Faculty Bibliography

BACKGROUND/UNASSIGNED:Effective management of alcohol withdrawal syndrome during hospitalization is paramount to patient safety and quality care. NYC Health + Hospitals initiated a quality improvement project to pilot an electronic health record (EHR) integrated, nurse-driven CIWA-Ar symptom-triggered protocol, including recommendations for medications for alcohol use disorder (MAUD), in medical and surgical units at 3 public hospitals. OBJECTIVE/UNASSIGNED:To describe implementation processes and to report related implementation outcomes (appropriateness, feasibility, and adoption) of the updated CIWA-Ar protocol in a safety net hospital setting. METHODS/UNASSIGNED:NYC Health + Hospitals implemented a standardized CIWA-Ar symptom-triggered, nurse-driven EHR protocol on March 15, 2022. The protocol included order sets, practice advisories, task lists, and reminders for assessments and orders. We measured nursing perspectives on feasibility and appropriateness at 6 months via a survey. We measured provider adoption as the proportion of admissions with a CIWA-Ar protocol ordered among admissions that triggered a recommendation, and MAUD use as the proportion of admissions with a MAUD order during hospitalization among all patients with a protocol ordered. RESULTS/UNASSIGNED:= .249). CONCLUSIONS/UNASSIGNED:The CIWA-Ar protocol was appropriate, feasible, and adopted at NYC public hospitals. Quality improvements to ensure protocol fidelity with benzodiazepine dosing and MAUD prescribing are needed.

BACKGROUND:Coronary microvascular dysfunction (CMD) is present in approximately 40% of patients with ischemia with no obstructive coronary arteries (INOCA) and has been associated with inflammation. We investigated associations between measures of inflammation of the coronary perivascular adipose tissue assessed by coronary computed tomography angiography (CCTA) and results of invasive coronary function testing (CFT) to diagnose CMD. METHODS:Adults referred for clinically indicated invasive coronary angiography who had less than 50% stenosis in all epicardial arteries were prospectively enrolled. CMD was defined as a coronary flow reserve (CFR) less than 2.5 or index of microvascular resistance (IMR) greater than or equal to 25 using bolus thermodilution in the left anterior descending (LAD) coronary artery. Coronary perivascular fat attenuation index was assessed by CCTA in the right coronary artery (RCA) and LAD. T tests were used to evaluate differences in perivascular FAI by CMD status. RESULTS:A total of 31 participants underwent CFT and CCTA. The mean age was 58 ± 11.7 years, 77% were female, and 61% were white. CMD was present in 15 participants (48%). No differences in perivascular FAI were observed in patients with and without CMD, either in the RCA [-74.2 ± 9.8 vs. -69.9 ± 10.3 Hounsfield units (HU), P = 0.24] or LAD (-76.4 ± 10.2 vs. -74.8 ± 12.7 HU, P = 0.69). Perivascular FAI was not correlated with CFR or IMR measurements in the RCA or LAD. CONCLUSION/CONCLUSIONS:There were no associations between CMD diagnosed by invasive CFT and perivascular FAI by CCTA in patients with INOCA. Further research is needed to understand the relationship between vascular inflammation and CMD in INOCA.

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluate vaccine effectiveness against reinfection with Omicron BA.1/BA.2, BA.4/BA.5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. children's hospitals and health institutions. We emulate target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/BA.2 period, vaccination reduces the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/BA.5 period, protection effectiveness in children was 57%, whereas no statistically significant protection is observed in adolescents. During the XBB and later period, no significant protection is observed in either group. In summary, COVID-19 vaccination provides protection against reinfection during the early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declines for later variants.

