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Coronavirus disease 2019 (COVID‐19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi‐targeted metabolomic analysis on 56 COVID‐19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID‐19 patients. A meta‐analysis was performed on published metabolic data of COVID‐19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; −log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs= 0.442, p = 0.005). Mini meta‐analysis indicated elevated glutamate was related to increased risk of COVID‐19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17–3.50) and severe COVID‐19 (pooled OR = 2.28; 95% CI: 1.14–4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID‐19, the pooled OR were 0.30 (95% CI: 0.20–0.44), and 0.44 (95% CI: 0.19–0.98), respectively. Glutamine and glutamate metabolism are associated with COVID‐19 severity in multiple populations, which might confer potential therapeutic target of COVID‐19, especially for severe patients. [ABSTRACT FROM AUTHOR]

Current guidelines provide recommendation for transcatheter aortic-valve replacement (TAVR) in severe aortic stenosis without emphasis on valve systems. The comparative performances of balloon-expandable valves (BEV) and self-expanding valves (SEV) remain unclear. We aim to compare the early (30-day) and midterm (1-year) mortality and cardiovascular outcomes of BEV with SEV. PubMed, CENTRAL, and EMBASE were searched from inception to February 13, 2020 for randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Odds ratios (ORs) for binary outcomes and mean differences for continuous outcomes were pooled using random-effect models (DerSimonian–Laird method) with Hartung-Knapp-Sidik-Jonkman variance correction. Primary outcomes were early and midterm all-cause mortality. We included 3 RCTs (1418 patients) and 12 PSM studies (36,540 patients). Compared with SEV, BEV was associated with significantly lower mortality at 30 days (OR 0.76, 95% CI 0.67–0.85, p < 0.001, I2 = 0) and 1 year (OR 0.87, 95% CI 0.77–0.99, p = 0.04, I2 = 20.4%) in PSM studies, but not RCTs with insufficient power. Similar findings were found in subgroups analysis based on valve generations and SEV types. The 30-day and 1-year cardiovascular mortality, 30-day incidences of moderate to severe paravalvular leak, procedural contrast agent volume, and procedure time were lower, but transvalvular pressure gradient was higher in BEV than SEV in PSM studies. The 30-day incidences of permanent pacemaker implantation (PPI), acute kidney injury, stroke, major bleeding, major vascular complications, and rehospitalization were not statistically different between BEV and SEV. Early-generation SEV was associated with a higher 30-day PPI risk than corresponding BEV comparators. PPI risk was lower in ACURATE neo (Boston Scientific, Natick, MA) but higher in Evolut R SEV (Medtronic Inc., Minneapolis, MN), both compared with SAPIEN 3 BEV (Edwards Lifesciences, Irvine, CA). PSM studies suggest lower early and midterm mortality in BEV than SEV, but the contribution of unmeasured confounders cannot be excluded. Results from adequately powered RCTs with long-term follow-up are critically needed to confirm these findings. [Display omitted] • Balloon-expandable valve (BEV) transcatheter aortic-valve replacement might be associated with lower early and midterm total mortality than self-expanding valve (SEV) replacement. • Early moderate to severe paravalvular leak was lower with BEV than SEV. • Early incidence of stroke, permanent pacemaker implantation, acute kidney injury, and major bleeding were not different. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To determine the 5-year and temporal performance of TAVR versus SAVR. Background: TAVR has become a valuable treatment for severe aortic stenosis but the long-term safety and efficacy remain unclear. Methods: Databases were searched until October 6, 2019 for randomized trials with ≥5 years' follow-up. Primary outcome was all-cause mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with random-effects models. Results: We included 4 trials with 3,758 patients. TAVR was associated with a significantly higher 5-year all-cause mortality than SAVR (OR, 1.19; 95% CI, 1.03–1.37; P = 0.02). Landmark analysis showed no significant difference within 2 years (OR, 0.92; 95% CI, 0.79–1.08; P = 0.33) but a statistically higher mortality in TAVR between 2 and 5 years (OR, 1.32; 95% CI, 1.14–1.52; P = 0.0002), with significant difference between