Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Pre-treatment of rapamycin transformed M2 microglia alleviates traumatic cervical spinal cord injury via AIM2 signaling pathway in vitro and in vivo.

BACKGROUND: Traumatic spinal cord injury (SCI) is still devastating. It was suggested that the inhibition of mTOR may alleviate neuronal inflammatory injury but its underlying mechanism remained to be elucidated. AIM2 (absent in melanoma 2) recruits ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 to form the AIM2 inflammasome, activate caspase-1, and elicit inflammatory responses. We designed this study to elucidate whether pre-treatments of rapamycin could suppress SCI induced neuronal inflammatory injury via AIM2 signaling pathway in vitro and in vivo. METHODS: We performed oxygen and glucose deprivation / re-oxygenation (OGD) treatment and rats clipping model to mimic neuronal injury after SCI in vitro and in vivo. Morphologic changes of injured spinal cord were detected by hematoxylin and eosin staining. The expression of mTOR, p-mTOR, AIM2, ASC, Caspase-1 and et al were analyzed by fluorescent staining, western blotting or qPCR. The polarization phenotype of microglia was identified by flow cytometry or fluorescent staining. RESULTS: We found BV-2 microglia without any pre-treatment cannot alleviate primary cultured neuronal OGD injury. However, pre-treated rapamycin in BV-2 cells could transform microglia to M2 phenotype and protects against neuronal OGD injury via AIM2 signaling pathway. Similarly, pre-treatment of rapamycin could improve the outcome of cervical SCI rats through AIM2 signaling pathway. CONCLUSIONS: It was suggested that resting state microglia pre-treated by rapamycin could protect against neuronal injury via AIM2 signaling pathway in vitro and in vivo. Pre-inhibition of mTOR pathway may improve neuronal protection after SCI.

Surgical outcomes of basilar invagination type B without atlantoaxial dislocation through simple posterior fossa decompression: a retrospective study of 18 cases.

BACKGROUND: Basilar invagination (BI) is a common disease in the craniocervical junction (CVJ) area. Posterior fossa decompression with/without fixation is a controversial surgical strategy for BI type B. This study aimed to evaluate the efficacy of simple posterior fossa decompression in treating BI type B. METHODS: This study retrospectively enrolled BI type B patients who underwent simple posterior fossa decompression at Huashan Hospital, Fudan University between 2014.12 and 2021.12. Patient data and images were recorded pre- and postoperatively (at the last follow-up) to evaluate the surgical outcomes and craniocervical stability. RESULTS: A total of 18 BI type B patients (13 females), with a mean age of 44.2±7.9 years (range 37-62 years), were enrolled. The mean follow-up period was 47.7±20.6 months (range 10-81 months). All patients received simple posterior fossa decompression without any fixation. At the last follow-up, compared with preoperation, the JOA scores were significantly higher (14.2±1.5 vs. 9.9±2.0, p = 0.001); the CCA was improved (128.7±9.6° vs. 121.5±8.1° p = 0.001), and the DOCL was reduced (7.9±1.5 mm vs. 9.9±2.5 mm, p = 0.001). However, the follow-up and preoperative ADI, BAI, PR, and D/L ratio were similar. No patients had an unstable condition between the C1-2 facet joints that was observed in the follow-up CT and dynamic X-ray. CONCLUSIONS: In BI type B patients, simple posterior fossa decompression could improve neurological function and will not induce CVJ instability in BI type B patients. Simple posterior fossa decompression could be a satisfactory surgical strategy for BI type B patients, but preoperative CVJ stability assessment is crucial.

Characteristics and therapeutic profile of TBI patients who underwent bilateral decompressive craniectomy: experience with 151 cases.

