UCLA Medical Center

ABSTRACTObjectivesHeart failure is a leading cause of mortality, necessitating identification of patients at increased risk needing intervention. In this study, we investigated if Fitbit data can reveal physiological trends associated with hospital visit risk.Materials and methodsIndividuals with heart failure (n=249) were randomized into three arms for prospective 180-day monitoring. All arms received a Fit-bit and wireless weight scale. Arm 1 received devices only; Arm 2 received a mobile app with surveys; Arm 3 received the app plus financial incentives.Results51 participants had hospital visits during the study period. These individuals took fewer steps (p=.002) and reported increased symptom severity (p=.044). Resting heart rate increased three days prior to a visit (p=.022). Baseline steps revealed a higher visit probability for less active participants (p=.003).Discussion and conclusionPassive physiological monitoring can effectively identify individuals at risk of health exacerbation, demonstrating the potential of wearable devices for timely clinical intervention.

Inflammation plays a crucial role in atherosclerosis and coronary artery disease progression. Colchicine, an inexpensive anti-inflammatory medication, has shown promising results in reducing cardiovascular events in patients with stable coronary artery disease (CAD). However, its effect on coronary plaque progression remains unclear. We investigated whether colchicine, as an adjunct to standard of care therapy, affects coronary plaque components in patients with stable CAD. We performed a prospective, randomized, double-blinded, placebo-controlled trial in 84 patients with stable CAD to receive either colchicine (0.5 mg/day) or placebo for 12 months. All enrolled patients had proven coronary artery disease as evidenced by coronary angiography, CT coronary angiography, or a Coronary Artery Calcium Score >400. The primary outcome was the rate of change in low attenuation plaque (LAP) volume, as measured by serial coronary computed tomography angiography (CCTA), utilizing volumetric plaque quantification software at 12 months between colchicine and placebo groups. The secondary endpoint was total plaque percent atheroma volume (PAV%). The sample size was set assuming a treatment difference of at least 8 mm³ change in LAP volume in favour of colchicine compared to placebo. The mean age of the 72 participants who completed the study was 64.6 ± 7.3 years, with 63 (88%) subjects being male. Baseline demographics, risk factors, medications, vitals, and inflammatory markers were not significantly different between the colchicine and placebo groups. One exception was that the colchicine group had significantly higher use of hypertension medications (75% vs. 44%) at the study start. There was no significant difference in the change in total LAP between the colchicine group with median (IQR) 0.1 (-02, 0.2) vs. 0.0 (-0.2, 0.3) in placebo, un-adjusted P = 0.342. Multivariable models, including known CV risk factors and baseline LAP, also showed no significant difference between the changes in LAP between treatment and placebo groups. A treatment effect was observed in the total PAV%. Follow-up total PAV at 12-month scan was significantly lower at median (IQR) 0.3 (-0.1, 1.3) in the colchicine group vs. 1.4 (0.4, 2.6) in placebo, P = 0.008 (unadjusted). In multivariate models, colchicine treatment was associated with lower PAV at 1 year, P = 0.015. Trends toward regression in non-calcified and fibro-fatty plaque were observed. Inflammatory markers were reduced with colchicine, but did not achieve statistical significance. In the EKSTROM trial, low-dose colchicine did not significantly reduce low attenuation plaque volume in patients with stable coronary artery disease over 12 months, but did achieve a significant reduction in total plaque burden (percent atheroma volume) and dense calcified plaque compared to placebo. Colchicine was well tolerated, with no major safety concerns. In this stable well-treated CAD population, LAP was rare and not significantly reduced; however, it slowed overall plaque progression, supporting further investigation of its role in secondary prevention of coronary artery disease. NCT06342609.

