Ginkgetin exhibits antifibrotic effects by inducing hepatic stellate cell apoptosis via STAT1 activation.

Liver fibrosis affects approximately 800 million patients worldwide, with over 2 million deaths each year. Nevertheless, there are no approved medications for treating liver fibrosis. In this study, we investigated the impacts of ginkgetin on liver fibrosis and the underlying mechanisms. The impacts of ginkgetin on liver fibrosis were assessed in mouse models induced by thioacetamide or bile duct ligation. Experiments on human LX-2 cells and primary mouse hepatic stellate cells (HSCs) were performed to explore the underlying mechanisms, which were also validated in the mouse models. Ginkgetin significantly decreased hepatic extracellular matrix deposition and HSC activation in the fibrotic models induced by thioacetamide (TAA) and bile duct ligation (BDL). Beneficial effects also existed in inhibiting hepatic inflammation and improving liver function. In vitro experiments showed that ginkgetin markedly inhibited HSC viability and induced HSC apoptosis dose-dependently. Mechanistic studies revealed that the antifibrotic effects of ginkgetin depend on STAT1 activation, as the effects were abolished in vitro after STAT1 silencing and in vivo after inhibiting STAT1 activation by fludarabine. Moreover, we observed a meaningful cross-talk between HSCs and hepatocytes, in which IL-6, released by ginkgetin-induced apoptotic HSCs, enhanced hepatocyte proliferation by activating STAT3 signaling. Ginkgetin exhibits antifibrotic effects by inducing HSC apoptosis via STAT1 activation and enhances hepatocyte proliferation secondary to HSC apoptosis via the IL-6/STAT3 pathway.

Beneficial effects of ginkgetin on improving nonalcoholic steatohepatitis characterized by bulk and single-cell RNA sequencing analysis.

Background and aims: Nonalcoholic steatohepatitis (NASH) has become one of the major causes of cirrhosis and liver failure. However, there are currently no approved medications for managing NASH. Our study was designed to assess the effects of ginkgetin on NASH and the involved mechanisms. Methods: We constructed a mouse model of NASH by high-fat diet for 24 weeks. The effects of ginkgetin on NASH were evaluated by histological study, Western blot, and biochemical analysis. RNA Sequencing (RNA-Seq) analysis was used to investigate the alteration in gene expression and signaling pathways at bulk and single-cell levels. Results: Administration of ginkgetin resulted in a marked improvement in hepatic lipid accumulation, inflammation, and fibrosis in the NASH model. And these results were supported by bulk RNA-Seq analysis, in which the related signaling pathways and gene expression were markedly downregulated. Furthermore, single-cell RNA-Seq (scRNA-Seq) analysis revealed that the effects of ginkgetin on NASH were associated with the reprogramming of macrophages, hepatic stellate cells, and endothelial cells. Especially, ginkgetin induced a marked decrease in macrophages and a shift from pro-inflammatory to anti-inflammatory phenotype in NASH mice. And the NASH-associated macrophages (NAMs), which emerge during NASH, were also significantly downregulated by ginkgetin. Conclusion: Ginkgetin exhibits beneficial effects on improving NASH, supported by bulk and single-cell RNA-Seq. Our study may promote pharmacological therapy for NASH and raise the existent understanding of NASH.

Reversion of liver cirrhosis after endovascular treatment in Chinese patients with Budd-Chiari syndrome.

AIMS: To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd-Chiari syndrome (BCS). METHODS: From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV-treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels. RESULTS: The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm3 vs. 771.36 ± 277.45 cm3 , p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment. CONCLUSIONS: BCS-induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis.

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.

