Risk factors for hemorrhage in patients with long-term aspirin therapy undergoing emergency external ventricular drainage/intracranial pressure probe placement.

Background: Studies have been inconclusive on the risk for hemorrhage in patients with a history of aspirin use who underwent emergency external ventricular drainage (EVD)/intracranial pressure (ICP) probe placement. The aim of this study was to explore hemorrhage-related risk factors in order to reduce the risk for hemorrhage in these patients. Methods: Between July 2014 and July 2020, patients were retrospectively divided into EVD/ICP-related hemorrhage and non-hemorrhage groups. The collected data included age, gender, major diagnosis, medical history, imaging examinations, conventional coagulation test data, thromboelastography with platelet mapping (TEG-PM), surgical procedures and discharge conditions. Results: In total 94 patients, 21 in the hemorrhage group (15 males, 6 females) and 73 in the non-hemorrhage group (52 males, 21 females) were included. The majority of hemorrhages were recorded in EVD patients (19/21; 90.5%). Platelet AA pathway inhibition rate of ≥75% (sensitivity: 79.45% specificity: 52.38%) (P = 0.014) and SBP ≥125 mmHg (P = 0.006) were significantly related to hemorrhage. When the platelet AA pathway inhibition rate was ≥75% and the during-procedure SBP was ≥125 mmHg, the hemorrhage rate was significantly higher (83.3%) than with SBP <125 mmHg (6.7%) (P < 0.001). When the inhibition rate was <75%, there were no significant differences in the hemorrhage rates between the during-procedure SBP ≥125 mmHg group (17.2%) and the SBP <125 mmHg group (13.2%) (P > 0.05). Multivariate logistic regression analysis revealed that a platelet AA pathway inhibition rate ≥75% (OR = 5.183, 95% CI: 1.683-15.960) and during-procedure SBP ≥125 mmHg (OR = 4.609, 95% CI: 1.466-14.484) were independent risk factors for EVD/ICP-related hemorrhage. Conclusion: Patients with long-term aspirin therapy, a platelet AA pathway inhibition rate ≥75% and during-procedure SBP ≥125 mmHg had a significantly higher risk of hemorrhage, which could be reduced by adjusting the SBP to <125 mmHg.

Clinical outcomes of solitary fibrous tumors and hemangiopericytomas and risk factors related to recurrence and survival based on the 2021 WHO classification of central nervous system tumors.

OBJECTIVE: The authors aimed to explore the clinical outcomes and risk factors related to recurrence of and survival from solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) that were reclassified according to the 2021 WHO classification of central nervous system (CNS) tumors. METHODS: The authors retrospectively collected and analyzed the clinical and pathological data of SFTs and HPCs recorded from January 2007 to December 2021. Two neuropathologists reassessed pathological slides and regraded specimens on the basis of the 2021 WHO classification. The prognostic factors related to progression-free survival (PFS) and overall survival (OS) were statistically assessed with univariate and multivariate Cox regression analyses. RESULTS: A total of 146 patients (74 men and 72 women, mean ± SD [range] age 46.1 ± 14.3 [3-78] years) were reviewed, and 86, 35, and 25 patients were reclassified as having grade 1, 2, and 3 SFTs on the basis of the 2021 WHO classification, respectively. The median PFS and OS of the patients with WHO grade 1 SFT were 105 months and 199 months after initial diagnosis; for patients with WHO grade 2 SFT, 77 months and 145 months; and for patients with WHO grade 3 SFT, 44 months and 112 months, respectively. Of the entire cohort, 61 patients experienced local recurrence and 31 died, of whom 27 (87.1%) died of SFT and relevant complications. Ten patients had extracranial metastasis. In multivariate Cox regression analysis, subtotal resection (STR) (HR 4.648, 95% CI 2.601-8.304, p < 0.001), tumor located in the parasagittal or parafalx region (HR 2.105, 95% CI 1.099-4.033, p = 0.025), tumor in the vertebrae (HR 3.352, 95% CI 1.228-9.148, p = 0.018), WHO grade 2 SFT (HR 2.579, 95% CI 1.343-4.953, p = 0.004), and WHO grade 3 SFT (HR 5.814, 95% CI 2.887-11.712, p < 0.001) were significantly associated with shortened PFS, whereas STR (HR 3.217, 95% CI 1.435-7.210, p = 0.005) and WHO grade 3 SFT (HR 3.433, 95% CI 1.324-8.901, p = 0.011) were significantly associated with shortened OS. In univariate analyses, patients who received adjuvant radiotherapy (RT) after STR had longer PFS than patients who did not receive RT. CONCLUSIONS: The 2021 WHO classification of CNS tumors better predicted malignancy with different pathological grades, and in particular WHO grade 3 SFT had worse prognosis. Gross-total resection (GTR) can significantly prolong PFS and OS and should serve as the most important treatment method. Adjuvant RT was helpful for patients who underwent STR but not for patients who underwent GTR.

