Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

BACKGROUND: Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. METHODS: We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. RESULTS: Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (ß -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). CONCLUSION: Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

Cost prediction for ischemic heart disease hospitalization: Interpretable feature extraction using network analysis.

OBJECTIVES: Ischemic heart disease (IHD) is a significant contributor to global mortality and disability, imposing a substantial social and economic burden on individuals and healthcare systems. To enhance the efficient allocation of medical resources and ultimately benefit a larger population, accurate prediction of healthcare costs is crucial. METHODS: We developed an interpretable IHD hospitalization cost prediction model that integrates network analysis with machine learning. Specifically, our network-enhanced model extracts explainable features by leveraging a diagnosis-procedure concurrence network and advanced graph kernel techniques, facilitating the capture of intricate relationships between medical codes. RESULTS: The proposed model achieved an R2 of 0.804 ± 0.008 and a root mean square error (RMSE) of 17,076 ± 420 CNY on the temporal validation dataset, demonstrating comparable performance to the model employing less interpretable code embedding features (R2: 0.800 ± 0.008; RMSE: 17,279 ± 437 CNY) and the hybrid graph isomorphism network (R2: 0.802 ± 0.007; RMSE: 17,249 ± 387 CNY). The interpretation of the network-enhanced model assisted in pinpointing specific diagnoses and procedures associated with higher hospitalization costs, including acute kidney injury, permanent atrial fibrillation, intra-aortic balloon bump, and temporary pacemaker placement, among others. CONCLUSION: Our analysis results demonstrate that the proposed model strikes a balance between predictive accuracy and interpretability. It aids in identifying specific diagnoses and procedures associated with higher hospitalization costs, underscoring its potential to support intelligent management of IHD.

The prognostic value of intraoperative HRV during anesthesia in patients presenting for non-cardiac surgery.

OBJECTIVE: To examine the prognostic value of HRV measurements during anesthesia for postoperative clinical outcomes prediction using machine learning models. DATA SOURCES: VitalDB, a comprehensive database of 6388 surgical patients admitted to Seoul National University Hospital. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Cases with ECG lead II recording duration of less than one hour were excluded. Cases with more than 20% of missing HRV measurements were also excluded. A total of 5641 cases were eligible for the analyses. METHODS: Six machine learning models including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Trees (GBT), Extreme Gradient Boosting (XGB), and an ensemble of the five baseline models were developed to predict postoperative clinical outcomes. The prediction models were trained using only clinical information, and using both clinical information and HRV features, respectively. Feature importance based on the SHAP method was used to assess the contribution of the HRV measurements to the outcome predictions. Subgroup analysis was also performed to evaluate the risk association between postoperative ICU stay and various HRV measurements such as heart rate, low-frequency power (LFP), and short-term fluctuation DFA [Formula: see text]. RESULT: The final cohort included 5641 unique cases, among whom 4678 (83.0%) cases had ages over 40, 2877 (51.0%) were male, 1073 (19.0%) stayed in ICU after surgery, 52 (0.9%) suffered in-hospital death, and 3167(56.1%) had a total length of hospital stay longer than 7 days. In the final test set, the highest AUROC performance with only clinical information was 0.79 for postoperative ICU stay, 0.58 for in-hospital mortality, and 0.76 for the total length of hospital stay prediction. Importantly, using both clinical information and HRV features, the AUROC performance was 0.83, 0.70, and 0.76 for the three clinical outcome predictions, respectively. Subgroup analysis found that patients with an average heart rate higher than 70, low-frequency power (LFP) < 33, and short-term fluctuation DFA [Formula: see text] < 0.95 during anesthesia, had a significantly higher risk of entering the ICU after surgery. CONCLUSION: This study suggested that HRV measurements during anesthesia are feasible and effective for predicting postoperative clinical outcomes.

Coronary stenosis is a risk marker for impaired cardiac function on cardiopulmonary exercise test.

