Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score.

Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model's efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

Using Hyperbaric Oxygen to Improve the Radiosensitivity of Human U251 Glioma Cells.

The aim of this study was to explore the use of hyperbaric oxygen to enhance the radiosensitivity of human glioma cells. Sub-cultured U251 human glioma cells were randomly divided into four groups: an untreated control group, cells treated with hyperbaric oxygen (HBO) only, cells treated with X-ray irradiation (X-ray) only, and cells treated with both HBO and X-ray. Cell morphology, cell proliferation activity, cell cycle distribution, and apoptosis were observed in these groups to evaluate the role of HBO in improving the radiosensitivity of glioma cells. With the increase in X-ray doses (0 Gy, 2 Gy, 4 Gy, 6 Gy, 8 Gy), the survival fraction (SF) of glioma cells gradually decreased. Significantly lower SF was observed for the cells treated with the HBO and X-ray together than in the X-ray group for each dose (all P < 0.05). The proliferation inhibition was significantly higher in the HBO combined with X-ray group than in the X-ray group for each dose (all P < 0.05) for the U251 cell line. The percentage of G2/M phase cells was significantly higher in the HBO combined with X-ray (2 Gy) group (26.70% ± 2.46%) and the HBO group (22.36% ± 0.91%) than in the control group (11.56% ± 2.01%) and X-ray (2 Gy) group (10.35% ± 2.69%) (all P < 0.05). U251 cell apoptosis was significantly higher in the HBO combined with X-ray (2 Gy) group than in the HBO group, the X-ray (2 Gy) group, and the control group (all P < 0.05). We conclude that HBO can enhance the proliferation inhibition and apoptosis of glioma U251 cells by blocking glioma cells in the G2/M phase and improve the radiosensitivity of U251 glioma cells.

The association between problematic smartphone use and the severity of temporomandibular disorders: A cross-sectional study.

Objective: To evaluate the prevalence of different types of temporomandibular disorders (TMD) symptoms in young adults and determine their associations with problematic smartphone use (PSU). Methods: The data of the study were collected from local university students through an online questionnaire survey. Demographic information, Fonseca Anamnestic Index (FAI), Smartphone Addiction Scale-Short Version (SAS-SV), and Patient Health Questionnaire-4 (PHQ-4) responses were gathered electronically and analyzed using multiple logistic regression analysis. Results: There were 163 male and 307 female respondents were participated in this study. The prevalence of PSU and TMD were 83.6% and 66.4%, respectively. There was a moderate statistical correlation between PSU and TMD among young adults (r = 0.31, p < 0.01). The logistic regression model revealed that the risk of TMD was 1.77 times higher in people with PSU than in those without PSU (OR = 1.77; 95% CI 1.04-3.06). PSU is a risk factor for pain-related TMD (OR = 1.81; 95% CI 1.08-3.04) but not intra-articular TMD. Conclusion: Subjects showed high prevalence of both TMD and PSU. People with PSU experienced more severe and frequent pain-related rather than intra-articular TMD symptoms than those without PSU. By reducing the problematic smartphone use, the risk factor of TMD might be avoided.

Association Between Insulin Resistance and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage.

Background: Abnormal glucose metabolism was shown to be associated with the occurrence of remote diffusion-weighted imaging lesions (R-DWILs) after primary intracerebral hemorrhage (ICH) onset. Insulin resistance is a metabolic disorder that was regarded as an indicator of chronic systemic inflammation. In this study, we aimed to determine the effect of insulin resistance on the occurrence of R-DWILs in ICH. Methods: Patients with primary ICH within 14 days after onset were prospectively enrolled from November 2017 to October 2019. R-DWILs was defined as remote focal hyperintensity from the hematoma in DWI, with corresponding hypointensity in apparent diffusion coefficient. The homeostasis model assessment of insulin resistance (HOMA-IR) was used for insulin resistance estimation and calculated as fasting insulin (µU/ml) × fasting glucose (mmol/L)/22.5. Patients in our cohort were divided into four groups according to HOMA-IR index quartiles. Logistic regression analysis and smoothing plots were used to evaluate the association of HOMA-IR with R-DWIL occurrence. Sensitivity analysis was performed in non-diabetic patients, non-obese patients, hypertensive ICH patients, and patients 60 years and older separately. The association between HOMA-IR and systemic inflammatory immune indices neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) was examined with multiple linear regression analysis. Results: Among the 345 patients, 54 (15.7%) had R-DWILs. Both the third and fourth quartiles of HOMA-IR index were robustly associated with an increased risk of R-DWIL occurrence (adjusted OR 3.58, 95% CI 1.33-9.65; adjusted OR 3.91, 95%CI 1.47-10.41) when compared with the first quartile. The association was consistent in non-diabetic, non-obese, hypertensive ICH patients, as well as in patients 60 years and older. Furthermore, both NLR and MLR were independently associated with HOMA-IR. Conclusions: Our study suggested that insulin resistance evaluated with HOMA-IR index was independently associated with the presence of R-DWILs in patients with acute and subacute primary ICH. It may provide new insights into the metabolism-related brain injury after ICH ictus.

