Karumanchi, Abhimanyu

Background: Stroke is a major health burden and the second leading cause of death globally, only after ischemic heart disease. While observational studies have elaborated on the effect of physical activity (PA) and sedentary behavior (SB) on stroke risk, their findings remain inconsistent and are often influenced by confounding factors and reverse causation. Mendelian randomization (MR) can help overcome these shortcomings and assess potential causal relationships using genetic variants as proxies for exposures. Methods: We conducted a systematic review and meta-analysis of MR studies investigating the effects of PA and SB on stroke risk. Following PRISMA guidelines, we searched PubMed and Google Scholar through May 2025. Eligible studies used two-sample MR designs to estimate the impact of moderate-to-vigorous physical activity (MVPA) and sedentary leisure behavior (SLB) on stroke outcomes. MVPA exposures included self-reported activity and accelerometer-derived measures (e.g., leisure time MVPA ≥425 mg), while SLB included television, screen time, sitting, etc. Key outcomes of interest were any stroke and ischemic stroke events. Random-effects models were used for meta-analysis and heterogeneity was assessed with the I2 statistic. Leave-one-out sensitivity analyses were performed to ensure robustness of the results. Results: Six studies met inclusion criteria. Genetically predicted MVPA was associated with a lower risk of stroke (pooled OR = 0.73; 95% CI: 0.53–1.01; p = 0.06), though the result was not statistically significant (I2= 79.5%). In contrast, SLB showed a significant association with increased stroke risk (pooled OR = 1.15; 95% CI: 1.01–1.31; p = 0.03; I2 = 89.9%). Sensitivity analyses confirmed that findings were not influenced by any single study. Conclusion: These findings support a causal association between SLB and increased stroke risk, with suggestive but non-significant evidence for MVPA’s protective role. Despite significant association, high heterogeneity warrants conscious interpretation of findings. Further MR studies using standardized exposure definitions and updated genetic data are needed to strengthen the results.

Background: Cardiac rehabilitation (CR) is emerging as an essential aspect of secondary prevention in patients recovering from acute myocardial infarction (AMI) or coronary artery disease (CAD). Exercise-based rehabilitation involves high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and maximum intensity interval training (MIIT). These are integral to improving cardiopulmonary fitness, cardiovascular outcomes, and affect health-related quality of life (HRQoL). HIIT is presumed to show better outcomes, though comparative evidence across exercise types remains inconsistent. Clarifying the differential impact of HIIT, MIIT, and MICT on physical and psychosocial outcomes is vital for optimizing CR. Methods: 5 studies involving 650 post-AMI adults enrolled in CR were included. Most studies compared HIIT and MICT; one study also included maximal-intensity interval training (MIIT), and all others used usual care as a control. Outcomes included cardiorespiratory fitness (VO2 max), functional capacity (6-minute walk test [6MWT]), HRQoL (EQ-5D-5L, MacNew), mental health (PHQ, vitality), sleep quality (PSQI), fatigue (FSS), and physiological measures (blood pressure (BP), lipid profile, stroke volume, VE_peak). A qualitative synthesis of findings was performed due to heterogeneity across studies. Results: All 5 studies indicated that structured exercise improved outcomes. HIIT led to greater gains in VO2max compared to MICT. MIIT, assessed in one study, showed the largest VO2max improvements. HRQoL improved in all modalities across EQ-5D-5L, MacNew, PHQ, and visual analog scales. Functional metrics (6MWT, PPO) and cardiovascular parameters (HDL-C, HR recovery) improved more with HIIT. BP, BMI, and HbA1c improved similarly across groups. In several studies, HIIT had a stronger effect on physical functioning and emotional health. Only HIIT led to a significant drop in depression scores. HDL cholesterol improved more with HIIT. Conclusion: HIIT provides superior gains in cardiorespiratory fitness and physical function compared to MICT or MIIT in CR participants, without compromising safety/quality of life. Mental health, HRQoL, and physiological parameters improve comparably across exercise modalities. These findings support that HIIT is an effective, time-efficient option in contemporary CR planning. Future standardized, large-scale, and long-term studies are needed to assess sustained clinical impact and cardiovascular event reduction.

BACKGROUND: Studies in the past have demonstrated an association between sarcoidosis and pulmonary embolism but little is known about its impact, especially in young adults. We aim to determine the burden and impact of pulmonary embolism (PE) in young adults hospitalized with sarcoidosis. METHOD: The study investigates the prevalence and consequences of PE in young adults aged 18-44 years hospitalized with sarcoidosis using data from the National Inpatient Sample (2016-2020) with relevant ICD-10 codes. This study aims to address the primary outcomes of the burden and trends of PE and its associated impact on in-hospital mortality. Additionally, it explores secondary outcomes such as healthcare resource utilization and discharge patterns. RESULT: Among 50,385 young adults (median age 37 years) hospitalized with sarcoidosis, 1120 had PE, showing a linear increase from 2% in 2016 to 2.9% (p<0.001) in 2020. Sarcoidosis-PE+ group, predominantly in young blacks, exhibited a higher prevalence of comorbidities such as obesity, smoking, drug use, peripheral vascular disease, hypothyroidism, and prior history of VTE. In contrast, the sarcoidosis-PE- group had a higher prevalence of diabetes (with/without chronic complication), hyperlipidemia, and chronic pulmonary disease. Multivariable regression analysis adjusted for all potential sociodemographic and comorbid variables showed higher odds of all-cause mortality (OR: 2.92, 95% CI: 1.18-7.24, p <0.02) in the sarcoidosis-PE+ group as compared to sarcoidosis-PE- group. The sarcoidosis-PE+ group also had higher hospital costs and length of stay. CONCLUSION: The higher odds of in-hospital mortality with an increased length of stay and hospital cost observed in the sarcoidosis-PE+ group highlight the often underreported complications of sarcoidosis, particularly in a younger demographic. The relevance of this study stems from its potential to uncover trends that could lead to improved diagnostic and therapeutic strategies.