ALTA: a simple nutritional prognostic score for patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Malnutrition, despite being a common complication, is often neglected in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). The objective of this study was to develop a simplified nutritional prognostic score to accurately predict mortality in HBV-ACLF patients. Methods: In this multicenter retrospective study, clinical data from 530 HBV-ACLF patients were used to create a new prognostic score, which was then validated in two external cohorts (n = 229 and 248). Results: Four independent factors were significantly associated with 28-day mortality in HBV-ACLF patients, forming a novel prognostic score (ALTA score = 0.187 × age-0.849 × lymphocyte count-2.033 × total cholesterol-0.148 × albumin-0.971). Notably, the AUROC of ALTA score for 28/90-day mortality (0.950/0.967) were significantly higher than those of three other ACLF prognostic scores (COSSH-ACLF II, 0.864/0.734; MELD, 0.525/0.488; MELD-Na, 0.546/0.517; all P < 0.001), and three known nutritional scores (CONUT, 0.739/0.861; OPNI, 0.279/0.157; NRS-2002, 0.322/0.286; all P < 0.001). The prediction error rates of ALTA score for 28-day mortality were significantly lower than COSSH-ACLF II (7.3%), MELD (14.4%), MELD-Na (12.7%), CONUT (9.0%), OPNI (30.6%), and NRS2002 (34.1%) scores. Further classifying ALTA score into two strata, the hazard ratios of mortality at 28/90 days were notably increased in the high-risk groups compared to the low-risk group (15.959 and 5.740). These results were then validated in two external cohorts. Conclusion: ALTA, as a simplified nutritional prognostic score for HBV-ACLF, demonstrates superiority over the COSSH-ACLF II and other scores in predicting short-term mortality among HBV-ACLF patients. Therefore, it may be used to guide clinical management, particularly in primary care settings.

Construction and validation of a perioperative concomitant lower extremity deep vein thrombosis line graph model in patients with aneurysmal subarachnoid hemorrhage.

Background: To develop and validate a nomogram for predicting the probability of deep venous thrombosis (DVT) in patients with aneurysmal subarachnoid hemorrhage (aSAH) during the perioperative period, using clinical features and readily available biochemical parameters. Methods: The least absolute shrinkage and selection operator (LASSO) regression technique was employed for data dimensionality reduction and selection of predictive factors. A multivariable logistic regression analysis was conducted to establish a predictive model and nomogram for post-aSAH DVT. The discriminative ability of the model was determined by calculating the area under the curve (AUC). Results: A total of 358 aSAH patients were included in the study, with an overall incidence of DVT of 20.9%. LASSO regression identified four variables, including age, modified Fisher grade, total length of hospital stay, and anticoagulation therapy, as highly predictive factors for post-aSAH DVT. The patients were randomly divided into a modeling group and a validation group in a 6:4 ratio to construct the nomogram. The AUCs of the modeling and validation groups were 0.8511 (95% CI, 0.7922-0.9099) and 0.8633 (95% CI, 0.7968-0.9298), respectively. Conclusions: The developed nomogram exhibits good accuracy, discriminative ability, and clinical utility in predicting DVT, aiding clinicians in identifying high-risk individuals and implementing appropriate preventive and treatment measures.

Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults.

BACKGROUND & AIMS: Following the classification of metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD and MASLD remain unclear. METHODS: We analysed data from 7519 participants in the third National Health and Nutrition Examination Surveys of United States (US) and their linked mortality until 2019. Survey weight-adjusted multivariable Cox proportional model was used to study the mortality over three terms. RESULTS: The prevalence of NAFLD, MAFLD and MASLD was 18.5%, 19.3% and 20.8%, respectively. Most individuals with NAFLD (94.5%) or MAFLD (100%) can be classified as MASLD, while a relatively low percentage of those with MASLD were also diagnosed with either NAFLD (84.1%) or MAFLD (92.7%). During a median follow-up of 26.9 years, both MAFLD and MASLD were associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04-1.33 and 1.19, 1.06-1.34, respectively), this association was mainly observed in NAFLD-/MASLD+ subgroups. NAFLD was not associated with all-cause mortality. However, all three terms were associated with an increased risk of all-cause mortality in individuals with advanced fibrosis (aHR: 1.71-1.81). Subgroup analyses showed that higher risk of all-cause mortality for both MAFLD and MASLD were observed among older adults (≥65 year), non-Hispanic whites and those without diabetes. CONCLUSIONS: Both MASLD and MALFD were linked to higher all-cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD.

Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage.

AIMS: Rasd1 has been reported to be correlated with neurotoxicity, metabolism, and rhythm, but its effect in case of subarachnoid hemorrhage (SAH) remained unclear. White matter injury (WMI) and ferroptosis participate in the early brain injury (EBI) after SAH. In this work, we have investigated whether Rasd1 can cause ferroptosis and contribute to SAH-induced WMI. METHODS: Lentivirus for Rasd1 knockdown/overexpression was administrated by intracerebroventricular (i.c.v) injection at 7 days before SAH induction. SAH grade, brain water content, short- and long-term neurobehavior, Western blot, real-time PCR, ELISA, biochemical estimation, immunofluorescence, diffusion tensor imaging (DTI), and transmission electron microscopy (TEM) were systematically performed. Additionally, genipin, a selective uncoupling protein 2(UCP2) inhibitor, was used in primary neuron and oligodendrocyte co-cultures for further in vitro mechanistic studies. RESULTS: Rasd1 knockdown has improved the neurobehavior, glia polarization, oxidative stress, neuroinflammation, ferroptosis, and demyelination. Conversely, Rasd1 overexpression aggravated these changes by elevating the levels of reactive oxygen species (ROS), inflammatory cytokines, MDA, free iron, and NCOA4, as well as contributing to the decrease of the levels of UCP2, GPX4, ferritin, and GSH mechanistically. According to the in vitro study, Rasd1 can induce oligodendrocyte ferroptosis through inhibiting UCP2, increasing reactive oxygen species (ROS), and activating NCOA4-mediated ferritinophagy. CONCLUSIONS: It can be concluded that Rasd1 exerts a modulated role in oligodendrocytes ferroptosis in WMI following SAH.

Establishment and multicenter external validation of a risk prediction model for de novo intracranial aneurysms based on a systematic review and meta-analysis of 19 cohorts.

OBJECTIVE: A de novo intracranial aneurysm (IA) is a second, new IA that develops in patients with IAs distant from where the initial IA was detected. This study aimed to identify risk factors for de novo IA formation and establish and externally validate a multicenter risk prediction model for de novo IAs. METHODS: A systematic review and meta-analysis of existing de novo IA cohorts was conducted to form the derivation cohort. The risk ratios and 95% CIs of each risk factor were calculated. In addition, risk scores included in the model were calculated based on the statistically significant risk factors with their weightings. Then the model was validated in a multicenter external cohort of Chinese patients, and receiver operating characteristic and calibration curves, decision curve analysis, and Kaplan-Meier curves were used to evaluate the model. RESULTS: Nineteen studies with 9351 patients, of whom 304 patients (3.25%) developed de novo IAs, were included in the derivation cohort. These patients developed de novo IAs at 2.5-18.5 years during a total follow-up of 3.3-18.8 years. The statistically significant risk factors were age < 60 years, female sex, smoking history, family history of IAs, multiple IAs at initial diagnosis, and initial IAs in the middle cerebral artery, with risk scores of 4, 5, 2, 6, 3, and 3, respectively. Then, a multicenter external cohort comprising 776 patients, of whom 45 patients (5.80%) developed de novo IAs, was included in the validation cohort. De novo IAs formed in these patients at a mean of 5.25 years during a mean follow-up of 6.19 years. The area under the curve of the model was 0.804, with a sensitivity of 0.667 and specificity of 0.900, at a cutoff value of 13. The calibration curve, decision curve analysis, and Kaplan-Meier curves also indicated good performance of the model. CONCLUSIONS: This prediction model is a convenient and intuitive tool for identifying high-risk patients with de novo IAs. Reasonable use of the model can not only aid in clinical decision-making but also play a positive role in the prevention of aneurysmal subarachnoid hemorrhage to a certain extent.

