Construction and verification of risk predicting models to evaluate the possibility of hydrocephalus following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Hydrocephalus following a ruptured aneurysm portends a poor prognosis. The authors aimed to establish a nomogram to predict the risk of hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A total of 421 patients with aSAH who were diagnosed by digital subtraction angiography in The General Hospital of Northern Theater Command center from January 2020 to June 2021 were screened to establish the training cohort. An additional 135 patients who enrolled between July 2021 and May 2022 were used for the validation cohort. Variate difference analysis and stepwise logistic regression (model A) and univariate and multivariate logistic regressions (model B) were respectively used to construct two models. Then, the net reclassification improvement (NRI), integrated discrimination improvement (IDI), and receiver operating characteristic (ROC) curve were used to compare the predictive abilities of the two models. Finally, two nomograms were constructed and externally validated. RESULTS: After screening, 556 patients were included. The area under the ROC curve of models A and B in the training cohort were respectively 0.884 (95 % confidence interval [CI]: 0.847-0.921) and 0.834 (95 % CI: 0.787-0.881). The prediction ability of the model A was superior to model B (NRI > 0, IDI > 0, p < 0.05). The C-index of models A and B was 0.8835 and 0.8392, respectively. Regarding clinical usefulness, the two models offered a net benefit with a threshold probability of between 0.12 and 1 in the decision curve analysis, suggesting that the two models can accurately predict hydrocephalus events. CONCLUSIONS: Both models have good prediction accuracy. Compared with model B, model A has better discrimination and calibration. Further, the easy-to-use nomogram can help neurosurgeons to make rapid clinical decisions and apply early treatment measures in high-risk groups, which ultimately benefits patients.

High-altitude cerebral hypoxia promotes mitochondrial dysfunction and apoptosis of mouse neurons.

Introduction: Neuronal cell death is an important factor in the pathogenesis of acute high-altitude cerebral hypoxia; however, the underlying molecular mechanism remains unclear. In this study, we tested if high-altitude hypoxia (HAH) causes neuronal death and mitochondrial dysfunction using various in vivo and in vitro approaches. Methods: Acute high-altitude cerebral hypoxia was induced by hypobaric hypoxia chamber in male mice. we explored the mechanisms of neuronal cell death using immunofluorescence, western blotting, transmission electron microscopy, and flow cytometry. Next, mitochondrial function and morphology were observed using Jc-1 staining, seahorse assay, western blotting, MitoTracker staining, and transmission electron microscopy. Moreover, open field test, elevated plus test, and Morris water maze were applied for animal behavior. Results: Results revealed that HAH disrupted mitochondrial function and promoted neuronal apoptosis and necroptosis both in HT-22 cells and in mouse hippocampal neurons. Moreover, the mitochondrial membrane potential and adenosine triphosphate production decreased in neurons after HAH, while oxidative stress and mitochondrial fission increased. Behavioral studies suggested that HAH induced anxiety-like behavior and impaired spatial memory, while it had no effect on athletic ability. Discussion: These findings demonstrated that HAH promotes mitochondrial dysfunction and apoptosis of mouse neurons, thus providing new insights into the role of mitochondrial function and neuronal cell death in acute high-altitude cerebral hypoxia.

The role of dynamin-related protein 1 in cerebral ischemia/hypoxia injury.

Mitochondrial dysfunction, especially in terms of mitochondrial dynamics, has been reported to be closely associated with neuronal outcomes and neurological impairment in cerebral ischemia/hypoxia injury. Dynamin-related protein 1 (Drp1) is a cytoplasmic GTPase that mediates mitochondrial fission and participates in neuronal cell death, calcium signaling, and oxidative stress. The neuroprotective role of Drp1 inhibition has been confirmed in several central nervous system disease models, demonstrating that targeting Drp1 may shed light on novel approaches for the treatment of cerebral ischemia/hypoxia injury. In this review, we aimed to highlight the roles of Drp1 in programmed cell death, oxidative stress, mitophagy, and mitochondrial function to provide a better understanding of mitochondrial disturbances in cerebral ischemia/hypoxia injury, and we also summarize the advances in novel chemical compounds targeting Drp1 to provide new insights into potential therapies for cerebral ischemia/hypoxia injury.

