Lower Serum Iron Level Predicts Postoperative Global Cerebral Edema Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Iron plays an important role in neuronal injury and edema formation after intracranial hemorrhage. However, the role of serum iron in aneurysmal subarachnoid hemorrhage (aSAH) is yet to be well-established. This study aims to identify whether serum iron could predict postoperative global cerebral edema (GCE) and poor outcome in aSAH. METHODS: 847 patients' aSAH clinical data were retrospectively collected at the First Affiliated Hospital of Fujian Medical University. Data on demographics, clinical characteristics, and laboratory values were collected and analyzed through univariate and multivariate analyses. Propensity score matching (PSM) analysis was performed to balance the baseline differences between the groups. RESULTS: The incidence of high-grade global cerebral edema (H-GCE) following aSAH was 12.99% (110/847). Serum iron levels [odds ratio (OR) = 1.143; 95% confidence interval (CI), (1.097-1.191); p < 0.001] were associated with the occurrence of H-GCE following aSAH in the univariate analysis. This association remained statistically significant even after adjusting for other variables in the multivariate model, with serum iron having an OR of 1.091 (95% CI, 1.043-1.141; p < 0.001) for GCE. After 1:1 PSM, serum iron levels ≤ 10.7 µmol/L remained a significant independent predictor of GCE (p = 0.002). The receiver operating characteristic (ROC) curve analysis determined that a serum iron cut-off value of ≤ 10.7 µmol/L was optimal for predicting H-GCE [Areas under the ROC curves (AUC) = 0.701, 95% CI, (0.669-0.732), p < 0.001; sensitivity, 67.27%; specificity, 63.77%] in patients with aSAH. Additionally, a trend was observed in which higher Hunt-Hess grades (HH grade) were associated with lower serum iron levels, and higher modified Fisher grades (mFisher grade) were associated with lower serum iron levels. In addition, the serum iron level was also associated with a 3-month functional neurological outcome (p < 0.001). CONCLUSIONS: The results of this study indicate that a decreased serum iron level serves as a clinically significant biomarker for the prediction of postoperative GCE and a poor outcome at 3-months in patients with aSAH.

Decreased SPTBN2 expression regulated by the ceRNA network is associated with poor prognosis and immune infiltration in low­grade glioma.

The majority of low-grade gliomas (LGGs) in adults invariably progress to glioblastoma over time. Spectrin ß non-erythrocytic 2 (SPTBN2) is detected in numerous tumors and is involved in tumor occurrence and metastasis. However, the specific roles and detailed mechanisms of SPTBN2 in LGG are largely unknown. The present study performed pan-cancer analysis for the expression and prognosis of SPTBN2 in LGG using The Cancer Genome Atlas and The Genotype-Tissue Expression. Western blotting was used to detect the amount of SPTBN2 between glioma tissues and normal brain tissues. Subsequently, based on expression, prognosis, correlation and immune infiltration, non-coding RNAs (ncRNAs) were identified that regulated SPTBN2 expression. Finally, tumor immune infiltrates associated with SPTBN2 and prognosis were performed. Lower expression of SPTBN2 was correlated with an unfavorable outcome in LGG. A significant correlation between the low SPTBN2 mRNA expression and poor clinicopathological features was observed, including wild-type isocitrate dehydrogenase status (P<0.001), 1p/19q non-codeletion (P<0.001) and elders (P=0.019). The western blotting results revealed that, compared with normal brain tissues, the amount of SPTBN2 was significantly lower in LGG tissues (P=0.0266). Higher expression of five microRNAs (miRs/miRNAs), including hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-34c-5p and hsa-miR-424-5p, correlated with poor prognosis by targeting SPTBN2 in LGG. Subsequently, four long ncRNAs (lncRNAs) [ARMCX5-GPRASP2, BASP1-antisense RNA 1 (AS1), EPB41L4A-AS1 and LINC00641] were observed in the regulation of SPTBN2 via five miRNAs. Moreover, the expression of SPTBN2 was significantly correlated with tumor immune infiltration, immune checkpoint expression and biomarkers of immune cells. In conclusion, SPTBN2 was lowly expressed and correlated with an unfavorable prognosis in LGG. A total of six miRNAs and four lncRNAs were identified as being able to modulate SPTBN2 in a lncRNA-miRNA-mRNA network of LGG. Furthermore, the current findings also indicated that SPTBN2 possessed anti-tumor roles by regulating tumor immune infiltration and immune checkpoint expression.

