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Purpose Aneurysmal rupture and subarachnoid hemorrhage (SAH) have an exceptionally high mortality and morbidity burden. The aim of this study was to develop interpretable machine learning models for predicting short-term poor outcomes defined by the National Inpatient Sample Subarachnoid Hemorrhage Outcome Measure (NIS-SOM). Methods The National Inpatient Sample (NIS) database was queried from 2008 to 2018 to identify patients diagnosed with SAH who had undergone endovascular coiling or clipping for intracranial aneurysm. Demographic, comorbidity, risk factor, and hospital characteristic variables were recorded. Variables were preprocessed, and the feature space was reduced to include the most important features. To predict poor outcomes, machine learning models were trained and cross-validated before being evaluated on a separate testing set. Shapley Additive exPlanations of the best performing model was used for general and local model interpretation. Results Among 18,149 admissions (mean age 55 ± 14 years, 68.8% women), 52.9% had a poor outcome. Test-set AUCs ranged 0.74–0.80; a multilayer perceptron performed best (AUC 0.80, precision 0.74, recall 0.82). SHAP ranked the ten most influential variables: age, neurological comorbidity, paralysis, Medicare insurance, smoking status, Elixhauser burden, fluid-electrolyte disorders, weight loss, arrhythmia, and heart failure. Conclusions The modeling predicted nationwide aSAH prognosis with decent accuracy and highlighted clinical, socioeconomic, and system-level drivers of determinants of poor short-term outcome. These results support the potential of explainable ML tools as complementary tools for early risk stratification, guiding resource allocation, and informing prospective multi-center validation and implementation studies.

Chronic kidney disease (CKD), heart failure with preserved ejection fraction (HFpEF), and the recently defined cardiovascular-kidney-metabolic (CKM) syndrome are important challenges for the health care system, associated with a staggering increase in morbidity and mortality rates. Unfortunately, the complex pathophysiology of these processes remains to be fully elucidated, imposing hurdles to prevent their development and decelerate their progression. Large animal models are critical for understanding cardio-renal pathophysiology and for the discovery of new therapies. Among them, pig models offer significant translational power to grasp cardio-renal pathophysiology and to test the feasibility and efficacy of new strategies. We recently developed and characterized swine models of CKD, HFpEF, and CKM syndrome that closely recapitulate human disease and allow for the study of the impact of biological variables, such as sex or age, on these conditions. Furthermore, data from these studies revealed key mechanisms implicated in the pathogenesis of CKD, HFpEF, and CKM syndrome and identified potential targets for intervention. This focused mini review highlights the main features of these novel swine models and discusses ongoing and future research aimed at developing novel therapies.

Background and Objective: Scleral-fixated intraocular lens (SFIOL), scleral-sutured IOL (SSIOL), anterior chamber IOL (ACIOL) are used to manage aphakia or lens subluxation. This study compared trends in surgical techniques and outcomes of secondary IOL implantation based on surgeon type. Patients and Methods: This retrospective study included patients from United States (US) retinal centers who underwent surgery by vitreoretinal (VR cohort) or VR and anterior segment (AS) (combined cohort) surgeons from 2015 to 2024. Complications assessed included retinal detachment, endophthalmitis, suture erosion, haptic erosion, repeat pas plana vitrectomy, and corneal edema. Results: VR surgeons performed 4,143 secondary IOL surgeries (1,977 ACIOL, 1,327 SFIOL, 839 SSIOL) while VR and AS surgeons performed 511 (342 ACIOL, 125 SFIOL, 44 SSIOL). SFIOL and SSIOL surgeries by VR surgeons increased, whereas ACIOL surgeries decreased. VR and AS surgeons maintained a steady but lower volume of SFIOL and SSIOL cases, with increasing ACIOL surgeries. Postoperative visual acuity for the VR and combination cohorts was 54.3 ± 27.8 and 51.5 ± 27.2 (≈ 20/100 Snellen) ( P value = 0.102), respectively. Complication rates were similar between cohorts, except for postoperative retinal detachment (VR: 144, 3.5%; combined: 26, 5.1%; P value < 0.001). Conclusion: ACIOLs were the most commonly performed secondary IOL surgery. However, a shift toward SFIOL and SSIOL techniques among vitreo-retinal surgeons emerged. Outcomes were comparable between approaches.

Importance The Implantable Neurostimulator for the Treatment of Parkinson’s Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD). Objective To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD. Design, Setting, and Participants This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson’s Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score. Intervention Bilateral STN-DBS for moderate to advanced PD. Main Outcomes and Measures Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs. Results A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P &amp;lt; .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P &amp;lt; .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P &amp;lt; .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P &amp;lt; .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P &amp;lt; .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P &amp;lt; .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P &amp;lt; .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study. Conclusions and Relevance Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P &amp;lt; .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P &amp;lt; .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

Background: Adductor avulsions are complex injuries often involving multiple structures, as indicated by several magnetic resonance imaging (MRI) studies. However, no studies have compared MRI assessments using a dedicated groin protocol with surgical findings. Hypothesis: It was hypothesized that MRI assessments using a dedicated groin protocol would correlate closely with surgical findings, applicable to both experienced and novice users of the pyramidalis–anterior pubic ligament–adductor longus complex (PLAC) classification. Study Design: Case series; Level of evidence, 4. Methods: This retrospective study analyzed 161 athletes who underwent MRI using a dedicated groin protocol, followed by surgical repair of the PLAC. Two musculoskeletal radiologists—1 experienced (rater A) and 1 inexperienced (rater B) in the use of the PLAC classification—independently assessed the MRI scans twice, 6 weeks apart, using a structured 3-step protocol to evaluate (1) adductor longus fibrocartilage (intact, partially avulsed, or completely avulsed), (2) pyramidalis separation from adductor longus (intact, partially separated, or completely separated), and (3) pectineus status (intact or partially avulsed). Agreement between MRI and surgical findings was evaluated using a PLAC injury classification (types 1-5), with intra- and interobserver reliability measured by Cohen kappa. Results: Among the 161 athletes, 93 played soccer, of whom 69 were professional. All athletes exhibited complete fibrocartilage avulsion, with 83 athletes (52%) showing adductor longus separation from the pyramidalis. Isolated adductor longus avulsions (PLAC type 1) were observed in only 36 athletes (22%). The interobserver kappa score between MRI assessments and surgical findings was 0.942 for rater A and 0.858 for rater B. Intraobserver ratings were 0.967 for rater A and 0.875 for rater B. Both inter- and intraobserver scores indicated almost perfect agreement. In combination, these statistical findings support the validity, reliability, and applicability of the MRI protocol using the PLAC classification system for 2 users with varying levels of experience. Conclusion: Adductor avulsions were rarely isolated, typically involving multiple muscles. The PLAC classification effectively captured the complexity of these injuries. When used in conjunction with a dedicated MRI protocol, the PLAC classification demonstrated almost perfect agreement and concordance with surgical findings. Together, the PLAC classification and MRI protocol offered a more comprehensive and accurate representation of patients’ clinical and radiological features and provided valuable guidance for surgical planning.