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Background and purpose: Spontaneous aneurysmal subarachnoid hemorrhage (aSAH) is a common acute cerebrovascular disease characterized by severe illness, high mortality, and potential cognitive and motor impairments. We carried out a retrospective study at Fujian Provincial Hospital to establish and validate a model for forecasting functional outcomes at 6 months in aSAH patients who underwent interventional embolization. Methods: 386 aSAH patients who underwent interventional embolization between May 2012 and April 2022 were included in the study. We established a logistic regression model based on independent risk factors associated with 6-month adverse outcomes (modified Rankin Scale Score = 3, mRS). We evaluated the model's performance based on its discrimination, calibration, clinical applicability, and generalization ability. Finally, the study-derived prediction model was also compared with other aSAH prognostic scales and the model's itself constituent variables to assess their respective predictive efficacy. Results: The predictors considered in our study were age, the World Federation of Neurosurgical Societies (WFNS) grade of IV-V, mFisher score of 3-4, secondary cerebral infarction, and first leukocyte counts on admission. Our model demonstrated excellent discrimination in both the modeling and validation cohorts, with an area under the curve of 0.914 (p < 0.001, 95%CI = 0.873-0.956) and 0.947 (p < 0.001, 95%CI = 0.907-0.987), respectively. Additionally, the model also exhibited good calibration (Hosmer-Lemeshow goodness-of-fit test: X2 = 9.176, p = 0.328). The clinical decision curve analysis and clinical impact curve showed favorable clinical applicability. In comparison to other prediction models and variables, our model displayed superior predictive performance. Conclusion: The new prediction nomogram has the capability to forecast the unfavorable outcomes at 6 months after intervention in patients with aSAH. [ABSTRACT FROM AUTHOR]

The prior trials investigating triple-H therapy for preventing delayed cerebral ischemia (DCI) enrolled patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent early aneurysm therapy within 3 days. However, surgical clipping might be performed during 4–7 days that high incidence cerebral vasospasm is likely. We examined effects of hypervolemia-augmented blood pressure (HV-ABP) protocol on DCI prevention when clipping was delayed. The study enrolled aSAH patients hospitalized during 2013–2019 who underwent clipping 4–7 days after rupture in a university hospital in Thailand. DCI and secondary outcomes were compared among patients who achieved the HV-ABP protocol (3–5 L/day fluid intake and 140–180 mmHg systolic blood pressure maintained for 72 hours postoperatively) and those who did not. The intervention-outcome associations were estimated using logistic regression for the whole group and a patient subgroup with similar propensity scores (PS) for protocol achievement. One hundred seventy-seven aSAH patients were clipped 4–7 days after rupture; 97 patients (54.8%) achieved the HV-ABP protocol, while 80 patients (45.2%) did not. One hundred twenty-two patients with one-to-one PS matching reduced the originally unequal patient characteristics. The observed DCI was lower in patients with protocol-achieved (8.3%) than in their nonachieved counterparts (22.5%). This resulted in an association with the HV-ABP intervention with adjusted odds ratios of 0.201 (95% confidence interval, 0.066–0.613) in the whole sample and 0.228 (0.065–0.794) in the PS-matched subsample. No statistically significant differences in the secondary outcomes were found. Achieving the targets recommended in the HV-ABP protocol was associated with reducing the DCI incidence in patients with aSAH who underwent delayed clipping. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Objectives Neurosurgical patients often receive 0.9% normal saline (NS) during the perioperative period. Theoretically, a balanced salt solution (BSS) is better than 0.9% saline. We compared the effects of two different fluids on acid–base balance, renal function, and neurological outcome in patients who underwent clipping following subarachnoid hemorrhage from a ruptured intracranial aneurysm. Materials and Methods Patients in group NS (n = 30) received 0.9% saline and group BSS (N = 30) received BSS (Plasmalyte-A) in the perioperative period for 48 hours. Comparison of arterial pH, bicarbonate, and base deficit measured preoperatively, intraoperatively (first and second hour), and postoperatively (at 24 and 48 hours) was the primary outcome of the study. The secondary outcome compared serum electrolytes, renal function tests, urine neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin C, and the neurological outcome using modified Rankin score (MRS) at discharge, 1, and 3 months. Results In group NS, significantly low pH at 1-hour intraoperative period was seen compared with group BSS (7.37 ± 0.06 vs. 7.40 ± 0.05, p = 0.024). The bicarbonate level in group NS was significantly lower and the base deficit was higher at second intraoperative hour (bicarbonate: 17.49 vs. 21.99 mEq/L, p = 0.001; base deficit: 6.41 mmol/L vs. 1.89 mmol/L, p = 0.003) and at 24 hours post-surgery (bicarbonate: 20.38 vs. 21.96 mEq/L, p = 0.012; base deficit: 3.56 mmol/L vs. 2.12 mmol/L, p = 0.034)). Serum creatinine was higher in group NS at 24 hours (0.66 vs. 0.52 mg/dL, p = 0.013) and 48 hours (0.62 vs. 0.53 mg/dL, p = 0.047). Serum urea, electrolytes, cystatin, urine NGAL, and MRS were comparable. Conclusion In neurosurgical patients undergoing clipping for ruptured intracranial aneurysm, using a BSS during the perioperative period is associated with a better acid–base and renal profile. However, the biomarkers of kidney injury and long-term outcomes were comparable. [ABSTRACT FROM AUTHOR]