Willis covered stent treatment for internal carotid artery pseudoaneurysm: A meta-analysis of efficacy and safety.

Background: Pseudoaneurysm (PSA) of internal carotid artery is a rare but severe cerebrovascular disease and difficult to repair surgically. A novel medical device called Willis covered stent (WCS) has been created especially for the treatment of complex cerebrovascular diseases. However, the efficacy and safety of WCS therapy for PSA are still debatable. Additional substantial proof is needed. Methods: To find research pertaining to WCS treatment for PSA, a systematic review of literature was conducted in the Medline, Embase, Web of Science, CNKI, Wanfang, and CBM databases. The results comprising the data of intraoperative situation, postoperative situation, and follow-up were then included in a meta-analysis. Results: The criteria were met by 11 noncomparative studies with 152 patients and 157 PSAs. Technical success rate was nearly 100 % (>0.999 (95 % confidence interval (CI), 0.958, 1.000)), complete occlusion rate was 97.8 % (95 % CI, 0.932, 1.000), and side branch occlusion rate was 0.5 % (95 % CI, 0.001, 0.045). The rates of acute in-stent thrombosis (<0.001 (95 % CI, 0.000, 0.013)) and hemorrhage (<0.001 (95 % CI, 0.000, 0.005)) were both less than 0.1 %. In postoperative situation, surgery-related mortality rate was less than 0.1 % (<0.001 (95 % CI, 0.000, 0.005)). The rates of recurrence (<0.001 (95 % CI, 0.000, 0.002)) and parent artery stenosis (<0.001 (95 % CI, 0.000, 0.008)) were both less than 0.1 %, while late in-stent stenosis occurred in 1.3 % (95 % CI, 0.000, 0.053) of patients. In the end, 98.5 % (95 % CI, 0.943, 1.000) of patients had a good outcome. Conclusion: The application of WCS could be effective and safe for PSAs. The findings of this study could serve as a reference for upcoming clinical trials.

Nomogram based on computed tomography images and clinical data for distinguishing between primary intestinal lymphoma and Crohn's disease: a retrospective multicenter study.

Background: Differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical diagnosis. Aims: To investigate the validity of the nomogram based on clinical and computed tomography (CT) features to identify PIL and CD. Methods: This study retrospectively analyzed laboratory parameters, demographic characteristics, clinical manifestations, and CT imaging features of PIL and CD patients from two centers. Univariate logistic analysis was performed for each variable, and laboratory parameter model, clinical model and imaging features model were developed separately. Finally, a nomogram was established. All models were evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, and decision curve analysis (DCA). Results: This study collected data from 121 patients (PIL = 69, CD = 52) from Center 1. Data from 43 patients (PIL = 24, CD = 19) were collected at Center 2 as an external validation cohort to validate the robustness of the model. Three models and a nomogram were developed to distinguish PIL from CD. Most models performed well from the external validation cohort. The nomogram showed the best performance with an AUC of 0.921 (95% CI: 0.838-1.000) and sensitivities, specificities, and accuracies of 0.945, 0.792, and 0.860, respectively. Conclusion: A nomogram combining clinical data and imaging features was constructed, which can effectively distinguish PIL from CD.

Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials.

