Identification of metabolites associated with preserved muscle volume after aneurysmal subarachnoid hemorrhage due to high protein supplementation and neuromuscular electrical stimulation.

The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and ß-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.

Letter to editor: Clinical severity of aneurysmal subarachnoid hemorrhage over time: systematic review.

The letter to the editor titled "Clinical severity of aneurysmal subarachnoid hemorrhage over time: systematic review" provides a comprehensive and systematic examination of the changing clinical landscape of aSAH, emphasizing the importance of advancements in medical technology and treatment protocols. The review's methodological rigor ensures reliable findings, highlighting the positive trends in clinical outcomes due to improved diagnostic tools and early interventions. However, potential publication bias and the need for a more detailed analysis of specific medical innovations and regional variations are notable limitations. Despite these, the letter is a valuable contribution, offering insights that could guide future research and improve patient outcomes.

A prognostic model incorporating the albumin-corrected anion gap in patients with aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients. Methods: Significant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC). Results: Among 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt-Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt-Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality. Conclusion: The ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies.

Relationship between stress hyperglycemia ratio and prognosis in patients with aneurysmal subarachnoid hemorrhage: a two-center retrospective study.

Previous research have demonstrated that the stress hyperglycemia ratio (SHR) accurately reflects acute hyperglycemic states and correlates with adverse outcomes. This study aims to explore the relationship between SHR and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH were categorized into four groups based on SHR tertiles. Functional outcomes were evaluated at 12 months using the modified Rankin Scale (mRS), with scores ranging from 0 to 2 indicating a good outcome and 3-6 indicating a poor outcome. The associations between SHR and functional outcomes were analyzed using logistic regression models and restricted cubic spline analysis. A total of 127 patients exhibited poor functional outcomes. Following comprehensive adjustments, those in the highest SHR tertile had a significantly increased risk of poor prognosis compared to those in the lowest tertile (odds ratio [OR], 4.12; 95% confidence interval [CI]: 1.87-9.06). Moreover, each unit increase in SHR was associated with a 7.51-fold increase in the risk of poor prognosis (OR, 7.51; 95% CI: 3.19-17.70). Further analysis using restricted cubic spline confirmed a linear correlation between SHR and poor prognosis (P for nonlinearity = 0.609). Similar patterns were observed across all studied subgroups. Elevated SHR significantly correlates with poor functional prognosis at one year in patients with aSAH, independent of their diabetes status.

Cerebrospinal fluid soluble growth stimulation expressed gene 2: A potential predictor of outcome for prognosis after aneurysmal subarachnoid hemorrhage.

Background: Serum concentration of soluble growth stimulation expressed gene 2 (sST2) appears to have prognostic value in patients with aneurysmal subarachnoid hemorrhage (aSAH) by now. This study aimed to investigate the relationship between cerebrospinal fluid (CSF) sST2 concentration and outcome in patients with aSAH. Methods: A total of 65 aSAH patients who met the inclusion criteria in the Neurosurgery Department of Jining No.1 People's Hospital from March 2021 to August 2022 were selected as the research objects. 35 patients with the third month Modified-Rankin-Scale (mRS) score of 0-2 were divided into good prognosis group, and 30 patients with the third month mRS score of 3-5 were divided into poor prognosis group. CSF was collected by lumbar puncture for the first 5 days after aneurysm surgery. CSF sST2 concentration was determined using an enzyme-linked immunosorbent assay. Results: In all patients, CSF sST2 concentrations initially increased, peaked on day 2, and then decreased. Compared with the good prognosis group, the sST2 concentration was significantly increased in the poor prognosis group at 1, 2, 3, 4 and 5 days after aSAH surgery. CSF sST2 concentration exhibited good diagnostic performance for predicting outcome (area under the receiver operating characteristic curve = 0.988). Additionally, CSF sST2 concentration has good performance for predicting cerebral edema, but only in the poor prognosis group (area under the curve = 0.93). Conclusions: Elevated CSF sST2 concentration is associated with poor outcome in aSAH patients. CSF sST2 may have a role as a predictive biomarker in these patients.

