[Analysis of the long-term prognosis of transjugular intrahepatic portosystemic shunt treatment for esophagogastric variceal hemorrhage concomitant with sarcopenia in cirrhotic patients].

Objective: To explore whether transjugular intrahepatic portosystemic shunt (TIPS) can improve the prognosis of esophagogastric variceal bleeding (EGVB) combined with sarcopenia in cirrhotic patients. Methods: A retrospective cohort study was performed. A total of 464 cases with cirrhotic EGVB who received standard or TIPS treatment between January 2017 and December 2019 were selected. Regular follow-up was performed for the long-term after treatment. The primary outcome was transplantation-free survival. The secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). The obtained data were statistically analyzed. The t-test and Wilcoxon rank-sum test were used to compare continuous variables between groups. The χ2 test, or Fisher's exact probability test, was used to compare categorical variables between groups. Results: The age of the included patients was 55.27±13.86 years, and 286 cases were male. There were 203 cases of combined sarcopenia and 261 cases of non-combined sarcopenia. The median follow-up period was 43 months. The two groups had no statistically significant difference in follow-up time. There was no statistically significant difference in transplant-free survival between the TIPS group and the standard treatment group in the overall cohort (HR=1.31, 95%CI: 0.97-1.78, P=0.08). The TIPS patient group with cirrhosis combined with sarcopenia had longer transplant-free survival (median survival: 47.76 vs. 52.45, χ2=4.09; HR=1.55, 95CI: 1.01~2.38, P=0.04). There was no statistically significant difference in transplant-free survival between the two kinds of treatments for patients without sarcopenia (HR=1.22, 95%CI: 0.78~1.88, P=0.39). Rebleeding time was prolonged in TIPS patients with or without sarcopenia combination (patients without combined sarcopenia: median rebleeding time: 39.48 vs. 53.61, χ2=18.68; R=2.47, 95CI: 1.67~3.65, P<0.01; patients with sarcopenia: median rebleeding time: 39.91 vs. 50.68, χ2=12.36; HR=2.20, 95CI: 1.42~3.40, P<0.01). TIPS patients had an increased 1-year OHE incidence rate compared to the standard treatment group (sarcopenia patients: 6.93% vs. 16.67%, χ2=3.87, P=0.049; patients without sarcopenia combination: 2.19% vs. 9.68%, χ2=8.85, P=0.01). There was no statistically significant difference in the long-term OHE incidence rate between the two kinds of treatment groups (P>0.05). Conclusion: TIPS can significantly prolong transplant-free survival compared to standard treatment as a secondary prevention of EGVB concomitant with sarcopenia in patients with cirrhosis. However, its advantage is not prominent for patients with cirrhosis in EGVB without sarcopenia.

[Status of HVPG clinical application in China in 2021].

Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

[Study of PA-HSOS severity grading to predict the prognosis of patients with PA-HSOS treated by transjugular intrahepatic portosystemic shunt].

Objective: To explore pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) severity grading to predict the prognostic value for PA-HSOS patients treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: Clinical data of patients with PA-HSOS who were critically ill or had ineffective drug treatment and underwent TIPS treatment from December 2013 to September 2019 were retrospectively analyzed. PA-HSOS severity grading criteria in adult was quoted, revised and defined from the European Group for Blood and Marrow Transplantation (EBMT). The survival time, the rate of shunt dysfunction and the incidence of postoperative hepatic encephalopathy in different severity groups after TIPS were compared. Univariate Cox or Binomial Logistic regression analysis was used to evaluate the impact of each variable. Variables with P < 0.1 were regarded as statistically significant variables for the prognosis, and were introduced into Cox or Binomial Logistic regression hierarchical regression analysis as controlled covariates. PA-HSOS severity grading was analyzed as dummy variables. Results: A total of 102 patient data were collected, and the median follow-up time was 14.52 months. The difference in survival time of patients with different severity levels was statistically significant (P = 0.023). The mortality risk in moderate patients was 1.575 times higher than that of mild patients (95%CI: 0.216-11.457, P = 0.654). The mortality risk of severe and very severe patients was 7.424 times higher than that of mild patients (95% CI: 1.612-34.197, P = 0.010). There was no statistically significant difference in postoperative hepatic encephalopathy recurrence rate and shunt dysfunction rate (P > 0.05). Conclusion: PA-HSOS severity grading has prognostic value for PA-HSOS patients receiving TIPS treatment, and can be used as an important reference for guiding the timing of TIPS intervention.

[Cross-sectional survey between schistosomiasis liver fibrosis and health-related quality of life among agricultural workers].