BACKGROUND: Cardiac function varies in different ways in ischemic heart disease (IHD). We aimed to evaluate the characteristics of cardiac function on cardiopulmonary exercise test (CPET) in IHD with different coronary stenoses. METHODS: Totally 614 patients with IHD were divided into non-obstructive coronary artery disease (NOCAD) (stenosis < 50%), obstructive coronary artery disease (OCAD) (stenosis 50-90%) and severe OCAD ( stenosis > 90%) according to the coronary angiography. And 101 healthy volunteers as controls. All participants performed CPET to assess cardiac function by oxygen uptake (VO2), estimated cardiac output (CO), and heart rate (HR). RESULTS: Generally, the values of VO2, CO, and HR in IHD were significantly lower than in healthy volunteers. Among 289 NOCAD, 132 OCAD, and 193 severe OCAD, significantly decreased values of VO2, CO, HR were observed (VO2 peak: 16.01 ± 4.11 vs. 15.66 ± 4.14 vs. 13.33 ± 3.4 mL/min/kg; CO: 6.96 ± 2.34 vs. 6.87 ± 2.37 vs. 6.05 ± 1.79 L/min; HR: 126.44 ± 20.53 vs. 115.15 ± 18.78 vs. 109.07 ± 16.23 bpm, P < 0.05). NOCAD had significantly lower VO2 at anaerobic threshold (-1.35, 95%CI -2.16 - -0.54) and VO2 peak (-2.05, 95%CI -3.18 - -0.93) compared with healthy volunteers after adjustment. All IHD patients were associated with low stroke volume and inefficient gas exchange (P < 0.05). CONCLUSION: IHD with increasing atherosclerotic burdens were associated with impaired cardiac output and chronotropic response on CPET. NOCAD should be given more early prevention and rigorous follow-up.

miR-202-5p protects rat against myocardial ischemia reperfusion injury by downregulating the expression of Trpv2 to attenuate the Ca 2+ overload in cardiomyocytes.

BACKGROUND: This study was aimed to unveil micro RNA (miRNA) expression profiles in myocardial ischemia-reperfusion (MI/R) rats and explore whether and how dysregulated miRNAs were involved in the initiation and progression of MI/R in a calcium-dependent manner. METHOD AND RESULTS: Rat model of MI/R was established and cardiomyocytes isolated from neonatal rats cardiomyocytes were induced. Both miRNA and messenger RNA expression profiles were analyzed by Microarray. Quantitative reverse-transcription polymerase chain reaction, immunoblotting, bioinformatics analysis, dual-luciferase reporter gene assay, hematoxylin and eosin, Evans blue, and triphenyl tetrazolium chloride were also used in this study. Serum concentrations of myocardial enzymes (phosphocreatine kinase [CK], creatine kinase [CK-MB], lactate dehydrogenase [LDH]), cardiomyocytes loadage of Ca2+ , as well as the expression level of inositol 1,4,5-trisphosphate receptors (IP3R) and sarcoplasmic reticulum Ca2+ -ATPase 2a (SERCA2a) were measured, respectively. Effects of upregulation or downregulation of miR-202-5p or Trpv2 on these indicators were investigated in vivo and in vitro. In MI/R rats and hypoxia/reoxygenation-induced NCMs, miR-202-5p was downregulated, while Trpv2 was upregulated. Trpv2 was a promising target of miR-202-5p and negatively regulated by miR-202-5p. Upregulation of miR-202-5p or downregulation of Trpv2 significantly reduced the serum concentration of myocardial enzymes, as well as cardiomyocyte-produced reactive oxygen species, but inhibition of miR-202-5p or overexpression of Trpv2 brought the worsening situation for these indicators. Besides, upregulation of miR-202-5p upregulation or downregulation of Trpv2 also inhibited Ca2+ overload in cardiomyocytes, accompanied with the increase of SERCA2a and suppression of IP3R. The reduced damage degree and infarct size in myocardial tissue were contrarily worsened by miR-202-5p inhibitor. CONCLUSION: Overexpression of miR-202-5p or downregulation of its downstream Trpv2 presented the cardioprotective effects to MI/R rats.

An application of RASER technique in the treatment of chronic total occlusion accompanied with stent fracture in right coronary artery: a case report.

BACKGROUND: The interventional treatment of chronic total occlusion (CTO) with stent fracture as well as severe calcification was extremely difficult and no effective technique has been reported. CASE PRESENTATION: A 50-year-old woman was hospitalized for angina, angiography revealed triple vessel disease, CTO accompanied with stent fracture in right coronary artery (RCA). Treatment using conventional coronary intervention was expected to be difficult. Therefore, we performed RASER technique, which was a combination of excimer laser coronary atherectomy (ELCA) with rotational atherectomy (RA), followed by the deployment of drug-eluting stents. Intravascular ultrasound (IVUS) revealed well attachment of the stents, the patient was discharged 3 days after the procedure and no recurrent chest discomfort was reported in a follow-up time of 10 months. CONCLUSION: This case report provided a first report of RASER technique in the treatment of CTO with stent fracture and severe calcification.

