Faculty Bibliography

BackgroundMisalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD).ObjectiveDetermine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition.MethodsActual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes were quality of life and cognitive domains frequently altered in people with PD (global cognition & executive function). Secondary cognitive domains assessed were attention, memory, visuo-spatial, verbal function, and information processing. Linear and non-linear models assessed the relationship between discordance, quality of life, and cognition.ResultsDiscordance related to mobility-related quality of life, such that under-confidence was related to poorer quality of life. Non-linear (quadratic) models were shown to fit the discordance-Global cognition (p = 0.02) data better than linear models such that over- and under-confidence related to poorer cognition. Secondary cognitive domains were not robustly related to discordance.ConclusionsIn a clinical sample of people with PD, discordance was related to mobility-related quality of life and global cognition. Global cognition further exhibited a possible non-linear relationship to discordance indicating that over- or under-confidence may relate to poorer cognition. This work underscores the functional relevance of misalignment of actual and balance abilities.

INTRODUCTION/BACKGROUND:Children with immune thrombocytopenia (ITP) may have an increased risk of perioperative bleeding. However, current pediatric ITP guidelines do not address this management setting. We aimed to describe perioperative management and outcomes in pediatric patients with ITP by platelet count, type of surgery, and ITP-directed treatment strategies. METHODS:We conducted a retrospective analysis of patients with ITP ages 0-24 years who underwent tooth extraction, tonsillectomy and adenoidectomy, appendectomy, and/or splenectomy at six centers in the United States and Canada between 2019 and 2024. RESULTS:/L where hematology was not involved in perioperative management. Medication side effects were reported in 7% (3/43) of patients receiving ITP-directed therapies. CONCLUSIONS:/L. Perioperative bleeding risk appears to be low in pediatric ITP under current management practices.

BACKGROUND:Tools for predicting heart failure (HF) in CKD patients remain limited. We aimed to study whether standard ECG features or heart rate variability parameters predict de novo HF hospitalization in individuals with CKD. METHODS:Utilizing a large NYU ECG database linked with electronic health records (2012-2021), we analyzed a cohort of patients with pre-existing CKD. Besides standard ECG features, we extracted heart rate variability (measures the time between consecutive heart beats in milliseconds) features from the ECGs as predictors. The index ECG was the first ECG performed after the index eGFR date (baseline) and was required to be done prior to initiation of dialysis, end-stage kidney disease (ESKD), or transplant. The primary outcome was time to index HF hospitalization (≥30 days after the index ECG) based on discharge ICD-10 codes. LASSO-penalized Cox regression was used to identify predictors. Sensitivity analyses used Fine-Gray competing risk models for death and ESKD. RESULTS:Among 11,409 individuals (median age: 72; ∼50% male) with a median of 976 days, 880 individuals (8%) experienced an index HF hospitalization. Models incorporating ECG and clinical parameters had excellent discrimination (C-statistic 0.76 in the training set and 0.73 in the validation set). Among ECG features, the PR interval, corrected QT, and T axis were independently associated with higher risks of index HF hospitalization ≥30 days after the index ECG in both primary models (p<0.001 for all) and in models accounting for competing risks (p<0.01 for all). History of arrhythmia (hazard ratio (HR, 1.60, 95% CI: 1.36-1.88), valvular disease (HR1.51, 95% CI: 1.27-1.81), and diabetes (HR 1.41, 95% CI: 1.22-1.65) were the strongest clinical predictors. HRV parameters were not independently associated with HF. CONCLUSIONS:Although ECG-derived HRV indices were not independently associated with risk of HF, several standard ECG features are associated with HF hospitalization in CKD.

BACKGROUND:Comparative trials evaluating surgical outcomes are critical in guiding treatment for hallux valgus. However, the statistical stability of these outcomes is not well documented. Purpose The purpose of this study was to evaluate the statistical fragility of comparative studies analyzing minimally invasive surgery (MIS) versus open techniques for hallux valgus correction. STUDY/METHODS:Design A systematic review identified comparative studies assessing MIS versus open hallux valgus correction. METHODS:Outcome data were extracted with Fragility Index (FI) and Continuous Fragility Index (CFI) calculated for significant outcomes, and reverse FI (rFI) and reverse CFI (rCFI) for nonsignificant outcomes. Fragility Quotient (FQ) was calculated for each and compared to the number of patients lost to follow-up (LTFU). RESULTS:Of 628 studies screened, 18 met inclusion criteria, totaling 1,369 patients. Among 88 dichotomous outcomes, the median FI was 2, FQ was 0.021, rFI was 4, and rFQ was 0.072. For 236 continuous outcomes, the median CFI was 8, CFQ was 0.116, rCFI was 19, and rCFQ was 0.280. CONCLUSION/CONCLUSIONS:This is the first study to evaluate fragility in comparative trials on MIS versus open hallux valgus correction and among the first to assess reverse fragility in continuous outcomes. Significant results were more fragile than nonsignificant data and dichotomous outcomes were more fragile than continuous ones with nearly a quarter having an FI lower than the number of patients LTFU. Both outcome types demonstrated considerable statistical fragility supporting the cautious interpretation of MIS vs open hallux valgus findings and the reporting of statistical fragility data alongside P-values to better contextualize the robustness of clinical research.