An alternative extension of telomeres related prognostic model to predict survival in lower grade glioma.

OBJECTIVE: The alternative extension of the telomeres (ALT) mechanism is activated in lower grade glioma (LGG), but the role of the ALT mechanism has not been well discussed. The primary purpose was to demonstrate the significance of the ALT mechanism in prognosis estimation for LGG patients. METHOD: Gene expression and clinical data of LGG patients were collected from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) cohort, respectively. ALT-related genes obtained from the TelNet database and potential prognostic genes related to ALT were selected by LASSO regression to calculate an ALT-related risk score. Multivariate Cox regression analysis was performed to construct a prognosis signature, and a nomogram was used to represent this signature. Possible pathways of the ALT-related risk score are explored by enrichment analysis. RESULT: The ALT-related risk score was calculated based on the LASSO regression coefficients of 22 genes and then divided into high-risk and low-risk groups according to the median. The ALT-related risk score is an independent predictor of LGG (HR and 95% CI in CGGA cohort: 5.70 (3.79, 8.58); in TCGA cohort: 1.96 (1.09, 3.54)). ROC analysis indicated that the model contained ALT-related risk score was superior to conventional clinical features (AUC: 0.818 vs 0.729) in CGGA cohorts. The results in the TCGA cohort also shown a powerful ability of ALT-related risk score (AUC: 0.766 vs 0.691). The predicted probability and actual probability of the nomogram are consistent. Enrichment analysis demonstrated that the ALT mechanism was involved in the cell cycle, DNA repair, immune processes, and others. CONCLUSION: ALT-related risk score based on the 22-gene is an important factor in predicting the prognosis of LGG patients.

Prognostic significance of perihematomal edema in basal ganglia hemorrhage after minimally invasive endoscopic evacuation.

OBJECTIVE: Spontaneous basal ganglia hemorrhage is a common type of intracerebral hemorrhage (ICH) with no definitive treatment. Minimally invasive endoscopic evacuation is a promising therapeutic approach for ICH. In this study the authors examined prognostic factors associated with long-term functional dependence (modified Rankin Scale [mRS] score ≥ 4) in patients who had undergone endoscopic evacuation of basal ganglia hemorrhage. METHODS: In total, 222 consecutive patients who underwent endoscopic evacuation between July 2019 and April 2022 at four neurosurgical centers were enrolled prospectively. Patients were dichotomized into functionally independent (mRS score ≤ 3) and functionally dependent (mRS score ≥ 4) groups. Hematoma and perihematomal edema (PHE) volumes were calculated using 3D Slicer software. Predictors of functional dependence were assessed using logistic regression models. RESULTS: Among the enrolled patients, the functional dependence rate was 45.50%. Factors independently associated with long-term functional dependence included female sex, older age (≥ 60 years), Glasgow Coma Scale score ≤ 8, larger preoperative hematoma volume (OR 1.02), and larger postoperative PHE volume (OR 1.03, 95% CI 1.01-1.05). A subsequent analysis evaluated the effect of stratified postoperative PHE volume on functional dependence. Specifically, patients with large (≥ 50 to < 75 ml) and extra-large (≥ 75 to 100 ml) postoperative PHE volumes had 4.61 (95% CI 0.99-21.53) and 6.75 (95% CI 1.20-37.85) times greater likelihood of long-term dependence, respectively, than patients with a small postoperative PHE volume (≥ 10 to < 25 ml). CONCLUSIONS: A large postoperative PHE volume is an independent risk factor for functional dependence among basal ganglia hemorrhage patients after endoscopic evacuation, especially with postoperative PHE volume ≥ 50 ml.