Deep learning for automatically predicting early haematoma expansion in Chinese patients.

BACKGROUND AND PURPOSE: Early haematoma expansion is determinative in predicting outcome of intracerebral haemorrhage (ICH) patients. The aims of this study are to develop a novel prediction model for haematoma expansion by applying deep learning model and validate its prediction accuracy. METHODS: Data of this study were obtained from a prospectively enrolled cohort of patients with primary supratentorial ICH from our centre. We developed a deep learning model to predict haematoma expansion and compared its performance with conventional non-contrast CT (NCCT) markers. To evaluate the predictability of this model, it was also compared with a logistic regression model based on haematoma volume or the BAT score. RESULTS: A total of 266 patients were finally included for analysis, and 74 (27.8%) of them experienced early haematoma expansion. The deep learning model exhibited highest C statistic as 0.80, compared with 0.64, 0.65, 0.51, 0.58 and 0.55 for hypodensities, black hole sign, blend sign, fluid level and irregular shape, respectively. While the C statistics for swirl sign (0.70; p=0.211) and heterogenous density (0.70; p=0.141) were not significantly higher than that of the deep learning model. Moreover, the predictive value for the deep learning model was significantly superior to that of the logistic model of haematoma volume (0.62; p=0.042) and the BAT score (0.65; p=0.042). CONCLUSIONS: Compared with the conventional NCCT markers and BAT predictive model, the deep learning algorithm showed superiority for predicting early haematoma expansion in ICH patients.

Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.

BACKGROUND AND AIMS: Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients. METHODS: In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400 mg rifaximin twice daily for 6 months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child-Pugh score and class. RESULTS: The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child-Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups. CONCLUSION: Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200 mg/day) rifaximin in preventing cirrhosis-related complications. CLINICAL TRIAL NUMBER: NCT02190357.

Second-look endoscopy-guided therapy under sedation prevents early rebleeding after variceal ligation for acute variceal bleeding.

OBJECTIVES: To investigate whether second-look endoscopy (SLE)-guided therapy could be used to prevent post-endoscopic variceal ligation (EVL) early bleeding. METHODS: Consecutive cirrhotic patients with large esophageal varices (EV) receiving successful EVL for acute variceal bleeding (AVB) or secondary prophylaxis were enrolled. The patients were randomized into a SLE group and a non-SLE group (NSLE) 10 days after EVL. Additional endoscopic interventions as well as proton pump inhibitors and octreotide administration were applied based on the SLE findings. The post-EVL early rebleeding and mortality rates were compared between the two groups. RESULTS: A total of 252 patients were included in the final analysis. Post-EVL early rebleeding (13.5% vs 4.8%, P = 0.016) and bleeding-caused mortality (4.8% vs 0%, P = 0.013) were more frequently observed in the NSLE group than in the SLE group. However, post-EVL early rebleeding and mortality rates were reduced by SLE in patients receiving EVL for AVB only but not in those receiving secondary prophylaxis. Patients with Child-Pugh classification B to C at randomization (hazard ratio [HR] 8.77, P = 0.034), AVB at index EVL (HR 3.62, P = 0.003), discontinuation of non-selective ß-blocker after randomization (HR 4.68, P = 0.001) and non-SLE (HR 2.63, P = 0.046) were more likely to have post-EVL early rebleeding. No serious adverse events occurred during SLE. CONCLUSION: SLE-guided therapy reduces post-EVL early rebleeding and mortality rates in cirrhotic patients with large EV receiving EVL for AVB.

Cap-Assisted Endoscopic Sclerotherapy vs Ligation in the Long-Term Management of Medium Esophageal Varices: A Randomized Trial.

INTRODUCTION: Compared with endoscopic variceal ligation (EVL), cap-assisted endoscopic sclerotherapy (CAES) improves efficacy in the treatment of small esophageal varices (EVs) but has not been evaluated in the management of medium EVs. The aim of this study was to compare CAES with EVL in the long-term management of patients exhibiting cirrhosis with medium EVs and a history of esophageal variceal bleeding (EVB), with respect to variceal eradication and recurrence, adverse events, rebleeding, and survival. METHODS: Cirrhotic patients with medium EVs and a history of EVB were divided randomly into EVL and CAES groups. EVL or CAES was repeated each month until variceal eradication. Lauromacrogol was used as a sclerosant. Patients were followed up until 1 year after eradication. RESULTS: In total, 240 patients (age: 51.1 ± 10.0 years; men: 70.8%) were included and randomized to the EVL and CAES groups. The recurrence rate of EVs was much lower in the CAES group than in the EVL group (13.0% vs 30.7%, P = 0.001). The predictors for variceal recurrence were eradication by EVL (hazard ratio [HR]: 2.37, P = 0.04), achievement of complete eradication (HR: 0.27, P < 0.001), and nonselective ß-blocker response (HR: 0.32, P = 0.003). There was no significant difference in the rates of eradication, rebleeding, requirement for alternative therapy, and mortality or the incidence of complications between groups. DISCUSSION: CAES reduces the recurrence rate of EVs with comparable safety to that of EVL in the long-term management of patients presenting cirrhosis with medium EVs and a history of EVB.

