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Leading with Innovation: Maternal Health Transformation in New York City Health + Hospitals.

New York City's (NYC) maternal health crisis drew close attention in the late 2010s, driven by alarming data: Approximately 30 women died annually during childbirth in NYC, Black non-Hispanic women were 12 times more likely to die than white women, and more than 3,000 women experienced life-threatening birth complications each year. In response, NYC committed $12.8 million in July 2018 to reduce maternal mortality and eliminate racial disparities.NYC Health + Hospitals (H+H)-the nation's largest public health system, serving 1.1 million patients annually with roughly 15,000 births per year-became the primary vehicle for this initiative. With 80 percent of the system's deliveries covered by Medicaid and a patient population that is 51.2 percent Hispanic and 27.1 percent Black, H+H is uniquely positioned to lead the fight against maternal health inequity.Three flagship programs anchor H+H's response to the city's maternal mortality rate. The OB Simulation Program, launched in 2012 and expanded in 2018, was the first in the nation to use mannequins of color to train thousands of providers in obstetric emergencies. The Maternal Home Program, piloted at H+H's Kings County Hospital in 2019 and scaled system-wide by 2021, has served more than 10,341 patients, generating more than 33,000 referrals for social, behavioral health, and community resources. The Cardio-Obstetrics Program located at Kings County Hospital targets cardiovascular disease-the leading cause of maternal death among Black women-through screening, education, and community outreach. These programs are a health equity imperative, made more urgent by impending federal Medicaid cuts resulting from the H.R.1 One Big Beautiful Bill Act (passed on July 4, 2025).

Humans

Presence of globally prominent multidrug-resistant genotypes of Salmonella enterica serovar Typhi in New York State, 2016-2023.

The human-restricted enteric pathogen Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of the life-threatening typhoid fever. Although S. Typhi incidence is relatively low in the USA, routine surveillance of S. Typhi is critical to track the emergence and spread of high-risk lineages in non-endemic areas. In this study, we analysed 151 genomes of S. Typhi isolates from patients who were clinically confirmed with typhoid fever across New York State between 2016 and 2023. We used the GenoTyphi classification scheme and identified established multidrug-resistant and extensively drug-resistant lineages. We detected the presence of the globally widespread genotype 4.3.1 (haplotype 58) and its derivative 4.3.1.1.P1, which recently emerged in Pakistan, as well as the Bangladesh-restricted lineages 3.3.2.Bd1 and 3.3.2.Bd2 in our dataset. Ten mutations and 14 acquired genes associated with antimicrobial resistance (AMR) were present across the entire population, with 86.8% of the genomes possessing at least one of these AMR determinants. The gyrA S83F mutation conferring quinolone and triclosan resistance was the most frequently detected (94 genomes). Combinations of dfrA7+catA1 (resistance to trimethoprim and chloramphenicol, respectively) and sul2+aph(3″)-Ib+aph(6)-Id (resistance to sulphonamide and aminoglycosides, respectively) co-occurred frequently and were associated with IncQ and IncY plasmid replicons. Phylogenetic contextualization against a global dataset of 1,643 genomes from 20 countries across five continents, including other parts of the USA, from the same time period showed geographic intermingling, suggesting the spread of high-risk genotypes of international origins to New York State. Altogether, these findings reveal the presence of globally dominant resistant genotypes that are likely facilitated by human travel in New York State, where typhoid fever is not endemic. Long-term genomic surveillance is critical to AMR profiling, identifying genotypic shifts in regional S. Typhi populations, monitoring transmission routes and guiding effective public health interventions.

Salmonella typhi

Clustering and Source Association of Clinical and Nonclinical Listeria monocytogenes Isolates, New York, USA, 2000-20211.