Highly parallel, wash-free, and ultrasensitive centrifugal droplet digital protein detection in sub-microliter blood.

The ability to efficiently detect low-abundance protein biomarkers in tiny blood samples is a significant challenge in clinical and laboratory settings. Currently, high-sensitivity approaches require specialized instrumentation, involve multiple washing steps, and lack the ability to parallelize, preventing their widespread implementation. Herein, we developed a parallelized, wash-free, and ultrasensitive centrifugal droplet digital protein detection (CDPro) technology that achieves a femtomolar limit of detection (LoD) of target proteins with sub-microliters of plasma. The CDPro combines two techniques, namely a centrifugal microdroplet generation device and a digital immuno-PCR assay. Miniaturized centrifugal devices enable emulsification of hundreds of samples within 3 minutes using a common centrifuge. The bead-free digital immuno-PCR assay not only eliminates the need for multistep washing, but also possesses ultra-high detection sensitivity and accuracy. We characterized the performance of CDPro using recombinant interleukins (IL-3 and IL-6) as example targets and reported a LoD of 0.0128 pg mL-1. We also quantified IL-6 from 7 human clinical blood samples using the CDPro with only 0.5 µL plasma, which showed excellent agreement with an existing clinical protein diagnostic system with 25 µL plasma from those samples (R2 = 0.98).

Optimal Timing of Cranioplasty and Predictors of Overall Complications After Cranioplasty: The Impact of Brain Collapse.

BACKGROUND: The optimal timing of cranioplasty (CP) and predictors of overall postoperative complications are still controversial. OBJECTIVE: To determine the optimal timing of CP. METHODS: Patients were divided into collapsed group and noncollapsed group based on brain collapse or not, respectively. Brain collapse volume was calculated in a 3-dimensional way. The primary outcomes were overall complications and outcomes at the 12-month follow-up after CP. RESULTS: Of the 102 patients in this retrospective observation cohort study, 56 were in the collapsed group, and 46 were in the noncollapsed group. Complications were noted in 30.4% (n = 31), 24 (42.9%) patients in the collapsed group and 7 (15.2%) patients in the noncollapsed group, with a significant difference ( P = .003). Thirty-three (58.9%) patients had good outcomes (modified Rankin Scale 0-3) in the collapsed group, and 34 (73.9%) patients had good outcomes in the noncollapsed group without a statistically significant difference ( P = .113). Brain collapse ( P = .005) and Karnofsky Performance Status score at the time of CP ( P = .025) were significantly associated with overall postoperative complications. The cut-off value for brain collapse volume was determined as 11.26 cm 3 in the receiver operating characteristic curve. The DC-CP interval was not related to brain collapse volume or postoperative complications. CONCLUSION: Brain collapse and lower Karnofsky Performance Status score at the time of CP were independent predictors of overall complications after CP. The optimal timing of CP may be determined by tissue window based on brain collapse volume instead of time window based on the decompressive craniectomy-CP interval.

Correction: Zhang et al. Admission Serum Iron as an Independent Risk Factor for Postoperative Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Matched Analysis. Brain Sci. 2022, 12, 1183.

We would like to submit the following corrections to our recently published paper [...].

Admission Serum Iron as an Independent Risk Factor for Postoperative Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Matched Analysis.

