Faculty Bibliography

PURPOSE/OBJECTIVE:Rare renal cell carcinoma (RCC) subtypes present unique challenges for clinical trial design and drug development. This consensus initiative aimed to provide actionable expert guidance on advancing preclinical and clinical development of rational therapeutic strategies for non-clear cell RCC variants, including papillary, chromophobe, MiT family/translocation, collecting duct, renal medullary carcinoma, and fumarate hydratase-deficient RCC. METHODS:A modified Delphi method was employed to develop consensus statements among a multidisciplinary panel of 46 experts in urologic oncology, medical oncology, radiation oncology, molecular biology, genetics, and biostatistics, with representatives from pharmaceutical industry, regulatory affairs, and patient advocacy. Over multiple rounds, including an in-person meeting on November 13, 2025, 20 initial statements were proposed, evaluated, refined, and voted on. Consensus was defined a priori as a median Likert score ≥8 out of 10. RESULTS:Twenty final consensus statements were endorsed across 5 thematic domains: (1) Trial Design and Endpoints; (2) Perioperative Trials; (3) Operations and Accrual; (4) Biology-driven and Histology/molecular Strategy Trials; and (5) Preclinical Efforts, Target Identification, and Early Signal Testing. Key recommendations include prioritizing histology-specific trial designs over pooled "non-clear cell" approaches, adopting innovative single-arm and adaptive designs for ultra-rare subtypes, leveraging patient advocacy collaborations and natural history registries, and pursuing mechanism-informed therapeutic development. CONCLUSIONS:These recommendations provide a framework to guide researchers, cooperative groups, regulatory bodies, and pharmaceutical industry partners in advancing evidence generation and therapeutic development for patients with rare kidney cancer variants.

Kaplan-Meier analysis of time to first all-cause readmission over 12 months among older adults with ischemic heart disease randomized to 3 months of mobile health cardiac rehabilitation (mHealth-CR) or usual care. There was no significant difference in time to first readmission between groups (log-rank P = 0.26).

BACKGROUND/UNASSIGNED:late-onset CRC (LOCRC). METHODS/UNASSIGNED:Using the National Inpatient Sample (NIS) (2016-2020), we identified hospitalizations with a primary diagnosis of CRC. Patients were categorized from a hospital-based classification of EOCRC (<50 years) or LOCRC (≥50 years). Multivariate logistic regression assessed associations between body mass index (BMI), demographics, and outcomes including inpatient mortality, length of stay (LOS), and chemotherapy use. RESULTS/UNASSIGNED:Among 246,231 CRC hospitalizations, 13.7% (n=33,662) were EOCRC. Compared to LOCRC, EOCRC patients were more likely to be female [odds ratio (OR): 1.09], Black (OR: 1.17), Hispanic (OR: 1.56), or Asian (OR: 1.29), and more often covered by Medicaid, private insurance, or have no coverage. EOCRC patients had higher rates of tobacco use disorder (OR: 1.26) and depression (OR: 1.13), but lower prevalence of diabetes, coronary artery disease (CAD), and alcohol use disorder. EOCRC hospitalizations had lower inpatient mortality (OR: 0.649). Inpatient chemotherapy was more common in EOCRC (OR: 1.78). Obesity was positively associated with EOCRC for BMI 30-39 (OR: 1.07) and BMI ≥40 (OR: 1.50), while LOCRC showed inverse associations for the same BMI groups. CONCLUSIONS/UNASSIGNED:EOCRC is associated with unique demographic and clinical profiles when compared to LOCRC, highlighting disparities by race, insurance status, and comorbidities. The higher rate of inpatient chemotherapy use in EOCRC warrants further study to evaluate its clinical necessity and outcomes. These findings reinforce the need for targeted screening and inpatient care strategies for younger and underserved patient populations.

