Citations

Abstract Background Red cell alloimmunization complicates sickle cell disease (SCD) management despite current widespread prophylactic Rh/K matching in the United States (US). Regional antibody patterns remain poorly characterized. Study Design and Methods We conducted a retrospective analysis of 2965 SCD patients from 9 US sites (2010–2022). All hospitals prophylactically match for Rh and K antigens. Each site collected demographics, antigen status, antibody histories, and antibody screen results from their laboratory information system. Results Overall antibody prevalence was 29.7% with dramatic institutional variation (17.9%–56.0%). Alloantibody prevalence was 27.5%. Most autoantibody‐positive patients (74.23%) also had alloantibodies, identifying a high‐risk population. A third of patients with positive antibody histories had negative screens. Pediatric patients showed markedly different antibody profiles than adults. Hospitals’ antibody patterns clustered by patient age rather than geography. Rh and K antibodies were the most common and also most likely to co‐occur, followed by S, Fya, and Jkb antibodies. Antibodies against Jsa (1.82%), V (1.75%), and Kpa (1.69%) were more prevalent than anti‐Jka (1.28%). Despite regional antibody variation, antigen frequencies remained overall consistent. In antigen–antibody pairwise comparisons, 3.15% were antigen‐negative and antibody‐positive reflecting alloimmunization; 0.47% were both antibody‐ and antigen‐positive, suggesting partial/variant antigens. Discussion Substantial institutional variation in antibody prevalence suggests need for site‐specific approaches to testing and prophylactic matching. High co‐occurrence of auto‐ and alloantibodies, antibody immunogenicity patterns, and antigen–antibody discordances support the need for further research and consideration of refined testing and/or matching strategies beyond the current Rh and K standard.

Purpose: To determine the incidence of secondary IOL implantation in a cohort of children randomized to aphakia after unilateral congenital cataract surgery. Setting: Twelve clinical sites in the United States. Design: Randomized clinical trial. Data regarding secondary IOL implantation was collected retrospectively when patients were age 10½ years. Methods: We calculated the cumulative incidence of secondary IOL implantation in participants in the Infant Aphakia Treatment Study (IATS) who were randomized to aphakia to age 4½ years and were followed at age 10½ years. Results: Twenty-two (43%, 95% CI 29%,58%) of the 51 participants left aphakic to age 4½ years who had better than light perception vision at age 4½ years received a secondary IOL by age 10½. More than half (59%) of these were implanted by age 6 (Median 64.5 months, IQR 60,80). Secondary IOLs were implanted in children with good visual acuity (<20/40), as well as those with poor visual outcomes (>20/200) (39% and 44% respectively). Children who received a secondary IOL did not report less contact lens wear than those remaining aphakic (average of 94% of waking hours versus 90%, respectively). However, the proportion of children receiving a secondary IOL varied substantially by study center. Conclusions: Many children with unilateral congenital cataract who are initially left aphakic remain aphakic throughout the elementary school years. Practice patterns and family preference seem to be important drivers of the decision to implant a secondary IOL in these children.

BACKGROUND: Burnout remains prevalent among anesthesiology residents. Contributing workplace factors include limited control over scheduling, unpredictable hours, critical patient care needs, and other residency challenges. The Family Anesthesia Experience (FAX) is a program designed to educate residents and their support persons on wellness and residency demands. The focus of this multisite study was to evaluate the impact of FAX on first year clinical anesthesiology (CA1, ie, PGY2s) residents’ wellness. METHODS: This was a prospective evaluation study involving 15 US anesthesiology residency programs, 13 of which completed FAX. CA1 wellness was evaluated through surveys assessing perceived stress as the primary outcome, with exploratory outcomes including burnout, depression, psychological wellness, and social support. Additionally, changes in support persons’ understanding and knowledge of residency demands were tracked over time. The study included a historical control group of 302 CA1s (2019-2021) who did not participate in FAX, and an intervention group of 88 CA1s that participated in FAX (2021-2022). Statistical analyses compared changes in metrics between groups using linear mixed models and generalized linear models. RESULTS: Significant reductions in perceived stress were observed in the intervention group at 6 months post-FAX (mean change = –2.14, 95% CI, –3.95 to –0.34; P = .021, effect size = 0.58) relative to the control group, but there was no sustained difference at 12 months. Compared to the control support persons, intervention support persons reported increased understanding of residency demands, with significant improvements at 6 (mean change = 2.80, 95% CI, 1.12–4.48; P = .001, effect size = 0.77) and 12 (mean change = 2.59, 95% CI, 0.12–5.05; P = .039, effect size = 0.71) months. Improvement in support persons’ understanding did not predict changes in CA1 wellness outcomes. First generation physician residents reported lower family support at baseline but showed significant improvements in family support at 6 months (mean change = 3.05 points; 95% CI, 0.25–5.84; P = .033; effect size = 1.23) compared to their non first generation peers. CONCLUSIONS: FAX participation was associated with reduced perceived stress in residents up to 6 months post-intervention. First generation physicians experienced greater improvements in perceived family support compared to their non first generation peers. Our findings suggest that resident wellness may be enhanced by engaging both residents and their support persons in an educational wellness program that outlines the professional expectations and demands of anesthesiology residency training.