A comparison study between wide-range and high-sensitivity C-reactive protein assays (Roche Cobas c702) for low C-reactive protein concentration in patients with cardiovascular risk.

BACKGROUND: Low concentration C-reactive protein (CRP) has favorable prognostic significance in patients with cardiovascular risks. METHODS: We compared the wr-CRP method with the hs-CRP method both on Roche Cobas c702 analyzer for the determination of low CRP concentration (<20 mg/L) including 200 patients treated in Cardiology Department in Beijing Tsinghua Changgung Hospital (Beijing, China) from December 2018 to March 2019. RESULTS: The two methods were highly correlated (Spearman's rho = 0.995). Deming regression was used to fit the regression analysis model, giving a slope of 1.058 with an intercept of 0.008. The median method difference (wr-CRP - hr-CRP) was 0.120 mg/L (95% CI, 0.086-0.200 mg/L), and the median percent differences were 7.34% (95% CI, 4.27%-8.47%). The percent bias between both methods at the given cutoff CRP values of 1, 3, and 10 mg/L evaluated by Deming regression was 6.60%, 6.07%, and 5.88%, respectively, all of which were less than the acceptable standard (12.50%). The percentage of sample results concordant by both methods for the risk stratification was 96.0% (kappa = 0.937, P < 0.001). CONCLUSIONS: Roche wr-CRP and hs-CRP assays are highly concordant in determining low concentration CRP. Wr-CRP may be used as an alternative to hs-CRP assay on Roche Cobas c702 analyzer to assess the cardiovascular risk, considering its convenience and lower costs.

Cytotropic heterogeneous molecular lipids inhibit the growth of glioma cells by inducing apoptosis and autophagy.

The cytotropic heterogeneous molecular lipid (CHML) is a mixture of lipids isolated from natural products. CHML is an effective therapy for various kinds of cancers; however, the effect of CHML on glioma cells was seldom reported. Here, we aim to explore the cytotoxicity of CHML on glioma cells, and analyze the possible mechanisms. U251 glioma cells were cultured with CHML at different concentration, and the growth inhibition was measured by CCK-8 assay. Induced apoptosis were detected by flow cytometry, and the induced autophagies were observed by a transmission electron microscope. The key molecules involved in apoptosis and autophagy were detected by quantitative PCR and western-blot. CHML might inhibit the growth of U251 cells and promote apoptosis by up-regulating the expressions of Caspase-8 and Caspase-3; CHML also induced autophagy of U251 cells by promoting the expressions of MAP LC-3 and Beclin-1. CHML can inhibit proliferation of U251 cells by promoting cell apoptosis and inducing autophagy.

Current evidences on the XPG Asp1104His polymorphism and melanoma susceptibility: a meta-analysis based on case-control studies.

Previous studies evaluating the association between the XPG Asp1104His polymorphism and melanoma susceptibility remained controversial. To draw a more precise estimation of the relationship, a total of eight published case-control studies containing 5,212 cases and 7,045 controls were included for meta-analysis. Overall, a significant association was found between the XPG Asp1104His polymorphism and melanoma susceptibility for the dominant model (OR = 2.42, 95 % CI = 2.26-2.60). In subgroup analysis by source of control, there was an obvious association was found among Population-based subgroup for the dominant model CC+GC vs GG (OR 2.51, 95 % CI 2.28-2.77), among the Hospital-based subgroup, an obvious association was also found for the dominant model CC+GC vs GG (OR 2.34, 95 % CI 2.12-2.58). This meta-analysis suggested that the XPG Asp1104His polymorphism was a risk factor for melanoma susceptibility.

[Efficacy analysis of endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas].

