Effects of elevated remnant cholesterol on outcomes of acute ischemic stroke patients receiving mechanical thrombectomy.

OBJECTIVE: Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. METHODS: This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. RESULTS: In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). CONCLUSION: In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.

Oral anticoagulants status after acute ischemic stroke and prognosis in patients with atrial fibrillation.

OBJECTIVES: To investigate the oral anticoagulants (OACs) use after acute ischemic stroke (AIS) and prognosis of patients with atrial fibrillation (AF). METHODS: This was a real-world follow-up research of AIS patients with AF admitted to 5 hospitals in northwestern China. We visited these individuals every 6 months to check the type, dosage of OACs, and to record IS recurrence, bleeding, and death events and modified Rankin Scale (mRS) scores until December 2022. When one of the following occurring first was endpoint: IS recurrence, death or study end. Patients were divided into continuous anticoagulation group and non-continuous anticoagulation group based on whether they continued to take OACs from the moment they were discharged until the endpoint. We further analyzed the association between anticoagulation persistence and outcomes. RESULTS: Among all 250 patients with OACs indication, 147 patients (58.8 %) received OACs at discharge. Only 37.9 % of patients (39/103) started OACs after discharge. Of the 147 patients treated with OACs, 21.8 % (32/147) discontinued anticoagulation after discharge. 239 of the 250 patients had completed the median 40-month follow-up with 91 patients in continuous anticoagulation group and 148 patients in non-continuous anticoagulation group. In the multivariate COX regression, non-continuous anticoagulation was an independent risk factor for poor prognosis (mRS>2) in AIS patients with AF (1.452[1.011, 2.086], p = 0.043). CONCLUSIONS: This study revealed an upward trend in the use rate of OACs, but low OACs rates that meet guideline-based criteria and low anticoagulation persistence in AF patients after AIS in the northwestern China. Discontinuous anticoagulation was associated with an increased risk of poor prognosis in these patients.

Multi-omics Mendelian randomization integrating GWAS, eQTL and pQTL data revealed GSTM4 as a potential drug target for migraine.

INTRODUCTION: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. METHOD: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. RESULT: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. CONCLUSION: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.

Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: For some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH. METHODS: SUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18-75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1-12 was the primary efficacy endpoint. RESULTS: Patients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1-12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints. CONCLUSION: All endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

Resting-state electroencephalography microstate dynamics altered in patients with migraine with and without aura-A pilot study.

OBJECTIVE: To evaluate electroencephalography (EEG) microstate differences between patients with migraine with aura (MWA), patients with migraine without aura (MWoA), and healthy controls (HC). BACKGROUND: Previous research employing microstate analysis found unique microstate alterations in patients with MWoA; however, it is uncertain how microstates appear in patients with MWA. METHODS: This study was conducted at the Headache Clinic of the First Affiliated Hospital of Xi'an Jiaotong University. In total, 30 patients with MWA, 30 with MWoA, and 30 HC were enrolled in this cross-sectional study. An EEG was recorded for all participants under resting state. The microstate parameters of four widely recognized microstate classes A-D were calculated and compared across the three groups. RESULTS: The occurrence of microstate B (MsB) in the MWoA group was significantly higher than in the HC (p = 0.006, Cohen's d = 0.72) and MWA (p = 0.016, Cohen's d = 0.57) groups, while the contribution of MsB was significantly increased in the MWoA group compared to the HC group (p = 0.016, Cohen's d = 0.64). Microstate A (MsA) displayed a longer duration in the MWA group compared to the MWoA group (p = 0.007, Cohen's d = 0.69). Furthermore, the transition probability between MsB and microstate D was significantly increased in the MWoA group compared to the HC group (p = 0.009, Cohen's d = 0.68 for B to D; p = 0.007, Cohen's d = 0.71 for D to B). Finally, the occurrence and contribution of MsB were positively related to headache characteristics in the MWoA group but negatively in the MWA group, whereas the duration of MsA was positively related to the visual analog scale in the MWA group (all p < 0.05). CONCLUSIONS: Patients with MWA and MWoA have altered microstate dynamics, indicating that resting-state brain network disorders may play a role in migraine pathogenesis. Microstate parameters may have the potential to aid clinical management, which needs to be investigated further.