This study aimed to investigate the association between serum iron (SI) and postoperative delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively analyzed 985 consecutive adult patients diagnosed with aSAH. Demographic, clinical, and laboratory data were recorded. Univariate and multivariate analyses were employed to assess the association between SI and DCI. Propensity-score matching (PSM) analysis was implemented to reduce confounding. Postoperative DCI developed in 14.38% of patients. Lower SI upon admission was detected in aSAH patients with severe clinical conditions and severe aSAH. SI was negatively correlated with WFNS grade (r = −0.3744, p < 0.001) and modified Fisher (mFisher) grade (r = −0.2520, p < 0.001). Multivariable analysis revealed lower SI was independently associated with DCI [odds ratios (OR) 0.281, 95% confidence interval (CI) 0.177−0.448, p < 0.001], while WFNS grade and mFisher grade were not. The receiver-operating characteristics (ROC) curve analysis of SI for DCI gave an area under the curve (AUC) of 0.7 and an optimal cut-off of 7.5 µmol/L (95% CI 0.665 to 0.733, p < 0.0001). PSM demonstrated the DCI group had a significantly lower SI than the non-DCI group (10.91 ± 6.86 vs. 20.34 ± 8.01 µmol/L, p < 0.001). Lower SI remained a significant independent predictor for DCI and an independent poor prognostic factor of aSAH in multivariate analysis (OR 0.363, 95% CI 0.209−0.630, p < 0.001). The predictive performance of SI for poor outcome had a corresponding AUC of 0.718 after PSM. Lower SI upon admission is significantly associated with WFNS grade, mFisher grade, and predicts postoperative DCI and poor outcome at 90 days following aSAH.

Elevated Hexose-6-Phosphate Dehydrogenase Regulated by OSMR-AS1/hsa-miR-516b-5p Axis Correlates with Poor Prognosis and Dendritic Cells Infiltration of Glioblastoma.

Objective Glioblastoma (GBM), a type of malignant glioma, is the most aggressive type of brain tumor and is associated with high mortality. Hexose-6-phosphate dehydrogenase (H6PD) has been detected in multiple tumors and is involved in tumor initiation and progression. However, the specific role and mechanism of H6PD in GBM remain unclear. Methods We performed pan-cancer analysis of expression and prognosis of H6PD in GBM using the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Subsequently, noncoding RNAs regulating H6PD expression were obtained by comprehensive analysis, including gene expression, prognosis, correlation, and immune infiltration. Finally, tumor immune infiltrates related to H6PD and survival were performed. Results Higher expression of H6PD was statistically significantly associated with an unfavorable outcome in GBM. Downregulation of hsa-miR-124-3p and hsa-miR-516b-5p in GBM was detected from GSE90603. Subsequently, OSMR-AS1 was observed in the regulation of H6PD via hsa-miR-516b-5p. Moreover, higher H6PD expression significantly correlated with immune infiltration of dendritic cells, immune checkpoint expression, and biomarkers of dendritic cells. Conclusions The OSMR-AS1/ miR-516b-5p axis was identified as the highest-potential upstream ncRNA-related pathway of H6PD in GBM. Furthermore, the present findings demonstrated that H6PD blockading might possess antitumor roles via regulating dendritic cell infiltration and immune checkpoint expression.

Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis.

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.

Viral Haplotypes in COVID-19 Patients Associated With Prolonged Viral Shedding.

Background: Recently, more patients who recovered from the novel coronavirus disease 2019 (COVID-19) may later test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) again using reverse transcription-polymerase chain reaction (RT-PCR) testing. Even though it is still controversial about the possible explanation for clinical cases of long-term viral shedding, it remains unclear whether the persistent viral shedding means re-infection or recurrence. Methods: Specimens were collected from three COVID-19-confirmed patients, and whole-genome sequencing was performed on these clinical specimens during their first hospital admission with a high viral load of SARS-CoV-2. Laboratory tests were examined and analyzed throughout the whole course of the disease. Phylogenetic analysis was carried out for SARS-CoV-2 haplotypes. Results: We found haplotypes of SARS-CoV-2 co-infection in two COVID-19 patients (YW01 and YW03) with a long period of hospitalization. However, only one haplotype was observed in the other patient with chronic lymphocytic leukemia (YW02), which was verified as one kind of viral haplotype. Patients YW01 and YW02 were admitted to the hospital after being infected with COVID-19 as members of a family cluster, but they had different haplotype characteristics in the early stage of infection; YW01 and YW03 were from different infection sources; however, similar haplotypes were found together. Conclusion: These findings show that haplotype diversity of SARS-CoV-2 may result in viral adaptation for persistent shedding in multiple recurrences of COVID-19 patients, who met the discharge requirement. However, the correlation between haplotype diversity of SARS-CoV-2 virus and immune status is not absolute. It showed important implications for the clinical management strategies for COVID-19 patients with long-term hospitalization or cases of recurrence.