We analyzed whole-genome sequencing data for 1,046 human clinical and 1,332 nonclinical Listeria monocytogenes isolates collected across New York, USA, during 2000-2021. Several hypervirulent clonal complexes (CCs) were significantly associated with clinical isolates, and several hypovirulent CCs were associated with nonclinical isolates. Specific CCs also showed association with specific food categories (e.g., processed meat); specific genetic markers (e.g., inlA premature stop codons) were also significantly associated with processed meat isolates. Analysis of clusters that contained food isolates, as well as subsequently identified clinical isolates, showed that time of isolation between food isolates and clinical isolates was significantly shorter for produce isolates than for isolates from meat, dairy, or fish. This finding suggests unique transmission pathways for produce, which might reflect short shelf life or limited L. monocytogenes persistence (e.g., in agricultural environments). This study highlights new opportunities for use of whole-genome sequencing to improve outbreak investigations and source attribution.

Listeria monocytogenes

Disparities in Outcomes for Patients With Inflammatory Bowel Disease at a Private vs Public Hospital in New York City.

BACKGROUND: In patients with inflammatory bowel disease (IBD), social determinants of health contribute to health inequalities. We aimed to compare patients with IBD treated at a private nonprofit vs public hospital in New York City. METHODS: We performed a retrospective study of adult patients with Crohn's disease or ulcerative colitis with established IBD care. Patient demographics, disease characteristics, healthcare utilization, treatment modalities, and clinical outcomes were collected. Using a series of linear mixed and logistic models, the differences between care at a private nonprofit vs public hospital were assessed while controlling for factors that differed between them. RESULTS: Our study included 418 patients with IBD, 209 from each hospital. Compared with public hospital patients, private hospital patients were more likely to be White, be non-Hispanic, and have private insurance (all P&#x2009;=&#x2009;.0005) and less likely to face housing instability (P&#x2009;<&#x2009;.0001), face unemployment (P&#x2009;=&#x2009;.0004), be current smokers (P&#x2009;=&#x2009;.03), or be foreign born (P&#x2009;<&#x2009;.0001). Patients at the private hospital were more likely to have multiple anti-tumor necrosis factor (P&#x2009;=&#x2009;.0001) and biologic use (P&#x2009;<&#x2009;.0001). Public hospital patients were less likely to be considered endoscopically adherent (odds ratio [OR], 0.377; P&#x2009;=&#x2009;.001) and more likely to visit the emergency department (OR, 5.01; P&#x2009;<&#x2009;.0001) and be hospitalized (OR, 1.92; P&#x2009;=&#x2009;.05). CONCLUSIONS: Our study is the first to identify significant differences in patient demographics, disease phenotype, treatments and clinical outcomes between patients treated for IBD at a private nonprofit vs public hospital. Our data suggest that social determinants of health drive disparities in the utilization of healthcare facilities.

Humans

Psychological impacts of APOE genotype disclosure among Latinos in New York City: a randomized controlled trial.

INTRODUCTION: Latinos face increased Alzheimer's disease (AD) risk but are underrepresented in studies of APOE genotype disclosure. We evaluated the psychological impacts of APOE disclosure in the Informaci&#xf3;n de la Enfermedad de Alzheimer para Latinos (IDEAL) study, a randomized controlled trial among Latinos in New York City. METHODS: Latino northern Manhattan residents without self-reported AD (mean age 52, 69% women, 49% college graduates) were randomized in the period August 2021 to July 2024 to receive AD risk estimates to age 85 incorporating APOE genotype, family history, and ethnicity (disclosure) or the same factors excluding APOE (non-disclosure). Bilingual genetic counselors delivered risk estimates to both groups, unmasked to randomization. Follow-up surveys were completed 6&#xa0;weeks, 9 months, and 15 months after risk delivery. Primary outcomes were impact of genetic testing in AD (IGT-AD) and Impact of Event Scale-Revised (IES-R). Secondary outcomes were changes from baseline in depression, anxiety, and perceived AD threat. Analyses used intention-to-treat with multiple imputation. RESULTS: Disclosure (N&#xa0;=&#xa0;194) and non-disclosure (N&#xa0;=&#xa0;180) groups did not differ on IGT-AD (mean disclosure-non-disclosure difference [MD] at 6 weeks: -1.5, p&#xa0;=&#xa0;0.14; 9 months: -1.2, p&#xa0;=&#xa0;0.35; 15 months: -2.0, p&#xa0;=&#xa0;0.07), IES-R (MD at 6 weeks: 0.00, p&#xa0;=&#xa0;0.98; 9 months: 0.01, p&#xa0;=&#xa0;0.84; 15 months: 0.03, p&#xa0;=&#xa0;0.64), or change in secondary outcomes. Occurrence of disclosure-related adverse events was similar in the disclosure (N&#xa0;=&#xa0;2) and non-disclosure (N&#xa0;=&#xa0;3) groups. DISCUSSION: In this Latino cohort, APOE disclosure did not have clinically significant adverse psychological effects, addressing an important evidence gap. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471779.