BACKGROUND: Decompressive craniectomy (DC) and intracranial pressure (ICP) monitoring are common approaches to reduce the death rate of Traumatic brain injury (TBI) patients, but the outcomes of these patients are unfavorable, particularly those who receive bilateral DC. The authors discuss their experience using ICP and other potential methods to improve the outcomes of TBI patients who receive bilateral DC. METHODS: Data from TBI patients receiving bilateral DC from Jan. 2008 to Jan. 2022 were collected via a retrospective chart review. Included patients who received unplanned contralateral DC after initial surgery were identified as unplanned secondary surgery (USS) patients. Patients' demographics and baseline medical status; pre-, intra-, and postoperative events; and follow-up visit outcome data were analyzed. RESULTS: A total of 151 TBI patients were included. Patients who underwent USS experienced more severe outcomes as assessed using the 3-month modified Rankin Scale score (P = 0.024). In bilateral DC TBI patients, USS were associated with worsen outcomes, moreover, ICP monitoring was able to lower their death rate and was associated with a lower USS incidence. In USS patients, ICP monitoring was not associated with improved outcomes but was able to lower their mortality rate (2/19, 10.5%, vs. 10/25, 40.0%; P = 0.042). CONCLUSION: The avoidance of USS may be associated with improved outcomes of TBI patients who underwent bilateral DC. ICP monitoring was a potential approach to lower USS rate in TBI patients, but its specific benefits were uncertain.

Blood Pressure Variability Associates with Six-Month Outcomes in Acute Cervical Spinal Cord Injury: An Analysis of 105 Patients.

OBJECTIVE: Blood pressure variability (BPV) has been shown to correlate with poor outcomes in patients with intracerebral hemorrhage (ICH) and traumatic brain injury. However, this association has not been elucidated in patients with traumatic cervical spinal cord injury (cSCI). We hypothesized that 24-hour BPV from time of admission is associated with worse outcomes in patients with cSCI. METHODS: We performed a retrospective chart review analysis of adult patients at Huashan Hospital Fudan University between January 2006 and September 2022. We included isolated patients with traumatic cSCI within 6 hours of injury. Outcomes of patients with cSCI were assessed using 6-month American Spinal Injury Association (ASIA) impairment scale grade, and were dichotomized into poor (ASIA grade A-C, or decreasing ASIA grade compared with baseline) and good (ASIA grade D and E, or increasing ASIA grade compared with baseline) outcome groups. Blood pressures (BPs) were recorded during the first 24 hours of hospital course. BP was analyzed in the hyperacute period, from 0 to 4-5 hours; and in the acute period, from 4-5 to 24-25 hours after admission. BPV was analyzed by standard deviation (SD), coefficient of variation (CV), and successive variation (SV) of systolic BP (SBP). RESULTS: We analyzed 105 patients' charts. The first BP assessment, on emergency department arrival, at median 267 minutes (interquartile range, 152-312 minutes) after onset of injury was mean 152.2 mm Hg (SD, 51.8 mm Hg). The second BP assessment, on neurosurgical intensive care unit arrival, was mean 148.1 mm Hg (53.2 mm Hg). Poor outcomes occurred in 63 patients (60%). In univariate analysis, univariate quintile analysis or multivariate analysis, SBPSD, SBPCV, and SBPSV were associated with poor outcomes in both the hyperacute and the acute period. CONCLUSIONS: BPV during the first 24 hours after injury in patients with traumatic cSCI was independently associated with poor functional outcome at 3 months. Stabilization of BPV during the hyperacute and acute period may be a therapeutic target to improve functional outcomes of these patients.

p53 Inhibition Protects against Neuronal Ischemia/Reperfusion Injury by the p53/PRAS40/mTOR Pathway.

The underlying mechanisms of cerebral ischemia/reperfusion (I/R) injury are unclear. Within this study, we aimed to explore whether p53 inhibition exerts protective effects via the p53/PRAS40/mTOR pathway after stroke and its potential mechanism. Both an in vitro oxygen-glucose deprivation (OGD) model with a primary neuronal culture and in vivo stroke models (dMCAO or MCAO) were used. We found that the infarction size, neuronal apoptosis, and autophagy were less severe in p53 KO mice and p53 KO neurons after cerebral I/R or OGD/R injury. By activating the mTOR pathway, p53 knockdown alleviated cerebral I/R injury both in vitro and in vivo. When PRAS40 was knocked out, the regulatory effects of p53 overexpression or knockdown against stroke disappeared. PRAS40 knockdown could inhibit the activities of the mTOR pathway; moreover, neuronal autophagy and apoptosis were exacerbated by PRAS40 knockdown. To sum up, in this study, we showed p53 inhibition protects against neuronal I/R injury after stroke via the p53/PRAS40/mTOR pathway, which is a novel and pivotal cerebral ischemic injury signaling pathway. The induction of neuronal autophagy and apoptosis by the p53/PRAS40/mTOR pathway may be the potential mechanism of this protective effect.

