Citations

Background Patients with single-ventricle physiology are often palliated with the Fontan operation, which may involve the creation of a fenestration. We aimed to evaluate differences in cardiopulmonary exercise test (CPET) performance between patients with fenestrated and non-fenestrated Fontan circulation. Methods Patients with a Fontan circulation referred to CPET between 2006 and 2024 were included and were categorised based on their fenestration status at the time of CPET. Logistic regression analyses were performed to assess the impact of fenestration on peak oxygen consumption (VO 2 ), and Cox proportional hazard to evaluate the impact of fenestration on cardiovascular outcomes (death, heart transplant and Fontan-related hospitalisation). Results Of the 184 patients, 141 were classified as non-fenestrated and 43 as fenestrated. The minute ventilation-carbon dioxide production (V E /VCO 2 slope) was higher in the fenestrated (36.9±7.9) versus (33.2±6.2; p=0.009) in the non-fenestrated group. There was no significant difference in predicted VO 2 between groups (non-fenestrated 51.9%±14.4 vs 51.3%±15.6; p=0.7). Resting oxygen saturation was higher in the non-fenestrated group (93%±4.7 compared with fenestrated group 90.1%±5; p<0.001). Fontan fenestration was not significantly associated with the composite outcome; older patient age at the time of the CPET, cirrhosis and ventricular ejection fraction <40% were significantly associated with higher risk, while higher resting systolic blood pressure, left ventricular morphology and higher predicted peak VO 2 were protective. Conclusions The increased hypoxia and reduced ventilatory efficiency associated with Fontan fenestration offset any potential benefits, resulting in similar exercise performance between the groups. Fontan fenestration was not significantly associated with cardiovascular outcomes.

ABSTRACT Alzheimer's disease (AD), a leading cause of dementia in the elderly, is traditionally characterized by neurodegeneration driven by amyloid‐beta plaques and tau tangles. However, emerging evidence reveals that AD's impact extends beyond the brain, significantly affecting skeletal health. This review integrates clinical and transgenic mouse model data to elucidate the mechanistic interplay between AD pathology and bone metabolism. AD patients exhibit increased risk for hip fractures and low bone mineral density (BMD), independent of cognitive impairment severity. We found altered calcium and alkaline phosphate levels in the blood of patients with mild cognitive impairment and AD, as assessed from the Alzheimer's Disease Neuroimaging Initiative data. Convergent risk factors—age, sex, APOE4 genotype, smoking, and vitamin D deficiency—contribute to both neurodegeneration and bone fragility. Key molecular pathways, such as Wnt/β‐catenin signaling and TREM2‐mediated osteoclast regulation, underscore shared mechanisms driving disease pathology in both systems. Mouse models of AD consistently demonstrate disrupted bone remodeling, impaired osteoblast function, and heightened osteoclast activity. Therapeutic strategies targeting overlapping pathways, including lithium, anti‐FSH antibodies, and NF‐κB inhibitors, show promise in mitigating both cognitive decline and bone loss. Collectively, these insights advocate for a more integrated view of AD that includes skeletal comorbidities, potentially guiding the development of dual‐purpose interventions.

ABSTRACT Background Intracranial and extracranial hemorrhages are significant causes of morbidity and mortality. Emergency medicine pharmacists (EMPs) can play a crucial role in anticoagulation reversal by identifying patients on anticoagulation, selecting the optimal anticoagulation reversal agent, and ensuring adequate dosing and prompt administration. The goal of this systematic review and meta‐analysis was to determine the impact EMPs have on time to anticoagulation reversal and patient outcomes in anticoagulation‐associated hemorrhages. Methods A medical librarian performed a literature search in EBSCO CINAHL, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection from inception to January 2025 for all types of oral anticoagulants and for life‐threatening bleeding that required emergent reversal. Newcastle‐Ottawa was used to assess the risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the level of certainty of the evidence. Random effects models estimating mean differences and 95% confidence intervals are reported. Results There were 2445 titles and abstracts screened, with 44 undergoing full‐text evaluation. Six observational studies including 219 patients who received an anticoagulation reversal agent with the presence of an EMP and 198 patients who received a reversal agent without an EMP were included. Time from emergency department (ED) presentation to anticoagulation reversal agent administration (75.60 min, 95% confidence interval [CI]: −101.7 to −49.5) and time from medication order to administration were faster with an EMP (−18.7 min, 95% CI: −23.5 to −14.0). There was no difference in short‐term mortality. The included studies had a high risk of bias and were deemed very low quality of evidence. Conclusion EMP involvement in patient care during anticoagulation reversal of acute hemorrhages improved time to anticoagulation reversal agent administration. Larger scale, higher‐quality studies are necessary to assess the value of EMPs in improving patient‐centered outcomes.