these 2 temporal phases (P for interaction = 0.001). Similar interaction was found for cardiovascular mortality and several other outcomes. Rates of all-cause mortality or disabling stroke, permanent pacemaker implantation, aortic-valve rehospitalization, and reintervention were higher, but rates of major bleeding and new-onset fibrillation were lower in TAVR at 5 years. The incidences of myocardial infarction, stroke, and transient ischemic attack were not statistically different between TAVR and SAVR. Conclusions: TAVR was associated with a significantly higher all-cause mortality at 5 years compared with SAVR. Of note, all-cause mortality presented a characteristic temporal pattern showing increased risk between 2 and 5 years but not within 2 years. Longer-term follow-up data are warranted. [ABSTRACT FROM AUTHOR]

The gene expression for interleukin-2 receptor subunit alpha (CD25/IL2RA) is frequently altered in adults with acute myeloid leukemia (AML). Increasing evidence indicates that the elevated expression of CD25 may be correlated with poor survival for AML patients. Thus, we performed this meta-analysis to further evaluate the prognostic value of elevated CD25 in AML. Eligible studies were gathered by searching on PubMed, Web of Science, and Embase. Using the R language 3.6.0 software, Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/event-free survival (EFS) for total and subgroup analyses were calculated to investigate the association of elevated CD25 and outcomes of AML patients. Ten studies with a total of 1640 participants were enrolled in this meta-analysis. Pooled HRs suggested that overexpression of CD25 predicted poor outcomes on both OS (HR = 2.27, 95%CI 1.95–2.64) and DFS/RFS/EFS (HR = 1.77, 95%CI 1.44–2.17) in overall population. Subgroup analyses stratified by ethnicity, AML subtype, cut-off value, statistical methodologies and detection method draw similar results. Our meta-analysis indicates that elevated CD25 expression is a poor prognostic factor for AML patients. Considering limited number of samples, further relevant studies are warranted. [ABSTRACT FROM AUTHOR]

Background: No consensus treatment has been reached for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Hepatic resection (HR) and transarterial chemoembolization (TACE) have been recommended as effective options, but which is better remains unclear. This meta-analysis is to compare the effectiveness of HR and TACE for HCC with PVTT patients.Methods: The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched for comparing HR and TACE treating PVTT.Results: Twelve retrospective studies with 3129 patients were included. A meta-analysis of 11 studies suggested that the 1-, 2-, 3-, and 5-year overall survival (OS) rates (OR = 0.48, 95% CI = 0.41-0.57, I2 = 37%, P < 0.00001; OR = 0.21, 95% CI = 0.12-0.38, I2 = 43%, P < 0.00001; OR = 0.35, 95% CI = 0.28-0.44, I2 = 53%, P < 0.00001; OR = 0.28, 95% CI = 0.14-0.54, I2 = 72%, P = 0.0001, respectively) favored HR over TACE. In a subgroup analysis, HR had better 1-, 2-,3, 5-year OS for type I PVTT (OR = 0.33, 95% CI = 0.17-0.64, I2 = 20%, P = 0.001; OR = 0.32, 95% CI = 0.16-0.63, I2 = 0%, P = 0.001; OR = 0.18, 95% CI = 0.09-0.36, I2 = 0%, P < 0.00001; OR = 0.07, 95% CI = 0.01-0.32, I2 = 0%, P = 0.0006, respectively) and better 1-, 3-, and 5-year OS for type II PVTT (OR = 0.37, 95% CI = 0.20-0.70, I2 = 59%, P = 0.002; OR = 0.22, 95% CI = 0.13-0.39, I2 = 0%, P < 0.00001; OR = 0.16; 95% CI = 0.03-0.91; I2 = 51%, P = 0.04, respectively). There was no difference in 1-, 3-, or 5-year OS between HR and TACE for type III PVTT (OR = 0.86, 95% CI = 0.61-1.21, I2 = 0%, P = 0.39; OR = 0.83, 95% CI = 0.42-1.64, I2 = 0%, P = 0.59; OR = 0.59, 95% CI = 0.06--6.04, I2 = 65%, P = 0.66, respectively).Conclusions: HR may lead to longer OS for some selected HCC patients with PVTT than TACE, especially for type I or II PVTT, with less difference being observed for type III or IV PVTT. [ABSTRACT FROM AUTHOR]

