Faculty Bibliography

OBJECTIVES/OBJECTIVE:The gut microbiome plays a crucial role in regulating systemic immunity and has been implicated in several chronic inflammatory diseases. Intestinal expansions of Ruminococcus gnavus (RG), a dominant gut commensal, correlate with disease flares in lupus nephritis (LN), but the underlying mechanism remains unknown. METHODS:In a Pilot cohort of patients with biopsy-proven LN, subsetted by gut microbiota community, immune status was characterised using bulk-blood RNA sequencing libraries, serum levels of representative host proteins, and levels of immunoglobulin (Ig)G antibodies to the novel lipoglycan (LG) produced by pathogenic RG strains. A Validation LN cohort was evaluated for blood transcriptomic profiles and levels of anti-LG antibodies. In murine models, mechanistic hypotheses were tested after RG gut colonisation or after intraperitoneal injection with an LG preparation, with outcomes determined by transcriptomic analyses, platelet functional readouts, and tissue histology. RESULTS:In a Pilot cohort of patients with LN, RG gut expansions were associated with high-level platelet, neutrophil, and monocyte activation. Serum levels of platelet factor 4 and release of neutrophil extracellular traps (NETs) were significantly higher in patients with high serum IgG antibody against the novel RG-specific LG, a marker of in vivo immune exposure. An LN Validation cohort confirmed these correlates and showed that anti-LG antibodies serve as a surrogate for thromboinflammatory profile in this LN-associated endotype. In mice, gut colonisation with LG-producing RG strains or a single LG injection caused megakaryocytosis and platelet activation; RG colonisation with LG-producing strains induced tubulointerstitial injury with NETosis. In vivo responses to LG toxin were Toll-like receptor 2-dependent. CONCLUSIONS:Gut expansions of the RG pathobiont may contribute to autoimmune pathogenesis through the LG toxin and cause LN flares through thromboinflammatory mechanisms in this previously unrecognised LN endotype.

BACKGROUND:Heart failure accounts for more than one million US hospitalizations annually, with 30-day all-cause readmission approaching 25% and triggering CMS Hospital Readmissions Reduction Program penalties. The 2022 ACC/AHA/HFSA guideline and the 2023 ESC focused update elevated SGLT2 inhibitors to Class I therapy for heart failure with reduced ejection fraction (HFrEF) [1, 2]. The DAPA ACT HF-TIMI 68 prespecified meta-analysis demonstrated reductions in cardiovascular death or worsening heart failure (HR 0.71) and all-cause mortality (HR 0.57). Real-world prescribing patterns and 30-day readmission outcomes in the post-guideline US era are not well characterized. The relative contribution of clinical stability variables versus co-prescribed guideline-directed medical therapy (GDMT) to confounding has not been directly quantified in this setting. METHODS:We conducted a retrospective cohort study at four NYU Langone Health hospitals from January 2023 to January 2026. Adults with a primary heart failure discharge diagnosis were included. The prespecified primary analysis was in the HFrEF subgroup (LVEF ≤ 40%). The primary outcome was 30-day all-cause readmission. Stabilized inverse probability of treatment weighting (IPTW) was the primary adjustment, with overlap weighting (ATO) as sensitivity analysis. Hierarchical logistic regression decomposed the confounding contribution of clinical stability parameters relative to GDMT. The E-value assessed robustness to unmeasured confounding. RESULTS:Among 438 patients, 122 (27.9%) received in-hospital SGLT2 inhibitor initiation. The HFrEF rate was 41.6%, a sixfold increase from 6.6% reported in INSIGHT-HF (2020-2021). Patients with prior heart failure hospitalization received SGLT2 inhibitors at 11.4% versus 29.7% in those without (p < 0.001). In HFrEF (n = 221), 30-day readmission was 12.1% versus 31.8% (crude OR 0.29, 95% CI 0.14-0.61). The primary IPTW estimate was OR 0.34 (95% CI 0.13-0.91, p = 0.032). Sensitivity analyses were directionally consistent. Clinical stability parameters contributed only 9.3% confounding attenuation; GDMT was the dominant confounder. CONCLUSIONS:In a contemporary US post-guideline cohort, in-hospital SGLT2 inhibitor initiation reached 41.6% in HFrEF but remained low in patients with recent heart failure hospitalization. In-hospital SGLT2 inhibitor initiation was associated with lower 30-day all-cause readmission, though initiation was strongly bundled with discharge GDMT optimization and cannot be distinguished from a GDMT optimization effect with this study design. These findings should be considered hypothesis-generating. Because short-term safety events and post-discharge persistence were not systematically captured, these findings should not be interpreted as establishing the benefit-risk profile of inpatient SGLT2 inhibitor initiation. The prescribing gap in high-risk patients is an actionable quality-improvement target.