Background: Ovarian cystectomy is standard treatment for endometrioma but is associated with decreased ovarian reserve. Catheter-directed sclerotherapy (CDS) is an ovary-sparing image-guided alternative; however, supporting evidence comprises retrospective comparative and prospective single-arm studies. Objective: To compare CDS and ovarian cystectomy in terms of therapeutic efficacy and effect on ovarian function in women with ovarian endometrioma through a randomized controlled trial. Methods: This prospective pilot study enrolled women evaluated for unilateral unilocular endometrioma measuring >3 cm from March 20221 to July 2024. Participants were randomized to treatment by fluoroscopic and ultrasound-guided CDS or laparoscopic cystectomy. The primary endpoint was percentage decline from baseline to 12 months in serum anti-Müllerian hormone (AMH) (an ovarian functional reserve marker). Additional procedural and 12-month outcomes were assessed including the Endometriosis Health Profile-30 (EHP-30) questionnaire addressing endometriosis-related symptoms and quality of life (lower score: better status). Results: The analysis included 40 participants: 20 randomized to CDS (mean age, 32.8 years), and 20 (mean age, 35.1.1 years) to cystectomy. Mean 12-month percentage decline in AMH (primary outcome) was smaller for CDS than cystectomy (14.9% vs 39.8%, P=.02). No complications occurred after CDS; one complication occurred after cystectomy. Hospital length of study was significantly shorter after CDS (2.3±0.5 days) than cystectomy (4.2±0.7 days) (P<.001). From baseline to 12 months, ultrasound-based cyst size significantly decreased for CDS (5.8±1.5 to 0.6±0.7 cm; P<.001) and cystectomy (5.3±1.4 to 0.0±0.0 cm; P<.001); mean AMH was not significantly different for CDS (3.1±2.2 to 2.7±1.7 ng/mL; P=.08) but decreased significantly for cystectomy (3.3±3.0 to 2.0±1.8 ng/mL; P<.001); mean CA-125 decreased significantly for CDS (69.2±61.7 to 17.3±14.2 U/mL; P<.001) and cystectomy (54.6±35.8 to 14.8±8.2 U/mL; P<.001); and mean EHP-30 score decreased significantly for CDS (31.3±12.8 to 6.3±6.9; P<.001) and cystectomy (34.5±18.0 to 8.1±4.3; P<.001). CA-125 and EHP-30 score were not significantly different between groups at 12 months (P>.05). No 12-month recurrence occurred in either group. Conclusion: CDS was associated with better preservation of ovarian reserve versus cystectomy, without significant difference for therapeutic efficacy measures. Clinical Impact: These results advance the level of evidence supporting CDS as an ovary-sparing cystectomy alternative for appropriately selected patients.

Abstract Background Non-ischemic cardiomyopathy (NICM) represents a major cause of heart failure with limited tools for early risk stratification. Atrial fibrillation (AF) is a well-established contributor to cardiomyopathy but is often clinically silent in its early stages. The atrial fibrillation polygenic risk score (AF-PRS) reflects genetic susceptibility to AF and may identify individuals at risk for AF-related cardiomyopathy. We hypothesized that higher AF-PRS is associated with greater risk of NICM. Methods This was a retrospective cohort study of 16,801 individuals of European ancestry from the Sanford Biobank and Imagenetics program with genetic sequencing and longitudinal electronic health record data. AF-PRS was calculated using 315 genome-wide significant single-nucleotide polymorphisms with standard quality control. NICM was defined by International Classification of Diseases, 10th Revision, Clinical Modification codes, excluding ischemic etiologies. Cox regression models evaluated the association between AF-PRS and incident NICM, adjusting for age, sex, smoking status, body mass index (BMI), hypertension, and diabetes. AF-PRS was analyzed both as a quasi-continuous variable (15% quartile increments) and dichotomized at the 85th percentile. Sensitivity analyses assessed associations with all-cause cardiomyopathy and ischemic cardiomyopathy. Survival analysis was used to model time-to-event outcomes. Results Among all participants, 418 (2.5%) had NICM. 99% were Caucasian. NICM cases were older and more often male (both p&lt;0.001) than those without a diagnosis. After multivariable adjustment for sex, smoking status, BMI, and hypertension, a linear AF-PRS (15% increments) was specifically predictive of increased hazard risk of NICM (HR = 1.09 [1.03, 1.15], p &lt; 0.001). Conclusion These findings complement recent evidence of bidirectional genetic relationships between cardiomyopathy and AF, supporting comprehensive genetic risk assessment in cardiovascular disease prevention. Clinical implementation requires validation in diverse populations and prospective evaluation. Future research should investigate the mechanistic pathways linking AF-associated genetic variants to cardiomyopathy development and evaluate whether AF-PRS-guided screening improves clinical outcomes. Visual abstract: Summary of study design, exposure, outcome, key findings, and clinical implications. This graphical abstract provides a comprehensive overview of the study investigating the association between atrial fibrillation polygenic risk score (AF-PRS) and non-ischemic cardiomyopathy (NICM). Abbreviations: AF, atrial fibrillation; AF-PRS, atrial fibrillation polygenic risk score; CI, confidence interval; HR, hazard ratio; ICD-10, International Classification of Diseases, 10th Revision; ICM, ischemic cardiomyopathy; NICM, non-ischemic cardiomyopathy; PPV, positive predictive value; PRS, polygenic risk score; SNP, single nucleotide polymorphism. Created in BioRender. https://BioRender.com/ k3t1w68

Celcomen leverages a mathematical causality framework to disentangle intra- and inter-cellular gene regulation programs in spatial transcriptomics data through a generative graph neural network. It is a first step towards perturbation models of Virtual Tissues and can generate post-perturbation counterfactual spatial transcriptomics, thereby offering access to experimentally inaccessible samples. We validated its disentanglement, identifiability of causal structure, and counterfactual prediction capabilities through simulations and in clinically relevant human glioblastoma, human fetal spleen, and mouse lung cancer samples. Celcomen provides the means to model disease- and therapy-induced changes allowing for new insights into single-cell spatially resolved tissue responses.