This article explores the management of patients with aneurysmal subarachnoid hemorrhage (aSAH) and the challenges in determining fluid balance and blood transfusion thresholds. The authors analyze a clinical trial and find that positive fluid balance is associated with lower hemoglobin levels and an increased risk of secondary infarctions and unfavorable neurologic outcomes. Packed red cell transfusions are also found to be predictive of worse neurologic outcomes. The study suggests that careful, goal-directed circulation management is crucial for maximizing favorable functional outcomes in patients with aSAH. The article emphasizes the importance of maintaining a mean daily neutral fluid balance and targeting euvolemia, while also highlighting the need for consensus among healthcare professionals on definitions and personalized management. It raises questions about the implementation of fluid balancing and the design of randomized trials for fluid management strategies. Overall, the article provides practical insights for managing patients with aSAH. [Extracted from the article]

Key Clinical Message: Accurately identifying the ruptured aneurysm in patients with subarachnoid hemorrhage and multiple aneurysms is critical to prevent rebleeding and optimize outcomes. Vessel wall MRI with contrast can aid in pinpointing the culprit aneurysm, informing a tailored surgical or endovascular management strategy for these complex cases. In patients with subarachnoid hemorrhage (SAH) and multiple intracranial aneurysms, MRI with contrast and DSA are crucial for identifying the ruptured aneurysm, guiding a shift from endovascular to microsurgical clipping. Successful single‐session treatment and absence of postsurgical deficits highlight the effectiveness of a multidisciplinary approach. Further research on optimal strategies is needed. Multiple intracranial aneurysms make up approximately 20% of cases of aneurysmal SAH. In patients with aneurysmal SAH and multiple intracranial aneurysms, definite treatment of the ruptured aneurysm causing SAH is of the highest priority. However, identifying the bleeding source can be challenging, and it may not be recognizable by the hemorrhage pattern. Misdiagnosis and mistreatment of a ruptured aneurysm in a patient with multiple aneurysms can lead to bleeding recurrence and an undesirable outcome. We report a 65‐year‐old woman who presented with severe sudden onset headache. Neuroimaging studies revealed diffuse SAH and concurrent PICA and ACom aneurysm with triplicate A2. However, the ruptured aneurysm responsible for the patient's symptoms was not obvious based on routine neuroimaging studies. Magnetic resonance imaging with contrast was performed, revealing circumferential enhancement of the PICA aneurysm. In this report, we demonstrate the real‐world effect of vessel wall MRI with contrast on decision‐making regarding identifying the ruptured aneurysm and surgical planning in cases of multiple aneurysms. Furthermore, we show that MRI and aneurysm wall enhancement could be a promising option in detecting ruptured aneurysms in cases of multiple aneurysms. [ABSTRACT FROM AUTHOR]

