Citations

BACKGROUND AND OBJECTIVES: The prospective single-arm nonrandomized SCENT (Surpass Intracranial Aneurysm Embolization System Pivotal) trial on flow diverter treatment of large and giant intracranial aneurysms (IA) was analyzed for patients' age and IA characteristics affecting stroke and occlusion rates over 5 years (Trial registration NCT01716117). METHODS: Impact on major ipsilateral stroke and IA occlusion was studied by stratifying age as 65 years and younger vs older than 65. Kaplan–Meier estimates of time to both endpoints, stratified by age, were created. Univariate predictors of time-to-stroke were analyzed using univariable proportional hazards regression models. Limited bivariable modeling was also attempted. RESULTS: Of 180 patients with large or giant IA enrolled, 119 were 65 years and younger, whereas 61 were older than 65 years. The 3-year risk of stroke for the older than 65 years group (19.7%) was more than double that of the 65 years and younger group (9.2%), P = .047. No new strokes were reported between 3 and 5 years. Four patients (2.2%) experienced aneurysm rupture within the first week post-treatment, 3 being 65 years and younger and the fourth older than 65 (>.99). Complete IA occlusion within age strata at 1 year was: older than 65 60% (33/55), 65 years and younger 79.1% (87/110), P = .009, 3 years: older than 65 67.6% (25/37), 65 years and younger 82.5% (66/80), P = .071, and 5 years: older than 65 85.7% (18/21), 65 years and younger 91.8% (56/61), P = .417. CONCLUSION: Age older than 65 was associated with an increased risk of stroke and predictive of incomplete healing and increased time to healing.

Abstract Background Interpretation of multi-analyte laboratory profiles, such as lupus anticoagulant (LAC) testing, requires integration of numerous test results and clinical information. However, this process is time-consuming, requires domain knowledge, and has limited scalability. Given that rule-based systems are rigid and difficult to maintain and large language models pose risks of “hallucinations,” we developed and evaluated a novel retrieval-based approach to automate LAC profile interpretation to improve efficiency while maintaining fidelity and reliability for clinical use. Methods Our method processes laboratory values through ensemble random forest (RF) models to retrieve the most similar expert interpretation from a curated database of 347 previously interpreted LAC profiles. The system's performance was assessed through technical accuracy metrics, a work flow efficiency timing study, and expert review of interpretation accuracy for held-out cases. Results Technical validation demonstrated high accuracy in retrieving correct interpretative elements (median: 93% accuracy, interquartile range [IQR]: 67% to 100%). Retrieval accuracy was highly correlated with the prevalence of a given element (ρ = 0.8307). In a timing study of 93 consecutive LAC profiles, ensemble-assisted interpretation achieved a median time of 22 s per report (IQR: 16 s to 31 s), representing a 78.6% total reduction compared to manual interpretation (median: 118 s, IQR: 96 s to 172 s; t = 18.61, P < 0.001). Furthermore, 92.5% of AI-assisted interpretations were completed within 60 s, exceeding the target of 85%. Expert review confirmed 100% concordance for LAC presence/absence. Conclusions The proposed approach significantly improves efficiency of complex laboratory interpretation for LAC profiles, while maintaining consistency and high fidelity. Future studies will explore the method’s inherent extensibility to the interpretation of other multi-analyte laboratory profiles.

ABSTRACT Extracellular vesicles (EVs) are non‐replicating, lipid membrane‐bound nanoparticles released by most eukaryotic cells into the extracellular space. When derived from platelets, a subset of EVs can exhibit remarkable anti‐inflammatory and antioxidant properties, making them attractive candidates to attenuate sterile inflammatory states such as limb skeletal muscle ischaemia‐reperfusion injury (IRI). Peripheral extremity IRI complicating acute limb revascularisation procedures, replantation of major traumatic amputations and limb allotransplants can trigger a life‐threatening reperfusion syndrome that leads to multi‐organ system failure and death. In this study, we used a platelet‐derived EVs‐enriched preparation as a therapeutic strategy for extremity IRI. To allow for a clinically translatable drug delivery strategy, we established and validated a catheter‐directed regional intra‐arterial limb infusion (RLI) delivery approach that permitted selective and effective targeting of pEVs to limb skeletal muscles and soft tissues in the vascularly isolated rodent extremity simulating pre‐reperfusion preservation and revascularisation conditions of the ischaemic or amputated extremity. In addition to being safe and feasible, we demonstrated robust retention of EVs by skeletal muscles of the operative limb during the early critical phase of reperfusion injury following RLI. We also show that pretreatment of ischaemic skeletal muscles using an pEVs‐enriched formulation just before reestablishing extremity blood flow alleviated metabolic derangements and suppressed the systemic and localised proinflammatory cytokine response associated with skeletal muscle reperfusion and reduced histologic markers of myofibre injury without adverse effects on serum chemistries. This work opens a new perspective to investigate novel approaches for regional delivery of therapeutic pEVs to skeletal muscle to mitigate limb IRI in vivo, and to achieve both in situ and ex vivo targeted delivery of nanocarriers to the isolated limb tissue for other therapeutic applications.

Abstract Study Objectives Narcolepsy is a chronic condition affecting the sleep/wake cycle that is challenging to diagnose. Epidemiological data from large US-focused studies remain limited, with no validated claims-based case selection definitions for narcolepsy. We estimated the prevalence/incidence of diagnosed narcolepsy (type 1 [NT1], type 2 [NT2], overall) in an insured US population using validated, claims-based narcolepsy case definitions. Materials and Methods This observational study used HealthVerity administrative claims-linked electronic medical records to develop case definitions identifying individuals with NT1, NT2, and overall narcolepsy from diagnosis, medication, and procedure codes. Claims-based case definition performance (NT1, NT2, overall narcolepsy) was assessed using positive predictive values (PPVs). Prevalence (per 100 000 persons, on December 31, 2023) and annual incidence (per 100 000 person-years [PY], 2020 − 2023) were calculated/adjusted using PPVs for each case definition. Results Unadjusted point prevalence among individuals with ≥12 months of continuous enrollment were 15.5/100 000 (NT1), 51.1/100 000 (NT2), and 67.0/100 000 (overall narcolepsy). Unadjusted incidence rates were stable from 2020 − 2023 for NT1 (range, 2.0 − 2.3/100 000 PY) but declined across years for NT2 (9.1 − 7.6/100 000 PY) and overall narcolepsy (11.3 − 9.6/100 000 PY). PPVs (95% confidence interval) of NT1, NT2, and overall narcolepsy were 0.81 (0.72 − 0.88), 0.84 (0.75 − 0.91), and 0.80 (0.71 − 0.87), contributing to epidemiologic estimates being reduced by ~20% after PPV adjustment. Prevalence and incidence were higher in females than males. Individuals with NT1 were ~ 4 years younger versus NT2. Conclusions Validated definitions for narcolepsy can reduce potential misclassification. Our findings highlight a relatively low NT1 prevalence in the US. In contrast, NT2 prevalence estimates were > 3 times higher than NT1.