Mild Prolongation of Prothrombin Time Does Not Affect the Safety and Prognosis of Transjugular Intrahepatic Portal Shunt: Based on Real-World Data.

BACKGROUND/AIMS: The aim was to investigate the safety and prognosis of transjugular intrahepatic portal shunt in patients with mildly prolonged prothrombin time. MATERIALS AND METHODS: Two hundred fifty-three patients with portal hypertension who received transjugular intrahepatic portal shunt from November 2015 to May 2021 in Wuhan Union Hospital were retrospectively selected. According to the preoperative prothrombin time, they were divided into 2 groups: 126 patients in the non-clinical significance group (prothrombin time prolongation <3 seconds) and 127 patients in the clinical significance group (3 seconds ≤ prothrombin time prolongation <6 seconds). A line chart of postoperative liver and kidney function was drawn, and Kaplan-Meier curve was used to analyze and compare the prognosis of the 2 groups. RESULTS: Transjugular intrahepatic portal shunt was successfully performed in all patients; the technical success rate was 100%, and no puncture-related complications occurred during perioperative period. The mean preoperative prothrombin time was 14.9 ± 0.7 seconds in the non-clinical significance group and 17.2 ± 0.8 seconds in the clinical significance group. During follow-up, 1-year stent dysfunction rates in the non-clinical significance group and clinical significance group were 3.5% and 6.9%, respectively, with no statistically significant difference (hazard ratio = 0.77, 95% CI = 0.30-1.93, log-rank P = .575). In addition, there were no significant differences in the cumulative survival rate (log rank P = .255), rebleeding rate (log-rank P = .392), and incidence of hepatic encephalopathy (log-rank P = .404) between the 2 groups. Subgroup analysis of the clinical significance group showed no significant difference in safety and prognosis between the 2 subgroups. CONCLUSION: Transjugular intrahepatic portal shunt is safe for portal hypertension patients with prothrombin time prolongation <6 seconds. There was no significant difference in prognosis between the non-clinical significance group and the clinical significance group.

Improvement of sarcopenia is beneficial for prognosis in cirrhotic patients after TIPS placement.

BACKGROUND: The relationship between the improvement of sarcopenia and post-TIPS prognosis has not been fully investigated. AIMS: To assess what level of sarcopenia improvement is required for potential benefits to post-TIPS prognosis. METHODS: In this retrospective study, 109 cirrhotic patients with sarcopenia who underwent TIPS between February 2016 and January 2021 were included. The change in skeletal muscle index (SMI) at 6 months post-TIPS was assessed and the correlations of SMI improvement with clinical outcomes were analyzed. RESULTS: During follow up, 59 (65.6%) patients reversed from sarcopenic to non-sarcopenic, and the cumulative mortality (8.5 % vs. 26.0%, log rank P = 0.013) and incidence of overt hepatic encephalopathy (OHE) (18.6% vs. 44.0%, log rank P = 0.004) in patients who reversed were significantly lower than who did not. SMI improvement rate was identified as an independent risk factor for mortality and OHE. In addition, the cumulative survival rate of patients with sarcopenia reversal or SMI improvement rate > 10.4% was significantly higher than that of patients with an SMI improvement rate ≤ 10.4% (92.5% vs. 58.6%, log rank P < 0.001). CONCLUSION: Reversal of sarcopenia or significant SMI improvement by TIPS could reduce the risk of death and OHE.

Dynamic changes in liver function after transjugular intrahepatic portosystemic shunt in patients with cirrhosis.

Purpose: To evaluate the dynamic changes in liver function after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with cirrhosis and to explore its association with clinical outcomes. Methods: This retrospective study included patients who underwent TIPS between August 2016 and December 2020. Liver function was primarily evaluated using the model for end-stage liver disease (MELD) score, which was analyzed at baseline, 1 week, 1 month, 3 months, 6 months, and 12 months using one-way repeated measures ANOVA. The Kaplan-Meier method, log-rank test, and multivariate analysis were used as appropriate. Results: In total, 235 patients were included in this study. The MELD score was significantly higher at 1 week (11.8 â€‹± â€‹3.1 vs 13.5 â€‹± â€‹3.5, p â€‹< â€‹0.05) and 1 month (11.8 â€‹± â€‹3.1 vs 13.2 â€‹± â€‹4.6, p â€‹< â€‹0.05) than the baseline level and recovered at 3 months (11.8 â€‹± â€‹3.1 vs 11.9 â€‹± â€‹3.9, p â€‹> â€‹0.05). At 12 months, the MELD score was higher than the baseline level (11.8 â€‹± â€‹3.1 vs 12.4 â€‹± â€‹3.2, p â€‹< â€‹0.05). Patients with a recovery of the MELD score (n â€‹= â€‹151) at 3 months had a lower probability of overt and severe HE (log-rank p â€‹= â€‹0.015 and p â€‹= â€‹0.027, respectively) than those without recovery (n â€‹= â€‹84). Logistic regression analysis revealed that albumin (odds ratio [OR], 0.926; 95% confidence interval [CI], 0.863-0.992; p â€‹= â€‹0.029) and platelet count (OR, 0.993; 95% CI, 0.987-0.999; p â€‹= â€‹0.033) were independent predictive factors for non-recovery of the MELD score at 3 months. Conclusions: Liver function after TIPS creation showed a trend of deterioration at first, followed by recovery. Recovery of liver function at three months was associated with reduced overt and severe HE.

