Citations

Abstract Background Global data demonstrate an inverse relationship between hospital ileoanal pouch volume and adverse outcomes, highlighting the need for quality metrics for this technically demanding procedure.1-4 Currently, there are no standardised quality indicators to define high-quality pouch surgery. This study aimed to establish international consensus on key performance indicators (KPIs) in pouch surgery. Methods A modified Delphi process was conducted among an international, multidisciplinary panel of experts. Participants were identified through professional networks, literature review, and direct email invitation; additional participants recruited via a snowball sampling approach over one month. Candidate KPIs were generated from literature review and expert input across 5 domains. Each item was rated on a 9-point Likert scale (1 = not important, 9 = critically important); consensus was predefined as ≥ 80% of respondents rating an item 7–9. Items not reaching consensus were re-rated in a second round following anonymized group feedback. Results Round 1 included 312 participants from 37 countries. Demographics (Table 1): 53% were age 45 years, 35.2% were female, and included surgeons (68.6%) and gastroenterologists (31.1%). Most (76.6%) practice at academic or university hospitals, with a median of 11 (5–17) years in practise; 78.9% perform >1 pouchoscopy per month, and 39.5% of surgeons perform 5 pouches/year. Respondents’ regions included North America (51%), Europe (26%), Oceania (9%), Asia (6%), Latin America (4%), and the Middle East/Africa (4%). Seven (18%) countries (Denmark, Lithuania, Malaysia, Norway, United Arab Emirates, Sweden, and Switzerland) reported pouch surgery is already centralised, while 70.6% agreed pouch centralisation should be implemented. Cost/logistics and professional autonomy were the most important barriers to centralisation, whereas capacity and training exposure were least important. Overall, 37/59 (62.7%) candidate KPIs reached consensus after Round 1. The Round 2 response rate was 61%, and 2 additional KPIs reached consensus (preop ileitis and long-term risk of pouchitis). Additionally, 14 of 25 (56%) informed consent items reached consensus, and 64% of respondents felt informed consent for pouch surgery requires 2 or more office visits. Consensus items were used to populate a KPIPS Checklist (Figure 1). Conclusion Through an international Delphi process, the KPIPS study identified a consensus-derived set of key performance indicators to measure quality in pouch surgery. These quality metrics provide a foundation for benchmarking outcomes and represent a critical step towards centralization and the development of designated pouch centres of excellence to improve global standards of care for pouch patients. References: 1. Worley GHT, Fearnhead NS, Brown SR, et al. Review of current practice and outcomes following ileoanal pouch surgery: Lessons learned from the ileoanal pouch registry and the 2017 ileoanal pouch report. Colorectal Dis 2018;20:913–22. 2. Giddings HL, Yang PF, Steffens D, Solomon MJ, Ng KS. Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: Systematic review. Br J Surg 2024;111. 3. Hoang CM, Maykel JA, Davids JS, et al. Distribution of elective ileal pouch-anal anastomosis cases for ulcerative colitis: A study utilizing the university health system consortium database. J Gastrointest Surg 2020;24:2613–9. 4. Moojen TB, Visser E, Reijntjes MA, et al. One-year stoma-free survival of ileoanal pouches for uc in european centers: The miracle project. Ann Surg Open 2025;6:e596. Conflict of interest: Prof. Holubar, Stefan: No conflict of interest Soop, Mattias: No conflict of interest Poskus, Tomas: No conflict of interest Neary, Peter: No conflict of interest Uchino, Tairin: No conflict of interest Yang, Song-soo: No conflict of interest Adamina, Michel: No conflict of interest Avellaneda, Nicolas Luis: No conflict of interest Barnes, Edward: No conflict of interest Brouquet, Antoine: No conflict of interest Brown, Steven Ross: No conflict of interest De Buck Van Overstraeten, Anthony: No conflict of interest Buskens, Christianne J.: No conflict of interest Chiorean, Michael: No conflict of interest Clark, David: No conflict of interest Cohen, Benjamin: No conflict of interest El Ouali, Sara: No conflict of interest Faiz, Omar Darius: No conflict of interest Fichera, Alessandro: No conflict of interest Hahnloser, Dieter: No conflict of interest Hancock, Laura: No conflict of interest Herfarth, Hans: No conflict of interest Johnston, Michael: No conflict of interest Kayal, Maia: No conflict of interest Laharie, David: No conflict of interest Liberman, Sender: No conflict of interest Loftus, Jr, Edward: No conflict of interest Moeslein, Gabriela: No conflict of interest Myrelid, Pär: No conflict of interest Poylin, Vitaliy: No conflict of interest Qazi, Taha: No conflict of interest Raffals, Laura: No conflict of interest Rubin, David T.: No conflict of interest Spinelli, Antonino: No conflict of interest Steinhagen, Emily: No conflict of interest Tozer, Philip: No conflict of interest Verstockt, Bram: No conflict of interest Warusavitarne, Janindra: No conflict of interest Wexner, Steven: No conflict of interest Winter, Desmond: No conflict of interest

