Citations

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Abstract Background aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

Abstract Objective Shunt-dependent hydrocephalus is a common and costly complication of aneurysmal subarachnoid hemorrhage (aSAH), affecting up to 28% of survivors. Existing prediction tools, including the Chronic Hydrocephalus Ensuing from SAH Score (CHESS), have limited discriminative accuracy. We developed the CHECKMATE score, a clinically practical tool to improve prediction of ventriculoperitoneal shunt dependency after aSAH. Methods In this multicenter retrospective cohort of 486 patients with aSAH from Mayo Clinic (January 1, 2006-December 31, 2021), we used multivariable logistic regression and machine learning to identify independent predictors of ventriculoperitoneal shunt placement. The CHECKMATE score was derived from 5 weighted variables: symptomatic hydrocephalus (10 points), intraventricular hemorrhage (5 points), SAH volume greater than 10 mL (3 points), neutrophil-to-lymphocyte ratio greater than 12 (2 points), and 10-year incremental age thresholds starting at older than 60 years (1 point each). Results Of 486 patients (mean age, 56.3 years; 64.6% female), 137 (28.2%) required ventriculoperitoneal shunt placement. The CHECKMATE score achieved an area under the curve of 0.808 (compared to 0.737 for CHESS), with a sensitivity of 0.85, specificity of 0.67, and negative predictive value of 0.92 at the optimal cutoff of 14 points. Conclusions The CHECKMATE score outperforms CHESS for predicting ventriculoperitoneal shunt dependency after aSAH and is easily used at the bedside. Its high negative predictive value helps identify low-risk patients who may benefit from earlier external ventricular drain weaning and shorter hospital stays.

Background Delayed aneurysm rupture (DAR) is a potentially devastating complication after flow-diverters (FD) deployment and their exact mechanisms are still unclear. The purpose of this meta-analysis is to synthesize the latest evidence on DAR after FD treatment and identify predictive factors. Methods A systematic review and meta-analysis were conducted according to established protocols. Searches were conducted in PubMed, Scopus, Web of Science, and Embase databases up to June 2024 using variations of “aneurysm “and “delayed aneurysm rupture” terms. Original studies reporting DAR and including more than five patients were included. All analyses were conducted in R software (version 4.4.2), employing the “meta” and “tableone” packages. Results 64 studies with 9820 patients were included, large aneurysm size (OR=1.08, 95% CI (1.02, 1.14), P value=0.008), intra-aneurysmal thrombus (OR=1.05, 95% CI (1.01, 1.09), P value=0.010) and posterior circulation location (OR=1.02, 95% CI (1.00, 1.04), P value=0.014) were significant risk factors for DAR. The pooled prevalence of DAR was 1.40%, with a rate of 1.18% after removing outliers. DAR occurred within 30 days in 66.7% of cases, with a mortality rate of 73.3% at discharge. Conclusion DAR following flow diversion treatment is an uncommon but devastating complication and remains a limitation of the technique. It is influenced by factors such as large aneurysm size, intra-aneurysmal thrombosis, and posterior circulation involvement. The first 30 days post-procedure represent a particularly high-risk period. Despite advancements in FD technology, significant gaps remain, highlighting the need for further research to improve risk assessment and treatment strategies.

Introduction Post‐market and multicenter studies report low complete occlusion rates (41‐49%) and higher retreatment rates (13%) following WEB deployment, compared to 3.8% with microsurgical clipping. While retreatment after WEB has been shown to be technically feasible, data on final angiographic outcomes remain limited. We performed a retrospective analysis of prospective databases from 14 cerebrovascular centers in the US to compare the safety and efficacy of retreatment versus continued observation for residual and recurrent aneurysms after initial WEB deployment. Materials/Methods Multinomial logistic regression was used to identify baseline characteristics of untreated and residual/recurrent aneurysms that may act as confounders, which then underwent propensity scored matching (PSM). Results Among 211 patients (125 observed, 86 retreated), retreatment was more common in initially ruptured aneurysms (p<0.001), which showed higher recurrence (p=0.036) and sac‐dominant residuals (p=0.004). These were primarily due to WEB compression on follow‐up (p=0.001), rather than incomplete occlusion with an appropriately sized device (p<0.001). Retreatment was associated with significantly higher rates of complete angiographic occlusion at last follow‐up compared to observation alone (p<0.001), a finding that remained consistent across subgroups defined by initial unruptured status, residual type, and recurrence patterns (all p<0.05). Clipping demonstrated higher, though statistically insignificant, rates of complete occlusion; flow diversion and stent‐assisted coil embolization yielded comparable complete occlusion rates at follow‐up. After propensity score matching, retreatment remained significantly associated with higher rates of complete angiographic occlusion (all p<0.05), with comparable outcomes observed between clipping and various endovascular approaches as above. Conclusion Retreatment improved complete occlusion rates; however, no aneurysmal hemorrhages occurred in either group. Further intervention may be unnecessary when the WEB device—whether compressed or intact (BOSS 0/1)—adequately protects the dome. In cases where WEB compression significantly exposes the aneurysm wall, stent‐assisted coiling or flow diversion can be performed safely and successfully, depending on vascular anatomy and surgeon preference. image image

