Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis

BackgroundConflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease.AimsTo identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations.MethodsA systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models.ResultsOf the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I² = 69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I² = 38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26–3.39; I² = 78%); stroke (HR 1.59, 95% CI 1.29–1.96; I² = 45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I² = 68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I² = 0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population.ConclusionQTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.     

Sofosbuvir-based regimens for HCV in stage 4–stage 5 chronic kidney disease. A systematic review with meta-analysis

BackgroundHepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4–5 CKD.Study aims and designWe performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4–5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses.ResultsThirty clinical studies (n = 1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I² = 99.8%) and 0.09 (95% CI, 0.05; 0.13, I² = 84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I² = 73.3%) (P < 0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, −0.01; 0.04, I² = 16.1%). Common serious adverse events were anemia (n = 26, 38%) and reduced eGFR (n = 14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I² = 80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I² = 95.8%). Six studies (n = 69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found.ConclusionsSOF-based regimens appear safe and effective in patients with stage 4–5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.     

A meta-analysis of efficacy of topical steroids in eosinophilic esophagitis: From the perspective of histologic,clinical, and endoscopic outcome

BackgroundSwallowed topical steroids are a mainstay drug therapy for eosinophilic esophagitis (EoE), studies have demonstrated good histologic response, but with enormous discrepancy in clinical and endoscopic improvement. We conducted this meta-analysis to investigate the efficacy of topical steroids in EoE in histological, clinical and endoscopic improvement.MethodsSeveral databases were searched from inception to August 1, 2019 for randomized controlled trials (RCTs) comparing topical steroids with placebo for EoE in the short-term. The outcomes of interest mainly included basic characteristics of the studies, histologic, clinical, endoscopic response rate and adverse events. The results were pooled together using Reviewer Manager 5.3.5 software, and inconsistency was quantified using I² statistics.ResultsNine studies were eventually selected. The results showed that topical steroids were effective in inducing histologic response compared with placebo for both complete (OR 35.82, 95% CI 14.98–85.64, P < 0.0001; I² = 0, P = 0.72) and partial response (OR 28.44, 95% CI 8.56–94.47, P < 0.0001; I² = 70%, P = 0.0009). Moreover, topical steroids were useful in gaining clinical response (OR 2.53, 95% CI 1.14–5.60, P = 0.02; I² = 60%, P = 0.02) and endoscopic response (OR 3.51, 95% CI 1.47–8.36, P = 0.005; I² = 0, P = 0.57). Generally, topical steroids are well tolerated. The most common adverse events are infections and infestations (59 cases).ConclusionTopical steroids were effective in inducing histological, clinical and endoscopic response in the short-term, and the adverse events were almost tolerable; however, we should interpret the result of clinical and endoscopic response with caution.     

Post-polypectomy bleeding after colonoscopy on uninterrupted aspirin/non steroideal antiflammatory drugs: Systematic review and meta-analysis

Background and aimThe aim of this systematic review and meta-analysis was to assess the risk of post-polypectomy bleeding (PPB) in patients that underwent colorectal polypectomy and exposed to ASA/NSAIDs.MethodsRelevant publications were identified in MEDLINE/EMBASE for the period 1950–2016. Studies with specified ASA/NSAIDs exposure and bleeding rate were included. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was based on fixed or random effect models in relation to the heterogeneity.Results11 studies (4 prospective and 7 retrospective) including 9307 patients were included in the analyses. Overall, 344 patients (OR 1.8; 95% CI 1.2–2.7; p-value 0.001, I² 52%) experienced rectal bleeding after procedure. While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR 1.1; CI 95% 0.6–2.1; d.f. = 1, p = 0.64, I² 0%), the risk of delayed PPB was augmented (OR 1.7; 95% CI 1.2–2.2; d.f. = 8, p = 0.127, I² 36%).ConclusionsASA/NSAIDs are not a risk factor for immediate PPB but the chance of delayed is increased.     