T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and management of T cell therapy-associated CRS and subsequent cardiotoxicity. We also explore how an improved understanding of CAR T cell therapy, and other emerging T cell-based treatments, will inform the prevention and management of adverse cardiovascular events.

In basketball, quadriceps strains and contusions are common due to the muscle’s role in knee extension and hip flexion, with the rectus femoris most prone to injury because it crosses both joints, making it vulnerable to eccentric loading. The purpose of this study was to describe the epidemiology of quadriceps injuries in National Basketball Association (NBA) players, assess changes in player performance statistics after injury, and to determine factors that were associated with a greater or equal player efficiency rating (PER) and usage percentage (USG%) 1 year and 2 years after a quadriceps injury. Quadriceps muscle injury data from the 2015 to 2020 NBA seasons were extracted using a publicly available database. Injury characteristics and player demographics were evaluated with descriptive statistics. PER, USG%, points per game (PPG), and minutes per game (MPG) were calculated for the season prior, 1 season after, and 2 seasons after injury. A Poisson logistic regression analysis was performed to identify risk factors associated with greater or equal PER and USG% at 1 year and 2 years after injury. A total of 116 quadriceps muscle injuries were sustained among 89 NBA players. Contusion was the most common injury type, and the majority of injuries resulted in less than ten games missed. PER at 1 year after injury (15.8; P = 0.015) was significantly lower than baseline PER (16.5), but recovered at 2 years post-injury (16.8; P = 0.166). Older age was associated with a relative risk of having a decreased USG% (relative risk [RR] 0.83; 95% confidence interval [CI] 0.76–0.90) and a decreased PER (RR 0.75; 95% CI 0.64–0.88) at 1 year after injury, but these associations were not significant at 2 years after injury (P = 0.084 and P = 0.431, respectively). Contusions are the most common quadriceps muscle injury sustained by NBA players. Older age may be associated with decreased usage and efficiency one year after injury. NBA players are likely to return to baseline PER and USG% statistics at two years post injury.

BACKGROUND:Venous thromboembolism (VTE) is a leading cardiovascular disease, yet its etiology is incompletely understood. This study used large-scale, high-throughput aptamer-based proteomics to identify new circulating protein biomarkers and biological pathways for incident VTE.METHODS:We included 4 longitudinal cohorts (the ARIC study [Atherosclerosis Risk in Communities], CHS [Cardiovascular Health Study], MESA [Multi-Ethnic Study of Atherosclerosis], and the HUNT study [Trøndelag Health]) that identified 1371 incident noncancer VTEs among 20 737 participants followed for a maximum of 10 to 29 years. We used the SomaScan to measure baseline plasma levels of ≈5000 to 7000 proteins and examined the prospective relationships between the protein biomarkers and noncancer VTE. We then conducted an external replication of top VTE proteins in 783 incident noncancer VTEs among 39 097 participants in the UKB study (UK Biobank) based on the Olink proteomics platform. We used Cox proportional hazards regression to estimate the association between each protein biomarker and VTE risk. Mendelian randomization (MR) analysis was used to assess the possible causal associations between identified proteins and VTE risk.RESULTS:There were 23 proteins that exceeded a false discovery rate–adjusted P<0.05 (unadjusted P<6.5×10-4) in the discovery meta-analysis of ARIC, CHS, and MESA and were replicated in HUNT at (unadjusted) P<0.05. Of these, 15 are new to VTE, and 3 of the 15 (transgelin, sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1, and TIMP4 [metalloproteinase inhibitor 4]) exceeded the Bonferroni corrected significance threshold in HUNT. Sixteen of the 23 top VTE proteins were available on the UKB Olink panel, of which 11 were replicated in the UKB study after Bonferroni correction. MR analysis of the 15 new proteins provided significant evidence for a possible causal role of TIMD4 (T-cell immunoglobulin and mucin domain-containing protein 4) (Bonferroni-corrected P<0.05) and suggestive evidence for TIMP4 and CST3 (cystatin-c) (unadjusted P<0.05) in VTE risk. The direction of association from the MR analyses was opposite of that from the VTE proteomics analysis for TIMP4 and TIMD4 but was consistent for CST3.CONCLUSIONS:We identified several novel plasma proteins for VTE that reflect biological processes outside established VTE pathophysiology, including extracellular matrix regulation, immunity, immune–vascular endothelium interactions, and vascular senescence. Results may provide new modifiable targets to improve VTE risk stratification, prevention, or treatment.