Objective: To assess the health-related quality of life in the agricultural workers with schistosomiasis liver fibrosis using Europe Health-Related Quality of Life Questionnaire 5 Dimensions (EQ-5D) . Methods: From January to December 2019, a cross sectional study was applied to 3507 agricultural workers at a township, Kaihua County, Zhejiang Province, of which 424 agricultural workers with schistosomiasis liver fibrosis as objective group and of which 3083 agricultural workers without schistosomiasis liver fibrosis as the control group whom were respectively evaluated by the EQ-5D scale. At the same time, aspartate aminotransferase (AST) and platelet (PLT) ratio index (APRI) was calculated, and B-type ultrasound was used to test the degree of liver fibrosis among two groups. Results: There were 424 patients in the objective group, aged (66.29±7.21) years, and 3083 person in the control group, aged (65.98±14.81) years. The APRI scores between the control group and the objective group were (0.74±0.51) points and (1.04±0.53) points, respectively (P<0.01) . The total score of 5 items of EQ-5D was (6.86±2.21) points and (7.88±2.71) points, respectively, in the objective group had 375 cases of liver fibrosis grade I and 49 cases of liver fibrosis grade Ⅱ, which were significantly higher than that of the control group[ (5.50±1.17) points] (P<0.01) . Among the respondents, EQ-VAS score was negative correlated with EQ-5D scores (r=-0.616, P<0.01) . Conclusion: The health-related quality of life of agricultural workers with schistosomiasis liver fibrosis at a township, Quzhou City Kaihua County decreased compared with the control group.

[Review on diagnostic criteria of hepatic sinusoidal obstruction syndrome].

Hepatic sinusoidal obstruction syndrome (HSOS) is a kind of hepatic vascular disease which is characterized by damage to hepatic sinusoidal endothelial cells, centrilobular hepatic vein and/or interlobular vein, resulting in stenosis or lumen occlusion, hepatic injury and acute sinusoidal portal hypertension. Generally, most patients with HSOS have mild manifestations, but in severely ill patients, the disease can lead to multiple organ dysfunction/failure, and the mortality rate can be as high as 70%-80%. Therefore, it is important to identify and treat HSOS as soon as possible. This paper introduces the current clinical diagnostic criteria of HSOS, including the Modified Seattle and Baltimore Criteria along with "Nanjing Criteria", and reviews their characteristics, scope of application and limitations.

[Protective effects of S-adenosylmethionine against CCl4 - and ethanol-induced experimental hepatic fibrosis].

In this study the effects of S-adenosylmethionine (SAM) on experimental hepatic fibrotic rats induced by carbon tetrachloride (CCl(4)) and ethanol and the relevant potential mechanisms were explored. Hepatic fibrotic rat models were established with CCl(4) diluted in olive oil being drunk with 10% ethanol in water. SAM was used both for prevention and treatment. Histological evaluation was carried out by hematoxylin-eosin (HE) and Masson staining of hepatic samples. Serum biochemical assays showed that alanine aminotransferase (ALT) was increased and albumin (ALB) was decreased by CCl(4) and ethanol, and both effects were suppressed by preventing and treating use of SAM. The model control rats got significantly higher scores in fatty degeneration, lobular inflammation, and hepatocyte ballooning. A significant improvement was observed in the SAM-prevented rats and SAM-treated rats, which was consistent with the change of fibrosis scoring in each group. Smad3 was induced by CCl(4) and ethanol in the model control group, which was significantly down regulated by SAM. SAM reduced both total Smad3 and phospho-Smad3 in vitro. SAM had a protective effect on hepatic fibrosis in rats induced by CCl(4) combined with ethanol and the down-regulation of activity and expression of Smad3 were involved in the potential mechanisms.

[Expression of renal PLA2R in patients with idiopathic membranous nephropathy and its relationship with the curative effect of immunotherapy].

OBJECTIVE: To detect the expression of renal M-type phospholipase A2 receptor (PLA2R) in patients with idiopathic membranous nephropathy (IMN), and to explore the relationship between renal PLA2R and the curative effect of immunotherapy. METHODS: A total of 56 patients who were diagnosed as IMN from January 2012 to June 2014 in the department of nephrology in First People's Hospital, Shanghai Jiaotong University, were included in this study. The expression of renal PLA2R was detected by immumofluorescence assay. The IMN patients were treated with corticosteroids and cyclophosphamide, and the relationship between renal PLA2R and the curative effect of immunotherapy was observed. RESULTS: The ratio of PLA2R related IMN (renal PLA2R-positive) patients was 71.4%(40/56). The recovery conditions in proteinuria and serum albumin were better in the non-PLA2R related IMN group since 6 months after the treatment (P<0.05). The overall response rate in PLA2R related IMN group was 58.3%, 62.5% and 62.5% after 6, 9, 12 months, respectively. However, the overall response rate in non-PLA2R related IMN group almost reached 100% after treatment for 6 months. Compared with PLA2R related IMN group, the time which patients reached complete remission was significantly shorter in the non-PLA2R related IMN group [(5.4±3.5) vs (10.5±1.6) months, P<0.05]. CONCLUSIONS: Detection of renal PLA2R can be helpful to diagnose IMN. Non-PLA2R related IMN patients usually have a better curative effect of immunotherapy and a shorter time to onset of efficacy.

A modified Child-Turcotte-Pugh score based on plasma ammonia predicts survival for patients with decompensated cirrhosis.