A Novel Titanium Cranioplasty Technique of Marking the Coronal and Squamosoparietal Sutures in Three-Dimensional Titanium Mesh as Anatomical Positioning Markers to Increase the Surgical Accuracy and Reduce Postoperative Complications.

Objective: The objective of this research is to modify the titanium cranioplasty (Ti-CP) technique to increase the surgical accuracy and preliminarily verify the effectiveness and safety of this improvement. Methods: We developed a novel technique of marking the coronal and squamosoparietal sutures in three-dimensional (3D) titanium mesh as anatomical positioning markers and designed a prospective trial in patients with a unilateral frontotemporoparietal skull defect. Patients were randomly divided into two groups by the presence or absence of the anatomical positioning markers, and the therapeutic effects of these two groups were compared. Results: Forty-four patients were included in this study, including 28 (64%) males and 16 (36%) females. The mean age was 44.8 ± 15.2 years (range, 13-75 years). Overall postoperative complication rate of the intervention group (18%) was significantly (P = 0.03) lower than the control group (50%). Surgical accuracy of the intervention group (97.8%) was significantly (P < 0.001) higher than the control group (94%). Visual analog scale for cosmesis (VASC) of the intervention group (8.4) was significantly (P < 0.001) higher than the control group (7). The overall postoperative complication rate was 34%. Multivariate analyses showed that surgical accuracy <95.8% (OR = 19.20, 95% CI = 3.17-116.45, P = 0.001) was significantly associated with overall postoperative complications. Independent predictor of overall postoperative complications was surgical accuracy (OR = 0.57, 95% CI = 0.40-0.82, P = 0.002). Conclusions: This novel technique for repairing frontotemporoparietal skull defects increases surgical accuracy, improves cosmetic prognosis, and reduces postoperative complications. Therefore, it is a safe and effective improvement for Ti-CP.

Acetylation Profiles in the Metabolic Process of Glioma-Associated Seizures.

Objective: We test the hypothesis that lysine acetylation is involved in the metabolic process of glioma-associated seizures (GAS). Methods: We used label-free mass spectrometry-based quantitative proteomics to quantify dynamic changes of protein acetylation between gliomas with seizure (CA1 group) and gliomas without seizure (CA2 group). Furthermore, differences of acetyltransferase and deacetylase expression between CA1 and CA2 groups were performed by a quantitative proteomic study. We further classified acetylated proteins into groups according to cell component, molecular function, and biological process. In addition, metabolic pathways and protein interaction networks were analyzed. Regulated acetyltransferases and acetylated profiles were validated by PRM and Western blot. Results: We detected 169 downregulated lysine acetylation sites of 134 proteins and 39 upregulated lysine acetylation sites of 35 proteins in glioma with seizures based on acetylome. We detected 407 regulated proteins by proteomics, from which ACAT2 and ACAA2 were the differentially regulated enzymes in the acetylation of GAS. According to the KEGG analysis, the upregulated acetylated proteins within the PPIs were mapped to pathways involved in the TCA cycle, oxidative phosphorylation, biosynthesis of amino acids, and carbon metabolism. The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, TCA cycle, and necroptosis. Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot. Conclusions: The data support the hypothesis that regulated protein acetylation is involved in the metabolic process of GAS, which may be induced by acetyl-CoA acetyltransferases.

Higher Serum Levels of Lactate Dehydrogenase Before Microsurgery Predict Poor Outcome of Aneurysmal Subarachnoid Hemorrhage.