OBJECTIVE: To analyze the safety and efficacy of surgical removal of recurrent or regrowing pituitary adenomas by endoscopic endonasal transsphenoidal approach. METHODS: The clinical data were retrospectively reviewed for 28 patients undergoing endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas between April 2010 and December 2013. There were 9 males and 19 females with a mean age of 44. 2 (11 - 73) years. The maximal tumor diameter ranged from 2. 1 to 6.9 cm. The Knosp grades were 1 -2 (n = 11), 3 (n =8) and 4 (n =9). Fifteen tumors were endocrinically functional and the remainder endocrinically nonfunctional. All operations were performed with an assistance of intraoperative neuronavigation. Neuro-ophthalmological, neuroimaging and endocrinological results were followed up postoperatively. And surgical outcomes and risk factors were analyzed for incomplete tumor resection in previous operations. RESULTS: The mean follow-up period was 19. 1 (3 - 45) months. Gross total resection(n = 18, 64. 3%), subtotal resection(n = 6, 21. 4%) and partial resection(n = 4, 14. 3%) were achieved. Postoperatively, visual acuity improved in 11 patients (73. 3%) and 6 patients (40. 0%) showed endocrine remission. Qne patient had short-term postoperative leakage of cerebrospinal fluid (CSF). CONCLUSION: Endoscopic endonasal transsphenoidal surgery is both safe and effective for recurrent or regrowing pituitary adenomas.

Random forest-based prediction of intracranial hypertension in patients with traumatic brain injury.

BACKGROUND: Treatment and prevention of intracranial hypertension (IH) to minimize secondary brain injury are central to the neurocritical care management of traumatic brain injury (TBI). Predicting the onset of IH in advance allows for a more aggressive prophylactic treatment. This study aimed to develop random forest (RF) models for predicting IH events in TBI patients. METHODS: We analyzed prospectively collected data from patients admitted to the intensive care unit with invasive intracranial pressure (ICP) monitoring. Patients with persistent ICP > 22 mmHg in the early postoperative period (first 6 h) were excluded to focus on IH events that had not yet occurred. ICP-related data from the initial 6 h were used to extract linear (ICP, cerebral perfusion pressure, pressure reactivity index, and cerebrospinal fluid compensatory reserve index) and nonlinear features (complexity of ICP and cerebral perfusion pressure). IH was defined as ICP > 22 mmHg for > 5 min, and severe IH (SIH) as ICP > 22 mmHg for > 1 h during the subsequent ICP monitoring period. RF models were then developed using baseline characteristics (age, sex, and initial Glasgow Coma Scale score) along with linear and nonlinear features. Fivefold cross-validation was performed to avoid overfitting. RESULTS: The study included 69 patients. Forty-three patients (62.3%) experienced an IH event, of whom 30 (43%) progressed to SIH. The median time to IH events was 9.83 h, and to SIH events, it was 11.22 h. The RF model showed acceptable performance in predicting IH with an area under the curve (AUC) of 0.76 and excellent performance in predicting SIH (AUC = 0.84). Cross-validation analysis confirmed the stability of the results. CONCLUSIONS: The presented RF model can forecast subsequent IH events, particularly severe ones, in TBI patients using ICP data from the early postoperative period. It provides researchers and clinicians with a potentially predictive pathway and framework that could help triage patients requiring more intensive neurological treatment at an early stage.

Allicin treats myocardial infarction in I/R through the promotion of the SHP2 axis to inhibit p-PERK-mediated oxidative stress.

OBJECTIVE: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice. METHODS: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3. RESULTS: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3. CONCLUSIONS: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.

Rethinking the effects of adjuvant beam radiation therapy on overall survival in atypical meningioma patients: age considerations.

Background: This study aimed to investigate the effects of adjuvant beam radiation therapy (ABRT) on overall survival (OS) in patients with primary single intracranial atypical meningioma (AM), with a focus on age-related outcomes. Methods: We conducted a retrospective study using data from SEER database. Our cohort consisted of patients diagnosed with a primary single intracranial AM tumor and had undergone surgery. The primary endpoint was OS. For survival analysis, univariable and multivariable Cox regression analysis were performed. A multivariable additive Cox model was used to assess the functional relationship between age and OS in patients with or without ABRT. Results: Of the 2,759 patients included, 1,650 underwent gross total resection and 833 received ABRT. Multivariable Cox analysis indicated that ABRT did not significantly influence OS across the entire cohort. According to the multivariable generalized additive Cox model, the relative risk of all-cause mortality increased with advancing age in both ABRT-yes and ABRT-no group. ABRT-yes had a lower relative risk than ABRT-no when age ≤ 55 years old while a higher relative risk when age > 55 years old. Subsequent multivariable Cox analysis showed that ABRT was associated with a significant lower risk for all-cause mortality in patients with age ≤ 55 years old while a significant higher risk in patients with age > 55 years old. Conclusion: Our study found that ABRT enhanced OS in younger primary single intracranial AM patients. But we also revealed a negative correlation between OS and ABRT in older patients.