Clinical effectiveness of nimodipine for the prevention of poor outcome after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

Objective: In clinical practice, nimodipine is used to control cerebral vasospasm (CVS), which is one of the major causes of severe disability and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the exact efficacy of nimodipine use for patients with aSAH is still controversial due to the lack of sufficient and up-to-date evidence. Methods: In this meta-analysis, the latest databases of the Cochrane Central Register of Controlled Trials, PubMed-Medline, Web of Science, Embase, Scopus, and OVID-Medline were comprehensively searched for retrieving all randomized controlled trials (RCTs) regarding the efficacy of nimodipine in patients with aSAH. The primary outcome was a poor outcome, and the secondary outcomes were mortality and cerebral vasospasm (CVS). After detailed statistical analysis of different outcome variables, further evidence quality evaluation and recommendation grade assessment were carried out. Results: Approximately 13 RCTs met the inclusion criteria, and a total of 1,727 patients were included. Meta-analysis showed that a poor outcome was significantly reduced in the nimodipine group [RR, 0.69 (0.60-0.78); I2 = 29%]. Moreover, nimodipine also dramatically decreased the mortality [RR, 0.50 (0.32-0.78); I2 = 62%] and the incidence of CVS [RR, 0.68 (0.46-0.99); I2 = 57%]. Remarkably, we found a poor outcome and mortality were both significantly lower among patients with aSAH, with the mean age < 50 than that mean age ≥ 50 by subgroup analysis. Furthermore, the evidence grading of a poor outcome and its age subgroup in this study was assessed as high. Conclusion: Nimodipine can significantly reduce the incidence of a poor outcome, mortality, and CVS in patients with aSAH. Moreover, we strongly recommend that patients with aSAH, especially those younger than 50 years old, should use nimodipine as early as possible in order to achieve a better clinical outcome, whether oral medication or endovascular direct medication. Systematic review registration: www.york.ac.uk/inst/crd, identifier: CRD42022334619.

Tumor necrosis factor-stimulated gene-6-a new serum identification marker to identify severe and symptomatic carotid artery stenosis.

BACKGROUND: The main pathological change causing carotid artery stenosis is atherosclerosis, and studies suggest that tumor necrosis factor-stimulated gene-6 (TSG-6) has an anti-atherogenic effect and may be a new target for the diagnosis of carotid artery stenosis disease. We hypothesized that serum TSG-6 levels might also be associated with carotid artery stenosis. The aim of this study was to evaluate the diagnostic significance and potential predictive value of serum TSG-6 levels in patients with severe carotid artery stenosis and symptomatic stenosis. METHODS: Serum TSG-6 levels were measured in 96 patients with carotid stenosis and 40 sex and age matched control healthy subjects. The expression of TSG-6 in carotid plaques (4 severe stenoses, 4 moderate stenoses, and 4 mild stenoses) and 4 superficial temporal artery vascular tissues of 12 patients with carotid stenosis who underwent endarterectomy at our hospital were detected by Western blot. Histological analysis of carotid plaque and superficial temporal artery tissues was also performed. RESULTS: Compared with controls, serum TSG-6 levels were higher in patients with carotid stenosis, TSG-6 expression was increased in tissues with moderate and severe stenosis, and TSG-6 expression was significantly higher in the fibrous cap component of the plaque than in the non-fibrous cap component. Serum TSG-6 levels were higher in patients with symptomatic stenosis than in patients with asymptomatic stenosis. Tissue TSG-6 staining levels and serum TSG-6 levels were positively correlated (r = 0.694, p < 0.05) and tissue TSG-6 staining levels were positively correlated with macrophage staining levels (r = 0.932, p < 0.05). Logistic regression analysis showed that serum TSG-6 was an independent factor for the presence of severe carotid stenosis and symptomatic stenosis in patients (p < 0.001). Serum TSG-6 levels were more diagnostically efficient than other indices in identifying severe and symptomatic carotid stenosis (p < 0.05), especially in identifying symptomatic stenosis (p < 0.01). We further significantly increased the diagnostic power of symptomatic stenosis using a combined model of serum TSG-6 and homocysteine (p < 0.05). CONCLUSIONS: Serum TSG-6 may serve as a new non-invasive and easily measured biomarker to better screen people with severe and symptomatic carotid stenosis in clinical practice.

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis.

BACKGROUND: Nivolumab is the human programmed cell death-1 (PD-1)-blocking antibody showing significant effect in many refractory cancers. However, little is known about its risks of hematological toxicities, rare but clinically serious and potentially life-threatening adverse events. We want to explore whether nivolumab can increase the risks of hematological toxicities compared with other immunotherapy or chemotherapy drugs. METHOD: The databases of PubMed, Embase, Web of science, and CNKI were searched. We used the medical subject heading terms "Nivolumab" plus keyword "Nivolumab" to search studies published from August 1990 to October 2021. For the included articles, we calculated the relative risks and the corresponding 95% confidence intervals (CIs) for the risks of anemia, neutropenia, and leukopenia in patients treated with nivolumab versus control drugs. RESULTS: Five original articles on the nivolumab trials were identified with 2399 patients enrolled in this meta-analysis. The relative risks of anemia, neutropenia, and leukopenia were 0.343 (95% CI: 0.177-0.663; P = .001), 0.020 (95% CI: 0.008-0.053; P = .000), and 0.054 (95% CI: 0.015-0.191; P = .000), respectively. CONCLUSION: The PD-1 inhibitor-nivolumab did not increase the risk of anemia, neutropenia and leukopenia. It may enhance awareness about lower risks of hematological toxicities when choosing nivolumab as PD-1 inhibitor among clinicians.