ABSTRACT The American College of Clinical Pharmacy (ACCP) first described the role and history of the pharmacist as principal investigator (PI) in 2000. An update was published in 2010, citing evidence from NIH and the ClinicalTrials.gov registry that showed an increase in the number of individuals with a Pharm.D. degree engaging in pharmacist‐directed research. The 2025 ACCP Publications Committee was charged with providing an update to the 2010 paper. Key findings include a substantial increase in the total amount of federal funding awarded to schools of pharmacy (SoP) between 2011 and 2023, a modest increase in the number of pharmacists receiving federal grants when comparing 2010 with 2024, and evidence of pharmacist leadership and engagement in Clinical and Translational Science Award networks and service on national grant review panels. It remains challenging, however, to ascertain accurate and reliable data on pharmacists serving in PI roles because of the limitations of currently available data sources. This is especially true for pharmacist PIs who receive non‐federal funding. Future opportunities include a continued emphasis on training programs to prepare pharmacists for PI roles, greater institutional support (e.g., research infrastructure, mentoring programs) for pharmacists serving in PI roles, better promotion of research career tracks to Pharm.D. students and trainees, enhanced efforts at SoP to pursue institutional training grants, and more collaborative efforts across professional organizations to advocate for pharmacist‐scientists. An urgent call to action is necessary to ensure the future growth and success of pharmacist‐directed research.

Abstract Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is a heterogeneous clinical syndrome associated with substantial morbidity and mortality. We developed a machine learning-based mortality model to identify features and patient subgroups associated with the largest change in mortality risk when evaluating treatment with Impella devices or intra-aortic Balloon Pump (IABP). Our cohort comprised 369 sites and 15,796 patient visits to the cardiac catheterization laboratory from the National Cardiovascular Data Registry. The estimated population mean excess mortality effect of treatment with Impella devices vs IABP was 10.4 ± 0.8%. However, we identified clinical subgroups of 282 patients for whom a decreased risk of mortality was associated with use of Impella as compared with IABP. Those patients were on average younger, presented with higher systolic blood pressure, higher rate of salvage percutaneous coronary intervention, higher initial creatinine, and lower hemoglobin. While Impella devices were associated with higher mortality risk overall, certain clinical profiles were associated with lower risk, illustrating heterogeneity of treatment effects.

Background Individuals with neurologic impairment, such as brain injury, are more likely to have autonomic dysfunction, including POTS, but often experience a lack of treatment options and access to quality care. Objective Examine the feasibility and outcomes of a group-based multimodal rehabilitation training program. Methods Nineteen females, ages 18–53 (M = 28.6) completed the outpatient training program. The intervention included eight 50-min weekly sessions using an interdisciplinary, multimodal approach, including education, movement, and mindful self-compassion. Participants completed demographic and medical history and assessment for baseline orthostatic intolerance. At pre-training, post-training, and follow-up, participants completed the Modified Fatigue Impact Scale (MFIS), Lower Extremity Functional Scale (LEFS), Rand 36-Item Health Survey 1.0 (RAND-36), Trail Making Test (A and B) (TMT-A, TMT-B), 10-Meter Walk Test (10MWT), and grip strength testing. Results At baseline, participants were significantly below norms in daily function (p < 0.001), grip strength (p ≤ 0.001) gait speed (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Between pre-training and follow-up, participants showed significant improvement across function in daily life tasks (p < 0.01); grip strength in the dominant (p < 0.01) and non-dominant (p < 0.01) hands; gait speed (p < 0.05); levels of fatigue (p < 0.05); cognitive performance (p < 0.05); and quality of life (p < 0.05). Conclusion Individuals with POTS face functional challenges that can be significantly and objectively improved through multimodal rehabilitation. There is a need for provider education and further research to optimize care and quality of life for individuals with POTS.

