BACKGROUND: This study aims to investigate the efficacy and safety of glibenclamide treatment in patients with acute aneurysmal subarachnoid hemorrhage (aSAH).
METHODS: The randomized controlled trial was conducted from October 2021 to May 2023 at two university-affiliated hospitals in Beijing, China. The study included patients with aSAH within 48 h of onset, of whom were divided into the intervention group and the control group according to the random number table method. Patients in the intervention group received glibenclamide tablet 3.75 mg/day for 7 days. The primary end points were the levels of serum neuron-specific enolase (NSE) and soluble protein 100B (S100B) between the two groups. Secondary end points included evaluating changes in the midline shift and the gray matter-white matter ratio, as well as assessing the modified Rankin Scale scores during follow-up. The trial was registered at ClinicalTrials.gov (identifier NCT05137678).
RESULTS: A total of 111 study participants completed the study. The median age was 55 years, and 52% were women. The mean admission Glasgow Coma Scale was 10, and 58% of the Hunt-Hess grades were no less than grade III. The baseline characteristics of the two groups were similar. On days 3 and 7, there were no statistically significant differences observed in serum NSE and S100B levels between the two groups (P > 0.05). The computer tomography (CT) values of gray matter and white matter in the basal ganglia were low on admission, indicating early brain edema. However, there were no significant differences found in midline shift and gray matter-white matter ratio (P > 0.05) between the two groups. More than half of the patients had a beneficial outcome (modified Rankin Scale scores 0-2), and there were no statistically significant differences between the two groups. The incidence of hypoglycemia in the two groups were 4% and 9%, respectively (P = 0.439).
CONCLUSIONS: Treating patients with early aSAH with oral glibenclamide did not decrease levels of serum NSE and S100B and did not improve the poor 90-day neurological outcome. In the intervention group, there was a visible decreasing trend in cases of delayed cerebral ischemia, but no statistically significant difference was observed. The incidence of hypoglycemia did not differ significantly between the two groups.

UNASSIGNED: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening medical condition with a high fatality and morbidity rate. There was a substantial link between the modified Fisher grade of aSAH and the neurological function deficit. This study aimed to analyze the factors associated with the modified Fisher grade of aSAH using a machine learning approach.
UNASSIGNED: A multi-center observational study was conducted. The patients with aSAH were recruited from five tertiary hospitals in China. The volume of hemorrhage in aSAH was measured using the modified Fisher grade scale. The risk factors responsible for the modified Fisher grade of aSAH were analyzed, which include sociodemographic factors, clinical factors, blood index, and ruptured aneurysm characteristics. We built several tree-based machine learning models (XGBoost, CatBoost, LightGBM) for prediction and used grid search to optimize model parameters. To comprehensively evaluate the model, we used Accuracy, Precision, Area Under the Receiver Operating Characteristic Curve (AUROC), Area Under the Precision-Recall Curve (AUPRC), and Brier as evaluation indicators to assess the model performance and select the best model.
UNASSIGNED: A total of 888 patients with aSAH were recruited, of whom 305 with modified Fisher grade of 3 and 4. The results show that the XGBoost model has the highest AUROC of 0.772, and the indicators are better than CatBoost and LightGBM. The feature importance graph shows that the top feature variables include platelet, thrombin time, fibrinogen, preadmission systolic blood pressure, activated partial thromboplastin time, and the time interval between the onset of aSAH and the first-time CT examination.
UNASSIGNED: The factors responsible for the modified Fisher grade of aSAH were identified, which offered valuable insights for future research and clinical intervention. These risk factors should be controlled in the treatment of unruptured aneurysms, and appropriate treatment can be given if necessary to reduce the risk of severe hemorrhage after aneurysm rupture.

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.

UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.
CONCLUSIONS: 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.
BACKGROUND: 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.
BACKGROUND: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: Early fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH.
METHODS: A total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association.
RESULTS: Of 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients.
CONCLUSIONS: Elevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.