Effects of prolonged use of azithromycin in patients with cystic fibrosis: A meta-analysis

Azithromycin has been studied as potential therapeutic anti-inflammatory agent for cystic fibrosis (CF) patients. Azithromycin (AZM) has been used as an immunomodulating agent, based on few small studies. Considering the cost and potential side effects of long-term azithromycin therapy, it is important to identify the group of patients that would benefit the most. Weighted mean difference was used for pulmonary function tests, and risk ratios for all other variables. The random-effects model was applied for all reports. Combining four studies (N = 368), azithromycin showed increase in FEV₁ (3.53%, 95% CI 0.00, 7.07, p = 0.05; I² = 38%) and FVC (4.24%, 95% CI 2.02, 6.45, p = 0.0002; I² = 0%). When trials were analyzed by baseline Pseudomonas sputum colonization, the heterogeneity decreased (I² = 0%), FEV₁ significantly increased to 4.66% (95% CI 1.18, 8.15, p = 0.009), and FVC increased to 4.64% (95% CI 2.11, 7.17, p = 0.0003). The GI side effects were 72% higher with azithromycin use (RR 1.72, 95% CI 1.33, 2.21, p = 0.00003), the main side effects being nausea (RR 2.04, 95% CI 1.19, 3.45, p = 0.009), and diarrhea (RR 2.12, 95% CI 1.10, 4.08, p = 0.02). Azithromycin improves lung function of CF patients, especially in the subgroup colonized with Pseudomonas. However, nausea and diarrhea are significantly more frequent with azythromycin.     

Thiazolidinedione use and cancer incidence in type 2 diabetes: A systematic review and meta-analysis

AimsEvidence suggests thiazolidinediones (TZDs) may modify the relationship between type 2 diabetes and cancer incidence. We aimed to summarize data from randomized controlled trials (RCTs) and observational studies to examine risk of overall and site-specific cancers with TZD use in individuals with type 2 diabetes.MethodsWe searched 12 key biomedical databases and seven grey literature sources up to June 2011, without language restrictions. We performed separate meta-analyses according to cancer site and study design, comparing ever-use to never-use of TZDs, and pioglitazone alone.ResultsThe search yielded 1338 unique citations; we included four RCT, seven cohort and nine nested case-control studies, contributing data from 2.5 million people. Estimates from observational studies suggested any TZD use was associated with a decreased risk of colorectal (pooled RR: 0.93, 95%CI 0.87–1.00, P = 0.04, I² = 30%), lung (pooled RR: 0.91, 95%CI 0.84–0.98, P = 0.02, heterogeneity (I²) = 35%) and breast (pooled RR: 0.89, 95%CI 0.81–0.98, P = 0.02, I² = 44%) cancer. Risk of overall cancer with TZD use was not significantly modified in RCTs (pooled RR: 0.92, 95%CI 0.79–1.07, P = 0.26, I² = 0%) or observational studies (pooled OR: 0.95, 95%CI 0.78–1.16, P = 0.63, I² = 70%). Pioglitazone use was, however, associated with a decreased risk of overall cancer (colorectal, lung, breast, prostate and renal sub-sites combined) in observational studies (pooled RR: 0.95, 95%CI 0.91–0.99, P = 0.009, I² = 0%).ConclusionsOur findings suggest that use of TZDs is associated with a modest but significantly decreased risk of lung, colorectal and breast cancers. Results were limited by the paucity of studies designed to answer our research question. Further evaluation of TZD use, cancer risk factors and potential confounders is required.     

Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis

Background and aimsFecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD.MethodsA systematic literature search was performed through May 2014. Inclusion criteria required FMT as the primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections.ResultsEighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow-up. Among the cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%–60.4%), with a moderate risk of heterogeneity (Cochran's Q, P = 0.011; I² = 37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%–40.8%) for UC (P = 0.37; I² = 0%) and 60.5% (95% CI 28.4%–85.6%) for CD (P = 0.05; I² = 37%). Six studies performed microbiota analysis.ConclusionsThis analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.     

