Citations

Objective The United Nations defines sustainability as meeting needs of the present without compromising future generations. While often equated to “saving the planet”, sustainability is a diverse topic. Healthcare generates >5% of CO 2 emissions worldwide, yet sustainability efforts in urology are limited. The North Central Section of the American Urological Association (NCSAUA) recently convened a Sustainability Task Force to address this topic. This study queried members on sustainability in urologic practice. Methods Following literature review on sustainability in surgery/urology, a 19-item anonymous REDCap survey was developed and distributed via email to NCSAUA members (N = 1607). The survey assessed current best practice, institutional/personal sustainability, and demographics. Responses were compiled and summarized using descriptive statistics. Results Survey response rate was 4.9% (79/1607). Respondents were most commonly from metropolitan areas (82%), male (71%), and in practice for 5–14 years (29%). Sustainability topics were prioritized as: (1) financial, (2) future workforce, (3) environmental. Over half (56%) reported no institutional sustainability programs or were unaware of them. Instrument (67%), computer (68%), and paper (65%) recycling were supported by a majority of respondents. However, only 28% and 29% of respondents reported current institutional use of instrument and computer recycling, respectively. Telemedicine was infrequent, with most urologists (58%) conducting 0-5% of visits virtually. Conclusions Current institutional and urologic practice emphasis on sustainability is low. Respondents ranked highest sustainability priorities as financial and future workforce. Efforts to address environmental sustainability were also supported, namely reduction of disposables and waste. The findings support the development of targeted programs to advance sustainability priorities widely.

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298

Background: Epstein–Barr virus (EBV) is a key environmental risk factor for multiple sclerosis (MS), and tonsils and adenoids serve as a primary viral reservoir. This study investigates the potential role of adenotonsillectomy in pediatric-onset multiple sclerosis (POMS) risk and relapse rate. Objectives: POMS participants and controls were recruited from 16 pediatric MS clinics between 1 November 2011 and 1 July 2017. Clinical and demographic information, including history of adenotonsillectomy, EBV serostatus, and HLA-DRB1*15:01:01 status, were collected. Multivariable logistic regression assessed the association between adenotonsillectomy and MS risk. In addition, negative binomial regression offset by follow-up time was used to assess the relationship between adenotonsillectomy and relapse rate in POMS participants with available follow-up data. Results: The case-control analysis included 359 POMS participants and 560 pediatric controls. Individuals with a history of adenotonsillectomy had a 63% increased odds of MS (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.01–2.64, p = 0.046). Among the 239 POMS participants with available follow-up data, adenotonsillectomy was associated with a twofold increase in annualized relapse rate (adjusted incidence rate ratio (IRR) = 2.00, 95% CI = 1.15–3.48, p = 0.013). Conclusions: Prior adenotonsillectomy was associated with increased risk of MS and greater relapse rate in pediatric patients, suggesting a potential interplay between EBV, immune regulation, and MS pathogenesis.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P &lt; 0.00001) and an earlier age of first exposure to tackle football (P &lt; 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P &lt; 0.04) and rotational force (P &lt; 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