Contribution of factor VII polymorphisms to coagulopathy in patients with isolated traumatic brain injury.

BACKGROUND: Coagulopathy is a severe complication of traumatic brain injury (TBI) and can cause secondary injuries and death. Decrease of FVII activity contributes to the coagulopathy and progressive hemorrhagic injury (PHI) in patients with isolated TBI. Some polymorphic loci of coagulation factor VII (FVII) are shown to be essential for FVII activity. However, the relationship between FVII gene polymorphisms and coagulopathy in patients with isolated TBI is still unknown. Therefore, the present study aimed to investigate the relationship between FVII gene polymorphisms and plasma FVIIa levels, and assess whether FVII polymorphisms were associated with TBI-related coagulopathy, PHI, and 6 months GOS in patients with isolated TBI. METHODS: One-hundred-forty-nine patients with isolated TBI (from East of China) admitted to Huashan Hospital's Neurological Trauma Center from March 2012 to March 2016 were enrolled in this study. The Polymorphism-Polymerase Chain Reaction (PCR) method was used to analyze the five FVII polymorphism loci (-323P0/P10, R353Q, -401G/T, -402G/A, and -670A/C) of these patients. Patients' blood was collected to test the activated partial thromboplastin time, international normalized ratio, platelet, and FVIIa concentrations. Other clinical characteristics were also recorded. RESULTS: The minor alleles of three genotypes of -323 P0/P10, R353Q, and -401G/T each independently associated with 23.3%, 28.6%, and 27.6% lower FVIIa levels, respectively. These polymorphisms explained 21% of the total variance of FVIIa levels (adjusted R2:0.206). The genotype of -323P0/P10 was an independent risk factor for coagulopathy (OR = 2.77, p = 0.043) and PHI (OR = 3.47, p = 0.03) after adjustment for confounding factors in the logistic regression model. Polymorphisms of FVII were not independently associated with 6 months Glasgow Outcome Scale (GOS) of isolated TBI patients. CONCLUSION: -323P0/P10, R353Q, and -401 G/T genotypes were associated with FVIIa levels. -323P0/P10 genotype was independently associated with traumatic coagulopathy and PHI in isolated TBI patients.

Hypoxia-Induced Glioma-Derived Exosomal miRNA-199a-3p Promotes Ischemic Injury of Peritumoral Neurons by Inhibiting the mTOR Pathway.

The underlying molecular mechanisms that the hypoxic microenvironment could aggravate neuronal injury are still not clear. In this study, we hypothesized that the exosomes, exosomal miRNAs, and the mTOR signaling pathway might be involved in hypoxic peritumoral neuronal injury in glioma. Multimodal radiological images, HE, and HIF-1α staining of high-grade glioma (HGG) samples revealed that the peritumoral hypoxic area overlapped with the cytotoxic edema region and directly contacted with normal neurons. In either direct or indirect coculture system, hypoxia could promote normal mouse hippocampal neuronal cell (HT22) injury, and the growth of HT22 cells was suppressed by C6 glioma cells under hypoxic condition. For administrating hypoxia-induced glioma-derived exosomes (HIGDE) that could aggravate oxygen-glucose deprivation (OGD)/reperfusion neuronal injury, we identified that exosomes may be the communication medium between glioma cells and peritumoral neurons, and we furtherly found that exosomal miR-199a-3p mediated the OGD/reperfusion neuronal injury process by suppressing the mTOR signaling pathway. Moreover, the upregulation of miRNA-199a-3p in exosomes from glioma cells was induced by hypoxia-related HIF-1α activation. To sum up, hypoxia-induced glioma-derived exosomal miRNA-199a-3p can be upregulated by the activation of HIF-1α and is able to increase the ischemic injury of peritumoral neurons by inhibiting the mTOR pathway.

