Citations

Abstract Background Hospital‐at‐home programs (HaH) in the United States have evolved to include a virtual‐hybrid delivery model, where all physician encounters are virtual and partnered with a home care team. Objective To examine whether a virtual hybrid HaH program enabled by technology has similar clinical outcomes to traditional brick‐and‐mortar (B&M) hospital care. Methods We conducted a pragmatic trial at three hospitals, randomizing 1150 acutely ill patients requiring hospital care between July 10, 2023, and October 31, 2023 one‐to‐one into two groups: intervention (HaH) and control (B&M). The primary analysis was an intention‐to‐treat non‐inferiority analysis of the primary outcome, which was a composite of 30‐day all‐cause mortality and unplanned readmissions. Secondary outcomes included 30‐day readmission, all‐cause mortality, and patient experience. Results The mean age was 67.8 (standard deviation [SD] 16.3) years, and 52.2% were female. The primary outcome occurred in 99 (17.3%) HaH patients and 114 (19.8%) B&M patients (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.63–1.14, p = .28), meeting the non‐inferiority criterion. Thirty‐day unplanned readmission occurred in 84 (14.7%) HaH patients and 101 (17.5%) B&M patients (OR 0.81, 95% CI 0.59–1.11, p = .19). Thirty‐day all‐cause mortality occurred in 25 (4.4%) HaH patients and 19 (3.3%) B&M patients (OR 1.34, 95% CI 0.73–2.46, p = .35). No HaH patients died while receiving their hospital care at home. HaH program was associated with a higher likelihood of patients reporting feeling extremely comfortable or very comfortable (84.4% HaH; 60.9% B&M, p = .001). Conclusion A hybrid HaH model is a safe and comfortable alternative to traditional B&M hospital care.

INTRODUCTION: The SPEC-AI Nigeria trial (NCT05438576) was designed to use artificial intelligence (AI) to screen for pregnancy-related cardiomyopathy in the peripartum period. Using data from this study, we evaluated the utility of AI-predicted delta age (adjusted AI-predicted age − chronological age) as a surrogate for biological age. METHODS: We included 1,187 pregnant and postpartum women enrolled between August 2022 and September 2023 with follow-up through May 2024. Standard 12-lead electrocardiograms (ECGs) were recorded at study entry to generate AI age predictions. Artificial intelligence-predicted age was adjusted using estimated reference ranges obtained from a community-dwelling cohort of 25,144 individuals with AI-ECG age estimated and documented chronological age. Logistic and Cox-proportional hazards regression were used to examine associations with comorbid cardiovascular conditions and maternal mortality, respectively. RESULTS: Adjusted AI-predicted age was significantly higher among women with any cardiovascular condition, peripartum cardiomyopathy, or who died within 18 months (7, 14, and 23 years older, respectively) compared to those without these conditions who had values similar to the normal reference ranges (adjusted AI-predicted age difference less than 1 year). Artificial intelligence-predicted delta age greater than the 75th percentile was associated with an odds ratio (OR) of 2.06 for any cardiovascular condition, OR of 4.98 for left ventricular systolic dysfunction, and a hazard ratio of 32.81 for all-cause mortality; all values of P<.001. CONCLUSIONS/IMPLICATIONS: Artificial intelligence-ECG-derived biological age appears to be a potentially useful measure of cardiovascular health status and risk among pregnant and postpartum women. However, its role in monitoring maternal health requires further exploration.

INTRODUCTION: Cardiovascular disease is a leading cause of maternal mortality. Our aim was to evaluate the feasibility and quality of artificial intelligence (AI)-guided focused cardiac ultrasound (FoCUS) by novice scanners to screen for left ventricular (LV) systolic dysfunction in pregnant individuals. METHODS: Patients were prospectively enrolled during routine obstetric appointments. FoCUS images were acquired by individuals without scanning or clinical experience using AI-guided image acquisition software (UltraSight) on a Philips Lumify device. Standard two-dimensional imaging views were attempted: parasternal long axis (PSLA), parasternal short axis mid-level (PSSA Mid), apical four chamber (A4C), three chamber (A3C), and two chamber (A2C). Two experienced cardiologists reviewed all images and graded diagnostic quality: poor, adequate, good, excellent. RESULTS: A total of 101 pregnant participants were enrolled; median age was 32 (interquartile range [IQR], 29, 35) years. The median gestational age was 23 (IQR, 16, 31) weeks; 16% first trimester, 45% second, and 39% third. The most feasible views were the PSLA and PSSA Mid, 98% and 97% with adequate or greater image quality, respectively. A3C and A2C were least feasible, acquired in 34% and 40% with adequate or greater image quality in 28% and 35%, respectively. Average scan time was 6 minutes, 46 seconds ± 0.2. The LV ejection fraction could be determined for the entire cohort and was normal (50–75%) for all. CONCLUSIONS/IMPLICATIONS: Implementation of AI-guided FoCUS in pregnant individuals is feasible, even in the absence of an experienced sonographer. This approach could allow for low-cost screening and early diagnosis of LV systolic dysfunction during pregnancy.