Background: Stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH), remains a leading cause of mortality globally. Different stroke subtypes have similar detrimental effects in multiple fields of health. Previous research has shown that metformin plays a neuroprotective role in experimental animal models of stroke; however, a preclinical quantitative analysis on the ability of metformin to treat stroke is still lacking. This meta-analysis evaluates the efficacy of metformin in improving stroke prognosis in rodent models of stroke. Methods: Relevant preclinical trials were retrieved from PubMed, EMBASE, and the Web of Science. The neurological score (NS), brain water content (BWC), infarct size, rotarod test, TUNEL, neuron quantity, microglia quantity, and p-AMPK levels were compared between a control group and a metformin group using the standardized mean difference (SMD) and corresponding confidence interval (CI). Quality was assessed with SYRCLE's risk of bias tool. Results: Fifteen articles published from 2010 to 2022 were included in the meta-analysis. The metformin group had statistically significant differences compared to the control group in the following aspects: NS (SMD -1.45; 95% CI -2.32, -0.58; p = 0.001), BWC (SMD -3.22; 95% CI -4.69, -1.76; p < 0.0001), infarct size (SMD -2.90; 95% CI -3.95, -1.85; p < 0.00001), rotarod test (SMD 2.55; 95% CI 1.87, 3.23; p < 0.00001), TUNEL (SMD -3.63; 95% CI -5.77, -1.48; p = 0.0009), neuron quantity (SMD 3.42; 95% CI 2.51, 4.34; p < 0.00001), microglia quantity (SMD -3.06; 95% CI -4.69, -1.44; p = 0.0002), and p-AMPK levels (SMD 2.92; 95% CI 2.02, 3.82; p < 0.00001). Furthermore, sensitivity analysis and stratified analysis were conducted for heterogeneous outcome indicators. Conclusion: Overall, metformin treatment improves severe outcomes triggered by stroke. Despite the limitations intrinsic to animal studies, this systematic review may provide a vital reference for future high-quality preclinical trials and clinical use.

Short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer.

Background: The aim of this study was to explore the short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer (ER). Methods: Eighty-eight patients with ER cancer and 82 healthy controls who had completed a full course of inactivated or peptide-based SARS-CoV-2 vaccines were recruited. Adverse events (AEs) were recorded. Responses to receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD+ memory B cells (MBCs) were evaluated. Results: Approximately 26.14% (23/88) of patients with ER cancer reported AEs within 7 days, which was comparable to that reported by healthy controls (24.39%, 20/82). Both the overall seroprevalence of anti-RBD-IgG and NAbs was obviously lower in the cancer group (70.45% vs. 86.59%, P < 0.05; 69.32% vs. 82.93%, P < 0.05, respectively). Anti-RBD-IgG and NAbs titers exhibited similar results, and dropped gradually over time. Patients with ongoing treatment had an attenuated immune response, especially in patients receiving active chemotherapy. The frequency of overall RBD+ MBCs was similar between the two groups, but the percentage of active MBCs was remarkably reduced in patients with ER cancer. Unlike antibody titers, MBCs responses were relatively constant over time. Conclusion: Inactivated and peptide-based COVID-19 vaccines were well tolerated, but with lower immunogenicity for ER cancer patients. More intensive antibody monitoring and timely booster immunization is recommended for patients with ER cancer presenting disordered subpopulations of RBD+ MBCs.

Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis.

Background: Subarachnoid hemorrhage (SAH) is a serious neurosurgical emergency with extremely high morbidity and mortality rates. Resveratrol (RES), a natural polyphenolic phytoalexin, is broadly presented in a wide variety of plants. Previous research had reasonably revealed its neuroprotective effects on experimental SAH animal models to some extent. But the results were more controversial. Therefore, we conducted a meta-analysis to evaluate the evidence on the effectiveness of RES in improving outcomes in SAH animal models. Methods: A systematic literature review was conducted in PubMed, EMBASE, and Web of Science databases to incorporate experimental control studies on the efficacy of RES on SAH models into our research. The standardized mean difference (SMD) was used to compare the brain water content (BWC) and neurological score (NS) between the treatment and control groups. Results: Overall, 16 articles published from 2014 to 2022 met the inclusion criteria. The meta-analysis of BWC showed a significant difference in favor of RES treatment (SMD: -1.026; 95% CI: -1.380, -0.672; p = 0.000) with significant heterogeneity (Q = 84.97; I2 = 60.0%; p = 0.000). Further stratified analysis was performed for methodological differences, especially dosage, time of treatments, and time-point of outcome assessment. The meta-analysis of NS showed a significant difference in favor of RES treatment (SMD: 1.342; 95% CI: 1.089, 1.595; p = 0.000) with low heterogeneity (Q = 25.58; I2 = 17.9%; p = 0.223). Conclusion: Generally, RES treatment showed an improvement in both pathological and behavioral outcomes in SAH animal models. The results of this study may provide a reference for preclinical and clinical studies in the future to some extent, with great significance for human health.