Effective translation relies on high performance teams integrating diverse disciplines to bring new drugs, medical devices, diagnostics or behavioral interventions into improved health. Despite substantial advancements informed by the Science of Team Science (SciTS), challenges remain in effective translational team (TT) operations, while limited institutional, scholarly, and practitioner legitimacy of team science expertise constrains efforts to address them. Here, we describe an essential member of the TT, the Team Science Professional (TSP). Serving as a team educator and facilitator of team interventions, the TSP plays a pivotal role in facilitating effective team performance. Current challenges faced by this nascent profession are defining career pathways and establishing competencies needed for expert performance. To address these challenges, the authors, representing a spectrum of academic universities organized as a special interest group (SIG) of the Association of Clinical and Translational Science (ACTS), propose a suite of individualized, standardized and pathway-selective micro-credentials (digital badges). Digital badges in “Team Science (TS) Fundamentals,” “TS Practitioner,” “TT Trainer” and “TT Intervention Expert” are described, along with preliminary feasibility and usability evaluations of the submission process. These stackable credentials provide a customizable, portable recognition of skills and help advance career pathways for TSPs. In so doing, the Digital Badge Initiative will enhance the capacity of translational science “Hubs” such as those supported by Clinical and Translational Science Awards to conduct effective and rigorous translation. Moving forward, the ACTS TSP SIG will be examining the impact of digital badging on standardization and its effect on career recognition and retention.

ABSTRACT Intrinsic Acinetobacter -derived cephalosporinases (ADCs) in Acinetobacter baumannii are AmpC-type β-lactamases that confer resistance to β-lactam agents, typically through insertion sequence (IS) element-driven overexpression. However, the contribution of ADCs to resistance against advanced β-lactam agents has not been systematically investigated. Given the increasing clinical use of these agents, including cefiderocol, we analyzed the diversity and function of ADC variants in a global collection of carbapenem-resistant A. baumannii (CRAb) isolates. We identified 52 distinct ADC variants in a collection of 428 CRAb clinical isolates from the United States. Among these, variants carrying both a valine substitution at position 292 in the R2 loop and an alanine duplication (ADUP) in the Ω loop consistently conferred stable resistance to cefiderocol. Biochemical and crystallographic analyses demonstrated that ADC-227, which harbors a V292W substitution with an ADUP at position 218a in the Ω loop, exhibits enhanced catalytic efficiencies for ceftazidime and cefiderocol and moderately reduced inhibition by avibactam, leading to resistance not only to cefiderocol but also to ceftazidime–avibactam. Structural studies revealed conformational flexibility of the R2 loop, allowing dynamic accommodation of substrates. Collectively, the findings identify Val292, in combination with an ADUP in the Ω loop, as a mutational “hot spot” for ADCs evolution that may undermine the efficacy of newer β-lactams, including cefiderocol. These results underscore the need for ongoing molecular surveillance of A. baumannii isolates to detect and track the emergence of such variants in clinical settings. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii (CRAb) has been designated as a critical priority pathogen by the World Health Organization (WHO). Cefiderocol has been introduced as a novel therapy against CRAb; however, recent clinical data highlight concerning treatment failures and excess mortality. Understanding resistance mechanisms is therefore essential to preserve the clinical utility of this agent. This study addresses a critical knowledge gap by investigating the role of intrinsic Acinetobacter -derived cephalosporinases (ADCs), which are ubiquitous in A. baumannii and diverse in sequence. By defining specific mutational patterns that endanger cefiderocol activity, this work highlights how chromosomally encoded enzymes can evolve to erode the effectiveness of newer β-lactams such as cefiderocol. These insights underscore the importance of integrating molecular surveillance into clinical practice and antimicrobial stewardship to ensure timely detection of emerging resistance in clinical A. baumannii isolates, ultimately informing treatment strategies and guiding future drug development.