OBJECTIVE:To evaluate the relationship between the Global Budget Revenue (GBR) model and surgical outcomes. SUMMARY BACKGROUND DATA/BACKGROUND:Medicare tested GBR in Maryland, wherein hospitals received a fixed annual revenue to cover healthcare delivery for their population. The relationship between GBR implementation and outcomes after cancer surgery is unclear. METHODS:Observational difference-in-differences analysis using 100% national Medicare data to compare changes in outcomes between GBR hospitals and matched control hospitals before (2011-2013) and after (2014-2018) policy implementation in Traditional Medicare beneficiaries undergoing cystectomy, prostatectomy, or nephrectomy for cancer. The primary outcome was achievement of a textbook outcome, defined as the absence of in-hospital and 30-day mortality, postoperative complications, a prolonged length of stay (i.e., above the 75th percentile by procedure and year) and readmission within 30 days of discharge. The secondary outcome was Medicare inpatient spending. RESULTS:This study included 23 Maryland hospitals with 4,910 beneficiaries and 371 control hospitals with 57,456 beneficiaries. Textbook outcomes increased from 72.8% to 76.1% in GBR hospitals and from 70.2% to 70.5% in matched controls, a differential increase of 2.9 percentage points (95% CI, 0.5 to 5.3; P=0.02). The greater improvement at GBR hospitals was a result of reducing complications (-1.5 percentage points; 95% CI, -2.9 to -0.1) and limiting prolonged lengths of stay (-1.8 percentage points; 95% CI, -2.9 to -0.7). Medicare inpatient spending declined by $771 (95% CI, -$1,275 to -$267) more at GBR hospitals. CONCLUSIONS:The GBR was associated with improved surgical outcomes and lower Medicare inpatient spending.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a disorder discovered in 2020 that bridges haematology, immunology and genetics. VEXAS syndrome arises from somatic mutations in UBA1, which encodes an E1 ubiquitin-activating enzyme, acquired in haematopoietic stem cells. These mutations disrupt ubiquitin-dependent protein homeostasis, triggering proteotoxic and inflammatory stress that drives systemic inflammation, cytopenias and clonal haematopoiesis. Clinically, VEXAS syndrome presents predominantly in older men with glucocorticoid-dependent inflammation, neutrophilic dermatoses, chondritis and myelodysplastic features. Diagnosis relies on characteristic clinical features and confirmation of UBA1 mutations. Prognosis is dismal in many patients, and treatment remains largely empirical. Glucocorticoids and cytokine blockade are used to provide transient control over inflammation, and hypomethylating agents aim to eradicate the mutant clone and induce disease remission. Allogeneic stem cell transplantation offers a potential cure. VEXAS syndrome exemplifies a new paradigm linking somatic genetics, inflammation and clonal haematopoiesis, reshaping our understanding of adult-onset inflammatory disease.

BACKGROUND:Poor documentation quality can significantly affect healthcare operations, but the feedback process for clinicians to improve clinical notes is time-consuming and often insufficient. Large language models (LLMs) such as Generative Pre-trained Transformer 4 (GPT-4) have the potential to streamline this process. OBJECTIVES/OBJECTIVE:To determine whether an LLM can generate feedback to improve the medical contingency and discharge planning (MCDP) component of clinical documentation that is non-inferior to feedback by physicians. METHODS:A cross-sectional study of GPT-4 feedback and physician feedback on inpatient progress notes was conducted. A random sample of 64 inpatient progress notes identified by the validated AI Audit Tool as having a low likelihood of containing MCDP was included from adult general medicine patients hospitalized at New York University Langone Health (NYULH) in December 2023. Both GPT-4 model and attending physicians generated feedback on these inpatient progress notes. A/B testing was then conducted on the measures of understandability, usefulness, acceptability, and impartiality. Evaluations employed 5-point Likert scales that were converted to 10-point bidirectional interval scales for interpretability, ranging from -10 (human suggestions significantly better) to +10 (GPT-4 suggestions significantly better), with a non-inferiority threshold set to -1 for the primary endpoint. RESULTS:64 inpatient progress notes were included, representing 55% female patients with a median age of 73. GPT-4 feedback was non-inferior to physician feedback in all measures: understandability (mean 1.27, 95% CI 0.73 to 1.8, P < 0.001), usefulness (mean 2.09, 95% CI 1.27 to 2.91, P < 0.001), acceptability (mean 2.07, 95% CI 1.33 to 2.81, P < 0.001), and impartiality (mean -0.20, 95% CI -0.52 to 0.12, P < 0.001). CONCLUSIONS:This study shows that an LLM can be leveraged to generate note quality feedback that is non-inferior to expert clinician feedback.