Aged

The impact of non-native trees on galling and herbivory in New York City across space and time.

Cities and suburbs frequently plant native and non-native trees as foundation species, with non-natives cultivated in these areas for centuries while remaining non-invasive. Although previous research has found that native trees often host more arthropods, studies have not simultaneously looked across space and time to determine the consistency of tree origin on urban arthropods. We combined varied methods across spatial and temporal scales in New York City to test if native tree leaves consistently have more insect and mite interactions than long-established non-native trees, predicting stronger effect sizes for specialists (galling arthropods) than generalists (herbivory). We examined (1) congeneric species pairs, controlled for growing conditions and stoichiometry in an arboretum, (2) diverse oaks at a botanical garden, (3) community science records across Brooklyn, and (4) herbarium specimens from 1883 through present across the city. Across spatiotemporal scales, we found consistent results. Specialist interactions were striking: contemporary native trees supported numerous galling species, while only one congeneric non-native species hosted any galls. For generalists, contemporary native trees had equivalent to slightly greater herbivory. Over the last century, herbarium records showed that herbivory increased on non-native trees to nearly the level of natives, whereas native trees increased in gall abundance while non-native trees remained rarely galled. Our results demonstrate the impact of tree origin on tree-arthropod interactions in a real-world urban setting, with far fewer galls even when non-native tree species have been cultivated locally for centuries. Our findings will help city planners and property owners confidently choose native trees to promote arthropod biodiversity.

Trees

Effects of Sacubitril/Valsartan on All-Cause Hospitalizations in Heart Failure: Post Hoc Analysis of the PARADIGM-HF and PARAGON-HF Randomized Clinical Trials.

