Citations

Introduction: Greater religiosity, or degree of involvement in religious activities, associates with better CV health profiles. Yet, studies of the association between religiosity and incident CV events have yielded mixed results. The southeastern US is characterized by strong religious practice but has among the highest rates of incident heart failure (HF). The relationship between religiosity and incident HF is not well characterized, particularly among low-income populations. Methods: We studied 23,893 Black or White Southern Community Cohort Study participants (median age 53 years, 70% Black, 64% women, 70% annual household income <$15k) without prevalent HF or CAD at enrollment (2002-2009). Religiosity, defined by religious service attendance, was ascertained at enrollment via a single item adapted from the Duke University Religion Index. Incident HF was determined using Centers for Medicare and Medicaid Services Research Identifiable Files (ICD-9/-10 codes 428.x or I50, I110) through December 31, 2016. We quantified the association of religious attendance with incident HF via Cox models adjusted for demographics, HF risk factors (HTN, HLD, DM, BMI, CVA), health behaviors (smoking, alcohol, physical activity, DASH diet), socioeconomic (income, education, employment, neighborhood deprivation, rurality) and psychosocial factors (marital status, social support, depressive symptoms, anti-depressant use). Results: Religious service attendance was common: >1/week (24%), 1/week (27%), <1/week (33%), and never (15%). Participants attending >1/week were more likely to be older and female, had relatively higher SES and more comorbidities, but better health behaviors and psychosocial support. HF developed in 6081 participants (25%; median 10-yr follow-up). Adjusting for demographics and HF risk factors, attendance >1/week associated with lower HF risk (HR 0.88 [0.82,0.94] and HR 0.92 [0.84,1.00] compared to <1/week or never, respectively). Attendance 1/week compared to <1/week showed similar association (HR 0.91 [0.85, 0.97]). Further adjustment for health behaviors, socioeconomic and psychosocial factors attenuated the association to non-significance. There was no interaction between religiosity and race. Conclusion: Greater frequency of religious service attendance associated with lower incident HF risk adjusting for demographics and HF risk factors; however, this association attenuated with adjustment for health behaviors, socioeconomic and psychosocial factors.

Introduction: Stroke is the second largest cause of death and third leading cause of disability worldwide. Some high-income countries have one in five lifetime cases and one in two in low-income countries. Due to the high stroke burden and aging population, better preventive and treatment approaches are needed. Recent research shows that stroke patients have a different gut microbiota than healthy people, suggesting a relationship between dysbiosis and stroke incidence and prognosis. Probiotics may improve stroke outcomes by strengthening the intestinal barrier and reducing inflammation. Hypothesis: Our study seeks to evaluate the potential benefits of probiotic supplementation in reducing the risk of ischemic stroke in healthy individuals as well as its impact on the prognosis of stroke patients, specifically in reducing gastrointestinal complications and improving gut microbiota balance (reduce dysbiosis). Methods: We conducted an umbrella meta-analysis of meta-analyses published in the last 10 years using PRISMA guidelines in PubMed. Using RevMan 5.4, we performed an inverse variance random effects model to calculate log (odds ratio) and converted it to pooled OR and 95% confidence interval to obtain a forest plot keeping alpha criteria 0.05. Heterogeneity and risk of bias assessment (by Newcastle-Ottawa Scale) were assessed. Results: While probiotic supplementation in healthy individuals did not significantly decrease the risk of ischemic stroke (OR 0.87 [95%CI 0.75-1.01]), it showed notable benefits in stroke patients. These positive effects included a substantial reduction in the odds of specific GI complications (constipation, diarrhea, gastric retention, esophageal reflux, vomiting, stress ulcers, and gastrointestinal bleeding) by 62% (0.38, 0.29-0.51), non-specific GI complications by 72% (0.28, 0.24-0.34), infection by 73% (0.27, 0.21-0.33) and a significant improvement in gut flora balance, reducing the odds of dysbiosis by 79% (0.21, 0.12-0.36). (p<0.00001) The inter-study heterogeneity was 91% with (p<0.00001, Chi 2 =128.76), a moderate risk of bias. Conclusion: Our umbrella meta-analysis highlights the potential benefits of probiotic supplementation in stroke patients, particularly in mitigating stroke-related GI complications and alleviating intestinal flora dysbiosis. These findings underscore the crucial role of gut-brain interactions in stroke and suggest that probiotics may serve as a promising component of stroke management.