Abstract Severe neuropathies with predominant involvement of motor fibres can resemble lower motor neuron disease (LMND) phenotypes. Given the fatal prognosis of LMND, identifying underlying autoimmune syndromes is crucial to provide treatment options to patients. We investigated a novel autoantibody binding pattern observed on murine teased sciatic nerve fibres. Target antigens were identified using immunoprecipitation combined with mass spectrometry. Target specificity of these autoantibodies was validated in cell-based assays, neutralization assays and knock-out models. A retrospective study cohort consisting of different neuropathies (chronic inflammatory demyelinating polyradiculopathy n = 86, Guillain–Barré syndrome n = 37, multifocal motor neuropathy n = 18, diabetic neuropathy n = 30, other inflammatory neuropathies n = 10), amyotrophic lateral sclerosis (n = 50), multiple sclerosis (n = 50) and healthy controls (n = 50) was negative for septin multimer autoantibodies. Histopathological analysis of skin and the sural nerve including electron microscopy was performed in one seropositive patient, and autoantibody binding was characterized in vitro. Extensive immunotherapy was initiated in one patient, with clinical and serological follow-up over 4 years. Among 3543 total samples tested, three patients (two male, one female)—diagnosed with the LMND variant of amyotrophic lateral sclerosis (aged 65, 72 and 79 years, respectively)—showed a novel and distinct autoantibody binding pattern of indirect immunofluorescence staining on peripheral nerves, targeting Schmidt–Lanterman incisures (SLIs), paranodes and the abaxonal myelin. Target identification and validation revealed septin multimers as autoantibody epitopes. Despite the primarily intracellular location of septins, autoantibody binding was evident in living myelinated dorsal root ganglia, primarily at SLIs (‘incisuropathy’). Septin multimer autoantibodies further initiated complement deposition on fixed and permeabilized cell-based assays. Sural nerve and skin biopsies showed inflammation, myelin and axonal pathology. Extensive immunotherapy in one patient was followed by disease stabilization over 3 years. The other two patients died of rapid disease progression: one of them received no immunotherapy while the other had ineffective treatments with single administrations of intravenous immunoglobulin and rituximab. Our data suggest that septin multimer autoimmunity occurs in severe motor-predominant neuropathies which can clinically resemble a neurodegenerative LMND. Screening for septin multimer autoantibodies should be considered in patients presenting with this phenotype. Follow-up studies need to determine the direct pathogenicity of septin multimer autoantibodies, their potential as a biomarker of an autoimmune syndrome and responses to immunotherapy in larger cohorts.

BACKGROUND AND OBJECTIVES: Stroke has the largest proportion of the global burden of neurological disorders with projected mortality rates to increase more rapidly in low- and middle-income countries than in high-income countries, and people of African descent are at greater risk. To better understand the burden, risk factors, and care pathways, this study aimed to review the risk factors, clinical presentation, and outcomes of patients presenting with stroke or stroke-like symptoms in a tertiary hospital in Sierra Leone. METHODS: A retrospective chart review was conducted of all patients presenting with neurological or neurosurgical conditions from January 2019 through December 2023 and those with stroke or stroke-like symptoms were included in this study. RESULTS: One thousand two hundred ninety-seven patients were diagnosed with stroke. Of these, a small majority were male (712, 54.9%), and the mean age was 57.8 years. About a third (38.1%) of the stroke patients were aged 60 years and above, and 562 (43.3%) were between 41 and 60 years. A majority of stroke patients (68.6%) had a prior diagnosis of hypertension, while significantly fewer had a documented diagnosis of diabetes (8.8%) and 4.6% of patients had a known prior stroke. Only half (50.8%) with ordered computed tomography scan were able to complete the ordered imaging. From these imaging findings, 123 patients (9.6%) were diagnosed with hemorrhagic stroke, while the remainder were diagnosed with ischemic stroke or transient ischemic attack vs hypertensive urgency. 32.9% experienced in-hospital mortality, while only 6.5% followed up. CONCLUSION: This study documents the significant stroke burden in Sierra Leone, much of which is unaddressed due to lack of specialty resources including inadequate community engagement to raise awareness of risk factors and preventative measures. Poor health-seeking behavior and access to medical services also contribute to this burden. These data are imperative to identify systems gaps and help support ongoing capacity building efforts.

TPS8124 Background: Immune checkpoint inhibitor (ICI)–based regimens are standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) without actionable driver mutations; however, most patients experience disease progression within 12 months. A subset develop oligoprogression, defined by progression at a limited number of metastatic sites with otherwise controlled disease. Oligoprogression represents a therapeutic window in which local ablative therapy could be used to prolong disease control. In the prior phase II CURB trial, SBRT was shown to significantly prolong progression-free survival (PFS) in patients with oligoprogressive NSCLC. Methods: CCTG-BR38 is an international, multicenter, open-label, randomized phase III trial conducted through the NCI National Clinical Trials Network. Adults with stage IV NSCLC receiving first-line ICI ± chemotherapy who develop ≤5 extracranial oligoprogressive lesions are randomized 1:1 to: (1) switch to second-line standard systemic therapy or (2) SBRT (30 Gy in 3 fractions) to all oligoprogressive sites followed by continuation of the same first-line systemic therapy. Randomization is stratified by type of first-line systemic therapy (ICI alone vs ICI + chemotherapy), number of oligoprogressive lesions (1–2 vs 3–5), and ECOG performance status (0-1 vs 2). Patients with treated, stable brain metastases are eligible. Primary Endpoints: Dual primary endpoints are PFS and overall survival (OS). Secondary endpoints include safety (CTCAE v5.0), patient-reported adverse events (PRO-CTCAE), quality of life (EORTC QLQ-C30/LC13), and cost-effectiveness (EQ-5D-5L; Canadian sites). Optional blood and tissue collection for exploratory biomarker analyses are planned. Statistical Considerations: A total of 320 patients (160 per arm) will be enrolled. The sample size is based on detecting a HR of 0.7 for OS (an improvement in median OS from 10 to 14.3 months) with 80% power using a 1-sided 2% level test (the overall 1-sided 2.5% type I error will be assigned 2% to OS and 0.5% to PFS). Interim analyses for futility and efficacy are planned. Current Status: The trial was centrally activated on April 3, 2025. Accrual is ongoing across Canadian and US NCTN sites. Clinical trial information: NCT06686771 .