Efficacy and safety of transjugular intrahepatic portosystemic shunt for the treatment of schistosomiasis-induced portal hypertension: a retrospective case series.

BACKGROUND AND AIM: The aim of this study was to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension caused by schistosomiasis. METHODS: This study included 43 patients with schistosomiasis-induced portal hypertension treated with TIPS in our institution from December 2015 to May 2021. The demographic, imaging, clinical and follow-up data of patients were recorded retrospectively to evaluate the efficacy and safety of the procedure. RESULTS: All patients were successfully implanted with stents to establish shunt, and 90.7% of the patients were in good postoperative condition with no complications. After TIPS, the Yerdel grade of portal vein thrombosis decreased, and the portal pressure gradient decreased from 27.0 ± 4.9 mmHg to 11.3 ± 3.8 mmHg (P < 0.001). Bleeding was effectively controlled, with a postoperative rebleeding rate of 9.3%, which was an 87.9% reduction from the preoperative rate. The cumulative incidence of postoperative refractory ascites, shunt dysfunction, overt hepatic encephalopathy (OHE) and death were all similar to those of TIPS for nonschistosomiasis portal hypertension. There were no differences in liver and kidney function and blood coagulation indexes before and 3 months after TIPS. Albumin was identified as an independent risk factor for mortality after TIPS for schistosomal liver fibrosis. CONCLUSION: TIPS can be used as a well-tolerated and effective treatment for schistosomiasis-induced portal hypertension, effectively reduce portal pressure gradient and improve portal vein thrombosis.

Transjugular intrahepatic portosystemic shunt in patients with autoimmune hepatitis-induced cirrhosis and variceal bleeding.

BACKGROUND AND AIM: An increasing number of patients with autoimmune hepatitis (AIH)-induced cirrhosis and variceal bleeding are currently referred for transjugular intrahepatic portosystemic shunt (TIPS). The aim of this study was to evaluate the safety and efficacy of TIPS in such patients, and to compare these results with data from patients with hepatitis B virus (HBV)-induced cirrhosis. MATERIALS AND METHODS: This retrospective study consisted of 211 patients between August 2016 and May 2021, and patients were allocated to AIH (n = 35) and HBV (n = 176) groups according to the etiology of the cirrhosis. The primary endpoint was mortality after TIPS use; the secondary endpoints were recurrent bleeding, overt hepatic encephalopathy (OHE), shunt dysfunction, and dynamic changes in liver function over time. RESULTS: During a median follow-up period of 27 months, 23 (10.9%) patients died, 22 (10.4%) experienced recurrent bleeding, 50 (23.7%) experienced OHE, and 25 (11.8%) developed shunt dysfunction. Compared with the HBV group, the AIH group exhibited a similar mortality risk (adjusted hazard ratio, HR 1.199; 95% confidence interval, CI 0.367-3.917; p = 0.764), OHE (adjusted HR 1.023, 95% CI 0.483-2.167, p = 0.954), and shunt dysfunction (adjusted HR 0.862, 95% CI 0.285-2.610, p = 0.792); but a higher risk of recurrent bleeding (adjusted HR 2.731, 95% CI 1.112-6.708, p = 0.028). The dynamic changes in liver function manifested an initial trend toward deterioration, and then subsequent recovery in both the AIH and HBV groups. CONCLUSIONS: TIPS is a safe and effective treatment, and should be considered for those patients with AIH-induced cirrhosis and variceal bleeding.

Assessing puberty-related health needs among 10-15-year-old boys: A cross-sectional study approach.

This study investigated the puberty-related health needs of 10-5-year-old boys in Iran. The literature shows that the growing health problems of adolescents are an important health issue worldwide. The present study was a cross-sectional descriptive survey that applied a stratified-cluster sampling technique to collect data from boys aged 10-15 years in order to assess puberty-related health problems. The survey used a self-reported questionnaire comprising 10 demographic questions with 35 research questions based on five categories: awareness of puberty changes, mood swings, sexual orientation, self-confidence, and health behaviors. Five questions examined education demands. The study used descriptive statistics, chi-square test, regression, and correlation coefficient for quantitative data analysis. The mean age of the adolescents was 11.38 ± ± 4.37 years. There was a significant link between the maternal and paternal educational level and awareness of puberty changes among adolescent boys (p < 0.001). Overall, 69.81% of teenage boys lacked puberty awareness and had not understood puberty and health behaviors, and 87% of the teenage boys had no access to desired educational resources. At the same time, 82% of the boys' families did not disclose puberty changes and hygiene practices. The results indicated a significant positive correlation between adolescents' health behaviors and awareness of puberty changes (r = 0.12 p < 0.007). The results also revealed a positive relationship between self-confidence and health behaviors (r = 0.14, p < 0.001). There is a need among adolescent boys to receive health-related information about puberty. Teenage boys' families play an indispensable role in educating adolescents about puberty and health-related changes.

