A Meta-Analysis of Atrial Septal Defect Closure in Patients With Severe Pulmonary Hypertension: Is There a Room for Poking Holes Amid Debate?

Severe pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) poses a challenge to a closure of ASD, particularly severe PAH that persists even after pharmacological therapeutic strategy. Our study was aimed to evaluate this matter. A systematic literature search from several databases was conducted up until August 1st, 2023. A meta-analysis was undertaken on studies that reported hemodynamic measurements in ASD patients with severe PAH before and after closure. The primary objectives were the extent of improvement in all hemodynamic parameters following closure, and the secondary outcomes were major adverse cardiac events (MACEs) during follow-up. Our study comprised 10 studies with a total of 207 participants. Patients were divided into treat-and-repair and straight-to-repair groups based on the therapeutic strategy. Meta-analysis of all studies demonstrated significant improvement in mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary vascular resistance index (PVRI), 6-minutes walking distance (6MWD), and lower prevalence of World Health Organization functional classes (WHO fc), particularly in the treat-and-repair strategy subgroup. Additionally, merely 4 of the 156 individuals died from cardiac causes, and only 1 required rehospitalization, indicating a low likelihood of MACEs arising. Our new findings support the notion that effective shunt closure can improve various hemodynamic parameters in carefully chosen patients with noncorrectable ASD-PAH. Further large and prospective observational studies are still warranted to validate these findings.

Prevention of Contrast-induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention.

Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury has varying definitions, but in general, increased serum creatinine level by ≥ 0.3 mg/dL (26.5 µmol/L) or 1.5x of baseline value or urine output <0.5 mL/kg/h within 1-7 days after contrast media (CM) administration can be considered as CIN. CIN is one of the most common complications and is associated with increased mortality in patients undergoing percutaneous coronary intervention (PCI). Thus, risk stratification for CIN should be made and preventive strategies should be employed in which the intensity of the approach must be tailored to patient's risk profile. In all patients, adequate hydration is required, nephrotoxic medications should be discontinued, and pre-procedural high-intensity statin is recommended. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, IV hydration should be started 12 hours pre-procedure up until 12-24 hours after the procedure. Remote ischemic preconditioning may be performed pre-procedurally. Radial first approach for vascular access is recommended. During the procedure, low or iso-osmolar CM should be used and its volume should be limited to eGFR x 3.7. In patients at high risk for CIN, additional contrast-sparing strategies may be applied, such as using a contrast reduction system, 5 Fr catheter with no sideholes, CM dilution, limiting test injection, confirming placement using guidewire, use of stent enhancing imaging technology, using metallic/software roadmap to guide PCI, use of IVUS or dextran-based OCT, and coronary aspiration. A more advanced hydration technique based on central venous pressure, left ventricular end-diastolic pressure, or using furosemide-matched hydration, might be considered.

The association between mean platelet volume and poor outcome in patients with COVID-19: Systematic review, meta-analysis, and meta-regression.

Introduction: This study aims to assess the association between mean platelet volume (MPV) and poor outcome in patients with COVID-19. Methods: We performed a comprehensive literature search using the PubMed, Embase and Scopus databases with keywords "2019-nCoV" OR "SARS-CoV-2" OR "COVID-19" AND "mean platelet volume" OR "MPV" on 8 July 2021. The primary outcome was composite poor outcome, defined as severe COVID-19 or mortality. The pooled effect estimate was reported as mean differences in terms of MPV between the group with and without outcome. Results: There were 17 studies which consist of 4549 patients with COVID-19 were included in this study. The incidence of poor outcome was 25% (20%-30%). Mean MPV was found to be higher in the poor outcome group in compare to no poor outcome group (10.3 ± 1.9 fL vs 9.9 ± 1.7 fL). The mean MPV difference between both group was 0.47 fL [95% CI 0.27, 0.67], p < 0.001; I2: 62.91%, p < 0.001). In the sub-group analysis, patients with severe COVID-19 had higher MPV (mean difference 0.54 fL [95% CI 0.28, 0.80], p < 0.001; I2: 54.84%, p = 0.014). Furthermore, MPV was also higher in the mortality group (mean difference 0.54 fL [95% CI 0.29, 0.80], p = 0.020; I2: 71.11%, p = 0.004). Meta-regression analysis showed that the association between MPV and poor outcome was not affected by age (p = 0.789), gender (p = 0.167), platelets (p = 0.056), white blood cells (p = 0.639), and lymphocytes (p = 0.733). Conclusion: This meta-analysis indicated that increased MPV was associated with severity and mortality in patients with COVID-19. Further research is needed to determine the optimum cut-off point.