OBJECTIVE The global need for neurosurgical care is significant and often unmet. Building partnerships between high-income countries (HICs) and lower-middle-income countries (LMICs) can help bridge the gap. Six features of sustainable global surgical partnerships have been identified; however, their application in neurosurgery has not been studied. The authors analyzed how the 6 pillars of sustainability are applied to neurosurgical partnerships established by the Neurosurgery Outreach Foundation (NOF) with hospitals in LMICs in Asia. METHODS NOF is an all-volunteer, nonprofit US foundation with the mission to advance neurosurgical care in underserved communities through education, service, and support. The authors examined the NOF programs and identified the characteristics associated with the 6 pillars of sustainability, which are community engagement, multidisciplinary collaboration, education and training, outcome measurement, multisource funding, and bilateral authorship. The authors discuss how these pillars contribute to the establishment of sustainable partnerships. RESULTS From 2010 to 2024, NOF has established partnerships at 4 sites: Cebu, Manila, and Davao, the Philippines; and Ulaanbaatar, Mongolia. Partnerships were established with tertiary or quaternary government hospitals to develop neurosurgical programs tailored to the needs of each site and remained sustained and active. Educational surgical missions were in-person outreach activities conducted annually or biennially and were supplemented with online or remote collaboration. The 5 pillars of sustainable partnerships present at all sites include community engagement, multidisciplinary collaboration, education and training, outcome measurement, and multisource funding. The sixth pillar, bilateral authorship, was present at University of the Philippines–Philippine General Hospital in Manila. CONCLUSIONS Using the 6 pillars of sustainable global partnerships, neurosurgical partnerships can be developed and maintained by all-volunteer nonprofit organizations such as NOF. Incorporating these pillars during the planning and executing of global neurosurgical partnerships are essential for long-term success.

Background The pipeline embolization device (PED) has been increasingly used to treat brain aneurysms; however, concerns have been raised about braid stability with newer drawn filled tubing technology devices. Objective To evaluate braid stability of PED early generations using data from the PREMIER trial. Methods All consecutive intracranial aneurysms treated with PED (Classic and Flex) within the PREMIER trial were reviewed for braid stability (fish mouthing, foreshortening, braid bump, braid collapsing). Immediate postprocedure cone-beam CT and angiography were compared with 1- and 2- years' follow-up. Analyses included safety, measured with the modified Rankin Scale (mRS) score, including +1 mRS point and a good clinical outcome (mRS score 0–2), vessel stenosis ≥50%, effectiveness measured with Raymond-Roy Scale, and re-treatment rates. Results 133/141 aneurysms had a complete dataset. 8/133 (6%) aneurysms showed braid deformations. Inter-reader agreement was excellent (κ=0.83). Braid deformations were statistically significantly associated with in-stent vessel stenosis >50% (P=0.029), without impact on effectiveness or safety. Fish mouthing was found in 1/133 (0.75%) at 1 year, causing >50% vessel stenosis. Foreshortening occurred in 6/133 (4.5%), and braid bump in 1/133 (0.75%) associated with severe in-stent stenosis. Four other cases (3.0%) of asymptomatic in-stent stenosis due to neointimal hyperplasia were seen without braid changes. No new braid stability deformations were found at the 2-year follow-up. Conclusion Our study demonstrates excellent braid stability among patients treated with the PED Classic and Flex in the PREMIER trial. Within the uncommon braid changes observed, none affected the PED safety or efficacy. Trial registration number NCT02186561 .

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P =1.6×10 −6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18–1.36]; P PRS =2.7×10 −11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14–1.35]; P PRS =1.27×10 −6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.