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.

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.

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.

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.

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.

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.

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.

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).
CONCLUSIONS: 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.

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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.