Basmah Safdar

This study examines the association of post-COVID cardiac symptoms with microvascular dysfunction in patients lacking epicardial stenoses.

Significant knowledge gaps persist on cardiovascular conditions that predominantly, disproportionately, or only affect women. Historically overshadowed by the focus on obstructive coronary artery disease, conditions such as myocardial infarction with nonobstructive coronary arteries, spontaneous coronary artery dissection, and Takotsubo cardiomyopathy have only recently gained research attention, despite substantial prevalence and impact among women. Similarly, coronary microvascular dysfunction and vasospastic angina, long dismissed as symptoms of psychological origin, are now recognized as common and underdiagnosed mechanisms of chest pain. Disparities in research also extend to heart failure with preserved ejection fraction, disproportionately affecting more women, and with comparable impacts on prognosis and quality of life, yet poorly understood compared with heart failure with reduced ejection fraction. Moreover, female hypertension is underestimated, underdiagnosed, and understudied. Furthermore, pregnancy‐related cardiovascular complications, including preeclampsia and peripartum cardiomyopathy underscore the urgent need for research into sex‐specific mechanisms and targeted preventive and therapeutic strategies, particularly in resource‐limited settings. This review consolidates knowledge on cardiovascular conditions with pronounced sex differences, focusing on translational discoveries that direct current strategies, but most of all, emphasizing the need for future research to bridge the gap between mechanistic insights and clinical application. By identifying knowledge gaps, this article provides a road map for advancing sex‐specific understanding and care in cardiovascular disease, ensuring progress in diagnosis, treatment, and prevention. Bridging the sex gap in cardiac research and care requires a multidisciplinary, globally inclusive approach. By integrating knowledge of biological, clinical, and sociocultural perspectives, we can move toward equitable and effective cardiovascular health for all.

Background: The US 2024–2025 influenza season was characterized by sustained elevated activity from November 2024 to April 2025, with circulation of both influenza A(H1N1)pdm09 and A(H3N2), the latter of which included some antigenically drifted viruses. Methods: From 1 October 2024 to 30 April 2025, a multistate respiratory virus surveillance network enrolled adults hospitalized with acute respiratory illness in 26 US medical centers. Influenza vaccine effectiveness (VE) against influenza-associated hospitalization and severe in-hospital outcomes was estimated using a test-negative study. The odds of influenza vaccination among influenza-positive case patients and influenza-negative control patients were compared using multivariable logistic regression; VE was calculated as (1−adjusted odds ratio for vaccination) × 100, expressed as a percent. Results: The 2024–2025 seasonal influenza vaccine was effective against influenza-associated hospitalization (VE: 40% [95% confidence interval (CI): 32%–47%]), consistent across age group and influenza type/A subtype. Influenza vaccination also reduced the overall risk of all severe in-hospital outcomes evaluated, including standard oxygen therapy (VE: 41% [95% CI: 31%–50%]), noninvasive advanced respiratory support (VE: 38% [95% CI: 19%–52%]), invasive organ support (VE: 58% [95% CI: 44%–69%]), intensive care unit admission (VE: 58% [95% CI: 47%–67%]), and death (VE: 52% [95% CI: 18%–71%]) with effectiveness varying by influenza A subtype and age. Conclusions: Influenza vaccination reduced the risk of influenza-related hospitalization and severe in-hospital outcomes in adults during the severe 2024–2025 influenza season compared with those not vaccinated.

Background: Human metapneumovirus (HMPV) is a significant cause of acute respiratory illness in both children and adults, yet its genomic epidemiology remains understudied compared to other respiratory viruses. Methods: Hybrid capture and whole-genome sequencing were performed on 616 HMPV-positive specimens from 2 cohorts: the household-based HIVE study (2010–2022) in Michigan and the multicenter IVY network (2022–2025) of hospitalized adults. Consensus sequences were generated using IRMA, clades were annotated using Nextclade, and phylogenetic trees were constructed separately for HMPV-A and HMPV-B using IQ-TREE and TreeTime. Analysis of selection by dN/dS was performed using SLAC. Results: We obtained complete genomes from 325 specimens. Our analyses revealed the continued predominance of the A2.2.2 clade and little geographic structure in the United States. Genomic diversity was highest in the glycoprotein (G); we identified a shift from variants bearing the 180nt duplication to ones with a 111nt duplication. Phylogenetic analyses supported the duplication-deletion model for the origin of the duplications. The conserved fusion (F) protein showed limited antigenic variation and low rates of nonsynonymous substitutions Conclusions: These findings underscore the utility of enhanced genomic surveillance for understanding HMPV evolution and informing vaccine development. There was little genomic diversity in vaccine-targeted epitopes.

