Faculty Bibliography

BACKGROUND:Using high-frequency jet ventilation (HFJV) to improve catheter stability with conventional energy sources during atrial fibrillation (AF) ablation is associated with higher ablation success and improved arrhythmic outcomes. The utility of HFJV with pulsed field ablation (PFA) for AF is unclear. We investigated the utility of HFJV vs. standard ventilation in PFA for AF. METHODS:We studied consecutive cases of patients with AF undergoing PFA between 5/6/24 to 10/10/24. Procedural data collected included total procedure time and major periprocedural complications. Clinical data collected included atrial tachyarrhythmia (ATA) recurrence, stroke, and major bleeding at one-year follow-up. Outcomes were compared in cases where HFJV was used vs. standard ventilation. RESULTS:A total of 512 patients were included in this study (307 standard ventilation, 205 HFJV). There was no difference in ATA recurrence by Kaplan-Meier survival analysis between standard ventilation and HFJV groups (log rank test p = 0.59). When comparing standard ventilation vs. HFJV groups, there was no difference in ATA recurrence at one year (23% vs. 26%; p = 0.43), AF burden on continuous monitoring (9 ± 5% vs. 8 ± 24%; p = 0.85), total procedure time (114 ± 38 vs. 115 ± 33 min; p = 0.78), or major periprocedural complications (3% vs. 2%; p = 0.64). There was no difference in arrhythmic outcomes when patients were stratified by AF type and whether patients presented for first-time or redo ablation. CONCLUSION/CONCLUSIONS:Using HFJV in PFA for AF produces similar sinus rhythm maintenance overall and when stratified by AF type without affecting procedure times or complication rate.

BACKGROUND:The optimal number of pulsed field ablation (PFA) applications during atrial fibrillation (AF) ablation is unclear. We hypothesized that the number of PFA applications would predict atrial tachyarrhythmia (ATA) recurrence rates. OBJECTIVE:To determine whether higher numbers of PFA applications would decrease ATA recurrence rates. METHODS:We studied cases of patients with AF undergoing first-time ablation with PFA between 5/6/24 and 10/7/24. All patients underwent pulmonary vein and posterior wall isolation. The primary outcome was ATA recurrence. Additional outcomes included stroke, post-procedural acute kidney injury (AKI), total procedure time, and major periprocedural complications. Univariable and multivariable analyses were performed to determine if the number of PFA applications predicted ATA recurrence. RESULTS:In a cohort consisting of 177 patients, univariable and multivariable analysis showed that the number of PFA applications split at the smallest quartile (< 57 applications) versus the largest three quartiles (≥ 57 applications) was the strongest predictor of ATA recurrence (p = 0.03). ATA recurrence at 1 year (29% vs. 8%; p < 0.01) and AF burden on continuous monitor (4% vs. 0%; p < 0.01) was higher with the standard (< 57 applications) vs higher (≥ 57 applications) PFA dose groups. When comparing the standard versus higher PFA dose groups, there was no difference in total procedure time (106 vs. 107 min; p = 0.77), major periprocedural complications (0% vs. 2%; p = 0.33), or post-procedural AKI (2% vs. 2%; p = 0.69). CONCLUSION/CONCLUSIONS:Increasing number of PFA applications is associated with reduced ATA recurrence. A higher number of PFA applications may decrease ATA recurrence without affecting procedure times or complication rate.

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.

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.

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.

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.

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.

OBJECTIVES/OBJECTIVE:Chronic hepatitis C can complicate the treatment of coronary artery disease (CAD), especially among racial and ethnic minority patients. This study explores racial and ethnic differences in the prevalence of hepatitis C and inpatient mortality among patients admitted to the hospital primarily for a CAD event in the USA. METHODS:An observational analysis was conducted using data from the 2016 to 2021 National Inpatient Sample, including 1,946,182 CAD patients, of whom 7426 (0.38%) had chronic hepatitis C. We performed weighted logistic regressions to analyze the relationship between race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and other races) regarding the prevalence of hepatitis C and inpatient mortality, adjusting for patient sociodemographic characteristics and comorbidities. RESULTS:Non-Hispanic Black patients had the highest prevalence of hepatitis C (adjusted odds ratio [aOR] = 1.57, 95% confidence interval [CI] 1.48-1.67) and Hispanic patients with underlying hepatitis C had the highest in-hospital mortality (aOR = 1.56, 95% CI 1.11-2.20) compared to non-Hispanic White patients and other racial groups. CONCLUSIONS:We found significant racial and ethnic differences in the prevalence of hepatitis C and mortality among patients with underlying chronic hepatitis C admitted primarily for CAD events in the USA. This disparity may exist due to lower rates of hepatitis C virus (HCV) treatment, higher severity and prevalence of underlying health conditions, poorer healthcare access and insurance coverage, and a higher rate of alcohol use and cirrhosis progression in minority populations.