P7C3-A20 Attenuates Microglial Inflammation and Brain Injury after ICH through Activating the NAD+/Sirt3 Pathway.

Intracerebral hemorrhage (ICH) is lethal but lacks effective therapies. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite indispensable for a broader range of fundamental intracellular biological functions. Reduction of NAD+ usually occurs after acute brain insults, and supplementation of NAD+ has been proven neuroprotective. P7C3-A20 is a novel compound featuring its ability to facilitate the flux of NAD+. In this study, we sought to determine the potential therapeutic value of P7C3-A20 in ICH. In collagenase-induced ICH mouse models, we found that P7C3-A20 treatment could diminish lesion volume, reduce blood-brain barrier (BBB) damage, mitigate brain edema, attenuate neural apoptosis, and improve neurological outcomes after ICH. Further, RNA sequencing and subsequent experiments revealed that ICH-induced neuroinflammation and microglial proinflammatory activities were significantly suppressed following P7C3-A20 treatment. Mitochondrial damage is an important trigger of inflammatory response. We examined mitochondrial morphology and function and found that P7C3-A20 could attenuate OxyHb-induced impairment of mitochondrial dynamics and functions in vitro. Mechanistically, Sirt3, an NAD+-dependent deacetylase located in mitochondria, was then found to play a vital role in the protection of P7C3-A20 against mitochondrial damage and inflammatory response. In rescue experiments, P7C3-A20 failed to exert those protective effects in microglia-specific Sirt3 conditional knockout (CKO) mice. Finally, preclinical research revealed a correlation between the plasma NAD+ level and the neurological outcome in ICH patients. These results demonstrate that P7C3-A20 is a promising therapeutic agent for neuroinflammatory injury after ICH and exerts protective actions, at least partly, in a Sirt3-dependent manner.

Predicting Neurological Deterioration after Moderate Traumatic Brain Injury: Development and Validation of a Prediction Model Based on Data Collected on Admission.

Moderate traumatic brain injury (mTBI) is a heterogeneous entity that is poorly defined in the literature. Patients with mTBI have a high rate of neurological deterioration (ND), which is usually accompanied by poor prognosis and no definitive methods to predict. The purpose of this study is to develop and validate a prediction model that estimates the ND risk in patients with mTBI using data collected on admission. Data for 479 patients with mTBI collected retrospectively in our department were analyzed by logistic regression models. Bivariable logistic regression identified variables with a p < 0.05. Multi-variable logistic regression modeling with backward stepwise elimination was used to determine reduced parameters and establish a prediction model. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. The prediction model was validated using data for 176 patients collected from another hospital. Eight independent prognostic factors were identified: hypertension, Marshall scale (types III and IV), subdural hemorrhage (SDH), location of contusion (frontal and temporal contusions), Injury Severity Score >13, D-dimer level >11.4 mg/L, Glasgow Coma Scale score ≤10, and platelet count ≤152 × 109/L. A prediction model was established and was shown as a nomogram. Using bootstrapping, internal validation showed that the C-statistic of the prediction model was 0.881 (95% confidence interval [CI]: 0.849-0.909). The results of external validation showed that the nomogram could predict ND with an area under the curve of 0.827 (95% CI: 0.763-0.880). The present model, based on simple parameters collected on admission, can predict the risk of ND in patients with mTBI accurately. The high discriminative ability indicates the potential of this model for classifying patients with mTBI according to ND risk.

The causal association between body mass index and type 2 diabetes mellitus-evidence based on regression discontinuity design.