Insulin use and cancer risk in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies

AimsTo determine whether data from observational studies supports the hypothesis of an increased risk of overall and site-specific cancer among individuals with diabetes using exogenous insulin therapies.MethodsWe conducted a comprehensive search of nine key biomedical databases for all years up to December 2011, restricted to the English language. Data from cohort and nested case-control studies were included in random effects meta-analyses of site-specific and overall cancer incidence comparing ever use and new use of: (1) insulin to no insulin and; (2) insulin glargine to other insulins.ResultsThe search yielded 3052 unique citations, of which 19 were selected for inclusion, representing data for 1,332,120 people and 41,947 cancers. Pancreatic cancer risk was increased among new users of insulin (RR: 3.18, 95%CI: 3.27–3.71, I² = 32%). New use of insulin glargine was associated with an increased risk of pancreatic cancer (RR: 1.63, 95%CI: 1.05–2.51, I² = 0%) and prostate cancers (RR: 2.68, 95%CI: 1.50–4.79, I² = 0%) but a decreased risk of colorectal cancer (RR: 0.78, 95%CI: 0.64–0.94, I² = 15%).ConclusionNew use of insulin or insulin glargine was associated with an increased risk of pancreatic cancer, possibly due to reverse causality. New use of insulin glargine was associated with a decreased risk of colorectal cancer but an increased risk of prostate cancer. Our results should be interpreted with caution due to limitations of included studies.     

Adiponectin Levels and Risk of Coronary Heart Disease: A Meta-analysis of Prospective Studies

BackgroundAdiponectin is the most abundant circulating protein secreted by adipocytes. There is uncertainty about the association between adiponectin levels and risk of coronary heart disease (CHD). We conducted this meta-analysis to summarize the effect of adiponectin on the risk of CHD.MethodsA comprehensive search was performed to identify all prospective studies on the association of adiponectin levels and risk of CHD. The quality of the eligible studies was evaluated by the Newcastle-Ottawa Scale. The fixed- or random-effects model was selected to pool the relative risk (RR) and 95% confidence interval (CI). Heterogeneity among studies was evaluated using Q test and the I² statistic. Publication bias was estimated using modified Egger’s linear regression test.ResultsTwelve prospective studies comprising 8 nested case-control studies and 4 cohort studies were included in the meta-analysis. A total of 14,960 participants were enrolled and 4,132 incident CHD events were observed. The pooled RR for CHD was 0.83 (95% CI, 0.69–0.98, P = 0.031). Subgroup analyses showed that the pooled RRs (95% CIs) for CHD risk were 0.78 (0.66–0.92) and 0.75 (0.59–0.94) for men and women, respectively. For studies with mean age less than 65 years, the pooled RR (95% CI) for CHD risk was 0.72 (0.59–0.87). For studies with 100 or more CHD cases, the pooled RR was marginally significant (RR = 0.83, 95% CI, 0.69–1.00; P = 0.051). No publication bias was found in our study (P = 0.911).ConclusionsThis meta-analysis showed that higher levels of adiponectin were associated with a low risk of CHD. The protective effect was consistently existed in men and women and in the middle-aged populations.     

Derivation and validation of the prediabetes self-assessment screening score after acute pancreatitis (PERSEUS)

Background and aimApproximately 40% of patients develop abnormal glucose metabolism after a single episode of acute pancreatitis. This study aimed to develop and validate a prediabetes self-assessment screening score for patients after acute pancreatitis.MethodsData from non-overlapping training (n = 82) and validation (n = 80) cohorts were analysed. Univariate logistic and linear regression identified variables associated with prediabetes after acute pancreatitis. Multivariate logistic regression developed the score, ranging from 0 to 215. The area under the receiver-operating characteristic curve (AUROC), Hosmer–Lemeshow χ² statistic, and calibration plots were used to assess model discrimination and calibration. The developed score was validated using data from the validation cohort.ResultsThe score had an AUROC of 0.88 (95% CI, 0.80–0.97) and Hosmer–Lemeshow χ² statistic of 5.75 (p = 0.676). Patients with a score of ≥75 had a 94.1% probability of having prediabetes, and were 29 times more likely to have prediabetes than those with a score of <75. The AUROC in the validation cohort was 0.81 (95% CI, 0.70–0.92) and the Hosmer–Lemeshow χ² statistic was 5.50 (p = 0.599). Model calibration of the score showed good calibration in both cohorts.ConclusionThe developed and validated score, called PERSEUS, is the first instrument to identify individuals who are at high risk of developing abnormal glucose metabolism following an episode of acute pancreatitis.     