Comparison of outcomes between intracapsular resection and pseudocapsule-based extracapsular resection for pituitary adenoma: a systematic review and meta-analysis.

BACKGROUND: Transsphenoidal surgery is the preferred first-line therapy for most pituitary adenoma(PA), and the conventional strategy of treatment is intracapsular resection(IR). The protocol of extracapsular resection(ER), which considers the pseudocapsule as the PA boundary for surgical removal, has also been introduced gradually. In this study, the clinical efficacies and complications were explored and compared between these two procedures. METHODS: A systematic literature review was performed in the PubMed, EMBASE, Web of Science and Cochrane databases. Articles comparing between IR and ER were included. RESULTS: There were 7 studies containing 1768 cases in accordance with the inclusion criteria. Although the meta-analysis showed no significant difference in complete resection, a sensitivity analysis revealed that ER was more conducive to total PA resection than IR. Moreover, we found a significant difference in favor of ER regarding biochemical remission. Furthermore, there was no significant difference in the incidence rate of certain complications, such as hormone deficiency, diabetes insipidus, intraoperative cerebrospinal fluid(CSF) and postoperative CSF leakage. However, a sensitivity analysis suggested that IR decreased the risk of intraoperative CSF leakage. CONCLUSIONS: This meta-analysis unveiled that ER contributed to biochemical remission. To some extent, our results also showed that ER played a positive role in complete resection, but that IR reduced the incidence of intraoperative CSF leakage. However, the available evidence needs to be further authenticated using well-designed prospective, multicenter, randomized controlled clinical trials.

Willis covered stent treatment for blood blister-like aneurysm: A meta-analysis of efficacy and safety.

Background: Blood blister-like aneurysm (BBA) is a rare and special type of intracranial aneurysm with extremely high rates of rupture, morbidity, mortality, and recurrence. Willis Covered Stent (WCS) is a new device that is specifically designed for the treatment of intracranial complex aneurysms. However, the efficacy and safety of WCS treatment for BBA remain controversial. Thus, a high level of evidence is required to prove the efficacy and safety of WCS treatment. Methods: A systematic literature review was performed using a comprehensive literary search in Medline, Embase, and Web of Science databases to identify studies related to WCS treatment for BBA. A meta-analysis was then conducted to incorporate the efficacy and safety outcomes, including intraoperative situation, post-operative situation, and follow-up data. Results: Eight non-comparative studies containing 104 patients with 106 BBAs met the inclusion criteria. In the intraoperative situation, the technical success rate was 99.5% [95% confidence interval (CI), 0.958, 1.000], the complete occlusion rate was 98.2% (95% CI, 0.925, 1.000), and the side branch occlusion rate was 4.1% (95% CI, 0.001, 0.114). Vasospasm and dissection occurred in 9.2% (95% CI, 0.000, 0.261) and 0.1% (95% CI, 0.000, 0.032) of the patients, respectively. In the post-operative situation, the rebleed and mortality rates were 2.2% (95% CI, 0.000, 0.074) and 1.5% (95% CI, 0.000, 0.062), respectively. In the follow-up data, recurrence and parent artery stenosis occurred in 0.3% (95% CI, 0.000, 0.042) and 9.1% (95% CI, 0.032, 0.168) of the patients, respectively. Ultimately, 95.7% (95% CI, 0.889, 0.997) of the patients had a good outcome. Conclusions: Willis Covered Stent could be effectively and safely applied for BBA treatment. The results provide a reference for clinical trials in the future. Well-designed prospective cohort studies must be conducted for verification.