IMPORTANCE: Sacubitril/valsartan is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalization for causes other than HF. OBJECTIVE: To assess the effects of sacubitril/valsartan on hospitalizations of any cause across the spectrum of left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: This post hoc, participant-level, pooled analysis of the PARADIGM-HF (in patients with an LVEF &#x2264;40%) and PARAGON-HF (in patients with an LVEF &#x2265;45%) randomized clinical trials was conducted from February 5, 2024, to April 5, 2024. Participants with chronic HF, New York Heart Association classes II through IV symptoms, and elevated natriuretic peptides were randomized to treatment with either sacubitril/valsartan or a renin-angiotensin system inhibitor (RASi)-enalapril in the PARADIGM-HF trial or valsartan in the PARAGON-HF trial. INTERVENTION: Sacubitril/valsartan vs RASi (enalapril or valsartan). MAIN OUTCOMES AND MEASURES: The effects of sacubitril/valsartan on time to first investigator-reported all-cause and cause-specific hospitalizations were examined using Cox proportional hazards models, stratified by geographic region and trial. Effect modification by LVEF as a continuous function was examined. RESULTS: Among 13&#x202f;194 participants in the PARADIGM-HF and PARAGON-HF trials, mean (SD) patient age was 67 (11) years, 8883 patients (67.3%) were male, and mean (SD) LVEF was 40% (15%). Sacubitril/valsartan significantly reduced the risk of all-cause hospitalization (ACH) compared with RASi over a median (IQR) follow-up period of 2.5 (1.8-3.1) years (hazard ratio [HR], 0.92; 95% CI, 0.88-0.97; P&#x2009;=&#x2009;.002). The incidence rate of first ACH was 25 (95% CI, 24-26) per 100 patient-years in the sacubitril/valsartan arm and 27 (95% CI, 26-28) per 100 patient-years in the RASi arm. The absolute risk reduction (ARR) was 2.1 per 100 patient-years, corresponding to a number needed to treat (NNT) of 48 patient-years of treatment exposure to prevent 1 ACH. Reductions in overall hospitalizations seemed primarily driven by lower rates of cardiac and pulmonary hospitalizations with sacubitril/valsartan. Patients in the 2 treatment arms had similar rates of composite noncardiac hospitalizations. Treatment heterogeneity on ACH by LVEF was observed (P for interaction&#x2009;=&#x2009;.03), with benefits most apparent in patients with an LVEF less than 60% (HR, 0.91; 95% CI, 0.86-0.96), but not in patients with an LVEF of 60% or more (HR, 0.97; 95% CI, 0.86-1.09). CONCLUSIONS AND RELEVANCE: In this post hoc pooled analysis of 13&#x202f;194 patients with chronic HF in the PARADIGM-HF and PARAGON-HF randomized clinical trials, sacubitril/valsartan significantly reduced hospitalization for any reason, with benefits most apparent in patients with an LVEF below normal. This reduction appeared to be principally driven by lower rates of cardiac and pulmonary hospitalizations. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifiers: NCT01035255 (PARADIGM-HF) and NCT01920711 (PARAGON-HF).

Humans

Heterogeneity of Apolipoprotein B Levels Among Hispanic or Latino Individuals Residing in the US.

IMPORTANCE: Apolipoprotein B (apoB) distribution and its implications as an atherosclerotic cardiovascular disease (ASCVD) risk-enhancing factor among individuals of diverse Hispanic or Latino backgrounds have not been described. OBJECTIVE: To describe the distribution of apoB in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort and to characterize associations of baseline sociodemographic and clinical variables with apoB and self-identified Hispanic or Latino background. DESIGN, SETTING, AND PARTICIPANTS: The HCHS/SOL was a prospective, population-based cohort study of diverse Hispanic or Latino adults living in the US who were recruited and screened between March 2008 and June 2011. Sampling weights were used to generate a population-based sample of Hispanic or Latino participants aged 18 to 74 years who resided in 4 US metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California). ApoB concentration was measured in participants from the HCHS/SOL, and apoB tertiles were compared across demographic groups, including self-identified Hispanic or Latino background. Median percentage continental genetic ancestry (West African, Amerindian, and European) was compared across apoB tertiles. EXPOSURE: ApoB measured in mg/dL from serum or plasma using an immunoturbidimetric assay. MAIN OUTCOMES AND MEASURES: ApoB tertiles were determined, and traditional lipids were evaluated across apoB tertiles. ApoB and traditional lipid measurements were assessed across ASCVD risk categories. Additionally, scatterplots were created to observe correlations between apoB and low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. RESULTS: Overall mean (SD) apoB concentration was 99.8 (0.4) mg/dL, with male participants displaying significantly higher mean levels than female participants (102.4 vs 97.4 mg/dL, respectively). Mean (SD) participant age was 41.1 (0.8) years, and 8376 participants (51.9%) were female. ApoB levels were higher among older age groups. There was significant heterogeneity in mean apoB concentrations across self-identified Hispanic or Latino background groups, ranging from 95.1 mg/dL in Dominican individuals to 104.8 mg/dL in Cuban individuals. The prevalence of elevated apoB (&#x2265;130 mg/dL) was greater across higher predicted ASCVD risk categories. Among participants with a 10-year predicted ASCVD risk of 7.5% or higher, 26.5% had an elevated apoB. Median West African ancestry was lower across higher tertiles of apoB. CONCLUSIONS AND RELEVANCE: In this cohort study among participants from the HCHS/SOL, elevated apoB was present in one-quarter of a diverse cohort study of Hispanic or Latino individuals who were at intermediate or high predicted ASCVD risk. Differences in apoB distribution among Hispanic or Latino individuals may have important implications for apoB's use in ASCVD risk assessment.

