OBJECTIVE:To examine characteristics associated with bacillus Calmette-Guerin (BCG) receipt and the impact of supply shortages on BCG utilization and potential healthcare disparities, given global supply shortages have strained access since 2012. METHODS:We analyzed 16,958 adults ≥66 years with newly diagnosed high-grade non-muscle invasive bladder cancer from 2002-2017 using SEER-Medicare. We examined the associations of baseline characteristics and 3 supply shortage events (in 2012, 2014, and 2017) with BCG receipt using multivariable regression, interrupted time series (ITS) analysis, and regression discontinuity analyses. RESULTS:BCG receipt increased from 37% in 2002 to 60% in 2017 in eligible patients. Overall, in multivariable analyses, later diagnosis year, higher income and education status, higher T stage, and higher annual surgeon TURBT volume were associated with increased likelihood of BCG receipt, while older age, single/widowed/divorced status, higher Charlson comorbidity index (CCI), and current/former smoking status were associated with lower likelihood. ITS and regression discontinuity analyses showed sustained growth in BCG utilization that was minimally impacted by supply shortages, aside from a significant growth acceleration after the 2014 shortage. Effect modification analyses demonstrated no consistent associations of patient or socioeconomic characteristics with supply shortage events to suggest a differential impact among specific subgroups. CONCLUSION:From 2002 to 2017, BCG utilization for high-risk NMIBC significantly increased from 37% to 60%, with minimal impact from supply shortages. While baseline characteristics influenced BCG receipt, there was no consistent evidence that BCG supply shortages exacerbated existing disparities.

INTRODUCTION:Non-muscle invasive bladder cancer (NMIBC) is a chronic disease with a lifelong treatment burden that may cause substantial urinary morbidity. Such quality-of-life changes remain understudied. We therefore evaluated the incidence and predictors of treatment for overactive bladder (OAB) among older adults following diagnosis of NMIBC. MATERIALS AND METHODS:We identified adults aged 66-89 years with newly diagnosed NMIBC from 2007 to 2017 in the linked SEER-Medicare database. We examined the incidence of treatment initiation for OAB following initial transurethral resection of bladder tumor (TURBT) and evaluated associations with baseline characteristics using Cox regression. RESULTS:We identified 9,819 patients, of whom 68% had Ta disease, 29% had T1 disease, and 4% had CIS. Within the first 12 months of TURBT, 7% of patients received treatment for OAB, and this increased to 15% of patients at 5 years. In the first year, the most utilized therapies were anticholinergic medications (early 3.72%, late 2.74%) and beta-3 agonists (early 0.11%, late 0.32%), while procedural OAB therapy utilization was rare (0.2%). On multivariable analysis, female gender (HR 1.26, 95% CI 1.11-1.42), congestive heart failure (HR 1.21, 95% CI 1.03-1.43), and T1 tumor stage (HR 1.27, 95% CI 1.12-1.44 vs. Ta) were independently associated with an increased risk of OAB treatment. CONCLUSIONS:The incidence of OAB requiring treatment among patients with NMIBC is substantial, with approximately one in six patients receiving treatment by 5 years after diagnosis. Predictive clinicopathologic features for OAB treatment-including, sex, high-risk tumor features, and repeat TURBT-may be useful for clinical counseling.