Role of N-terminal pro-B type natriuretic peptide as a predictor of poor outcomes in patients with HFrEF receiving primary prevention implantable cardioverter-defibrillator therapy: a systematic review and dose-response meta-analysis.

INTRODUCTION: Several studies have demonstrated that combining left ventricular ejection fraction and New York Heart Association functional class is insufficient for predicting risk of appropriate implantable cardioverter-defibrillator (ICD) shock in primary prevention candidates. Hence, our aim was to assess the relationship between N-terminal pro-B type natriuretic peptide (NT-pro BNP) along with appropriate ICD shock and all-cause mortality in order to improve the stratification process of patients with heart failure with reduced ejection fraction (HFrEF) being considered for primary preventive ICD therapy. METHODS: A systematic literature search from several databases was conducted up until 9 June 2022. Studies were eligible if they investigated the relationship of NT-pro BNP with all-cause mortality and appropriate ICD shock. RESULTS: This meta-analysis comprised nine studies with a total of 5117 participants. Our study revealed that high levels of NT-pro BNP were associated with all-cause mortality (HR=2.12 (95% CI=1.53 to 2.93); p<0.001, I2=78.1%, p<0.001 for heterogeneity) and appropriate ICD shock (HR=1.71 (95% CI=1.18 to 2.49); p<0.001, I2=43.4%, p=0.102 for heterogeneity). The adjusted HR for all-cause mortality and appropriate ICD shock increased by approximately 3% and 5%, respectively per 100 pg/mL increment pursuant to concentration-response model (Pnon-linearity <0.001). The curves became steeper after NT-pro BNP reached its inflection point (3000 pg/mL). CONCLUSION: A positive concentration-dependent association between elevated NT-pro BNP levels along with the risk of all-cause mortality and appropriate ICD shock was found in patients with HFrEF with ICD. PROSPERO REGISTRATION NUMBER: CRD42022339285.

Very-high-power Short-duration Ablation versus Conventional Ablation for Pulmonary Vein Isolation in Atrial Fibrillation: Systematic Review and Meta-analysis.

The aim of this study was to compare the effectiveness and safety of very-high-power short-duration (VHPSD) ablation (70-90 W/4-7 s) with conventional ablation (30-40 W/>20 s, 50 W/7-11 s) for pulmonary vein isolation (PVI) in patients with AF. A total of 13 studies were included in this analysis (1,527 patients). AF recurrence occurred in 14% (95% CI [11-18%]) of the VHPSD group. VHPSD was associated with lower AF recurrence (OR 0.65; 95% CI [0.48-0.89]; p=0.006) compared with the conventional ablation group. Subgroup analysis showed that additional ablation beyond PVI had a similar rate of AF recurrence (16% versus 10%) compared with PVI alone. Procedure and ablation durations were significantly shorter in the VHPSD group with a mean differences of -14.4 minutes (p=0.017) and -14.1 minutes (p<0.001), respectively. Complications occurred in 6% (95% CI [3-9%]) of the VHPSD group, and the rate was similar between the two groups (OR 1.03; 95% CI [0.60-1.80]; p=0.498). VHPSD ablation resulted in less AF recurrence and a shorter procedure time. Additional ablation beyond PVI alone in VHPSD may not provide additional benefits.

Managing Covid-19 in patients with heart failure: current status and future prospects.

INTRODUCTION: COVID-19 may contribute to decompensation of previously stable chronic HF or cause a de-novo heart failure, which may come from the hyperinflammatory response and subsequent increase in metabolic demand. AREAS COVERED: Two independent investigators searched MEDLINE (via PubMed), Europe PMC, and ScienceDirect databases with the following search terms: COVID-19, heart failure, COVID-19 drugs, heart failure drugs, and device therapy. All of the included full-text articles were rigorously evaluated by both authors in case there was disagreement about whether research should be included or not. In total, 157 studies were included and underwent extensive reading by the authors. EXPERT OPINION: The World Health Organization (WHO) and the National Institute of Health (NIH) have published COVID-19 drug recommendations, although recommendations for HF-specific drug choices in COVID-19 are still lacking. We hope that this review can answer the void of comprehensive research data regarding the management options of HF in the COVID-19 condition so that clinicians can at least choose a more beneficial therapy or avoid combination therapies that have a high burden of side effects on HF; thus, morbidity and mortality in COVID-19 patients with HF may be reduced.