Adolescent

Finerenone in Heart Failure With Improved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: Patients with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) less than 40% who experience LVEF improvement to 40% or higher (HFimpEF) may still face residual risks. OBJECTIVE: To assess the clinical profiles, risk, and treatment response to finerenone in participants with HFimpEF. DESIGN, SETTING, AND PARTICIPANTS: A total of 6001 patients with HE, LVEF of 40% or higher, New York Heart Association class II to IV symptoms, and elevated natriuretic peptide levels, were enrolled between September 14, 2020, and January 10, 2023. Patients with a prior history of LVEF less than 40% were included. Data analysis was conducted between September 1 to December 10, 2024. INTERVENTION: Participants received finerenone (titrated to 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular (CV) death and total (first and recurrent) worsening HF events. RESULTS: Of the 6001 participants (mean [SD] age, 72 [9.7], years; 3269 male [55%]), 273 (5%) had a prior LVEF less than 40%. Among those with a prior LVEF of less than 40%, the median recorded prior LVEF was 35% [IQR, 30%-37%], with a median improvement of 12% [IQR, 8%-17%]. Over a median follow-up of 2.6 years, those with a history of LVEF of less than 40% experienced higher rates of the primary outcome of a composite of CV death and worsening of HF events (21.4 per 100 patient-years vs 16.0 per 100 patient-years) than did those whose LVEF was consistently 40% or higher. After adjustment for clinically relevant covariates; however, this rate ratio (RR) was not statistically different (absolute RR, 1.13; 95% CI, 0.85-1.49, P&#x2009;=&#x2009;.39). The treatment effect of finerenone on the primary outcome was consistent among those with a history of LVEF less than 40% and those with LVEF that was consistently 40% or higher (P for interaction&#x2009;=&#x2009;.36). Owing to higher baseline risk, the absolute risk reduction was greater among those with HFimpEF (9.2 vs 2.5 per 100 patient-years). Patients with HFimpEF tended to develop more hypotension with finerenone treatment, but otherwise, the safety profile of finerenone was similar in patients with and without previous LVEF less than 40%. CONCLUSIONS AND RELEVANCE: In this prespecified analysis of a randomized clinical trial, patients with HFimpEF remained at high risk of CV events, underscoring the need for continued management despite LVEF improvement. The treatment benefits of finerenone observed among the overall population of patients with HF with preserved EF were consistent among patients with HFimpEF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans

Cellular Adhesion Molecules and Adverse Outcomes in Chronic Heart Failure: Findings From the DAPA-HF Randomized Clinical Trial.

