BACKGROUND: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear.
METHODS: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed.
RESULTS: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively.
CONCLUSIONS: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L.
BACKGROUND: ClinicalTrials.gov ID: NCT02633358.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies.
METHODS: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature.
RESULTS: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24 hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects.
CONCLUSIONS: The impact of ECMO on an infant\'s nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes.
METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage.
RESULTS: Of the 3649 consecutive AVMs treated at the authors\' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97).
CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

BACKGROUND: Malnutrition is a common complication after stroke and may worsen neurological outcomes for patients. There are still no uniform tools for screening nutritional status for the patients with stroke. We aimed to explore the relationship between the baseline geriatric nutritional risk index (GNRI) and neurological function at the convalescence stage for patients with stroke and assessed the predictive value of the GNRI for adverse neurological outcomes.
METHODS: A total of 311 patients with stroke were enrolled retrospectively. Basic information and laboratory results on admission since onset of stroke were collected. The GNRI on admission was calculated and neurological outcomes evaluated by the Barthel index at 1 month after the onset of stroke. Statistical analyses, including correlation coefficient tests, multivariate regression analyses, and receiver operating characteristic (ROC) analyses, were applied in this study.
RESULTS: Compared with the good outcome group, the poor outcome group showed a significantly lower GNRI on admission (P < 0.05). GNRI was associated with Barthel index (r = 0.702, P < 0.01). The GNRI was independently correlated with the Barthel index (Standardization β = 0.721, P < 0.01) and poor outcome 0.885 (95% CIs, 0.855-0.917, P < 0.01) after adjusting for covariates. Compared with no nutritional risk grades (Q4), the OR of GNRI to poor neurological outcome increased across increasing nutritional risk grades of GNRI (OR = 2.803, 95% CIs = 1.330-5.909 in Q3, 7.992, 95% CIs = 3.294-19.387 in Q2 and 14.011, 95% CIs = 3.972-49.426 in Q1, respectively, P for trend < 0.001). The area under ROC curves (AUC) of the GNRI was 0.804, which was larger than that of the NIHSS, BMI, or Albumin (P < 0.01), with an optimal cut-off value of 97.69, sensitivity of 69.51% and specificity of 77.27%. Combined GNRI with NIHSS gained the largest AUC among all the variables (all P < 0.05), with an AUC of 0.855, sensitivity of 84.75 and specificity of 72.73%.
CONCLUSIONS: For patients with stroke, higher nutritional risk grades at baseline indicated worse neurological function at the convalescence stage. Compared with NIHSS, BMI, and Albumin, GNRI was a competitive indicator for the risk of poor neurological outcome. The predictive property of GNRI for adverse neurological outcomes might be more powerful when combined with NIHSS.

Cardiac injury and dysfunction following aneurysmal subarachnoid hemorrhage (aSAH) negatively impact the neurological outcomes. This study aimed to determine the association between N-terminal pro-brain-type natriuretic peptide (NT-pro BNP) levels at admission and neurological outcomes at six months in aSAH patients following endovascular treatment. Patients diagnosed with aSAH who underwent NT-pro BNP measurement at admission at our department between January 2018 and April 2021 were retrospectively analyzed. Neurological outcomes were evaluated based on the six-month modified Rankin Scale score. The associations between admission NT-pro BNP levels and neurological outcomes were investigated. In total, 471 patients were included in the analysis. The serum NT-pro BNP levels were significantly lower in patients with a favorable outcome than those with an unfavorable outcome. The area under the receiver operating characteristic curve (AUC) of NT-pro BNP was 0.687. The optimal cutoff value of serum NT-pro BNP level as a predictor of unfavorable outcome was 253.4 pg/mL. Multivariate analysis revealed that admission NT-pro BNP level of >253.4 pg/mL was significantly associated with unfavorable outcomes. After propensity score-matching, admission NT-pro BNP level of >253.4 pg/mL was an independent predictor of unfavorable outcomes. Admission NT-pro BNP level added a slight value to other clinical variables for the prediction of unfavorable outcomes (0.877 vs 0.871 in AUC, respectively; p = 0.084). In conclusion, higher admission NT-pro BNP levels were independently associated with six-month unfavorable outcomes in aSAH patients treated with endovascular treatment. However, it added only minor prognostic value to clinical information alone.

OBJECTIVE: To perform an updated meta-analysis to comprehensively assess the efficacy and safety of cilostazol in preventing aneurysmal subarachnoid hemorrhage (SAH)-related secondary complications.
METHODS: Electronic databases of PubMed, the Cochrane library, CNKI and Wanfang were searched on August 2021. Pooled odds ratio (OR) and standardized mean difference (SMD) were calculated for dichotomous and continuous outcomes, respectively.
RESULTS: A total of 14 studies [comprising 18,726 aneurysmal SAH patients (6654 in the cilostazol group and 12,072 in the control group)] performed in Japan or China were included. Compared with the control group, cilostazol treatment significantly reduced the median cerebral artery (SMD = -0.49; p < 0.001), improved the therapeutic efficacy (OR = 2.37; p = 0.009), decreased the incidence of symptomatic vasospasm/delayed cerebral ischemia (OR = 0.42; p < 0.001), severe angiographic vasospasm (OR = 0.54; p < 0.001), new cerebral infarction (OR = 0.33; p < 0.001), poor outcomes (OR = 0.86; p = 0.001), mortality (OR = 0.62; p < 0.001) and increased the incidence of no or mild angiographic vasospasm (OR = 1.94; p = 0.004), but did not induce more adverse events (OR = 1.08; p = 0.871). The mechanism of cilostazol treatment was to inhibit the production of tenascin-C (SMD = -1.46; p < 0.001). These results were hardly changed by subgroup analysis.
CONCLUSIONS: This meta-analysis indicates cilostazol may be an effective and safe drug for aneurysmal SAH patients. However, further trials involving other world populations are required to demonstrate the generalization of treatment effects of cilostazol.