Expression of TNF­α and IL­ß can be suppressed via the PPAR­Î³/mTOR signaling pathway in BV­2 microglia: A potential anti­inflammation mechanism.

Currently, microglia are considered as crucial factors in suppressing inflammatory reactions, but the specific molecular mechanism remains unknown. To elucidate whether peroxisome proliferator­activated receptor­Î³ (PPAR­Î³) can inhibit neuroinflammatory cytokine expression via the mTOR signal pathway, the BV­2 cell line was incubated with lipopolysaccharide (10 mM/ml) to induce an inflammatory injury. PPAR­Î³ was activated by rosiglitazone, and was inhibited by GW9662. The mTOR signal pathway was activated by phosphatidic acid (P.A.), while it was inhibited by rapamycin. Western blotting and reverse transcription­quantitative PCR were used to evaluate the expression levels of PPAR­Î³/mTOR signal pathway related proteins and neuroinflammatory cytokines, including NF­κB, tumor necrosis factor (TNF)­α and interleukin (IL)­1ß. When treated with P.A., the expression levels of phosphorylated (p)mTOR and p­ribosomal protein S6 kinase (pS6K) were significantly increased and the expression levels of TNF­α and IL­1ß were significantly lower. However, the expression of PPAR­Î³ was similar in P.A. treated cells and cells treated with rapamycin. When PPAR­Î³ was activated, pmTOR and pS6K protein expression levels were significantly decreased, and the mRNA expression levels of TNF­α and IL­1ß were significantly reduced, but this inhibition could be alleviated by administrating GW9662. Collectively, it was indicated that the mTOR signal pathway may be located downstream of PPAR­Î³. Furthermore, neuroinflammatory reactions could be inhibited via the activation of PPAR­Î³ by suppressing the mTOR signal pathway in microglia.

Circulating neutrophil-to-lymphocyte ratio at admission predicts the long-term outcome in acute traumatic cervical spinal cord injury patients.

BACKGROUND: The prognostic value of Neutrophil-to-Lymphocyte Ratio (NLR) for the outcome of acute cervical traumatic spinal cord injury (tSCI) patients has rarely been studied by now throughout the world. METHODS: We performed a single-center retrospective cohort study to evaluate the prognostic value of NLR from peripheral whole blood count in patients with acute cervical tSCI. Patients within 6 h of acute cervical tSCI treated between Dec 2008 and May 2018 in Huashan Hospital of Fudan University were enrolled. Outcomes of patients with tSCI were assessed using American spinal injury association Impairment Scale (AIS). 6-month outcomes were dichotomized into poor outcome group (AIS A to C) and good outcome group (AIS D and E). Uni- and multivariate analyses were performed to assess the independent predictors of 6-month outcome. Two prediction models based on admission characteristics were built to evaluate the prognostic value of NLR. The discriminative ability of predictive models was evaluated using the area under the curve (AUC). RESULTS: A total of 377 patients were identified from our single center in China PR. Multivariate analysis showed that age, AIS grade at admission, NLR (p < 0.001) and coagulopathy (p = 0.003) were independent predictors of the 6-months outcome for acute cervical tSCI patients. The model combing NLR and standard variables (AUC = 0.944; 95% CI, 0.923-0.964) showed a more favorable prognostic value than that without NLR (AUC = 0.841; 95% CI, 0.798-0.885) in terms of 6-month outcome. CONCLUSIONS: NLR is firstly identified as an independent predictor of the 6-month outcome in acute cervical tSCI patients worldwide. The prognostic value of NLR is favorable, and a high NLR is associated with poor outcome in patients with acute cervical tSCI.

ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats.

OBJECTIVE: To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism. MATERIAL AND METHODS: The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 µl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated. RESULTS: IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662. CONCLUSIONS: This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression.

Risk factors for potential pulmonary embolism in the patients with deep venous thrombosis: a retrospective study.