The Hounsfield Unit of Perihematomal Edema Is Associated With Poor Clinical Outcomes in Intracerebral Hemorrhage.

BACKGROUND: Hounsfield unit (HU) of perihematomal edema (PHE) may be a predictor of prognosis of intracerebral hemorrhage (ICH). Our study evaluated whether PHE mean HU at the 72 hours after ICH predicts outcome, and how it compares against other PHE measures. METHODS: Patients with ICH from a tertiary medical institution were included. PHE was segmented by the semiautomatic plane method to measure volume and mean HU. Outcomes of interest was poor 90-day prognosis (modified Rankin Scale score ≥3). Logistic regression was used to assess relationships with outcome. RESULTS: Data from a total of 159 patients with ICH were collected. The median mean HU of PHE at 72 hours was 22.1 (IQR: 19.2-25.0). Binary logistic regression showed that the 72-hour PHE mean HU was negatively correlated with the poor prognosis of patients with ICH (OR 0.59, 95% CI 0.47-0.75, P < 0.05). The receiver operator curves of meaningful indicators revealed that the area under the curve (AUC) of PHE mean HU at 72 hours was larger and the difference of AUC between PHE mean HU with PHE absolute volume or extension distance were statistically significant (P < 0.05). The 72-hour PHE mean HU has a higher value in predicting adverse prognosis of patients with ICH. CONCLUSIONS: The PHE mean HU at 72 hours was negatively correlated with the poor prognosis of patients with ICH. The prediction ability of PHE mean HU at 72 hours was better than PHE absolute volume and extension distance, contributing to a rather good index for predicting outcome of ICH.

Intracellular and extracellular S100A9 trigger epithelial-mesenchymal transition and promote the invasive phenotype of pituitary adenoma through activation of AKT1.

Pituitary adenoma (PA) is mostly benign intracranial tumor, but it also displays invasive growth characteristics and provokes challenging clinical conditions. S100A9 protein enhances tumor progression. In this study, we firstly demonstrated that both intracellular and extracellular S100A9 promoted the expression of Vimentin and Intercellular cell adhesion molecule-1 (ICAM-1), coupled with reduced E-cadherin in PA. As a result, PA acquired the phenotype of Epithelial-Mesenchymal Transition (EMT), leading to proliferation, cell cycle progression, migration and invasion. In addition, we indicated S100A9-induced EMT was mediated by activation of AKT1. Furthermore, immunohistochemistry showed that S100A9 expression was higher in invasive PA than that in non-invasive PA. These data extended our understanding for the effects of S100A9 on PA invasion and contributed to further development of a promising therapeutic target for invasive PA.

Intraoperative lumbar drainage can prevent cerebrospinal fluid leakage during transsphenoidal surgery for pituitary adenomas: a systematic review and meta-analysis.

BACKGROUND: Perioperative cerebrospinal fluid (CSF) leakage is a major complication of pituitary adenomas transsphenoidal surgery. Lumbar drainage (LD) is a common method of treating CSF leakage. But whether intraoperative LD can prevent CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery remains controversial. Clarity on the appropriate use of LD is needed. METHODS: A systematic literature review was conducted in the PubMed, EMBASE, and Web of science databases. Articles were included when they compared intraoperative LD with intraoperative no-LD CSF leakage rates during pituitary adenomas transsphenoidal surgery. RESULTS: Overall, 5 studies containing 678 cases met the inclusion criteria. When data were provided on intraoperative CSF leakage rates, the meta-analysis showed a significant difference in favor of intraoperative LD. When data were provided on postoperative CSF leakage rates, the meta-analysis also demonstrated a significant difference in favor of intraoperative LD. CONCLUSIONS: Although the results of this meta-analysis suggest intraoperative LD can reduce the risk of CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery, the available evidence is indefinite. To some extent the results suggest intraoperative LD's potential positive role. Further studies that include well-designed prospective, randomized controlled clinical trials are necessary for further verification.