Aerobic exercise and vitamin E improve high-fat diet-induced NAFLD in rats by regulating the AMPK pathway and oxidative stress.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver disease. We explored simple and effective ways to improve NAFLD and investigate the mechanism of action. METHODS: NAFLD was induced in 40 rats fed a high-fat diet (HFD). Magnetic resonance imaging was used to evaluate the progression and improvement of NAFLD. The treatment-related interventions included aerobic exercise (E) and vitamin E (VE) supplementation. Expression levels of proteins related to fat metabolism were also assessed. The activities of antioxidant enzymes in the liver and serum lipid metabolism were analyzed using biochemical methods. RESULTS: Aerobic exercise and vitamin E effectively improved NAFLD in rats, resulting in decreased hepatic fat accumulation, reduced hepatocyte ballooning, and decreased triglyceride levels. Combination therapy achieved the best effect. Both aerobic exercise and vitamin E activate the AMPK pathway to phosphorylate acetyl-CoA carboxylase (ACC) and reduce fatty acid synthesis. The expression of sterol regulatory element-binding protein-1 (SREBP-1) was decreased significantly in the treated groups, particularly in the E + VE + HFD group. The expression of carnitine palmitoyl-transferase 1C (CPT1C) significantly increased in the treated groups, particularly in the E + VE + HFD group. Compared with the control group, reactive oxygen species (ROS) in the E + HFD group were slightly decreased, while that in the VE + HFD group were significantly decreased, with the even greater reduction observed in the E + VE + HFD group. CONCLUSION: Aerobic exercise and vitamin E supplementation can improve HFD-induced NAFLD in rats by regulating the AMPK pathway and reducing oxidative stress.

Changes and influencing factors of liver volume after transjugular intrahepatic portosystemic shunt: a retrospective cohort study.

Background: Liver volume is an important measure of liver reserve and helps to determine the course of liver disease. This study aimed to observe the dynamic changes of liver volume after transjugular intrahepatic portosystemic shunt (TIPS) and analyze the related factors. Methods: Clinical data of 168 patients who underwent TIPS procedures between February 2016 and December 2021 were collected and analyzed retrospectively. The changes in liver volume after TIPS in the patients were observed, and the independent predictors affecting increases in liver volume were analyzed using a multivariable logistic regression model. Results: The mean liver volume was decreased by 12.9% at 2±1 months post TIPS and rebounded at 9±3 months post TIPS, but did not recover to its pre-TIPS level completely. Most patients (78.6%) had decreased liver volume at 2±1 months post TIPS, and in multivariable logistic regression, a lower albumin (ALB) level, a lower subcutaneous fat area at L3 (L3-SFA), and a higher degree of ascites were identified as independent factors predicting increased liver volume. The risk score model for predicting increased liver volume was Logit(P)=1.683-0.078 (ALB) -0.01 (pre TIPS L3-SFA) +0.996 (grade 3 ascites =1; non-grade 3 ascites =0). The area under the curve of the receiver operating characteristic curve was 0.729, and the cut-off value was 0.375. The rate of liver volume change at 2±1 months post TIPS was significantly correlated with that of spleen volume change (R2=0.378, P<0.001). The rate of subcutaneous fat change at 9±3 months post TIPS was significantly correlated with that of liver volume change (R2=0.782, P<0.001). In patients with a liver volume increase, the mean computed tomography value (Hounsfield units) decreased significantly after TIPS placement (65.9±17.7 vs. 57.8±18.2, P=0.009). Conclusions: Liver volume was decreased at 2±1 months post TIPS and slightly increased at 9±3 months post TIPS; however, it did not recover to its pre-TIPS level completely. A lower ALB level, a lower L3-SFA, and a higher degree of ascites were all predictors for increased liver volume post TIPS.

Management of traumatic peripheral artery pseudoaneurysm: A 10-year experience at a single center.

Purpose: This study aimed to report our 10-year experience with the management of iatrogenic (penetrating trauma) and traumatic (blunt or penetrating trauma) peripheral artery pseudoaneurysms, based on data from a tertiary referral center. Methods: From January 2012 to December 2021, the medical records of consecutive patients with iatrogenic and traumatic peripheral artery pseudoaneurysms were retrospectively reviewed. Patient demographics, clinical features, imaging data, treatment details, and follow-up results were analyzed. Results: Sixty-one consecutive patients were included in this study; 48 (79%) were men and 13 (21%) women, with a mean age of 49.4 â€‹± â€‹13.4 years (range 24-73 years). There were 42 patients (69%) who underwent open surgery, 18 (29%) undergoing endovascular embolization or stent implantation, and one (2%) undergoing ultrasound-guided thrombin injection. All patients successfully underwent open or interventional treatment. The median follow-up was 46.8 months (2.5-117.9 months), and the overall reintervention rate was 10%. Of these, one (5%) patient in the interventional treatment group and five (12%) patients in the open surgery group underwent reintervention. The overall complication rate was 8%, with complications occurring only in the open surgery group. No deaths occurred in the peri-operative period. No late complications, such as thrombosis or pseudoaneurysm recurrence, were observed. Conclusion: Peripheral artery pseudoaneurysms arising from iatrogenic or traumatic causes can be effectively treated by both open surgery and interventional procedures in selected patients with acceptable mid- and long-term outcomes.