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis

BackgroundTo systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus.MethodsWe searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months.Results7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83–1.02, p = 0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI 0.85–1.06; p = 0.33), cardiovascular mortality (0.95, 95% CI 0.71–1.27; p = 0.71), stroke (0.83, 95% CI 0.63–1.10; p = 0.20), or myocardial infarction (MI) (0.85, 95% CI 0.65–1.11; p = 0.24). There was no significant increased risk of major bleeding in aspirin group (2.46, 95% CI 0.70–8.61; p = 0.16). Meta-regression suggested that aspirin agent could reduce the risk of stroke in women and MI in men.ConclusionsIn patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.     

Risk factors for foot ulcers—A cross sectional survey from a primary care setting in Brazil

AimsTo identify the prevalence of higher risk of foot ulceration and associated factors among patients with diabetes mellitus (DM) at primary health care services.MethodsIndividuals with DM, registered at primary health care services in a municipality in southern Brazil, were interviewed and underwent foot examinations. Their risk of ulceration was classified in accordance with the recommendations of the International Working Group on the Diabetic Foot. Poisson bivariate and multivariate analyses were performed and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) were calculated.ResultsThe prevalence of higher risk of foot ulceration among the 337 interviewees was 27.9% (95% CI 23.1–32.9). The following factors were associated with this risk: having been diagnosed with DM for more than 10 years (Adjusted-PR 1.669; 95% CI 1.175–2.373; p = 0.004); having had previous diagnoses of acute myocardial infarction (Adjusted-PR 1.873; 95% CI 1.330–2.638; p < 0.001) and stroke (Adjusted-PR 1.684; 95% CI 1.089–2.604; p = 0.019); presenting interdigital mycosis (Adjusted-PR 1.539; 95% CI 1.030–2.300; p = 0.035) and calluses (Adjusted-PR 1.654; 95% CI 1.117–2.451; p = 0.012).ConclusionsThe prevalence of higher risk of ulceration was high, which reinforces the importance of continued education for health care professionals in order to prevent complications in the feet of these patients.     

ACOD frente a AVK en pacientes con fibrilación auricular y bioprótesis: revisión sistemática y metanálisis

Introduction and objectivesDirect oral anticoagulant (DOAC) therapy has been shown to be safe and effective in patients with atrial fibrillation (AF). However, outcomes in AF patients with bioprosthetic valves are unclear, as this population has been underrepresented in clinical trials. The aim of this study was to assess the safety and efficacy of DOACs in this population based on the existing published literature.MethodsA systematic search and review were conducted to identify randomized clinical trials and comparative observational studies published from 2017 to January 2022 that compared DOACs and vitamin K antagonists (VKAs) in AF patients with bioprosthetic valves. Hazard ratios (HR) were collected to compare the 2 treatments in terms of cardiovascular and all-cause mortality, stroke/systemic embolism, and major bleeding. A meta-analysis combining the results was performed.ResultsWe included 12 studies (30 283 patients). DOACs and VKAs were compared based on HRs at the 95% confidence interval. DOAC therapy was associated with a significant 9% reduction in all-cause mortality (HR, 0.91; 95%CI, 0.85-0.97; P = .0068; I² = 8%), with no significant differences in the risk of stroke/systemic embolism (HR, 0.87; 95%CI, 0.67-1.14; P = .29; I² = 45%) or major bleeding (HR, 0.82; 95%CI, 0.67-1.00; P = .054; I² = 48.7%).ConclusionsDOAC therapy in AF patients with bioprosthetic valves may be associated with a significant reduction in all-cause mortality, with no reduction in the efficacy of stroke/systemic embolism prevention or increase in major bleeding risk.     

