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ABSTRACTRecanalization of chronic occluded internal carotid arteries has the potential to provide significant benefits for patients in the future, but the procedure is technically challenging. Therefore, this study aimed to identify a better method to predict the success of recanalization for patients with chronic internal carotid artery occlusion. The study’s overall success rate was 73.77%. The multivariate logistic regression analysis revealed that two factors were independent predictors of successful recanalization: the continuous low signal lumen in the occluded segment of the internal carotid artery on the MRI image without contrast (OR: 15.9; 95% CI: 2.67–94.63) and the architecture of the clinoid segment of the internal carotid artery on the MRI image with contrast (OR: 11.97; 95% CI: 2.44–58.79). Based on the model coefficient, the researchers established an MRI score system. The MRI score system’s area under the curve (AUC) in predicting successful recanalization was 0.916 (95% CI: 0.815 to 0.972; p < 0.001) with a sensitivity of 83.33% and a specificity of 72.22%. Compared to the previous score system based on the DSA morphology, the MRI system had a similar sensitivity and a better specificity. Therefore, the continuous low signal lumen in the occluded segment of the internal carotid artery on the MRI image without contrast and the architecture of the clinoid segment of the internal carotid artery on the MRI image with contrast were identified as independent predictors for successful recanalization in patients with chronic internal carotid artery occlusion (CICAO)

BackgroundThis study aimed to investigate the natural history of re-rupture in ruptured brain arteriovenous malformations (AVMs) and to provide comprehensive insights into its associated factors and prevention.MethodsThis study included 1712 eligible ruptured AVMs from a nationwide multicenter prospective collaboration registry between August 2011 and September 2021. The natural rupture risk before intervention and the annual rupture risk after intervention were both assessed. Cox proportional hazard regression models and Kaplan–Meier survival curves were used to explore independent factors associated with AVM re-rupture. The correlation between these factors and AVM re-rupture was verified in multiple independent cohorts, and the prevention effect of intervention timing and intervention strategies on AVM re-rupture was further analyzed.ResultsThe annual re-rupture risk in ruptured AVMs was 7.6%, and the cumulative re-rupture risk in the first 1, 3, 5, and 10 years following the initial rupture were 10%, 25%, 37.5%, and 50%, respectively. Cox proportional hazard regression analysis confirmed adult patients, ventricular system involvement, and any deep venous drainage as independent factors associated with AVM re-rupture. The intervention was found to significantly reduce the risk of AVM re-rupture (annual rupture risk 11.34% vs 1.70%, p<0.001), especially in those who underwent surgical resection (annual rupture risk 0.13%).ConclusionsThe risk of re-rupture in ruptured AVMs is high. Adult patients, ventricular system involvement, and any deep venous drainage are independent risk factors for re-rupture. Applying the results universally to all ruptured AVM cases may be biased. Intervention could effectively reduce the risk of re-rupture.

BackgroundTo compare the long-term outcomes of stereotactic radiosurgery (SRS) with or without prior embolization in brain arteriovenous malformations (AVMs) (volume ≤10 mL) for which SRS is indicated.MethodsPatients were recruited from a nationwide multicenter prospective collaboration registry (the MATCH study) between August 2011 and August 2021, and categorized into combined embolization and SRS (E+SRS) and SRS alone cohorts. We performed propensity score-matched survival analysis to compare the long-term risk of non-fatal hemorrhagic stroke and death (primary outcomes). The long-term obliteration rate, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes, and embolization complications were also evaluated (secondary outcomes). Hazard ratios (HRs) were calculated using Cox proportional hazards models.ResultsAfter study exclusions and propensity score matching, 486 patients (243 pairs) were included. The median (IQR) follow-up duration for the primary outcomes was 5.7 (3.1–8.2) years. Overall, E+SRS and SRS alone were similar in preventing long-term non-fatal hemorrhagic stroke and death (0.68 vs 0.45 per 100 patient-years; HR=1.46 (95% CI 0.56 to 3.84)), as well as in facilitating AVM obliteration (10.02 vs 9.48 per 100 patient-years; HR=1.10 (95% CI 0.87 to 1.38)). However, the E+SRS strategy was significantly inferior to the SRS alone strategy in terms of neurological deterioration (worsened mRS score: 16.0% vs 9.1%; HR=2.00 (95% CI 1.18 to 3.38)).ConclusionsIn this observational prospective cohort study, the combined strategy of E+SRS does not show substantial advantages over SRS alone. The findings do not support pre-SRS embolization for AVMs with a volume ≤10 mL.