Introduction: We explored whether higher preoperative serum levels of lactate dehydrogenase (LDH) predicted outcome 3 months after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH) treated using microsurgical clipping in our institution. Methods: Patients with aSAH treated at our institution between 2010 and 2018 were enrolled. The following parameters were recorded: age, sex, smoking and drinking history, medical history, Hunt-Hess and Fisher grades, aneurysm location, aneurysm size, surgical treatment, delayed cerebral ischemia (DCI), intracranial infection, hydrocephalus, pneumonia, and preoperative serum LDH levels within 24 h of aSAH. We investigated whether preoperative serum LDH levels were associated with Hunt-Hess grade, Fisher grade, and functional neurological outcome. Results: In total, 2,054 patients with aSAH were enrolled, 874 of whom were treated using microsurgical clipping. The average serum LDH level (U/L) was significantly lower in the good outcome group (180.096 ± 50.237) than in the poor outcome group (227.554 ± 83.002; p < 0.001). After propensity score matching, the average serum LDH level (U/L) was still lower in the good outcome group (205.356 ± 76.785) than in the poor outcome group (227.119 ± 86.469; p = 0.029). The area under the receiver operating characteristic (ROC) curve was 0.702 (95% confidence interval [CI]: 0.650-0.754; p < 0.001). Based on the ROC curve, the optimal cutoff value for serum LDH levels as a predictor of poor 3-month outcome (modified Rankin Scale score > 2) was 201.5 U/L. The results revealed that Hunt-Hess grade, Fisher grade, DCI, pneumonia, and serum LDH (>201.5 U/L) were significantly associated with poor outcome. After propensity score matching, serum LDH levels > 201.5 U/L were still considered an independent risk factor for poor outcome (odds ratio: 2.426, 95% CI = 1.378-4.271, p = 0.002). Serum LDH levels were associated with Hunt-Hess and Fisher grades and were correlated with functional neurological outcomes (p < 0.001). Conclusions: Our findings showed that higher preoperative serum levels of LDH correlated with Hunt-Hess grade, Fisher grade, and neurological functional outcome, and predicted the outcome of aSAH treated by microsurgical clipping at 3 months, which was involved in the related mechanisms of early brain injury and showed its potential clinical significance in patients with aSAH.

Structure and function of corticospinal projection originating from supplementary motor area.

PURPOSE: The importance of supplementary motor area (SMA) for motor function and compensation for primary motor area (M1) has received increased attention. METHODS: We used diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) to evaluate structure and function of corticospinal projection originating from SMA. Fibers of corticospinal projection originating from M1 (CST) and SMA (ACST) were analyzed. ACST originating from mesial SMA area formed separate white matter bundles leaving the anterior part of M1 area, which then entered the posterior limb of the internal capsule. Projection and overlap of both CST and ACST were detected on medulla. RESULTS: Fibers of contralesional ACST were more than that of ipsilesional ACST in patients with SMA tumors (p<0.05). In patients with SMA tumor, all patients experienced temporary akinesia postoperatively. Seven hundred forty-one fibers of ipsilateral ACST and no fibers of ipsilateral CST were detected in the patient with M1 glioma, while most of contralateral limb movement was preserved. MEP could be evoked by stimulating SMA area as well as M1 area. ACST originated from SMA area and projected to the medial medulla. CONCLUSION: SMA area and ACST integrity contributed to contralateral motor function and were a compensation for M1 lesion and damaged CST.

Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: An exploratory clinical trial.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.

Efficacy of Neuroendoscopic Treatment for Septated Chronic Subdural Hematoma.

Objective: Neuroendoscopic treatment is an alternative therapeutic strategy for the treatment of septate chronic subdural hematoma (sCSDH). However, the safety and efficacy of this strategy remain controversial. We compared the clinical outcomes of neuroendoscopic treatment with those of standard (large bone flap) craniotomy for sCSDH reported in our center. Furthermore, the safety and efficacy of the neuroendoscopic treatment procedure for sCSDH were evaluated. Methods: We retrospectively collected the clinical data of 43 patients (37 men and six women) with sCSDH who underwent either neuroendoscopic treatment or standard (large bone flap) craniotomy, such as sex, age, smoking, drinking, medical history, use of antiplatelet drugs, postoperative complications, sCSDH recurrence, length of hospital stay, and postoperative hospital stay. We recorded the surgical procedures and the neurological function recovery prior to surgery and 6 months following the surgical treatment. Results: The enrolled patients were categorized into neuroendoscopic treatment (n = 23) and standard (large bone flap) craniotomy (n = 20) groups. There were no differences in sex, age, smoking, drinking, medical history, antiplatelet drug use, postoperative complications, and sCSDH recurrence between the two groups (p > 0.05). However, the patients in neuroendoscopic treatment group had a shorter length of total hospital stay and postoperative hospital stay as compared with the standard craniotomy group (total hospital stay: 5.26 ± 1.89 vs. 8.15 ± 1.04 days, p < 0.001; postoperative hospital stay: 4.47 ± 1.95 vs. 7.96 ± 0.97 days, p < 0.001). The imaging and Modified Rankin Scale at the 6-month follow-up were satisfactory, and no sCSDH recurrence was reported in the two groups. Conclusions: The findings of this study indicate that neuroendoscopic treatment is safe and effective for sCSDH; it is minimally invasive and could be clinically utilized.