Abstract Background The ataxia-telangiectasia mutated (ATM) protein coordinates the cellular response to therapeutic radiation, and ATM inhibitors can potentially enhance the efficacy of radiation in otherwise radiation-resistant tumors. Methods The small molecule ATM kinase inhibitor WSD0628 was specifically designed for enhanced distribution across the blood-brain barrier to more effectively treat glioblastoma (GBM) and brain metastases in combination with radiation therapy (RT). GBM and brain metastasis patient-derived xenograft models were used to understand target inhibition, radiosensitization, inhibition of the DNA damage response, and in vivo efficacy. Results Initial in vitro characterization of WSD0628 demonstrates a high level of selectivity across kinase families, limited aldehyde oxidase liability, and low risk of hERG interactions. Consistent with a central role for ATM in radiation response, WSD0628 blocked radiation-induced signaling and enhanced radiosensitivity in U251 glioma cells and brain tumor PDXs GBM120 and M12. In comparison to control or RT alone in orthotopic PDXs, the combination of WSD0628 with RT markedly prolonged median survival—GBM12 (19, 55, and 408 days, respectively); GBM43 (26, 44, and 143 days, respectively); GBM120 (51, 89, and 231 days, respectively); M12 (17, 39, and 190 days, respectively). Pharmacokinetic and pharmacodynamic testing after treatment in orthotopic GBM43 tumors showed inhibitory levels of WSD0628 and a reduction of γH2AX foci in the combination-treated tumors. Conclusions Collectively, these results suggest a promising role for WSD0628 in combination with RT in brain tumors and provide the rationale for an ongoing Phase 0/1A clinical trial testing this combination in recurrent GBM.

Background We automated subarachnoid hemorrhage volume (SAHV) calculation with artificial intelligence (SAHVAI) and created 3‐dimensional volumetric images (SAHVAI‐3D) using noncontrast head computed tomography data for patients with aneurysmal SAH. We also defined 4‐dimensional SAHVAI (SAHVAI‐4D), representing SAHV over time. We aimed to compare automated SAHVAI values and computational times to manual SAHV measurement methods, explore the potential of imaging biomarkers to identify at‐risk brain regions for delayed cerebral ischemia and explore potential insights in future neurotherapeutic interventions for patient recovery after SAH. Methods A training set of 10 consecutive patients with aneurysmal SAH was used to manually compute SAHV, SAHVAI‐3D, and SAHVAI‐4D, including 92 noncontrast computed tomography scans (182 slices each). The SAHVAI deep learning algorithm generated automated SAHV values in cubic centimeters. A 3‐dimensional SAH brain map was created for each patient for the SAHVAI and manual evaluations. Blood volumetric outputs were analyzed and compared to neurologic outcomes at discharge, including delayed cerebral ischemia events, symptomatic vasospasm, and areas with the thickest SAH blood concentration. Results SAHVAI quantified SAHV in a mean of 6.7 seconds per scan, significantly faster than the manual method, which took >60 minutes per scan (Fisher exact test, P <0.001). SAHVAI demonstrated an accuracy of 99.8%, Dice score of 0.701, false‐positive rate of 0.0005, and negative predictive value of 0.999. The mean absolute error between SAHVAI and manual methods was 5.67 mL. SAHVAI‐3D brain map and total SAHV at admission were inversely associated with Glasgow Coma Scale (R 2 = 0.23, P = 0.017) and directly associated with length of hospital stay (R 2 = 0.175, P = 0.004), especially in regions with dense blood concentration. Conclusion SAHVAI‐3D and SAHVAI‐4D brain mapping techniques represent innovative imaging biomarkers for SAH. These advancements enable rapid evaluation and targeted interventions, potentially improving patient care in SAH management.

Gastric cancer is a significant global health concern, with CDH1-associated gastric cancer representing a small but important subset of cases. Historically, individuals with CDH1 pathogenic germline variants were advised to undergo prophylactic total gastrectomy due to the high reported risk of gastric cancer and the limited sensitivity of upper endoscopy in detecting signet ring cell carcinoma (SRCC). However, emerging data suggest that the cumulative lifetime risk of advanced gastric cancer among CDH1 germline pathogenic variant carriers is lower than previously thought, and early-stage SRCC detected on endoscopy does not necessarily indicate imminent—or even eventual—progression to advanced cancer. The near-universal presence of T1a SRCC in gastrectomy specimens from asymptomatic CDH1 pathogenic variant carriers calls into question the reflexive recommendation for gastrectomy, including upon detection of SRCC during surveillance. Furthermore, the morbidity and quality-of-life impact associated with total gastrectomy require careful consideration. Active endoscopic surveillance has shown promise as an alternative management strategy for gastrectomy in patients lacking indicators of >T1a SRCC, though current data are limited by short follow-up periods and selection bias. This review synthesizes recent findings on the natural history of CDH1-associated gastric cancer and evaluates the risks and benefits of gastrectomy versus active endoscopic surveillance, with the goal of helping clinicians provide personalized and evidence-based recommendations for patients with CDH1 pathogenic variants.