Prophylactic donor lymphocyte infusion for relapse prevention: a meta-analysis.

OBJECTIVE: Primary disease relapse (PDR) of malignant hematologic conditions after standard hematopoietic stem cell transplant (HSCT) is one of the most challenging diseases; therefore ongoing researches are aiming at relapse prevention and minimizing the transplant-related side effects. Prophylactic donor lymphocytes (pDLI) had been proposed as a valuable strategy for PDR prevention, but early studies had been discouraging due to the limited benefit and possible association with acute graft-versus-host disease (aGVHD). Therefore, we conducted a meta-analysis to evaluate the association between pDLI use, PDR, aGVHD and OS. METHOD: We performed a comprehensive literature search in MEDLINE, Cochrane library and Embase database from inception to May 2019 for studies that evaluated the association between pDLI and PDR. We conducted a random effect meta-analysis of 9 studies involving a total of 748 participants (pDLI = 398, non-pDLI = 350) and reported the pooled odd ratio (OR) for association of pDLI use, PDR, aGVHD and OS. RESULT: We found a significant decreased odd of PDR in the pDLI group (pooled OR = 0.42, 95% CI 0.30-0.58, I2 = 0%), but there was no significant increased odd of aGVHD (pooled OR of 0.98, 95% CI 0.56-1.72, I2 = 0.8%). We also found that there was an increased odd of overall survival (OS) (pooled OR 3.17, 95% CI 1.85-5.45, I2 = 50.2%). CONCLUSION: There are significantly decreased odd of PDR and increased odd of OS in the pDLI group compared to the control group, but there is no statistically significant increased odd of aGVHD as suggested by previous studies. We concluded that pDLI is a potentially valuable method for post-transplant PDR prevention.

Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis.

OBJECTIVES: Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis. METHODS: We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups. RESULTS: We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57-0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02-1.95, I2=56.8%, and 1.77, 95% CI 1.1-2.87, I2=82.5%, respectively. CONCLUSION: Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant.

The presence of atrial fibrillation in Takotsubo cardiomyopathy is predictive of mortality: Systematic review and meta-analysis.

INTRODUCTION: Atrial fibrillation (AF) is known as the most common arrhythmia and an independent risk factor for mortality. Recent studies suggest that AF is associated with morbidity and mortality in Takotsubo cardiomyopathy (TTC). However, a systematic review and meta-analysis of the literature have not been done. We assessed the association between AF in patients with TTC and mortality by a systematic review of the literature and a meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to January 2018. Included studies were published prospective or retrospective cohort studies that compared all-cause mortality in TTC with AF versus without AF. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Five studies from August 2008 to October 2017 were included in this meta-analysis involving 2,321 subjects with TTC (243 with AF and 2,078 without AF). The presence of AF was associated with all-cause mortality (pooled odds ratio = 2.19, 95% confidence interval: 1.57-3.06, p < 0.001, I 2  = 0%). CONCLUSION: Atrial fibrillation increased all-cause mortality by double among patients with TTC compared to without it. Our study suggests that the presence of AF in TTC is prognostic for all-cause mortality.

Contrast-induced nephropathy is associated with new-onset atrial fibrillation in acute coronary syndrome after cardiac catheterization: Systemic review and meta-analysis.

INTRODUCTION: Contrast-induced nephropathy (CIN) is associated with increased cardiovascular morbidity and mortality in patients with acute coronary syndrome (ACS). Recent studies suggest that CIN is associated with new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) who underwent catheterization. However, a systematic review and meta-analysis of the literature have not been done. We assessed the association between CIN in patients with ACS and new-onset AF by a systematic review of the literature and a meta-analysis. HYPOTHESIS: CIN is associated with new-onset AF in patients with ACS. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to April 2018. Included studies were published cohort studies that compared new-onset AF after cardiac catheterization in ACS patient with CIN versus without CIN. Data from each study were combined using the random effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Five studies from December 2009 to February 2018 were included in this meta-analysis involving 5,640 subjects with ACS (1,102 with CIN and 4,538 without CIN). Contrast-induced nephropathy significantly correlates with new-onset AF after cardiac catheterization (pooled risk ratio = 2.84, 95% confidence interval: 1.66-4.87, p < 0.001, I2  = 58%) CONCLUSIONS: Contrast-induced nephropathy is associated with new-onset AF threefold among patients with ACS after cardiac catheterization. Our study warranted further study to establish the causality between CIN and new-onset AF.

