Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Lipoprotein assembly in the small intestine and liver is critical for the transport of dietary and endogenous lipids. Pla2g12b has recently been shown to play a role in lipoprotein assembly in mice livers and zebrafish larvae. Pla2g12b knockout and mutant (MUT) mice with the C129Y missense mutation have low plasma cholesterol levels. However, the role of Pla2g12b in the intestine and the reason why C129Y mutation decreases plasma lipids are unknown. METHODS:) and WT control mice were used in parallel to study plasma lipids and lipoproteins, lipid absorption and hepatic lipoprotein production studies. Transmission electron microscopy was used to visualize lipid transit through enterocytes. RESULTS:We observed that Pla2g12b expression was the highest in the duodenum. Furthermore, male and female chow fed 3-month-old MUT mice and wildtype (WT) mice expressed similar amounts of Pla2g12b protein and several genes in lipid metabolism. Nonetheless, the MUT mice had significantly lower plasma triglyceride (TG), cholesterol, HDL-C, LDL-C, apoB48, and apoB100 levels than WT mice. Several mechanisms for lower plasma lipids and lipoproteins in MUT mice were investigated. C129Y mutation had no effect on the expression of Pla2g12b and several other proteins necessary for lipid transport. Therefore, the low plasma lipid levels in MUT mice were neither due to the absence of Pla2g12b protein nor due to reductions in critical proteins in lipid transport. Next, we addressed the role of Pla2g12b in hepatic lipid mobilization and intestinal lipid absorption. MUT livers exhibited normal TG synthesis, defective TG secretion, and enhanced fat accumulation. MUT mice also showed defective intestinal TG absorption, intracellular lipid accumulation, and elevated TG excretion in the feces. CONCLUSIONS:We propose that C129 in Pla2g12b is critical for the assembly and secretion of lipoproteins by the liver and intestine.

IMPORTANCE/UNASSIGNED:Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. OBJECTIVE/UNASSIGNED:To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. DESIGN, SETTING, AND POPULATION/UNASSIGNED:Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. EXPOSURE/UNASSIGNED:Device-enabled TTVR. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. RESULTS/UNASSIGNED:Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality (P = .47), heart failure hospitalization (P > .99), and functional outcomes (P = .55) when patients were stratified by baseline CIED status. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