OBJECTIVES/OBJECTIVE:Recent reports have identified a concerning reversal of previously declining trends in major lower extremity amputations, driven by a combination of cardiovascular, societal, and hospital system-level factors. Our objective was to determine major lower extremity amputation risk by patient resources and hospital setting - the former represented by zip code-based income quartile, race, and ethnicity (surrogates for socioeconomic status) and the latter characterized by hospital Medicaid proportion. METHODS:Using the National Inpatient Sample, we identified inpatient admissions with diagnoses codes for atherosclerosis, chronic limb-threatening ischemia, and chronic occlusions between 1993 and 2021. Procedure codes identified below-knee (BKA) and above-knee (AKA) amputations. We calculated sample-weighted, population standardized incidence rates per 100,000 people by hospital Medicaid proportions (defined as quantiles with increasing proportions), zip code-based income quartile, race, and ethnicity. Landmark multivariable logistic regressions - with inflection points at 2010 for BKA and 2012 for AKA - identified adjusted associations between amputation risk, hospital Medicaid proportion quantile, income quartile, race, and ethnicity. RESULTS:In a sample of 2,769,388 admissions, there were 197,018 BKA and 151,018 AKA. Almost 42% of amputations, both AKA and BKA, were reported in the lowest income quartile, while 79% of major amputations were performed in the highest Medicaid proportion facilities. Pre-inflection points for both AKA and BKA, we note a clear, linearly increasing association between increasing hospital Medicaid proportion, low income, Black race and amputation risk. In more recent periods, elevated risk persisted but became more evenly distributed across hospitals with moderate to high Medicaid burden. Notably for income, there was a widening gap in protective effect - adversely affecting those at the lowest quartiles. CONCLUSION/CONCLUSIONS:As amputation incidence rises, associated hospital and patient characteristics have changed accordingly. Previously concentrated in extreme settings, amputation burden now spans more hospital systems and pronouncedly impacts lower income groups. These findings strongly encourage reevaluating the process of care for patients at risk for major amputations.