The impact of thrombocytopenia on variceal bleeding in cirrhotic patients with transjugular intrahepatic portosystemic shunt.

Thrombocytopenia is the most frequent haematologic disorder in patients with cirrhosis, and it is perceived as a contributory factor for bleeding events. Cirrhosis patients with portal hypertension (PHT) is often accompanied with mild to moderate thrombocytopenia when they treated with transjugular intrahepatic portosystemic shunt (TIPS). To address whether the risk of variceal hemorrhage after TIPS varies with different platelet count in patients with normal platelet count and thrombocytopenia, we conducted the retrospective controlled study to evaluate the association of platelet count with the risk of variceal bleeding after TIPS. 304 patients were selected to the study. Propensity score matching was performed to adjust for potential selection bias. 63 patients from each group could be paired. Cox proportional hazards models were used to evaluate the association between platelet and variceal bleeding after TIPS. Platelet counts of two groups are 185.0 ± 98.7 × 109/L (normal platelet count) and 70.6 ± 39.3 × 109/L (thrombocytopenia) respectively. The bleeding rates of two groups in overall cohort are 10.9% (normal platelet count) and 12.9% (thrombocytopenia). After matched, the bleeding rates of two groups are 11.1% (normal platelet count) and 14.3% (thrombocytopenia) There was no statistically significant difference in bleeding rates between the two groups, either in the whole cohort (P = 0.671) or in the matched cohort (P = 0.593). Platelet count was not associated with bleeding events after TIPS (hazard ratio (HR) 95% confidence interval: 0.986-1.005, P = 0.397 in normal platelet count and 95% confidence interval: 0.968-1.020, P = 0.648 in thrombocytopenia). Thrombocytopenia in patients with cirrhosis was not associated with the risk of variceal bleeding episodes post-TIPS. Thrombocytopenia should not be viewed as an absolute contraindication for TIPS.

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.

Sarcopenia Defined by Psoas Muscle Thickness Predicts Mortality After Transjugular Intrahepatic Portosystemic Shunt.

PURPOSE: To assess and compare the value of psoas muscle thickness at the level of the third lumbar (L3) vertebra (TPML) or umbilicus (TPMU) and skeletal muscle index (SMI) for diagnosing sarcopenia and predicting mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: Two hundred forty-nine patients undergoing TIPS were included in this retrospective study. The cut-offs of L3-SMI for sarcopenia were 42.0 cm2/m2 in men and 38.0 cm2/m2 in women. The cut-offs for TPML/height and TPMU/height to predict mortality was established using a receiver-operating characteristic analysis. The Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Compared with TPMU/height, TPML/height was more consistent with L3-SM for the diagnosis of sarcopenia (Kappa coefficient: 0.63 vs. 0.36 in men; 0.61 vs. 0.45 in women). The Cox analysis showed that both TPML/height and TPMU/height were independent risk factors for mortality. The optimal cut-off values of TPML/height and TPMU/height for mortality in men and women were 11.2 mm/m, 9.4 mm/m, 18.4 mm/m, 15.1 mm/m, respectively. There were 119 (47.8%), 87 (34.9%), and 82 (32.9%) patients diagnosed with sarcopenia in the TPMU/height, TPML/height, and L3-SMI models, respectively. Kaplan-Meier analysis showed that the overall survival was significantly lower in the sarcopenia group in all three models. CONCLUSION: TPMU/height and TPML/height have a similar survival prognostic value as L3-SMI. TPML/height has better consistency with L3-SMI in diagnosing sarcopenia and is a more stable alternative to L3-SMI for diagnosing sarcopenia in patients undergoing TIPS.

