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.

Breast Cancer Mutations HER2V777L and PIK3CAH1047R Activate the p21-CDK4/6-Cyclin D1 Axis to Drive Tumorigenesis and Drug Resistance.

In metastatic breast cancer, HER2-activating mutations frequently co-occur with mutations in PIK3CA, TP53, or CDH1. Of these co-occurring mutations, HER2 and PIK3CA are the most commonly comutated gene pair, with approximately 40% of HER2-mutated breast cancers also having activating mutations in PIK3CA. To study the effects of co-occurring HER2 and PIK3CA mutations, we generated genetically engineered mice with the HER2V777L; PIK3CAH1047R transgenes (HP mice) and studied the resulting breast cancers both in vivo as well as ex vivo using cancer organoids. HP breast cancers showed accelerated tumor formation in vivo and increased invasion and migration in in vitro assays. HP breast cancer cells were resistant to the pan-HER tyrosine kinase inhibitor, neratinib, but were effectively treated with neratinib plus the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan. Proteomic and RNA-seq analysis of HP breast cancers identified increased gene expression of cyclin D1 and p21WAF1/Cip1 and changes in cell-cycle markers. Combining neratinib with CDK4/6 inhibitors was another effective strategy for treating HP breast cancers, with neratinib plus palbociclib showing a statistically significant reduction in development of mouse HP tumors as compared to either drug alone. The efficacy of both the neratinib plus trastuzumab deruxtecan and neratinib plus palbociclib combinations was validated using a human breast cancer patient-derived xenograft with very similar HER2 and PIK3CA mutations to the HP mice. Further, these two drug combinations effectively treated spontaneous lung metastasis in syngeneic mice transplanted with HP breast cancer organoids. This study provides valuable preclinical data to support the ongoing phase 1 clinical trials of these drug combinations in breast cancer. SIGNIFICANCE: In HER2-mutated breast cancer, PIK3CA mutation activates p21-CDK4/6-cyclin D1 signaling to drive resistance to HER2-targeted therapies, which can be overcome using CDK4/6 inhibitors.

Prediction of in-hospital hypokalemia using machine learning and first hospitalization day records in patients with traumatic brain injury.

AIMS: Hypokalemia is a common complication following traumatic brain injury, which may complicate treatment and lead to unfavorable outcomes. Identifying patients at risk of hypokalemia on the first day of admission helps to implement prophylactic treatment, reduce complications, and improve prognosis. METHODS: This multicenter retrospective study was performed between January 2017 and December 2020 using the electronic medical records of patients admitted due to traumatic brain injury. A propensity score matching approach was adopted with a ratio of 1:1 to overcome overfitting and data imbalance during subgroup analyses. Five machine learning algorithms were applied to generate a best-performed prediction model for in-hospital hypokalemia. The internal fivefold cross-validation and external validation were performed to demonstrate the interpretability and generalizability. RESULTS: A total of 4445 TBI patients were recruited for analysis and model generation. Hypokalemia occurred in 46.55% of recruited patients and the incidences of mild, moderate, and severe hypokalemia were 32.06%, 12.69%, and 1.80%, respectively. Hypokalemia was associated with increased mortality, while severe hypokalemia cast greater impacts. The logistic regression algorithm had the best performance in predicting decreased serum potassium and moderate-to-severe hypokalemia, with an AUC of 0.73 ± 0.011 and 0.74 ± 0.019, respectively. The prediction model was further verified using two external datasets, including our previous published data and the open-assessed Medical Information Mart for Intensive Care database. Linearized calibration curves showed no statistical difference (p > 0.05) with perfect predictions. CONCLUSIONS: The occurrence of hypokalemia following traumatic brain injury can be predicted by first hospitalization day records and machine learning algorithms. The logistic regression algorithm showed an optimal predicting performance verified by both internal and external validation.

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.

Prediction of Intracranial Infection in Patients under External Ventricular Drainage and Neurological Intensive Care: A Multicenter Retrospective Cohort Study.