IMPORTANCE/UNASSIGNED:Individuals with mood and psychotic disorders are at an increased risk for dementia. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of antidiabetic medications with mitochondrial and metabolic properties, may offer protective benefits. OBJECTIVE/UNASSIGNED:To evaluate whether treatment with SGLT2 inhibitors is associated with reduced risk of incident dementia and other neuropsychiatric outcomes in patients with psychiatric disorders. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used a target trial emulation design and data from the US Department of Veterans Affairs databases from January 1, 2016, to June 1, 2024. Participants were 65 years or older with a diagnosis of major depressive disorder, bipolar disorder, or schizophrenia spectrum disorder but without prior dementia diagnosis at baseline or history of SGLT2 inhibitor use. Analyses used marginal structural models weighted by inverse probability of treatment and censoring. INTERVENTIONS/UNASSIGNED:Initiation and noninitiation of SGLT2 inhibitor were calculated using intention-to-treat (ITT) analysis, and sustained and nonsustained use of SGLT2 inhibitor for ≥3 months were estimated using per-protocol (PP) analysis. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was incident all-cause dementia, as defined by International Classification of Diseases-coded diagnoses. Secondary outcomes were time to psychiatric emergency department (PED) visit and time to psychiatric hospitalizations. Covariates included demographic characteristics, comorbidities, psychiatric diagnoses, and medication use. RESULTS/UNASSIGNED:In total, there were 112 725 individuals in the sample, of whom 7631 (6.8%) were exposed to an SGLT2 inhibitor. The sample had a median (IQR) age of 74.1 (69.7-77.6) years and predominantly consisted of males (104 818 [92.8%]); 49.3% of the patients had obesity. In the ITT analysis, SGLT2 inhibitor use was associated with reduced odds of all-cause dementia (odds ratio [OR], 0.61; 95% CI, 0.52-0.73) and PED visits (OR, 0.80; 95% CI, 0.66-0.97) but not psychiatric hospitalizations (OR, 0.68; 95% CI, 0.44-1.04). In the PP analysis, SGLT2 inhibitor use was associated with lower odds of all-cause dementia (OR, 0.54; 95% CI, 0.40-0.73) and psychiatric hospitalizations (OR, 0.56; 95% CI, 0.31-1.00) but not PED visits (OR, 0.74; 95% CI, 0.53-1.05). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of older adults with mood and psychotic disorders, SGLT2 inhibitor use was associated with lower risk of dementia and PED visits. The results support a neuroprotective role of SGLT2 inhibitors in a high-risk psychiatric population.

BACKGROUND:While there is evidence of the benefits of healthy maternal lifestyle behaviors (eg, physical activity plus a healthy diet) on cardiometabolic health, there are limited data on the independent association between physical activity and cardiometabolic health among women with a history of gestational diabetes mellitus (GDM). OBJECTIVE:In this study, our aim was to explore the association between device-assessed physical activity and cardiometabolic outcomes in Chinese American women, a group disproportionately affected by GDM and type 2 diabetes. METHODS:A cross-sectional study was conducted among 33 Chinese American women (0.5-5 years after delivery) with a history of GDM in New York City in 2023 to 2024, in which we collected their device-assessed physical activity data, online survey data (in Mandarin and English), and cardiometabolic data (via fasting blood samples). Descriptive, unadjusted, and adjusted regression analyses were performed. RESULTS:Participants' mean age was 38.2 ± 3.3 years (2.6 ± 1.5 years after delivery), and body mass index was 23.5 (interquartile range: 21.7-25.1) kg/m 2 . Among the 33 participants, 27.3% had prediabetes, 51.5% had lipid dysregulation, and 21.2% had elevated blood pressure. The duration of moderate-to-vigorous physical activity per week was 132.4 (interquartile range: 90.5-272.0) minutes, and 46.9% of the cohort met the physical activity recommendation of ≥150 minutes moderate-to-vigorous physical activity per week. In regression models, meeting the physical activity recommendations was inversely associated with total cholesterol (-27.6 ± 12.7 mg/dL) and low-density lipoprotein cholesterol (-25.5 ± 10.6 mg/dL) levels (both P <.04). CONCLUSIONS:The majority of participants engaged in suboptimal physical activity levels. However, meeting physical activity recommendations was associated with better total and low-density lipoprotein cholesterol levels. Targeting physical activity may be a key strategy for improving cardiometabolic health in Chinese American women recently diagnosed with GDM.

