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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 β-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.

BackgroundAbnormal 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.MethodsPatients 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.ResultsAmong 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.ConclusionsOur 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.

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.

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.

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 β-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.

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.

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.

Background and purposeEarly 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.MethodsData 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.ResultsA 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).ConclusionsCompared with the conventional NCCT markers and BAT predictive model, the deep learning algorithm showed superiority for predicting early haematoma expansion in ICH patients.