• The meta -analysis included 11 studies (7 RCTs and 4 cohort studies) with varied geographical representation and patient demographics. Most studies were rated as having low to moderate risk of bias. However, some outcomes displayed heterogeneity, which was addressed through sensitivity analyses to ensure robust results. • Clazosentan significantly reduces the incidence of vasospasm, including moderate to severe vasospasm, and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The risk ratios for vasospasm, moderate to severe vasospasm, and DCI were 0.49, 0.53, and 0.70 respectively, indicating a substantial reduction compared to placebo. • The use of clazosentan significantly lowers the need for rescue therapy among aSAH patients. The pooled analysis showed a risk ratio of 0.65, suggesting a 35 % reduction in the requirement for additional interventions. • Clazosentan is associated with increased rates of specific adverse events such as pulmonary complications (RR = 1.89), hypotension (RR = 2.47), and anemia (RR = 1.49). However, it does not increase the risk of hepatobiliary adverse events or cerebral hemorrhage. • Despite its efficacy in reducing vasospasm and DCI, clazosentan does not show a significant improvement in functional outcomes (measured by GOSE and mRS) or mortality rates. This suggests that while it mitigates certain complications, it does not necessarily enhance overall survival or recovery quality. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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 β-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. [ABSTRACT FROM AUTHOR]

We aimed to synthesize evidence from published clinical trials on the efficacy and safety of tranexamic acid (TXA) administration in patients with aneurysmal subarachnoid hemorrhage (aSAH). We followed the standard methods of the Cochrane Handbook of Systematic Reviews for interventions and the PRISMA statement guidelines 2020 when conducting and reporting this study. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until 1 January 2022. We selected observational studies and clinical trials comparing TXA versus no TXA in aSAH patients. Data of all outcomes were pooled as the risk ratio (RR) with the corresponding 95% confidence intervals in the meta-analysis models. Thirteen studies with a total of 2991 patients were included in the analysis. TXA could significantly cut the risk of rebleeding (RR 0.56, 95% CI 0.44 to 0.72) and mortality from rebleeding (RR 0.60, 95% CI 0.39 to 0.92, p = 0.02). However, TXA did not significantly improve the overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus (all p > 0.05). In terms of safety, no significant adverse events were reported. No statistical heterogeneity or publication bias was found in all outcomes. In patients with aSAH, TXA significantly reduces the incidence of rebleeding and mortality from rebleeding. However, current evidence does not support any benefits in overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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 β-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.

Background: Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). Methods: In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of − 5 to − 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. Results: We included 19 patients with a median age of 61 years (range 46–78 years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2 mm Hg), PBrO2 (31.0 ± 13.2 vs. 32.2 ± 12.4 mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9 mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6 µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8 mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6 mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. Conclusions: Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered. [ABSTRACT FROM AUTHOR]

Abstract 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.

Tu Li,1 Runting Li,1 Fa Lin,1 Xiaolin Chen1– 3 1Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, People’s Republic of China; 2Stroke Center, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xiaolin Chen, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, Fengtai District, 100070, People’s Republic of China, Email chenxiaolin@bjtth.orgPurpose: 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.Keywords: aneurysmal subarachnoid hemorrhage, systemic inflammation response index, complications, functional outcomes, mediation analysis

Abstract Background Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results. Methods This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature. Results A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model. Conclusions In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention.

Abstract Purpose QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. Methods We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. Results After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. Conclusions QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.

Abstract Objective Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH. Methods This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM). Results A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P

Objective To analyze the therapeutic effect of microsurgery on patients with severe aneurysmal subarachnoid hemorrhage (SaSAH). Methods A retrospective analysis was conducted on 14 SaSAH patients admitted to Beijing Chao-Yang Hospital, Capital Medical University from December 2017 to November 2019. General information, Hunt Hess grading, Glasgow Coma Scale (GCS), time of rebleeding, surgery time, examination method, aneurysm size, prognosis, and postoperative follow-up were collected. Results A total of 14 patients with SaSAH were enrolled, including 5 males and 9 females, 8 patients with Hunt-Hess grade Ⅳ and 6 with grade Ⅴ. Seven cases experienced rebleeding after admission, with an average time between the onset of symptoms and rebleeding being 11.21 hours. Intracranial aneurysm rupture was confirmed by computed tomography angiography (CTA) or digital subtraction angiography (DSA) before operation in 13 cases. All 14 patients underwent microsurgical aneurysm clipping after definite diagnosis. There were 5 cases of transtentorial herniation and 3 cases of subfalcine herniation. Bone flaps were removed during surgery for all patients with cerebral herniation. In 14 cases, Glasgow prognostic score (GOS) was 4 in 2 cases, 3 in 3 cases, 2 in 7 cases, and 1 in 2 case at 6 months follow-up. Conclusion Treating SaSAH responsible aneurysms within 24 hours is an important principle for preventing intracranial rebleeding, reducing mortality, and improving prognosis. Microsurgery remains an important method for treating SaSAH, especially for patients with intracranial hematoma and progressive intracranial hypertension."