OBJECTIVE: This study aimed to investigate and determine the precise causal association between body mass index (BMI) and type 2 diabetes mellitus (T2DM) using a regression discontinuity design (RDD). METHODS: The cross-sectional data of 8550 participants were from the China Health and Nutrition Survey (CHNS) in 2015. Influencing factors with statistically significant were selected with logistic regression analysis, and a risk prediction model was established to obtain the risk of individuals suffering from T2DM. RDD was performed with BMI as the grouping variable and the risk of individuals suffering from T2DM as the outcome variable. RESULTS: The predictive factors in the T2DM risk prediction model were age, gender, BMI, habitation, education, physical activity level, preference for sugary beverages, walking, self-evaluation health status and history of hypertension. The AUC (area under receiver operating characteristic curve) of the T2DM risk prediction model was 0.849 (95% CI: 0.833, 0.866). BMI was an independent risk factor for T2DM (OR = 1.109, p < 0.001); at BMI = 31 kg/m2 , the risk of T2DM increased sharply by 5.03% (p = 0.006). CONCLUSIONS: There was a positive causal association between BMI and T2DM; when BMI = 31 kg/m2 , the risk of individuals suffering from T2DM was sharply increased.

Trends in the age-related incidence of colon and rectal cancers in China, 2005-2015.

BACKGROUND: Recent evidences showed that the incidence of colorectal cancer decreased among older adults, yet this decline didn't appear in adults younger than 50 years. Our aim was to evaluate age-related incidence trends of colon and rectal cancers in China during 2005-2015. METHODS: A retrospective study of colon and rectal cancers was conducted using population-based data from the Chinese Cancer Registry Annual Report. Age at diagnosis was analyzed in five sub-groups (0-19, 20-34, 35-49, 50-64 and 65 years). Data including new cases, incidence, and age-standardized rates (ASRs) were classified by sex and area. Temporal trends of ASRs were determined with Joinpoint regression analysis. RESULTS: From 2005 to 2015, colon cancer incidence decreased by -2.2% (95%CI: -3.1, -1.3) per year. A more steady decrease was seen in rectal cancer with AAPC of -0.9% (95%CI: -1.4, -0.4). Stratified by age at diagnosis, incidence trends followed a similar pattern, without age-related disparity. Females showed pronounced declines relative to males. The exception was that rural individuals showed opposite increasing trends, with 2.7% of AAPCs for colon cancer and 2.0% for rectal cancer. CONCLUSION: A slight decline was observed in colon and rectal cancers during 2005-2015, regardless of age at diagnosis.

Linear association between grip strength and all-cause mortality among the elderly: results from the SHARE study.

BACKGROUND: Grip strength had become a potential tool for clinical assessments, while the predictive value of the grip strength of community-based populations had some limitations. AIMS: To identify the shapes of the association between grip strength and all-cause mortality in the Survey of Health, Ageing and Retirement in Europe (SHARE) cohort. METHODS: Based on the SHARE cohort, 13,231 subjects aged 65 years and older were included in this study. Cox models with penalized splines (P-splines) were employed to characterize the shapes of the association between grip strength and all-cause mortality with the adjustment of covariates including sociodemographic characteristics, health characteristics, behavioral habits, and illness status. Then grip strength was analyzed as a categorical variable in quintile to examine the impact of low grip strength on all-cause mortality. RESULTS: Inversely linear associations were found between grip strength and mortality both in males and females after adjustment for covariates. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for each 5 kg decrease in grip strength to all-cause mortality were 1.11 (1.06-1.18) in males and 1.17 (1.08-1.28) in females. In comparison with subjects in the fifth quintile, the adjusted HRs and 95% CIs of all-cause mortality in the first quintile was 2.39 (1.79-3.19) in males and 1.84 (1.34-2.51) in females. Which were statistically significant in the second quintile compared with the fifth quintile [Males: 2.06 (1.56, 2.74), Females: 1.83 (1.35, 2.48)]. CONCLUSIONS: Grip strength is inversely linear association with all-cause mortality and the low grip strength at the first and second quintile are a robust predictor of all-cause mortality.

[Multi-correspondence analysis of the status and related factors of chronic diseases multimorbidity in middle-aged and elderly people in China in 2009].