Revisiting exercise-induced premature ventricular complexes as a prognostic factor for mortality in asymptomatic patients: A systematic review and meta-analysis.

Background: Recent investigations suggest that premature ventricular complexes (PVCs) during an exercise test are associated with an elevated risk of mortality in asymptomatic individuals. However, given the small number of studies included, the association between these two entities in the asymptomatic population remains obscure. Our aim was to evaluate this matter. Methods: A comprehensive literature search was conducted utilizing several online databases up to April 2022. The study comprised cohort studies examining the relationship between exercise-induced premature ventricular complexes (EI-PVCs) and all-cause mortality (ACM) as well as cardiovascular mortality (CVM) in asymptomatic populations. To provide diagnostic values across the statistically significant parameters, we additionally calculated sensitivity, specificity, and area under the curve (AUC). Results: A total of 13 studies consisting of 82,161 patients with a mean age of 49.3 years were included. EI-PVCs were linked to an increased risk of ACM (risk ratio (RR) = 1.30 (95% confidence interval (CI) = 1.18-1.42); p < 0.001; I 2 = 59.6%, p-heterogeneity < 0.001) and CVM (RR = 1.67 (95% CI = 1.40-1.99); p < 0.001; I 2 = 7.5%, p-heterogeneity = 0.373). Subgroup analysis based on the frequency of PVCs revealed that frequent PVCs were similarly related to a higher risk of ACM and CVM, but not infrequent PVCs. Moreover, diagnostic test accuracy meta-analysis showed that recovery phase EI-PVCs have a higher overall specificity than exercise phase EI-PVCs regarding our outcomes of interest. Conclusion: EI-PVCs are correlated with a higher risk of ACM and CVM. When compared to the exercise phase, the specificity of PVCs generated during the recovery period in predicting interest outcomes is higher. As a result, we propose that the exercise ECG be utilized on a regular basis in middle-aged asymptomatic individuals to measure the frequency of PVCs and stratify the risk of mortality. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=328852], identifier [CRD42022328852].

Electrocardiographic Markers Indicating Right Ventricular Outflow Tract Conduction Delay as a Predictor of Major Arrhythmic Events in Patients With Brugada Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Risk stratification in Brugada Syndrome (BrS) patients is still challenging due to the heterogeneity of clinical presentation; thus, some additional risk markers are needed. Several studies investigating the association between RVOT conduction delay sign on electrocardiography (ECG) and major arrhythmic events (MAE) in BrS patients showed inconclusive results. This meta-analysis aims to evaluate the association between RVOT conduction delay signs presented by aVR sign and large S wave in lead I, and MAE in BrS patients. Methods: The literature search was performed using several online databases from the inception to March 16th, 2022. We included studies consisting of two main components, including ECG markers of RVOT conduction delay (aVR sign and large S wave in lead I) and MAE related to BrS (syncope/VT/VF/SCD/aborted SCD/appropriate ICD shocks). Results: Meta-analysis of eleven cohort studies with a total of 2,575 participants showed RVOT conduction delay sign was significantly associated with MAE in BrS patients [RR = 1.87 (1.35, 2.58); p < 0.001; I 2= 52%, P heterogeneity = 0.02]. Subgroup analysis showed that aVR sign [RR = 2.00 (1.42, 2.83); p < 0.001; I 2= 0%, P heterogeneity = 0.40] and large S wave in lead I [RR = 1.74 (1.11, 2.71); p = 0.01; I 2= 60%, P heterogeneity = 0.01] were significantly associated with MAE. Summary receiver operating characteristics analysis revealed the aVR sign [AUC: 0.77 (0.73-0.80)] and large S wave in lead I [AUC: 0.69 (0.65-0.73)] were a good predictor of MAE in BrS patients. Conclusion: RVOT conduction delay sign, presented by aVR sign and large S wave in the lead I, is significantly associated with an increased risk of MAE in BrS patients. Hence, we propose that these parameters may be useful as an additional risk stratification tool to predict MAE in BrS patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022321090.

Preoperative Third Ventricle Floor Bowing is Associated with Increased Surgical Success Rate in Patients Undergoing Endoscopic Third Ventriculostomy - A Systematic Review and Meta-analysis.