PURPOSE/OBJECTIVE:Secondary brain injury is a common cause of poor outcome after trauma, subarachnoid hemorrhage, and intracerebral hemorrhage, and optimizing treatment requires real-time insight into cerebral metabolism. Cerebral microdialysis (CMD) uniquely provides key related information, yet consensus on its use has not been updated since publication of the consensus statement from the 2014 International Microdialysis Forum. We aimed to assess expert consensus on the use of CMD in critical care and provide contemporary guidance to standardize practice and advance clinical implementation. METHODS:We conducted a 3-round modified Delphi study with international experts in CMD and neurocritical care. Consensus was defined as ≥ 75% agreement among non-abstaining respondents, with a minimum of 30 non-abstaining respondents required per statement. Statements not reaching consensus were iteratively revised based on panelist feedback. RESULTS:Forty of 67 invited experts (60%) from 9 countries participated. Sixty of 62 individual items achieved consensus (97%) across 9 domains: indications and patient selection, technical and procedural considerations, detecting deterioration and secondary injury, metabolic interpretation, treatment algorithms, glucose management, sampling frequency, core reporting items, and barriers to clinical implementation. CONCLUSION/CONCLUSIONS:This consensus statement provides updated, evidence-informed recommendations for the use of CMD in critical care. The panel reaffirmed many core recommendations from the 2014 consensus while making targeted advances: cautious extension of guidance to intracerebral hemorrhage, comprehensive reporting guidance addressing frequently omitted elements (19 items vs. 6 in 2014), and identification of 10 key barriers to routine clinical adoption.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Most patients with high-risk localized prostate cancer (HRLPC) do not undergo stereotactic body radiotherapy (SBRT) in part because of the limited evidence of long-term outcomes. We report long-term efficacy and toxicity outcomes for men treated with SBRT for HRLPC. METHODS:Individual patient data from ten prospective clinical studies evaluating SBRT for HRLPC across nine institutions were pooled in the Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate consortium. The Kaplan-Meier method was used to estimate 5-yr biochemical recurrence (BCR) and distant metastasis (DM), stratified by receipt of intensified treatment (≥12 mo of androgen deprivation therapy [ADT] with extremely dose-escalated [≥8 Gy/fraction] prostate-directed SBRT). The impact of intensified treatment on BCR-free survival and DM-free survival was evaluated using multivariable Cox proportional hazards models. Late Common Terminology Criteria for Adverse Events grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity was analyzed using time-to-event models. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:In 440 patients with a median follow-up time of 60.4 mo, 5-yr BCR and DM rates were 22% (95% confidence interval [CI] = 17-26%] and 9.2% (95% CI = 6.2-12%), respectively. In the 93 patients (21%) who received intensified treatment, 5-yr BCR and DM rates were 7.4% (95% CI = 1.7-13%) and 3.7% (95% CI = 0-7.9%), respectively. Receipt of intensified therapy was associated with a significant reduction in both BCR (hazard ratio [HR] = 0.38 [95% CI = 0.20-0.74], p = 0.005) and DM (HR = 0.43 [95% CI = 0.18-0.99], p = 0.049). For the overall cohort, 5-yr rates of grade ≥2 GU and GI toxicity were 23% (95% CI = 19-27%) and 10% (95% CI = 7-13%), respectively. Limitations include heterogeneous treatment techniques and the nonrandomized nature of the study. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:The safety and efficacy profile of SBRT for HRLPC remains favorable at long-term follow-up, and SBRT should be integrated into shared decision-making for treatment of HRLPC.

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.

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:The objectives of this study were to determine if financial considerations affect reconstructive decision-making, and conversely if reconstructive choice affects downstream financial burden. METHODS:We conducted mixed-methods study with a convergent design. Patients undergoing mastectomy with or without reconstruction were administered the Comprehensive Score for Financial Toxicity (COST) questionnaire before and after surgical treatment, where COST ≤20 indicated financial toxicity (FT). Multivariable regression models were used to identify predictors of FT and changes in COST score. Additionally, we conducted semi-structured interviews with patients who screened positive for FT to comprehensively capture experiences with financial burden. RESULTS:There were 1,029 patients with a COST score prior to mastectomy, with a 30.6% rate of FT. Significant predictors of FT included age (OR 0.97), race (Asian OR 2.12, Black OR 2.66, compared to White), marital status (divorced/separated OR 2.70, single OR 2.43, compared to partnered), and neighborhood-level socioeconomic deprivation (OR 1.15) (p<0.02). Receipt of reconstruction was not significantly associated with baseline FT, nor were type and timing among those who underwent reconstruction (N=739). Additionally, receipt, type, and/or timing of reconstruction were not significantly associated with a change in COST score (full cohort N=446, reconstruction cohort N=297). Interviews yielded 3 themes: prioritizing outcomes over financial implications, difficulties navigating and maintaining insurance coverage, and a need for greater transparency and access to financial resources. CONCLUSION/CONCLUSIONS:Bidirectional relationships between FT and receipt, type, and timing of reconstruction did not reach statistical significance. Additional patient-centric financial navigation and price transparency are warranted to mitigate financial burden.