OBJECTIVE: To study the status of chronic disease multimorbidity of middle-aged and elderly people over 45 years old in China, and to analyze the influencing factors. METHODS: Using the data of the"China Health and Nutrition Survey(CHNS)", this survey has been carried out in 10 rounds nationwide since 1989. Multi-stage cluster random sampling was used to investigate rural and urban areas in 9 provinces and cities in China. In this study, the general socio-demographic characteristics, disease history, living habits and other information in the 2009 database were used to analyze the subjects who were collected blood samples. The prevalence of 8 common chronic diseases and multimorbidity such as hypertension, mixed-hyperlipidemia and hyperuricemia were described respectively. The Venn diagram in the R software package was used to calculate the multimorbidity of the disease. The χ~2 test and multiple correspondence analysis were used to explore the influencing factors of chronic disease multimorbidity in the middle-aged and elderly people in China. RESULTS: Among the 5316 subjects, the highest prevalence among 8 chronic diseases was hypertension(2143, 40. 3%). The lowest prevalence was myocardial infarction(87, 1. 4%). There were all together 1498 patients who had two kinds or more than two kinds of chronic diseases with a detection rate of 28. 18%. The most common multimorbidity were hypertension+hyperuricemia(199, 13. 30%), followed by hypertension + mixed-hyperlipidemia(191, 12. 77%). Hypertension+hyperuricemia+mixed-hyperlipidemia was the most common combination of the three chronic diseases(103, 6. 89%). Age(Kendull=0. 158, P<0. 001), region(χ~2=30. 129, P<0. 001), BMI(Kendull=0. 344, P<0. 001) and marital status(χ~2=21. 923, P<0. 001) were associated with the number of multimorbidities. Correspondence analysis showed that subjects aged 65 to 74, living in cities and sleeping less than 7 hours were more likely to have multimorbidity. CONCLUSION: The prevalence of chronic disease multimorbidity among middle-aged and elderly residents in China is high. Older age, unmarried, overweight and obesity, too little or too much sleep may increase the risk of multimorbidity.

Body mass index increases the lymph node metastasis risk of breast cancer: a dose-response meta-analysis with 52904 subjects from 20 cohort studies.

BACKGROUND: Since body mass index (BMI) is a convincing risk factor for breast cancer, it is speculated to be associated with lymph node metastasis. However, epidemiological studies are inconclusive. Therefore, this study was conducted to investigate the effect of BMI on the lymph node metastasis risk of breast cancer. METHODS: Cohort studies that evaluating BMI and lymph node metastasis in breast cancer were selected through various databases including PubMed, PubMed Central (PMC), Web of science, the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals (VIP) and Wanfang Data Knowledge Service Platform (WanFang) until November 30, 2019. The two-stage, random effect meta-analysis was performed to assess the dose-response relationship between BMI and lymph node metastasis risk. Between-study heterogeneity was assessed using I2. Subgroup analysis was done to find possible sources of heterogeneity. RESULTS: We included a total of 20 studies enrolling 52,904 participants. The summary relative risk (RR) (1.10, 95%CI: 1.06-1.15) suggested a significant effect of BMI on the lymph node metastasis risk of breast cancer. The dose-response meta-analysis (RR = 1.01, 95%CI: 1.00-1.01) indicated a positive linear association between BMI and lymph node metastasis risk. For every 1 kg/m2 increment of BMI, the risk of lymph node metastasis increased by 0.89%. In subgroup analyses, positive linear dose-response relationships between BMI and lymph node metastasis risk were observed among Asian, European, American, premenopausal, postmenopausal, study period less than 5 years, and more than 5 years groups. For every 1 kg/m2 increment of BMI, the risk of lymph node metastasis increased by 0.99, 0.85, 0.61, 1.44, 1.45, 2.22, and 0.61%, respectively. CONCLUSION: BMI significantly increases the lymph node metastasis risk of breast cancer as linear dose-response reaction. Further studies are needed to identify this association.

Molecular Pathological Markers Correlated With the Recurrence Patterns of Glioma.