Treatments and outcomes of untreated cerebral cavernous malformations in China: study protocol of a nationwide multicentre prospective cohort study.

INTRODUCTION: The treatment decision and long-term outcomes of previously untreated cerebral cavernous malformation (U-CCM) are still controversial. Therefore, we are conducting a nationwide multicentre prospective registry study in China to determine the natural history and effect of surgical treatment on long-term outcomes in Chinese people with U-CCM. METHODS AND ANALYSIS: This study was started on 1 January 2018 and is currently ongoing. It is a cohort follow-up study across a 5-year period. Patients will be followed up for at least 3 years after inception. Patients with U-CCM will be enrolled from 24 Grade III, level A hospitals distributed all over China. The cohort size is estimated to be 1200 patients. Patients are registered in surgically treated group and conservatively treated group. Clinical characteristics, radiology information and laboratory data are prospectively collected using an electronic case report form through an electronic data capture system. The primary outcome of this study is poor clinical outcome at the last follow-up (modified Rankin Scale score >2 lasting at least 1 year). The secondary outcome includes symptomatic haemorrhage, drug refractory epilepsy, focal neurological deficits, morbidity and all-cause mortality during follow-up. Univariate and multivariate regression analysis will be performed to determine the risk factors for poor outcomes in all patients, and to estimate the effect of surgery. Life tables, Kaplan-Meier estimates, log-rank test and proportional hazards Cox regression will be used to analyse the follow-up data of conservatively treated patients to determine the natural history of U-CCM. Initial presentation and location of U-CCM are prespecified subgroup factors. ETHICS AND DISSEMINATION: The study protocol and informed consent form have been reviewed and approved by the Research Ethical Committee of First Affiliated Hospital of Fujian Medical University (FAHFMU-2018-003).Written informed consent will be obtained from each adult participant or from the guardian of each paediatric participant. The final results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03467295.

Invasive Pulmonary Aspergillosis in Adults With Avian Influenza A (H7N9) Pneumonia in China: A Retrospective Study.

Cases of severe influenza with Aspergillus infection are commonly reported in patients with severe influenza. However, the epidemiology, risk factors, and outcomes of invasive pulmonary aspergillosis (IPA) in patients with avian influenza A (H7N9) infection remain unclear. We performed a retrospective multicenter cohort study. Data were collected from patients with avian influenza A (H7N9) infection admitted to 17 hospitals across China from February 2013 through February 2018. We found that IPA was diagnosed in 18 (5.4%) of 335 patients; 61.1% of patients with IPA (11 of 18) were identified before or within 2 days after an H7N9 virus-negative result. The median hospital stays in patients with or without IPA were 23.5 and 18 days, respectively (P < .01), and the median intensive care unit stays, respectively, were 22 and 12 days (P < .01). Smoking in the past year and antibiotic use for >7 days before admission were independently associated with IPA (adjusted odds ratio [95% confidence interval], 6.2 [1.7-26] for smoking and 4.89 [1.0-89] for antibiotic use). These findings provided important insights into the epidemiology and outcomes of IPA in patients with H7N9 infection in China.

Reduced Admission Serum Fibrinogen Levels Predict 6-Month Mortality of Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To retrospectively analyze the relationship between fibrinogen levels and outcomes in poor-grade aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We recruited 66 patients with poor-grade aSAH who were treated by neurosurgical clipping between January 2010 and December 2015. Serum samples were taken immediately on admission. Baseline information, complications, and outcomes at 6 months were recorded. Univariate and multivariate logistic regression analyses were used to explore the relationship between fibrinogen levels and clinical outcomes. RESULTS: Nineteen men and 47 women were included; the average age was 57.2 years. The median of the admission serum fibrinogen level was 3.3 g/L. Of the 66 patients, 18 had died by 6 months after initial hemorrhage, whereas 48 patients survived. Multivariate analyses showed that Hunt and Hess grade V (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.06-14.20; P = 0.04) and admission serum fibrinogen level <2.5 g/L (OR, 6.15; 95% CI, 1.67-22.67; P = 0.006) were significantly associated with 6-month mortality. In addition, admission serum fibrinogen level was negatively correlated with delayed cerebral ischemia, and admission serum fibrinogen level <2.5 g/L (OR, 3.86; 95% CI, 0.99-15.09; P = 0.05) was also significantly associated with delayed cerebral ischemia. CONCLUSIONS: Patients with poor-grade aSAH with reduced admission fibrinogen level have a higher risk of delayed cerebral ischemia and 6-month mortality compared with those without. The admission serum fibrinogen level might be useful as a predictor and treatment target in patients with poor-grade sSAH who have undergone surgical treatment.