INTRODUCTION/UNASSIGNED:Recent federal funding cuts have created pauses in admissions, hiring, and execution of research studies at academic medical centers internationally. These monetary reductions have also impacted allowances for non-essential faculty travel. As a result, faculty may now be faced with challenges in how they obtain professional development. METHODS/UNASSIGNED:A cross-sectional, exploratory study was implemented to discover the impact of funding cuts on faculty travel for professional development opportunities, as well as strategies medical educators are using to mitigate the current landscape. RESULTS/UNASSIGNED:Findings indicate that faculty now must use alternative methods to obtain professional development and that institutional guidance is lacking in how to do so. DISCUSSION/UNASSIGNED:Authors provide concrete action steps for faculty to take amidst this challenge to remain engaged in professional development.

Enteric hyperoxaluria (EH) results from increased oxalate bioavailability in the gastrointestinal (GI) tract, often affecting patients with inflammatory bowel disease (IBD). We investigated the pathophysiology of EH in an ileitis mouse model, hypothesizing that fat malabsorption, increased gut permeability, and microbial shifts collectively contribute to the hyperoxaluric phenotype in the setting of GI tract inflammation. SAMP1/YitFc (SAMP1) mice and their parental AKR controls were fed one of three diets varying in fat content (10%, 45%, or 60% kcal), each supplemented with 1% oxalate, for 6 weeks. Plasma (P), urine (U), oxalate (Ox), and creatinine (Cr) levels were measured, while stool lipid species were analyzed using mass spectrometry. Intestinal permeability was assessed using sucralose and ¹³C₂ oxalate gastric gavage in SAMP1 and AKR mice. Histology, qPCR, and Western blotting were performed on kidney, liver, and GI tissues. Microbial DNA was analyzed at the community, genus, and functional levels. Changes in bacterial metabolic pathways were investigated in the mice fed the highest fat content. The oxalobiome of SAMP1 and AKR mice was characterized using our bioinformatics pipeline. On high-fat diets, SAMP1 mice had higher UOx, POx, and PCr levels than AKR mice. Increased levels of diacylglycerols and free fatty acids in SAMP1 stool samples suggested fat malabsorption. A decrease in ZO1 and occludin intestinal expression, coupled with significantly increased urinary sucralose and oxalate levels, indicated increased intestinal permeability. Microbiome analysis revealed the enrichment of Lactobacilli and Bacteroides in SAMP1 mice, with bacterial pathways favoring lipid synthesis and glyoxylate metabolism. Ileal SLC26A6 protein expression was significantly reduced in SAMP1 mice. SAMP1 mice also developed progressive kidney injury with interstitial inflammation. These findings highlight fat malabsorption as a central pathophysiologic disturbance in EH that reduces luminal calcium availability for oxalate binding, is associated with enhanced intestinal permeability, and accompanies microbiome and enzymatic pathway alterations.

PURPOSE OF REVIEW/OBJECTIVE:To describe the relationship between reflux and bronchiectasis and to appraise recent literature on reflux characterization, clinical outcomes, and management strategies in patients with bronchiectasis. RECENT FINDINGS/RESULTS:Reflux is common in bronchiectasis and has been linked to worse respiratory symptoms and quality of life, more exacerbations and healthcare use, lower lung function, and higher mortality. These associations are seen across several cohorts, but nearly all data are observational, use variable reflux definitions, and cannot determine whether reflux contributes to bronchiectasis progression or simply identifies patients with more severe disease. Proposed pathways include microaspiration-related airway injury, reflex-mediated cough amplification, and microbial dysbiosis. No randomized bronchiectasis-specific trial has shown improved respiratory outcomes with reflux-directed therapy, and acid suppression alone is unlikely to address nonacid reflux, microaspiration, cough-reflex pathways, or airway dysbiosis. SUMMARY/CONCLUSIONS:In bronchiectasis, reflux should be separated into clinically relevant phenotypes, including typical gastroesophageal reflux disease, proximal or nonacid reflux, laryngopharyngeal symptoms, dysphagia, and aspiration. Management should be guided by the suspected reflux or aspiration pattern because acid suppression alone may not address airway-relevant reflux. Future studies should pair objective reflux and swallowing measures with bronchiectasis-specific outcomes.