Importance:Until 2021, national guidelines upheld race-based equations that assigned higher kidney function estimates to Black patients, delaying subspecialist referral and transplant waitlisting. In 2023, the Organ Procurement and Transplantation Network (OPTN) mandated that US kidney transplants programs submit wait time modifications for Black candidates who were disadvantaged by these equations. Objective:To evaluate whether implementation of the OPTN wait time modification policy was associated with changes in kidney transplant rates by race and ethnicity in the US. Design, Setting, and Participants:This quasi-experimental study analyzed an OPTN database of all US adult kidney candidates actively waitlisted between January 2022 and June 2025. Interrupted time series analysis evaluated the association of policy implementation with changes in transplant rates using generalized estimating equations adjusted for secular trends, time-varying and time-invariant confounding factors, and a first-order autoregressive covariance structure. Data analyses were performed from July 2024 to July 2025. Intervention:Implementation of the OPTN wait time modification policy in January 2023. Main Outcomes and Measures:Kidney transplant rates by race/ethnicity and dialysis status, with outcome stratification by living and deceased donor kidney transplant (LDKT and DDKT). Results:The analysis included 181 314 kidney transplant candidates (mean [SD] age, 52.8 [13.1] years; 68 517 females [37.8%] and 112 797 males [62.2%]), including 56 344 Black candidates (31.1%) and 124 970 candidates of all other racial and ethnic groups (68.9%; including American Indian/Alaska Native, Asian, Hispanic/Latino, Native Hawaiian/Other Pacific Islander, White, multiracial, and unknown). From January 2023 through June 2025, 21 119 transplant candidates received wait time modifications, which added a median (IQR; range) of 1.7 (0.9-3.0; 0-21.2) years, and a total of 51 061 person-years of waitlist time. In interrupted time series analyses, among Black candidates, policy implementation was associated with an increase of 5.3 transplants per 1000 listings (95% CI, 3.5 to 7.0), with decreasing transplant rates thereafter (-0.10 transplants per 1000 listings per month; 95% CI, -0.17 to -0.03). Among all other candidates, implementation was associated with no significant change in overall transplant (0.6 transplants per 1000 listings; 95% CI, -1.8 to 0.7) and a parallel decreasing trend thereafter (-0.10 transplants per 1000 listings per month; 95% CI, -0.15 to -0.05). In secondary analyses, policy implementation was associated with increased overall and DDKT rates among Black preemptive and postdialysis candidates, no significant changes in LDKT for either group or DDKT for non-Black and/or Hispanic candidates, and a small secular increase in overall transplant rates. Conclusions and Relevance:This quasi-experimental study found that implementation of the wait time modification policy was associated with increased transplant rates among Black preemptive and postdialysis candidates. These findings provide evidence that remedying the harms of race-based medicine may be a promising approach to address racial kidney transplant inequities.

Objective:To evaluate whether superficial lymphatic anatomy and functional lymph node drainage are symmetric between the right and left upper extremities of healthy female volunteers and whether handedness is associated with symmetry of superficial lymphatic anatomy.Background:Symmetry of lymphatic anatomy has been assumed historically. This assumption of individual anatomic symmetry is being utilized clinically and in research without validation.Methods:Thirty-six normal female volunteers underwent bilateral indocyanine green (ICG) lymphography and lymphoscintigraphy of the upper extremities. Eight collecting vessel pathways of each upper extremity were mapped on ICG lymphography. Thirteen lymph node groups were visualized on lymphoscintigraphy. Symmetry of lymphatic anatomy and functional drainage were established by comparing the right and left extremities of each participant. Hand dominance was assessed by hand grip strength on a hand dynamometer.Results:Among the 36 participants, 10 (28%) showed symmetry of all 8 upper extremity lymphatic pathways with ICG. However, only 2 (6%) participants demonstrated complete symmetry among the 13 lymph node groups. Total symmetry of lymphatic channels was observed on ICG in 7 (39%) participants with hand dominance and 3 (17%) participants without hand dominance (X2 = 2.215, P = 0.137).Conclusions:Lymphatic anatomy and functional drainage of the upper extremities are not consistently symmetric. Functional nodal drainage as demonstrated by lymphoscintigraphy shows less symmetry than anatomic studies of lymphatic channels using ICG. Symmetric lymphatic anatomy does not appear to correlate with hand dominance. These findings challenge the prevailing assumption of left-right lymphatic symmetry.

INTRODUCTION:A delay beyond 12 weeks from diagnosis to radical cystectomy (RC) is considered to impart worse oncologic outcomes for patients with muscle-invasive bladder cancer (MIBC); however, no randomized clinical trials have examined this question. We therefore emulated a hypothetical target clinical trial using contemporary data to evaluate the association between time from diagnosis to RC and oncologic outcomes. METHODS:We conducted observational analyses using the National Cancer Database from 2006-2015 to emulate a hypothetical target trial in adults aged 40-79 years with incident cT2-4 N0 M0 urothelial carcinoma of the bladder, treated with RC from 4-18 weeks after diagnosis. We evaluated the association of late RC with pathologic upstaging at RC and overall survival (OS) and conducted exploratory analyses evaluating the association of time to RC with each outcome modeled flexibly. RESULTS:A total of 3747 patients were included, of which 2992 underwent early RC. Median followup was 32.2 months. In adjusted analyses, late RC was not associated with an increased risk of pathologic upstaging compared to early RC. In addition, there was no statistically significant difference in adjusted OS for late and early RC, respectively. Similar findings were observed across categories of cT stage, age, Charlson index, and gender. CONCLUSIONS:In observational analyses designed to emulate a hypothetical target trial of early vs. late RC, the timing of RC was not associated with a statistically significant increase in pathologic upstaging or a difference in OS when performed from 4-18 weeks after diagnosis. These results suggest the need to re-examine the traditional recommendations for timing of RC following diagnosis.

