LBA5500 Background: Optimal timing of cytoreduction in non-frail patients (pts) with seemingly resectable stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma (OC) remains controversial. Methods: TRUST is an international randomized multicenter phase III trial in pts with stage IIIB-IVB OC and good performance status (ECOG 0/1) comparing primary cytoreductive surgery (PCS) followed by 6 cycles of intravenous (iv) chemotherapy to 3 cycles of neoadjuvant iv chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) and 3 further iv cycles. Maintenance treatment with bevacizumab and/or PARP inhibitors was allowed if selection criteria was similar for both arms. Pts were eligible for the study if preoperative clinical and radiologic assessment identified them as potential candidates for PCS. To ensure surgical quality, participating centers complied with an onsite surgery quality assurance audit, had adequate infrastructure, surgical proficiency (complete resection rates ≥50% in PCS) and sufficient volume (≥36 PCS/year). The intent to treat analysis population included all eligible pts with confirmed stage IIIB-IVB disease. The primary endpoint was overall survival (OS). Superiority was tested using a two-sided stratified log-rank test with significance level 0.05. Secondary endpoints were progression-free survival (PFS) and surgical complications. Results: A total of 688 eligible pts (median age: 63y; range: 32-83) underwent randomization: 345 were assigned to PCS and 343 to NACT/ICS. 91% had high-grade serous histology. Complete resection was achieved in 61.7%/62.9% of all randomized/all operated pts in the PCS group and 72%/76.6% in the ICS group. Median PFS was 22.2 months in the PCS group, and 19.7 months in the ICS group (HR 0.80 95%CI: 0.66-0.96; p=0.02). Median OS was 54.3 months in the PCS group and 48.3 months in the ICS group (HR 0.89 95%CI: 0.74-1.08; p=0.24). Pts with complete cytoreduction after PCS had the most favorable outcome, with a median PFS and OS of 27.9 and 67.0 months, respectively. A long-term benefit from PCS was seen in all analyzed subgroups. The benefit of PCS was most prominent in stage III pts (n=468): median PFS for PCS vs ICS, 26.3 vs 21.4 mos; median OS for PCS vs ICS, 63.7 vs 53.2 months. Major postoperative complication rates were acceptable, with a 30-day postoperative mortality rate of < 1% in both groups. Conclusions: In expert centers with proven surgical quality, PCS followed by iv chemotherapy resulted in a significantly longer median PFS and a numerically longer OS compared to NACT/ICS in non-frail OC pts. Although statistical significance in the primary endpoint was not reached, this is the first randomized trial to show a benefit of PCS over ICS. This benefit is likely to be associated with the high complete resection rate, reinforcing PCS as a standard of care in non-frail pts with seemingly resectable advanced OC. Clinical trial information: NCT02828618 .
Abstract Background The Chronic Otitis Media Questionnaire-12 (COMQ-12) is a disease-specific health-related quality of life (HRQoL) instrument originally developed in English for patients with chronic otitis media (COM). This study aimed to translate the COMQ-12 into German and to validate the resulting German version, and assess its psychometric properties. Methods The COMQ-12 underwent forward–backward translation into German. Seventy-nine patients with COM who underwent middle ear surgery were prospectively enrolled. HRQoL was assessed preoperatively and 6 months postoperatively via the German COMQ-12. Additionally, pure tone audiometry was performed at both time points. Psychometric properties, including internal consistency, test–retest reliability, discriminant validity, agreement validity, responsiveness, and response shift, were evaluated. Results The German COMQ-12 demonstrated high internal consistency both preoperatively (Cronbach’s α = 0.87) and postoperatively (Cronbach’s α = 0.84). The test–retest reliability was high (r = 0.89). It significantly discriminated between COM patients and healthy controls (p < 0.001) and showed strong convergent validity with a global health-specific question (r = 0.64, p < 0.001). The questionnaire exhibited high responsiveness (standardized response mean = -0.80) with minimal response shift effects (effect size = 0.30). The correlations with the audiometric parameters were weak (r = 0.11–0.16). Conclusions The German version of the COMQ-12 has satisfactory psychometric properties and can be recommended for assessing HRQoL in German-speaking population with COM. Its suitability for evaluating symptom-related quality of life is due to its symptom-focused design and high level of responsiveness. Its low response shift also makes it ideal for longitudinal monitoring of treatment outcomes.
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
Abstract Artificial intelligence has transformed digital pathology by enabling biomarker prediction from high-resolution whole-slide images. However, current methods are computationally inefficient, processing thousands of redundant tiles per slide and requiring complex aggregation models. We introduce EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework that emulates pathologists by selectively analyzing informative regions. EAGLE combines task-agnostic tile selection with detailed feature extraction and is benchmarked against leading slide- and tile-level foundation models across 43 tasks from nine cancer types spanning morphology, biomarker prediction, treatment response and prognosis. EAGLE outperforms patch aggregation methods by up to 23% and achieves the highest overall classification performance. It processes one slide in 2.27 s, reducing computational time by more than 99% compared with existing models. This efficiency supports rapid and auditable workflows by enabling review of the exact tiles used for each prediction and reducing dependence on high-performance computing. By reliably identifying informative regions and minimizing artifacts, EAGLE provides robust and auditable outputs, supported by systematic negative controls and attention concentration analyses. Its unified embedding enables rapid slide search, integration into multi-omics pipelines and emerging clinical foundation models.
Imitation learning has achieved remarkable success in robotic manipulation, yet its application to surgical robotics remains challenging due to data scarcity, constrained workspaces, and the need for an exceptional level of safety and predictability. We present a supervised Mixture-of-Experts (MoE) architecture designed for phase-structured surgical manipulation tasks, which can be added on top of any autonomous policy. Unlike prior surgical robot learning approaches that rely on multi-camera setups or thousands of demonstrations, we show that a lightweight action decoder policy like Action Chunking Transformer (ACT) can learn complex, long-horizon manipulation from less than 150 demonstrations using solely stereo endoscopic images, when equipped with our architecture. We evaluate our approach on the collaborative surgical task of bowel grasping and retraction, where a robot assistant interprets visual cues from a human surgeon, executes targeted grasping on deformable tissue, and performs sustained retraction. Our results show that generalist Vision Language Action models fail to acquire the task entirely, even under standard in-distribution conditions. Furthermore, while standard ACT achieves moderate success in-distribution, adopting a supervised MoE architecture significantly boosts its performance, yielding higher success rates in-distribution and demonstrating superior robustness in out-of-distribution scenarios, including novel grasp locations, reduced illumination, and partial occlusions. Notably, it generalizes to unseen testing viewpoints and also transfers zero-shot to ex vivo porcine tissue without additional training, offering a promising pathway toward in vivo deployment. To support this statement, we present qualitative preliminary results of policy roll-outs during in vivo porcine surgery.