SCN5A mutation status increases the risk of major arrhythmic events in Asian populations with Brugada syndrome: systematic review and meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmic disease linked to SCN5A mutations. It is controversial whether SCN5A mutation carriers possess a greater risk of major arrhythmic events (MAE). We examined the association of SCN5A mutations and MAE in BrS patients. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published cohort and case-control studies that compared MAE in BrS patients with and without SCN5A mutations. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Seven studies from March 2002 to October 2017 were included (1,049 BrS subjects). SCN5A mutations were associated with MAE in Asian populations (RR = 2.03, 95% CI: 1.37-3.00, p = 0.0004, I2  = 0.0%), patients who were symptomatic (RR = 2.66, 95% CI: 1.62-4.36, p = 0.0001, I2  = 23.0%), and individuals with spontaneous type-1 Brugada pattern (RR = 1.84, 95% CI: 1.05-3.23, p = 0.03, I2  = 0.0%). CONCLUSIONS: SCN5A mutations in BrS increase the risk of MAE in Asian populations, symptomatic BrS patients, and individuals with spontaneous type-1 Brugada pattern. Our study suggests that SCN5A mutation status should be an important tool for risk assessment in BrS patients.

ASSOCIATION OF RETINAL VEIN OCCLUSION WITH CARDIOVASCULAR EVENTS AND MORTALITY: A Systematic Review and Meta-analysis.

PURPOSE: Previous studies examining the association of retinal vein occlusion (RVO) and cardiovascular events have been inconsistent and have mostly focused on stroke and myocardial infarction. The goal of this study is to use meta-analysis to examine the available evidence examining the association of RVO with incident cardiovascular events and mortality. METHODS: Systematic review and meta-analysis of all longitudinal cohort studies published in PubMed, Embase, and the Cochrane Library from inception to April 7, 2018, that evaluated the association of baseline RVO and incident cardiovascular events and/or mortality, that provided multivariate-adjusted risk estimates with 95% confidence intervals (95% CIs), and that had average follow-up ≥1 year. The Newcastle-Ottawa scale was used to assess study quality. Multivariate-adjusted risk estimates with 95% CI along with study characteristics were extracted from each study, and pooled risk ratios (RRs) with 95% CI were generated using a random-effects model with inverse-variance weighting to account for heterogeneity. Main outcomes were incident stroke (fatal or nonfatal), myocardial infarction, heart failure, peripheral arterial disease, all-cause mortality, and cardiovascular mortality. RESULTS: Fifteen cohort studies with a total of 474,466 patients (60,069 with RVO and 414,397 without RVO) were included. Each study had Newcastle-Ottawa scale score ≥6, indicating moderate-to-high quality. Retinal vein occlusion was associated with increased risk of stroke (RR = 1.45; 95% CI, 1.31-1.60), myocardial infarction (RR = 1.26; 95% CI, 1.17-1.37), heart failure (RR = 1.53; 95% CI, 1.22-1.92), peripheral arterial disease (RR = 1.26; 95% CI, 1.09-1.46), and all-cause mortality (RR = 1.36; 95% CI, 1.02-1.81), but was not associated with increased risk of cardiovascular mortality (RR = 1.78; 95% CI, 0.70-4.48). CONCLUSION: This review suggests patients with RVO have an increased risk of cardiovascular events and all-cause mortality. More studies are needed to determine the highest risk periods for cardiovascular events and mortality after RVO and whether immediate cardiovascular evaluation and intervention will improve outcomes.

