Faculty Bibliography

DESCRIPTION/UNASSIGNED:A work group representing the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) prepared a new VA/DoD clinical practice guideline (CPG) for tobacco use treatment. This article provides a synopsis of the 2026 CPG, which addresses use of commercially available tobacco and nicotine products. METHODS/UNASSIGNED:A multidisciplinary work group developed 19 key questions on clinical topics of highest priority for the VA and DoD populations. Published literature from 1 January 2014 to 10 December 2024 was systematically reviewed using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) framework. Recommendations were made by consensus and informed by evaluation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method, which assesses quality of evidence and balances benefits and harms, patient preferences, and feasibility. The final document incorporated input from peer review by an external group of experts. RECOMMENDATIONS/UNASSIGNED:The 2026 guideline includes 32 recommendations across 10 topic areas. Key recommendations for increasing abstinence from combustible tobacco include recommending motivational interviewing to increase engagement in treatment of tobacco and nicotine use (strong) and use of U.S. Food and Drug Administration-approved pharmacotherapies (strong), with varenicline recommended over monotherapy with other agents (strong), combination nicotine replacement therapy ([NRT] for example, patch plus lozenge) recommended over NRT monotherapy (single agent) (strong), and extending use of bupropion sustained release beyond 12 weeks (weak). Other key recommendations include varenicline for increasing abstinence from smokeless tobacco (strong) and electronic nicotine delivery systems (weak) and use of NRT or varenicline to increase quit attempts and abstinence in patients not ready to quit in the next 30 days (weak).

BACKGROUND:Fewer than 20% of donated lungs are transplanted. We examined the impacts of donor management and recovery at an in-hospital donor care unit (DCU) established in 2021 versus the donor hospital (DH). METHODS:(P/F ratio) were examined as a hypothesized effect modifier. We projected the national impact of improved utilization on lung transplant volume. RESULTS:After adjusting for donor differences, lung utilization was 88% higher (aRR: 1.88; 95% CI: 1.40, 2.53) in the DCU versus DH setting. Median P/F ratio increased from 275 to 348 mmHg (p<0.0001) in the DCU and explained approximately 38% of the improvement in lung utilization. Non-lung organ utilization was either improved or non-inferior in the DCU. Lung graft survival and pulmonary function were similar for recipients of DCU versus DH-managed donors. Nationally, an 88% improvement in lung utilization among donors not currently transferred to a DCU could theoretically result in ≥300 more lung transplants per year. CONCLUSIONS:Lung transplantation can be nearly doubled through lung-centric donor management in a DCU, without sacrificing recipient outcomes nor the utilization of other organs. Donor management practices to optimize lung utilization should be proliferated by establishing more DCUs and, where feasible, applying lung-centric protocols in donor hospitals.

The liver is the primary site of metastasis in pancreatic ductal adenocarcinoma (PDAC), and liver metastases are a major cause of mortality^1,2. Nutrient availability in the metastatic niche influences colonization efficiency; however, the metabolic heterogeneity of disseminated tumour cells can also reshape the local microenvironment^3-5. Loss of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in de novo serine biosynthesis, is observed in nearly 40% of PDACs, and renders these cells dependent on exogenous serine (exSer)⁶. Although a neuron-tumour metabolic cross-talk supports exSer-dependent PDAC cells at the primary site⁶, it remains unclear how these cells adapt to the metastatic liver niche. Here we show that exSer-dependent PDAC cells reprogram neighbouring hepatocytes through a CXCL5-CXCR2 axis. Activation of CXCR2 in hepatocytes promotes PI3K-AKT signalling, leading to the sequestration of FOXO3A in the cytoplasm and derepression of PHGDH transcription, thereby enhancing serine production in hepatocytes. This hepatocyte-derived serine supports the outgrowth of exSer-dependent PDAC liver metastases. Accordingly, genetic or pharmacological inhibition of individual nodes within the CXCL5-CXCR2-PI3K-AKT-FOXO3A axis, or hepatocyte-specific deletion of Phgdh or Cxcr2, markedly reduces the liver-metastasis burden in mice and prolongs survival, particularly when dietary serine is restricted. Our findings reveal a cancer cell-hepatocyte metabolic cross-talk and identify therapeutic targets for exSer-dependent PDAC liver metastases.