PURPOSE: Glioma is one of the most common tumors of the central nervous system, and many patients suffer from recurrence even after standard comprehensive treatment. However, little is known about the molecular markers that predict the recurrence patterns of glioma. This study aimed to demonstrate the correlations between molecular markers and glioma recurrence patterns, which included local/nonlocal recurrence and paraventricular/nonparaventricular recurrence. METHODS: Immunohistochemical techniques were used to assess the molecular markers of 88 glioma tissues following surgical resection. The recurrence patterns were divided into local recurrence, marginal recurrence, distant recurrence, multirecurrence, and subarachniod recurrence, with the last four recurrence patterns being collectively called nonlocal recurrence. According to whether the recurrence invaded ventricles, the nonlocal recurrence patterns were divided into paraventricular and nonparaventricular recurrence. Then, we compared the different recurrence patterns and their clinical characteristics, focusing on the expression of molecular markers. RESULTS: More patients in the nonlocal recurrence group received combined radiotherapy and chemotherapy than patients in the local recurrence group (p=0.019). Sex, age, extent of surgery, time to recurrence, tumor location, size, and WHO grade were not different in the defined groups (P>0.05). Recurrent tumor volume and WHO grade were significantly different between the paraventricular and nonparaventricular recurrence groups (p=0.046 and 0.033). The expression of Ki-67, P53, and PCNA in the nonlocal recurrence group was significantly higher than that in the local recurrence group (p=0.015, 0.009, and 0.037), while the expression of S-100 in the nonlocal recurrence group was significantly lower than that in the local recurrence group (p=0.015). Cox regression indicated hazard ratio (HR) for high expression level of PCNA associated with non-local recurrence was 3.43 (95% CI, 1.15, 10.24), and HR for high expression level of MGMT associated with paraventricular recurrence was 2.64 (95% CI, 1.15,6.08). CONCLUSIONS: Ki-67, P53, PCNA, and MGMT might be important clinical markers for nonlocal recurrence and paraventricular recurrence.

[Relationship between serum magnesium concentration and obesity in Chinese adults].

OBJECTIVE: To explore the relationship between concentration of serum magnesium with overweight/obesity and abdominal obesity in Chinese adults. METHODS: Data from China Health and Nutrition Survey investigated in 2009 was analyzed. Rank correlation analysis, univariate analysis and binary Logistic regression analysis were performed to analyze influence of serum magnesium concentrations, regions and gender on the prevalence of overweight/obesity and abdominal obesity. RESULTS: The prevalence of overweight/obesity was 40. 2%. The concentration of serum magnesium in people withoverweight/obesity was higher than that in people with non-overweight/obesity( 0. 95 mmol/L vs. 0. 93 mmol/L, t = 7. 021, P < 0. 001). The prevalence of overweight/obesity was 33. 2%. The concentration of serum magnesium in people with abdominal obesity was higher than that in people with non-abdominal obesity( 0. 95 mmol/L vs. 0. 93 mmol/L, t = 5. 712, P < 0. 001). The serum magnesium concentration, prevalence of overweight/obesity and abdominal obesity were higher in magnesium-rich area than in the nonmagnesium-rich areas, which showed significant differences between two groups( serum magnesium: t = 8. 012, P < 0. 001; overweight/obesity: χ~2= 138. 252, P < 0. 001;abdominal obesity: χ~2= 134. 999, P < 0. 001). The rank correlation coefficients between serum magnesium concentration and prevalence of overweight/obesity and abdominal obesity were 0. 952 and 0. 796 in male, and 0. 794 and 0. 903 in female, respectively. Serum magnesium concentration was divided into four grades according to quartiles. The risk of overweight/obesity increased by 1. 207 times( 95% CI 1. 138-1. 281) when the serum magnesium increased a level, and the risk of abdominal obesity increased by 1. 187 times( 95% CI 1. 114-1. 266). CONCLUSION: Higher serum magnesium concentration may be a risk factor for overweight/obesity and abdominal obesity. Serum magnesium concentration is moderately and even highly correlated with prevalence of obesity, and there is a gender difference in this relationship.