OBJECTIVE: Volatile anesthetics (VAs) are gaining renewed interest as a sedation strategy in the intensive care, offering an alternative to traditional IV agents. VAs provide several pharmacologic advantages, including rapid onset and offset, minimal systemic metabolism, and favorable recovery profiles. Advances in delivery systems enabled the safe and practical administration of volatile agents in the ICU. Thus, we aimed to describe the pharmacology and safety aspects of inhaled agents as well as the systems designed to deliver VAs in the ICU. DATA SOURCES: Relevant literature was identified through PubMed and MEDLINE databases. STUDY SELECTION: Original research, review articles, commentaries, and guidelines addressing safety, efficacy, and use of VAs in adult ICU patients were included. DATA EXTRACTION: Studies were reviewed by the authors, with key findings summarized and organized by pharmacologic properties, delivery systems, and safety domains. DATA SYNTHESIS: VAs are halogenated hydrocarbons whose mechanism of action is not fully understood. Although the CNS is the primary site of action, the end-tidal concentration of exhaled anesthetic is used to monitor clinical effects such as immobility to a noxious stimulus. Inhaled agents have unique pharmacokinetics, minimal metabolisms, and distinct recovery. The side effect profile is also unique, with malignant hyperthermia being the most feared, yet rare complication. Two systems for inhalational sedation delivery are available internationally, with one currently under evaluation in the United States. The systems are composed of a miniature vaporizer, delivery controller, and a monitor. The systems have distinct safety considerations, such as tidal volume limits. CONCLUSIONS: VAs can be used as sedative agents in the ICU. This article comprehensively reviews the pharmacology of VAs along with their safety profile and describes the structure and function of miniature vaporizers currently available on the world market.

Abstract Introduction Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts (p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). Conclusions Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.

Abstract Background Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect. Methods Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0–2) at 90 days. Recanalization, symptomatic intracranial hemorrhage (sICH), mortality, and the effect of M2 laterality, division occlusion and procedure time were assessed. Results About 1734 patients with M2 occlusions underwent either frontline aspiration (n = 711) or SR/combined (n = 958) thrombectomy between 2013 and 2024. PSM analysis favored aspiration for functional independence (49.9% vs 44.0%, OR 1.27 (1.03–1.57)), complete recanalization (61.2% vs 48.7%, OR 1.66 (1.34–2.05)), complete first pass effect (35.0% vs 27.6%, OR 1.42 (1.13–1.78)), and sICH (3.5% vs 6.2%, OR 0.55 (0.33–0.91)), with no difference in mortality. Frontline aspiration had significantly shorter procedural times (median 28 [IQR 15–49.5] vs 51 [IQR 35–78] minutes; p < 0.001). For every minute increase in procedure time, the probability of functional independence decreased significantly (p < 0.001) less with frontline aspiration (0.35%) compared to SR/combined (1.61%). Conclusion Frontline aspiration for M2 occlusions resulted in better clinical and angiographic outcomes compared to SRs. Future trials for MeVO with a focus on contact aspiration thrombectomy may succeed where recent trials have failed.

Abstract Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies—often severe and genetically complex—pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research. Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical ontology, and patient community advocates systematically reviewed and revised the epilepsy hierarchy in Mondo, aligning it with the International League Against Epilepsy (ILAE) classification system. These updates include reclassification of epilepsy subtypes, including syndromes, age-related epilepsies, and developmental epileptic encephalopathies, resulting in a more granular, standardized, and clinically relevant structure. Mondo now offers an enhanced framework for integrating epilepsy data across resources, enabling improved interoperability and facilitating rare disease research and data curation, with continued efforts underway to further refine and expand this integration.