Red blood cell count in cerebrospinal fluid was correlated with inflammatory markers on the seventh postoperative day and all associated with the outcome of aneurysmal subarachnoid hemorrhage patients.

Background: Exploring factors associated with the outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) has become a hot focus in research. We sought to investigate the associations of inflammatory markers and blood cell count in cerebrospinal fluid with the outcome of aSAH patients. Methods: We carried a retrospective study including 200 patients with aSAH and surgeries. The associations of neutrophil, lymphocyte, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII), system inflammation response index (SIRI), and blood cell count in cerebrospinal fluid on the 1st and 7th postoperative days with the outcome of aSAH patients were investigated by univariate analysis and multivariate logistic regression model. Results: According to the modified Rankin scale (mRS) score, there were 147 patients with good outcome and 53 patients with poor outcome. The neutrophil, NLR, SIRI, and SII levels on the seventh postoperative day in patients with poor outcome were all significantly higher than patients with good outcome, P < 0.05. The multivariate logistic regression model including inflammatory markers and blood cell counts in cerebrospinal fluid on the 1st postoperative day confirmed that red blood cell count in cerebrospinal fluid (≥177 × 109/L; OR: 7.227, 95% CI: 1.160-45.050, P = 0.034) was possibly associated with poor outcome of aSAH patients, surgical duration (≥169 min), Fisher grade (III-IV), hypertension, and infections were also possibly associated with the poor outcome. The model including inflammatory markers and blood cell counts in cerebrospinal fluid on the 7th postoperative day confirmed that red blood cell count in cerebrospinal fluid (≥54 × 109/L; OR: 39.787, 95% CI: 6.799-232.836, P < 0.001) and neutrophil-lymphocyte ratio (≥8.16; OR: 6.362, 95% CI: 1.424-28.428, P = 0.015) were all possibly associated with poor outcome of aSAH patients. The NLR (r = 0.297, P = 0.007) and SIRI (r = 0.325, P = 0.003) levels were all correlated with the count of red blood cells in cerebrospinal fluid. Discussion: Higher neutrophil-lymphocyte ratio and higher red blood cell count in cerebrospinal fluid were all possibly associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage. However, we need a larger sample study.

Blood Pressure Management in Early Aneurysmal Subarachnoid Hemorrhage: A National Cross-Sectional Survey of Canadian Intensivists and Cerebrovascular Neurosurgeons.

BACKGROUND: In aneurysmal subarachnoid hemorrhage (aSAH), rebleeding of the culprit aneurysm is associated with significant morbidity and mortality. Blood pressure reduction to specific target levels, with the goal of preventing rebleeding, has been a mainstay of care prior to definitively securing the aneurysm. Clinical practice guidelines have recently changed and no longer recommend specific blood pressure targets. This survey aims to identify the reported practice patterns and beliefs regarding blood pressure management during the early phase of aSAH. METHODS: We conducted a self-administered, Web-based survey of critical care physicians and cerebrovascular neurosurgeons practicing in Canada. The questionnaire contained 21 items, including 3 case-based scenarios to elicit blood pressure target selection, both before and after aneurysm securing. RESULTS: In the presecured period, systolic blood pressures of 160 mm Hg (50% [144 of 287]) and 140 mm Hg (42% [120 of 287]) were the most frequently selected upper-limit targets. In the postsecured period, a systolic blood pressure of 180 mm Hg (32% [93 of 287]) was the most frequently selected upper-limit target, but there was a wide distribution of targets selected across all three cases ranging from 100 to > 200 mm Hg. A mean arterial pressure of 65 mm Hg was the most common lower-limit target in both the presecured and postsecured periods. There was little change in blood pressure targets with increasing clinical severity. Predictors of higher or lower blood pressure target selection and barriers to implementation of the desired target were identified. CONCLUSIONS: During the presecured period, nearly half of the reported upper-limit blood pressure targets are lower than previous guideline recommendations. These targets remain consistent despite increasing clinical severity and could potentially exacerbate cerebral ischemia and negatively impact clinical outcomes. In the postsecured period, there is wide variation in the reported blood pressure targets. A clinical trial is urgently needed to guide decision-making.