Background Endotracheal intubation (EI) in ICU patients is associated with an increased risk of life-threatening adverse events due to unstable conditions, rapid deterioration, limited preparation time, and variability in the expertise of operators. The goal of this study was to compare the effect of video laryngoscopy (VL) and direct laryngoscopy (DL) in ICU patients requiring EI. Methods We searched for relevant studies in PubMed, Embase, and the Cochrane database from inception through January 30, 2017. Randomized controlled trials were included if they reported data on any of the predefined outcomes in ICU patients requiring EI and managed with VL or DL. Results were expressed as risk ratios (RRs) or mean differences (MDs) with accompanying 95% CIs. Results Five randomized controlled trials with 1,301 patients were included. Despite better glottic visualization with VL (RR = 1.24; 95% CI, 1.07 to 1.43; P =.003), use of VL did not result in a significant increase in the first-attempt success rate (RR = 1.08; 95% CI, 0.92-1.26; P =.35) compared with DL. In addition, time to intubation (MD = 4.12 s; 95% CI, –15.86-24.09; P =.69), difficult intubation (RR = 0.72; 95% CI, 0.30-1.70; P =.45), mortality (RR = 1.02; 95% CI, 0.84-1.25; P =.83), and most other complications were similar between the VL and DL groups. Conclusions The VL technique did not increase the first-attempt success rate during EI in ICU patients compared with DL. These findings do not support routine use of VL in ICU patients. [ABSTRACT FROM AUTHOR]

Background: Many recent trials have investigated the long-term efficacy and safety of endarterectomy versus stenting in treating patients with carotid artery stenosis. We aimed to determine the long-term comparative efficacy and safety of both procedures by pooling this evidence in a meta-analysis. Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published until May 6, 2016. Randomized controlled trials, which reported outcomes of interest with a median follow-up of at least 4-year, were included. Results: Eight trials involving 7005 patients and 41824 patient-years of follow-up were included. In terms of the periprocedural outcomes, stenting was associated with a lower risk of myocardial infarction (OR: 0.51; 95% CI: 0.33 to 0.80; P = 0.003) but a higher risk of death or stroke (the composite endpoint, OR: 1.76; 95% CI: 1.38 to 2.25; P < 0.0001), a result that was primarily driven by minor stroke (OR: 2.19; 95% CI: 1.59 to 3.01; P < 0.0001), less so by periprocedural death (OR: 1.68; 95% CI: 0.82 to 3.44; P = 0.16) and major stroke (OR: 1.41; 95% CI: 0.95 to 2.09; P = 0.09). In terms of the long-term outcomes, stenting was associated with a higher risk of stroke (OR 1.45; 95% CI: 1.22 to 1.73; P < 0.0001) and the composite outcome of death or stroke (OR 1.25; 95% CI: 1.05 to 1.48; P = 0.01). No difference was found in long-term all-cause mortality between stenting and endarterectomy (OR: 1.09; 95% CI: 0.95 to 1.26; P = 0.21) and restenosis (OR: 1.48 (95% CI: 0.93 to 2.35; P = 0.10). No evidence of significant heterogeneity was found in any of the analyses. Conclusions: Carotid endarterectomy was found to be superior to stenting for short- and long-term outcomes, although endarterectomy was associated with a higher risk of periprocedural myocardial infarction. Carotid endarterectomy should be offered as the first choice for carotid stenosis at present, however, more evidence is needed because rapid progress in concurrent devices and medical treatments is being made. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported prognosis differences between male and female heart failure patients following cardiac resynchronization therapy (CRT). However, the potential clinical factors that underpin these differences remain to be elucidated. Methods: A meta-analysis was performed to investigate the factors that characterize sex-specific differences following CRT. This analysis involved searching the Medline (Pubmed source) and Embase databases in the period from January 1980 to September 2016. Results: Fifty-eight studies involving 33445 patients (23.08% of whom were women) were analyzed as part of this study. Only patients receiving CRT with follow-up greater than six months were included in our analysis. Compared with males, females exhibited a reduction of 33% (hazard ratio, 0.67; 95% confidence interval, 0.62–0.73; P < 0.0001) and 42% (hazard ratio, 0.58; 95% confidence interval, 0.46–0.74; P = 0.003) in all-cause mortality and heart failure hospitalization or heart failure, respectively. Following a stratified analysis of all-cause mortality, we observed that ischemic causes (p = 0.03) were likely to account for most of the sex-specific differences in relation to CRT. Conclusion: These data suggest that women have a reduced risk of all-cause mortality and heart failure hospitalization or heart failure following CRT. Based on the results from the stratified analysis, we observed more optimal outcomes for females with ischemic heart disease. Thus, ischemia are likely to play a role in sex-related differences associated with CRT in heart failure patients. Further studies are required to determine other indications and the potential mechanisms that might be associated with sex-specific CRT outcomes. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory failure (ARF) remains a common hazardous complication in immunocompromised patients and is associated with increased mortality rates when endotracheal intubation is needed. We aimed to evaluate the effect of early noninvasive ventilation (NIV) compared with oxygen therapy alone in this patient population.Methods: We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane database up to 25 July 2016. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in immunocompromised patients managed with NIV or oxygen therapy alone. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI).Results: Five RCTs with 592 patients were included. Early NIV significantly reduced short-term mortality (RR 0.62, 95% CI 0.40 to 0.97, p = 0.04) and intubation rate (RR 0.52, 95% CI 0.32 to 0.85, p = 0.01) when compared with oxygen therapy alone, with significant heterogeneity in these two outcomes between the pooled studies. In addition, early NIV was associated with a shorter length of ICU stay (MD -1.71 days, 95% CI -2.98 to 1.44, p = 0.008) but not long-term mortality (RR 0.92, 95% CI 0.74 to 1.15, p = 0.46).Conclusions: The limited evidence indicates that early use of NIV could reduce short-term mortality in selected immunocompromised patients with ARF. Further studies are needed to identify in which selected patients NIV could be more beneficial, before wider application of this ventilator strategy. [ABSTRACT FROM AUTHOR]

Objective: A number of studies have evaluated the efficacy and safety of fondaparinux versus low-molecular-weight heparin (LMWH) in patients with acute coronary syndrome (ACS), but the findings were not consistent across these studies. Methods: Electronic databases and article references were searched for studies that assessed fondaparinux versus LMWH in ACS patients. Results: Six studies met the inclusion criteria. There was a lower risk of major adverse cardiac events (MACE) with fondaparinux-based regimens both in randomized controlled trials (RCT; risk ratio, RR: 0.91, p = 0.04) and observational studies (RR: 0.85, p < 0.0001). Mortality decreased in fondaparinux-treated patients in RCT (RR: 0.84, p = 0.02), but not in observational studies (RR: 1.44, p = 0.64). For the analysis of myocardial infarction (MI), recurrent ischemia and stroke, none of the studies showed significant results. In addition, fondaparinux lowered the risk of major bleeding in RCT (RR: 0.62, p < 0.0001) and observational studies (RR: 0.65, p < 0.0001). The net clinical outcome also favored fondaparinux over LMWH in RCT (RR: 0.82, p < 0.0001) and observational studies (RR: 0.84, p < 0.0001). Conclusions: Among ACS patients, a fondaparinux-based regimen presented advantages regarding MACE and major bleeding, and a net clinical benefit compared with LMWH, although the benefit is minimal regarding MACE. For death, MI, recurrent ischemia and stroke, fondaparinux has not shown significant benefits. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: A number of studies have assessed the predictive effect of QRS-T angles in various populations since the last decade. The objective of this meta-analysis was to evaluate the prognostic value of spatial/frontal QRS-T angle on all-cause death and cardiac death. Methods: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from their inception until June 5, 2014. Studies reporting the predictive effect of spatial/frontal QRS-T angle on all-cause/cardiac death in all populations were included. Relative risk (RR) was used as a measure of effect. Results: Twenty-two studies enrolling 164,171 individuals were included. In the combined analysis in all populations, a wide spatial QRS-T angle was associated with an increase in all-cause death (maximum-adjusted RR: 1.40; 95% confidence interval [CI]: 1.32 to 1.48) and cardiac death (maximum-adjusted RR: 1.71; 95% CI: 1.54 to 1.90), a wide frontal QRS-T angle also predicted a higher rate of all-cause death (maximum-adjusted RR: 1.71; 95% CI: 1.54 to 1.90). Largely similar results were found using different methods of categorizing for QRS-T angles, and similar in subgroup populations such as general population, populations with suspected coronary heart disease or heart failure. Other stratified analyses and meta-analyses using unadjusted data also generated consistent findings. Conclusions: Spatial QRS-T angle held promising prognostic value on all-cause death and cardiac death. Frontal QRS-T angle was also a promising predictor of all-cause death. Given the good predictive value of QRS-T angle, a combined stratification strategy in which QRS-T angle is of vital importance might be expected. [ABSTRACT FROM AUTHOR]