Background: Endoscopic third ventriculostomy (ETV) is a procedure that involves devising an opening in the third ventricle floor, allowing cerebrospinal fluid to flow into the prepontine cistern and the subarachnoid space. Third ventricular floor bowing (TVFB) serves as an indicator of intraventricular obstruction in hydrocephalus and existence of pressure gradient across third ventricular floor, which is the prerequisite of a successful ETV. Objective: In this systematic review and meta-analysis, we aimed to synthesize the latest evidence on the TVFB as a marker for surgical success in patients undergoing ETV. Material and Methods: We performed a comprehensive search on topics that assesses the association of TVFB with the surgical success in patients undergoing ETV from several electronic databases. Results: There was a total of 568 subjects from six studies. TVFB was associated with 85% (81-88%) ETV success. TVFB was associated with OR 4.13 [2.59, 6.60], P < 0.001; I2: 6% for ETV success. Subgroup analysis on pediatric patients showed 86% (82-91%) success rate. In terms of value for ETV success compared to ETV Success Score (ETVSS), a high ETVSS does not significantly differ (P = 0.31) from TVFB and TVFB was associated with OR 3.14 [1.72, 5.73], P < 0.001; I2: 69% compared to intermediate/moderate ETVSS. Funnel plot analysis showed an asymmetrical funnel plot due to the presence of an outlier. Upon sensitivity analysis by removing the outlier, the OR was 3.62 [2.22, 5.89], P < 0.001; I2: 0% for successful surgery in TVFB. Conclusions: TVFB was associated with an increased rate of successful surgery in adults and children undergoing ETV.

Cardiometabolic risk factors in adults with normal weight obesity: A systematic review and meta-analysis.

Normal weight obesity (NWO) is a new emerging phenotype of obesity, defined as a normal body mass index with a high body fat percentage. While several studies have described the impact of NWO on cardiometabolic risk factors, the association between them remains uncertain. This meta-analysis systematically evaluated cardiometabolic risk factors in adults with NWO compared to adults with normal weight lean (NWL). A systematic literature search was performed from the inception until September 21, 2021 in order to comprehensively search for all observational studies that had three important variables, including adults (age ≥18 years old), NWO and cardiometabolic risk factors including metabolic syndrome, hypertension, diabetes mellitus, dyslipidaemia or all laboratory findings related to cardiometabolic risk factors. Twenty-four cross-sectional studies with a total of 75 201 subjects are included in the qualitative and quantitative analysis. Overall, older age and female sex are more likely in NWO population. Compared to NWL, NWO is significantly associated with cardiometabolic risk factors, including metabolic syndrome (OR = 2.24 [1.74, 2.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), hypertension (OR = 1.60[1.36, 1.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), diabetes mellitus (OR = 1.72[1.54, 1.92]; p < .001; I2  = 47%, Pheterogeneity < 0.001), dyslipidaemia (OR = 1.50 [1.03, 2.18]; p = .03; I2  = 94%, Pheterogeneity < 0.001) and other laboratory findings, except for C-reactive protein in both sexes group; and adiponectin levels in female group. Our meta-analysis showed that NWO was associated with cardiometabolic risk factors. Thus, the traditional definition of obesity using the BMI criteria should be challenged, as those with NWO might still be exposed to a heightened risk of cardiometabolic disorders. Nonetheless, further prospective cohort studies are needed better to understand this syndrome.