In 1996, Ciucci et al. described the presence of a lymphatic channel in the palmar skin that spanned the first interdigital space and anastomosed with lymphatic collaterals on the dorsal surface of the hand. This palmar lymphatic channel (a pathway we have named the Ciucci pathway) has yet to be described with in-vivo imaging. As the Ciucci pathway is a superficial-to-deep lymphatic communication, its visualization may provide insight into altered lymphatic routing following axillary lymph node dissection (ALND). Therefore, we investigated our ability to image this pathway with indocyanine green (ICG) lymphography. Healthy female volunteer and female breast cancer survivors without a history of BCRL at least two years after ALND underwent lymphatic mapping of the upper extremities with ICG lymphography. ICG was injected in six standard sites in the hand/wrist and upper arm. The presence of the Ciucci pathway was recorded and compared between cohorts with Fisher’s exact test. 110 arms of 55 healthy volunteers and 31 at-risk arms of 31 breast cancer survivors without BCRL were included. The Ciucci pathway was present in one of 110 (0.9

BACKGROUND:Lymphatic anatomy has primarily been described in cadaveric dissections. Mapping of the upper extremity superficial lymphatic system with indocyanine green (ICG) lymphography provides functional insights and detail to major anatomic variations. METHODS:Healthy female volunteers underwent lymphatic mapping of the upper extremities with ICG lymphography. ICG was injected in six standard sites in the hand/wrist and upper arm. Major anatomic variations of four main forearm pathways and connectivity to four upper arm pathways were described. RESULTS:90 arms of 45 volunteers were included. The posterior radial channel predominantly courses in the dorsal forearm (98%). The posterior ulnar forearm pathway courses in the dorsal forearm in the majority of arms (70%). The anterior radial and anterior ulnar forearm channels exclusively course in the volar forearm (100%). The posterior radial pathway connects to the bicipital (80%), lateral (48%), medial (9%), and tricipital (7%) upper am pathways. The posterior ulnar pathway connects to the lateral (54%), tricipital (51%), medial (21%), and bicipital (14%) upper arm pathways. The anterior radial pathway connects to the medial (50%) and bicipital (60%) pathways. The anterior ulnar pathway connects to the medial (54%) and bicipital (59%) pathways. CONCLUSIONS:Upper extremity lymphatic drainage to the lateral and tricipital pathways is enabled exclusively by the dorsal forearm channels suggesting their importance in BCRL risk. Variations of upper extremity lymphatic anatomy are relevant to the risk, prevention, and treatment of breast cancer-related lymphedema risk and warrant further study.

BACKGROUND:Lost wages following living donation may deter patients from pursuing living donor kidney transplantation (LDKT) and potential donors from being evaluated. METHODS:We randomized patients undergoing transplant evaluation to 1 of 2 donor wage reimbursement groups ($1500 or $3000 maximum) and encouraged them to discuss this reimbursement program with their social network. These patients were compared with matched historical controls (HCs) on the likelihood of LDKT and ≥1 donor evaluation within 1 y of transplant evaluation. Multivariable logistic regression adjusted for demographic and clinical factors known to be associated with LDKT. RESULTS:Access to any donor wage reimbursement (lost wages $1500 maximum reimbursement and lost wages $3000 maximum reimbursement combined versus HC) was not significantly associated with LDKT occurrence (adjusted odds ratio [aOR], 0.85; 95% confidence interval [CI], 0.39-1.85; P  = 0.68) or with the likelihood of having at least 1 donor evaluated within 1 y of initial evaluation (aOR, 1.07; 95% CI, 0.76-1.50; P  = 0.70) after covariate adjustment. Also, donor wage reimbursement level (lost wages $1500 maximum reimbursement versus lost wages $3000 maximum reimbursement) was not associated with LDKT (aOR, 0.73; 95% CI, 0.22-2.44; P  = 0.61) or with having a donor evaluation initiated (aOR, 0.65; 95% CI, 0.40-1.05; P  = 0.11). In an exploratory analysis extending follow-up to account for COVID-related shutdowns, access to wage reimbursement was associated with higher odds of LDKT compared with HC (aOR, 2.16; 95% CI, 1.12-4.18; P  = 0.02). CONCLUSIONS:Donor wage reimbursement, at the levels tested, did not increase LDKT or living donor evaluation likelihood in primary analyses, although exploratory findings suggest that effects may emerge with longer follow-up. Wage reimbursement alone may be insufficient to meaningfully expand LDKT.