Abstract Rationale: MUC5B and MUC5AC are neighboring genes on chromosome 11p15 that encode the two predominant mucins secreted in the respiratory airways. Increased airway mucin concentrations and an imbalance between these two mucins drive COPD symptoms and the development of airflow obstruction or COPD, but the epigenomic regulation of this loci has not been characterized in the airways. Methods: We isolated DNA from bronchial airway brushings of 72 participants with &gt;20 pack-years smoking history from the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS). 36 participants had GOLD-based moderate-to-severe COPD (FEV1/FVC&lt;0.70, FEV1&lt;80%) and 36 were without or with mild COPD. We used the Illumina Infinium Methylation EPIC BeadChip Array to assess proportion of DNA methylation (β) spanning 689,937 CpG sites. We evaluated proportional DNA methylation (β) at 96 CpG loci within a 103kB region using matrixQTL for cis-expression quantitative trait methylation (eQTM: 10kB flanks relative to MUC5AC/MUC5B) integrating bulk RNA-seq data and mQTL models integrating gene sequencing data to identify DNA variation associated with proportion eQTM methylation. Models included age, sex, BMI, clinical site, current smoking vs past smoking, total pack-years, three ancestral components of ancestry, chipset, and position. Results: We identified a top eQTM, cg00524486, marginally associated with MUC5B expression (coefficient estimate=8.75, punadjusted=0.0014, pFDR=0.065, Figure 1B). This eQTM was associated with CT scan parametric response mapping-based functional small airways disease (PRM-fSAD, beta coefficient[β]=3.64, p=0.011). We tested for DNA variation associated with methylation of this top eQTM which identified two methylation quantitative trait loci (mQTL: rs885454 [β=0.044, minor allele frequency[MAF]=0.09, pFDR=0.01], rs868902 [β=0.020, MAF=0.43, pFDR=0.08, Figure 1A) associated with cg00524486 methylation, of which the more frequent mQTL, rs868902, was marginally associated with PRM-fSAD (p=0.07) in the larger SPIROMICS cohort with MUC5B DNA sequencing data. Conclusions: This preliminary multi-omic study of the lower airway epithelium demonstrates that the expression of MUC5B is epigenetically regulated by neighboring CpG probe methylation (eQTM) represented by DNA variation (mQTL). These studies require further confirmation in a larger dataset of airway samples and support a role for epigenetic variation as a biologic contributor and biomarker of early COPD pathogenesis.

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

Abstract Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease (SCD). Although SCD is associated with increased morbidity and shortened life span, SCT has a life span comparable with that of the general population. However, “sickle cell crisis” has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody. To appraise this practice, the American Society of Hematology convened an expert panel of hematologists and forensic pathologists to conduct a systematic review of the literature relating to the occurrence of sickle cell pain crises and exertion-related mortality in people with SCT. Multiple bibliographic databases were searched with controlled vocabulary and keywords related to “sickle cell trait,” “vaso-occlusive pain,” and “death,” yielding 18 of 1474 citations. Independent pairs of reviewers selected studies and extracted data. We found no studies comparing uncomplicated acute pain crises in individuals with SCT and SCD. Additionally, no study was identified to support the occurrence of acute vaso-occlusive pain crises in individuals with SCT. Furthermore, this systematic review did not identify any evidence to support an association between SCT and sudden unexplained death in the absence of exertion-related rhabdomyolysis. We conclude that there are no data to support the diagnosis of acute vaso-occlusive sickle cell crisis as a cause of death in SCT, nor does the available evidence support the use of SCT as a cause of exertion-related death without rhabdomyolysis.

Abstract Studies suggest varying atherosclerotic cardiovascular disease (ASCVD) prevalence across arterial beds. Factors such as smoking expedite ASCVD progression in the abdominal aorta, while diabetes accelerates plaque development in lower limb arteries, and hypertension plays a significant role in ASCVD development in the coronary and carotid arteries. Moreover, superficial femoral atherosclerosis advances slower compared with atherosclerosis in coronary and carotid arteries. Furthermore, femoral atherosclerosis exhibits higher levels of ossification and calcification, but lower cholesterol concentrations compared with atherosclerotic lesions of other vascular beds. Such disparities exemplify the diverse progression of ASCVD across arterial beds, pointing towards differential mechanistic pathways in each vascular bed. Hence, this review summarizes current literature on immune-inflammatory mechanisms in various arterial beds in ASCVD to advance our understanding of this disease in an aging society with increased need of vascular bed and patient-specific treatment options.

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. Design, Setting, and Participants Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. Main Outcomes and Measures Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. Results In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. Conclusions and Relevance Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.