The phase III CEPHEUS trial (ClinicalTrials.gov identifier: NCT03652064) of patients with transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM; N = 395) demonstrated improved overall minimal residual disease (MRD) negativity rates among patients achieving ≥complete response and progression-free survival (PFS) with daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd. We present efficacy and safety outcomes in the CEPHEUS TIE subgroup (N = 289; DVRd, n = 144; VRd, n = 145). Patients were either age 18-70 years with ≥1 comorbidity likely to negatively affect tolerability of high-dose chemotherapy with autologous stem cell transplantation or age ≥70 years. At a median follow-up of 58.7 months, the MRD negativity rate (10^-5) was 60.4% (DVRd) versus 39.3% (VRd; P = .0004). Rates of sustained MRD negativity (10^-5) for ≥12 months (47.2% v 28.3%; P = .0010) and ≥24 months (40.3% v 22.8%; P = .0015) were significantly higher with DVRd. Risk of disease progression or death was 49% lower for DVRd versus VRd (hazard ratio [HR], 0.51 [95% CI, 0.35 to 0.74]; P = .0003). Although immature, overall survival favored DVRd (HR, 0.66 [95% CI, 0.42 to 1.03]). Adverse events were consistent with known safety profiles. This analysis demonstrates that the deep responses achieved with DVRd translate into improved PFS in patients with TIE NDMM, reinforcing DVRd as a standard of care.

INTRODUCTION/UNASSIGNED:Associations between unhealthy food environments and increased risk of diabetes or obesity have been studied extensively in urban areas but less so in rural areas. To address this gap, we performed a geographically detailed study of the rural food environment, summarizing and assessing various measures and identifying their association with a higher rate of diabetes and obesity. METHODS/UNASSIGNED:We surveyed 1,311 residents of Sullivan County, New York, collecting data on demographic characteristics and health status in January 2021. We assessed the food environment by cataloging restaurants and retail food stores and used least absolute shrinkage and selection operator (LASSO) regression to identify metrics strongly associated with diabetes and obesity (body mass index >30.0). We compared absolute proximity, density, relative proportions, and modified retail food environment index metrics. We applied fixed distance bands and nearest-neighbor approaches for proportions. RESULTS/UNASSIGNED:Older age (LASSO = +0.276), nearest-neighbor proportion of fast food restaurants (LASSO = +0.155), and low income (LASSO = +0.150) were associated with higher diabetes rates. Nearest-neighbor proportion (LASSO = +0.269), density per square mile of groceries/supermarkets (LASSO = +0.247), and Hispanic ethnicity (LASSO = +0.181) were the strongest predictors of obesity. Nearest-neighbor metrics helped with the problem of frequent zeros: the least skewed measures were fast food restaurants with 20 nearest neighbors (P = .37 for skewness) and counter-service restaurants with 20 nearest neighbors (P = .81). CONCLUSION/UNASSIGNED:Nearest-neighbor approaches were less skewed to other metrics based on fixed distance bands, proximity, and density. Food environment metrics must be fully described and validated, especially in rural environments, before they are applied in research on critical health outcomes.

BACKGROUND:Fast-track (FT) protocol is an established but not standardized approach in cardiac surgery. We aimed to describe our FT protocol and to compare outcomes before and after the protocol implementation (non-FT group and FT group, respectively). METHODS:Fast-track protocol was implemented in March 2021 in our institution. All patients who underwent median sternotomy from January 2018 to June 2024 were identified. Patient characteristics and outcomes were compared between the FT group and non-FT group, using propensity-score matching. RESULTS:A total of 456 patients, primarily aortic valve replacement, mitral valve repair or replacement, and root and ascending aortic surgery, were included. Of 456, 261 patients were the FT group and 195 patients were the non-FT group. In the FT group, 91.6% of patients were extubated in the OR (vs. 42.1% in the non-FT group, p < 0.001). In the FT group, 193 (73.9%) were discharged within 2 or 3 days after surgery. After propensity-score matching, the median hospital length of stays (LOS) was significantly shorter in the FT group (3 days vs. 4 days, p < 0.001). Baseline characteristics, operations, and perioperative outcomes were similar between the groups, including 30-day mortality (0.5% vs. 0.5%, p = 1.0), prolonged ventilation (1.1% vs. 1.1%, p = 1.0), discharge to home (1.6% vs. 2.2%, p = 0.72), and readmission (3.8% vs. 4.3%, p = 0.80). CONCLUSIONS:The FT protocol was associated with decreased hospital LOS. Additionally, this study suggested that discharge within 3 postoperative days is feasible after most valve surgeries.