Predictors of Improvement of Sarcopenia after Transjugular Intrahepatic Portosystemic Shunt Creation in Cirrhotic Patients.

To investigate the risk factors affecting the improvement of sarcopenia after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients, this study retrospectively analyzed the data of 111 cirrhotic patients with sarcopenia who underwent TIPS creation. Computed tomography-based measurement of skeletal muscle area was used to calculate skeletal muscle index (SMI) in all patients at baseline and 6 months after TIPS creation. Multivariate logistic regression analysis was used to identify independent risk factors, which showed a significant increase in 6-month post-TIPS SMI compared with that at baseline in both men and women (for both, P < .001). Pre-TIPS SMI (odds ratio [OR], 0.93; 95% CI, 0.87-0.99; P = .031) and change in portal pressure gradient (OR, 1.13; 95% CI, 1.03-1.24; P = .009) were found to be independent risk factors for experiencing substantial improvement in post-TIPS SMI.

Nanoscale CaO2 materials for synergistic transarterial chemoembolization in a VX2 orthotopic rabbit liver cancer model.

Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of hepatocellular carcinoma (HCC), but its efficacy is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). Herein, we synthesized polyvinyl pyrrolidone (PVP)-coated CaO2 nanoparticles (CaO2 NPs) and applied them as a synergistic agent to improve the antitumor efficacy of TACE. After injection into the tumor, CaO2 NPs reacted with water to generate abundant oxygen, hydroxyl ions (OH-), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing acid, and overloading Ca2+ to mediate antitumor effects. Moreover, the effect of chemotherapeutic drugs within the TACE was improved due to the modulated TME. CaO2 NPs efficiently regulated the TME and improved the antitumor effect of doxorubicin under hypoxia conditions in vitro. Compared to other groups, the TACE+CaO2 NPs group achieved the lowest tumor growth rate, highest tumor necrosis rate, lowest expression of histological markers associated with hypoxia and angiogenesis (HIF-α, VEGF, and CD31), and highest CD8+ T cell recruitment in vivo. Thus, these findings demonstrated that CaO2 NPs provide synergy for TACE therapy in the VX2 orthotopic rabbit liver cancer model, suggesting that they have a potential broad clinical application. STATEMENT OF SIGNIFICANCE: The efficacy of transcatheter arterial chemoembolization (TACE) for treatment of hepatocellular carcinoma is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). To address this issue, we synthesized CaO2 nanoparticles (CaO2 NPS) which would react with water to generate abundant oxygen, hydroxyl ions (OH-), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing the acidic TME, and inducing Ca2+ overloading. The efficacy of CaO2 NPs in combination with TACE was investigated in an orthotopic rabbit liver cancer model, and the results showed the great synergetic antitumor effect of TACE and CaO2 NPs.

A VEGFR targeting peptide-drug conjugate (PDC) suppresses tumor angiogenesis in a TACE model for hepatocellular carcinoma therapy.

Transcatheter arterial chemoembolization (TACE) has become the preferred therapy for unresectable advanced hepatocellular carcinoma (HCC). However, the embolization of tumor-feeding arteries by TACE always leads to hypoxia-related tumor angiogenesis, which limited the therapeutic effect for HCC. In this paper, we used a VEGFR targeting peptide VEGF125 - 136 (QKRKRKKSRYKS) to conjugate with a lytic peptide (KLUKLUKKLUKLUK) to form a peptide-drug conjugate (PDC). We used cell affinity assay to detect the peptide binding ability to VEGFR highly expressed cell lines, and CCK8, cell apoptosis to confirm the cellular toxicity for different cell lines. Meanwhile, we created a VX2 tumor-bearing rabbit model to assess the in vivo anti-tumor effect of the peptide conjugate in combination with TAE. HE staining was used to verify the in vivo safety of the peptide conjugate. IHC was used to assess the anti-angiogenesis and cell toxicity of the peptide conjugate in tumor tissues. The peptide conjugate could not only target VEGFR in cell surface and inhibit VEGFR function, but also have potent anti-cancer effect. We luckily found the peptide conjugate showed potent cytotoxicity for liver cancer cell Huh7 (IC50 7.3 ± 0.74 µM) and endothelial cell HUVEC (IC50 10.7 ± 0.292 µM) and induced cell apoptosis of these two cell lines. We also found the peptide conjugate inhibited cell migration of HUVEC through wound healing assay. Besides, these peptides also showed better in vivo anti-tumor effect than traditional drug DOX through TACE in VX2 rabbit tumor model, and efficiently inhibit angiogenesis in tumor tissues with good safety. In conclusion, our work may provide an alternative option for clinical HCC therapy via TACE combination.

