Interpreting complex non-linear survival models while maintaining proportional hazards semantics remains a significant challenge in statistical learning. This work introduces GhostCox, a novel method designed to enhance the interpretability of non-linear proportional hazard models by quantifying covariate contributions to the risk function via ghost variables. Our approach evaluates the unique conditional relevance of each covariate by substituting its values with their estimated conditional expectations, given the remaining features. Numerical experiments and real-world applications demonstrate that GhostCox effectively identifies true predictors and is significantly more computationally efficient than established benchmarks, such as the Holdout Randomization Test (HRT). Furthermore, GhostCox yields compact feature sets with robust predictive performance. Overall, GhostCox provides a transparent, statistically grounded, and scalable framework for interpreting complex survival models, offering actionable insights into covariate effects.
OBJECTIVE:A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN:Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING:Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS:A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS:A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS:A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.
Placenta accreta spectrum (PAS) is a life-threatening obstetric condition associated with increasing cesarean delivery rates worldwide. Existing classifications, such as the World Health Organization International Statistical Classification of Diseases and Health-Related Problems and the International Federation of Gynecology and Obstetrics system, describe depth of invasion and histopathological features but do not adequately predict surgical outcomes or guide individualized management. The PAS topographic classification describes the anatomical extent of uterine wall remodeling and the presence of uterovesical adhesions, allowing surgical teams to anticipate intraoperative complexity, organ involvement, and appropriate therapeutic strategies. Although successfully applied in selected centers, its broader evaluation across diverse healthcare settings is lacking. We designed a prospective, multicenter, international cohort study enrolling patients with a high prenatal suspicion of PAS. Eligible patients are aged ≥ 18 years, undergoing surgery after 20 weeks’ gestation, and managed by multidisciplinary PAS teams familiar with the topographic classification. Standardized prenatal ultrasound staging and intraoperative surgical staging are required, with photographic and video documentation. Surgical strategies include one-step conservative surgery, total hysterectomy, and modified subtotal hysterectomy, guided by intraoperative classification. The primary outcome is intraoperative blood loss, measured using a standardized protocol. Secondary outcomes include intraoperative complications, operative time, treatment type, and usability assessments of the classification through structured surveys. Data are collected in REDCap with external review of imaging records. This study will provide the first prospective, multicenter evaluation of the PAS topographic classification, assessing its correlation with clinical outcomes and its feasibility across hospitals with varying resources and surgical expertise. Preliminary results indicate successful implementation in both high- and low-volume centers, with promising adoption of prenatal ultrasound staging and surgical protocols. The collaborative, image-based, and open-access methodology aims to strengthen the reliability of PAS research by harmonizing surgical strategies and allowing external supervision. Ultimately, this project will generate robust multicenter data to inform individualized management strategies and support the integration of the topographic classification into routine clinical practice worldwide. ClinicalTrials.gov Identifier: NCT05922397. Registered on 21 May 2023.
BACKGROUND:Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. METHODS:In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. RESULTS:Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. CONCLUSIONS:Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).
Abdominal organ segmentation is a rapidly advancing area in medical imaging, boasting numerous remarkable applications in clinical and research settings. Despite these advancements, most existing segmentation models are developed using single-source data. This homogeneity raises concerns regarding the applicability of these models to more diverse and complex clinical scenarios. This study aimed to develop a generalizable model for the semantic segmentation of abdominal organs using three widely recognized public datasets: BTCV, AMOS, and TotalSegmentator. Extensive cleaning and preprocessing were undertaken to address the challenges posed by data heterogeneity. The merging process resulted in a diverse and comprehensive dataset of 680 CT scans encapsulating varied image conditions and anatomical representations. The comparative analysis utilized two architectural frameworks: nnUNet, representing Convolutional Neural Networks, and Swin-UNETR, embodying Vision Transformers. Results demonstrate the superiority of the nnUNet model across all experiments, demonstrating superior robustness and adaptability under diverse conditions and unseen cases. However, further research could contribute to achieving a more balanced performance across patient groups. With an average Dice Similarity Coefficient of 92.3%, the developed nnUNet model establishes itself as a highly effective and competitive approach in abdominal organ segmentation.
