight, 101.6 kg; and body mass index [BMI], 36.3 kg/m2). Lifestyle interventions (diet, exercise, or both), pharmacotherapy, and bariatric surgery were associated with reduced triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) concentrations and increased high-density lipoprotein cholesterol (HDL-C) at 6 and 12 months. The following data are for changes in lipid parameters after 12 months of the intervention with 95% CI. Following lifestyle interventions, per 1 kg of weight lost, TGs were reduced by –4.0 mg/dL (95% CI, –5.24 to –2.77 mg/dL), LDL-C was reduced by –1.28 mg/dL (95% CI, –2.19 to –0.37 mg/dL), and HDL-C increased by 0.46 mg/dL (95% CI, 0.20 to 0.71 mg/dL). Following pharmacologic interventions, per 1 kg of weight lost, TGs were reduced by –1.25 mg/dL (95% CI, –2.94 to 0.43 mg/dL), LDL-C was reduced by –1.67 mg/dL (95% CI, –2.28 to –1.06 mg/dL), and HDL-C increased by 0.37 mg/dL (95% CI, 0.23 to 0.52 mg/dL). Following bariatric surgery, per 1 kg of weight lost, TGs were reduced by –2.47 mg/dL (95% CI, –3.14 to –1.80 mg/dL), LDL-C was reduced by –0.33 mg/dL (95% CI, –0.77 to 0.10 mg/dL), and HDL-C increased by 0.42 mg/dL (95% CI, 0.37 to 0.47 mg/dL). Low-carbohydrate diets resulted in reductions in TGs and increases in HDL-C, whereas low-fat diets resulted in reductions in TGs and LDL-C and increases in HDL-C. Results were consistent across malabsorptive and restrictive surgery. Conclusions Weight loss in adults is associated with statistically significant changes in serum lipids. The reported magnitude of improvement can help in setting expectations, inform shared decision making, and facilitate counseling.

Purpose: Postural orthostatic tachycardia syndrome has been recognized for decades, but treatment is largely based on anecdotal experience and expert opinion. Pharmacologic treatment is inconsistent and unstandardized. We did a systematic review to identify controlled studies from which informed treatment decisions can be made. Method: Through a standard systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified all English-language studies of a medication treatment for postural orthostatic tachycardia syndrome that included a comparison or control group and followed outcomes for at least 1 week of treatment. Results: A total of 626 studies were identified by the search criteria, and 8, involving a total of 499 patients, met the criteria. No studies were adequately similar to allow for meta-analysis. Of the identified 8 studies, 2 were randomized controlled trials and 4 had been subjected to peer review. In individual studies, there was some favorable effect with fludrocortisone, beta blockers, midodrine, and selective serotonin reuptake inhibitors. Conclusion: There is a paucity of high-quality data about effectiveness of medication in the treatment of postural orthostatic tachycardia syndrome. Nonetheless, 2 randomized trials and 6 other reports show some favorable effects of medication.

Introduction Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, usually caused by tobacco smoking, but other important risk factors include exposures to combustion products of biomass fuels and environmental pollution. The introduction of several new (combination) inhaler therapies, increasing uncertainty about the role of inhaled corticosteroids and a rapid proliferation of the literature on management of stable COPD in general, call for novel ways of evidence synthesis in this area. A systematic review and evidence map can provide the basis for shared decision-making tools and help to establish a future research agenda. Methods and analysis This systematic review will follow an umbrella systematic review design (also called overview of reviews). We plan to conduct a comprehensive literature search of Ovid MEDLINE (including epub ahead of print, in process and other non-indexed citations), Ovid Embase, Ovid Cochrane Database of Systematic Reviews and Scopus from database inception to the present. We will include systematic reviews that assessed the effectiveness of any pharmacological or non-pharmacological intervention on one or more patient-important outcomes and/or lung function in patients with stable COPD. For every intervention/outcome pair, one systematic review will be included. An a priori protocol will guide, which systematic reviews will be chosen, how their credibility will be evaluated, and how the quality of the body of evidence will be rated. Data will be synthesised into an evidence map that will present a matrix that depicts each available treatment for stable COPD with a quantitative estimate on symptoms/outcomes from the patient perspective, along with an indication of the size and certainty in the evidence. Ethics and dissemination Approval by a research ethics committee is not required since the review will only include published data. The systematic review will be published in a peer-reviewed journal. PROSPERO registration number CRD42018095079

Background. This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). Methods. We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. Results. Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. Conclusions. Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.