Effect of underdilated transjugular intrahepatic portosystemic shunt on prognosis in patients with prior splenectomy: a propensity score-matched case-control study.

PURPOSE: This study aimed to investigate whether underdilated transjugular intrahepatic portosystemic shunt (TIPS) could reduce the risk of hepatic encephalopathy (HE) and ameliorate impaired hepatic function in patients with a history of splenectomy. METHODS: A retrospective case-control study was conducted with 96 patients who had prior splenectomy and TIPS placement from August 2016 to May 2022. All patients were divided into two groups based on the diameter of expansion balloon catheters, the underdilated group (6-mm balloon catheter, n = 60) and a control group (8-mm balloon catheter, n = 36). Following the 1:1 propensity score matching (PSM), 33 patients in the underdilated group and 33 patients in the control group were included. RESULTS: During a median follow-up of 36 months, a quicker recovery in liver function after TIPS placement was showed in the underdilated group. The mean TBIL content (16.562 ± 6.549 µmol/L vs 23.871 ± 11.609 µmol/L, P = 0.019) and the mean CLIF-C AD score (41.108 ± 5.223 vs 45.100 ± 4.429, P = 0.033) in the underdilated group were significantly lower than those in the control group during 6 to 12 months after the procedure. In line with the control group, the ability to reduce portal pressure gradient (PPG) and achieve a significantly clinical remission of PVT and ascites severity was showed in the underdilated group 3 months after TIPS creation (P < 0.001). The Kaplan-Meier analysis demonstrated that no statistically significant differences were found in the cumulative incidence of no overt HE (OHE) (log-rank P = 0.383), cumulative incidence without shunt dysfunction (log-rank P = 0.283), cumulative incidence of no variceal rebleeding (log-rank P = 0.696), and survival (log-rank P = 0.341) (log-rank P = 0.341) between the two groups during the follow-up period. CONCLUSION: For patients with prior splenectomy, it is safe to employ underdilated TIPS, as the stents will eventually self-expand to 8 mm. The present study has shown some degree of liver function preservation in the underdilated group, which may be related to slower progressive changes in the portal hemodynamics.

Portal flow diversion based on portography is superior than puncture site in the prediction of overt hepatic encephalopathy after TIPS creation.

BACKGROUND: Targeted puncture of an appropriate portal venous branch during transjugular intrahepatic portosystemic shunt (TIPS) procedure may reduce the risk of postprocedural overt hepatic encephalopathy (HE). This study aimed to describe blood distribution under portography and combined it with puncture site to determine portal flow diversion, and to evaluate its prognostic value in predicting post-TIPS overt HE. METHODS: In this retrospective analysis of patients with cirrhosis undergoing TIPS, we included 252 patients to describe blood distribution under portography and 243 patients to assess the association between portal flow diversion and post-TIPS overt HE. RESULTS: At the first stage, 51 (20.2%) patients were identified as type A (unilateral type with the right portal branch receives blood from splenic vein [SV]), 16 (6.4%) as type B (unilateral type with the right branch receives blood from superior mesenteric vein [SMV]) and 185 (73.4%) as type C (fully mixed type). At the second stage, 40 patients were divided into the SV group, 25 into the SMV group and 178 into the mixed group. Compared with the mixed group, the risk of post-TIPS overt HE was significantly higher in the SMV group (adjusted HR 3.70 [95% CI 2.01-6.80]; p < 0.001), whereas the SV group showed a non-significantly decreased risk (adjusted HR 0.57 [95% CI 0.22-1.48]; p = 0.25). Additionally, the SMV group showed a substantial increase in ammonia level at 3 days and 1 month after procedure. CONCLUSIONS: Our results support the clinical use of portal flow diversion for risk stratification and decision-making in the management of post-TIPS overt HE.