Reinforcing and toughening bacterial cellulose/MXene films assisted by interfacial multiple cross-linking for electromagnetic interference shielding and photothermal response.

Ultrathin MXene composite films, with their flexibility, metal-level conductivity, and multifunction compatibility, are an ideal choice for electromagnetic interference (EMI) shielding materials in future developments. Nonetheless, the dilemma between electrical conductivity and robustness in these composite films remains a challenge. Herein, an ammonium polyphosphate (APP) assisted interfacial multiple cross-linking strategy, achieved via simple solution blending and filtration, was employed to reinforce and toughen the "brick-mortar" layered MXene/bacterial cellulose (MBCA) films without compromising their conductivity and EMI shielding ability. The introduction of a small amount of APP leads to multiple interfacial interactions between MXene and bacterial cellulose, resulting in significant enhancements in mechanical strength (360.8 MPa), Young's modulus (2.8 GPa), fracture strain (17.3%), and toughness (34.1 MJ/m3). Concurrently, the MBCA film displayed satisfactory conductivity values of 306.7 S/cm and an EMI SE value of 41 dB upon optimizing the MXene content. Additionally, the MBCA film demonstrated a consistent, rapid-response photothermal conversion capability, achieving a photothermal conversion temperature of 97 °C under a light intensity of 200 mW/m2. Consequently, this tough and multifunctional EMI shielding film holds substantial promise for protecting electronic equipment.

Non-Invasive Assessment of Intracranial Hypertension in Patients with Traumatic Brain Injury Using Computed Tomography Radiomic Features: A Pilot Study.

This study aimed to assess intracranial hypertension in patients with traumatic brain injury non-invasively using computed tomography (CT) radiomic features. Fifty patients from the primary cohort were enrolled in this study. The clinical data, pre-operative cranial CT images, and initial intracranial pressure readings were collected and used to develop a prediction model. Data of 20 patients from another hospital were used to validate the model. Clinical features including age, sex, midline shift, basilar cistern status, and ventriculocranial ratio were measured. Radiomic features-i.e., 18 first-order and 40 second-order features- were extracted from the CT images. LASSO method was used for features filtration. Multi-variate logistic regression was used to develop three prediction models with clinical (CF model), first-order (FO model), and second-order features (SO model). The SO model achieved the most robust ability to predict intracranial hypertension. Internal validation showed that the C-statistic of the model was 0.811 (95% confidence interval [CI]: 0.691-0.931) with the bootstrapping method. The Hosmer Lemeshow test and calibration curve also showed that the SO model had excellent performance. The external validation results showed a good discrimination with an area under the curve of 0.725 (95% CI: 0.500-0.951). Although the FO model was inferior to the SO model, it had better prediction ability than the CF model. The study shows that the radiomic features analysis, especially second-order features, can be used to evaluate intracranial hypertension non-invasively compared with conventional clinical features, given its potential for clinical practice and further research.

Association between P2Y12 inhibitor reloading and in-hospital outcomes for patients with non-ST-segment elevation acute coronary syndrome already on chronic P2Y12 receptor inhibitors therapy in China: findings from the CCC-ACS (improving care for cardiovascular disease in China-acute coronary syndrome) project.

BACKGROUND: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined. METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted. RESULTS: The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P = 0.007), and all-cause death (0.36% vs. 0.99%, P = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16-0.78; (P = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14-0.94; (P = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups. CONCLUSIONS: In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014).

Pituitary adenoma with cavernous sinus compartment penetration and intracranial extension: surgical anatomy, approach, and outcomes.

