Arul, Santhosh

Importance Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States. Objective To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI). Design, Setting, and Participants This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes and age groups were included in the GBD. Exposure CNS cancer diagnosis. Main Outcomes and Measures Overall and age-standardized estimates of the incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability per 100 000 population, including 95% uncertainty intervals (UIs), and time trends. Results In 2021, for all age groups and sexes across the US, there were 31 780 incident cases (95% UI, 29971.1 to 32843.9). Age-standardized incidence, DALYs, and mortality rates per 100 000 population were 6.91 (95% UI, 6.58 to 7.12), 134.38 (95% UI, 129.83 to 137.95), and 4.1 (95% UI, 3.87 to 4.22), respectively. Despite no significant change observed in the overall incidence between 1990 and 2021, DALY and mortality rates decreased by 15.77% (95% UI, −17.75% to −13.68%) and 8.41% (95% UI, −11.09% to −6.22%), respectively. Substantial geographic variability was noted. Mississippi, Alabama, Kentucky, and Kansas (West North Central and East South Central divisions) and West Virginia faced persistently high burdens over the past 30 years. Sex differences were evident; disease burden was consistently higher in males compared with females. Age-specific estimates showed a bimodal distribution: the youngest group (<5 years) showed a significant decrease in incidence rate (−34.42% to −11.56%), whereas older age groups (>70 years) experienced increasing trends. DALYs and mortality rates were negatively correlated with SDI (ρ = −0.6860 and ρ = −0.6391; P < .001). Conclusions and Relevance These findings provide valuable insights into the CNS cancer burden across the US by age, sex, location, and SDI, enabling better public health status assessments, health care policy restructuring, and resource redistribution for improved care.

Background Aneurysm treatments are crucial to minimize the rupture risk. The underlying molecular processes mediating cellular remodeling, endothelialization, and aneurysm healing following endovascular treatment are poorly understood. The current study aims to explore circulating miRNA as a treatment and outcome-associated biomarkers in patients undergoing endovascular treatment. Methods Patients undergoing endovascular interventions for unruptured intracranial aneurysms, using either flow diverter placement or coil embolization, were enrolled. Blood samples were collected before the intervention and during a follow-up period between 6 and 18 months. Total mRNA/miRNA was isolated from plasma, followed by RNA-seq analysis. Gene Ontology analysis was used to identify pathways linked to altered miRNA expression. Results Twenty-three patients participated, with 13 (56.5%) undergoing flow diversion and 10 (43.5%) coil embolization. The median follow-up sample collection time was 10.70 months (SEM ± 1.32). No significant differences in angiographic occlusion were noted between intervention groups. Differentially expressed miRNAs were not identified between groups at baseline. However, at follow-up, 39 miRNAs were upregulated and 41 were downregulated, independent of intervention. Notably, three miRNAs (miR-4746-5p, miR-4685-3p, and miR-490-3p) were downregulated in the flow diversion group compared to the coil embolization group. Bioinformatics analysis revealed associations with upregulated fluid shear stress, p53, adherens junction pathways, along with downregulated apoptosis pathways. Conclusions This study suggests that fluid shear stress and apoptosis may influence aneurysm healing or thromboembolic events in flow diverter-treated patients. Further research is warranted to elucidate the functional significance of these findings in treatment outcomes, providing valuable insights for improved patient care in intracranial aneurysm management.

Background The flow diversion treatment of aneurysms located distal to the Circle of Willis has recently increased in frequency. We conducted a systematic review and meta-analysis of the clinical and radiological outcomes of flow diverter (FD) embolization in treating M1 aneurysms. Methods PubMed, Web of Science, Ovid Medline, Ovid Embase, and Scopus were searched up to May 2024 using the Nested Knowledge platform. We included studies assessing the long-term clinical and radiological outcomes for M1 aneurysms. Results of FDs classified as Pipeline Embolization Devices (PED) versus other types of FDs. Angiographic occlusion rates, ischemic and hemorrhagic complications, and favorable clinic outcomes were included. All data were analyzed using R software version 4.2.2. Results Thirteen studies with 112 total patients (58 patients for PED and 54 patients for other FD devices) were included in our meta-analysis. The overall adequate (complete + near-complete) occlusion rates were 85.1%. The complete occlusion rate was higher with PED than with other FD devices (72.9% PED and 41.6% for non-PED FDs, respectively, p -value <.01). The ischemic complications were 9.9% and 9.0% for the PED and non-PED groups, respectively ( p -value = .89). The overall modified Rankin Scale 0–2 was 100% for the non-PED and 97.1% for the PED group ( p -value = .51). In-stent stenosis rate was 7.5% for PED devices compared to 2.6% in the non-PED group ( p -value = .35). Conclusions This relatively small meta-analysis showed high rates of adequate and complete occlusion in FD treatment of M1 segment aneurysms, with favorable safety profiles. PEDs were associated with higher rates of complete aneurysm occlusion compared to other types of FDs.