Post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia: a case report.

BACKGROUND: Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. CASE PRESENTATION: A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. CONCLUSIONS: This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.

Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study.

BACKGROUND: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. METHODS: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. RESULTS: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. CONCLUSIONS: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. TRIAL REGISTRATION: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

Platelet Distribution Width: A Significant Predictor of Poor Outcome After Mechanical Thrombectomy.

OBJECTIVES: Elevated platelet distribution width (PDW) is a recognized marker of platelet activity. Herein, we investigated the association between admission PDW values and clinical outcome at 3 months in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: We retrospectively collected consecutive patients diagnosed with AIS following MT from two stroke centers. PDW was measured on admission. Subjects were divided into two groups according to the clinical outcome using the modified Rankin Scale at 3 months. Multiple regression analyses and receiver operating characteristic (ROC) curves were performed to determine the associations between admission PDW values, clinical parameters, and functional outcome. RESULTS: A total of 162 subjects were enrolled. Patients in the poor outcome group had a significantly higher percentage of PDW >16.0 fL compared with the good outcome group (57.3% vs. 26.9%, P < 0.001). After adjusting for a range of confounding factors, multiple regression analysis showed that PDW >16.0 fL was an independent predictor of poor outcome at 3 months (odds ratio 4.572, 95% confidence interval 1.896-11.026, P = 0.001). ROC curve analysis revealed that PDW >16.0 fL predicted poor outcome with 57.3% sensitivity and 73.1% specificity (the area under the ROC curve 0.637, 95% confidence interval 0.558-0.711, P = 0.004). CONCLUSIONS: Elevated PDW is an independent predictor of poor functional outcome in patients with anterior circulation AIS undergoing MT at 3 months.

Comparison of 3 Treatment Methods for Distal Tibial Fractures: A Network Meta-Analysis.

BACKGROUND The choice of optimal internal fixation device for distal tibial fractures remains controversial. The purpose of our study was to evaluate the effectiveness and safety of open reduction and internal fixation, minimally invasive percutaneous osteosynthesis, and intramedullary nailing of distal tibial fractures in adults using network meta-analysis of data from clinical trials. MATERIAL AND METHODS The studies were abstracted from MEDLINE, EMBASE, CNKI, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials meeting inclusion and exclusion criteria were selected. Statistical analyses were conducted using Stata software, version 13.0 (Stata Corporation, College Station, Texas, USA). RESULTS Eleven randomized controlled trials were included. The total number of participants was 710 and the studies were published between 2005 and 2017. There were no significant differences in rates of delayed union, nonunion, or malunion among the various treatments (all p>0.05). The intramedullary nailing group had a lower incidence of wound complications than did the open reduction and internal fixation group and minimally invasive percutaneous osteosynthesis technique group. The SUCRA probabilities were 28.6% for ORIF, 98.4% for IMN, and 22.9% for MIPPO. CONCLUSIONS Given the superior results for intramedullary nailing in terms of wound complications, we recommend this procedure for treatment of distal tibial fractures. More RCTs focused on distal tibial fractures are needed to support the current evidence.

Association of white matter hyperintensities with migraine features and prognosis.

BACKGROUND: White matter hyperintensities (WMHs) are frequently detected in migraine patients. However, their significance and correlation to migraine disease burden remain unclear. This study aims to examine the correlation of WMHs with migraine features and explore the relationship between WMHs and migraine prognosis. METHODS: A total of 69 migraineurs underwent MRI scans to evaluate WMHs. Migraine features were compared between patients with and without WMHs. After an average follow-up period of 3 years, these patients were divided into two groups, according to the reduction of headache frequency: improved and non-improved groups. The percentage and degree of WMHs were compared between these two groups. RESULTS: A total of 24 patients (34.8%) had WMHs. Patients with WMHs were significantly older (39.0 ± 7.9 vs. 30.6 ± 10.4 years, P < 0.001) and had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013). Furthermore, 33 patients completed the follow up period (15 patients improved and 18 patients did not improve). Patients in the non-improved group had a higher frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs. 0.0, P = 0.030). CONCLUSIONS: WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a closer association with age than migraine features.

