Citations

(1) Background: Mammographic breast density (MBD) is a well-established predictor of breast cancer risk, yet the biological mechanisms underlying this association remain incompletely understood. MBD is characterized by alterations in breast stromal architecture, including increased collagen deposition and changes in immune cell composition. Given emerging evidence that the breast harbors a resident microbiome, we investigated whether the breast tissue microbiome correlates with MBD. (2) Methods: Adjacent normal breast tissue was collected under sterile conditions from 33 women undergoing surgery for benign or malignant breast disease. DNA was extracted and subjected to 16S rRNA gene sequencing (Illumina MiSeq). (3) Results: We observed a non-significant trend toward lower α-diversity in high-MBD samples compared to low-MBD samples, p = 0.13. β-Diversity analyses identified a modest association between MBD and microbial community composition (MiRKAT p = 0.049). A random forest-based model incorporating genus-level relative abundances improved prediction of MBD over clinical characteristics alone, identifying Corynebacterium (Actinobacteria) and other genera as key predictors. (4) Conclusions: Breast tissue microbial features vary with mammographic breast density, suggesting a potential association with density-associated breast cancer risk. These exploratory findings warrant validation in larger cohorts to better elucidate biological mechanisms and clinical relevance.

Abstract INTRODUCTION Guidelines recommend non-surgical biopsy for indeterminate pulmonary lesions > 8 mm. Shape-sensing robotic-assisted bronchoscopy (ssRAB) is growing in use to biopsy small pulmonary nodules; however current literature is limited to single center studies with limited follow-up. This study, PRECIsE, assessed safety and performance of the first ssRAB iteration across multiple sites and nascent users. METHODS Prospective, multicenter, observational study evaluating ssRAB without cone-beam CT guidance in patients with nodules 10–30 mm located in or beyond the sub-segmental airways. Patients were followed for 2 years; the primary endpoint was sensitivity for malignancy with diagnostic yield, and safety as secondary endpoints. Multilevel logistic regression models were used to control for factors associated with sensitivity and diagnostic yield. RESULTS A total of 305 procedures were performed across 6 centers. Median nodule size was 17.0 mm (IQR: 14.0–23.0) with bronchus sign present in 37% of cases. Sensitivity for malignancy through 2 years was 81.3% (95% CI: 75.7, 86.1). Multi-level modelling demonstrated female sex, smaller nodule size, lower lobe location, semi-solid density, and higher body-mass-index were associated with lower sensitivity. Diagnostic yield was 74.1% (95% CI: 68.8, 78.9) according to the ATS/ACCP criteria and 77.5% [95% CI: 72.4, 81.8] according to the intermediate criteria. Multi-level modeling demonstrated a non-significant site/center level effect on ATS/ACCP diagnostic yield (P = .36). Pneumothorax requiring intervention was 1.6% (5/305); bleeding was 1.0% (3/305) with two (2) Nashville grade 2 and one (1) Nashville grade 3 events. CONCLUSIONS The first iteration of ssRAB demonstrated encouraging performance and a strong safety profile among nascent users for the biopsy of small peripheral nodules.

Background Prior authorization (PA) is a major source of administrative burden, treatment delay, and clinician burnout. Artificial intelligence (AI), particularly large language models (LLMs), is increasingly used to assist with clinical documentation, yet its reliability for payer-facing administrative tasks remains uncertain. Objective To evaluate the quality of PA letters drafted by ChatGPT-5 for commonly used medications requiring PA in nephrology. Quality was evaluated based on correctness and strength of clinical reasoning. Methods We created a single standardized prompt and applied it across 29 nephrology scenarios to generate PA letters. Each PA letter was reviewed against four criteria: 1) absence of false statements or hallucinations, 2) correctness of ICD-10 coding, 3) presence and validity of citations, and 4) clinical reasoning, rated on a 4-point Likert scale (illogical, weak, adequate and strong). FDA drug labels, KDIGO guidelines and related randomized controlled trials were used as reference standards. Results Out of 29 letters, one letter (3.5%) contained false statements mentioning an irrelevant clinical trial. The ICD-10 diagnosis code was correct in 23 letters (79.3%), most errors were related to chronic kidney disease (CKD) staging or internal diagnostic inconsistencies. 27 letters (93.1%) cited valid references, with one letter citing an incorrect trial and another one citing a correct KDIGO guideline with inaccessible link. Twenty-six letters (89.7%) demonstrated strong clinical reasoning, supported by guideline-oriented or FDA label–aligned justification. The remaining 3 letters were rated as adequate reasoning. The main areas for improvement involved citing relevant references and emphasizing special considerations, for example Risk Evaluation and Mitigation Strategy (REMS) compliance for eculizumab. Conclusions ChatGPT-5 can generate clinically coherent PA drafts for nephrology medications, but limitations in coding precision and citation reliability persist. With appropriate oversight, AI-assisted documentation may reduce administrative burden while maintaining safety and accuracy.

Background Uncontrolled hypertension is common in chronic kidney disease (CKD) patients. Electro-hydraulic acoustic therapy (eHAT) is a non-invasive treatment that may lower blood pressure (BP), but its safety and efficacy in CKD remain unclear. This study aimed to evaluate eHAT's feasibility and safety in this population. Methods In this single-arm, prospective, single-center proof-of-concept study, CKD patients received six eHAT treatments over three weeks. BP was assessed in-office (attended and unattended) at baseline and at 4-, 12-, 24-, and 48-weeks post-treatment. Ambulatory BP monitoring (ABPM) was performed at baseline, 12, and 48 weeks. The primary endpoint was change in systolic office BP (OBP) from baseline to 12 weeks. Secondary endpoints included additional BP measurements, kidney function, and safety. Results Fifteen patients completed all follow-ups. At 12 weeks, mean systolic OBP decreased by 9.73 mmHg (SD 14.77; p = 0.0032) and remained significantly lower at 24 weeks (−7.67 mmHg; p = 0.0335) and 48 weeks (−19.40 mmHg; p < 0.0001). Diastolic OBP reductions were significant at 12 ( p = 0.0413) and 48 weeks ( p = 0.0022). By 12 weeks, 26% of participants reduced the number or dose of antihypertensive medications. Kidney function remained stable throughout. No safety signals were detected. Conclusion Our study highlights the feasibility and tolerability of eHAT in patients with CKD and HTN. Nonetheless, due to the small sample size and lack of a control group, these findings should be considered preliminary.