IMPORTANCE: Vascular cell adhesion molecule 1 (VCAM-1) and intracellular cell adhesion molecule 1 (ICAM-1) are responsible for immune cell-cell interactions. Systemic levels of VCAM-1 are associated with incident heart failure (HF). OBJECTIVES: To determine if VCAM-1 and ICAM-1 levels are associated with progression of established HF. DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the biomarker substudy of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) randomized clinical trial had VCAM-1 and ICAM-1 levels measured at baseline and 12 months. The DAPA-HF trial was conducted at 410 sites in 20 countries. Patients with HF and reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) class II to IV with elevated natriuretic peptides were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Data were analyzed from January 2023 to January 2025. INTERVENTIONS: Dapagliflozin, 10 mg, once daily vs placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of a worsening HF event or cardiovascular death. The associations between VCAM-1 and ICAM-1 levels at baseline and the primary outcome, its components, and all-cause death were analyzed using Cox proportional hazards regression models adjusted for known prognostic variables including estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT), as well as high-sensitivity C-reactive protein. RESULTS: A total of 3051 participants (mean [SD] age, 67.2 [10.5] years; 2386 male [78.2%]) were included in this study. Mean (SD) follow-up time was 17.6 (5.2) months. The median (IQR) baseline VCAM-1 level was 997 (816.7-1218.8) ng/mL. Compared with patients with lower concentrations of VCAM-1, those with higher concentrations of VCAM-1 were older (mean [SD] age T3 vs T1, 69.7&#x2009;[9.7] years vs 64.1&#x2009;[10.7] years; P&#x2009;<&#x2009;.001), in worse NYHA class (T3 vs T1, NYHA class III/IV 35.6% [362 of 1017] vs 26.5% [269 of 1017]; P&#x2009;<&#x2009;.001), and had higher NT-proBNP (median [IQR] T3 vs T1, 2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL) and hs-TnT (median [IQR] T3 vs T1, 24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L) concentrations, and lower eGFR (mean [SD] T3 vs T1, 58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2). Patients in tertile 3 of VCAM-1, compared with tertile 1, had the highest risk of each outcome (eg, adjusted hazard ratio [HR] for primary outcome 1.40; 95% CI, 1.11-1.77; P&#x2009;=&#x2009;.004). ICAM-1 level was not associated with an elevated risk of any outcome. The benefit of dapagliflozin vs placebo in reducing the risk of the primary outcome was consistent across VCAM-1 tertiles: HR, 0.76 (95% CI, 0.54-1.06), 0.82 (95% CI, 0.59-1.12), and 0.77 (95% CI, 0.61-0.98) for tertiles 1, 2 and 3, respectively (P for interaction&#x2009;=&#x2009;.93). There was no significant change in VCAM-1 level with dapagliflozin at 52 weeks. CONCLUSIONS AND RELEVANCE: Results of this substudy of the DAPA-HF randomized clinical trial demonstrate that higher VCAM-1 levels, possibly reflecting a distinct inflammatory/immune pathophysiological pathway in HFrEF, were associated with worse outcomes, even after adjustment for conventional prognostic variables. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124.

Aged

Finerenone According to Frailty in Heart Failure: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: Patients with frailty are often perceived to have a less favorable benefit-risk profile for novel therapies and therefore may be less likely to receive these. OBJECTIVE: To examine the efficacy and safety of finerenone, compared with placebo, according to frailty status in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF). DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of a phase 3 randomized clinical trial, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), conducted across 653 sites in 37 countries. Patients with HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of 40% or higher, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized between September 2020 and January 2023. Data analysis was conducted from October 1 to November 30, 2024. INTERVENTION: Addition of once-daily finerenone or placebo to usual therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death and total worsening HF events. Frailty was measured using the Rockwood cumulative deficit approach. RESULTS: Of the 6001 patients randomized in FINEARTS-HF, a frailty index (FI) was calculable in 5952 patients (mean [SD] age, 72.0 [9.6] years; 3241 [54.4%] male). In total, 1588 patients (26.7%) had class I frailty (FI &#x2264;0.210 [not frail]), 2141 (36.0%) had class II frailty (FI 0.211-0.310 [more frail]), and 2223 (37.3%) had class III frailty (FI &#x2265;0.311 [most frail]). Compared with patients with class I frailty, those with class II and III frailty had a higher risk of the primary outcome (unadjusted rate ratio [RR], 1.88 [95% CI, 1.54-2.28] for class II and 3.86 [95% CI, 3.22-4.64] for class III). The effect of finerenone on the primary outcome did not vary significantly by frailty class (class I: RR, 1.07 [95% CI, 0.77-1.49]; class II: RR, 0.66 [95% CI, 0.52-0.83]; class III: RR, 0.91 [95% CI, 0.76-1.07]; P for interaction&#x2009;=&#x2009;.77). Frailty class did not modify the effects of finerenone on the components of the primary outcome, all-cause death, or improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. The effects of finerenone, compared with placebo, on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class. CONCLUSIONS AND RELEVANCE: In FINEARTS-HF, finerenone reduced the risk of total worsening HF events and cardiovascular death, and it improved symptoms; these effects were not modified by frailty status. In addition, the effects of finerenone on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans

EMPEROR-Preserved Risk Model and Outcomes in the FINEARTS-HF Trial: A Prespecified Secondary Analysis of FINEARTS-HF.