Right-to-left shunt may be prone to affect the white matter integrity of posterior circulation in migraine without aura.

Numerous studies have indicated an association between migraine and right-to-left shunt. However, little is known about whether right-to-left shunt has an effect on the migraine brain. This observational study aims to explore the impact of right-to-left shunt on the brain of migraine without aura on microstructural level. Thirty-five patients with migraine without aura were enrolled in this study. Contrast-enhanced Transcranial Doppler was performed to evaluate the status of right-to-left shunt. Three-dimensional T1-weighted and diffusion tensor images were acquired for data analysis. We employed voxel-based morphometry and tract-based spatial statistical analyses to assess the differences of gray and white matter between migraineurs with and without right-to-left shunt, respectively. Among the 35 patients, 19 (54.3%) patients had right-to-left shunt. There were no significant differences in headache features between migraineurs with and without right-to-left shunt. There were significant increases of mean and radial diffusivity in migraineurs with right-to-left shunt compared with migraineurs without right-to-left shunt. The alterations were primarily located in the right posterior thalamic radiation, secondly in the body of corpus callosum and the right superior corona radiata. No significant differences were observed in values of fractional anisotropy and axial diffusivity. No significant between-group differences were found in gray matter volume. Right-to-left shunt may cause alterations of white matter integrity in migraine without aura, and the alterations are more likely to be located at the posterior circulation.

Migraine and percutaneous patent foramen ovale closure: a systematic review and meta-analysis.

BACKGROUND: The association between patent foramen ovale (PFO) and migraine with aura (MA) is well established. However, the benefits of PFO closure are less certain in patients with migraine without aura (MwoA). METHODS: We systematically searched Pubmed for pertinent clinical studies published from January 2000 to July 2015. The primary end-point was the elimination or significant improvement of migraine symptoms after PFO closure. RESULTS: Upon screening an initial list of 315 publications, we identified eight studies that included 546 patients. Overall, our analysis indicated a significant improvement of migraine in 81% of MA cases compared to only 63% of MwoA cases. The summary odds ratio was 2.5 (95% confidence interval 1.09-5.73), and the benefits of PFO closure were significantly greater for patients with MA compared to patients with MwoA (P = 0.03). CONCLUSIONS: The presence of aura provides a reference standard for the clinical selection of patients with migraine for PFO closure intervention.

The Design and Rationale of a Clinical Trial Evaluating Limb Postconditioning in Young Patients with Intracranial Arterial Stenosis.

OBJECTIVES: To examine the effectiveness of bilateral arm remote ischemic postconditioning (RIPC) on the rehabilitation of nerve function and collateral circulation in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). SETTING: Open, controlled, prospective trial (EPIC-sICAS trial) in Xi'an, Shaanxi, China. PARTICIPANTS: Up to 100 sICAS patients (age: 18-45 years, gender balance) who fulfill the inclusion and exclusion criteria will be enrolled and randomized to intervention group and control group (n ~ 50/group). INTERVENTIONS: The intervention group will undergo ischemia and reperfusion on both arms twice a day for 6 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Mean changes in collateral circulation from baseline to the end of the 6-month RIPC treatment period, measured by dynamic contrast-enhanced magnetic resonance imaging, will be the primary outcome. Clinical symptoms, serum levels of vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be compared as secondary outcome. RESULTS: A safety evaluation and preliminary experiment of the EPIC-sICAS trial were completed in November 2014 and March 2015, respectively. Overall and regional brain hemodynamics remained stable throughout RIPC. Activities of daily living score and serum VEGF and bFGF levels were significantly higher (P < .05) in the intervention group. CONCLUSIONS: Repetitive bilateral arm RIPC appears to have protective effects in the brain related to angiogenesis promotion and neuroprotection in the acute phase of sICAS. Assessment of the role of RIPC in collateral circulation requires imaging tests and longer follow-up, as planned in the EPIC-sICAS trial.

Variance of Serum Lipid Levels in Stroke Subtypes.