TPS7100 Background: Bruton tyrosine kinase covalent inhibitors (cBTKi) have been transformative in CLL treatment. Despite achieving extended remissions, in most patients disease still relapses despite cBTKi therapy, often associated with BTK C481 mutations. Non-covalent BTKi (ncBTKi), including pirtobrutinib, can overcome this resistance (Sharman et al. ASCO . 2025). Pirtobrutinib received FDA approval in Dec 2025, for R/R CLL/CLL patients pretreated with cBTKi. Rocbrutinib (LP-168) is a highly selective next-generation BTKi that can covalently bind wild-type and gatekeeper mutations (T474X, commonly seen in patients relapsed after pirtobrutinib) and non-covalently target C481-mutated BTK , with preclinical efficacy in treatment-naïve and BTKi-resistant CLL (Gordon et al. IWCLL . 2025). In the rocbrutinib phase 1 trial (NCT04775745), encouraging safety and efficacy have been observed in CLL patients with prior exposure to BTKi and/or BCL2 inhibitor (BCL2i) (Woyach et al. Blood. 2025). Presented here is the design of a phase 3 trial aiming to compare the efficacy of rocbrutinib versus pirtobrutinib in cBTKi-pretreated R/R CLL/SLL patients. Methods: ROCKET-CLL (NCT07342478) is a randomized, open-label, multicenter, phase 3 study comparing rocbrutinib (Arm 1) to pirtobrutinib (Arm 2) in R/R CLL/SLL subjects who previously received treatments including covalent BTKi. Eligible subjects must require treatment per 2018 iwCLL criteria, have measurable lesions by CT, an ECOG performance score of 0-2, and adequate hematologic and other organ functions. About 306 subjects will be randomized 1:1 based on stratification factors such as 17p deletion/ TP53 mutation presence, reasons for discontinuing prior cBTKi, prior BCL2i treatment, and geographic region. Participants assigned to each arm will receive rocbrutinib (200 mg QD) or pirtobrutinib (200 mg QD) tablets continuously until disease progression, unacceptable toxicity, withdrawal, or other study discontinuation criteria are met. The primary endpoint is progression-free survival (PFS), assessed by an independent review committee (IRC) per iwCLL 2018 criteria with CLL (Hallek et al. 2018) and Lugano 2014 criteria with SLL (Cheson et al. 2014). Important secondary endpoints include overall survival (OS), time to next treatment (TTNT), event-free survival (EFS), overall response rate (ORR), duration of response (DOR), PFS assessed by investigator (INV), concordance between IRC and INV PFS, safety and tolerability, and population PK. Exploratory endpoints include health-related quality of life and biomarker assessment. Recruitment is ongoing. Clinical trial information: NCT07342478 .