OBJECTIVE:Exposure to antidepressants, particularly agents that work through serotonin-reuptake inhibition, may increase potential for bleeding, especially among patients with other bleeding risk factors. There is limited guidance for clinicians in the use of serotonin reuptake inhibitors (SRIs) and other antidepressants in the setting of increased bleeding risk. METHODS:A PubMed literature search was conducted for English-language articles (1992-2024) examining the bleeding risk associated with antidepressants. Physicians from the Association of Medicine and Psychiatry then convened to develop consensus recommendations. RESULTS:Consensus recommendations were established for managing antidepressant use in patients with medical and psychiatric comorbidities. Additionally, a clinical decision algorithm was created to assist clinicians in assessing the appropriateness of antidepressant prescribing in patients at risk for bleeding. CONCLUSIONS:The proposed algorithm can aid clinicians in determining whether antidepressant (including SRI) initiation, discontinuation, or dose adjustment should be considered for patients susceptible to bleeding. These guidelines preserve a role for clinical judgment in selection of treatments that balance the risks and benefits, which may be particularly relevant for patients with complex medical and psychiatric comorbidities. Additional studies are needed to better guide clinical decision making.

INTRODUCTION/BACKGROUND:Biliary strictures (BS) are a significant challenge, with malignant strictures frequently diagnosed at advanced stages, limiting curative options. Digital single-operator cholangioscopy (D-SOC) enables high-resolution, direct visualization of the bile duct, yet with suboptimal accuracy. Artificial intelligence (AI) has shown promise for detection and differentiation of BS in frame-level analysis and small clinical series. This study aimed to validate a deep learning model for AI-assisted D-SOC image analysis. METHODS:This multicenter study included 135 D-SOC exams from 129 patients (61 with malignant BS) across 14 centers in the United States, Brazil, Spain, Colombia, Australia, and Saudi Arabia. For each exam, up to 25 clinically relevant frames were selected and uploaded to a web-based platform for AI analysis. The model performed both detection and differentiation of BS: detection was assessed by comparing AI-generated bounding boxes with expert-defined annotations using intersection-over-union (IoU), while differentiation was benchmarked against histopathology. Performance metrics included accuracy, sensitivity, specificity, and positive and negative predictive values (PPV and NPV). RESULTS:At the patient level, malignant BS were identified with 86.0% accuracy, 84.1% sensitivity and 85.7% specificity, with an AUC of 0.904. The model demonstrated robust detection performance, achieving a mean IoU of 70.3%. Performance was maintained across demographic variables and centers. DISCUSSION/CONCLUSIONS:This first multicentric validation study demonstrates real-world performance of AI-assisted D-SOC analysis across multiples continents and devices, with robust accuracy for BS detection and differentiation. These findings support AI as an adjunctive tool in D-SOC, enhancing a more accurate evaluation of patients with indeterminate BS.

Segmental peripheral nerve injuries, particularly those involving long nerve gaps, pose a significant challenge in reconstructive surgery. Conventional strategies, such as nerve autografts or processed allografts, are often limited by inadequate length or poor regenerative outcomes, especially in traumatized wound beds. Nerve flaps offer the theoretical advantage of enhanced axonal regeneration through improved perfusion and support of Schwann cell viability but are rarely used due to technical complexity and limited donor options. We present a unique case of a free sural nerve flap used to reconstruct a 7-cm segmental defect of the tibial nerve following blast trauma in a 23-year-old man. A composite flap consisting of the sural nerve and lesser saphenous vein was harvested with preservation of the bridging adipofascial tissue to maintain perfusion to the nerve. The lesser saphenous vein was anastomosed to the retrograde peroneal artery distally and ligated proximally, whereas the sural nerve was divided and used as a double-barrel cable graft across the defect. Intraoperative Doppler and SPY angiography confirmed perfusion of the nerve through the preserved adipofascial connections. The patient was recently seen in our clinic at 17 weeks postoperation. He demonstrated undetectable 2-point discrimination in all nerve distributions of his foot but is ambulatory. This case demonstrates the feasibility and potential utility of a free vascularized sural nerve flap for reconstructing extensive peripheral nerve defects, particularly in cases where standard techniques are inadequate.

BACKGROUND:Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC. METHODS:Patients with locally advanced or metastatic PDAC after one prior regimen received 50 mg/m2 subcutaneous azacitidine on days 1-5 of a 28-day cycle, starting week 1, and pembrolizumab 200 mg intravenously every 3 weeks starting week 3. Baseline and on-treatment blood and tumor was collected for exploratory biomarker analysis. RESULTS:Thirty-six patients enrolled between October 2017 and September 2021 (median age: 62.5 years); 34 were evaluable for safety; 31 for efficacy. Treatment was generally well-tolerated, with Grade 1-2 fatigue and diarrhea most common AEs. Three patients (9.7%) had a partial response, and the disease control rate was 35.5%. Median progression-free and overall survival was 1.51 and 4.83 months, respectively. Exploratory analysis suggested higher baseline CD8+ T cells and lower tumor Ki-67 was associated with response, whereas low baseline CD8+ T cell and Granzyme B infiltration correlated with higher exponential tumor growth rate. PD-L1 and CD68 expression were not predictive of benefit. CONCLUSION/CONCLUSIONS:Azacitidine plus pembrolizumab demonstrated limited clinical activity in second line, locally advanced or metastatic PDAC. Biomarker analysis suggests higher baseline CD8+ T-cell infiltration and lower proliferative index may identify patients more likely to benefit. (NCT03264404).