BackgroundIntracranial fusiform aneurysms are less common than saccular aneurysms, but are associated with higher mortality and morbidity. We conducted this study to determine the safety and efficacy of the pipeline embolization device (PED) to treat intracranial fusiform aneurysms.MethodsThis was a multicenter, retrospective, and observational study. Data for this study came from the PLUS study conducted from 2014 to 2019 across 14 centers in China. Univariate and multivariable logistic regression analyses were performed to evaluate predictors of the occlusion rate and complication.ResultsA total of 1171 consecutive patients with 1322 intracranial aneurysms participated in this study. Among the participants, 104 patients with 109 fusiform aneurysms were eligible for this analysis (mean age 49 years, 36.5% women, aneurysm mean size 14.7 mm, 55% in the posterior circulation, and 6% in the basilar artery). Mean follow-up time was 9.0 months (range 3–36 months). The last DSA angiographic follow-up was available for 85 patients, and 58 aneurysms (68.2%) were completely occluded. The overall complication rate and mortality were 17.3% and 2.8%, respectively. Multivariate analysis demonstrated that age (OR=1.007, p=0.037) and cerebral atherosclerosis (OR=1.441, p=0.002) were associated with incomplete occlusion of fusiform aneurysms after PED treatment.ConclusionPEDs may be an effective treatment for intracranial fusiform aneurysms, with a favorable occlusion rate. However, because these treatments have a relatively high rate of complications, PED treatment for fusiform aneurysms should be carefully and strictly controlled. Our analysis showed that PEDs with adjunctive coiling did not significantly improve the occlusion rate of fusiform aneurysms.

BackgroundAlthough coiling with a flow diverter may provide immediate dome protection, no studies have evaluated the effect on complications of postoperative occlusion degree immediately postoperatively. The purpose of this study was to determine whether postoperative occlusion degree immediately after flow-diverter placement with adjunctive coiling was associated with complications.MethodsAll patients’ data were collected from the post-market multi-center cohort study of embolization of intracranial aneurysms with a pipeline embolization device (PED) in China (PLUS) registry. We divided patients into those treated with a PED alone (PED-only (PO) group), those treated with a PED with coils and incomplete occlusion (PED + coils + incomplete occlusion (PCIO) group), and those treated with a PED with coils and complete occlusion (PED + coils + complete occlusion (PCCO) group).ResultsWe evaluated 1171 consecutive patients with 1322 aneurysms treated with a PED: 685 aneurysms were treated with PO, 444 with PCIO, and 193 with PCCO. The PCCO group had a higher rate of aneurysm occlusion at the last follow-up than the PCIO and PO groups (P<0.0001). Multivariate analysis of the predictors of ischemic stroke and modified Rankin Scale score (mRS) deterioration showed that PCCO was an independent predictor of ischemic stroke (HR, 2.03; 95% CI, 1.12 to 3.67; P=0.019) and mRS deterioration (HR, 2.59; 95% CI, 1.57 to 4.26; P<0.0001).ConclusionsAlthough postoperative complete occlusion with a PED and adjunctive coiling can increase the rate of aneurysm occlusion, this approach may also increase the risk of ischemic stroke and lead to poor postoperative functional outcomes.

BackgroundTo explore the hemodynamic changes after embolization of arteriovenous malformations (AVMs) using quantitative digital subtraction angiography (QDSA).MethodsWe reviewed 74 supratentorial AVMs that underwent endovascular embolization and performed a quantitative hemodynamic analysis comparing parameters in pre- and post-operative DSA in correlation with rupture. The AVMs were further divided into two subgroups based on the embolization degree: Group I: 0%–50%, Group II: 51%–100%. In the intergroup analysis, we examined the correlations between embolization degree and hemodynamic parameter changes.ResultsA longer time to peak (TTP) of the main feeding artery (OR 11.836; 95% CI 1.388 to 100.948; P=0.024) and shorter mean transit time (MTT) of the nidus (OR 0.174; 95% CI 0.039 to 0.766; P=0.021) were associated with AVM rupture. After embolization, all MTTs were significantly prolonged (P<0.05). The full width at half maximum (FWHM) duration of the main feeding artery was significantly shortened (P<0.001), and several hemodynamic parameters of the main draining vein changed significantly (TTP: prolonged, P=0.005; FWHM: prolonged, P=0.014; inflow gradient: decreased, P=0.004; outflow gradient: decreased, P=0.042). In the subgroup analysis, several MTT parameters were significantly prolonged in both groups (P<0.05), and the MTT increase rate in Group II was greater than in Group I (P<0.05).ConclusionsEmbolization can significantly change the hemodynamics of AVMs, especially when an embolization degree >50% is obtained. Partial embolization may reduce the AVM rupture risk in hemodynamics perspective.