BACKGROUND/UNASSIGNED:weeks to detect genetic abnormalities; however, a majority of providers opt to perform CVS after 11 weeks. This study evaluated the feasibility of CVS performed at varying gestational ages, comparing chorionic villi (CV) yield and procedural outcomes among early, typical, and late procedures. MATERIALS AND METHODS/UNASSIGNED:weeks). The primary outcome was median CV weight. Secondary outcomes included need for culture, time to microarray results, and a subanalysis of abnormal chromosomal microarray analysis (CMA) results, obstetric, and neonatal outcomes. RESULTS/UNASSIGNED:Of 719 patients, 8.1% underwent early, 83.2% typical, and 8.8% late CVS. The early cohort had a lower body mass index (BMI). Early CVS was most frequently performed transvaginally and for the indication of prior affected pregnancy, and less likely for abnormal genetic screening or ultrasound findings. Median villi weight did not differ significantly, and 89% of all procedures yielded adequate tissue, defined as ≥5 mg. The time to the microarray result was shortest in the typical group. There were no significant differences in other secondary outcomes of need for culture, number of passes, or procedure-related complication rates. There was no case of limb anomalies. CONCLUSION/UNASSIGNED:CVS performed before 11 weeks and after 14 weeks demonstrated comparable microarray outcomes and demonstrate the technical feasibility and diagnostic adequacy of CVS performed outside the typical gestational window. The results also support the availability of early CVS for cytogenetic testing in early pregnancy loss, where management may not allow for direct tissue testing. Prospective studies are warranted to validate these results and refine recommendations for optimal timing of CVS.

BACKGROUND/UNASSIGNED:For over a decade, STAT surgery has been the standard of care (SOC) for treating significant cauda equina syndromes (CES). Nevertheless, too many spinal surgeons, physician extenders, and other medical professionals still wrongly believe they have up to 24-48 hours to treat CES. METHODS/UNASSIGNED:To counter this misconception, we reviewed the evolution of treatment for significant CES from the outdated dominant protocols of < 48 h, to 24 - < 48 h, to < 24 h, to 0-< 24 h, to the present SOC; STAT, "prompt", surgery performed "the sooner the better". RESULTS/UNASSIGNED:A 2014 study found that there is no support in the literature for delaying CES surgery for up to 48 h, and further; "... the earlier the surgical intervention, the more beneficial the effect for compressed nerves." Subsequent studies advocated for < 24 h for early CES, finding they resulted in improved outcomes including bladder function especially for those with incomplete/partial (ICES) vs. total/retention CES (RCES). One study, involving 20,924 CES patients, showed the best improvement for surgery performed within 0 - < 24 h, leading to the present SOC for treating significant CES, as STAT or "the sooner the better". CONCLUSION/UNASSIGNED:Based on the up-to-date literature, the present SOC for managing significant CES is STAT surgery. Notably, the American Association of Neurological Surgeons (AANS) "guidelines" (published 4/5/24 on (www. aans.org)) cited the present treatment for CES; "Prompt surgery is the best treatment for patients with CES;" with the Merriam-Webster definition of prompt as "immediate" or "without delay". We agree that the present SOC for treating significant CES is STAT or "prompt" surgery.

BACKGROUND:Nondiagnostic cytology for thyroid nodules, consistent with The Bethesda System for Reporting Thyroid Cytopathology category I (B1) poses a management dilemma for clinicians. The objective of this study was to define the malignancy risk of nodules with B1 cytology using American College of Radiology Thyroid Imaging Reporting & Data System (TI-RADS) and to assess whether TI-RADS can help guide the decision to perform a repeat biopsy of these nodules. MATERIALS AND METHODS/METHODS:This retrospective cohort study evaluated 139 B1 nodules that had a definitive diagnosis on repeat biopsy or surgical excision. Sonographic features were evaluated and classified according to TI-RADS. TI-RADS category and total points were compared to the final diagnosis to determine the malignancy risk of B1 thyroid nodules. RESULTS:Of the 139 nodules, 11 (7.9%) were malignant. The malignancy risk of nodules assigned TI-RADS category 1 and 2 were both 0%, TI-RADS 3 was 2.9%, whereas TI-RADS 4 and 5 were 5.9% and 46.2%, respectively. The optimal cutoff for TI-RADS points predicting malignancy was 5 points. CONCLUSION/CONCLUSIONS:B1 thyroid nodules in TI-RADS categories 1-3 may not require repeat biopsy given low malignancy risk. However, B1 nodules in TI-RADS categories 4 and 5 have a higher malignancy risk and thus should undergo repeat biopsy.