Sedation is often required to facilitate comfort and provide necessary care for patients who are critically ill and require mechanical ventilation. Intravenous sedatives are the current standard of care in this patient population. Inhaled volatile agents that are routinely used for general anesthesia, like isoflurane and sevoflurane, are also being explored for their potential role in the ICU setting. Already, inhaled volatile agents are prescribed for routine ICU sedation in several countries, though their use for ICU sedation is not approved by United States regulatory authorities as of the time of this writing. The efficacy and safety profiles of inhaled sedatives for short-term use are well understood through decades of experience in the operating room. Their rapid onset and elimination via the lungs, potential opioid-sparing effects, and preservation of spontaneous breathing make them intriguing potential alternatives or adjuncts to standard-of-care sedation during critical illness. Technological advancements, consisting of compact vaporizers, volatile agent reflectors, and scavenger systems, allow the delivery of inhaled sedatives via modern ICU ventilators. However, these systems require specialized clinical training and considerations. Rigorous clinical trials evaluating the use of inhaled volatile agents for prolonged sedation of patients receiving mechanical ventilation remain limited, and whether these theoretical advantages translate to patient-centered benefit, relative to intravenous agents, remains unknown. Recent findings suggest prolonged deep sedation with inhaled sevoflurane predisposes to nephrogenic diabetes insipidus and acute kidney injury during critical illness, and that it is potentially harmful in patients with ARDS. Isoflurane may have a more favorable safety profile, but rigorous data are sparse on isoflurane use for more than a few days. This narrative review evaluates the evidence regarding the use of inhaled sedatives in patients in ICU who require mechanical ventilation. It also provides an overview of the clinical and technical aspects of this therapy to inform health care providers of a novel option, in many countries, for the sedation of patients undergoing mechanical ventilation.

OBJECTIVES/OBJECTIVE:Medicare-funded home health (HH) provides short-term nursing, physical therapy, and other services to over 3.5 million older adults each year. Currently, half of HH episodes are "community-entry," meaning the patient was referred without an immediately preceding hospitalization. The 2020 implementation of a new payment system-the Patient-Driven Groupings Model (PDGM)-reduced traditional Medicare reimbursement for community-entry HH (CEHH). We investigated shifts in CEHH care delivery following PDGM implementation. DESIGN/METHODS:Cross-sectional study of national 2019 and 2021 linked HH claims, assessment, HH agency, and geographic data. SETTING AND PARTICIPANTS/METHODS:Traditional Medicare beneficiaries receiving a CEHH episode in 2019 or 2021 (n = 577,602). METHODS:HH is provided through clinician visits to the patient's home; therefore, visits are the primary unit of care delivery. We modeled the number of visits overall and by service type (eg, nursing, physical therapy) using national data for CEHH patients pre-PDGM (ie, 2019) and post-PDGM (ie, 2021). Models adjust for relevant patient, HH agency, and geographic characteristics (including monthly county-level COVID-19 infection rates). RESULTS:Following PDGM, there was an 18% decrease in total visits received, with the largest decreases in the number of physical therapy (-13%), occupational therapy (-17%), and aide (-16%) visits. Reductions in visits were greatest at HH agencies with lower Medicare Advantage penetration (and thus, greater exposure to PDGM) and for-profit agencies. CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:Findings raise questions about HH agencies' ongoing ability to meet the needs of patients with complex, overlapping clinical and social needs following PDGM implementation. Ongoing monitoring of how these care delivery changes impact outcomes for CEHH patients is essential to ensure that HH can continue to help high-need older adults safely age in place.

From 2014 to 2025, accelerated 3-year MD programs (A3YP) have expanded significantly, such that 20% of allopathic medical schools offer a program to earn the MD degree in three years. While maintaining rigorous and comparable educational standards as traditional 4-year programs, A3YPs aim to address physician workforce shortages, reduce student debt, and provide individualized education pathways into specific specialties. Among the thirty-two A3YPs in existence, twenty-two medical schools have graduated 1141 students to date, with numbers increasing annually. Nineteen programs are linked to a residency program, though six of these programs consistently match students outside their linked program. As more medical schools implement A3YPs and an increasing number of graduates enter the National Residency Matching Program (NRMP), residency program directors will encounter A3YP applicants more frequently. The proliferation of A3YPs presents both challenges and opportunities for residency program directors in evaluating applicants. Despite the differences in their applications, including limited extracurricular activities and time for visiting rotations, these applicants have been found to perform similarly in standardized testing and residency milestones, and have similar well-being and satisfaction as traditional students. This perspective outlines key considerations for PDs and provides a foundation for contextually evaluating the increasing numbers of these applicants graduating from A3YPs.