Duration of Intracranial Pressure Increase after Aneurysmal Subarachnoid Hemorrhage: Prognostic Factors and Association with the Outcome.

OBJECTIVE: A rupture of the intracranial aneurysm is frequently complicated, with an increase of intracranial pressure (ICP) requiring conservative and/or surgical treatment. We ana- lyzed the risk factors related to the duration of pathologic ICP increase and the relationship be- tween ICP burden and the outcome of subarachnoid hemorrhage (SAH). METHODS: Consecutive cases with aneurysmal SAH treated at our institution between 01/2003 and 06/2016 were eligible for this study. Different admission variables were evaluated to predict the duration of ICP increase >20 mmHg in univariate and multivariate analyses. The association of the ICP course with SAH outcome parameters (risk of cerebral infarction, in-hospital mortali- ty, and unfavorable outcome at 6 months defined as modified Rankin scale >3) was adjusted for major outcome-relevant confounders. RESULTS: Of 820 SAH patients, 378 individuals (46.1%) developed at least one ICP increase re- quiring conservative and/or surgical management after aneurysm treatment (mean duration: 1.76 days, range: 1 - 14 days). In the multivariable linear regression analysis, patients' age (unstand- ardized coefficient [UC]=-0.02, p <0.0001), World Federation of Neurosurgical Societies (WFNS) grade 4-5 at admission (UC=0.71, p <0.004), regular medication with the angiotensin- converting enzyme (ACE) inhibitors (UC=-0.61, p =0.01), and presence of intracerebral hemor- rhage (UC=0.59, p =0.002) were associated with the duration of ICP increase. In turn, patients with longer ICP elevations were at higher risk for cerebral infarction (adjusted odds ratio [aOR]=1.32 per-day-increase, p <0.0001), in-hospital mortality (aOR=1.30, p <0.0001) and un- favorable outcome (aOR=1.43, p <0.0001). SAH patients who underwent primary decompres- sive craniectomy (DC) showed shorter periods of ICP increase than patients with a secondary decompression (mean: 2.8 vs 4.9 days, p <0.0001). CONCLUSION: The duration of ICP increase after aneurysm rupture is a strong outcome predictor and is related to younger age and higher initial severity of SAH. Further analysis of the factors impacting the course of ICP after SAH is essential for the optimization of ICP management and outcome improvement.

The Difference in Serum Metabolomic Profiles between the Good and Poor Outcome Groups at 3 Months in the Early and Late Phases of Aneurysmal Subarachnoid Hemorrhage.

We aimed to investigate the characteristics of serum metabolomics in aneurysmal subarachnoid hemorrhage patients (aSAH) with different 3-month outcomes (good = modified Rankin score: 0-3 vs. poor = mRS 4-6). We collected serum samples from 46 aSAH patients at 24 (D1) and 168 (D7) hours after injury for analysis by liquid chromatography-mass spectrometry. Ninety-six different metabolites were identified. Groups were compared using multivariate (orthogonal partial least squares discriminant analysis), univariate, and receiving operator characteristic (ROC) methods. We observed a marked decrease in serum homocysteine levels at the late phase (D7) compared to the early phase (D1). At both D1 and D7, mannose and sorbose levels were notably higher, alongside elevated levels of kynurenine (D1) and increased 2-hydroxybutyrate, methyl-galactoside, creatine, xanthosine, p-hydroxyphenylacetate, N-acetylalanine, and N-acetylmethionine (all D7) in the poor outcome group. Conversely, levels of guanidinoacetate (D7) and several amino acids (both D1 and D7) were significantly lower in patients with poor outcomes. Our results indicate significant changes in energy metabolism, shifting towards ketosis and alternative energy sources, both in the early and late phases, even with adequate enteral nutrition, particularly in patients with poor outcomes. The early activation of the kynurenine pathway may also play a role in this process.

