Faculty Bibliography

PURPOSE/UNASSIGNED:Vesicourethral anastomotic stenosis (VUAS) occurs after 1 to 3% of robotic-assisted radical prostatectomies (RARPs). Pelvic fascia-sparing techniques preserve more native anatomy and may reduce stenoses, but evidence is lacking. The aim of this study was to compare stenosis incidence, management, and outcomes after standard vs pelvic fascia-sparing RARP. MATERIALS AND METHODS/UNASSIGNED:We conducted a multi-institutional retrospective study of 910 standard, 409 Retzius-sparing, and 272 hood RARP during February 2012-September 2025. Standard and hood techniques used 18Fr urethral catheters, and the Retzius-sparing technique used 18Fr suprapubic catheters. The primary end point was cystoscopically confirmed VUAS requiring intervention within 12 months. Urinary continence was assessed using the validated Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Multivariable logistic regression assessed factors associated with VUAS. RESULTS/UNASSIGNED:= .046). CONCLUSIONS/UNASSIGNED:There were no VUAS after Retzius-sparing RARP, and Retzius-sparing vs standard approach was associated with lower odds of stenosis. Endoscopic management with structured self-catheterization achieved high success without worsening incontinence. Prospective studies are needed to validate our findings.

Immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival for patients with early-stage NSCLC who are candidates for surgical resection. ICIs enhance antitumor responses and improve a variety of perioperative outcomes when used in the neoadjuvant, adjuvant, or perioperative setting. This review summarizes immunotherapies currently approved for neoadjuvant, adjuvant, and perioperative treatment of resectable NSCLC and the supporting evidence for approval. Gaps in data and future areas of clinical interest of using immunotherapies to maximize survival outcomes are also discussed.

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/UNASSIGNED:Cardiac stress testing is a cornerstone of risk stratification and management in patients with chronic coronary disease, yet the consistency and accuracy of its interpretation remain poorly defined. This analysis evaluated variation in the interpretation of myocardial ischemia between enrollment sites and core laboratories in the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches). METHODS/UNASSIGNED:ISCHEMIA was a global (37 countries, 2012-2018) randomized trial of an initial invasive versus conservative strategy in patients with chronic coronary disease and moderate or severe ischemia. This analysis included participants with site-interpreted qualifying stress tests-nuclear, echocardiography (echo), cardiac magnetic resonance, or exercise tolerance test-and independent core laboratory adjudication. Core laboratories, serving as the reference standard, reinterpreted tests blinded to site results. A trinary outcome variable (site underestimation, concordance, or overestimation) was defined by comparing site-determined ischemia levels to standardized core lab assessments. Adjusted mixed-effects logistic regression models with random site intercepts assessed variability. RESULTS/UNASSIGNED:Among 6971 participants (mean age, 62.8 years; 73% men), site interpretations showed 0% no/mild (by design), 43% moderate, and 57% severe ischemia. Core labs reclassified these as 8% none, 11% mild, 30% moderate, and 51% severe ischemia. For the imaging modalities, median site-core lab agreement rates were ≈55%; nearly 25% of site-classified moderate/severe cases were downgraded to no or mild ischemia by core labs. Adjusted median odds ratios for site overestimation were 2.36 (95% CI, 2.02-2.82; nuclear), 1.98 (95% CI, 1.62-2.60; echo), 1.89 (95% CI, 1.0-5.41; cardiac magnetic resonance), and 2.15 (95% CI, 1.76-2.79; exercise tolerance test). Adjusted median odds ratios for underestimation ranged from 1.25 to 1.77. CONCLUSIONS/UNASSIGNED:In ISCHEMIA, enrollment sites frequently overestimated or underestimated the severity of myocardial ischemia compared with core laboratory assessments, highlighting the need for strategies to improve the consistency and accuracy of stress testing interpretation in patients with chronic coronary disease. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

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.

Concentrated bone marrow aspirate (cBMA) is an autologous biologic increasingly used in orthopaedic surgery for its regenerative potential. It contains mesenchymal stem cells (MSCs), growth factors, and cytokines that contribute to tissue repair and immunomodulation. Mesenchymal stem cells primarily exert their effects through paracrine signaling and macrophage reprogramming, promoting a shift from a pro-inflammatory (M1) to a reparative (M2) phenotype. Emerging evidence also suggests a role for mitochondrial transfer in this process. In foot and ankle surgery, cBMA has been investigated in the management of osteochondral lesions of the talus, fracture healing, and tendon disorders. Early clinical studies suggest potential improvements in functional outcomes, healing rates, and revision rates; however, the available evidence remains heterogeneous and is largely limited to small, non-randomized studies. Variability in cBMA preparation and reporting further limits comparability across studies. As such, while cBMA represents a promising adjunct in foot and ankle surgery, its clinical role is not yet fully defined. Future research should focus on prospective, controlled studies with standardized methodologies and explore emerging cell-free approaches, including MSC-derived extracellular vesicles, to optimize regenerative strategies.