TPS2673 Background: The main challenge for developing CAR T therapies for solid tumors is the lack of targets that distinguish tumor from normal cells, resulting in on-target, off-tumor toxicity. Tmod logic-gated CAR T therapy addresses this challenge by incorporating 2 CARs on the same T cell: an activator targeting a marker on both tumor and normal cells, and a blocker targeting HLA-A*02 that inhibits CAR T activity against normal cells while allowing activation against tumor cells (with HLA-A*02 LOH), improving tumor selectivity and decreasing toxicity. Early safety results from 3 ongoing phase 1/2 clinical trials of logic-gated, Tmod CAR T therapy (EVEREST-1, EVEREST-2, and DENALI-1) have demonstrated manageable safety and tolerability in patients with advanced solid tumors (Grierson et al, SITC , 2024; Ward et al, SITC 2025; Specht et al, SABCS , 2025). Early efficacy results include the first ever reported complete response in a patient with non-small cell lung cancer following treatment with a CAR T-cell therapy (A2B694). A2B543 is an autologous Tmod CAR T therapy that contains the same Tmod construct as A2B694 with an added membrane-tethered IL-12 (memIL12) booster. Specifically, A2B543 is comprised of autologous Tmod cells transduced with 2 lentiviral vectors: one expressing both the HLA-A*02-targeted blocker and the mesothelin-targeted CAR activator; and a second expressing the memIL12 booster. Interleukin 12 (IL-12) is a potent, pro-inflammatory cytokine that plays a crucial role in inducing antitumor immune responses; however, systemic IL-12 can be prohibitively toxic (Jia et al, Front Immunol , 2022). In A2B543, expression of the memIL12 cassette is under the control of an NFAT promoter and is induced during antigen engagement or T cell activation. This inducible memIL12 is designed to reduce the toxicity associated with systemic IL-12 while enhancing the long-term potency and persistence of Tmod (Zhang et al, J Immunother Cancer , 2025). Methods: EVEREST-2 (NCT06051695) is a phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B543 in adults with recurrent/metastatic mesothelin-expressing cancers with tumor-associated HLA-A*02 LOH, including mesothelioma, colorectal, non-small cell lung, pancreatic, or ovarian cancer. Patients are enrolled through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA LOH via next-generation sequencing and cryopreserves leukapheresis product. Upon progression, A2B543 is manufactured and then administered after lymphodepletion. The phase 1 primary objective is to evaluate the safety and tolerability of A2B543 and identify a recommended phase 2 dose (RP2D). The phase 2 primary objective is to assess overall response rate. Clinical trial information: NCT06051695 .

TPS11598 Background: Fibroblast Activation Protein (FAP) is expressed on the surface of cancer-associated fibroblasts and is involved in the formation, maintenance, and spread of tumors. Sarcoma frequently demonstrates high expression of FAP on the tumor cells themselves in contrast to other solid tumors, where it is mainly expressed on CAFs within the tumor stroma. Radioligand therapies utilizing alpha emitting isotopes such as Ac-225 have emerged as promising treatment strategies across multiple targets and indications in oncology. Ac-225 and its daughter radionuclides emit high-energy alpha particles capable of inducing double-stranded DNA breaks, leading to significant cytotoxic effects within cells. Early clinical data for other Ac-225-labeled compounds have shown promising outcomes, particularly in settings where traditional therapies have failed. [Ac-225] RTX-2358 (Ratio Therapeutics Inc, Boston, MA) is a novel FAP-targeted radioligand designed for specific high-affinity binding, resulting in prolonged tumor residence and limited normal tissue uptake. This sustained tumor retention leads to extended delivery of cytotoxic radiation to FAP-expressing tumors. A beta-emitting analog, [Lu-177]RTX-2358, has been administered to more than 25 patients under the German §13.2b compassionate use framework across multiple tumor types. Longitudinal SPECT imaging performed as late as 14 days after administration demonstrated persistent tumor retention with minimal washout. Based on time–activity curve analysis from these data, tumor biological half-time is estimated to be well in excess of 1,000 hours. Renal clearance was observed to be consistent with that reported for established lutetium-177–labeled radioligand therapies. Methods: This study is a seamless Phase 1 / 2 dose escalation study. The Phase 1 portion consists of a 3 x 3 dose escalation design, with patients treated in 3 planned dose escalation cohorts (7.5, 11.25 and 15 MBq) with up to 6, 8-week cycles of [Ac-225]RTX-2358. Backfill of phase 1 cohorts is permitted to facilitate selection of the recommended administered activity level for the subsequent Phase 2 expansion cohort. Dose escalation / de-escalation decisions will be made by a Safety Review Committee. Patients over 18yrs with a history of histologically confirmed relapsed or refractory soft tissue sarcoma (measurable disease per RECIST v1.1) are eligible if they have a positive [Cu-64]LNTH-1363S FAP PET, an ECOG PS 0 to 1, and adequate organ reserve and renal function. Recruitment of the first cohort was completed in December 2025. The ATLAS Study: NCT07156565 Clinical trial information: NCT07156565 .