An intraventricular fetus-in-fetu, a malformed monochorionic diamniotic twin, was identified in a 1-year-old girl with motor delay and enlarged head circumference (Figure 1). After surgical removal, whole-genome sequencing revealed identical single-nucleotide variants in the host child and fetus-in-fetu, with extensive de novo copy number gains in the fetus-in-fetu (Figure 2, eMethods, links.lww.com/WNL/C529), suggesting the significance of copy number variation during embryogenesis.

IMPORTANCE: Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH. OBJECTIVE: To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. DESIGN, SETTING, AND PARTICIPANTS: The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified. INTERVENTIONS: Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week. RESULTS: One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported. CONCLUSIONS AND RELEVANCE: Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024373

The swamp eel (Monopterus albus) is a commonly cultured freshwater fish. Selection and cultivation of fecund broodstock is crucial for efficient artificial reproduction in this species. However, there are currently no guidelines for selecting high-quality males in M. albus. This study quantitatively investigated the sperm motility of male swamp eels during the breeding season by using computer-assisted sperm analysis system. Variability in the proportion and number of motile sperm was observed between individual males. The testes were grouped into high-quality and low-quality according to sperm quality. Morphometric parameters of the two groups were analyzed. We found that high-quality testes were longer (150 ​± ​27 ​mm verses 127 ​± ​19 ​mm) than low-quality testes. Besides, the proportion of testes with a dark appearance was slightly higher (58.3% verses 48.1%) in the high-quality group than in the low-quality group. Metabolomic analysis was conducted to compare the metabolite profiles of high-quality and low-quality testes. Glycerophospholipids, organic acids, glycerolipids, amino acids, sphingolipids, and nucleotides were the most abundant metabolites in the testes of swamp eels. Moreover, 135 differential metabolites were identified. Several nucleotide derivatives, including 5′-deoxyadenosine, 2′-deoxyadenosine, and ribosyl adenosine, were the most significantly enriched metabolites in high-quality testes. These metabolites are potential indicators for the testis quality in M. albus. Altogether, our work provides systematic and quantitative data about the physiological and biochemical characteristics of M. albustestis, which provides an evidential basis for the selection of high-fecundity parents to improve artificial reproduction efficiency of M. albus.

Introduction:The long-term effects of interventional treatment (with surgery, stereotactic radiosurgery, or endovascular embolization) for unruptured brain arteriovenous malformations (uBAVM) are uncertain. We address this in a large multi-center international cohort study comparing risk of intracranial hemorrhage (ICH) in the treated and untreated course of uBAVM patients.Methods:We pooled individual patient data (n=3,291) from 10 cohorts and imputed missing data. Survival analysis was performed from time of uBAVM diagnosis to intracranial hemorrhage (ICH) using Cox models, stratified by cohort, censoring at death or last follow-up, and including BAVM interventional treatment as a time-varying covariate. We tested for an interaction of treatment with follow-up time, then estimated the association of interventional treatment with ICH, adjusting for propensity quintile. Individual treatment propensity scores were calculated using logistic regression with Spetzler-Martin grade, sex, diagnosis age and year, cohort, and presence of presenting symptoms (seizures, headaches, and/or deficits).Results:Median cohort age was 36 years, 48% were female, and 77% received ≥1 treatment modality for uBAVM during follow-up. 373 ICH occurred during 32,054 person-years of follow-up (median=6.6y), for an ICH rate of 1.16 per 100 P-Y. Overall, treatment was not associated with risk of ICH (HR=1.12, 95% CI=0.89-1.51, p=0.33). However, we observed a strong interaction between treatment and follow-up time (p<0.001): between 0-1 year, treatment was associated with higher risk of ICH (HR=3.48, 95% CI: 2.26-5.37, p<0.001); between 1-10 years, we found no association between treatment and risk of ICH (HR=1.02, 95% CI: 0.73-1.45, p=0.87); after 10 years, treatment was associated with a lower risk of ICH (HR=0.46, 95% CI: 0.30-0.70, p<0.001). Survival curves for untreated and treated courses crossed around 17 years.Conclusion:After accounting for treatment propensity for uBAVM, we found an initial increased risk of ICH in the treated relative to untreated course, which continually declined over time with survival curves crossing around 17 years. These results require confirmation in a randomized controlled trial of uBAVM with long-term follow-up.