Decompression Alone Compared to Decompression With Fusion in Patients With Lumbar Spondylolisthesis: Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: We aimed to synthesize the latest evidence on the efficacy and safety of decompression alone compared to decompression with fusion in patients with lumbar spondylolisthesis. We also aimed to evaluate factors affecting the efficacy and complications. METHODS: A systematic literature search was conducted using PubMed, Scopus, Europe PMC, Cochrane Central Database, and ClinicalTrials.gov. The main outcome was improvement in Oswestry Disability Index (ODI). The secondary outcome was back pain and leg pain improvement, complications, reoperation rate, duration of surgery, length of hospital stay, and blood loss. RESULTS: There were 3993 patients from 13 studies. Decompression with fusion was associated with greater reduction in ODI (mean difference 4.04 [95% CI 0.95, 7.13], P = 0.01) compared to decompression alone. Greater reduction in back (standardized mean difference [SMD] 0.27 [95% CI 0.00, 0.53], P = 0.05) and leg pain (SMD 0.13 [95% CI 0.06, 0.21], P < 0.001) was observed in the decompression with fusion group. Complications were similar in the 2 groups (OR 0.60 [95% CI 0.34, 1.04], P = 0.07). The reoperation rate was similar in both groups (P = 0.54). Decompression alone resulted in shorter duration of surgery (mean difference -85.18 minutes [95% CI -122.79, -47.57], P < 0.001), less blood loss (mean difference -262.65 mL [95% CI -313.45, -211.85], P < 0.001), and shorter hospital stay (mean difference -2.64 days [95% CI -3.58, -1.70], P < 0.001). Empirical Bayes random-effects meta-regression showed that the rate of complication was influenced by age (coefficient 0.172, P = 0.004). CONCLUSION: Decompression with fusion had greater efficacy than decompression alone but was associated with more blood loss, lengthier surgery, and hospitalization. In terms of complications, decompression alone may be beneficial in younger patients. (PROSPERO CRD42020211904) LEVEL OF EVIDENCE: 2A.

Drug-Coated Balloon Versus Drug-Eluting Stent in Patients With Femoropopliteal Artery Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: In this systematic review and meta-analysis, we aimed to compare drug-coated balloon (DCB) to drug-eluting stent (DES) in patients with femoropopliteal lesions in terms of restenosis, target lesion revascularization (TLR), and mortality. METHODS: A comprehensive literature search was performed through PubMed, Scopus, and Embase databases. The intervention group was patients receiving percutaneous balloon angioplasty using the DCB. The control group was patients receiving percutaneous intervention using the DES. The primary outcome was restenosis, and the secondary outcomes were TLR and mortality. RESULTS: There were 4 studies comprising 812 patients (906 lesions) included in this systematic review and meta-analysis. The rate of restenosis was .19 [.13, .26] in DCB and .24 [.20, .28] in DES. There was a trend toward lower rate of restenosis (OR .73 [.52, 1.03], P = .074; I2: 46.3%) for DCB use compared to DES use. The rate of TLR was .11 [.08, .14] in DCB and .17 [.14, .21] in DES. TLR was lower (OR .61 [.41, .92], P = .017; I2: 1.2%) in the DCB group compared to the DES group. There were no significant differences in mortality (OR 1.38 [.78, 2.44], P = .268; I2: 0%) among the two groups. Meta-regression analysis showed that the rate of restenosis in DCB in this pooled analysis was affected by sex (reference: male, coefficient -.004, P = .009), smoking (coefficient: .003, P = .010), and total occlusion (coefficient: .008, P = .004). CONCLUSION: DCB use in patients with femoropopliteal lesion was associated with similar rate of restenosis, lower TLR, and similar mortality rate compared to DES use.

Endotheliopathy marked by high von Willebrand factor (vWF) antigen in COVID-19 is associated with poor outcome: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to compare the levels of von Willebrand Factor (vWF) antigen in patients with coronavirus disease 2019 (COVID-19) with a poor outcome compared with those with a good outcome, and explored factors that may affect the difference in terms of vWF antigen between the two groups. METHODS: A comprehensive literature search of PubMed, Embase and Scopus databases was undertaken from inception until 7 April 2021. The primary outcome was poor outcome, which is a composite of mortality and severity of COVID-19. RESULTS: Ten studies including a total of 996 patients were included in this systematic review and meta-analysis. vWF antigen was higher in patients with poor outcomes [standardized mean difference (SMD) 0.84 [0.45-1.23], P<0.001; I2=87.3, P<0.001). For subgroup analysis on studies that reported the vWF antigen level as a percentage, the mean difference was 121.6 [(53.7-189.4), P<0.001; I2=92.0, P<0.001]. Meta-regression showed that the SMD between poor outcome and good outcome was affected by the platelet count (coefficient 0.0061, P=0.001), d-dimer level (coefficient 0.0007, P=0.026) and factor VIII level (coefficient 0.0057, P=0.031), but not by age (coefficient -0.0610, P=0.440), gender (coefficient 0.0135, P=0.698), obesity (coefficient 0.0282, P=0.666), hypertension (coefficient 0.0273, P=0.423), diabetes (coefficient 0.0317, P=0.398) or malignancy (coefficient 0.0487, P=0.608). CONCLUSION: This meta-analysis showed that the level of vWF antigen was significantly higher in patients with COVID-19 with a poor outcome, signalling marked endotheliopathy. Meta-regression showed that the differences became larger as the platelet count, d-dimer level and factor VIII level increased.

