Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthetic therapy, including those cases where SE recurs on the reduction or withdrawal of anesthesia (usually propofol, midazolam, or pentobarbital/thiopental).¹ Despite substantial improvements in the understanding, diagnosis, and treatment of nonrefractory SE, SRSE is still considered an evidence-free area.²

Large abdominal aortic aneurysms (AAAs) present a significant mortality risk. While numerous medical interventions have been proposed, no drugs have convincingly reduced AAA progression, rupture rates, or repair risk. This systematic review and meta-analysis aimed to assess the impact of repurposed drugs or dietary supplements on slowing expansion rates, reducing the risk of rupture, or minimising the risk of repair for individuals with AAA. A systematic search was conducted in five databases. Both observational studies and randomised controlled trials were included. Unpublished data from two screening trials were incorporated. Risk of bias was assessed using the Newcastle-Ottawa scale and revised Cochrane risk of bias tool. Meta-analyses were performed for each identified drug subclass and were stratified by overall risk of bias. Results were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of 7 484 screened studies, 39 met the inclusion criteria. No studies on dietary supplements were included. A total of 84 cohorts were derived from the included studies, and twelve distinct drug groups underwent meta-analyses. Two drug groups, metformin and statins, were statistically significant in slowing AAA growth. No low risk of bias studies were included for these two drug groups, and the results had very high heterogeneity (I² > 80%). Both groups had a GRADE certainty of very low. Metformin, excluding high risk of bias studies, presented an estimated mean growth difference of AAA diameter between users and non-users of -0.73 mm/year, whilst statins had an overall estimated mean difference of -0.84 mm/year. This systematic review and meta-analysis suggests that metformin and statins may provide some effect in slowing AAA progression. However, no definitive evidence was found for any of the investigated drugs included in this study. Further research is needed to identify effective medical treatments for AAA progression with more robust methodology.

This study aimed to develop a prediction tool to identify abdominal aortic aneurysms (AAAs) at increased risk of rupture incorporating demographic, clinical, imaging, and medication data using artificial intelligence (AI). A development and validation study for individual prognosis using AI in a case-control design. From two Danish hospitals, all available ruptured AAA cases between January 2009 and December 2016 were included in a ratio of 1:2 with elective surgery controls. Cases with previous AAA surgery or missing preoperative scans were excluded. Features from computed tomography angiography scans and hospital records were manually retrieved. The sample was divided randomly and evenly into developmental and internal validation groups. A SHapley Additive exPlanations Feature Importance Rank Ensembling (SHAPFire) AI tool was developed using a gradient boosting decision tree framework. The final SHAPFire AI model was compared with models using (1) solely infrarenal anterior-posterior diameter and (2) all available features. The study included 637 individuals (84.8% men, mean age 73 ± 7 years, 213 ruptured AAAs). The SHAPFire AI incorporated 20 of 68 available features, and aneurysm size, blood pressure, and relationships between height and weight were given highest rankings. The receiver operating characteristic curve for the SHAPFire AI model displayed a significant increase in accuracy identifying ruptured AAA cases compared with the conventional model based solely on diameter with areas under the curves of 0.86 ± 0.04 and 0.74 ± 0.03 (P = .008), respectively. SHAPFire AI was comparable in performance with the model using all features. This study successfully developed a SHAPFire AI tool to identify AAAs at increased risk of rupture with significantly higher accuracy than diameter alone. External validation of the model is warranted before clinical implementation.

BACKGROUND: Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death. METHODS: The study population included all men with screening-detected AAAs (30–55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008–2011) and the Danish Cardiovascular Screening trial (inclusion, 2014–2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021. RESULTS: A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67–72] years; median AAA diameter, 35.4 [IQR, 32–41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of −0.22 mm/year [95% CI, −0.39 to −0.06]; P =0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70–0.97]; P= 0.023), which was significant after 2.5 years. Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner, with an adjusted HR of 0.83 ([95% CI, 0.73–0.94]; P =0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses. CONCLUSIONS: High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.

BACKGROUND: The somatic JAK2 ^V617F sequence variation, a key driver of myeloproliferative neoplasms, has been associated with increased risk of aortic aneurysms. This study aimed to explore associations between the JAK2 ^V617F variant allele frequency (VAF) and ascending, descending, and abdominal aortic aneurysms. METHODS: In the DANCAVAS I and II trials (Danish Cardiovascular Screening), 15 000 individuals underwent cardiovascular risk assessments including blood samples and noncontrast ECG-gated computed tomography scans. In this cross-sectional substudy, individuals with screening-detected aortic aneurysms (≥45 mm ascending, ≥35 mm descending, or ≥30 mm abdominal), random aneurysm-free male controls, and all women (only included during the DANCAVAS I pilot study) were tested for the JAK2 ^V617F sequence variation. RESULTS: A total of 8056 individuals (90.9% men, mean age 68±4 years) were tested for the JAK2 ^V617F sequence variation, which presented an overall prevalence of 7.1%. Ascending, descending, and abdominal aneurysm prevalences were 6.6%, 2.9%, and 6.8%, respectively. In JAK2 ^V617F -negative participants (n=7486), JAK2 ^V617F -positive participants with VAF <1% (n=491), and JAK2 ^V617F -positive participants with VAF ≥1% (n=79), ascending aortic aneurysms were observed in 6.4%, 9.0%, and 16.5%, respectively ( P <0.001). No significant differences were observed across sequence variation groups for descending and abdominal aneurysms. Among JAK2 ^V617F -positive individuals, the median VAF was higher in those with ascending aneurysm (9.5%; interquartile range, 3.0–40.0) than in controls (4.4%; interquartile range, 1.8–20.0; P =0.021). Ascending aortic diameter correlated modestly with VAF (Spearman ρ=0.10; P =0.026). No significant correlations were observed for descending or abdominal diameters. For ascending aneurysms, JAK2 ^V617F VAF <1% and ≥1% presented adjusted odds ratios of 1.4 (95% CI, 1.01–2.0; P =0.045) and 2.7 (95% CI, 1.5–5.1; P =0.002), respectively, compared with JAK2 ^V617F -negative controls. For each doubling in VAF, the risk for ascending aneurysm increased by 11% ( P _adjusted =0.013). The JAK2 ^V617F sequence variation was not significantly associated with descending or abdominal aneurysms after adjusting for covariates and using these VAF thresholds. CONCLUSIONS: In a study population of primarily men 60 to 74 years of age, the somatic JAK2 ^V617F sequence variation was strongly and independently associated with ascending aortic aneurysms, presenting a positive correlation between aneurysm size and JAK2 ^V617F VAF. No convincing associations were observed for descending or abdominal aneurysms. Screening patients with larger ascending aortic aneurysms for the JAK2 ^V617F sequence variation, and vice versa, screening JAK2 ^V617F -positve individuals presenting higher VAFs for ascending aneurysms, may be clinically appropriate.