Faculty Bibliography

PURPOSE/UNASSIGNED:To compare a strategy utilizing testing to guide treatment, also known as selective therapy, to a strategy of initiating interventions without testing, termed empiric therapy, on urinary supersaturation of calcium oxalate and calcium phosphate. MATERIALS AND METHODS/UNASSIGNED:In this single-center trial, adult individuals with recurrent idiopathic calcium stone disease were randomized to either an empiric or selective strategy. Participants received 24-hour urine testing at baseline, 4 weeks, and 8 weeks. Treatment in the empiric arm was comprised of dietary and fluid counseling and pharmacologic treatment with indapamide and potassium citrate irrespective of 24-hour urine results. For the selective arm, diet and pharmacologic treatments, which included indapamide, potassium citrate, and/or allopurinol, were tailored based on urine testing at baseline and 4 weeks. The primary outcome was urinary supersaturation of calcium oxalate and calcium phosphate at 8 weeks. RESULTS/UNASSIGNED:= 0.58). Similarly, there were no significant differences at 8 weeks in urine volume and pH, or in excretion of calcium, oxalate, citrate, uric acid, and sodium. CONCLUSIONS/UNASSIGNED:In this short-term trial among individuals at high-risk for stone recurrence, there was no statistically significant difference in the urinary stone risk comparing an empiric versus selective strategy for kidney stone prevention.

BACKGROUND:Acute GI bleeding (AGIB) can be associated with significant mortality. Topical endoscopic hemostatic powders (TEHPs) have become established as one of the endoscopic treatment modalities for AGIBs. There is no dedicated consensus on the role of TEHPs in the GIB algorithm. OBJECTIVE:We aimed to develop expert-led consensus statements to provide guidance on the use of TEHPs in AGIBs. DESIGN/METHODS:A team of 15 experts in the field of acute AGIB from 8 countries was recruited to construct consensus statements on the use of TEHPs. A first meeting was held to define statements. Using the RAND/UCLA appropriateness method, they voted on statements by combining expert collective judgment and best available evidence in a 2-round voting process. Statements were rated on a 9-point interval scale (1 to 9). Four statistical methods were used to delineate statements that satisfied all criteria of appropriateness. For a statement to be considered appropriate, it had to meet all statistical definitions of appropriateness showing consensus agreement. RESULTS:Following round 2, 11 final statements were scored as appropriate, reaching overall consensus. Key recommendations include that TEHPs are effective in achieving hemostasis in malignancy-related GIBs, can be used as "salvage" therapy for nonvariceal GIBs and can be used as a bridge to definitive nonendoscopic therapy. CONCLUSION/CONCLUSIONS:We present a dedicated international consensus statement aimed at providing guidance to clinicians on best practice use of TEHPs in patients with AGIBs. There was consensus among the panel on the need for future trials to compare the use of different hemostatic powders in patients presenting with GIB.

BACKGROUND:Emerging evidence suggests endocrine disrupting chemicals, including bisphenols and phthalates, may affect behavioral development in children and adolescents. Risk behavior constitutes a potentially sex hormone sensitive behavioral construct. Here, we examined longitudinal associations of phthalate and bisphenol exposure with performance-based tasks and self-reported risk-taking behaviors. METHODS:Within a population-based birth cohort in the Netherlands, urinary bisphenols and phthalate metabolite concentrations were measured in women during pregnancy (three times, n = 1379) and in children (once at 6 years, n = 775). At 10 years, child risk-taking behavior was assessed with the computerized experimental Columbia Card Task (CCT). At 14 years, adolescents completed a computerized self-assessment of real-life risk-taking behaviors. Linear regression and hurdle models adjusted for confounders were applied in the whole sample and stratified by sex at birth. RESULTS:After multiple testing correction, no associations in all children or in boys were found for prenatal or childhood phthalate exposure with the average CCT-score. In girls, prenatal mono-isobutyl phthalate was associated with a higher average CCT-score, indicting more risk-taking (B per 10-fold increase in creatinine-adjusted average prenatal levels = 2.10, 95% CI: 0.69,3.52). No associations were observed for bisphenol exposure nor for self-reported risk-taking. CONCLUSIONS:Prenatal phthalate exposure was associated with more risk-taking in an experimental task at 10 years-of-age in girls only. The task reflects risky decision-making, which may be a hormonally sensitive construct. Risky decision making potentially precedes real-life risk-taking, which was captured by the self-reported measure and was limited in this young sample.