BACKGROUND:Right ventricular ejection fraction (RVEF) is a known predictor of adverse outcomes; however, its prognostic value diminishes in tricuspid regurgitation (TR). OBJECTIVES/OBJECTIVE:This study aims to assess whether effective right ventricular ejection fraction (eRVEF) offers a more physiologic assessment of RV function and improves risk stratification in patients with TR. METHODS:The derivation cohort comprised 453 consecutive patients with at least moderate functional TR (regurgitant fraction ≥30% or volume ≥30 mL) on cardiac magnetic resonance (CMR). eRVEF was calculated as the ratio of forward volume to RV end-diastolic volume. The eRVEF threshold (≤25%) was derived based on all-cause mortality data. Clinical data were collected from standardized questionnaires at the time of CMR and supplemented with electronic health records; the primary outcome was all-cause mortality. External validation was performed in 2 independent cohorts, totaling 316 patients using identical inclusion criteria. RESULTS:In the derivation cohort, impaired eRVEF was associated with more advanced biventricular remodeling, worse biventricular function, and greater burden of late gadolinium enhancement (P < 0.05 for all), which was paralleled by higher TR volume and fraction (both P < 0.05). Over a median follow-up period of 2.7 years (Q1-Q3: 0.6-6.6 years), 20% of the patients died; mortality was higher in patients with impaired versus preserved eRVEF (28% vs 12%; HR: 1.72 [95% CI: 1.16-2.54]; P = 0.007). After adjusting for known TR risk markers including age, RV size, TR severity, conventional RVEF, and clinical markers of right-sided congestion, eRVEF remained independently predictive of mortality (HR: 0.49 [95% CI: 0.24-0.97]; P = 0.042). Adding eRVEF to a model inclusive of RVEF improved mortality prediction (chi-square from 30.6 to 37.0; P = 0.011) whereas adding RVEF to eRVEF did not (chi-square from 35.4 to 37.0; P = 0.199). External validation confirmed the prognostic significance of eRVEF ≤25% in both cohorts (HR: 2.66-2.86; both P < 0.05). CONCLUSIONS:eRVEF independently predicts mortality in TR and provides incremental prognostic value over conventional prognostic markers.

OBJECTIVE:The objective of this scoping review was to synthesize evidence on the proportion of individuals living with Sjögren's disease who experience central nervous system (CNS) manifestations. METHODS:We searched MEDLINE (via PubMed) and Embase from 1980 through January 29, 2026, and the ECRI Guidelines Trust from 2020 through January 29, 2026. Title and abstract screening, followed by full-text review, were performed in duplicate using prespecified inclusion and exclusion criteria. One reviewer extracted data, with an independent audit completed by one of the project co-leads. Meta-analyses of proportions were conducted. Sensitivity analyses were planned a priori to evaluate the influence of statistical outliers. RESULTS:We identified 22,857 citations, of which 108 met the inclusion criteria. Pooled proportion estimates were generated for 23 CNS manifestations. Several manifestations occurred at frequencies exceeding those reported in the general population, including depression, migraine, insomnia, cognitive dysfunction, psychosis, movement disorders, aseptic meningoencephalitis, neuromyelitis optica spectrum disorder, optic neuritis, multiple sclerosis, cerebral vasculitis, cerebellar syndrome, spinal cord involvement, and non-localizing somatosensory complaints. The degree of increased frequency differed substantially across manifestations, and several estimates were highly influenced by individual studies, as indicated by sensitivity analyses. CONCLUSION/CONCLUSIONS:The spectrum of CNS involvement in Sjögren's disease is broad and heterogeneous. Attributing CNS manifestations to direct SjD involvement or coexisting conditions remains unclear and cannot be assumed to be causally linked. Our findings underscore the complexity of CNS manifestations in Sjögren's disease and highlight the need for evidence-informed guidance to support accurate diagnosis, attribution, and management of neurologic manifestations.