Prognostic significance of fibrinogen and neutrophil/lymphocyte ratio score and D-dimer/Albumin ratio for prognosis in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Recent research indicates that systemic inflammation significantly affects the overall prognosis of individuals with aneurysmal subarachnoid hemorrhage. To delve deeper into this issue, a retrospective study was undertaken. The study aimed to investigate the relationship between fibrinogen and neutrophil/lymphocyte ratio scores, D-dimer/Albumin ratios, and the Glasgow Outcome Scale at 6 months post-discharge for patients with aSAH. METHODS: A retrospective analysis was conducted on 321 patients who experienced aneurysmal subarachnoid hemorrhage. These patients were monitored using the Glasgow Outcome Scale six months after being discharged from Huizhou Central People's Hospital. Patients with GOS scores between 1 and 3 were classified as having a poor prognosis, while those with scores ranging from 4 to 5 were considered to have a good prognosis. To create distinct sets, patients were randomly divided into both training and validation groups. The best cut-off value for the D-dimer/Albumin ratio was established through ROC curves, and the scores for fibrinogen and the neutrophil/lymphocyte ratio were calculated. Utilizing multivariate logistic regression analysis, independent risk factors linked to an unfavorable prognosis in aSAH patients were identified. A nomogram model was developed and validated based on these findings, providing an improved approach for evaluating the prognostic influence of risk factors. To gauge the model's predictive performance, several analytical tools such as ROC curves, calibration curves, and decision curve analysis were employed. This comprehensive approach ensured a thorough assessment of the prognostic prediction capabilities of the model. RESULTS: Multivariate regression analysis revealed that Age (OR=3.87, 95%CI=1.54-9.73, p=0.004), Pneumonia (OR=3.54, 95%CI=1.41-8.86, p=0.007), WFNS (OR=3.24, 95%CI=1.23-8.54, p=0.017), DAR (OR=2.88, 95%CI=1.13-7.34, p=0.027), and F-NLR (OR=3.12, 95%CI=1.22-7.97, p=0.017) were identified as independent risk factors influencing the prognosis of patients with aSAH. Additionally, the area under the ROC curve was 0.866 (95%CI=0.805-0.927) for the training set and 0.924 (95%CI=0.849-0.999) for the validation set. The calibration curve analysis demonstrated a minor error of 0.02 for the training set and 0.051 for the validation set. Furthermore, both the training set and validation set displayed significant clinical benefits according to the DCA curves, underscoring the meaningful utility of the developed nomogram. CONCLUSIONS: Fibrinogen and neutrophil/lymphocyte ratio scores, and the D-dimer/Albumin ratio emerged as significant independent risk factors for prognosticating the outcomes of patients with aSAH. Leveraging these factors, a robust nomogram model was meticulously developed, showcasing its impressive precision in prognostic predictions. These results underscore the promising clinical applicability of these biomarkers as effective prognostic indicators for individuals afflicted by aSAH.

Regulation of FOXO3 on neuronal ferroptosis after intracerebral hemorrhage via modulating NOX4 transcription.

INTRODUCTION: Intracerebral hemorrhage (ICH) is known to trigger neuronal ferroptosis while forkhead box O3 (FOXO3) is implicated in ICH. This study aimed to determine the specific effect of FOXO3 on neuronal ferroptosis after ICH. METHODS: The ICH mouse model was established through the injection of bacterial collagenase type IV and the cell model was established in Hemin-induced HT-22 cells. Subsequently, neurological functions, brain water content, and histopathological changes in mice were assessed. HT-22 cell activity was examined via cell counting kit-8 (CCK-8) method, and the levels of FOXO3, NADPH oxidase 4 (NOX4), and glutathione peroxidase 4 (GPX4) in brain tissues and HT-22 cells were measured. Fe2+ concentration and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) in the tissues and cells were examined. The binding relationship between FOXO3 and the NOX4 promoter region was determined via chromatin-immunoprecipitation (Ch-IP). Rescue experiments were designed to probe the role of NOX4 in the regulation of FOXO3 on neuronal ferroptosis. RESULTS: FOXO3 was highly-expressed in ICH models while silencing FOXO3 alleviated brain damage, edema, and inflammatory infiltration in ICH mice. Meanwhile, silencing FOXO3 enhanced cell activity, diminished ROS and MDA activities and Fe2+ concentration, and elevated GSH and GPX4 levels in the tissues or cells. FOXO3 could bind to the NOX4 promoter and upregulate NOX4 transcription. NOX4 overexpression partially neutralized the repressive role of silencing FOXO3 in neuronal ferroptosis. CONCLUSION: Silencing FOXO3 attenuated ICH-induced neuronal ferroptosis via down-regulating NOX4 transcription levels, thus ameliorating post-ICH brain damage.

Systemic immune inflammatory index is an independent predictor for the requirement of decompressive craniectomy in large artery occlusion acute ischemic stroke patients after mechanical thrombectomy.

