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Background and objectivesWhile somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.MethodsWe performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.ResultsSomatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway.DiscussionWe propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Background and purposePrevious studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors.MethodsA cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted.ResultsIn this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p

BackgroundCranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage.MethodsPatients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference.ResultsOf 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026).ConclusionsThe risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

While neck pain can be defined in clinical terms, in most cases the underlying pathophysiology is largely unknown. Regional cervical spine range of motion is often found to be reduced in patients with neck pain compared to persons without pain although it is not clear if the decreased range is cause or effect. Less is known about the role of intervertebral kinematics and how that might be related to the presence of disc degeneration. In this study, the prevalence of intervertebral disc degeneration and continuous cervical intervertebral motion were both measured utilizing quantitative fluoroscopy (QF) in patients with subacute or chronic neck pain (n = 29) and gender-matched healthy controls (n = 30). A composite disc degeneration (CDD) score was calculated for each participant from the first, neutral, lateral fluoroscopic image. Intervertebral motion sharing parameters of motion-sharing inequality (MSI) and motion-sharing variability (MSV) were derived from the active cervical motion sequences obtained while patients were seated. The objective was to determine if average age, CDD, MSI, and MSV values were correlated and if there were differences in these variables between the neck pain group and the healthy control group. Correlation analysis was conducted for age, CDD, MSI, and MSV in each group. Age was moderately correlated with MSV in cervical spine extension in patients only (r = 0.63, p < 0.001). There were no significant differences in the prevalence of disc degeneration (CDD) between patients, who had on average mild pain and related disability, and healthy controls (median CDD 2 both groups, p = 0.94). There were also no significant differences in either flexion or extension intervertebral motion-sharing inequality or variability (MSI or MSV) between groups as measured during active cervical motion.

Abstract Spinal control at intervertebral levels is dependent on interactions between the active, passive and neural control elements. However, this has never been quantifiable, and has therefore been outside the reach of clinical assessments and research. This study used fluoroscopy during repeated unconstrained flexion and return neck movements to calculate intersegmental motor control (MC), defined as the difference and variation in repeated continuous angular motion from its average path. The study aimed to determine control values for MC at individual levels and its variability. Twenty male volunteers aged 19–29 received fluoroscopic screening of their cervical spines during 4 repetitions of neutral to full flexion and return motion. Moving vertebral images from C0–C1 to C6–C7 were tracked using cross-correlation codes written in Matlab. MC for each level was defined as the mean of the absolute differences between each repetition’s angular path and their mean and its variability as represented by the SD. 1-way ANOVA and Tukey multiple comparisons were used to identify significant contrasts between levels. The mean MC differences and SDs were highest at C1-2, suggesting that this level has the least control and the most variability. Results at this level alone were highly significant (F-ratio 10.88 and 9.79 P

Abstract Background A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial. Objectives We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders. Global summit The Global Summit took place on September 14–15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence. Systematic review of the literature We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus. Results We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report. Conclusion Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.

Simple Summary: This review discusses new treatments for high-grade gliomas (HGGs), aggressive brain tumors that are difficult to treat. It focuses on emerging endovascular therapies and future directions. Endovascular methods use catheters in a minimally invasive manner to deliver drugs to the tumor through blood vessels in the brain while limiting harm to the rest of the body. Super-selective intra-arterial cerebral infusion (SSIACI) is an endovascular technique that aims to deliver treatments directly to the tumor by reaching the closest blood vessels supplying the tumor. Many challenges remain to fully adopting these techniques in clinical practice, including the ability of drugs to cross the blood–brain barrier, and getting the drugs to stay in the tumor for long enough before they are washed out by normal blood in the brain. Focused ultrasound and hyperosmotic disruption are techniques which might help with these challenges. Researchers are investigating new drugs beyond traditional chemotherapies, such as radiation embedded molecules and immune-based therapies. Future directions include monitoring tumors with endovascular sampling; changing drug formulations to stay in the tumor longer; and investigating other treatments, like radioembolization. These endovascular strategies have the potential to improve how HGGs are treated, but more research is needed to ensure they work well and are safe for patients. High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood–brain barrier (BBB) penetration, hemodynamic complexities, and drug–tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care. [ABSTRACT FROM AUTHOR]