INTRODUCTION: The risk factors for the detachment of big thrombi from the vessel wall in patients with deep venous thrombosis (DVT) are still not clear, which are potential risks for pulmonary embolism (PE). This study was aimed to identify the risk factors for big thrombi detaching from the vessel wall in the patients with lower extremity DVT and to identify the role of the lower limb immobilization. METHODS: We retrospectively reviewed the patients whose inferior vena cava (IVC) filter were removed in our hospital. Baseline data and clinical characteristics of all patients were reviewed, including hypertension, diabetes, D-dimer, the onset site of the thrombus, major surgery and lower limb immobilization. The size of the thrombus in the removed IVC filter was assessed by digital subtraction angiography. The thrombus above 1 cm in diameter was defined as potential thrombus of PE and the thrombus below 1 cm as non-potential thrombus of PE. The characteristics and potential risk factors of the patients with potential thrombus of PE were compared with those with non-potential thrombus of PE. Independent risk factors were further analyzed using multivariable regression analyses. RESULTS: Three hundred and forty-nine patients were included in the study. There is no significant difference in age, gender, hypertension, diabetes, D-dimer, or the thrombus site between the two groups. Major surgery and mobile lower limb were independent risk factors for potential thrombus of PE. CONCLUSION: The results suggested that major surgery and mobile lower limb were independent risk factors for potential thrombus of PE in patients with DVT. Immobilization of lower limb might play a protective role in preventing big thrombi from detaching from the vessel wall in patients with DVT.

Role of Vascular Endothelial-Cadherin and p120-Catenin in the Formation of Experimental Intracranial Aneurysm in Animals.

BACKGROUND: Dysfunction of endothelial cells (ECs) constitutes a critical factor in the formation of intracranial aneurysms (IAs). However, little is known about the response of ECs to hemodynamic insults and its contribution to IA formation. METHODS: IAs models were constructed in both adult female New Zealand white rabbits and male Sprague-Dawley rats. Morphologic changes of vessel wall were detected by hematoxylin and eosin staining. Molecular and cellular changes, including p120-catenin (p120ctn) and vascular endothelial-cadherin, in the median sagittal section of the artery bifurcation were analyzed by fluorescent staining. RESULTS: Destructive aneurysmal remodeling and the formation of morphologic IAs were observed at the basilar termini of experimental rabbits and the anterior cerebral artery-olfactory artery bifurcation of rats. The expression of p120ctn colocalized with vascular endothelial-cadherin in ECs decreased. Moreover, the expression of p120ctn colocalized with nucleus of ECs increased. These events suggested that p120ctn was transported from the membrane to the nucleus of ECs. CONCLUSIONS: The potential mechanism, that IAs are always localizing in the bifurcation apices, may be that the endothelium injury of vessel wall can be induced by different hemodynamic conditions. Hemodynamic changes in artery bifurcation may initiate the formation of IAs.

Intensive blood pressure control reduces the risk of progressive hemorrhage in patients with acute hypertensive intracerebral hemorrhage: A retrospective observational study.

OBJECTIVE: To investigate the impact of intensive blood pressure control on progressive intracerebral hemorrhage and outcome in patients with high blood pressure and intracerebral hemorrhage. PATIENTS AND METHODS: A retrospective study was conducted recruiting 659 patients with acute hemorrhagic stroke between Jan. 2012 and May 2018. Patients recruited before May 2015 were treated with a target systolic level of <180 mm Hg, while those recruited after May 2015 received intensive blood pressure control treatment with a target systolic level of <140 mm Hg within 1 h. Uni- and multi-variate analysis were conducted to illustrate the association between intensive blood pressure control and progressive intracerebral hemorrhage. Mortality, rates of operation, length of ICU stay, modified Rankin scores at 90 days, and the rate of serious adverse events were also compared between the two groups. RESULTS: A total of 351 and 308 patients with acute hypertensive intracerebral hemorrhage were recruited before and after May 2015, respectively. Progressive intracerebral hemorrhage was identified among 111 out of 659 patients. Patients who received intensive blood pressure control showed a statistically lower rate of hematoma enlarging (43 of 308, 13.9% vs. 74 of 351, 21.1%, p = 0.018). The rates of operation and modified Rankin scores at 90 days were statistically lower with intensive blood control, while the mortality, length of ICU stay and rate of serious adverse events were similar between the two groups. Intensive BP control is an independent factor in predicting hematoma growing, with a more favorable discrimination (AUC = 0.889; 95%CI, 0.859-0.917) than other two models (AUC = 0.821; 95%CI, 0.791-0.852; and AUC = 0.635; 95%CI, 0.588-0.682). CONCLUSION: Intensive blood pressure control reduce the risk of progressive intracerebral hemorrhage and improved functional outcomes in patients with acute hemorrhagic stroke.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Predicting the 6-Month Outcome of Patients with Traumatic Brain Injury: A Retrospective Study.