IMPORTANCE: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved EF (HFpEF) show substantial heterogeneity in prognosis. OBJECTIVES: To evaluate the performance of biomarker-driven prognostic models derived from the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) Trial in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to examine whether baseline risk modified the therapeutic effect of finerenone. DESIGN, SETTING, AND PARTICIPANTS: This is a prespecified secondary analysis of the FINEARTS-HF trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with symptomatic HF and left ventricular EF (LVEF) of 40% or greater. Patients were randomized between September 2020 and January 2023, and data analysis for this study was conducted from September to October 2025. The median (IQR) follow-up period was 32 (23-37) months. INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: EMPEROR-Preserved risk scores for the outcomes of first HF hospitalization or cardiovascular death, cardiovascular death, and all-cause death were calculated in FINEARTS-HF using models incorporating N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, New York Heart Association functional class, history of chronic obstructive pulmonary disease and diabetes, insulin use, and-depending on outcome-age, hemoglobin and albumin levels, HF duration, time from prior HF hospitalization, and sodium-glucose transporter 2 inhibitor use. Estimated risks were compared with observed event rates, and model performance was assessed using Harrell C statistic. Treatment effects were evaluated across risk quintiles (Q1 to Q5) and across the continuous risk distribution. RESULTS: Among 6001 patients (mean [SD] age, 72.0 [9.6] years; 2732 [45.5%] women; 3003 randomized to finerenone and 2998 randomized to placebo), the EMPEROR-Preserved risk model estimated risk of outcomes, with Q5 vs Q1 hazard ratios (HRs) of 10.49 (95% CI, 8.14-13.52) for the composite of HF hospitalization or cardiovascular death and 13.47 (95% CI, 8.79-20.64) for cardiovascular death. The model demonstrated good discrimination. The treatment effect of finerenone was consistent across risk quintiles for first HF hospitalization or cardiovascular death (Q1: HR, 0.93 [95% CI, 0.58-1.49]; Q2: HR, 1.04 [95% CI, 0.76-1.43]; Q3: HR, 0.82 [95% CI, 0.62-1.07]; Q4: HR, 0.81 [95% CI, 0.65-1.01]; and Q5: HR, 0.88 [95% CI, 0.74-1.05]; P for interaction&#x2009;=&#x2009;.68) and remained uniform across the continuous risk spectrum. CONCLUSIONS AND RELEVANCE: The EMPEROR-Preserved risk models demonstrated good performance in FINEARTS-HF. Baseline risk did not modify the relative treatment effect of finerenone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets&#x2009;+&#x2009;vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans

Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (&#x3b2;: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (&#x3b2;: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (&#x3b2;: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (&#x3b2;: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (&#x3b2;: 0.020 for anticipated discrimination; &#x3b2;: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (&#x3b2;: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans

Targeting peptide antigens using a multiallelic MHC I-binding system.

Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions. We demonstrate rapid screening of TRACeR-I against a panel of disease-relevant HLAs with peptides derived from human viruses (human immunodeficiency virus, Epstein-Barr virus and severe acute respiratory syndrome coronavirus 2), and oncoproteins (Kirsten rat sarcoma virus, paired-like homeobox 2b and New York esophageal squamous cell carcinoma 1). TRACeR-based bispecific T cell engagers and chimeric antigen receptor T cells exhibit on-target killing of tumor cells with high efficacy in the low nanomolar range. Our platform empowers the development of broadly applicable MHC I-targeting molecules for research, diagnostic and therapeutic applications.

