A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma.

Introduction: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Methods: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Results: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. Discussion: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

Management of immune check-point inhibitor-associated colitis in patients with advanced metastatic cancers: A review article.

Immune check-point inhibitors (ICPi) are immunomodulating agents, which have revolutionized the management of advanced metastatic cancers. Being immunomodulating agents, they are predisposed to causing colitis. This descriptive review article emphasized on the management of ICPi-associated colitis in advanced metastatic cancers. We used PubMed, Google Scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were "management," "immune check-point inhibitors," "colitis," "metastatic," "cancers," "literature," and "review." We reviewed a total of 11 articles done in the last 15 years relevant to ICPi colitis and its management; all the articles showed that diarrhea and colitis are the most common adverse effects observed in patients on ICPi, but prior to establishing the diagnosis of ICPi-causing colitis, possibility of Clostridium difficle or cytomegalovirus infections should be ruled out. Once the diagnosis of ICPi colitis is established, treatment should be started depending upon the severity of colitis. In mild severity, discontinuation of ICPi can resolve the symptoms but, in most of the patients with moderate to high severity of colitis, corticosteroids are considered a cornerstone treatment. Patients unresponsive to steroid treatment should be re-evaluated for infections after which anti-TNF therapy-infliximab or vedolizumab, cyclosporine, mycophenolate mofetil-can be considered.

Outcomes of Device-detected Atrial High-rate Episodes in Patients with No Prior History of Atrial Fibrillation: A Systematic Review and Meta-analysis.

Background: Outcomes of device-detected AF remain unclear in individuals without a prior history of AF. Methods: A meta-analysis was conducted to evaluate outcomes in individuals with no prior history of AF who experienced device-detected AF. Outcomes assessed were clinical AF, thromboembolism and all-cause mortality. A fixed-effects model was used to calculate RRs with 95% CI. Results: Compared to individuals who did not experience device-detected AF, those who did had increased risks of clinical AF (RR 3.33, 95% CI [1.99.5.57]; p<0.0001) and thromboembolic events (RR 2.21; 95% CI [1.72.2.85]; p<0.0001). The risk of all-cause mortality was similar between both groups (RR 1.19; 95% CI [0.95.1.49]; p=0.13). Subgroup analysis revealed an increased risk of thromboembolic events among device-detected AF .24 hours (RR 12.34; 95% CI [2.70.56.36]). Conclusion: While there is an increased risk of clinical AF and thromboembolism in individuals with device-detected AF, mortality was insignificant.

Sex Differences in the Clinical Outcomes of Patients With Takotsubo Stress Cardiomyopathy: A Meta-Analysis of Observational Studies.

The incidence of takotsubo stress cardiomyopathy (TSCM) in males is low compared with females. Gender-based differences in clinical outcomes of TSCM are not well characterized. The aim of this meta-analysis was to analyze whether gender-based differences are observed in TSCM clinical outcomes. A comprehensive literature search of PubMed, Embase, Cochrane Library database, and Web of Science was performed from inception to June 20, 2022, for studies comparing the clinical outcomes between male and female patients with TSCM. The primary outcome of interest was in-hospital all-cause mortality and cardiogenic shock. The secondary outcomes were cardiovascular mortality, receipt of mechanical ventilation, intra-aortic balloon pump, occurrence of ventricular arrhythmia, and left ventricular thrombus. A random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). Heterogenicity was assessed using the Higgins I2 index. Twelve observational studies involving 51,213 patients (4,869 males and 46,344 females) were included in the meta-analysis. Male gender was associated with statistically significant higher in-hospital all-cause mortality compared with females in patients with TSCM (RR 2.17, 95% CI 1.77 to 2.67, p <0.001). The rate of cardiogenic shock was significantly higher in males with TSCM compared with females (RR 1.66, 95% CI 1.29 to 2.12, p <0.001). Our meta-analysis showed a difference in the clinical outcomes of TSCM between men and women. Male gender was associated with a two-fold greater in-hospital all-cause mortality risk compared with female gender. The higher mortality risk associated with male gender deserves further study, particularly whether it represents later recognition of the condition and disparities in treatments.

The Prevalence of Chagas Disease Among Latin American Immigrants with Pacemakers in Los Angeles, California.

AbstractChagas disease (CD), with associated conduction abnormalities, is a common indication for pacemaker implantation in Latin America. The prevalence of CD in Latin American immigrants with pacemakers residing in the United States has never been studied. This single-center cross-sectional study included pacemaker patients who were aged 18 years or more with a previous residence in Latin America for at least 6 months. Patients with an implantable cardioverter-defibrillator, cardiac resynchronization therapy, or iatrogenic and/or congenital heart block were excluded. Serological testing for Trypanosoma cruzi was performed at enrollment. A total of 80 patients were enrolled, and CD was diagnosed in six patients (7.5%). Patients with CD were more likely to be from El Salvador (P = 0.001). Other clinical, therapeutic, electrocardiographic, and echocardiographic variables were similar between the CD and non-CD groups. There is a high prevalence of CD among Latin American immigrants with pacemakers in Los Angeles.

Prevalence of Chagas Disease in a U.S. Population of Latin American Immigrants with Conduction Abnormalities on Electrocardiogram.

Chagas disease (CD) affects over six million people and is a leading cause of cardiomyopathy in Latin America. Given recent migration trends, there is a large population at risk in the United States (US). Early stage cardiac involvement from CD usually presents with conduction abnormalities on electrocardiogram (ECG) including right bundle branch block (RBBB), left anterior or posterior fascicular block (LAFB or LPFB, respectively), and rarely, left bundle branch block (LBBB). Identification of disease at this stage may lead to early treatment and potentially delay the progression to impaired systolic function. All ECGs performed in a Los Angeles County hospital and clinic system were screened for the presence of RBBB, LAFB, LPFB, or LBBB. Patients were contacted and enrolled in the study if they had previously resided in Latin America for at least 12 months and had no history of cardiac disease. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA) tests were utilized to screen for Trypanosoma cruzi seropositivity. A total of 327 consecutive patients were screened for CD from January 2007 to December 2010. The mean age was 46.3 years and the mean length of stay in the US was 21.2 years. Conduction abnormalities were as follows: RBBB 40.4%, LAFB 40.1%, LPFB 2.8%, LBBB 5.5%, RBBB and LAFB 8.6%, and RBBB and LPFB 2.8%. Seventeen patients were positive by both ELISA and IFA (5.2%). The highest prevalence rate was among those with RBBB and LAFB (17.9%). There is a significant prevalence of CD in Latin American immigrants residing in Los Angeles with conduction abnormalities on ECG. Clinicians should consider evaluating all Latin American immigrant patients with unexplained conduction disease for CD.