The Effectiveness of Target Temperature Management on Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk (RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, p = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, p = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.

Targeted Temperature Management for Poor Grade Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.

OBJECTIVE: We assessed the effectiveness and safety of target temperature management (TTM) in treating patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). The primary objective was to evaluate the neurological outcome at 3 months. Secondary objectives were to assess mortality, delayed cerebral ischemia, cerebral edema, hydrocephalus, midline shift, and laboratory indicators related to TTM. METHODS: A single-blind, nonrandomized controlled trial was conducted. After admission, patients with poor-grade aSAH (Hunt-Hess scores IV âˆ¼ V) were assigned to a TTM group or a control group in a 1:1 ratio. TTM with core temperatures ranging from 36°C to 37°C was performed immediately and maintained until microclipping or endovascular embolization. Subsequently, rapid induction to 33°C ∼ 35°C was carried out and maintained for 3 to 5 days. Then, the patients underwent slow rewarming to 36°C ∼ 37°C and maintained at that temperature for a minimum of 48 hours. RESULTS: Sixty patients (30 treated with TTM and 30 with standard treatment) were included in the study. At 3 months, a favorable prognosis (modified Rankin scale score 0 to 3) was significantly higher in the TTM group than in the control group (n = 14, 46.7% vs. n = 6, 20.0%, P = 0.028). Adjusted multivariate logistics regression analysis indicated that TTM (odds ratio = 0.20, 95% confidence interval: 0.05-0.77, P = 0.019) reduced the number of unfavorable prognoses 3 months after admission. CONCLUSIONS: This study demonstrated the effectiveness and safety of TTM in patients with poor-grade aSAH, and its implementation improved neurological outcomes. Multicenter randomized controlled studies with a large number of patients are needed to confirm these observations.

Effect of Sophocarpine on the Pharmacokinetics of Umbralisib in Rat Plasma Using a Novel UPLC-MS/MS Method.

Umbralisib is a dual inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ) and casein kinase 1 epsilon (CK1ε) for treating marginal zone lymphoma (MZL) and follicular lymphoma (FL). This study aimed to develop a fast and stable ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantitative analysis of umbralisib in rat plasma and its application for evaluating the effect of sophocarpine on the pharmacokinetics of umbralisib. A direct protein preparation with acetonitrile was used to deal with rat plasma. Umbralisib and duvelisib (internal standard, IS) were isolated on a Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile and 0.1% formic acid in water. The linear range was from 0.5 to 1,000 ng/ml. Both of the precision (RSD%) and accuracy (RE%) were less than 15% in a permissible range. The mean recovery and matrix effect of umbralisib were 86.3-96.2% and 97.8-112.0%, respectively. When umbralisib was combined with sophocarpine, AUC0→∞ of umbralisib was significantly reduced to 2462.799 ± 535.736 ng/ml•h from 5416.665 ± 1,451.846 ng/ml•h, and Cmax also was markedly diminished. Moreover, CLz/F was increased more than two times. This developed, optimized and technical UPLC-MS/MS method was extremely suitable for detecting the concentrations of umbralisib in rat plasma after an oral administration, and sophocarpine significantly changed the pharmacokinetics of umbralisib in rats. This obvious pharmacokinetic changes indicates that there seems to exist herb-drug interaction between sophocarpine and umbralisib.