The Link Between Vitamin D and the Risk of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

BACKGROUND: Vitamin D (VD) is one of the fat-soluble vitamins proposed to be associated with aSAH. According to the clinical evidence, this investigation explores the link between VD concentrations and clinical outcomes in aSAH patients. METHODS: This systematic review was executed based on the PRISMA 2020 statement. Observational studies that evaluated the serum VD concentrations in aSAH patients were considered as included articles. Review articles, case reports, letters, commentaries, non-English papers, and conference abstracts were excluded. Five online databases-Scopus, PubMed, Web of Science, Embase, and Ovid-were searched up to November 23, 2023, and based on the Newcastle-Ottawa Scale, the risk of bias was assessed. RESULTS: Out of 383 articles initially identified, eventually 7 studies were included in the systematic review. These studies were conducted between 2016 and 2023 and included a total of 333,907 patients. The varying results suggest that VD may impact clinical outcomes in aSAH patients. CONCLUSIONS: This study highlights the complex association between VD concentration and the risk of aSAH. The observed inconsistencies in study outcomes suggest that the relationship between VD and aSAH is multifaceted and may be influenced by various factors, including study population, geographical location, and methodological approach.

Advances and Future Trends in the Diagnosis and Management of Subarachnoid Hemorrhage.

Major advances in neurocritical care and the modalities used to treat aneurysms have led to improvement in the outlook of patients with aneurysmal subarachnoid hemorrhage. Yet, several knowledge gaps remain widely open. Variability in practices stems from the lack of solid evidence to guide management, which recent guidelines from professional organizations aim to mitigate. In this article, the authors review some of these gaps in knowledge, highlight important messages from recent management guidelines, emphasize aspects of our practice that we consider particularly useful to optimize patient outcomes, and suggest future areas of research.

The effectiveness and safety of clazosentan in treating aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality. METHODS: We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software. RESULTS: A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta-analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34-0.70), moderate to severe vasospasm (R/R = 0.53: 0.46-0.61), DCI (R/R = 0.70: 0.59-0.82), and the need for rescue therapy (R/R = 0.65: 0.52-0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64-2.18), hypotension (R/R = 2.47: 1.79-3.42), and anemia (R/R = 1.49: 1.23-1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage. CONCLUSIONS: Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm.

Plasma Neurofilament Light Chain as a Biomarker for Poor Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Neurofilament light chain (NfL), a biomarker reflecting neuro-axonal damage, may be useful in improving clinical outcome prediction after aneurysmal subarachnoid hemorrhage (aSAH). We explore the robust and additional value of NfL to neurologic and radiologic grading scales in predicting poor outcome after aSAH. METHODS: In this prospective cohort study conducted in a single tertiary center, blood samples were collected of aSAH patients within 24 hours after ictus and before endovascular/surgical intervention. The primary endpoint was poor outcome at 6 months' follow-up. Receiver operating curves (ROC), area under the curve (AUC, 95% CI) and model-fit (Nagelkerke R2) were calculated for NfL, neurologic grading scale (WFNS), modified Fisher, age ,and sex. A combined ROC and AUC were calculated for variables with an AUC ≥ 0.70. RESULTS: A total of 66 (42%) had poor outcome. The AUC of NfL for poor outcome was 0.70 (0.62-0.78). Combining NfL and WFNS resulted in a slightly higher model fit and not-significantly higher AUC for predicting poor outcome (R2 0.51; AUC 0.86, 0.80-0.92) compared with WFNS alone. When patients were stratified according to hemorrhage severity, median NfL [IQR] levels were significantly higher in poor grade (14 [7-32] pg/mL) than good grade patients (7 [5-14] pg/mL). Within poor grade patients, median NfL [IQR] levels were significantly higher in non-survivors (19 [11-36] pg/mL) than survivors (7 [6-13] pg/mL). CONCLUSION: In the entire aSAH cohort, plasma NfL has an acceptable predictive performance but does not improve clinical outcome prediction. However, NfL may have potential value in subgroups based on hemorrhage severity.