BACKGROUND: Peripheral white blood cells are regularly analyzed on admission for patients with traumatic brain injury (TBI). The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in predicting the 6-month outcome of patients with TBI is unclear. METHODS: We designed a single-center retrospective cohort study. Patients admitted to Fudan University Huashan Hospital within 6 hours after TBI were identified between December 2004 and December 2017. The primary outcome was 6-month Glasgow Outcome Scale score. Independent predictors of 6-month outcome were assessed using uni- and multivariate analyses. Three models based on admission characteristics were built to evaluate the prognostic value of the NLR in predicting the outcome of patients with TBI. The discriminative ability of predictive models was evaluated by the area under the curve (AUC). RESULTS: A total of 1291 patients with TBI were included. Multivariate analysis showed age, Glasgow Coma Scale scores at admission, subdural hematoma, intraparenchymal hemorrhage, traumatic subarachnoid hemorrhage, NLR (P < 0.001), and coagulopathy (P = 0.028) were independent predictors of 6-month outcome. The model combining the NLR and standard variables (AUC = 0.936; 95% confidence interval [CI], 0.923-0.949) was more favorable in predicting 6-month outcome of patients with TBI than the model without the NLR (AUC = 0.901; 95% CI, 0.883-0.919) and the model based only on the NLR (AUC = 0.827; 95% CI, 0.802-0.852). CONCLUSIONS: NLR is an independent prognostic factor of predicting 6-month outcome of patients with TBI. A high NLR in patients with TBI is associated with poor outcome. The prognostic value of the NLR in predicting 6-month outcome of patients with TBI is favorable.

Selection of Patients' Recumbent Position Laterality According to Physician Handedness Bias Increases the Success Rate of Lumbar Puncture: A Multicenter Study.

BACKGROUND: Lumbar puncture (LP) is a medical procedure required during spinal anesthesia and for obtaining cerebrospinal fluid samples in the diagnosis of neurological disorders. The aim of this study was to assess the effects of physicians' handedness bias and the laterality of patients' recumbent position on the success rate of LPs. METHODS AND PATIENTS: A prospective multicenter study including 36 physicians (18 left-handed and 18 right-handed) and 7200 patients was conducted in 6 medical centers. In each center, 1200 patients were randomized into group L (LPs performed by left-handed physicians) or group R (LPs performed by right-handed physicians). Each physician performed 200 cases of LPs, of which the laterality of the recumbent position (either on the left or right side) was decided after a second randomization. A successful LP was considered when the free flow of cerebrospinal fluid was observed upon the first attempt. RESULTS: There was no significant difference in patient characteristics between groups L and R. Right-handed physicians had a significantly higher LP success rate with patients in the left lateral recumbent position (LRP) (1595/1800 vs. 1408/1800; odds ratio, 0.539; 95% confidence interval, 0.348-0.836; P=0.006). For left-handed physicians, the LP success rate was higher when patients were in the right LRP (1424/1800 vs. 1593/1800, odds ratio, 0.449; 95% confidence interval, 0.283-0.711; P=0.001). Patients' age, sex, height, and weight were not statistically related to LP success during multivariate analyses. CONCLUSIONS: Physicians handedness bias and patient laterality of recumbent position affects the success of LPs. Right-handed physicians have a greater chance of performing successful LPs when patients are in the left LRP, and vice versa.

Knockdown of P120 catenin aggravates endothelial injury under an impinging flow by inducing breakdown of adherens junctions.

