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We developed an agent-based model using a trial emulation approach to quantify effect measure modification of spillover effects of pre-exposure prophylaxis (PrEP) for HIV among men who have sex with men (MSM) in the Atlanta-Sandy Springs-Roswell metropolitan area, Georgia. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomised trial with eligible components (≥3 agents with ≥1 HIV+ agent) first randomised to intervention or control (no PrEP). Within intervention components, agents were randomised to PrEP with coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component-level characteristics and estimated spillover effects on HIV incidence using an extension of randomisation-based estimators. We observed an attenuation of the spillover effect when agents were in components with a higher prevalence of either drug use or bridging potential (if an agent acts as a mediator between ≥2 connected groups of agents). The estimated spillover effects were larger in magnitude among components with either higher HIV prevalence or greater density (number of existing partnerships compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.

We describe a first suspected case of fibrosing mediastinitis following anti-programmed death (PD)-1 therapy, pembrolizumab. Multimodality imaging, including cardiac magnetic resonance imaging, and a multidisciplinary team approach were integral to the diagnosis. If further substantiated, systematic surveillance after anti-PD-1 therapy for fibrosing mediastinitis may be warranted. (

Background Disruptions in access to in-person human immunodeficiency virus (HIV) preventive care during the coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. Methods We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men in Mississippi over 5 years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new pre-exposure prophylaxis (PrEP) starts, and HIV incidence. Results We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. Conclusions Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately after the disruption period.

Graphical abstract, Highlights • Adults with congenital heart disease have a high incidence of stroke. • Agitated saline administration via the left upper extremity was used to detect PLSVC. • Cardiac MRI was used to accurately diagnose PLSVC. • Bicuspid aortic valve can coexist in patients with PLSVC.

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms of the disease. The use of cardiac magnetic resonance (CMR) imaging and nuclear magnetic resonance (NMR) imaging in preclinical models allows the non-invasive study of subclinical pathophysiological processes that influence cardiac function and establish imaging parameters that can be adopted into clinical practice to predict cardiovascular outcomes. Given the rising population of cancer survivors and the current lack of effective therapies for the management of cardiotoxicity, research combining clinically relevant animal models and non-invasive cardiac imaging remains essential to improve methods to monitor, predict, and treat cardiovascular adverse events. This comprehensive review summarizes the lessons learned from animal models of cardiotoxicity employing CMR and tissue characterization techniques and discusses the ongoing challenges and hopes for the future.

Background: Cardiac resynchronization therapy (CRT) has significant nonresponse rates. We assessed whether machine learning (ML) could predict CRT response beyond current guidelines. Methods: We analyzed CRT patients from Cleveland Clinic and Johns Hopkins. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprised the testing cohort. Response was defined as ≥10% increase in left ventricular ejection fraction. ML models were developed to predict CRT response using different combinations of classification algorithms and clinical variable sets on the training cohort. The model with the highest area under the curve was evaluated on the testing cohort. Probability of response was used to predict survival free from a composite end point of death, heart transplant, or placement of left ventricular assist device. Predictions were compared with current guidelines. Results: Nine hundred twenty-five patients were included. On the training cohort (n=470: 235, Johns Hopkins; 235, Cleveland Clinic), the best ML model was a naive Bayes classifier including 9 variables (QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial left ventricular lead). On the testing cohort (n=455, Cleveland Clinic), ML demonstrated better response prediction than guidelines (area under the curve, 0.70 versus 0.65; P =0.012) and greater discrimination of event-free survival (concordance index, 0.61 versus 0.56; P P Conclusions: ML with 9 variables incrementally improved prediction of echocardiographic CRT response and survival beyond guidelines. Performance was not improved by incorporating more variables. The model offers potential for improved shared decision-making in CRT (online calculator: http://riskcalc.org:3838/CRTResponseScore ). Significant remaining limitations confirm the need to identify better variables to predict CRT response.

Ventricular tachycardia (VT), which can lead to sudden cardiac death, occurs frequently in patients with myocardial infarction. Catheter-based radiofrequency ablation of cardiac tissue has achieved only modest efficacy, owing to the inaccurate identification of ablation targets by current electrical mapping techniques, which can lead to extensive lesions and to a prolonged, poorly tolerated procedure. Here we show that personalized virtual-heart technology based on cardiac imaging and computational modelling can identify optimal infarct-related VT ablation targets in retrospective animal (5 swine) and human studies (21 patients) and in a prospective feasibility study (5 patients). We first assessed in retrospective studies (one of which included a proportion of clinical images with artifacts) the capability of the technology to determine the minimum-size ablation targets for eradicating all VTs. In the prospective study, VT sites predicted by the technology were targeted directly, without relying on prior electrical mapping. The approach could improve infarct-related VT ablation guidance, where accurate identification of patient-specific optimal targets could be achieved on a personalized virtual heart prior to the clinical procedure.

Persistent left superior vena cava (PLSVC) is a rare congenital malformation which results in a right-to-left intracardiac shunt when the left superior vena cava persists and drains into the left atrium. Acute stroke is an unusual presenting symptom. We present a case of PLSVC diagnosed after

Anthracycline-based chemotherapy (Anth-bC) is associated with vascular (including microcirculatory) dysfunction. In this study, we compared a MRI non-contrast T1 mapping measure of microcirculatory function with a more traditional gadolinium contrast enhanced measure (myocardial perfusion reserve

Patients with severe left ventricular dysfunction were under-represented in clinical trials of cardiac resynchronization therapy (CRT). Whether patients with the most extreme forms of systolic dysfunction improve with CRT, and if so, what predicts such improvement remain unclear. We analyzed 231

Brugada syndrome is a genetic disorder that results in decreased expression of cardiac Na+ channels, leading to abnormal electrical activity with onset in the right ventricle (RV). Given that INa is reduced globally, it remains unclear why the RV is more susceptible to arrhythmogenesis. This study tests the hypothesis that differences in geometry between left ventricle (LV) and RV promote altered conduction patterns under reduced INa. Using a 3D rabbit ventricular model that incorporates realistic geometry, simulations were performed where INa maximal conductance was varied from 60 to 100% of the normal level. Reentry was induced via diastolic stimulation of the LV or RV epicardium. Sustained reentry developed only at the 60% INa level for RV stimulation, while no reentry was induced for the LV regardless of INa levels. Activation map (figure) for the 60% INa model shows conduction block at the RV insertion region, where the safety factor (the ratio of total intracellular current vs. current needed to excite the cell) was zero. Propagation from the thin RV has insufficient current to excite tissue in the septum/LV, resulting in source-sink mismatch and block, thus predisposing the RV to arrhythmogenesis under reduced INa.View Large Image | View Hi-Res Image | Download PowerPoint Slide