Background: Transanal total mesorectal excision (taTME) facilitates sphincter preservation in low rectal cancer. Preliminary results and functional outcomes from the North American multicenter phase II taTME trial (NCT03144765) have been published. Three-year outcomes are reported. Methods: Patients with stage I to III rectal adenocarcinoma were enrolled across 11 centers (2017–2022). Endpoints included TME grade, 3-year overall survival, disease-free survival, cancer-specific survival, recurrence, late (beyond 90 d) complications, and stoma-free survival. Surveillance followed National Comprehensive Cancer Network guidelines, with pelvic magnetic resonance imaging (MRI) at 3 years to assess for pelvic sidewall recurrence when possible. Kaplan–Meier analysis assessed oncologic outcomes. Results: One hundred patients underwent taTME for tumors at a median of 5.8 cm from the anal verge, with intersphincteric resection in 36% and handsewn anastomosis in 54%. Median follow-up was 50.9 months. Late complications occurred in 32 patients, including 21 severe (Clavien-Dindo ≥3). Late anastomotic complications occurred in 5 patients; one required surgical revision. Estimated 3-year overall survival, cancer-specific survival, and disease-free survival were 93.7%, 96.6%, and 84.6%, respectively. Distant recurrence occurred in 15 patients (median: 17.6 months), most commonly in the lung and liver. Locoregional recurrence occurred in 2 patients. Preoperative N stage, lymph node yield, tumor deposits, and perineural invasion were associated with recurrence. Among 100 patients diverted at taTME, 97% were stoma-free at 3 years; 4 patients later underwent secondary diversion. Conclusions: Three-year outcomes of this multicenter trial support the safety and efficacy of taTME in resectable mid and low rectal tumors, with outcomes comparable to contemporary studies. Longer-term oncologic and functional outcomes are needed.

Abstract Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein–RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. One Sentence Summary Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance

Pediatric obesity represents an urgent public health concern, with rapidly increasing prevalence across all regions. While genetic susceptibility contributes significantly to interindividual variability in weight, the significant increase in obesity prevalence over the last 30 years is driven by shifts in environmental contributors. This narrative review will summarize evidence on the major environmental determinants of childhood obesity. Environmental contributors to obesity include the food environment, physical activity and built environments, socioeconomic and community context, home and family environments, digital exposures, early life and chemical obesogens and policy drivers. These environmental factors influence activity patterns, dietary habits, sleep, and stress. Additionally, many of these contributing factors cluster within communities that are disadvantaged, thereby increasing predisposition of specific racial, ethnic and socioeconomic groups to childhood obesity. We highlight research gaps and opportunities for multisectoral interventions aligned to impact the growing prevalence of childhood obesity.

TPS913 Background: A subset of patients with MIBC who receive neoadjuvant therapy (NAT) prior to radical cystectomy (RC) have a pathologic complete response (pCR) at the time of RC. With pCR rates of 22-42% in patients with MIBC following NAT (+/- ICI), whether a subset of patients with good clinical response to NAT can avoid RC is an important unanswered question, especially with the development of more active systemic therapies. HCRN 16-257 evaluated maintenance nivolumab in lieu of cystectomy in patients with MIBC who experienced clinical complete response (cCR) following neoadjuvant GC and nivolumab. The cCR rate was 48%, but 8/33 (24%) patients who elected bladder preservation subsequently underwent cystectomy for local disease recurrence. The RETAIN trial also evaluated omission of local therapy following neoadjuvant therapy with a 2-year bladder preservation rate in patients with ≤T1 disease following NAC of 54% (22/41). Of the 9/25 (36%) patients on that trial developed metastatic disease, 8/9 developed localized disease before metastasizing. These data illustrate the critical role that local therapy plays in patients with MIBC. For this reason, we believe that radiotherapy to the bladder combined with ICI will improve bladder intact event-free survival (BI-EFS). This trial also allows for patients to opt for bladder preservation based on a good clinical response to NAT. Methods: This is a single arm, phase 2 trial (NCT07061964) evaluating risk-adapted bladder preservation therapy for patients with MIBC following NAT. NAT consists of any NCCN guideline concordant therapy for MIBC. Patients with cT2-T4aN0M0 MIBC who complete NAT will be eligible if they have ≤T1 disease on post-NAT TURBT, confirmed by biopsies of prior tumor sites and systematic sampling (left/right lateral walls, dome, posterior wall, trigone). Patients will receive 55 Gray (Gy) in 20 fractions of radiotherapy (RT) to the bladder with 1 year of pembrolizumab. The primary objective is to evaluate whether 3-year BI-EFS is at least 70% in participants with < = T1 (without multifocal CIS) following NAT and RT with 1 year of pembrolizumab. Secondary objectives include local muscle invasive recurrence-free survival, metastasis-free survival (MFS), overall survival (OS), the rate of salvage cystectomy, and evaluation of the frequency and severity of toxicities in participants who receive RT and pembrolizumab. Plasma and urine will be banked for future correlative studies. S2427 was activated in September 2025 with an accrual goal of 111 patients. Clinical trial information: NCT07061964 .