Sharing research code in an open access version-controlled repository offers significant benefits for both science as a whole and for individual researchers. In this article, we focus on this practice, which is fully aligned with the NIH’s Gold Standard Science (GSS) program as well as FAIR (findable, accessible, interoperable, reusable) and TRUST (transparency, responsibility, user focus, sustainability, technology) principles. Gold Standard Science supports open science by emphasizing transparency, reproducibility, and the use of best practices that enable others to verify and extend research. Pairing a research article’s cited data snapshot with a versioned, environment-specific code release, deposited in a companion code repository, ensures that, upon submission to a medical journal, readers and reviewers can directly verify results. An executable and updatable companion code repository complements, rather than replaces, established research data repositories. When code underlying medical research results is made openly available, then other scientists can inspect, run, and validate analyses. These activities enhance reproducibility, which is a core aim of GSS. Shared code also facilitates collaborative innovation by allowing researchers to extend the utility of the code to new datasets and applications. For researchers, code sharing can increase visibility, credibility, and citation impact. Demonstrating transparency through shared executable and updatable code builds trust with journal readers, peer reviewers, funders, and peers. Shared code in an open access repository signals adherence to high standards of scientific integrity and attracts opportunities for collaboration. A researcher who shares code receives recognition as a leader in reproducible, trustworthy research consistent with NIH’s GSS principles.

Background Dual antiplatelet therapy (DAPT) is recommended around carotid artery stenting (CAS) to reduce periprocedural stroke risk. Clopidogrel is widely used, but response variability related to pharmacokinetics and CYP2C19 polymorphisms may limit its effectiveness. Ticagrelor is a more potent, direct acting P2Y12 inhibitor, but its comparative effectiveness in CAS remains uncertain. Methods We conducted a retrospective cohort study in the TriNetX database, identifying adults with carotid artery stenosis who underwent CAS between January 2016 and August 2025 and received either ticagrelor or clopidogrel. Primary outcomes at 180 days included ischemic stroke, major hemorrhage, intracranial hemorrhage, and all cause mortality. Secondary outcomes included inpatient readmission and emergency department (ED) visits. Propensity score matching (1:1), Kaplan–Meier survival, and Cox proportional hazards analysis were used. Results Among 6996 patients, 378 received ticagrelor and 6618 received clopidogrel; aspirin co-use was similar (89.7% vs 91.7%). After matching, 377 patients remained in each cohort. Ischemic stroke (2.7% vs 4.2%; HR 0.56, 95% CI 0.25 to 1.27; P=0.159) and major hemorrhage (2.9% vs 4.8%; HR 0.61, 95% CI 0.29 to 1.30; P=0.197) were numerically lower with ticagrelor. Rates of intracranial hemorrhage were similar (2.7% vs 2.7%; HR 0.61, 95% CI 0.14 to 2.53; P=0.488). Mortality was numerically higher with ticagrelor (3.4% vs 2.7%; HR 1.64, 95% CI 0.68 to 3.97; P=0.263). ED visits were similar (14.3% vs 14.6%; HR 0.97, 95% CI 0.67 to 1.42; P=0.895). Inpatient readmission was numerically lower with ticagrelor (15.9% vs 19.1%; HR 0.81, 95% CI 0.57 to 1.14; P=0.223). Conclusion Ticagrelor and clopidogrel showed comparable safety and effectiveness following CAS. Future prospective genotype informed trials are warranted to confirm these findings.