Background: The relative short-, long- and overall-term efficacy and safety of sirolimus-eluting stents (SES, Cypher) compared with paclitaxel-eluting stents (PES, Taxus) in large head-to-head comparisons still remain to be defined. Methods: We searched Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for articles comparing outcomes of interest between SES and PES without language restriction. Short- (≤1 year), long- (>1 year), and overall-term (the longest follow-up of each study) outcomes were evaluated. The primary endpoint was target lesion revascularization (TLR). Other outcomes of interest were target vessel revascularization (TVR), myocardial infarction, all-cause death, cardiac death, stent thrombosis, major adverse cardiac events (MACEs), restenosis and late lumen loss. Results: Seventy-six studies including more than 15000 patients in randomized controlled trials and over 70000 patients in adjusted observational studies were included. At overall-term follow-up, SES significantly reduced TLR (relative risk [RR]: 0.61; 95% confidence interval [CI]: 0.49–0.76), TVR (RR: 0.67; 95% CI: 0.54–0.83), MACE (RR: 0.79; 95% CI: 0.72–0.87), myocardial infarction (RR: 0.85; 95% CI: 0.73–0.99), in-segment restenosis (RR: 0.50; 95% CI: 0.38–0.65), and in-segment late lumen loss (weighted mean difference [WMD]: −0.19; 95% CI: −0.24–−0.14) in randomized controlled trials compared with PES. In addition, lower rates of death (RR: 0.91; 95% CI: 0.83–1.00), any stent thrombosis (RR: 0.62; 95% CI: 0.45–0.86), definite stent thrombosis (RR: 0.59; 95% CI: 0.45–0.77) were found in patients receiving SES in adjusted observational studies. Largely similar results were found at short- and long-term follow-up, and in patients with diabetes, acute myocardial infarction or long lesions. Conclusions: SES significantly reduced the short-, long- and overall-term risk of TLR/TVR, MACE, and restenosis, and overall-term risk of myocardial infarction in randomized controlled trials, as compared with PES. Lower rates of death and stent thrombosis were also observed in observational studies in SES-treated patients. [ABSTRACT FROM AUTHOR]

Background: Prescriptions of off-label under- and overdosing of direct oral anticoagulants (DOACs) are common for patients with atrial fibrillation, but their efficacy and safety remain unknown.Methods: Databases were searched for randomized controlled trial or adjusted observational study that compared an off-label versus on-label dosing of DOACs through June 15, 2021. The primary efficacy outcome was ischemic stroke/system embolism (IS/SE), and primary safety outcome was major bleeding. Net clinical outcome was generally defined as the composite of IS/SE, major bleeding, and all-cause death. Hazard ratios (HRs) with 95% CIs were pooled with random-effects models with Hartung-Knapp-Sidik-Jonkman method for adjustment.Results: Sixteen studies with 130 609 patients were included. Compared with on-labeling dosing, off-label underdosing of DOACs was associated with a higher risk of IS/SE (HR, 1.22 [95% CI, 1.05-1.42], P=0.01). The incidence of major bleeding was similar (HR, 0.95 [95% CI, 0.82-1.11], P=0.48). Off-label underdosing was associated with a higher risk of net clinical outcome (HR, 1.19 [95% CI, 1.04-1.40], P=0.04) and all-cause death (HR, 1.24 [95% CI, 1.04-1.48], P=0.02). Stratified analysis of off-label underdosing of DOACs for IS/SE showed subgroup differences among different DOAC types and study regions. Limited data showed that off-label overdosing was associated with a higher risk of IS/SE (HR, 1.26 [95% CI, 1.11-1.43], P=0.003) and major bleeding (HR, 1.30 [95% CI, 1.04-1.62], P=0.025).Conclusions: Compared with on-label dosing, off-label underdosing of DOACs increased the risk of thromboembolic events but did not decrease the risk of bleeding. Limited data for off-label overdosing showed higher risks of thromboembolic and bleeding. Further studies are warranted to confirm the results of off-label overdosing DOACs and subgroup results of underdosing DOACs. [ABSTRACT FROM AUTHOR]