Association of beta-blocker therapy at discharge with clinical outcomes in patients without heart failure or left ventricular systolic dysfunction after acute coronary syndrome: An updated systematic review and meta-analysis

BackgroundBeta-blockers are the standard treatment for acute coronary syndrome (ACS) based on evidence from the prethrombolytic era.We sought to examine the effect of beta-blocker treatment on patients without heart failure or left ventricular systolic dysfunction after ACS in the contemporary percutaneous coronary intervention (PCI) era.MethodsWe systematically searched PubMed, Web of Science, Cochrane Library, ClinicalTrials.gov and Google Scholar for studies comparing beta-blockers versus no beta-blockers in ACS patients in the contemporary PCI era. The primary outcome was all-cause death. Pooling unadjusted and multivariable adjusted results were calculated under random-effects models.ResultsData from 15 studies (n = 205,672), including 1 randomized trial, were analysed. Compared with no beta-blockers, beta-blocker therapy at discharge may reduce the risk of all-cause death (odds ratio [OR] 0.66, 95% confidence interval [CI]: 0.50–0.86; I² = 81.9%). Subgroup analysis according to single or multicentre studies indicated similar results. Prospective studies suggested that all-cause death was less common in the beta-blocker group. After multivariable adjustment, a lower risk of all-cause death was still observed with beta-blockers (OR: 0.74, 95% CI: 0.59–0.94; I² = 40.1%). No differences existed in major adverse cardiovascular events (MACE), cardiac death, myocardial infarction, heart failure, revascularization or stroke, before and after multivariable adjustment.ConclusionsIn patients without heart failure or left ventricular systolic dysfunction after ACS in the contemporary PCI era, beta-blocker therapy may still be beneficial due to a potential reduced risk of all-cause death.     

The metabolic syndrome in early pregnancy and risk of gestational diabetes mellitus

AimThe objective of the present study was to determine whether or not maternal metabolic syndrome in early pregnancy in women without previous diabetes is associated with the development of gestational diabetes mellitus (GDM).MethodsA total of 508 women from the Rhea study—involving a pregnant cohort in Crete, Greece (2007–2009)—with singleton pregnancies were included in the present analysis. Maternal fasting serum samples were collected and blood pressure measured before gestational week 15. The metabolic syndrome in early pregnancy was defined according to NHLBI/AHA criteria. Pregnant women were screened for GDM between weeks 24 and 28 of gestation, as defined by Carpenter and Coustan criteria. Multivariable log-binomial regression models were used to estimate the effect of the metabolic syndrome in early pregnancy on the risk of GDM, after adjusting for confounding factors.ResultsWomen with the metabolic syndrome were at high risk of GDM (RR = 3.17; 95% CI: 1.06–9.50). Among the components of the metabolic syndrome, the most significant risk factors were impaired fasting glucose (RR = 4.92; 95% CI: 1.41–17.23) and pre-pregnancy obesity (RR = 2.65; 95% CI: 1.23–5.70). A 10-mmHg rise in systolic and diastolic blood pressure increased the relative risk of GDM by 49% (RR = 1.49; 95% CI: 1.10–2.02) and 34% (RR = 1.34; 95% CI: 1.04–1.73), respectively, whereas a 1-unit increase in pre-pregnancy BMI increased the relative risk of GDM by 6% (RR = 1.06; 95% CI: 1.01–1.12).ConclusionThese findings suggest that women with the metabolic syndrome in early pregnancy have a greater risk of developing GDM.     