TPS646 Background: SSTR-targeted RPT has transformed the treatment landscape for NETs, significantly improving clinical outcomes in phase 3 studies versus other targeted therapies. Nevertheless, disease progression and renal toxicity after treatment highlight the need for further improvement. Use of the α-emitter 225 Ac as the radioactive component has shown promising results in clinical studies: initial data from ACTION-1 suggest promising efficacy for RYZ101, a first-in-class, highly potent α-emitting RPT, in patients with SSTR+ GEP-NETs progressing after 2–4 cycles of 177 Lu-somatostatin analogs. RYZ401 is a cyclic 6-amino acid SSTR-targeting peptide agonist conjugated to a DOTA chelator bound to 225 Ac. Preclinical data have shown an improved therapeutic window versus DOTATATE. RYZ401 has the potential to deliver higher radiation doses to tumors, with improved renal clearance and lower kidney absorbed dose, potentially eliminating the need for amino acid infusion. Methods: RYZ401-101 is a global, multicenter, phase 1, first-in-human, dose-escalation/-expansion study designed to determine the recommended phase 2 dose (RP2D) and optimal treatment regimen, safety and tolerability, and preliminary efficacy of RYZ401 in patients with NETs and other selected solid tumors expressing SSTRs. Key eligibility criteria: histologically confirmed metastatic or unresectable well-differentiated NETs; WHO grade 1–3 (Ki-67 ≤55%); ≥1 SSTR PET-positive measurable lesion; and disease progression after ≥1 prior treatment line. In dose escalation, 6–18 patients will receive escalating doses of RYZ401 (2.0–11.1 MBq IV Q6W × 2–4 cycles); no amino acid co-infusion is planned. In dose expansion, approximately 80 patients will receive RYZ401 at the RP2D, 40 patients with well-differentiated GEP-NETs (cohort A) and 40 with other SSTR+ tumors including non-GEP-NETs (cohort B). Primary endpoints: dose-limiting toxicities in weeks 1–4 of treatment (dose escalation) and safety (dose expansion). Secondary endpoints: safety, pharmacokinetics, and efficacy outcomes (dose escalation and expansion). RYZ401 dosimetry will be evaluated in a sub-study of 10−16 patients. Enrollment is ongoing in the USA. Clinical trial information: NCT07165132 .

TPS611 Background: GPC3 is an oncofetal protein expressed in up to 75% of hepatocellular carcinomas (HCCs) and associated with poor prognosis. Its selective expression in tumor and not in normal tissue makes it a promising target for radiopharmaceutical imaging and therapy (theranostics). The GPC3-selective diagnostic RYZ811 ([ 68 Ga]Ga-RAYZ-8009) and therapeutic α particle-emitting RYZ801 ([ 225 Ac]Ac-RAYZ-8009) are a theranostic pair. Previous studies show high uptake of RYZ811 in intrahepatic and extrahepatic HCCs, with low normal liver background uptake. In GPC3+ HCC mouse models, single administrations of RYZ801 significantly inhibited tumor growth. Methods: RYZ801-101 is a single-arm, open-label, phase 1/1b study of RYZ811 and RYZ801 in previously treated patients with GPC3+ unresectable HCC. The study has two parts: dose escalation (part 1) and dose expansion (part 2). Each part consists of two stages: RYZ811 imaging and RYZ801 treatment. The aim of imaging is to determine if RYZ811 safely and adequately identifies patients with GPC3+ tumors. The aim of treatment is to determine the safety, pharmacokinetics (PK), recommended phase 2 dose (RP2D; part 1), and preliminary antitumor activity (part 2) of RYZ801. Key eligibility criteria are: confirmed HCC; Barcelona Clinic Liver Cancer stage B or C; Child-Pugh A; ≥1 RECIST v1.1-measurable lesion (treatment stage); and disease progression after ≥1 systemic therapy in part 1 and 1 prior line in part 2. In part 1, approximately 60 patients will receive RYZ811 (185 MBq) in the imaging stage; up to 30 of these will receive escalating doses of RYZ801 (2.6–5.5 MBq × 4 doses) in the treatment stage. In part 2, approximately 80 patients will receive RYZ811 (185 MBq) in the imaging stage; up to 40 of these will receive RYZ801 at the RP2D in the treatment stage. Primary RYZ811 objectives are to assess the safety/tolerability and biodistribution of RYZ811. Secondary objectives are to determine absorbed doses (ADs) to organs and tissues and any association between RYZ811 uptake and RYZ801 efficacy. Primary RYZ801 objectives are to identify the RP2D and safety/tolerability of RYZ801. Secondary objectives are to assess PK, ADs to critical organs and tumors, and preliminary antitumor activity. Enrollment for Part 1 is ongoing in the USA. Clinical trial information: NCT06726161 .