Penicillin allergy labels are common and clinically consequential. Approximately 10% of patients report a penicillin allergy, yet most are not truly allergic and can safely receive beta-lactams. In the inpatient setting, these labels drive use of broader-spectrum agents, contributing to increased healthcare-associated infections, antimicrobial resistance, longer hospital stays, and higher costs. Recent evidence supports delabeling as a key antimicrobial stewardship strategy. The PEN-FAST clinical decision rule enables identification of low-risk patients suitable for streamlined evaluation. The PALACE randomized trial demonstrated that, among low-risk adults, direct oral penicillin challenge is noninferior to traditional skin testing and associated with very low rates of adverse reactions. This narrative review summarizes current evidence on epidemiology, mechanisms, risk stratification, and delabeling strategies, and provides practical recommendations for integrating penicillin allergy delabeling into routine clinical practice.

BACKGROUND:Living systematic reviews (LSRs) aim to synthesize all available evidence meeting pre-specified eligibility criteria to answer a research question and to continually update the review by incorporating new evidence as it becomes available. Through the initial version of an LSR is published, researchers determine whether a full update should be triggered. Over periodic iterations, modifications may be needed. Emerging evidence, external factors, methodological developments, and other considerations may necessitate adjustments to the original eligibility criteria, scope, or methods. However, guidance is limited on when cumulative changes warrant a new review rather than a continued update. DISCUSSION/CONCLUSIONS:In this paper, we provide rationale and guidance for deciding when updating an existing LSR is appropriate and when initiating a new, separate review is more appropriate. Several considerations should be considered, including changes in scope, eligibility criteria, or research question, reformulation of the conceptual framework, major methodological overhauls, foundational concerns with the original review, and practical, logistical, or publication considerations. In some circumstances, a hybrid approach involving continual updating of an existing review alongside development of a complementary new review may also be appropriate. Clear guidance on when to continue, restart, or branch into a new review will support the integrity, transparency, and usability of living evidence synthesis.

OBJECTIVE:The PDN-Sensory randomized controlled trial (RCT) evaluated the effects of high-frequency 10-kHz spinal cord stimulation (10-kHz SCS) on pain and sensory function in individuals with painful diabetic neuropathy (PDN). RESEARCH DESIGN AND METHODS/METHODS:Participants were randomized 1:1 to conventional medical management (CMM) alone or 10-kHz SCS plus CMM. The primary and key secondary end points were the proportions of participants with pain response (≥50% lower limb pain relief) and sensory improvement (≥3-point reduction in modified Toronto Clinical Neuropathy Score [mTCNS]). Hierarchical secondary outcomes included intraepidermal nerve fiber density (IENFD), sleep, and health and neuropathy-related quality of life (QoL). IENFD and mTCNS assessments were allocation blinded. RESULTS:A total of 91 participants were randomly assigned to CMM alone (n = 50) or 10-kHz SCS plus CMM (n = 41). In a modified intention-to-treat worst-case analysis, 27 of 34 participants in the 10-kHz SCS group who underwent a temporary trial achieved the primary outcome, versus 2 of 50 CMM-alone participants (P < 0.001). Among those with 6-month data, mTCNS sensory improvement was observed in 16 of 29 (55.2%) 10-kHz SCS participants versus 12 of 48 (25.0%) CMM-alone participants (P = 0.01). The mean change in lower-calf IENFD was 0.58 fibers/mm with 10-kHz SCS versus -0.07 with CMM alone (P = 0.03). Eight of 10 hierarchical secondary end points were met (including sleep and QoL). CONCLUSIONS:The PDN-Sensory RCT replicated previous pain-reduction findings and showed prespecified, objective improvements in sensory function and IENFD. These 6-month findings support clinically meaningful benefit and are consistent with a potential disease-modifying effect that requires longer-term confirmation.