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.

BACKGROUND: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. METHODS: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. FINDINGS: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0·93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. INTERPRETATION: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. FUNDING: The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.

Hepatitis B Virus X Protein Upregulates Intracellular Calcium Signaling by Binding C-terminal of Orail Protein.

Hepatitis B virus X (HBx) protein plays a pivotal role in the development of hepatitis B virus (HBV)-associated hepatocellular carcinoma. Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein, the mechanism of HBx protein regulating intracellular calcium level remains poorly understood. The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry (SOCE) components, Orail and stromal interaction molecule 1, and then identified the targets of HBx protein, with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis. By employing co-immunoprecipitation and GST-pull-down assay, we found that Orail protein interacted with HBx protein, and the C-terminus of Orail was implicated in the interaction. Confocal microscopy also revealed that HBx protein could co-localize with full-length Orail protein in HEK293 cells. Moreover, live cell calcium imaging exhibited that HBx protein elevated intracellular calcium, possibly by binding to SOCE components. Our results suggest that HBx protein binds to STIM1-Orail complexes to positively regulate the activity of plasma membrane store-operated calcium channels.

Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries.

The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase. Working in vitro with H9c2 cardiomyoblasts subjected to 9-h hypoxia followed by 6-h reoxygenation (H/R), and analyzing changes occurring in areas-at-risk (AARs) of murine hearts subjected to a 30-min ischemia followed by 24-h reperfusion (I/R) protocol, we found: (i) that blocking TRPC with SKF96365 significantly ameliorated damage induced by H/R, including development of the mitochondrial permeability transition and proapoptotic changes in Bcl2/BAX ratios; and (ii) that AAR tissues had increased TUNEL+ cells, augmented Bcl2/BAX ratios, and increased p(S240)NFATc3, p(S473)AKT, p(S9)GSK3ß, and TRPC3 and -6 proteins, consistent with activation of a positive-feedback loop in which calcium entering through TRPCs activates calcineurin-mediated NFATc3-directed transcription of TRPC genes, leading to more Ca2+ entry. All these changes were markedly reduced in mice lacking TRPC3, -6, and -7. The changes caused by I/R in AAR tissues were matched by those seen after H/R in cardiomyoblasts in all aspects except for p-AKT and p-GSK3ß, which were decreased after H/R in cardiomyoblasts instead of increased. TRPC should be promising targets for pharmacologic intervention after cardiac infarcts.

Rapid Regulation of Depression-Associated Genes in a New Mouse Model Mimicking Interferon-α-Related Depression in Hepatitis C Virus Infection.

Major depression is a serious side effect of interferon-α (IFN-α), which is used in the therapy of hepatitis C virus (HCV) infection. Due to the lack of reproducible animal models, the mechanisms underlying IFN-α-related depression are largely unknown. We herein established a mouse model, in which murine IFN-α (250 IU/day) and polyinosinic/polycytidylic acid (poly(I:C); 1 µg/day), a toll-like receptor-3 (TLR3) agonist that mimics the effect of HCV double-strand RNA, were continuously infused into the lateral ventricle via miniosmotic pumps over up to 14 days. The delivery of IFN-α and poly(I:C), but not of IFN-α or poly(I:C) alone, resulted in a reproducible depression-like state that was characterized by reduced exploration behavior in open-field tests, increased immobility in tail suspension and forced swimming tests, and a moderate loss of body weight. In the hippocampus and prefrontal cortex, the pro-inflammatory genes TNF-α, IL-6, tissue inhibitor of metalloproteinases-1 (Timp-1), CXC motif ligand-1 (Cxcl1), Cxcl10, and CC motif ligand-5 (Ccl5) were synergistically induced by IFN-α and poly(I:C), most pronounced after 14-day exposure. In comparison, the interferon-inducible genes of signal transducer and activator of transcription-1 (Stat1), guanylate binding protein-1 (Gbp1), proteasome subunit-ß type-9 (Psmb9), ubiquitin-conjugating enzyme E2L-6 (Ube2l6), receptor transporter protein-4 (Rtp4), and GTP cyclohydrolase-1 (Gch1), which had previously been elevated in the blood of IFN-α-treated patients developing depression, in the brains of suicidal individuals, and in primary neurons exposed to IFN-α and poly(I:C), were induced even earlier, reaching maximum levels mostly after 24 hours. We propose that interferon-inducible genes might be useful markers of imminent depression.