BACKGROUND: Plasma ammonia has been shown to be an independent prognostic factor for patients with liver cirrhosis. AIM: We aimed to investigate the discrimination and calibration of a new prognostic model (aCTP) based on plasma ammonia (Amm) replacing hepatic encephalopathy (HE) in the Child-Turcotte-Pugh (CTP) score. DESIGN: Diagnostic test, paired design. METHODS: Baseline Amm levels were corrected to the upper limit of normal (Amm-ULN). We designed the new model based on the cut-off value of Amm-ULN in the observational cohort of 554 clinically stable cirrhotic patients from January 2012 to July 2019. External validation was carried out using prospective data from 185 patients with liver cirrhosis. RESULTS: Our analysis showed that each 1-point increase in Amm-ULN was associated with a 2-fold increase in the likelihood of mortality [hazard ratio (HR), 2.06; 95% CI: 1.81-2.36, P < 0.001]. In the aCTP score, Amm-ULN < 1.0 was defined as a score of 1, 1.0 ≤ Amm-ULN < 1.4 as 2 and ≥1.4 as 3. The survival curves among three aCTP grades were significantly different (P < 0.0001). The aCTP score showed the better agreements between predicted and observed events in the validating cohorts than the CTP score (C-statistics: 0.75 and 0.69, P < 0.001). The aCTP score showed inspiring power to predict acute decompensation (C-statistics: 0.76; 95% CI: 0.71-0.81) and acute-on-chronic liver failure (C-statistics: 0.81; 95% CI: 0.77-0.86). CONCLUSION: This study demonstrates the feasibility and the potential for plasma Amm replacing HE (aCTP) to enhance the prognostication of transplant-free survival provided by the CTP score for patients with decompensated cirrhosis.

AI-Driven Image Analysis in Central Nervous System Tumors-Traditional Machine Learning, Deep Learning and Hybrid Models.

The interpretation of imaging in medicine in general and in oncology specifically remains problematic due to several limitations which include the need to incorporate detailed clinical history, patient and disease-specific history, clinical exam features, previous and ongoing treatment, and account for the dependency on reproducible human interpretation of multiple factors with incomplete data linkage. To standardize reporting, minimize bias, expedite management, and improve outcomes, the use of Artificial Intelligence (AI) has gained significant prominence in imaging analysis. In oncology, AI methods have as a result been explored in most cancer types with ongoing progress in employing AI towards imaging for oncology treatment, assessing treatment response, and understanding and communicating prognosis. Challenges remain with limited available data sets, variability in imaging changes over time augmented by a growing heterogeneity in analysis approaches. We review the imaging analysis workflow and examine how hand-crafted features also referred to as traditional Machine Learning (ML), Deep Learning (DL) approaches, and hybrid analyses, are being employed in AI-driven imaging analysis in central nervous system tumors. ML, DL, and hybrid approaches coexist, and their combination may produce superior results although data in this space is as yet novel, and conclusions and pitfalls have yet to be fully explored. We note the growing technical complexities that may become increasingly separated from the clinic and enforce the acute need for clinician engagement to guide progress and ensure that conclusions derived from AI-driven imaging analysis reflect that same level of scrutiny lent to other avenues of clinical research.

Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier.

Cell migration and proteolysis are two essential processes during tumor invasion and metastasis. Matrix metalloproteinase (MMP)-2 (type IV collagenase; gelatinase A), is implicated in tumor metastasis as well as in primary tumor growth. The Rho family of small GTPases regulates the dynamics of actin cytoskeleton associated with cell motility. In this report, we provide evidence that Rac1, one member of Rho-related small GTPases, is a mediator of MMP-2 activation in HT1080 fibrosarcoma cells cultured in three-dimensional collagen gel (3D-col) and that MMP-2 activation is required for Rac1-promoted cell invasion through collagen barrier. Stable expression of dominant negative (Rac1V12N17) and constitutively active Rac1 (Rac1V12), respectively, in HT1080 cells demonstrates that Rac1 promoted cell invasiveness across type I collagen and collagen-dependent MMP-2 activation. Active Rac1 is sufficient to induce MMP-2 activation in cells cultured in fibrin gel, an extracellular matrix component that does not support MMP-2 activation. The Rac1-dependent MMP-2 activation occurred in a cell-associated fashion and required MMP activities. Because the cell membrane-mediated MMP-2 activation requires MT1-MMP and low amount of issue inhibitor of matrix metalloproteinase-2 (TIMP-2), their expression was examined. Rac1 modulated MT1-MMP mRNA level and the accumulation of a 43-kDa form of MT1-MMP protein, in correlation with MMP-2 activation profile. However, TIMP-2 expression was independent of Rac1 activity. The coordinate modulation of MMP-2 activity and MT1-MMP expression/processing by Rac1 is consistent with cell collagenolytic activity. The C-terminal hemopexin-like domain of MMP-2, which interferes with the cell membrane activation of MMP-2, reduced Rac1-promoted cell invasiveness as monitored by collagen invasion assay. These results suggest that collagen-dependent MMP-2 activation and MT1-MMP expression/processing contribute to Rac-promoted tumor cell invasion through interstitial collagen barrier.