BACKGROUND: An increasing number of epidemiological studies have identified a close relationship between dyslipidemia and atherosclerotic stroke. Indeed, lipid metabolism is significantly different among the different ischemic stroke subtypes. There are few studies available regarding risk factors for specific subtypes of ischemic stroke, and in particular, there is little evidence about the role of dyslipidemia. The aim of this study is to determine the relationship between acute ischemic stroke subtype and serum lipid level. METHODS: The levels of serum lipid including TC, TG, LDL-C, HDL-C, apoA, apoB, apoE, and LP (a) were tested in 362 ischemic stroke patients and 181 healthy controls. Lipid levels were analyzed in stroke subtypes according to the TOAST classification. RESULTS: Levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP (a) were significantly higher and HDL-C levels were significantly lower in the patient group relative to control. The TC/HDL-C ratio, TG/HDL-C ratio, and LDL-C/HDL-C ratio were remarkably higher in the patient group. The levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP(a) were markedly higher and HDL-C was markedly lower in the large-artery atherosclerosis stroke subtype relative to the cardioembolism subtype. Compared with the small-vessel occlusion group, the level of LP(a), TC, and TC/HDL-C were strikingly higher in the cardioembolism group. The TC/HDL-C ratio was different among subgroups, with the large-artery atherosclerosis group exhibiting the highest value. For TC, TG, LDL-C, apoA, apoB, apoE, LP(a), TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels a statistically significant difference was found between the large-artery atherosclerosis group and the small-vessel occlusion group. CONCLUSIONS: We found that LDL-C and TC levels may be independent predictors for the occurrence of large-artery atherosclerotic stroke.

Remote ischemic postconditioning alleviates cerebral ischemic injury through SERCA2/endoplasmic reticulum stress-mediated apoptosis.

Remote ischemic postconditioning (RIPostC) alleviates brain ischemic injury through several pathways, including endoplasmic reticulum (ER) stress modulation. Sarco endoplasmic reticulum Ca2+ -ATPase(SERCA2) which plays vital role in calcium homeostasis regulation could modulate ER stress logically. This study aimed to investigate whether RIPostC exerts its neuroprotective effect by reducing ER stress mediated by SERCA2. Male SD rats underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by reperfusion, with the RIPostC group undergoing 3 cycles of bilateral femoral artery clamping and reperfusion at the beginning of reperfusion. Stroke outcome was assessed based on infarct volume and neurological function evaluation. Protein levels of SERCA2 and other ER stress markers were measured using Western blotting, immunofluorescence, and immunohistochemistry techniques. Compared to the sham group, we observed that RIPostC can effectively reduce cerebral infarct volume after I/R (34.55%: 21.03%; p = .004) and improve neurological function deficit (9.67:12.5; p = .029). Additionally, RIPostC increased SERCA2 protein expression and decreased the protein level of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/EBP homologous protein (CHOP). Furthermore, B-cell lymphoma-2 (Bcl-2) expression was increased, while Bcl-2-associated X protein (Bax) and cleaved-caspase-3 was decreased in response to application of RIPostC. Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation. The significance of this study is to provide a theoretical basis for further exploring the protective mechanism of ischemic stroke by RIPostC. RESEARCH HIGHLIGHTS: Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation, thus achieving a neuroprotective effect.

Association between blood pressure control during aneurysm clipping and functional outcomes in patients with aneurysmal subarachnoid hemorrhage.

Objectives: We explored the relationship between blood pressure variability (BPV) during craniotomy aneurysm clipping and short-term prognosis in patients with aneurysmal subarachnoid hemorrhage to provide a new method to improve prognosis of these patients. Methods: We retrospectively analyzed the differences between patient groups with favorable modified Rankin Scale (mRS ≤ 2) and unfavorable (mRS > 2) prognosis, and examined the association between intraoperative BPV and short-term prognosis. Results: The intraoperative maximum systolic blood pressure (SBPmax, p = 0.005) and the coefficient of variation of diastolic blood pressure (DBPCV, p = 0.029) were significantly higher in the favorable prognosis group. SBPmax (OR 0.88, 95%CI 0.80-0.98) and Neu% (OR 1.22, 95%CI 1.03-1.46) were independent influence factors on prognosis. Patients with higher standard deviations of SBP (82.7% vs. 56.7%; p = 0.030), DBP (82.7% vs. 56.7%; p = 0.030), and DBPCV (82.7% vs. 56.7%; p = 0.030) had more favorable prognosis. Conclusion: Higher SBPmax (≤180 mmHg) during the clipping is an independent protective factor for a 90-day prognosis. These results highlight the importance of blood pressure (BP) control for improved prognosis; higher short-term BPV during clipping may be a precondition for a favorable prognosis.