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is preferentially treated by prompt endovascular coiling, which is not available in Guadeloupe. Subsequently, patients are transferred to Paris, France mainland, by commercial airplane (6751 km flight) after being managed according to guidelines. This study describes the characteristics, management and outcomes related to these patients. Methods Retrospective observational cohort study of 148 patients admitted in intensive care unit for a suspected aSAH and transferred by airplane over a 10-year period (2010–2019). Results The median [interquartile range] age was 53 [45–64] years and 61% were female. On admission, Glasgow coma scale was 15 [13–15], World Federation of Neurological Surgeons (WFNS) grading scale was 1 [1–3] and Fisher scale was 4 [2–4]. External ventricular drainage and mechanical ventilation were performed prior to the flight respectively in 42% and 47% of patients. One-year mortality was 16% over the study period. By COX logistic regression analysis, acute hydrocephalus (hazard ratio [HR] 2.34, 95% confidence interval [CI] 0.98–5.58) prior to airplane transfer, WFNS grading scale on admission (HR 1.53, 95% CI 1.16–2.02) and age (OR 1.03, 95% 1.00–1.07) were associated with one-year mortality. Conclusion When necessary, transatlantic air transfer of patients with suspected aSAH after management according to local guidelines seems feasible and safe.

Objective: Pulmonary edema is a common complication in patients receiving clazonsentan. Here, we report our experience in managing fluid balance with loop diuretics in patients with aneurysmal subarachnoid hemorrhage (aSAH) treated with clazosentan. Methods: Patients with aSAH who received prophylactic agents for vasospasm after aneurysm obliteration between June 2021 and April 2023 were enrolled. Fluid balance parameters and asymptomatic and symptomatic vasospasm and pulmonary edema incidence were compared in three periods: 1st period (fasudil therapy), 2nd period (clazosentan therapy alone), and 3rd period (clazosentan with loop diuretic therapy). Results: Fluid intake and urine volume during the 2nd and 3rd periods were considerably lesser than those during the 1st period. Asymptomatic vasospasm incidence was considerably lesser in the 3rd period than that in the 1st and 2nd periods. However, the incidences of symptomatic vasospasm and rescue endovascular treatment were comparable among the three groups. Although the clinical outcomes at the last follow-up were comparable among the three groups, pulmonary edema incidence was markedly higher during the 2nd period than that in the 1st and 3rd periods. Conclusion: Thus, proper management of fluid balance with clazosentan and diuretics would help in effective clazosentan therapy for vasospasm prophylaxis.

Objective: Pulmonary complications, which are occasionally severe, are common adverse events following the administration of clazosentan. This study aimed to identify factors associated with severe pulmonary adverse events due to clazosentan after aneurysmal subarachnoid hemorrhage (aSAH). Methods: We conducted a retrospective study of 59 patients transported to our hospital and diagnosed with aSAH between April 2022 and May 2023. Results: The analysis included 33 patients who were treated with clazosentan. Pulmonary complications occurred in 20 patients (61 %) and clazosentan administration was discontinued due to severe pulmonary complications in 7 patients (21 %). The cardiothoracic ratio on admission was significantly higher (57 % vs. 49 %, p = 0.0081) and clazosentan was initiated earlier after aSAH onset (42 vs. 66 h, p = 0.047) in patients who discontinued clazosentan compared with patients who completed administration of clazosentan. The median duration of clazosentan administration was 3.2 days in the discontinuation group. No significant associations were found between the time of clazosentan initiation and the incidence of angiographic vasospasm, delayed cerebral ischemia, or 90-day modified Rankin scale. Conclusions: The risk of severe pulmonary complications is higher in patients with high cardiothoracic ratios on admission, and delaying clazosentan initiation may prevent pulmonary complications even in high-risk cases.

An aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event associated with a high mortality and morbidity rate. Though numerous medications are used to prevent cerebral vasospasm and vasospasm-related cerebral infarction after aSAH, no effective pharmacological treatment has been established. Clazosentan, a highly selective endothelin receptor type A antagonist, was approved for use in Japan in April 2022 based on results of two pivotal randomized, placebo-controlled phase 3 studies (JapicCTI-163369, JapicCTI-163368). These studies indicated that clazosentan significantly reduced the incidence of vasospasm-related morbidity and all-cause mortality after aneurysm coiling and clipping. Clazosentan is thus expected to become a “game changer” for improving the neurological prognosis after aSAH. However, other reports indicate that even when clazosentan or nimodipine are administered for prophylaxis against delayed neurological decline, patients treated with increased colloid administration or hypertonic saline (3% sodium chloride) load exhibit poor functional outcome and higher mortality, suggesting that extra fluid and sodium derived from prophylactic colloid administration contribute to negative outcomes after aSAH. Pharmacological treatments such as clazosentan in addition to perioperative management involving delivery of less water and sodium might be crucial for achieving better outcomes than conventional therapy. Based on a literature review, we present here the future perspectives regarding clazosentan and the necessity for modifying management of the water-electrolyte balance by focusing on endothelin-1 and blood–brain barrier disruption.

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. [ABSTRACT FROM AUTHOR]

Magnesium sulfate (MgSO 4) is a potential neuroprotective agent for patients with aneurysmal subarachnoid hemorrhage (SAH). We analyzed the effect of early application of intraoperative intravenous MgSO 4 and compared cerebral vasospasm (CV), delayed cerebral ischemia (DCI), and neurological outcome in 2 patient cohorts. A retrospective matched-pair analysis from patients at a single center in Germany was performed without (group A) and with (group B) MgSO 4 application <24 hours after diagnosis. Pairs were matched according to the known risk factors for DCI and CV (age, Fisher grade, smoking, severity of SAH). Incidence of CV and DCI and neurological outcome using the modified Rankin Scale score 3 and 12 months after SAH were recorded. The inclusion criteria were met by 196 patients. After risk stratification, 48 patients were included in the final analysis (age 54.2 ± 8.1 years; 30 women and 18 men) and were assigned to group A (n = 24) or group B (n = 24). CV occurred less frequently in group B (33%) than in group A (46%). Likewise, DCI was present in 13% in group B compared with 42% in group A. After 12 months, 22 patients in group B had a favorable functional outcome (modified Rankin Scale score 0–3) compared with 15 patients in group A. In this study, the incidence of CV and DCI was lower in patients receiving intravenous MgSO 4 within 24 hours after aneurysmal SAH onset. Favorable functional outcome was more likely in the MgSO 4 group after 12 months of follow-up. [ABSTRACT FROM AUTHOR]

To explore the predictive value of transcranial Doppler ultrasound (TCD) combined with quantitative electroencephalogram (QEEG) in delayed cerebral ischemia (DCI) caused by aneurysmal subarachnoid hemorrhage (aSAH). The participants were 105 patients with aSAH treated from June 2020 to December 2022. Patients were divided into DCI group (n = 34) and non-DCI group (n = 71) according to the presence of DCI 14 days after onset. Further comparison was conducted on the baseline data as well as the parameters of QEEG and TCD within 24 hours after admission. Multivariate logistic analysis was performed to investigate risk factors related to DCI within 14 days of admission in aSAH patients. There were significant differences in the comparison of the proportion of Hunt-Hess grading, relative δ power (RDP), relative α power (RAP), relative α/ β power ratio (ADR), as well as peak systolic velocity (Vs), mean blood flow velocity (MBFV) and pulsatility index (PI) of middle cerebral artery between the two groups (P < 0.05). Furthermore, Logistic regression analysis revealed that ADR (odds ratio 1.668, 95% CI 1.369–4.345) and MBFV of middle cerebral artery (odds ratio 3.279, 95% CI 2.332–6.720) were risk factors for the occurrence of DCI in aSAH patients (P < 0.05). In addition, evaluation of the predictive value revealed that combined use of the 2 indicators showed the highest predictive value (area under the curve 0.959, 95% CI 0.896–0.993). Patients with aSAH complicated by DCI have relatively higher MBFV of middle cerebral artery and ADR. Combined use of the 2 indicators can provide reference for early prediction of DCI in aSAH patients. [ABSTRACT FROM AUTHOR]