Statin and mortality in COVID-19: a systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts.

PURPOSE: Statin potentially improved outcome in patients with COVID-19. Patients who receive statin generally have a higher proportion of comorbidities than those who did not, which may introduce bias. In this meta-analysis, we aimed to investigate the association between statin use and mortality in patients with COVID-19 by pooling the adjusted effect estimates from propensity-score matching (PSM) matched studies or randomised controlled trials to reduce bias. METHODS: A systematic literature search using the PubMed, Scopus and Embase databases were performed up until 1 March 2021. Studies that were designed the study to assess statin and mortality using PSM with the addition of Inverse Probability Treatment Weighting or multivariable regression analysis on top of PSM-matched cohorts were included. The effect estimate was reported in term of relative risk (RR). RESULTS: 14 446 patients were included in the eight PSM-matched studies. Statin was associated with decreased mortality in patients with COVID-19 (RR 0.72 (0.55, 0.95), p=0.018; I2: 84.3%, p<0.001). Subgroup analysis in patients receiving statin in-hospital showed that it was associated with lower mortality (RR 0.71 (0.54, 0.94), p=0.030; I2: 64.1%, p<0.025). The association of statin and mortality was not significantly affected by age (coefficient: -0.04, p=0.382), male gender (RR 0.96 (0.95, 1.02), p=0.456), diabetes (RR 1.02 (0.99, 1.04), p=0.271) and hypertension (RR 1.01 (0.97, 1.04), p=0.732) in this pooled analysis. CONCLUSION: In this meta-analysis of PSM-matched cohorts with adjusted analysis, statin was shown to decrease the risk of mortality in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42021240137.

Prognostic value of elevated lactate dehydrogenase in patients with COVID-19: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the prognostic performance of elevated lactate dehydrogenase (LDH) in patients with COVID-19. METHODS: A systematic literature search was performed using PubMed, Embase and EuropePMC on 19 November 2020. The outcome of interest was composite poor outcome, defined as a combined endpoint of mortality, severity, need for invasive mechanical ventilation and need for intensive care unit care. Severity followed the included studies' criteria. RESULTS: There are 10 399 patients from 21 studies. Elevated LDH was present in 44% (34%-53%) of the patients. Meta-regression analysis showed that diabetes was correlated with elevated LDH (OR 1.01 (95% CI 1.00 to 1.02), p=0.038), but not age (p=0.710), male (p=0.068) and hypertension (p=0.969). Meta-analysis showed that elevated LDH was associated with composite poor outcome (OR 5.33 (95% CI 3.90 to 7.31), p<0.001; I2: 77.5%). Subgroup analysis showed that elevated LDH increased mortality (OR 4.22 (95% CI 2.49 to 7.14), p<0.001; I2: 89%). Elevated LDH has a sensitivity of 0.74 (95% CI 0.60 to 0.85), specificity of 0.69 (95% CI 0.58 to 0.78), positive likelihood ratio of 2.4 (95% CI 1.9 to 2.9), negative likelihood ratio of 0.38 (95% CI 0.26 to 0.55), diagnostic OR of 6 (95% CI 4 to 9) and area under curve of 0.77 (95% CI 0.73 to 0.80). Elevated LDH would indicate a 44% posterior probability and non-elevated LDH would in indicate 11% posterior probability for poor prognosis. Meta-regression analysis showed that age, male, hypertension and diabetes did not contribute to the heterogeneity of the analyses. CONCLUSION: LDH was associated with poor prognosis in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020221594.

Coffee and tea consumption and the risk of glioma: a systematic review and dose-response meta-analysis.