Objective: To generate an optimal prediction model along with identifying major contributors to intracranial infection among patients under external ventricular drainage and neurological intensive care. Methods: A retrospective cohort study was conducted among patients admitted into neurointensive care units between 1 January 2015 and 31 December 2020 who underwent external ventricular drainage due to traumatic brain injury, hydrocephalus, and nonaneurysmal spontaneous intracranial hemorrhage. Multivariate logistic regression in combination with the least absolute shrinkage and selection operator regression was applied to derive prediction models and optimize variable selections. Other machine-learning algorithms, including the support vector machine and K-nearest neighbor, were also applied to derive alternative prediction models. Five-fold cross-validation was used to train and validate each model. Model performance was assessed by calibration plots, receiver operating characteristic curves, and decision curves. A nomogram analysis was developed to explicate the weights of selected features for the optimal model. Results: Multivariate logistic regression showed the best performance among the three tested models with an area under curve of 0.846 ± 0.006. Six variables, including hemoglobin, albumin, length of operation time, American Society of Anesthesiologists grades, presence of traumatic subarachnoid hemorrhage, and a history of diabetes, were selected from 37 variable candidates as the top-weighted prediction features. The decision curve analysis showed that the nomogram could be applied clinically when the risk threshold is between 20% and 100%. Conclusions: The occurrence of external ventricular-drainage-associated intracranial infections could be predicted using optimal models and feature-selection approaches, which would be helpful for the prevention and treatment of this complication in neurointensive care units.

A functional assembly framework based on implementable neurobionic material.

Neurobionic material is an emerging field in material and translational science. For material design, much focus has already been transferred from von Neumann architecture to the neuromorphic framework. As it is impractical to reconstruct the real neural tissue solely from materials, it is necessary to develop a feasible neurobionics framework to realize advanced brain function. In this study, we proposed a mathematical neurobionic material model, and attempted to explore advanced function only by simple and feasible structures. Here an equivalent simplified framework was used to describe the dynamics expressed in an equation set, while in vivo study was performed to verify simulation results. In neural tissue, the output of neurobionic material was characterized by spike frequency, and the stability is based on the excitatory/inhibitory proportion. Spike frequency in mathematical neurobionic material model can spontaneously meet the solution of a nonlinear equation set. Assembly can also evolve into a certain distribution under different stimulations, closely related to decision making. Short-term memory can be formed by coupling neurobionic material assemblies. In vivo experiments further confirmed predictions in our mathematical neurobionic material model. The property of this neural biomimetic material model demonstrates its intrinsic neuromorphic computational ability, which should offer promises for implementable neurobionic device design.

Machine learning models predict coagulopathy in spontaneous intracerebral hemorrhage patients in ER.

AIMS: Coagulation abnormality is one of the primary concerns for patients with spontaneous intracerebral hemorrhage admitted to ER. Conventional laboratory indicators require hours for coagulopathy diagnosis, which brings difficulties for appropriate intervention within the optimal window. This study evaluates the possibility of building efficient coagulopathy prediction models using data mining and machine learning algorithms. METHODS: A retrospective cohort enrolled 1668 cases with acute spontaneous intracerebral hemorrhage from three medical centers, excluding those under antithrombotic therapies. Coagulopathy-related clinical parameters were initially screened by univariate analysis. Two machine learning algorithms, the random forest and the support vector machine, were deployed via an approach of four-fold cross-validation to screen out the most important parameters contributing to the occurrence of coagulopathy. Model discrimination was assessed using metrics, including accuracy, precision, recall, and F1 score. RESULTS: Albumin/globulin ratio, neutrophil count, lymphocyte percentage, aspartate transaminase, alanine transaminase, hemoglobin, platelet count, white blood cell count, neutrophil percentage, systolic and diastolic pressure were identified as major predictors to the occurrence of acute coagulopathy. Compared to support vector machine, the model based on the random forest algorithm showed better accuracy (93.1%, 95% confidence interval [CI]: 0.913-0.950), precision (92.4%, 95% CI: 0.897-0.951), F1 score (91.5%, 95% CI: 0.889-0.964), and recall score (93.6%, 95% CI: 0.909-0.964), and yielded higher area under the receiver operating characteristic curve (AU-ROC) (0.962, 95% CI: 0.942-0.982). CONCLUSION: The constructed models exhibit good prediction accuracy and efficiency. It might be used in clinical practice to facilitate target intervention for acute coagulopathy in patients with spontaneous intracerebral hemorrhage.

Baicalein Ameliorates Epilepsy Symptoms in a Pilocarpine-Induced Rat Model by Regulation of IGF1R.

Treatment for epilepsy, particularly temporal lobe epilepsy, is challenging. Baicalein has multiple effects, including anti-inflammatory action. However, little is known about its efficacy in treatment of epilepsy. In this study, we established a pilocarpine-induced rat model and used it for assessment of baicalein efficacy in vivo. We predicted the pharmacological mechanism of baicalein by network pharmacology and RNA sequencing analyses. Pilocarpine epileptic rats treated with baicalein exhibited improved average seizure severity, seizure frequency, seizure duration, and survival time. Network pharmacology and RNA sequencing identified the differentially expressed genes between the baicalein treatment and epileptic groups. Insulin-like growth factor 1 receptor (IGF1R) was chosen as the top candidate target because of its overlapping findings in RNA sequencing and network pharmacology data. Western blotting, immunofluorescence, and polymerase chain reaction analyses showed that baicalein inhibited microglial proliferation, IGF1R, and inflammatory cytokine expression. Moreover, baicalein improved epilepsy symptoms. Inhibition of IGF1R function by blocking with AXL1717 enhanced baicalein treatment efficacy both in vivo and in vitro. In conclusion, baicalein exerted antiepileptic effects by regulation of IGF1R in a pilocarpine-induced rat model.