Objectives: To understand the different characteristics and growth corridors of knosp grade 4 pituitary adenomas (Knosp4PA) with cavernous sinus (CS) compartments penetration and intracranial extension, aiming to improve the safety, effectiveness, and total resection rate of surgery. Methods: A case series of 120 Knosp4PA patients with 187 invaded compartments were retrospectively reviewed. A novel surgery-relevant grading system was proposed according to the CS penetrating features. The details of approach drafting, risk prediction, and complication avoidance were analyzed and integrated through illustrated cases. Results: All enrolled tumor was Knosp4PA which was derived from Knosp subgrades 3A(62.5%) and 3B(37.5%). Based on the tumor growth pathway and its relevant features, five subclassifications of intracranial extension(n=98,81.7%) were classified, which derived from the superior (Dolenc's and Oculomotor subtype, 5% and 24.2%), lateral (Parkinson's subtype,18.3%), and posterior (cerebral peduncle and Dorello's subtype, 5.8% and 1.7%) CS compartment penetration. The size of intracranial extension is assessed by Lou's scale proposed here based on preoperative MRI characteristics. Under Lou's scale, the gross total rate (GTR) decreased (82%, 53%, 22%, and 19%) with grades increased (grade 0,1,2,3, respectively), and presents significant difference between the four groups (p=0.000), as well as between single and multiple compartments involved (p=0.001). Preoperative cranial nerve deficits included the optic nerve (53%), oculomotor nerve (24.2%), and abducent nerve (4.2%), with an overall rate of visual function improvement in 68.1%. Postoperative complications of transient diabetes insipidus, cerebrospinal fluid (CSF) leakage, and cranial nerve deficits were 6.7%, 0.8%, and 0%. No new cranial nerve deficits occurred. The mortality rate was 0.8%. Conclusion: The concept of "penetration" refines the extracavernous growth pattern, and the five intracranial subclassifications help to understand the potential extension corridors, enhancing adequate exposure and targeted resection of Knosp4PA. This grading system may benefit from its predictive and prognostic value, from which a higher GTR rate can be achieved.

Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological conditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the expression and cellular location of TAM (Tyro3, Axl, and Mertk) receptors and their ligands growth arrest-specific 6 (Gas6) and Protein S (ProS1) were examined by PCR, western blots, and fluorescence immunostaining. Thirty minutes after SAH, mice received an intraventricular injection of recombinant Gas6 (rGas6) or recombinant ProS1 (rPros1) and underwent evaluations of inflammatory mediator expression, neurological deficits, and blood-brain barrier integrity at 24 h. Microglia efferocytosis of apoptotic neurons was analyzed in vivo and in vitro. The potential mechanism was determined by inhibiting or knocking down TAM receptors and Rac1 by specific inhibitors or siRNA. SAH induced upregulation of Axl and its ligand Gas6. The administration of rGas6 but not rPros1 promoted microglia efferocytosis, alleviated inflammation, and ameliorated SAH-induced BBB breakdown and neurological deficits. The beneficial effects of rGas6 were arrogated by inhibiting or knocking down Axl and Rac1. We concluded that rGas6 attenuated the development of early brain injury in mice after SAH by facilitating microglia efferocytosis and preventing inflammatory response, which is partly dependent on activation of Axl and Rac1.

Acute traumatic coma awakening by right median nerve electrical stimulation: a randomised controlled trial.

PURPOSE: Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI. METHODS: This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7-14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 µs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set. RESULTS: Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2-78.7% vs. 56.8%, n = 92, 95% CI 49.1-64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3-7] vs. 4 [IQR 2-6], p = 0.002; 6 [IQR 3-7] vs. 4 [IQR 2-7], p = 0.0005) and FOUR at 28 days (15 [IQR 13-16] vs. 13 [interquartile range (IQR) 11-16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device. CONCLUSION: Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.

Is high PEEP ventilation strategy safe for acute respiratory distress syndrome after severe traumatic brain injury?

PRIMARY OBJECTIVE: To investigate the safety and efficacy of high positive end-expiratory pressure (PEEP) ventilation strategy for acute respiratory distress syndrome (ARDS) after traumatic brain injury. RESEARCH DESIGN: A case report and discussion based on literature review. METHODS AND PROCEDURES: This article reports the case of a 17-year-old male patient who developed ARDS after severe traumatic brain injury. PEEP was applied and adjusted to appropriate levels on the basis of information obtained from continuous monitoring of cerebral and systemic haemodynamics. Data from medical charts, surgical notes and radiographic findings were reviewed and analysed. MAIN OUTCOMES AND RESULTS: With the application of high PEEP ventilation, the patient survived ARDS following severe traumatic brain injury and achieved a favourable neurological outcome. A titration of PEEP levels from 5-15 cm H2O in the patient resulted in acceptable changes of cerebral and systemic haemodynamics, including an increase of intracranial pressure (ICP) from 15 to 18 mmHg and a decrease of cerebral perfusion pressure (CPP) from 78 to 72 mmHg. CONCLUSIONS: With close monitoring of cerebral and systemic haemodynamics, PEEP can be safely applied and titrated to an optimal level in the management of ARDS following traumatic brain injury.