Terminal QRS Distortion in ST Elevation Myocardial Infarction as a Prediction of Mortality: Systematic Review and Meta-Analysis.

BACKGROUND: Terminal QRS distortion reflects advanced stage and large myocardial infarction predisposing the heart to adverse outcomes. Recent studies suggest that terminal QRS distortion is associated with morbidity and mortality in ST elevation myocardial infarction (STEMI). However, a systematic review and meta-analysis of the literature have not been done. OBJECTIVE: We assessed the association between terminal QRS distortion in patients with STEMI and mortality by a systematic review of the literature and a meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published prospective or retrospective cohort studies that compared all-cause mortality in subjects with STEMI with QRS distortion versus those without QRS distortion. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Fifteen studies from January 1993 to May 2015 were included in this meta-analysis involving 7,479 subjects with STEMI (2,906 QRS distortion and 4,573 non-QRS distortion). QRS distortion was associated with increased mortality (pooled risk ratio = 1.81, 95% confidence interval: 1.37-2.40, p < 0.000, I2 = 41.6%). Considering the introduction of clopidogrel in 2004, we performed subgroup analyses before and after 2004, and the associated with higher mortality was still present (before 2004, RR 1.75, 95% CI 1.08-2.82, p = 0.022, I2 = 66.1%; after 2004, RR 1.96, 95% CI 1.44-2.65, p < 0.001, I2 = 0%). CONCLUSIONS: Terminal QRS distortion increased all-cause mortality by 81%. Our study suggests that terminal QRS distortion is an important tool to assess the risk in patients with STEMI.

Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta-analysis.

BACKGROUND: Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with major arrhythmic events in Brugada syndrome. However, a systematic review and meta-analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in Brugada syndrome by a systematic review of the literature and a meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (ventricular fibrillation, sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in Brugada syndrome with fQRS versus normal QRS. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Nine studies from January 2012 to May 2017 were included in this meta-analysis involving 2,360 subjects with Brugada syndrome (550 fQRS and 1,810 non-fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio =3.36, 95% confidence interval: 2.09-5.38, p < .001, I2  = 50.9%) as well as fatal arrhythmia (pooled risk ratio =3.09, 95% confidence interval: 1.40-6.86, p = .005, I2  = 69.7%). CONCLUSIONS: Baseline fQRS increased major arrhythmic events up to 3-fold. Our study suggests that fQRS could be an important tool for risk assessment in patients with Brugada syndrome.

Fragmented QRS and mortality in patients undergoing percutaneous intervention for ST-elevation myocardial infarction: Systematic review and meta-analysis.

BACKGROUND: Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with mortality in ST-elevation myocardial infarction (STEMI) patients who underwent percutaneous coronary intervention (PCI). However, a systematic review and meta-analysis of the literature has not been done. We assessed the association between fQRS and overall mortality in STEMI patients who subsequently underwent PCI by a systematic review and meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Studies included in our analysis were published cohort (prospective or retrospective) and case-control studies that compared overall mortality among STEMI patient with and without fQRS who underwent PCI. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian, and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Six studies from 2014 to 2017 were included in this meta-analysis involving 2,516 subjects with STEMI who underwent PCI (888 fQRS and 1,628 non-fQRS). Fragmented QRS was associated with overall mortality in STEMI patients who underwent PCI (pooled risk ratio = 3.87; 95% CI 1.96-7.66, I2  = 43%). CONCLUSION: Fragmented QRS was associated with increased overall mortality up to threefold. Our study suggests that fQRS could be an important tool for risk assessment in STEMI patients who underwent PCI.

Frequent premature atrial complexes as a predictor of atrial fibrillation: Systematic review and meta-analysis.