Dynamic Changes in the Aorta During the Cardiac Cycle Analyzed by ECG-Gated Computed Tomography.

Background: To characterize the difference in aortic dimensions during the cardiac cycle with electrocardiogram (ECG)-gated computed tomography angiography (CTA) and to determine whether other parameters in comparison to diameter could potentially provide a more accurate size reference for stent selection at the aortic arch and the proximal thoracic descending aorta. Methods: The CTA imaging of 90 patients during the cardiac cycle was reviewed. Three anatomic locations were selected for analysis (level A: 1 cm proximal to the innominate artery; level B: 1 cm distal to the left common carotid artery; and level C: 1 cm distal to the left subclavian artery). We measured the maximum diameter, the minimum diameter, the lumen area, the lumen perimeter, and the diameter derived from the lumen area, and the changes of each parameter at each level during the cardiac cycle were compared. Results: The mean age was 60.9 ± 12.4 years (range, 16-78 years). There was a significant difference in the aortic dimensions during the cardiac cycle (p < 0.001). The diameter derived from the lumen area at all three levels was changed least over time when compared to the area, perimeter, and the maximum aortic diameter (all p < 0.01). Conclusion: The aortic dimensional differences during the cardiac cycle are significant. The aortic diameter derived from the lumen area over other parameters may provide a better evaluation for selecting the size of the stent at the aortic arch and the proximal thoracic descending aorta. A prospective study comparing these different measurement parameters regarding the outcomes is still needed to evaluate the clinical implications.

Shape Designed Implanted Drug Delivery System for In Situ Hepatocellular Carcinoma Therapy.

In this study, an intelligent drug delivery system (DDS) based on implanted triboelectric nanogenerator (iTENG) and red blood cell (RBC) is established for in situ hepatocellular carcinoma (HCC) therapy. Apatinib (APA), as an oral antitumor drug, which can inhibit the expression of vascular endothelial growth factor receptor-2 (VEGFR2) is loaded inside RBC, realizing the transform from oral formulation to injection preparation. Multishape designed iTENG adapted for different implant sites and environments can harvest biomechanical energy efficiently. The electric field (EF) generated by the iTENG can increase the release of APA, and the release will decrease quickly when the EF disappears, which shows that the DDS is highly controllable. The controllable DDS demonstrates an exciting killing ability of HCC cells both in vitro and in vivo with strikingly reduced APA dosage. After implantation, the self-powered DDS has a prominent therapeutic effect of HCC-bearing rabbits, which is expected to be applied in clinical medicine.

Inclusion of sarcopenia improves the prognostic value of MELD score in patients after transjugular intrahepatic portosystemic shunt.

OBJECTIVE: To explore the predictive value of model for end-stage liver disease (MELD)-Sarcopenia score for survival of cirrhotic patients after transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: 289 patients who underwent TIPS between February 2016 and December 2020 were included, they were divided into the sarcopenia group ( n = 138) and non-sarcopenia group ( n = 151) according to whether they were complicated with sarcopenia. Kaplan-Meier curve was used to analyze and compare the prognosis of the above two groups and multivariate Cox regression analysis was used to identify the independent prognostic factors. The performance of different predictive models was compared using C-index. RESULTS: During the follow-up, Kaplan-Meier analyses indicated that cumulative survival was significantly lower in sarcopenia group than that in non-sarcopenia group [74.6% vs. 92.7%, HR, 0.24 (95% confidence interval (CI), 0.12-0.46), Log-rank P < 0.001]. After multivariate Cox analysis, age [HR, 1.040 (95% CI, 1.015-1.065), P = 0.002], sarcopenia [HR, 3.948 (95% CI, 1.989-7.838), P < 0.001], albumin [HR, 0.945 (95% CI, 0.897-0.997), P = 0.037], and MELD score [HR, 1.156 (95% CI, 1.097-1.217), P < 0.001] were identified as the independent risk factors for mortality after TIPS. The C-indexes of MELD-Sarcopenia, Child-Pugh, MELD, MELD-Na, and the Freiburg index of post-TIPS survival (FIPS) scores were 0.782, 0.688, 0.719, 0.734, and 0.770, respectively. CONCLUSION: Sarcopenia is independently correlated with post-TIPS mortality, and MELD-Sarcopenia score showed the best performance in predicting post-TIPS mortality than the traditional predictive models.