A Mediation Analysis of the Association Between Systemic Inflammation Response Index, in-Hospital Complications, and Poor Long-Term Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: Insights from a Large Prospective Cohort Study.

Purpose: Early systemic inflammatory changes are increasingly recognized as factors influencing outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Systemic inflammation response index (SIRI), an inflammation biomarker, was thought to be associated with adverse outcomes in many other diseases. However, in aSAH, research on SIRI remains limited. Thus, our objective was to investigate the association between SIRI and poor long-term functional outcomes while evaluating the mediating role of in-hospital complications in this association. Patients and Methods: SIRI was defined as neutrophil count × monocyte count/lymphocyte count. Patients were categorized according to SIRI quartiles. Stabilized inverse probability of treatment weighting (sIPTW) was utilized to minimize group differences. The association between SIRI and in-hospital complications as well as poor 90-day functional outcomes (mRS 3-6) was estimated by multivariable logistic regression analyses. Mediation analysis was performed to investigate the relationship between SIRI and poor functional outcomes mediated by in-hospital complications. Results: A total of 650 patients were prospectively included. After sIPTW, compared to the lowest quartile, an elevated SIRI was associated with delayed cerebral ischemia (DCI) (OR 2.12, 95% CI 1.20-3.74), post-operative pneumonia (POP) (OR 2.16, 95% CI 1.29-3.62) and poor 90-day functional outcomes (OR 3.03, 95% CI 1.55-5.91). In-hospital complications including DCI (mediation proportion, 18.18% before sIPTW and 20.0% after sIPTW) and POP (mediation proportion, 18.18% before sIPTW and 26.7% after sIPTW) partially mediated the association between SIRI and poor 90-day functional outcomes. Mediation analysis yielded comparable results in subgroups stratified by age and sex. Conclusion: In this study, SIRI was associated with poor long-term functional outcomes in aSAH, which was partially mediated by DCI and POP with a mediation proportion exceeding 18%. Our findings might underscore the potential utility of SIRI in prompting physicians to address systemic inflammatory status timely to prevent in-hospital complications, including DCI and POP, and ultimately improve long-term functional outcomes.

Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

Efficacy of endovascular therapy for cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Background: Cerebral vasospasm (CV) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), leading to increased morbidity and mortality rates. Endovascular therapy, particularly intra-arterial vasodilator infusion (IAVI), has emerged as a potential alternative treatment for CV. Methods: A systematic review and meta-analysis were conducted to compare the efficacy of endovascular therapy with standard treatment in patients with CV following aSAH. The primary outcomes assessed were in-hospital mortality, discharge favorable outcome, and follow-up favorable outcome. Secondary outcomes included major infarction on CT, ICU stay duration, and total hospital stay. Results: Regarding our primary outcomes of interest, patients undergoing intervention exhibited a significantly lower in-hospital mortality compared to the standard treatment group, with the intervention group having only half the mortality risk (RR = 0.49, 95% CI [0.29, 0.83], p = 0.008). However, there were no significant differences between the two groups in terms of discharge favorable outcome (RR = 0.99, 95% CI [0.68, 1.45], p = 0.963) and follow-up favorable outcome (RR = 1.09, 95% CI [0.86, 1.39], p = 0.485). Additionally, there was no significant difference in major infarction rates (RR = 0.79, 95% CI [0.34, 1.84], p = 0.588). It is important to note that patients undergoing endovascular treatment experienced longer stays in the ICU (MD = 6.07, 95% CI [1.03, 11.12], p = 0.018) and extended hospitalization (MD = 5.6, 95% CI [3.63, 7.56], p < 0.001). Subgroup analyses based on the mode of endovascular treatment further supported the benefits of IAVI in lowering in-hospital mortality (RR = 0.5, 95% CI [0.27, 0.91], p = 0.023). Conclusion: Endovascular therapy, particularly IAVI, holds promising potential in reducing in-hospital mortality for patients with CV following aSAH. However, it did not show significant improvement in long-term prognosis and functional recovery. Further research with larger sample sizes and randomized controlled trials is necessary to validate these findings and optimize the treatment strategy for cerebral vasospasm in aSAH patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023451741.