A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes

AimsConflicting evidence exists regarding the benefits of physical activity for long-term blood glucose control in adults with type 1 diabetes (T1D). The object of this systematic review was to determine the effects of physical activity on long-term blood glucose control in T1D adults.MethodsPubMed/Medline, Embase, CENTRAL, SPORTdiscus, Global Health and ICTRP were searched up to October 2013 for randomized trials of aerobic or resistance exercise training in T1D adults. Exercises had to be performed at least twice weekly for a minimum of two months. The primary outcome was glycated hemoglobin (HbA_1c). Secondary outcomes included cardiorespiratory fitness and insulin dose.ResultsSix randomized trials were identified (323 adults); sample sizes ranged from n = 6 to n = 148 participants receiving the intervention. Five trials had an unknown risk of bias; one trial was deemed to be at high risk of bias. Exercise frequency varied from twice weekly to daily, with intensities (50–90% VO_2peak), and session durations (20–120 min) varying widely. Four trials reported HbA_1c, which decreased with exercise training (mean difference [MD] −0.78% (−9 mmol/mol), 95% CI −1.14 (−13 mmol/mol) to −0.41 (−5 mmol/mol); p < 0.0001; I² 0%) compared with controls. Exercise training improved cardiorespiratory fitness by 3.45 ml/kg/min (95% CI 0.59 to 6.31, p = 0.02, I² 0%) compared with controls. One trial reported an effect on insulin dose (MD −0.4 U/kg, 95% CI −0.53 to −0.27, p < 0.00001) compared to controls.ConclusionThere are currently insufficient well-designed studies to ascertain the true effect of exercise training on HbA_1c in individuals with T1D, but current results are promising.     

Prevalence and risk factors for wheezing and allergic diseases in preschool children: A perspective from the Mediterranean coast of Turkey

ObjectivesThe aim of the present study was to determine the prevalence and risk factors of allergic diseases in preschool children from one of the biggest cities in the Mediterranean Region of Turkey.MethodsThe study population included 396 preschool children attending to urban daycare centres in Mersin. In the first stage, a comprehensive standardised questionnaire modified from the International Study of Asthma and Allergies in Childhood (ISAAC) was employed. In the second stage, serum food and inhalant specific IgE, and skin tests were performed in 45 children with frequent wheezing and 28 children with no wheezing.ResultsThe prevalence of ever wheezing, current wheezing, physician-diagnosed asthma, allergic rhinitis and eczema were 53% (210), 33.3% (132), 27.3% (108), 13.4% (53) and 8.3% (33), respectively. A family history of atopy (OR = 2.5, 95% CI: 1.3–4.7, p = 0.004), dampness at home (OR = 2.4, 95% CI: 1.2–4.8, p = 0.008), a history of intestinal parasites (OR = 4.3, 95% CI: 1.7–10.9, p = 0.002), previous history of pneumonia (OR = 6.9, 95% CI: 1.9–25.9, p = 0.004), initiation of complementary foods before the age of three months (OR = 6.1, 95%CI: 1.4–26.9, p = 0.02) and presence of food allergy (OR = 3.1, 95% CI: 1.1–9.2, p = 0.03) were found to be significant risk factors for physician-diagnosed asthma. The risk factors for frequent wheezing were maternal smoking during pregnancy (OR = 5.2, 95% CI: 0.9–28.7, p = 0.05) and high serum IgE levels (OR = 2.9, 95% CI: 0.9–9.0, p = 0.05) at borderline significance.ConclusionOur study was the first epidemiological study in preschool children in the Mediterranean region of Turkey and demonstrated a high prevalence of asthma and allergic diseases, probably related to humid climatic properties in addition to other environmental and genetic factors.     

Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study

Introduction and objectivesAcute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting.Patients and methodsWe performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019.ResultsAKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p = 0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p = 0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p < 0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p = 0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p = 0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p = 0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p = 0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p = 0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p = 0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival.ConclusionPatients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.     

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue

ObjectiveThe objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk.MethodsAll eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software.ResultsIn overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients.ConclusionACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.     

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials

Background and aimsA dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF.MethodsSystematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator.ResultsThe initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I² = 74%, Chi² = 11.57, p = 0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio = 0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio = 0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF.ConclusionIn a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.