In this systematic review and dose-response meta-analysis, we aimed to assess whether coffee and tea consumption is related to the risk of glioma. We performed a systematic literature search using PubMed, Embase, Scopus and the EuropePMC from the inception of database up until 1 October 2020. Exposures in the present study were coffee and tea consumption, the main outcome was the incidence of glioma. The present study compares the association between the exposure of coffee and tea with the incidence of glioma, and the results are reported in relative risks (RR). There are 12 unique studies comprising of 1 960 731 participants with 2987 glioma cases. Higher coffee consumption was associated with a statistically non-significant trend towards lower risk of glioma (RR 0·77 (95 % CI 0·55, 1·03), P= 0·11; I2:75·27 %). Meta-regression showed that the association between coffee and glioma was reduced by smoking (P= 0·029). Higher tea consumption was associated with a lower risk of glioma (RR 0·84 (95 % CI 0·71, 0·98), P= 0·030; I2:16·42 %). Sensitivity analysis by removal of case-control studies showed that higher coffee consumption (RR 0·85 (95 % CI 0·72, 1·00), P= 0·046; I2:0 %) and higher tea consumption (RR 0·81 (95 % CI 0·70, 0·93), P= 0·004; I2:0 %, Pnon-linearity = 0·140) were associated with lower risk of glioma. Dose-response meta-analysis showed that every one cup of coffee per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 0·99), P= 0·016, Pnon-linearity = 0·054) and every one cup of tea per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 1·00), P= 0·048). This meta-analysis showed apparent association between coffee and tea intake and risk of glioma.

Pars-plana vitrectomy combined with retinectomy in severe open-globe injuries: A systematic review and meta-analysis.

BACKGROUND: This review summarized prophylactic retinectomy technique and its effect on anatomic and functional outcomes in severe open globe injuries (OGIs). METHODS: A comprehensive search in PubMed (MEDLINE), Embase, Scopus, and EuropePMC databases was performed up until 8 January 2020. Enrolled studies include case series, studies involving pars plana vitrectomy (PPV) combined with retinectomy in severe penetrating injuries with or without IOFB, perforating injuries, and globe ruptures. Primary outcome was best-corrected visual acuity (BCVA) ⩾20/200 at the end of the study. Secondary outcomes were the rate of proliferative retinopathy (PVR), globe survival rate and retinal reattachment rate. RESULTS: A total of seven studies, involving 275 eyes with severe OGIs, is included in this study. Meta-analysis indicates that final BCVA ⩾20/200 was achieved in 61% (95% CI 49%-73%). Meta-regression analysis showed that improvement was inversely affected by the presence of pre-operative direct macular injury (p = 0.001) and corneal scar (p = 0.015). The proportion of pre-operative BCVA <20/200 was statistically insignificant to the final BCVA ⩾20/200 (p = 0.569). One study showed that the rate is higher in the retinectomy group than the non-retinectomy group (54% vs 11%). Meta-analysis showed that anatomical success can be achieved in 85% (95% CI 78%-91%) of the patients. Meta-regression analysis indicates that the anatomical success did not vary with age (p = 0.653), retinal detachment (p = 0.525), corneal scar (p = 0.596), and lens involvement (p = 0.450). CONCLUSION: Early PPV combined with retinectomy was associated with acceptable visual improvement and anatomical success.

Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19. METHODS: We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs). RESULTS: There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000. CONCLUSION: SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery. PROTOCOL REGISTRATION: PROSPERO: CRD42021247510.

Dose response relationship between D-dimer level and mortality in critically ill COVID-19 patients: a retrospective observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. Coagulopathy is one of the most common complications characterized by increased D-dimer level. We aimed to investigate the dose-response relationship between elevated D-dimer level and mortality in critically ill COVID-19 patients. METHODS: This was a retrospective observational study in 259 critically ill COVID-19 patients requiring intensive care unit admission between March and December 2020. We compared the mortality rate between patients with and without elevated D-dimer. Receiver operating characteristic (ROC) curve analysis, Fagan's nomogram, and dose-response relationship were performed to determine the association between D-dimer level and mortality. RESULTS: Overall mortality rate was 40.9% (106 patients). Median D-dimer level was higher in non-survivor group (10,170 ng/mL vs 4,050 ng/mL, p=0.028). The association remained significant after multivariate logistic regression analysis (p=0.046). The optimal cut-off for D-dimer level to predict mortality from ROC curve analysis was 9,020 ng/mL (OR (odds ratio) 3.73 [95% CI (confidence interval) 1.91 - 7.28], p<0.001). D-dimer level >9,020 ng/mL confers 67% posterior probability of mortality and D-dimer level <9,020 ng/mL had 35% probability of mortality. CONCLUSIONS: There was a non-linear dose-response relationship between D-dimer level and mortality with P nonlinearity of 0.004. D-dimer level was associated with mortality in critically ill COVID-19 patients in the non-linear dose-response relationship.

Corrigendum: Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fnut.2021.660420.].