Abstract Purpose: This multicenter, multi-surgeon retrospective study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leak following endonasal resection of craniopharyngioma, while evaluating the "perception gap" through a surgeon survey. Methods: A retrospective review was conducted on 416 patients who underwent endoscopic transsphenoidal surgery (ETS) for craniopharyngioma from 20 institutions. Factors were compared between patients with and without postoperative CSF leak, and between Early (2007-2015) and Late (2016-2025) Epochs. Complementing the clinical data, a survey of 19 neurosurgeons captured expert perspectives on risk stratification and management strategies. Results: Overall postoperative CSF leak rate was 13.5% (56/416 patients). Univariate analysis identified predominantly cystic tumors (34% vs. 21%, p = 0.034)and intraoperative lumbar drain (LD) use ( p < 0.028) as associated with postoperative CSF leak. BMI ( p = 0.587), prior surgery ( p = 0.576), and tumor size ( p = 0.363) were not significant. In the multivariable analysis, LD use was associated with a higher postoperative CSF leak rate (OR 1.91, 95% CI 1.06–3.46; p = 0.030). Between Epochs, nasoseptal flap (NSF) utilization increased from 70.7% to 87.6% ( p <0.001). NSF was protective (OR 0.28, 95% CI 0.07–0.92; p = 0.037) in the Early Epoch; no factors were significant in the Late Epoch. The surgeons’ survey identified prior surgery and intraoperative high flow leaks as primary risks; however, their LD protocols diverged from clinical data. Conclusion: Despite increased use of NSF, CSF leak persists. The study highlights a significant divergence between expert perception and clinical data regarding lumbar drains.

Background Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID‐19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. Methods Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient‐Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12‐month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). Results Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65–85 years, 52.9% men, 66.2% non‐Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65–85 years, 47.1% men, 62.7% non‐Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, −2.6 percentage points [95% CI, −5.0 to −0.2]). Non‐Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. Conclusions BP control was disrupted during the COVID‐19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.

ABSTRACT Importance Rural-urban disparities in chronic disease prevalence are well established; however, the extent to which individual-level socioeconomic status (SES) contributes to these disparities remains unclear. Objective To examine the associations of rurality and SES with the prevalence of five most burdensome chronic diseases among adults. Design We conducted a retrospective cross-sectional study of adults across 27 Upper Midwest counties using the Expanded Rochester Epidemiology Project (E-REP) medical record data linkage system to evaluate associations between rurality, SES and chronic disease prevalence. Prevalence of clinically diagnosed asthma, diabetes, hypertension, coronary heart disease, and mood disorders was identified from International Classification of Diseases ICD9/10 codes over a five-year period (2014-2019). Setting Population based Participants Adults over 18 years residing in the 27 E-REP counties, excluding those missing rural-urban residence status. Exposure HOUSES index, an individual-level measure of SES, served as the primary measure, while rurality based on Rural Urban Commuting Area (RUCA) codes 4-10 was the secondary measure. Main Outcome Prevalence of the five clinically diagnosed chronic diseases was identified using ICD9/10 codes from 2014–2019. Mixed effect logistic regression models were used and adjusted for demographics and general medical examination receipt, to assess rural-urban and SES differences for prevalence of each chronic disease. Results Among 455,802 adults with available HOUSES index, 42.8% lived in rural areas, 53.8% were female and 87.4% were non-Hispanic White. In the unadjusted analysis, rural and urban populations showed comparable asthma and CHD prevalence, while mood disorders, hypertension, and diabetes were more common in urban areas. After adjusting for demographic factors and healthcare utilization, rural-urban differences were no longer statistically significant, whereas SES remained strongly associated with all diseases in a dose response manner (e.g., adjusted Odds Ratio for hypertension (ref: HOUSES index Q4): 1.14, 1.27, and 1.42 for HOUSES index Q3, Q2, and Q1, respectively). Conclusions and Relevance Individual-level SES measured by the HOUSES index, was more strongly associated with chronic disease prevalence than rurality, supporting its integration into population health assessment and risk stratification.