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.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Compartmentalized CNS inflammation involving B cells is implicated in gray matter injury and disease progression in multiple sclerosis (MS). Products secreted by B cells of patients with MS can kill oligodendrocytes and neurons, a cytotoxicity conferred by their exosome-enriched extracellular vesicle (Ex En) fraction. METHODS:To explore the potential molecular mediators of this cytotoxicity, we profiled proteomic and transcriptomic cargo of Ex En isolated from B cells of patients with treatment-naive MS and matched healthy controls. RESULTS:MS B-cell-derived Ex En appeared enriched in cell-death-associated proteins (including fibrinogen, complement C9, APP, and SPARC) and deficient in cell-survival-associated proteins (such as galectin-3). Abnormal enrichment for cell-death proteins was supported by gene set enrichment analysis. Protein pathway analysis revealed densely connected prodeath modules in the MS B-cell-derived Ex En, contrasting with homeostatic signatures in controls. Transcriptomic analysis further revealed that Ex En of MS B cells appeared to carry reduced levels of miRNAs (miR-182, miR-212, and miR-1270) known to inhibit apoptosis. DISCUSSION/CONCLUSIONS:Our findings indicate that B-cell-derived Ex En of patients with MS, previously shown to impair neuronal and glial survival, harbor an abnormal cytotoxic molecular profile that may contribute to CNS-compartmentalized injury and progressive MS biology.

The upper extremity is a structure of incredible complexity able to perform unique tasks that span from the most delicate and intricate to highly strenuous and forceful. Fully functional and aesthetic replacement of the upper extremity after loss remains a medical and technological aspiration. Meaningful advancements continue to be made in all areas of upper extremity limb loss, specifically in traditional surgical reconstruction and prosthetics. This has generated a new field of treatment that is most accurately titled Bionic Reconstruction. Essentially, successful bionic reconstruction allows for the human body to effectively communicate and work in concert with the man-made technology.

BACKGROUND/UNASSIGNED:Racial and ethnic disparities are a concern in lung cancer screening. OBJECTIVE/UNASSIGNED:To investigate the performance of risk prediction models to define screening eligibility across 4 U.S. racial and ethnic groups. DESIGN/UNASSIGNED:Cohort study. SETTING/UNASSIGNED:United States, Lung Cancer Cohort Consortium. PARTICIPANTS/UNASSIGNED:641 830 participants aged 50 to 80 years with a smoking history from 12 U.S. cohorts, including 6390 Asian, 9781 Hispanic, 39 872 non-Hispanic Black, and 585 787 non-Hispanic White participants. MEASUREMENTS/UNASSIGNED:Calibration and discrimination were quantified for 16 lung cancer prediction models. Then, screening-related metrics were calculated after applying model thresholds to select the same number of eligible participants as the 2021 criteria from the U.S. Preventive Services Task Force (USPSTF-2021). These included eligibility, sensitivity, and efficiency measured as estimated number needed to screen (NNS; the ratio between participants and lung cancer cases) for each strategy or prediction model in each racial and ethnic group. RESULTS/UNASSIGNED:General patterns across the 16 models included substantial underestimation of lung cancer risk in non-Hispanic Black participants (expected-observed ratio < 0.75 for 11 of 16 models), lower discrimination in Asian participants than all other groups (13 of 16 models), and lower discrimination in non-Hispanic Black than non-Hispanic White participants (15 of 16 models). When a same-sized screening-eligible population as USPSTF-2021 (38.0%) was enforced, all risk-based strategies achieved better average estimated screening efficiency and reduced racial and ethnic differences in efficiency compared with USPSTF-2021. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOm2012) and Life Years gained From Screening-Computed Tomography model (LYFS-CT) performed best (mean estimated NNS, 36.5 [SD, 8.8] and 40.1 [SD, 8.2], respectively). However, no strategy could simultaneously optimize eligibility, sensitivity, and efficiency while also reducing racial and ethnic differences. LIMITATION/UNASSIGNED:Smaller sample for Asian and Hispanic participants. CONCLUSION/UNASSIGNED:To optimize efficiency and minimize its variation across racial and ethnic groups, risk-based strategies were superior to USPSTF criteria. Further optimization of prediction models for the diverse U.S. population is needed. PRIMARY FUNDING SOURCE/UNASSIGNED:U.S. National Cancer Institute, Lung Cancer Research Foundation, and Cancer Research UK.

Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.