BACKGROUND:)-mutant non-small-cell lung cancer (NSCLC). Zongertinib is an oral, irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing wild-type epidermal growth factor receptor (EGFR), thereby minimizing associated toxic effects. METHODS:-mutant NSCLC. Here, we evaluated zongertinib at a dose of 120 mg once daily in patients who had not previously received treatment (cohort 2). The primary end point was objective response as assessed by blinded independent central review. Secondary end points included duration of response and progression-free survival. In addition, zongertinib was evaluated in patients with active brain metastases (exploratory cohort 4). RESULTS:In cohort 2, a total of 74 previously untreated patients received zongertinib at a dose of 120 mg. As of August 21, 2025, the percentage of patients with a confirmed objective response was 76% (95% confidence interval [CI], 65 to 84); the median duration of response was 15.2 months (95% CI, 9.8 to not evaluable), and the median progression-free survival was 14.4 months (95% CI, 11.1 to not evaluable). Adverse events of any grade occurred in 73 patients (99%), including events of grade 3 or higher in 33 patients (45%). Treatment-related adverse events occurred in 67 patients (91%), including events of grade 3 or higher in 14 patients (19%). In cohort 4, a total of 30 patients with active brain metastases received zongertinib at a dose of 120 mg; of these, 47% (95% CI, 30 to 64) had a confirmed intracranial objective response according to Response Assessment in Neuro-Oncology Brain Metastases criteria. In this cohort, treatment-related adverse events of grade 3 or higher occurred in 5 patients (17%). CONCLUSIONS:-mutant NSCLC. Treatment-related adverse events were predominantly low-grade. (Funded by Boehringer Ingelheim; Beamion LUNG-1 ClinicalTrials.gov number, NCT04886804.).

BACKGROUND/UNASSIGNED:The metabolic mechanisms underlying right ventricular (RV) dysfunction are poorly understood, particularly outside of group 1 pulmonary hypertension (PH). We aimed to identify metabolites and pathways associated with RV systolic function and explored whether associations differed by pulmonary vascular resistance, PH group 1 status, and sex. METHODS/UNASSIGNED:We analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. RV systolic function metrics included fractional area change (echo), global longitudinal strain (echo), and ejection fraction (cardiac magnetic resonance). We used linear regression adjusted for age, sex, body mass index, and PH group to assess associations between metabolites and RV function. Pathway enrichment analyses were used to identify pathways significantly associated with RV function. Interaction terms were assessed to determine whether metabolite associations were modified by pulmonary vascular resistance, group 1 PH status, or sex. Least absolute shrinkage and selection operator regression was used to develop metabolite-based scores for RV function, and prognostic performance was assessed. RESULTS/UNASSIGNED:There were 979 participants with plasma metabolomics and RV function data. Linear regression identified 170 metabolites that were significantly associated with all 3 RV metrics. Androgenic steroid, gamma-glutamyl amino acid, polyamine, vitamin A, fatty acid, and sterol pathways are most strongly associated with RV systolic function. Two metabolites interacted with group 1 PH status, and 6 interacted with pulmonary vascular resistance. Four androgenic steroids are associated more strongly with RV systolic function in females compared with males. Metabolite-based scores were prognostically equivalent to RV systolic function metrics and less accurate than REVEAL Lite 2 scores. CONCLUSIONS/UNASSIGNED:We provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Novel links to vitamin A and glutathione metabolites were observed. We detected few metabolites that associated with RV systolic function differentially by group 1 PH status or degree of pulmonary vascular resistance elevation. Androgenic steroids may associate more strongly with RV systolic function in females compared with males.

PURPOSE/OBJECTIVE:We used Delphi methodology to provide guidance on gender equality and equity issues in professional life in intensive care, where information is evolving and no clear standard exists. METHODS:A 12-member Steering Committee (7 women, 5 men) from 7 countries and 46 international panelists [(23 women, 21 men, 2 preferred not to disclose; median age 52 (33-75) years] from 32 countries (43% low- and middle-income) including intensive care practitioners, scientists, researchers, and trainees voted on 57 statements addressing issues related to gender equality and equity in 10 domains of professional life. Delphi rounds were conducted using online surveys. Consensus (at least 75% of panelists voting for a response option) and stability (consistent responses on iterative rounds) were assessed. RESULTS:Six Delphi rounds were conducted between May and July 2025. A 100% response rate was achieved in each round. Consensus and stability were achieved on 43 (75%) of 57 statements from which 37 professional practice guidance statements were developed. Across domains, greater consensus was achieved on equality [23/27 (85.2%)] versus equity [12/18 (66.7%)] statements. Discordant equity statements primarily pertained to academia and engagement in multiprofessional meetings and the workplace. CONCLUSION/CONCLUSIONS:Using a Delphi method, international experts reached consensus to generate 37 professional practice guidance statements. The consensus statements provide needed guidance for professional engagement and highlight areas for policy development to advance gender equity and equality for healthcare workers in intensive care. The discordant statements highlight areas for future research.