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.

Reconfigurable Soft Actuators with Multiple-Stimuli Responses.

Multiple-stimuli responsive soft actuators with tunable initial shapes would have substantial potential in broad technological applications, ranging from advanced sensors, smart robots to biomedical devices. However, existing soft actuators are often limited to single initial shape and are unable to reversibly reconfigure into desirable shapes, which severely restricts the multifunctions that can be integrated into one actuator. Here, a novel reconfigurable supramolecular polymer/polyethylene terephthalate (PET) bilayer actuator exhibiting multiple-stimuli responses is presented. In this bilayer actuator, the supramolecular polymer layer constructed of poly(5-Norbornene-2-carboxylic acid-1,3-cyclooctadiene) (PNCCO) and azopyridine derivative (PyAzoPy) via H-bonds provides multiple-stimuli responses: PyAzoPy offers light response and carboxylic groups in PNCCO endow the actuator with humidity response. Meanwhile thermoplastic PET layer enables the bilayer actuators to be reconfigured into various shapes by thermal stimuli. The rationally designed actuators exhibit versatile capabilities to reversibly reconfigure into a set of initial shapes and carry out multiple functions, such as photo-driven "foldback-clip" and Ω-shaped crawling robots. In addition, bio-inspired plants constructed by reconfiguration of such actuators demonstrate reversible multiple-stimuli responses. It is anticipated that these novel actuators with highly tunable geometries and actuation modes would be useful to develop multifunctional devices capable of performing diverse tasks.

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.

Job satisfaction, engagement, and burnout in the population of orthopedic surgeon and neurosurgeon trainees in mainland China.

OBJECTIVE: In China, orthopedics and neurosurgery are among the most desired majors for medical students. However, little is known about the working and living status of specialists in these two fields. This study was aimed at evaluating job satisfaction, engagement, and burnout in the population of Chinese orthopedist and neurosurgeon trainees. METHODS: A nationwide online survey was administered in mainland China. Questionnaires were answered anonymously. Job satisfaction, engagement, and burnout were assessed using the Job Descriptive Index, the Utrecht Work Engagement Scale, and the Maslach Burnout Inventory, respectively. RESULTS: Data were collected from 643 orthopedist trainees and 690 neurosurgeon trainees. Orthopedists and neurosurgeons showed no statistical difference in terms of age, sex, job titles, and preference for working in tertiary hospitals. Orthopedists had a higher marriage rate (p < 0.01), a lower divorce rate (p = 0.017), relatively shorter working hours (p < 0.01), and a higher annual income (p = 0.023) than neurosurgeons. Approximately 40% of respondents experienced workplace violence in the last 5 years. Less than 10% of respondents were satisfied with their pay, and over 70% would not encourage their offspring to become a doctor. Orthopedists were more satisfied with their careers than neurosurgeons (p < 0.01) and had a higher level of work engagement (p < 0.01). In addition, a higher proportion of orthopedists were burnt out (p < 0.01) than neurosurgeons, though the difference between the two groups was not significant (p = 0.088). Multivariate regressions suggested that younger age (≤ 25 years old), being a senior trainee, getting divorced, working in a regional hospital, long working hours (≥ 71 hrs/wk), a low annual income (<¥100,000), sleeping < 6 hrs/day, and experience with workplace violence were significantly related to burnout for both groups. CONCLUSIONS: Chinese orthopedic surgical and neurosurgical trainees are under significant stress. Orthopedic surgeons showed relatively optimistic data in their assessments of job satisfaction, engagement, and burnout. This study may provide valuable information for orthopedic and neurosurgical candidates considering either specialty as a career.

Academic versus non-academic neurosurgeons in China: a national cross-sectional study on workload, burnout and engagement.