Introduction Efficacy and safety of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) is still debatable. However, IVT's efficacy on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes specifically remain unclear. In our meta‐analysis, we aimed to explore the effects of IVT on SR and ASP thrombectomy outcomes. Methods A systematic literature review was steered using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases, according to PRISMA guidelines. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), functional independence (modified Rankin Scale (mRS) ≤2), modified first pass efficacy (mFPE), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). Results We included four randomized controlled trials with 1176 patients. SR and ASP had similar mTICI ≥2b, mFPE, and mRS 0‐2 rates whether they received IVT or not. SR without IVT was associated with a lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Additionally, ASP without IVT resulted in a lower rate of mRS 0‐2 than the ASP+IVT (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. Conclusion Our analysis suggests that SR and ASP thrombectomy have equivalent efficacy and safety outcomes regardless of prior IVT administration. Moreover, our results indicate that administration of IVT before MT may improve certain outcomes based on the used first‐line MT technique.

Background The comparison of mechanical thrombectomy (MT) outcomes between patients with the hyperdense middle cerebral artery sign (HMCAS) and non-HMCAS is important to evaluate the impact of this radiological finding on treatment efficacy. This meta-analysis aimed to assess the association between HMCAS and clinical outcomes in patients undergoing thrombectomy, comparing the outcomes over non-HMCAS. Methods A systematic literature search was conducted in PubMed, Ovid Embase, Google Scholar, and Cochrane Library to identify studies on MT outcomes for M1 occlusions of HMCAS over non-HMCAS. Inclusion criteria encompassed modified Rankin Scale (mRS) score, mortality, symptomatic intracranial hemorrhage (sICH), and successful recanalization. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). Results The meta-analysis was performed for 5 studies with 724 patients. There was no association found between presence of HMCAS and achieving mRS 0–2 (OR = 0.65, 95% CI: 0.29–1.47; p = .544). Mortality analysis also showed no significant association with presence of HMCAS (OR = 0.78, 95% CI: 0.37–1.65; p = .520). No significant difference in sICH risk (OR = 1.54, 95% CI: 0.24–9.66; p = .646) was found between groups. Recanalization analysis showed a non-significant positive association (OR = 1.23, 95% CI: 0.67–2.28; p = .501). Heterogeneity was observed in all analyses. Conclusion Our findings showed that there is no statistically significant difference in mRS scores, mortality, sICH, and recanalization success rates between the HMCAS and non-HMCAS groups.

Background The presence of an outer shell has been recently described as a common feature of acute ischemic stroke (AIS) thrombi. We performed a systematic review of the current literature on shell genesis, structure, and clinical significance. Methods Following PRISMA guidelines, we searched Ovid Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science for studies reporting the composition and structure of AIS thrombi and clot analogs. Identified studies were added to Covidence software for primary screening. Two reviewers independently screened titles and abstracts followed by full-text screening. Results From 1290 identified studies, 10 were included in this review. Studies using histology/immunohistochemistry/immunofluorescence described fibrin, platelets, von Willebrand factor, and neutrophil extracellular traps as the main components of the shell. Scanning electron microscopy demonstrated a dense, compact fibrin/platelet-rich shell, and a core rich in polyhedrocytes. Microfluidics studies identified highly activated P-selectin-positive platelets and fibrin forming the core while secondary agonists adenosine diphosphate and thromboxane, along with loosely packed P-selectin-negative platelets constituted the shell. Conclusions The composition, compaction, and integrity of the shell may impact thrombolysis and revascularization outcomes. The preponderance of studies supported this conclusion.

Background Distal transradial artery access (dTRA) has received increasing consideration for performing diagnostic cerebral angiography and neurointerventional procedures. In this meta-analysis, we aim to evaluate the safety and efficacy of dTRA compared to conventional transradial access (cTRA) for cerebral angiography and neurointerventions. Method A systematic review and meta-analysis were conducted on studies investigating outcomes of dTRA and cTRA in neurointerventions. The primary outcome was technical success rates. Secondary outcomes included access site complication rates, crossover rates to alternative vessels, fluoroscopy time, and contrast volume. The random effects model was used to calculate the mean difference (MD) and odds ratios (OR) with 95% confidence intervals (Cl). Results Eight retrospective observational studies with a total of 1477 patients who underwent 1175 diagnostic cerebral angiography and 516 neurointerventional procedures using 546 dTRA and 1164 cTRA approaches were included in our meta-analysis. The technical success rate was similar between dTRA and cTRA groups (95.8% vs 91.4%; OR:1.65; 95% Cl: 0.52 to 5.22; P = 0.40). Similarly, no difference was seen in dTRA and cTRA regarding access site complications (2% vs 1.4%; OR: 1.31; 95% CI: 0.47 to 3.61; P = 0.61) and access site crossover (2.1% vs 5.3%; OR: 0.55; 95% Cl: 0.28 to 1.05; P = 0.07). After resolving heterogeneity among included studies, dTRA was associated with a shorter fluoroscopy time (MD: −0.91 min; 95% CI: −1.74 to −0.09; P = 0.03) and lower contrast volume (MD: −8.32 mL; 95% CI = −14.7 to −1.94; P = 0.011). Conclusion Our findings suggest that the dTRA approach is a safe and effective alternative to the cTRA approach in patients undergoing cerebral angiography and neurointerventions.