At present, the mechanisms underlying intracranial aneurysm (IA) development remain unclear; however, hemodynamics is considered a crucial factor in the induction of IA. To elucidate the association between hemodynamics and endothelial cell (EC) functions, a modified T chamber system was designed to simulate the adjustable hemodynamic conditions of an artery bifurcation. Normal human umbilical vein ECs (HUVECs) and HUVECs with P120 catenin (P120ctn) knockdown were cultured on coverslips and placed in the chamber. A flow rate of 250 or 500 ml/min impinged on the cell layer. Subsequently, the expression levels of P120ctn and other proteins, and EC morphological alterations, were examined. In normal HUVECs, after 3 h under a flow rate of 500 ml/min, the expression levels of P120ctn, vascular endothelial (VE)­Cadherin, Kaiso and α­catenin were decreased, whereas matrix metalloproteinase­2 (MMP­2) was increased. In HUVECs with P120ctn knockdown, the period during which ECs adhered to the coverslip was reduced to 1 h under a flow rate of 500 ml/min. In addition, the expression levels of VE­Cadherin, Kaiso and α­catenin in ECs were decreased, whereas those of MMP­2 were increased after 1 h; more prominent alterations were detected under a 500 ml/min flow rate compared with a 250 ml/min flow rate. Adherens junctions (AJs) are critical to the maintenance of normal morphology and EC functioning in the vascular wall, and P120ctn is an important regulator of AJs. Loss of P120ctn may be induced by hemodynamic alterations. In response to changes in hemodynamic conditions, a loss of P120ctn may aggravate AJs between ECs, thus inducing inflammation in the vascular wall. Clinically, hemodynamic alterations may result in a loss of P120ctn and endothelial injury; therefore, P120ctn may have a critical role in inducing intracranial aneurysms.

Different Doses of Clazosentan for Aneurismal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials.

Clazosentan therapy has been found to be effective in reducing the incidence of vasospasm after aneurismal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to determine whether different doses of clazosentan treatment significantly reduced the incidence of delayed ischemic neurological deficits (DINDs) and new cerebral infarction (NCI). We systematically searched PubMed, Embase, Cochrane library and Medline from inception until October, 2015. All randomized controlled trials related to the functions of clazosentan in aSAH were included. Analyses were performed following the method guideline of Cochrane Back Review Group. Four randomized placebo-controlled trials met eligibility criteria and enrolled a total of 2159 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk, 0.49 and 95% CI, 0.33-0.73) and NCI (relative risk, 0.42 and 95% CI, 0.25-0.71) in patients treated with a high dose of clazosentan (15 mg/h) after aSAH. In addition, a high dose of clazosentan (15 mg/h) had no more effect on the incidence of adverse events than that of a low dose (1-5 mg/h). The results of the present meta-analysis show that a high dose of clazosentan significantly reduced the incidence of the vasospasm-related DINDs and NCI. Further study is required to fully understand the potential usefulness of clazosentan in patients with aSAH.

Effects of preadmission beta-blockers on neurogenic stunned myocardium after aneurysmal subarachnoid hemorrhage: A meta- analysis.

OBJECTIVE: Spontaneous subarachnoid hemorrhage is mostly caused by the rupture of an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads to subendocardial ischemia or coronary artery spasm. We designed this meta-analysis to find out whether beta-blockers (BB) can significantly reduce the incidence of NSM and improve the outcomes of aSAH. PATIENTS AND METHODS: We systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline from inception to Feb 2016. All studies related to the preadmission beta-blocker with aSAH were included. RESULTS: Three retrospective studies and 691 patients were included. The incidence of mortality [OR=0.68, 95%CI (0.08-3.50), P=0.57], cardiac dysfunction [OR = 0.55, 95% CI (0.05-6.49), P=0.63], cerebral vasospasm (OR=0.52 95% CI(0.18-2.56), P=0.50] had no statistical difference between the preadmission BB group and no BB group. CONCLUSION: The preadmission beta-blocker cannot decrease the incidence of mortality, cardiac dysfunction, cerebral vasospasm in patients with aSAH. A further research of the usefulness of preadmission beta-blocker in patients with aSAH will be needed.