PURPOSE/OBJECTIVE:Mobile health cardiac rehabilitation may improve access to care among older adults with ischemic heart disease, but engagement remains poorly understood. We analyzed weekly engagement data from the RESILIENT (Rehabilitation Using Mobile Health for Older Adults with Ischemic Heart Disease in the Home Setting) trial, a large, randomized trial of mobile health cardiac rehabilitation in older adults conducted in the United States. METHODS:Data from 298 intervention participants were analyzed. Weekly engagement was scored from 0 to 11 based on exercise entry (7 points), communication with exercise therapist (2 points), video viewing (1 point), and blood pressure measurement (1 point). Latent class analysis identified digital engagement phenotypes. Participant characteristics were compared, and multivariable logistic regression identified factors associated with phenotype membership. RESULTS:Median age was 71.0 years, 28% were women, 23% were non-White, and 62% were enrolled after elective percutaneous coronary intervention. Latent class analysis identified 3 phenotypes: persistently low (n = 81), intermediate declining (n = 93), and persistently high (n = 124). Participants with persistently low engagement were more likely to be non-White (48% vs 12% vs 15%, P < .001), Medicaid enrolled (22% vs 8% vs 7%, P = .001), have less than high school education (16% vs 4% vs 3%, P < .001), have frailty phenotype (28% vs 10% vs 7%, P < .001), and have a greater mean number of comorbidities (3.1 vs 3.0 vs 2.6; P = .012). After adjustment, non-White race and frailty remained independently associated with low engagement. Improvement in 6-minute walk test distance varied: 20.8 m (low), 29.7 m (intermediate), and 54.5 m (high) (P = .003). CONCLUSIONS:Three distinct digital engagement phenotypes emerged. Persistently low engagement was more common among non-White and frail participants, underscoring ongoing disparities despite efforts to overcome the digital divide.

BACKGROUND AND AIMS/UNASSIGNED:Pancreatic cystic lesions (PCLs) are increasingly detected because of the widespread use of imaging techniques. Among them, mucinous PCLs carry a higher malignancy risk, with intraductal papillary mucinous neoplasms (IPMNs) being the most frequent subtype. Accurate stratification based on the degree of dysplasia-low-grade dysplasia (LGD) versus high-grade dysplasia or carcinoma (HGD/C)-is essential to guide clinical management and avoid unnecessary surgical interventions. This study aimed to develop and evaluate a deep learning model for stratifying IPMNs into HGD/C and LGD using endoscopic ultrasound (EUS) images. METHODS/UNASSIGNED:This multicenter study included EUS images collected from 5 centers across Spain, Brazil, and the United States. Ground truth classification of IPMNs was established through cytologic and biochemical analysis of cyst fluid, EUS-guided through-the-needle biopsy, or surgical specimens. A deep learning model was trained to distinguish LGD from HGD/C. Model performance was assessed on the basis of sensitivity, specificity, accuracy, and area under the precision-recall curve. RESULTS/UNASSIGNED:A total of 51,046 EUS images were extracted from 30 examinations performed at 5 centers in Portugal, Spain, Brazil, and the United States. The model distinguished IPMNs with HGD/C from those with LGD with a sensitivity of 95.7%, a specificity of 88.7%, and an overall accuracy of 87.2%. The area under the receiver operating characteristic curve was 0.951. CONCLUSIONS/UNASSIGNED:To our knowledge, this is one of the first studies to evaluate the potential of an artificial intelligence model for dysplasia grading of IPMNs. Prospective validation of our model is necessary to ensure clinical benefit.