Background Chronic subdural hematoma (cSDH) is a challenging and common neurosurgical condition. Our goal is to demonstrate that middle meningeal artery (MMA) embolization combined with surgical evacuation can be a promising adjuvant option for treatment of cSDHs and prevent recurrence in symptomatic patients who require surgical treatment. Method We retrospectively collected data from patients who underwent MMA embolization using polyvinyl alcohol particles and surgical evacuation with burr hole or craniotomy in a single center for the treatment of new and recurrent cSDHs. The primary outcome was recurrence of cSDH requiring surgical rescue during follow up, and secondary outcomes were defined as >50% decrease in the maximum width of cSDHs on the longest follow-up computed tomography (CT) scan, complications following procedure, and improvement in modified Rankin scale (mRS) score. Results A total of 51 patients successfully underwent 72 MMA embolization procedures (96% of the total 75 cases in the cohort) combined with surgical evacuation. Seventy cases (93.3%) achieved at least 50% reduction in the size of the cSDHs on the last CT imaging. A surgical evacuation was required in five cases (6.7%) due to cSDH recurrence during the follow-up period. There were three complications (6.0%) related to embolization procedure. Forty patients (78.4%) showed improvement in mRS score. There was one mortality (2%) regardless of the embolization and evacuation. Conclusions Our study demonstrates the safety and efficacy of adjunct MMA embolization in significantly reducing size and recurrence of cSDHs.

Background Vertebrobasilar junction (VBJ) aneurysms represent a relatively rare and often anatomically complex subgroup of saccular aneurysms. This systematic review and meta-analysis aimed to assess the safety and efficacy of endovascular treatment (EVT) of VBJ aneurysms. Methods PubMed, Web of Science, Ovid Medline, Ovid Embase, and Scopus were searched from inception to 20 December 2022. We included primary studies assessing the long-term clinical and angiographic outcomes for VBJ aneurysms treated with endovascular techniques. We excluded surgically managed studies. All data were analyzed using R software version 4.2.1. We calculated pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results In this meta-analysis, a total of 76 VBJ aneurysms from seven studies were included for quantitative analysis. The results showed that the rate of adequate occlusion (complete + near complete occlusion) was 94.1% (95% CI = 76.71–98.71), and the rate of complete occlusion was 77.7% (95% CI = 63.07–87.65). A modified Rankin Scale (mRS) score of 0–2 was achieved in 93.9% of patients (95% CI = 67.65–99.14). The mortality rate was found to be 5.9% (95% CI = 0.97–28.55), and the retreatment rate was 4.6% (95% CI = 1.50–13.36). The overall ischemic complication rate was 4.7% (95% CI = 0.73–25.4), while the overall hemorrhagic complication rate was 4.6% (95% CI = 1.5–13.36). Conclusions The treatment of VBJ aneurysms with EVT is effective in achieving curative treatment and is associated with good clinical outcomes and low mortality rates. These findings provide important insights into the clinical and angiographic outcomes and the complication rates of EVT for VBJ aneurysms.

Background Procedural success following mechanical thrombectomy for acute ischemic stroke is assessed using the thrombolysis in cerebral infarction scale. We conducted a systematic review and meta-analysis to determine whether outcomes differed between first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. Methods We conducted a systematic review of the literature using PubMed, Embase, Scopus, and Web of Science. We included original studies in which outcomes were stratified based on first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. The primary outcome of interest was the rate of modified Rankin Scale 0-2. Secondary outcomes of interest were rates of modified Rankin Scale 0-1, symptomatic intracranial hemorrhage, and mortality. We calculated odds ratios and corresponding 95% confidence intervals. Results Four studies with 1554 patients were included in the quantitative analysis. Rate of modified Rankin Scale 0–2 (odds ratio = 0.91, 95% confidence interval = 0.70–1.18; P -value = 0.49), modified Rankin Scale 0–1 (odds ratio = 1.21, 95% confidence interval = 0.86–1.71; P -value = 0.27), symptomatic intracranial hemorrhage (odds ratio = 1.36, 95% confidence interval = 0.47–3.98; P -value = 0.57), and mortality (odds ratio = 0.91, 95% confidence interval = 0.67–1.25; P -value = 0.56) did not differ between first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. There was no heterogeneity among included studies for modified Rankin Scale 0–2, modified Rankin Scale 0–1, or mortality; however, there was moderate heterogeneity among studies for symptomatic intracranial hemorrhage ( I 2 = 53%, P -value = 0.12). Conclusions Clinical and safety outcomes did not differ between first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. Future prospective studies and clinical trials should determine whether first pass thrombolysis in cerebral infarction 2b is a viable endpoint to thrombolysis in cerebral infarction 2c-3.