CD200Fc Improves Neurological Function by Protecting the Blood-brain Barrier after Intracerebral Hemorrhage.

CD200 is widely distributed in the central nervous system and plays an essential role in the immune response in neurological diseases. However, little is currently known about the effects of CD200 signaling on the blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of CD200 during ICH in an autologous blood induced mouse ICH model was investigated. Following ICH, critical protein expression, BBB permeability, and neurological function were measured with or without CD200Fc administration. Our results showed that both the expression of CD200 and CD200R1 decreased after ICH and administration of CD200Fc attenuated BBB leakage and improved neurological functions. In conclusion, our work demonstrated that CD200Fc might be a potential treatment option for ICH by protecting the BBB and improving functional outcomes.

IL-25 protects against high-fat diet-induced hepatic steatosis in mice by inducing IL-25 and M2a macrophage production.

Interleukin (IL)-25 is a cytokine that has previously been shown to have a protective role against nonalcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophage differentiation. However, the direct relationships between IL-25 expression regulation, M2 induction and NAFLD remain unknown. In this study, we demonstrate that IL-25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL-13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high-fat diet HFD-induced hepatic steatosis. Furthermore, we found that IL-25 treatment, both in vitro and in vivo, promotes direct binding of STAT6 to the IL-25 gene promoter region. This binding of STAT6 in response to IL-25 treatment also resulted in the increase of IL-25 expression in hepatocytes. Together, these findings identify IL-25 as a protective factor against HFD-induced hepatic steatosis by inducing an increase of IL-25 expression in hepatocytes and through promotion of M2a macrophage production.

Duodenal variceal bleeding secondary to idiopathic portal hypertension treated with transjugular intra-hepatic porto-systemic shunt plus embolization: A case report.

BACKGROUND: Duodenal varices are a lesser-known complication with non-cirrhotic portal hypertension. We report a circuitous route from missed diagnosis of duodenal varices to correction. An extremely rare case of duodenal variceal bleeding secondary to idiopathic portal hypertension (IPH) is expounded in this study, which was controlled by transjugular intra-hepatic porto-systemic shunt (TIPS) plus embolization. CASE SUMMARY: A 46-year-old woman with anemia for two years was frequently admitted to the local hospital. Upon examination, anemia was attributed to gastrointestinal tract bleeding, which resulted from duodenal variceal bleeding detected by repeated esophagogastroduodenoscopy. At the end of a complete workup, IPH leading to duodenal varices was diagnosed. Portal venography revealed that the remarked duodenal varices originated from the proximal superior mesenteric vein. TIPS plus embolization with coils and Histoacryl was performed to obliterate the rupture of duodenal varices. The anemia resolved, and the duodenal varices completely vanished by 2 mo after the initial operation. CONCLUSION: TIPS plus embolization may be more appropriate to treat the bleeding of large duodenal varices.

Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients.

AIM: To explore the natural history of covert hepatic encephalopathy (CHE) in absence of medication intervention. METHODS: Consecutive outpatient cirrhotic patients in a Chinese tertiary care hospital were enrolled and evaluated for CHE diagnosis. They were followed up for a mean of 11.2 ± 1.3 mo. Time to the first cirrhosis-related complications requiring hospitalization, including overt HE (OHE), resolution of CHE and death/transplantation, were compared between CHE and no-CHE patients. Predictors for complication(s) and death/transplantation were also analyzed. RESULTS: A total of 366 patients (age: 47.2 ± 8.6 years, male: 73.0%) were enrolled. CHE was identified in 131 patients (35.8%). CHE patients had higher rates of death and incidence of complications requiring hospitalization, including OHE, compared to unimpaired patients. Moreover, 17.6% of CHE patients developed OHE, 42.0% suffered persistent CHE, and 19.8% of CHE spontaneously resolved. In CHE patients, serum albumin < 30 g/L (HR = 5.22, P = 0.03) was the sole predictor for developing OHE, and blood creatinine > 133 µmol/L (HR = 4.75, P = 0.036) predicted mortality. Child-Pugh B/C (HR = 0.084, P < 0.001) and OHE history (HR = 0.15, P = 0.014) were predictors of spontaneous resolution of CHE. CONCLUSION: CHE exacerbates, persists or resolves without medication intervention in clinically stable cirrhosis. Triage of patients based on these predictors will allow for more cost-effect management of CHE.