Objectives Hyperkalaemia (HK) is common in the emergency department (ED) and can cause life-threatening arrhythmias. Patiromer is a potassium binder whose role in acute HK management is uncertain; therefore, we investigated the efficacy and safety of patiromer as an adjunct to the standard of care treatment of HK in the ED. Design A prospective, randomised, double-blind, placebo-controlled study. Setting 16 ED sites across the USA. Participants Patients aged ≥18 years treated at a participating ED who were found to have serum potassium ≥5.8 mEq/L. Interventions Participants were randomised 1:1 to standard combination therapy (25 g intravenous dextrose, 5 units intravenous insulin and 10 mg albuterol) with either patiromer or placebo. The initial dose was given within 1 hour of the potassium result, and the second dose 24 hours later. Primary and secondary outcome measures The primary endpoint was net clinical benefit (NCB) at 6 hours, defined as the change in number of potassium-lowering interventions minus change in serum potassium. Adverse events (AEs) were also recorded. Results The study was terminated early and did not reach the prespecified sample size. Overall, 111 patients (53 patiromer and 58 placebo) were analysed. Mean (SD) age was 61.34 (15.21) years, 34% were female, 48% white and 22.5% received chronic haemodialysis. Mean baseline potassium was 6.5 mmol/L. NCB at 6 hours was similar between patiromer and placebo (−0.6 vs −0.4; p=0.44). Potassium levels at 2, 4 and 6 hours were similar between the groups (5.50 vs 5.70, 5.45 vs 5.65, 5.50 vs 5.60; patiromer and placebo (all p>0.05)). The number of interventions per patient was similar (p>0.05) between groups at each time point. The proportion of patients experiencing AEs was not significant between the patiromer and placebo groups (16.98% vs 32.76%; p=0.08). Conclusions No differences in efficacy were reported in this study, which was underpowered to detect statistical efficacy of patiromer over placebo. Trial registration number NCT04443608.

Human metapneumovirus (HMPV) is a significant cause of acute respiratory illness in both children and adults, yet its genomic epidemiology remains understudied compared to other respiratory viruses. Here, we report an expanded genomic surveillance of HMPV in the United States, utilizing 325 newly sequenced samples from two cohorts: the household-based HIVE study (2010–2022) in Michigan and the multicenter IVY network (2022–2025) of hospitalized adults. Our analyses revealed the continued predominance of the A2.2.2 clade and little geographic structure in the US. Genomic diversity is highest in the glycoprotein (G); we identified a shift from variants bearing the 180nt duplication to ones with a 111nt duplication. Phylogenetic analyses supported the duplication-deletion model for the origin of the duplications. The conserved fusion (F) protein shows limited antigenic variation and low rates of nonsynonymous substitutions, suggesting stability in epitopes targeted by vaccine candidates. These findings underscore the utility of enhanced genomic surveillance for understanding HMPV evolution and informing vaccine development. Summary: Genomic surveillance of HMPV in the United States over a 15 year period reveals extensive genetic diversity and more rapid evolution in the G protein compared to the F protein, which is targeted by vaccines under development.

Background: Adults hospitalized with acute respiratory infections, including respiratory syncytial virus (RSV), often have multiple underlying conditions. Few data are available on the combined effect of conditions on risk of severe outcomes from RSV disease. Methods: We enrolled adults hospitalized with RSV at 26 hospitals in 20 US states admitted January 2022–July 2024. Seventeen underlying conditions were selected after excluding those with rare prevalence (≤1%) or high pairwise correlation (≥0.7). We applied Bayesian profile regression to identify profiles of conditions associated with increased risk of RSV severe outcomes, stratifying among adults aged 18–59 and ≥60 years. Results: We analyzed data from 1111 adults hospitalized with RSV (median [IQR] age, 66 [53–75] years). Among 397 adults aged 18–59 years, 2 profiles were identified: (1) minimal prevalence with fewer underlying conditions and a posterior median intensive care unit (ICU) admission risk of 21% (95% credible interval, 16%–25%) and (2) cardiorenal/diabetes with frequent heart failure, chronic kidney disease, diabetes, and increased ICU admission risk (37% [27%–48%]). Among 714 adults aged 60 years and older, 4 profiles were identified: (1) minimal prevalence (ICU admission risk, 22% [18%–26%]), (2) cardiorenal/diabetes (27% [21%–34%]), (3) hematologic malignancy and transplant receipt (12% [6%–21%]), and (4) chronic pulmonary disease with home oxygen dependence (44% [25%–66%]). Conclusions: Distinct underlying condition profiles with varying risks of critical illness were observed among inpatients with RSV. These findings could support recognition of high-risk patients to inform RSV prevention strategies and suggest that the role of multimorbidity in severe RSV disease risk warrants further attention.

Background: The 2023–2024 influenza season included sustained elevated activity from December 2023 to February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season. Methods: During 1 September 2023 to 31 May 2024, a multistate sentinel surveillance network of 24 medical centers in 20 US states enrolled adults aged ≥18 years hospitalized with acute respiratory illness. Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccine effectiveness (VE) against influenza-associated hospitalization was calculated as (1 − adjusted odds ratio for vaccination) × 100%. Results: Among 7690 patients, including 1170 influenza cases (33% vaccinated) and 6520 controls, VE was 40% (95% confidence interval [CI], 31%–48%) with varying estimates by age: 18–49 years, 53% (95% CI, 34%–67%); 50–64 years, 47% (95% CI, 31%–60%); ≥ 65 years, 31% (95% CI, 16%–43%). Protection was similar among immunocompetent patients (40%; 95% CI, 30%–49%) and immunocompromised patients (32%; 95% CI, 7%–50%). VE was statistically significant against influenza B (67%; 95% CI, 35%–84%) and A(H1N1) (36%; 95% CI, 21%–48%) and crossed the null against A(H3N2) (19%; 95% CI, −8% to 39%). VE was higher for patients 14–60 days from vaccination (54%; 95% CI, 40%–65%) than >120 days (18%; 95% CI, −1% to 33%). Conclusions: During 2023–2024, influenza vaccination reduced the risk of influenza A(H1N1)- and influenza B-associated hospitalizations among adults; effectiveness was lower in patients vaccinated >120 days prior to illness onset compared with those vaccinated 14–60 days prior.