OBJECTIVE:The oncologic benefit of the extent of lymphadenectomy at the time of radical cystectomy (RC) for bladder cancer is uncertain. Although two randomized clinical trials have reported no difference in disease-free or overall survival for extended LND (eLND) compared to standard LND (sLND), real-world data are lacking. We therefore emulated a pragmatic clinical trial using a large, nationwide dataset. METHODS:We used SEER-Medicare to emulate the LEA AUO AB 25/02 clinical trial. We identified adults 66-79 years diagnosed with high-grade T1 or cT2-T4a, Nany, M0 urothelial carcinoma of the bladder from 2000 to 2017 and treated with RC with LND. sLND and eLND were defined as removal of 4-11 and >12 lymph nodes, respectively. A propensity score (PS) was estimated for receipt of eLND. Associations of LND type with cancer-specific (CSS) and overall survival (OS) were evaluated. RESULTS:A total of 1204 patients were included in the study cohort, of whom 794 underwent eLND and 410 underwent sLND. Pre-treatment characteristics were well-balanced after PS adjustment. Compared to sLND, eLND was not associated with a statistically significant difference in 5-year CSS (68% vs 64%; HR 0.83, 95% CI 0.64-1.06; P = .14) or OS (56% vs 55%; HR 0.82; 95% CI 0.68-1.01; P = .06). Results were similar when examining heterogeneity of treatment effects according to T stage, pN stage and age. CONCLUSION:In observational analyses designed to emulate the completed LEA AUO AB 25/02 trial, eLND was not associated with improved CSS or OS compared to sLND among patients undergoing RC.

Background and Objectives The posterior upper arm (PUA), or tricipital, pathway is a superficial lymphatic channel that has been postulated to be a compensatory pathway for lymphatic drainage of the upper extremity following axillary lymph node dissection (ALND). The PUA pathway has been characterized in the breast cancer population but not in the healthy population.Methods Healthy female volunteers were recruited for bilateral mapping of the upper extremities using indocyanine green (ICG) lymphography. Phenotypic variants of the PUA pathway were recorded.Results 57 volunteers underwent ICG lymphography of the bilateral arms. The PUA pathway was visualized in 100% of arms. In 46% of arms, the pathway was continuous with the forearm (long bundle phenotype), whereas in 54% of arms, the pathway had no continuity with the forearm (short bundle phenotype).Conclusion The PUA pathway was universally present in healthy volunteers. However, in comparison to our prior study, which was performed in patients with breast cancer prior to ALND, healthy volunteer arms more often displayed the short bundle phenotype. Defining the incidence of PUA pathway anatomic variants in healthy subjects is important to further understand its potential role in the development of lymphedema.

BACKGROUND AND OBJECTIVE:The addition of prostate radiation (RT) to androgen deprivation therapy (ADT) improves oncologic outcomes in patients with locally-advanced prostate cancer (PCa). However, this approach remains underutilized in older adults. We therefore emulated the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) PR3/MRC PR07 clinical trial of ADT + RT versus ADT alone to examine clinical outcomes and the role of frailty as an effect modifier. METHODS:We included adults aged 66-89 yr with locally-advanced PCa (cT3-T4, N1, T2 + PSA ≥ 40, or Gleason ≥ 8 + prostate-specific antigen [PSA] ≥ 20) treated with ADT + RT or ADT alone in Surveillance, Epidemiology, and End Results (SEER)-Medicare from 2004-2017. Frailty was assessed using the claims-based frailty index (CFI). We evaluated oncologic outcomes adjusted using stabilized inverse probability of treatment weights (sIPW), and explored the association of treatment intensity with CFI. KEY FINDINGS AND LIMITATIONS:A total of 5494 patients were included, of whom 3378 were treated with ADT + RT. Baseline characteristics were balanced after sIPW reweighting. Median follow-up was 64.0 mo. ADT + RT was associated with reduced cancer-specific mortality (hazard ratio [HR] 0.61; p < 0.01) and all-cause mortality (HR 0.84; p < 0.01) in the overall cohort. Findings were consistent across CFI, T stage, N stage, Gleason score, and PSA. However, increasing frailty was associated with a reduced probability of receiving ADT + RT (adjusted odds ratio [OR] 0.81 per unit CFI). CONCLUSIONS AND CLINICAL IMPLICATIONS:In observational analyses designed to emulate a real-world target trial in older adults, increasing frailty was associated with a reduced likelihood of receiving more intensive treatment, despite a consistent benefit in cancer-specific mortality. These findings underscore the need to re-evaluate treatment disparities in older adults with locally-advanced PCa.