BACKGROUND:Chronic axial spinal pain is one of the leading causes of disability. The literature demonstrates that expenditures for low back and neck pain continue to rise, not only in parallel with increasing disability, but also with escalating healthcare costs, accounting for the highest spending among multiple disease categories. Based on current evidence utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been identified as potential sources of spinal pain. STUDY DESIGN/METHODS:A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks. OBJECTIVE:To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain. METHODS:Methodological quality of the included studies was assessed using the Quality Appraisal of Reliability Studies (QAREL) instrument. Only diagnostic accuracy studies meeting at least 50% of the predefined inclusion criteria were included in the analysis.The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Levels of evidence were classified using a modified best evidence synthesis, ranging from Level I to Level V.Data sources included relevant literature identified through PubMed and other electronic searches published from 1966 through September 2025, Cochrane reviews, and manual searches of the bibliographies of primary and review articles. OUTCOME MEASURES/METHODS:Eligible studies were required to use placebo-controlled or comparative local anesthetic blocks. A positive diagnostic standard was defined as at least 50% pain relief from baseline scores along with the ability to perform previously painful movements. RESULTS:The available evidence demonstrated Level I for lumbar facet joint nerve blocks, based on 18 studies employing dual diagnostic blocks, demonstrating 75% to 80% pain relief, with an average prevalence of 16% to 45% and estimated or presumed false-positive rates of 25% to 50%.Evidence for the diagnosis of cervical facet joint pain using cervical facet joint nerve blocks is Level II, derived from 12 controlled diagnostic accuracy studies, showing substantial heterogeneity and internal inconsistency. Reported prevalence ranged from 36% to 67% with ≥ 80% pain relief and estimated or presumed false-positive rates of 26% to 63%.The level of evidence for the diagnostic accuracy of thoracic facet joint nerve blocks is Level II, based on 3 studies using dual diagnostic blocks, demonstrating 80% or greater pain relief, with prevalence ranging from 34% to 48% and estimated or presumed false-positive rates ranging from 42% to 58%. LIMITATIONS/CONCLUSIONS:Limitations of this systematic review include the limited number of studies involving the thoracic spine, ongoing debate regarding the appropriate reference standard, challenges in determining false-positive rates, concerns regarding the appropriateness of diagnostic blocks, the scarcity of recent publications, and issues related to clinical utility. CONCLUSION/CONCLUSIONS:There is Level I evidence for the diagnostic accuracy of lumbar facet joint nerve blocks and Level II evidence for cervical and thoracic facet joint nerve blocks in the evaluation of chronic spinal pain.

PURPOSE/UNASSIGNED:Patients with breast cancer isolated local-regional recurrence (iLRR) can benefit from salvage reirradiation (reRT) to provide durable control and prevent further progression. Conformal radiation techniques like pencil beam scanning (PBS) proton beam therapy (PBT) may improve the reRT therapeutic ratio by limiting cumulative dose and improving target region dose delivery. MATERIALS AND METHODS/UNASSIGNED:Consecutive patients between 8/2019-9/2025 treated with PBS-PBT reRT for breast cancer iLRR with prior dose overlap were identified. Clinicopathologic, treatment, and outcomes details were collected. Associations between clinical/treatment factors and time to recurrence and grade (G) ≥2 adverse events (AEs) were evaluated with Fine-Gray models and logistic regression, respectively. Correlations between DVH metrics and late AEs were assessed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS/UNASSIGNED:Seventy patients were identified with median first course (C1), reRT course (C2), and cumulative doses of 53, 50, and 106Gy(RBE), respectively. During C2, 82.2% received comprehensive nodal irradiation. Median follow-up was 30 months. Two- and three-year rates of any recurrence were 14% and 17%, and OS were 100% and 95%, respectively. Maximum acute G2 and G3 AEs occurred in 50% and 7%, and late G2 and G3 AEs in 34% and 10%, respectively. Rib fractures developed in 21.1% and were associated with C1 and C2 chest wall D200cc and C1 rib D10cc. CONCLUSION/UNASSIGNED:In the largest experience of PBT reRT for breast cancer iLRR to date, we report promising disease control and limited severe AEs despite a high-risk patient cohort. We provide dose metrics that can serve as the foundation for reRT dose constraints and be further refined in future reRT investigations.