Prevalence of Enteropathogens in Outpatients with Acute Diarrhea from Urban and Rural Areas, Southeast China, 2010-2014.

Acute diarrhea is an important public health issue. Here, we focused on the differences of enteropathogens in acute diarrhea between urban and rural areas in southeast China. Laboratory- and sentinel-based surveillance of acute diarrhea (≥ 3 loose or liquid stools/24 hours) was conducted at 16 hospitals. Fecal specimens were tested for bacterial (Aeromonas sp., Campylobacter sp., diarrheagenic Escherichia coli, Plesiomonas shigelloides, non-typhoidal Salmonella, Shigella sp., Vibrio sp., and Yersinia sp.) and viral (adenovirus, astrovirus, Norovirus, Rotavirus, and Sapovirus) pathogens. Descriptive statistics were used. Between January 1, 2010, and December 31, 2014, 4,548 outpatients with acute diarrhea were enrolled (urban, n = 3,220; rural, n = 1,328). Pathogens were identified in 2,074 (45.6%) patients. Norovirus (25.7%), Vibrio parahaemolyticus (10.2%), enteroaggregative Escherichia coli (EAEC) (8.8%), group A Rotavirus (7.0%), and enterotoxigenic Escherichia coli (ETEC) (5.6%) were the most common pathogens. Enteropathogens were less common in urban than in rural areas (42.0% versus 54.4%, P < 0.001). In urban areas, EAEC and ETEC were more common in high-income than in middle-income regions. Interventions targeting the most common enteropathogens can substantially reduce the burden of acute diarrhea in southeast China.

Lower Serum Iron and Hemoglobin Levels are Associated with Acute Seizures in Patients with Ruptured Cerebral Aneurysms.

BACKGROUND AND OBJECTIVE: The aim of the study is to investigate the value of serum iron and hemoglobin levels for predicting acute seizures following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Clinical and laboratorial data from patients with ruptured intracranial aneurysms were collected in the retrospective study. Age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, serum potassium, sodium, calcium, phosphorus, and iron were collected. Acute seizures were determined as seizures within 1 week following aSAH. Propensity score matching (PSM) analyses were performed to correct imbalances in patient characteristics between seizure and non-seizure groups. RESULTS: A total of 760 patients were included. Incidence of acute seizures following aSAH was 6.4%. In the univariate analysis, significant differences were detected in age, admission Hunt-Hess grade, Fisher grade, hemoglobin, serum sodium, and serum iron between seizure and non-seizure groups. In multivariate logistic regression model, lower serum iron was considered as a risk factor for acute seizures (OR 0.182, 95% CI 0.084-0.393, p = 0.000), as well as lower hemoglobin (OR 0.977, 95% CI 0.962-0.993, p = 0.004) and higher serum sodium (OR 1.072, 95% CI 1.003-1.145, p = 0.039). After PSM, there were no significant differences in age, admission Hunt-Hess grade, Fisher grade, and serum sodium between seizure and non-seizure groups. The matched seizure group had lower serum iron and hemoglobin levels compared with the matched non-seizure group (p < 0.05). The optimal cutoff value for serum iron and hemoglobin levels as a predictor of acute seizure after aSAH was determined as 9.9 mmol/L (sensitivity was 81.63% and the specificity was 65.40%) and 119 g/L (sensitivity was 63.27% and the specificity was 70.18%), respectively. CONCLUSIONS: Serum iron and hemoglobin levels were inversely associated with a high risk of acute seizures following aSAH.