Background and purpose: Following mechanical thrombectomy (MT), patients with large artery occlusive acute ischemic stroke (LAO-AIS) often have cerebral herniation due to its complications, resulting in poor prognosis. Decompressive craniectomy (DC) can markedly improve patient prognosis. This study aimed to verify the predictive value of clinical parameters such as the systemic immune-inflammatory index (SII) for DC in patients with LAO-AIS after MT. Methods: Clinical data of a total of 173 patients with LAO-AIS treated with MT between January 2020 and January 2022 were retrospectively analyzed. Patients receiving DC were grouped into an experimental group or a control group (no DC). The patients were randomly divided into the training set (n = 126, 75%) and validation set (n = 43, 25%). Multivariate logistic regression was used to construct a nomogram predictive model. Results: The SII value in the experimental group (median: 2851.1×109/L) was significantly higher than that in the control group (median: 1898.6 × 109/L) (P = 0.019). Receiver operating characteristic (ROC) analyses showed that the best cutoff value of the SII was 2505.7 × 109/L with a sensitivity of 55%, a specificity of 75.8%, and an area under the curve (AUC) of 0.649. Multivariate logistic regression indicated that the SII was an independent predictor for performing DC in patients with LAO-AIS after MT (OR = 3.579, 95% CI = 1.360-9.422, P = 0.01). The AUC was 0.728 in the training set and 0.583 in the validation set. The average error of the calibration curve was 0.032 in the training set and 0.023 in the validation set. The average error was relatively small and consistent in the training set and validation set. The C-index of the nomogram was 0.804 suggesting good accuracy. Conclusions: The SII at admission is an independent predictor for the requirement of DC in patients with LAO-AIS after MT. The SII-based nomogram helps doctors make decisions on whether DC is needed timely and rationally, and thereby may improve the prognosis of these patients.

To clip or to coil for unruptured intracranial aneurysm?: A protocol of randomized controlled trial.

INTRODUCTION: Microsurgical clipping and endovascular coiling are the main methods against unruptured intracranial aneurysm (UIA). The craniotomy of surgical clipping may increase the risk of cerebrospinal fluid leakage and infection, damage the brain tissue, produce excessive stimulation to the nerves and blood vessels around the aneurysm, and cause the corresponding neurological deficit. Endovascular coiling could significantly reduce the mortality and disability rate than surgical clipping technique, which made endovascular coiling to become the first choice for the treatment of UIA. However, the long-term results showed attenuated favorable outcomes of coiling over clipping, so it is still in debate whether to clip or to coil. Therefore, we try to conduct a randomized, controlled, prospective trial to assess the long term safety of endovascular coiling therapy against UIA compared with microsurgical clipping technique. METHODS: Parallel-group randomization (1:1) is generated through the random number generator in Microsoft Excel 2010. In this trial, blinding to patients, physicians, and outcome assessors is not possible. Endovascular coiling or surgical clipping will be performed once for each patient in treatment group or control group, respectively. The mRS, overall mortality rate, disability rate, morbidity rate, and occurrence of a major aneurysm recurrence measured at 6 month and 1 year will be recorded. CONCLUSIONS: The findings will be helpful for the choice of endovascular coiling or surgical clipping by assessing the long term efficacy and safety of both operations against UIA. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/QYE9F.

A new modified dura mater implant: characteristics in recipient dogs.

Duraplasty is critical to the maintenance of anatomical integrity and the protection of brain tissue. Allotransplantation of cadaveric dura mater was abandoned after it was found to transmit Creutzfeldt-Jakob disease (CJD). In this study, the usefulness of a xenogeneic dura mater for dural reconstruction was tested. Twelve dogs were randomly assigned to 4 groups. To simulate the condition of patients with brain surface injury, an area of approximately 2 cm x 1.5 cm of the dura mater was removed to create a defect. Xenogeneic dura mater derived from porcine pericardium was trimmed to the shape and size of the defect and sutured to the endogenous dura mater. Muscles at the apex of the skull and scalp were also sutured. Three dogs were euthanized at 3, 6, 9, and 12 months after implantation and the xenogeneic dura mater and surrounding endogenous tissue were examined macroscopically and microscopically. Three months after implantation, the graft site had begun to heal. Macroscopically, at 6, 9, and 12 months after implantation, the graft had healed completely with the surrounding tissue. No boundary between the graft and surrounding tissue was distinguishable, and the two could not be separated. The graft was smoothly epithelialized and nonadherent to the brain surface. Microscopically, the inner surface of the implant was covered with epithelial cells, and internal capillaries, subepithelial fibrous tissue deposition, and fibroblast proliferation were observed. The xenogeneic dura mater progressively degraded over time. No cysts and no neutrophilic or lymphocytic inflammatory cell response developed between the implant and the recipient brain parenchyma. The modified xenogeneic dura mater is sufficiently biocompatible to allow epithelialization of its inner surface without adherence to brain tissue. No abnormalities develop in recipients, and the xenograft is gradually biodegraded and replaced by endogenous tissue identical to the endogenous dura mater.