Context.— Optical genome mapping (OGM) represents a promising cytogenomic technology that detects structural variants, including fusions, rearrangements, copy number variants, and loss of heterozygosity, in a single assay. Unlike karyotyping, fluorescence in situ hybridization, or chromosomal microarray, OGM leverages long-molecule imaging to map the whole genome with high resolution. This positions OGM as a novel tool for constitutional and somatic/cancer genomics. However, its current and planned utilization in clinical and research settings remains unknown, necessitating further investigation. Objective.— To investigate the current utilization of OGM in clinical and research laboratories, assess its applications, and evaluate future utilization strategies. Design.— In 2024, a supplemental questionnaire was incorporated into 6 College of American Pathologists proficiency testing programs to evaluate OGM’s utilization. Results.— Of 921 returned questionnaires, 712 were analyzed after duplicates were removed. Sixty-seven (9.4%) currently offered OGM testing: 5.2% (37) for research only, 1.8% (13) for only clinical use, and 2.4% (17) for both. Future adoption plans showed 7.6% (53 of 700 laboratories) and 7.9% (55 of 700 laboratories) aiming to implement OGM clinically within 12 and 24 months, respectively. The most common applications included hematologic malignancies and constitutional/germline postnatal disorders, followed by prenatal testing. International laboratories demonstrated statistically higher utilization rates than domestic laboratories ( P = .001). Conclusions.— This first survey on OGM clinical utilization reveals its status as a niche technology, with 67 laboratories currently using it. Its primary clinical applications are in constitutional/germline analysis and hematologic malignancies. Although international laboratories led in 2024, 108 laboratories (domestic and international) plan clinical adoption within 24 months, signaling OGM’s potential for broader integration.

Abstract Background Valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist, presenting complex clinical challenges despite advances in diagnostics and therapeutics. Together, they contribute substantially to cardiovascular mortality. However, epidemiological patterns vary across demographics and regions Methods Mortality data from 1999–2023 were obtained from the CDC WONDER database. Deaths attributed to VHD (ICD-10: I30-I52) with co-diagnosed AF (ICD-10: I48) among adults ≥ 45 were included. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated. Autoregressive integrated moving average (ARIMA) models were used to project mortality trends through 2035. Results From 1999 to 2023, there were 172,511 VHD and Afib-related deaths in adults ≥ 45. AAMRs increased until 2021, followed by a slight decline to 8.86. The overall AAPC for VHD with AF was 4.01%. AAMR increase was consistent across all age groups, highest seen in 65 + individuals. Males had consistently higher AAMRs than females. AAPC for males was 4.44% and for females 3.52%. Non- Hispanic White had the highest AAMR (10.56 in 2021), followed by Hispanics (4.19). Regionally, the West had the highest AAMR (11.27), followed by Mid-West (9.94). Non-metropolitan areas had higher AAMR 8.96 compared to metropolitan areas (AAMR: 7.59). Most VHD related deaths were reported in inpatient settings (n = 396,451) and 12% involved co-diagnosed AF. Conclusion Mortality associated with VHD and AF in the U.S population aged ≥ 45 has shown a concerning increase. Predictive models indicate this trend may persist, highlighting the need for early detection, equitable healthcare access and public health interventions tailored to high-risk populations.

The 2 main subgroups of autoimmune myasthenia gravis, a neuromuscular junction disorder associated with muscle weakness, are early- and late-onset forms, defined by onset before or after 50 years of age. Both carry acetylcholine-receptor autoantibodies but differ in sex ratios, genetics, and occurrence of disease-specific thymus inflammation. To distinguish the 2 forms by cellular immune phenotyping, we applied multimodal techniques, including deep spectral cytometric phenotyping and single-cell sequencing. Analysis of 2 independent cohorts identified immunological differences driven by 3 main lymphocyte populations. Lower frequencies of mucosa-associated invariant T cells and naive CD8 + T cells were observed in late-onset myasthenia, suggesting enhanced immune senescence. A highly differentiated, canonical NK cell population was reduced in early-onset myasthenia and negatively correlated with the degree of thymic hyperplasia. Using only the frequency of these 3 populations, correct myasthenia subgroup assignment could be predicted with 90% accuracy. These distinct immunocellular endophenotypes for early- and late-onset disease suggest differences in immunopathogenic processes. Along with demographic factors and other disease subgroup–specific features, the frequency of the identified cell subpopulations may improve clinical classification.