Benign prostatic hyperplasia (BPH) is closely associated with obesity and metabolic syndrome. Although 5α-reductase inhibitors (5ARIs) are widely used to treat BPH, their effectiveness varies significantly, particularly in obese patients. However, the mechanisms by which obesity affects prostate growth and modulates therapeutic responses remain poorly understood. In mice, high⍰fat diet (HFD) increased prostate weight and induced SRD5A2-independent epithelial remodeling with expansion of proximal urethral luminal epithelial cells. ScRNA-seq of prostate tissues from Srd5a2⍰null and control mice on HFD showed enrichment of proximal stem-like populations, reduced androgen signaling, and activation of WNT and NOTCH pathways via heightened stromal-epithelial crosstalk. Clinically, BMI gain, regardless of 5ARI use, correlated with transition zone growth, stronger activity of stem-cell signatures, reduced SRD5A2, and androgen signaling downregulation. Xenium spatial profiling indicated that BMI gain expands stem-like epithelial populations and a NOTCH⍰enriched periepithelial stromal niche surrounding epithelial compartments, supporting stemness. Patients with substantial BMI gain were less responsive to 5ARI, whereas weight control plus 5ARI therapy synergistically improved outcomes. In conclusion, BMI gain promotes proximal prostate enlargement through an SRD5A2-independent stem-like cell mediated pathway that blunts 5ARI efficacy. Combining pharmacotherapy with weight control yields superior efficacy and supports individualized management of BPH. ### Competing Interest Statement The authors have declared no competing interest. NIH Common Fund, https://ror.org/001d55x84, 1R01DK124502, 1R01DK140473, 1R01DK142211, X01DK131477

OBJECTIVES:Regionalization of care and changes in hospital and provider networks have led to increased transfer of patients to an accredited trauma center. We aimed to identify trends in trauma transfers and injury patterns that are likely to result in tertiary center admission versus discharge from the emergency department (ED). METHODS:All patients transferred from 2014 to 2021 to a single level I tertiary trauma center were identified. Using demographic, encounter, and diagnosis coding data from our trauma registry, specific injuries were stratified based on body system or type of injury. Numbers of transfers by year were analyzed using Wilcoxon rank sum test and chi-squared or Fisher's exact test. Univariable and multivariable logistic regression was used to identify injury patterns that correlated with tertiary hospital admission/intervention or discharge from the ED. RESULTS:9307 trauma transfer patients were included. On multivariable regression, thoracic or orthopedic injuries were less likely to result in discharge from the ED (OR 0.34, 95% CI 0.27-0.42; OR 0.33, 95%CI 0.28-0.39). GCS of < 14 was also associated with a decreased likelihood of discharge (OR 0.13, 95% CI 0.08-0.22). Soft tissue injuries, spinal injuries, and head injuries were more likely to be discharged from the ED without requiring admission (OR1.24, 95%CI 1.09-1.40; OR 1.68, 95%CI 1.43-2.00; OR 2.77, 95%CI 2.30-3.34). During the study period, odds ratio of transfer patients being discharged directly from the ED increased. CONCLUSION:In parallel with a growing number of patient transfers over the study period, there was also a trend where patients were more likely to be discharged straight from the ED. An opportunity exists to develop transfer protocols to reduce some transfers for soft tissue injuries and certain spine/head injuries.

INTRODUCTION:Although a single randomized trial demonstrated improved survival with adjuvant chemotherapy (AC) for locally advanced (pT2-4 or N+) upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU), this survival benefit was not observed in pT2 or N+ patients, and real-world data are lacking. We therefore emulated the completed POUT trial using a large, nationwide cancer registry. METHODS:We identified patients aged 50-79 years with pT2-4 or pN+, non-metastatic UTUC treated with RNU from 2006-2020 in the National Cancer Database (NCDB). A propensity score for receipt of multiagent AC within three months of RNU was estimated using logistic regression, and the associations of AC with overall survival (OS) were evaluated after reweighting by stabilized inverse probability of treatment weights (sIPW). RESULTS:The study cohort comprised 3206 patients, of whom 802 (25%) received AC. pT stage was £pT2 in 954 (30%) patients, and 167 (5%) patients had pN+ disease. Median followup was 47.0 (interquartile range 24.0-86.0) months. After IPW-reweighting, AC was not associated with improved OS compared to observation, with five-year OS of 60% vs. 58%, respectively (hazard ratio 0.92, 95% confidence interval 0.79-1.08, p=0.30). When examining treatment effects across baseline characteristics, AC was not associated with improved survival for any pT or pN category. CONCLUSIONS:In analyses designed to emulate the POUT trial, we did not observe improved OS with AC in the overall cohort, nor in specific pT or pN categories. These findings suggest the need to examine the real-world comparative effectiveness of AC in locally advanced UTUC in further studies.