BACKGROUND: Frequent premature atrial complexes (PACs) are associated with higher morbidity and mortality. Recent studies suggest that frequent PACs are associated with new onset atrial fibrillation (AF). However, a systematic review and meta-analysis of the literature has not been done. We assessed the association between frequent PACs and new onset AF by a systematic review and a meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published cohort (prospective or retrospective) that compared new onset AF among patients with and without frequent PACs documented by Holter monitoring or 12-lead electrocardiogram. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Twelve studies from 2009 to 2017 were included in this meta-analysis involving 109,689 subjects (9217frequent and 100,472 non-frequent PACs). Frequent PACs were associated with increased risk of new onset AF (pooled risk ratio = 2.76, 95% confidence interval: 2.05-3.73, p < 0.000, I2 = 90.6%). CONCLUSION: Frequent PACs are associated with up to three-fold increased risk of new onset AF. Our study suggests that frequent PACs in general population is an independent predictor of new onset AF.

Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam.

The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38+HLA-DR+, PD1+, and TIGIT+ CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p < .01). Most parameters did not normalize despite 72 weeks of ART. In particular sCD163 persisted at high levels. Improvement over 72 weeks in fibrosis as assessed by FibroScan® correlated with reductions in plasma sCD163 and in the frequencies of T cell activation, single PD1+, TIGIT+, and dual PD1+TIGIT+ CD8 T cells. A nonsignificant tendency toward more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared with EFV-based therapy. The initiation of ART in HIV/HCV-coinfected individuals is associated with incomplete improvement in monocyte and T cell immune activation and exhaustion, which was associated with some corresponding improvement in liver fibrosis.

Comparison of infective endocarditis risk between balloon and self-expandable valves following transcatheter aortic valve replacement: systematic review and meta-analysis.

This study aimed to compare incidence of IE between BE and SE valves by performing a systematic review and meta-analysis of the literature. We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2019. Included studies were published observational studies that compared the risk of IE among patients undergoing TAVR employing BE versus SE valves, using the random-effects to calculate risk ratios and 95% confidence intervals (CIs).Ten cohort studies from April 2013 to November 2019 were included in this meta-analysis involving 13,478 subjects (6289 SE and 7189 BE types). Our study showed no statistical difference in IE rates between each type of valves (pooled OR 0.96, 95% CI: 0.68-1.35, p = 0.801 with I2 = 14.7%). There was no difference in IE rate between BE and SE valves following TAVR. Further studies are warranted to confirm our findings.

Fibroelastic Tissue Ring Causing ECMO Catheter Obstruction: An Unusual Complication of Avalon Elite Catheter Insertion.

The Avalon Elite catheter (Maquet Cardiopulmonary, Rastatt, Germany) is a bicaval catheter for single-site cannulation that can be used in the initiation of venovenous extracorporeal membrane oxygenation (ECMO) or as a transition from venoarterial ECMO. We report a unique complication of tissue obstructing the outflow aperture during insertion. (Level of Difficulty: Advanced.).

Engraftment Syndrome and Acute Graft-versus-Host Disease: A Meta-Analysis.

Engraftment syndrome (ES) has been associated with the surge of neutrophils and cytokines, which is similar to the presumed underlying pathophysiology behind acute graft-versus-host disease (aGVHD). However, there has been no meta-analysis to evaluate the association; therefore, the team attempted to verify an association between ES and aGVHD through meta-analysis. The team searched for titles of articles in MEDLINE (PubMed), the Cochrane Library, and the EMBASE database up until December 2018 that evaluated the association between ES and aGVHD and conducted a random effect meta-analysis of 8 studies involving a total of 1,945 participants to report the pooled odds ratio (OR) for association of ES and aGVHD. The team found a significantly increased odds of developing aGVHD in patients with ES with the pooled OR of 2.76 (95% confidence interval [CI]: 1.64-4.63) and an I2= 64.5%. In conclusion, patients with ES have significantly higher odds of developing aGVHD compared to patients without ES.