Joint effect of abnormal systemic immune-inflammation index (SII) levels and diabetes on cognitive function and survival rate: A population-based study from the NHANES 2011-2014.

OBJECTIVE: The purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted. RESULTS: The RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (ß:-0.76, P<0.05) and Digit Symbol Substitution tests (ß:-5.02, P<0.05). Nevertheless, these results showed marginal significance in Total Word Recall test as well as Animal Fluency test. Among all subgroup analyses performed, participants with both abnormal SII levels and diabetes exhibited the greatest decline in cognitive function compared to those with only diabetes. Furthermore, KM curve demonstrated that the combination of abnormal SII levels and diabetes decreased survival rate among participants. CONCLUSION: The findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

The relationship between atrial cardiopathy biomarkers and prognosis of patients with acute ischemic stroke after endovascular treatment.

Thromboembolism is a possible consequence of underlying atrial cardiopathy, which can occur even before the onset of atrial fibrillation. Our objective was to examine the association between biomarkers of atrial cardiopathy and outcomes of acute ischemic stroke (AIS) following endovascular treatment (EVT). We conducted a retrospective study that collected data from patients with AIS who underwent EVT and compared the outcomes between those with and without atrial cardiopathy. Neurological function was assessed using the modified Rankin Scale (mRS), with an mRS score >2 indicating poor function at day 90. Additionally, we evaluated secondary consequences, including symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), and malignant cerebral edema (MCE). Our study included 87 patients (77.6 â€‹% male; mean age 60.93 â€‹± â€‹12.47 years). Among these patients, 29 (33.3 â€‹%) had atrial cardiopathy, while the remaining 58 (66.7 â€‹%) did not. In the atrial cardiopathy group, 12 patients (41.4 â€‹%) had poor functional outcomes (mRS>2), compared to 19 (32.8 â€‹%) in the non-atrial cardiopathy group. We observed sICH in 22 (25.3 â€‹%) patients, END in 14 (16.1 â€‹%) patients, MCE in 11 (12.6 â€‹%) patients, and two (2.3 â€‹%) patients who died in the hospital. We found that patients with PTFV1>5000 â€‹µV/ms (OR: 8.39, 95 â€‹% CI: 1.43-105.95, P â€‹= â€‹0.02) and NT-proBNP>250 â€‹pg/mL (OR: 5.09, 95 â€‹% CI: 1.20-27.63, P â€‹= â€‹0.03) had significantly higher risk of END. After adjusting for covariates in the Firth logistic regression, we further found that atrial cardiopathy was significantly associated with END, as revealed by both univariate (OR: 6.31, 95 â€‹% CI: 1.42-59.87, P â€‹= â€‹0.01) and multivariable firth regression models (Modle 1, OR: 7.10, 95 â€‹% CI: 1.57-67.38, P â€‹< â€‹0.01; Modle 2, OR: 7.82, 95 â€‹% CI: 1.69, 76.36, P â€‹< â€‹0.01; Modle 3, OR: 8.59, 95 â€‹% CI: 1.72-91.70, P â€‹< â€‹0.01). Moreover, we observed that atrial cardiopathy was associated with an increased risk of END in AIS patients with large artery atherosclerosis (LAA) receiving EVT. Therefore, clinicians should consider atrial cardiopathy as a possible underlying cause of AIS in their patients. Further investigation is warranted to elucidate the relationship between atrial cardiopathy and AIS's occurrence, progression, and prognosis.

Safety and efficacy of magnesium-rich artificial cerebrospinal fluid for subarachnoid hemorrhage.

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT04358445.