Early focal electroencephalogram and neuroimaging findings predict epilepsy development after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Seizures are a common complication of subarachnoid hemorrhage (SAH) in both acute and late stages: 10-20 % acute symptomatic seizures, 12-25 % epilepsy rate at five years. Our aim was to identify early electroencephalogram (EEG) and computed tomography (CT) findings that could predict long-term epilepsy after SAH. MATERIAL AND METHODS: This is a multicenter, retrospective, longitudinal study of adult patients with aneurysmal SAH admitted to two tertiary care hospitals between January 2011 to December 2022. Routine 30-minute EEG recording was performed in all subjects during admission period. Exclusion criteria were the presence of prior structural brain lesions and/or known epilepsy. We documented the presence of SAH-related cortical involvement in brain CT and focal electrographic abnormalities (epileptiform and non-epileptiform). Post-SAH epilepsy was defined as the occurrence of remote unprovoked seizures ≥ 7 days from the bleeding. RESULTS: We included 278 patients with a median follow-up of 2.4 years. The mean age was 57 (+/-12) years, 188 (68 %) were female and 49 (17.6 %) developed epilepsy with a median latency of 174 days (IQR 49-479). Cortical brain lesions were present in 189 (68 %) and focal EEG abnormalities were detected in 158 patients (39 epileptiform discharges, 119 non-epileptiform abnormalities). The median delay to the first EEG recording was 6 days (IQR 2-12). Multiple Cox regression analysis showed higher risk of long-term epilepsy in those patients with CT cortical involvement (HR 2.6 [1.3-5.2], p 0.009), EEG focal non-epileptiform abnormalities (HR 3.7 [1.6-8.2], p 0.002) and epileptiform discharges (HR 6.7 [2.8-15.8], p < 0.001). Concomitant use of anesthetics and/or antiseizure medication during EEG recording had no influence over its predictive capacity. ROC-curve analysis of the model showed good predictive capability at 5 years (AUC 0.80, 95 %CI 0.74-0.87). CONCLUSIONS: Focal electrographic abnormalities (both epileptiform and non-epileptiform abnormalities) and cortical involvement in neuroimaging predict the development of long-term epilepsy. In-patient EEG and CT findings could allow an early risk stratification and facilitate a personalized follow-up and management of SAH patients.

Association of geographical disparities and segregation in regional treatment facilities for Black patients with aneurysmal subarachnoid hemorrhage in the United States.

Background and objectives: This study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations. Methods: This cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed. Results: 142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division (D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic (D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p < 0.001) were associated a lower likelihood of mortality (OR 0.91, 95% CI 0.82-1.00, p = 0.044 vs. OR 0.75, 95% CI 0.68-0.83, p < 0. 001) (p = 0.049), greater likelihood of tracheostomy tube placement (OR 1.45, 95% CI 1.22-1.73, p < 0.001 vs. OR 1.87, 95% CI 1.59-2.21, p < 0.001) (p < 0. 001), and lower likelihood of receiving palliative care (OR 0.88, 95% CI 0.76-0.93, p < 0.001 vs. OR 0.67, 95% CI 0.59-0.77, p < 0.001) (p = 0.029). Conclusion: This study demonstrates regional differences in disparities for Black patients with aSAH, particularly in end-of-life care, with varying levels of segregation in regional treatment facilities playing an associated role. The findings underscore the need for targeted interventions and policy changes to address systemic healthcare inequities, reduce segregation, and ensure equitable access to high-quality care for all patients.