Humans

Emergence of Fusarium oxysporum f. sp. fragariae in the Eastern United States.

Historically, Fusarium oxysporum f. sp. fragariae (Fof), the causal agent of Fusarium wilt in strawberry, has been a major problem for strawberry production in California but has been largely absent in the rest of the United States. During the growing seasons of 2023 to 2025, independent detections of Fof were made on strawberry plants exhibiting symptoms of Fusarium wilt in the eastern U.S. states of Florida, North Carolina, New York, Connecticut, and Virginia. Sixteen isolates were obtained from symptomatic plants across this region, and a subset (n = 14) were confirmed to be Fof by pathogenicity testing, morphological characterization, PCR diagnostics, and whole-genome sequencing. Specifically, these tests demonstrated that all tested isolates were virulent on susceptible (fw1) strawberry cultivars but not on resistant (FW1) cultivars, classifying them as race 1. Although all isolates tested positive with the more recently developed Fof-specific PCR assay by Burkhardt et al. (2019), many (43.75%) failed detection with the commonly used Suga et al. (2013) assay. Comparative genomics revealed that these isolates represent at least three distinct phylogenetic clades (Y1, Y2, and the putative Y10), suggesting multiple independent introductions rather than a single dissemination event. The genetic diversity of the eastern U.S. Fof populations and their likely origin from nursery stock highlight the need for more robust diagnostics, certified clean planting stock, and region-specific resistance trials to manage Fusarium wilt beyond California.

Fusarium

CLINICAL AND COGNITIVE PHENOTYPING OF COPY NUMBER VARIANTS ASSOCIATED WITH NEURODEVELOPMENTAL DISORDERS FROM A MULTI-ANCESTRY BIOBANK.

Clinical biobanks with electronic health records (EHRs) linked to genotype data continue to expand yielding an opportunity to further characterize disease-relevant genomic risk factors, yet few recall-by-genotype studies from biobanks have been published to date. For example, copy number variants (CNVs) that significantly increase risk for multiple neurodevelopmental disorders (NDDs) and negatively affect neurocognition, may present in up to 2% of population cohorts, with public health implications for ascertaining NDD CNV carriers. From BioMe, a multi-ancestry biobank derived from the Mount Sinai healthcare system (New York, NY), 892 adult participants were recontacted for deep phenotyping, including 335 NDD CNV carriers as well as comparators, 217 individuals with schizophrenia and 340 controls. Clinical and cognitive assessments were administered to each participant. There was no disclosure of genetic information. Eight percent of recontacted biobank participants completed the study (30 NDD CNV carriers across 15 unique loci, 20 schizophrenia and 23 controls). The study sample had a mean age of 48.8 (10.2) years, was 66% female and of diverse ancestry, 36% African, 34% Hispanic, and 26% European. Overall, 70% of 30 NDD-CNV carriers harbored at least one neuropsychiatric or developmental phenotype, including 40% with mood or anxiety disorders. Further, 22 NDD CNV carriers were significantly impaired compared to controls on digit span backwards (Beta=-1.76, FDR=0.04) and digit span sequencing (Beta=-2.01, FDR=0.04), but higher performing than schizophrenia on verbal learning (Beta=4.5, FDR=0.05). Thirty NDD CNV carriers were successfully recruited from a multi-ancestry biobank, as well as healthy controls and low-functioning individuals with schizophrenia. Deep phenotyping corroborated past reports, while also identifying discordance with EHRs. Future recall-by-genotype studies may further benchmark the study design and elucidate feasibility.

Biobank

The Genomics and Genetics of Rare Disease Illuminate Human Biology.

Richard Gibbs interviews James (Jim) Lupski about his training in New York and work in Houston to elucidate the role of complex genomic rearrangements in human genetic diseases. The challenges and excitement of developing human personalized genomics and the advantages of clinical translation of genome methods for both patients and researchers are discussed.

Humans