Electroacupuncture (EA) has been widely used for functional restoration after stroke. However, its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood. In this study, we applied EA to the Zusanli (ST36) and Quchi (LI11) acupoints in rats with middle cerebral artery occlusion and reperfusion. We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B, synapsin-1, postsynaptic dense protein 95, and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion. Moreover, EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra. Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA. These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion, possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway. All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine, China (approval No. PZSHUTCM200110002) on January 10, 2020.

Microvascular failure is one of the key pathogenic factors in the dynamic pathological evolution after traumatic brain injury (TBI). Our laboratory and others previously reported that Annexin A2 functions in blood-brain barrier (BBB) development and cerebral angiogenesis, and recombinant human Annexin A2 (rA2) protected against hypoxia plus IL-1β-induced cerebral trans-endothelial permeability in vitro, and cerebral angiogenesis impairment of AXNA2 knock-out mice in vivo. We thereby hypothesized that ANXA2 might be a cerebrovascular therapy candidate that targets early BBB integrity disruption, and subacute/delayed cerebrovascular remodeling after TBI, ultimately improve neurological outcomes. In a controlled cortex impact (CCI) mice model, we found rA2 treatment (1 mg/kg) significantly reduced early BBB disruption at 24 h after TBI; and rA2 daily treatment for 7 days augmented TBI-induced mRNA levels of pro-angiogenic and endothelial-derived trophic factors in cerebral microvessels. In cultured human brain microvascular endothelial cells (HBMEC), through MAPKs array, we identified that rA2 significantly activated Akt, ERK, and CREB, and the activated CREB might be responsible for the rA2-induced VEGF and BDNF expression. Moreover, rA2 administration significantly increased cerebral angiogenesis examined at 14 days and vessel density at 28 days after TBI in mice. Consistently, our results validated that rA2 significantly induced angiogenesis in vitro, evidenced by tube formation and scratched migration assays in HBMEC. Lastly, we demonstrated that rA2 improved long-term sensorimotor and cognitive function, and reduced brain tissue loss at 28 days after TBI. Our findings suggest that rA2 might be a novel vascular targeting approach for treating TBI.

Kernicterus is a severe complication of extreme neonatal hyperbilirubinemia. Prolonged exposure to high-level unconjugated bilirubin (UCB) directly damages brain tissue. Neuroinflammation is believed to contribute to UCB-induced neurotoxicity. Pyroptosis has been as a highly inflammatory form of programmed cell death. Therefore, this study aimed to explore whether pyroptosis was involved in the pathogenesis of UCB neurotoxicity in kernicterus model rats. VX-765, a specific inhibitor of caspase-1, was intraperitoneally administered to the model rats to observe its effects on the short-term and long-term outcomes of the model animals at the molecular, cellular, morphological, and behavioral levels. The results indicated that UCB significantly induced the activation of caspase-1 and gasdermin D(GSDMD), and VX-765 inhibited caspase-1-GSDMD pathway. Compared with those of the UCB group and the vehicle+UCB group, VX-765-treated rats released lower levels of IL-1β and IL-18. Furthermore, H&E and TUNEL staining showed that nerve cells in the VX-765-treated group were better preserved and had less DNA fragmentation. Most importantly, VX-765 improved both the short-term and long-term neurological functions of kernicterus model rats. This study demonstrated that pyroptosis was involved in the pathogenesis of kernicterus through caspase-1 activation, which could be inhibited by VX-765, exerting a neuroprotective effect in kernicterus model rats.

The aim of this meta-analysis was conducted to assess the effects of different doses of prophylactic rhEPO on neurodevelopmental outcomes and provide reference for rational drug use. The primary outcome was the number of infants with a Mental Developmental Index (MDI) <70 on the Bayley Scales of Infant Development. Five RCTs, comprising 2282 infants, were included in this meta-analysis. Overall, prophylactic rhEPO administration reduced the incidence of infants with an MDI <70, with an odds ratio (95% confidence interval) of 0.55 (0.38-0.79), P <0.05. The low-dose rhEPO subgroup was superior to the placebo subgroup, with an OR (95% CI) of 0.47 (0.25-0.87), P <0.05. However, high-dose rhEPO subgroup had no significant impact on MDI <70 in infants <28 weeks\' gestational age. The definitions of the secondary outcome showed that there was no significant effect of rhEPO on cerebral palsy. For neonatal complications, although four studies showed that there were no differences in the pooled results of BPD and ICH events between rhEPO treatment and placebo, the ICH events were significantly lower in the low-dose rhEPO (OR 0.36; 95% CI 0.23-0.59). In addition, in the pooled results of NEC and ROP events, there were significant differences between the two groups (OR 0.63; 95% CI 0.43-0.93) (OR 0.80; 95% CI 0.65-0.98). And the NEC events were significantly lower in the low-dose rhEPO (OR 0.45; 95% CI 0.27-0.73). Sustained low-dose prophylactic early erythropoietin might be more superior than high-dose for improvement of neurological outcomes and several neonatal complications in preterm infants.