Coronary Angiography in Patients with Arteria Lusoria via Right Radial Access: A Case Series and Literature Review.

Transradial is becoming the access of choice for coronary angiography (CAG). Arteria lusoria (AL) poses a challenge for right transradial access because it can cause difficulty in accessing the ascending aorta. Of 18,686 patients who underwent CAG in Geisinger Medical Center from 2012 to 2018, 6 had a diagnosis of AL. Four underwent attempted right radial access, in 3 cases before AL was identified. All were successful, and one patient had successful right transradial percutaneous coronary intervention. CAG and PCI can be successfully performed using right radial access in patients with AL.

Budesonide for Protein Losing Enteropathy in Patients with Fontan Circulation: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies have shown that oral budesonide can be used to improve albumin level in patients with protein-losing enteropathy (PLE) following Fontan procedure. However, there has never been a systematic review and meta-analysis to confirm this finding. We performed a systematic review and meta-analysis to explore the therapeutic effect of budesonide in patients with PLE post-Fontan procedure. METHODS: We searched the databases of MEDLINE and EMBASE from inception to January 2019. Included studies were published studies that evaluate albumin level before and after budesonide therapy in patients with PLE following Fontan procedure. Data from each study were combined using the random-effects model. RESULTS: Five studies with 36 post-Fontan operation patients with PLE were included. In random-effects model, there was a statistically significant difference in albumin level between before and after budesonide treatment (weighted mean difference = 1.28, 95% confidence interval: 0.76-1.79). No publication bias was observed on a funnel plot and Egger test with a P value of .676. CONCLUSIONS: The results of this systematic review and meta-analysis show that budesonide can be used to increase albumin level in patients with PLE following Fontan operation. Further studies may focus on the impact of outcome of budesonide in this population.

Total Body Irradiation and Risk of Diabetes Mellitus; A Meta-Analysis

Objective: Hematopoietic stem cell transplant (HSCT) has recently emerged as a cure for previously "incurable" diseases and is being explored and attempted in many other fields including congenital and acquired non-malignant diseases. However, the long-term side effect associated with HSCT especially Total Body Irradiation (TBI) is still understudied. Therefore, we attempted to establish association between TBI and risk of developing Diabetes Mellitus (DM) or impaired glucose metabolism (IGM). Methods: We searched for titles of articles in MEDLINE (PubMed), EMBASE, and Cochrane library in August 2018 that evaluated the association between TBI in the setting of HSCT and DM or IGM. We conducted a random effect meta-analysis of 11 studies involving a total of 13,191 participants and reported the pooled MD (mean difference) for the development of DM/IGM after TBI as part of the conditioning regimen for HSCT. Results: We found a significant increase in the risk of developing DM/IGM after TBI is used as part of the conditioning regimen compared to other types of conditioning regimen with the pooled MD being 5.42, 95% Confidence Interval (CI) 2.51-11.71, I2=92.4%. Conclusion: TBI as a conditioning regimen in the setting of HSCT significantly increases the risk of developing DM/IGM. Therefore, we recommend close monitoring and screening for diabetes mellitus in patients who underwent TBI before HSCT.

Chronic graft-versus-host disease and the risk of primary disease relapse: A meta-analysis.

Both primary disease relapse (PDR) and chronic graft-versus-host disease (cGVHD) have long been the dreaded outcomes for patients with hematologic malignancies. Previous theories have speculated an inverse relationship between the two; therefore, we attempted to verify the described association. We searched for titles of articles in MEDLINE (PubMed), Cochrane library, and EMBASE database that evaluated the association between PDR and cGVHD and conducted a random effect meta-analysis of 11 studies involving a total of 64,239 participants. We found a significantly decreased risk of developing PDR in patients with cGVHD, with a pooled risk ratio of 0.49 (95% confidence interval: 0.40-0.61, I2 = 69.3%). We concluded that patients with cGVHD have a significantly lower risk of developing PDR compared with patients without cGVHD.