The application of nanomaterial in cancer treatment is promising and intriguing. Anti-tumor immunotherapy has the potential to significantly improve the prognosis of cancer treatment, though the efficacy of immunotherapy generally needs further improvement. One way to improve the efficacy is using immune adjuvants, but the adjuvants for anticancer immunotherapy have to be more potent than for prophylactic vaccines. Here, we report that compared to conventional alum adjuvant, aluminum oxide nanoparticles (nano-alum) may further enhance the anticancer effects of an immunotherapy that employs tumor cell vaccine (TCV). The average tumor size tends to be lower in animals that receive the combinational treatment of nano-alum and TCV. The anticancer cytotoxicity by the lymphocytes was also significantly higher in the treatment group that received both TCV and nano-alum. These results suggest that nano-alum may potentially serve as a potent immune adjuvant and have prospective applications in anticancer immunotherapy.

BackgroundThe Pipeline Embolization Device (PED) is reported to be a safe treatment tool for aneurysms. However, mortality occurs in a few cases, and this has not been clearly studied. We conducted a multicenter study to retrospectively evaluate the causes of, and risk factors for, mortality in patients with intracranial aneurysms treated with the PED.MethodsWe retrospectively reviewed the prospectively maintained databases of patients with intracranial aneurysms treated by PED placement at 14 academic institutions from 2014 to 2019. Patients’ data, including clinical and radiographic information, were analyzed with an emphasis on mortality-related complications.ResultsA total of 1171 consecutive patients underwent 1319 PED procedures to treat 1322 intracranial aneurysms. The mortality rate was 1.5% (17/1171), and in 1.3% of the patients (15/1171), deaths were caused by delayed aneurysmal rupture, distal intraparenchymal hemorrhage, and neurological compression symptoms associated with PED procedures. Multivariate analysis showed that previous treatment (OR, 12.657; 95% CI, 3.189 to 50.227; P<0.0001), aneurysm size ≥10 mm (OR, 4.704; 95% CI, 1.297 to 17.068; P=0.019), aneurysm location (basilar artery) (OR, 10.734; 95% CI, 2.730 to 42.207; P=0.001), and current subarachnoid hemorrhage (OR, 4.505; 95% CI, 0.991 to 20.474; P=0.051) were associated with neurological complications resulting in mortality.ConclusionsDelayed aneurysm rupture, distal intraparenchymal hemorrhage, and neurological compression were the main causes of mortality in patients with intracranial aneurysms treated with the PED. Large basilar aneurysms are associated with an increased risk of postoperative death and require increased attention and caution.

Background:Accurate and reliable models of intracranial hemorrhage (ICH) risk in the untreated course of brain arteriovenous malformation (BAVM) patients are needed to help weigh the risk-benefit of treatment. We present preliminary estimates of rates and risk factors for ICH or death in the Multicenter AVM Research Study (MARS), which is the largest individual patient data meta-analysis (IPDMA) of cohort studies of unruptured BAVM.Methods:Longitudinal data from 9 cohorts comprising 2,839 unruptured BAVM at time of diagnosis were included: UCSF (n=557), Macquarie (n=462), Kaiser Permanente Northern California (n=354), Columbia (n=335), Barrow Neurological Institute (n=324), Tiantan Hospital (n=303), Mayo Clinic-Rochester (n=244), Scottish Intracranial Vascular Malformation Study (n=194), and Toronto Western Hospital (n=66). Clinical and angiographic data were collected using standardized definitions across cohorts. Cox proportional hazards analysis of time-to-event (ICH or death) in the untreated course after diagnosis was performed, censoring at first treatment or last visit. Baseline hazard rates were stratified by cohort to account for different rates and follow-up times.Results:The combined cohort was 49% female, 72% white race, and 17% Hispanic ethnicity; mean age at diagnosis was 37±17 years and mean follow-up was 3.4±7.0 years. The most common presenting symptom was seizures (43%). Mean AVM size was 3.5±1.9 cm and 46% were Spetzler-Martin grade I-II. Overall, 123 ICH and 131 deaths occurred over 9,608 person-years (PY) for an event rate of 2.64 per 100 PY [95% CI: 2.34-2.99]. Cox regression analyses adjusting for age at diagnosis (HR=1.67 [1.54, 1.82], P<0.001) identified cerebellar location (HR=1.73 [1.03-2.93], P=0.040) and exclusively deep venous drainage (HR=1.83 [1.09-3.09], P=0.022) as predictors.Conclusion:Our current model identified increasing age, exclusively deep venous drainage, and cerebellar location as risk factors for ICH or death in the untreated course of unruptured bAVM patients. Review of imaging data, multiple imputation of missing angioarchitectural data, and additional data from pending cohorts will provide greater power to search for additional risk factors in this ongoing IPDMA.