Background: The relationship of fibrin(ogen) degradation products (FDPs) and potassium with the functional outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) is still uncertain. This study aims to evaluate the predictive value of a novel combination biomarker, the FDP-to-potassium ratio (FPR), for poor functional outcomes in patients with aSAH. Methods: A total of 425 consecutive patients with aSAH at a single center were retrospectively enrolled in our study. An unfavorable outcome was defined as a modified Rankin Scale (mRS) score of 3–6 at 3 months after discharge. Univariate analysis and multivariable logistic regression were performed for baseline information and laboratory parameters recorded at admission. In addition, the receiver operating characteristic curve was plotted, and propensity score matching was performed based on the FPR. Results: On the basis of mRS grade, 301 patients were classified as having favorable outcomes, and 124 patients were assessed as having unfavorable outcomes. FPR levels were significantly correlated with mRS grade (r[Spearman] = 0.410; P < 0.001). Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.016–1.071; P = 0.002), white blood cell count (OR 1.150, 95% CI 1.044–1.267; P = 0.005), potassium (OR 0.526, 95% CI 0.291–0.949; P = 0.033), World Federation of Neurosurgical Societies grade (OR 1.276, 95% CI 1.055–1.544; P = 0.012), and FPR (OR 1.219, 95% CI 1.102–1.349; P < 0.001) at admission were independently associated with poor functional outcomes. The DeLong test showed that the area under the receiver operating characteristic curve of FPR was higher than that of age, white blood cell count, potassium, World Federation of Neurosurgical Societies grade, or FDP alone, indicating that FPR had better predictive potential than these other variables. After 1:1 propensity score matching (FPR ≥ 1.45 vs. FPR < 1.45), the rate of poor prognosis was still significantly increased in the high-FPR group (48/121 [39.7%] vs. 16/121 [13.2%], P < 0.001). Conclusions: Fibrin(ogen) degradation product-to-potassium ratio is an independent predictor of poor outcomes for patients with aSAH and may be a promising tool for clinicians to evaluate patients' functional prognosis. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to develop a nomogram that integrates clinical and radiological data obtained from computed tomography (CT) scans, enabling the prediction of chronic hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH). Method: A total of 318 patients diagnosed with subarachnoid hemorrhage (SAH) and admitted to the Department of Neurosurgery at the Affiliated People's Hospital of Jiangsu University between January 2020 and December 2022 were enrolled in our study. We collected clinical characteristics from the hospital's medical record system. To identify risk factors associated with chronic hydrocephalus, we conducted both univariate and LASSO regression models on these clinical characteristics and radiological features, accompanied with penalty parameter adjustments conducted through tenfold cross-validation. All features were then incorporated into multivariate logistic regression analyses. Based on these findings, we developed a clinical-radiological nomogram. To evaluate its discrimination performance, we conducted Receiver Operating Characteristic (ROC) curve analysis and calculated the Area Under the Curve (AUC). Additionally, we employed calibration curves, and utilized Brier scores as an indicator of concordance. Additionally, Decision Curve Analysis (DCA) was performed to determine the clinical utility of our models by estimating net benefits at various threshold probabilities for both training and testing groups. Results: The study included 181 patients, with a determined chronic hydrocephalus prevalence of 17.7%. Univariate logistic regression analysis identified 11 potential risk factors, while LASSO regression identified 7 significant risk factors associated with chronic hydrocephalus. Multivariate logistic regression analysis revealed three independent predictors for chronic hydrocephalus following aSAH: Periventricular white matter changes, External lumbar drainage, and Modified Fisher Grade. A nomogram incorporating these factors accurately predicted the risk of chronic hydrocephalus in both the training and testing cohorts. The AUC values were calculated as 0.810 and 0.811 for each cohort respectively, indicating good discriminative ability of the nomogram model. Calibration curves along with Hosmer-Lemeshow tests demonstrated excellent agreement between predicted probabilities and observed outcomes in both cohorts. Furthermore, Brier scores (0.127 for the training and 0.09 for testing groups) further validated the predictive performance of our nomogram model. The DCA confirmed that this nomogram provides superior net benefit across various risk thresholds when predicting chronic hydrocephalus. The decision curve demonstrated that when an individual's threshold probability ranged from 5 to 62%, this model is more effective in predicting the occurrence of chronic hydrocephalus after aSAH. Conclusion: A clinical-radiological nomogram was developed to combine clinical characteristics and radiological features from CT scans, aiming to enhance the accuracy of predicting chronic hydrocephalus in patients with aSAH. This innovative nomogram shows promising potential in assisting clinicians to create personalized and optimal treatment plans by providing precise predictions of chronic hydrocephalus among aSAH patients. [ABSTRACT FROM AUTHOR]