Urban environments contribute substantially to the rising burden of cardiometabolic diseases worldwide. Cities are complex adaptive systems that continually exchange resources, shaping exposures relevant to human health such as air pollution, noise, and chemical exposures. In addition, urban infrastructure and provisioning systems influence multiple domains of health risk, including behaviors, psychological stress, pollution, and nutrition through various pathways (eg, physical inactivity, air pollution, noise, heat stress, food systems, the availability of green space, and contaminant exposures). Beyond cardiometabolic health, city design may also affect climate change through energy and material consumption that share many of the same drivers with cardiometabolic diseases. Integrated spatial planning focusing on developing sustainable compact cities could simultaneously create heart-healthy and environmentally healthy city designs. This article reviews current evidence on the associations between the urban exposome (totality of exposures a person experiences, including environmental, occupational, lifestyle, social, and psychological factors) and cardiometabolic diseases within a systems science framework, and examines urban planning principles (eg, connectivity, density, diversity of land use, destination accessibility, and distance to transit). We highlight critical knowledge gaps regarding built-environment feature thresholds for optimizing cardiometabolic health outcomes. Last, we discuss emerging models and metrics to align urban development with the dual goals of mitigating cardiometabolic diseases while reducing climate change through cross-sector collaboration, governance, and community engagement. This review demonstrates that cities represent crucial settings for implementing policies and interventions to simultaneously tackle the global epidemics of cardiovascular disease and climate change.

Balloon aortic valvuloplasty (BAV) improves the hemodynamics and symptoms of patients with severe aortic stenosis in the short term with low rates of complications, but has not been shown to be an effective destination therapy. Our pooled analysis of >14,300 patients from studies published between January 1, 1991, and April 31, 2022, reported intraprocedural mortality and in-hospital mortality rates as 1.94% (95% CI, 1.39%-2.59%) and 6.02% (95% CI, 4.83%-7.32%), respectively. Hence, BAV is primarily indicated as a bridge to aortic valve replacement/decision with secondary uses as bridge to noncardiac surgery and palliative therapy. Recent advancements in alternative access sites, balloon catheters, and lithotripsy for BAV have opened opportunities for expanded use and further improvements in complication rates. As the utilization of BAV has continually increased since the advent of transcatheter aortic valve replacement, reexamining the role and outcomes of BAV in the era of transcatheter aortic valve replacement has become increasingly important. This review focuses on the outcomes, indications, advances, and technical considerations for BAV.

Lung cancer is the leading cause of cancer-related death worldwide, and patients with operable early-stage NSCLC are typically managed surgically. While effective, surgical resection can significantly impact pulmonary function and quality of life. Pulmonary rehabilitation (PR) is a comprehensive, multimodal approach that is an established cornerstone in the treatment of COPD. It has similarly demonstrated multiple benefits in patients with lung cancer who have undergone lobectomy or resection by improving pulmonary function, increasing exercise tolerance, improving nutritional status, providing psychological support, and enhancing quality of life. Despite this, PR for early-stage operable NSCLC is oftentimes not standardized, and challenges to adherence remain. In this review, we examine the components of PR, the role of PR in pre- and postoperative settings in patients with early-stage NSCLC, implementation strategies for PR, and future directions and challenges of PR in operable NSCLC.

Background: Anitens are a family of oral N-terminal domain inhibitors of the androgen receptor (AR). In prostate cancer, they may help overcome AR resistance mechanisms at the ligand-binding domain, which is the binding site of approved androgen receptor pathway inhibitors like enzalutamide. Masofaniten (EPI-7386) is a next-generation aniten with promising activity and safety in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods: In this investigator-initiated, phase II, single-arm, single-institution trial, patients with treatment-naïve metastatic hormone-sensitive prostate cancer (mHSPC) were enrolled in a Simon 2-stage study design to receive the combination of masofaniten 600 mg BID and enzalutamide 160 mg daily with androgen deprivation therapy (ADT). The study was designed to enroll 35 patients (13 patients in stage 1, then 22 patients in stage 2). The trial would move to stage 2 if 9 or more subjects achieved a biochemical response at 6 months. Results: Thirteen patients were screened and enrolled into stage 1. Five were African American, and 8 were Caucasian. The median age was 68 years (range 52-75) at time of enrollment. Median follow-up time was 9.9 months (range 7.7-13.6). Ten of 13 patients (77% with 95% CI: 50%-92%) achieved a PSA <0.2 ng/mL at 6 months, achieving the threshold to move on to stage 2. Only one patient had disease progression to mCRPC and died of disease at the time of data cutoff. Patients continued enzalutamide and ADT after trial closure. Conclusion: The combination of masofaniten and enzalutamide for treatment-naïve mHSPC did show efficacy and had an acceptable safety profile. These results support further investigation of the dual AR blockade in mHSPC (ClinicalTrials.gov Identifier: NCT06312670).

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph digitizer software IPDfromKM R package to extract coordinates of points on the curves and to apply a numerical algorithm to reconstruct progression-free survival (PFS) and overall survival (OS) results. Durable response (DR) was defined as PFS ≥ 24 months, extreme durable response (EDR) as PFS ≥ 36 months, and long-term OS as OS ≥ 48 months. Results: For the favorable risk group, lenvatinib-pembrolizumab had the highest DR and EDR, while ipilimumab-nivolumab had the lowest DR, and cabozantinib-nivolumab had the lowest EDR; there was no difference in long-term OS among the regimens ( p = 0.11). For the intermediate/poor risk group, lenvatinib-pembrolizumab also had the highest DR and EDR compared to other regimens with similar DR and EDR; there was also no difference in long-term OS among the regimens ( p = 0.22). Conclusion: TKI-ICI was overall associated with higher DR and EDR regardless of risk status compared to ICI doublet. Yet, OS at 48 months were similar when stratified by favorable versus intermediate/poor risk.