OBJECTIVES: Chinese neurosurgery has made great progress during the past decades; yet, little is known about the working status of neurosurgeons. This study aimed to evaluate the difference between academic and non-academic neurosurgeons, focusing on their professional burnout, job satisfaction and work engagement. DESIGN: Cross-sectional nationwide survey. STUDY SETTING: The survey was conducted in China between 2017 and 2018. PARTICIPANTS: A total number of 823 academic neurosurgeons and 379 non-academic neurosurgeons participated in this study. OUTCOME MEASURES: Professional burnout, job satisfaction and work engagement were assessed using the Maslach Burnout Inventory, the Job Descriptive Index and the Utrecht Work Engagement Scale, respectively. RESULTS: The majority of respondents were male (92.93%), less than 45 years old (85.27%) and married (79.53%). Chinese neurosurgeons worked 63.91±11.04 hours per week, and approximately 45% experienced burnout. Compared with non-academic respondents, academic neurosurgeons had longer working hours (p<0.01), higher income (p<0.01) and were less willing to get married (p<0.01). In addition, they showed a lower degree of burnout (p<0.01), a higher level of job satisfaction (p<0.01) and were more enthusiastic at work (p=0.015). Multivariate regression analyses indicated that divorced (OR 7.02, 95% CI 2.37 to 15.08) and workplace violence (OR 1.52, 95% CI 1.18 to 2.24) were associated with burnout for both academic and non-academic respondents. Long working hours (≥71 hours per week) and low annual income (<1 00 000 RMB) were risk factors for burnout among academic neurosurgeons. For non-academic neurosurgical surgeons (age 36-45 years), working as attending doctors, serving in public hospitals and having the first house-living child were all closely related to the incidence of burnout. CONCLUSION: Chinese neurosurgeons are under significant stress particularly for the non-academic neurosurgeons. Offering better opportunities for training, promotion, higher income and safer working environments could be solutions to relieve burnout and improve career satisfaction and engagement. TRIAL REGISTRATION NUMBER: ChiCTR1800014762. This article is not linked to a clinical trial.

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.

Intra-Extracranial Primary Clear Cell Sarcoma: The First Report and Review of the Literature.

BACKGROUND: Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor with poor prognosis owing to metastasis and insensitive response to chemotherapy and radiotherapy. METHODS: We first searched PubMed and Embase using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," "head," and "neck." In the 15 articles selected for literature review, only 27% (4/15) of patients were diagnosed with primary CCS of the head. Pathologically, those tumors arose from either the scalp or the superficial temporal fascia, but none invaded the skull and brain. Next, the search was performed in the same database using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," and "bone," and only 24 articles were selected. RESULTS: In the case reported here, a 36-year-old woman was found to have a palpable mass located at the left temporal-occipital region, and surgical finding confirmed the invasion into the skull and the brain. The diagnosis of primary CCS was made because of the detection of t(12;22)(q13;q12) in >50% of tumor cells by fluorescence in situ hybridization, and metastasis to the lymph nodes and lungs was discovered by postoperative positron emission tomography-computed tomography. CONCLUSIONS: To the best of our knowledge, this is the first case of primary central nervous system CCS. Primary CCS may involve the skull and should be one of the differential diagnoses for intra-extracranial communicating tumors. Further research on biological characteristics and molecular targeted therapy of CCS are needed to improve its poor prognosis.

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.

Diagnosis and Management for Secondary Low- or Negative-Pressure Hydrocephalus and a New Hydrocephalus Classification Based on Ventricular Pressure.

BACKGROUND: Low-pressure hydrocephalus (LPH) and negative-pressure hydrocephalus (NegPH), secondary to traumatic brain injury, cerebral hemorrhage, tumor resection, and central nervous system (CNS) infection in adults, are seldom reported. They have not been recognized enough pathophysiologically in previous clinical practice. They used to have poor prognosis, and routine shunt surgery has unsatisfactory outcomes. The current classifications of hydrocephalus do not provide proper guidance for clinical practice, especially for LPH and NegPH. METHODS: Thirty-nine cases of LPH and NegPH were included from January 2013 to March 2018. Clinical features and image characteristics were reviewed. The prognosis of these patients were evaluated by Glasgow Outcome Scale-Extended (GOS-E) within 3 months after external ventricular drainage or ventriculoperitoneal (VP) shunt accepted. Management strategies were discussed in detail. RESULTS: Ventricular pressure was lower than 70 mm H2O in all 39 patients, and the lowest value was -10 cm H2O. About an average of 3.5 operations were completed for every patient. Eighteen cases had CNS infection. Eight patients died. Besides 2 patients lost to follow-up, all patients had a poor prognosis with an average GOS-E score of 2.7. For the 29 surviving patients, the time interval from onset to last VP shunt achieved was 31-3880 days, with an average of 376 days. CONCLUSIONS: Both LPH and NegPH used to have poor prognosis. However, a good prognosis can be achieved by proper management with a further understanding of the pathophysiology. A new classification for hydrocephalus was proposed according to ventricular pressure, which is necessary and reasonable.