Sarcopenia in Patients with Cirrhosis after Transjugular Intrahepatic Portosystemic Shunt Placement.

Background Sarcopenia is frequently found in patients with cirrhosis and is associated with liver dysfunction, cirrhosis-related complications, and poorer quality of life. Purpose To evaluate changes in skeletal muscle and fat mass at CT and to evaluate the relationship of sarcopenia to mortality in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. Materials and Methods Patients who underwent TIPS between August 2016 and May 2020 were included in this retrospective study. Skeletal muscle and fat mass were evaluated at CT at the L3 vertebra at baseline and at 2 months, 5 months, and 1 year after TIPS. Sarcopenia was defined as L3 skeletal muscle index (SMI) less than 50 cm2/m2 for men and less than 39 cm2/m2 for women. The primary end point was change in skeletal muscle and fat mass, and secondary end points included survival and the predictive factors for survival. Changes in skeletal muscle and fat mass over time were analyzed by generalized estimating equations. Results A total of 224 patients (159 men [113 with and 46 without sarcopenia] and 65 women [32 with and 33 without sarcopenia]) were included. In male patients with sarcopenia, the mean L3 SMI increased from 41.8 cm2/m2 (baseline) to 49.1 cm2/m2 (at 5-month follow-up; P < .001) and 49.6 cm2/m2 (at 1-year follow-up; P < .001) after TIPS. In female patients with sarcopenia, SMI increased from 33.7 cm2/m2 (at baseline) to 40.6 cm2/m2 (at 5-month follow-up; P < .001) and 42.0 cm2/m2 (at 1-year follow-up; P < .001) after TIPS. Sarcopenia (hazard ratio, 3.0; 95% CI: 1.2, 7.8) was identified as an independent risk factor for mortality after TIPS, and the patients who converted from sarcopenic to nonsarcopenic had higher cumulative survival rate than those who did not (96.4% vs 82.1%; log-rank P = .04). Conclusion In patients with sarcopenia, both skeletal muscle and fat mass increased after transjugular intrahepatic portosystemic shunt placement. The reversal of sarcopenia could reduce the risk of death. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee in this issue.

Natural History and Influence on Long-term Outcomes of Isolated Type II Endoleak after Endovascular Aneurysm Repair: A 10-year Experience at a Single Center.

BACKGROUND: The management of type II endoleaks (T2ELs) remains controversial in current literature. Hence, this study aimed to explore the natural history of isolated type II endoleak after endovascular aneurysm repair (EVAR) and its influence on long-term outcomes based on a 10-year follow-up at a tertiary medical center. METHODS: From January 2011 to April 2021, consecutive patients who underwent elective EVAR were reviewed. The demographics, clinical characteristics, treatment details, imaging information, in the event of T2ELs, and outcomes were extracted. RESULTS: A total of 287 patients were included for analysis. Isolated T2EL was identified in 79 patients (27.5%), while no endoleak was found in 208 patients (72.5%). The mean age at EVAR was 68.1 ± 8.9 years (range, 41-92 years) and the majority of patients were male (81.5%). The mean follow-up duration was 42.7 months (range, 2-119.7 months). Among the 79 patients with isolated T2ELs, 33 (41.8%, 33/79) were early and 46 (58.2%, 46/79) were late. Spontaneous resolution of T2ELs was identified in 29 patients (36.7%, 29/79). Persistent T2ELs were observed in 50 patients (63.3%, 50/79). No sac growth was seen in 33 patients (66%, 33/50) and these patients were managed conservatively. The remaining 17 patients (34%, 17/50) showed significant sac growth. Six of them declined intervention due to various reasons and the remaining 11 patients underwent interventional embolization for T2ELs. Following the embolization, 2 patients had complete resolution of T2ELs and 9 patients had persistent T2ELs. Among the patients with persistent T2ELs, 2 patients (2/9) still showed progressive sac growth, and one of them died from aneurysm rupture; the remaining 7 patients (7/9) showed no sac growth. Patients with isolated T2ELs had a higher incidence of sac growth than patients without any endoleak (21.5% vs 4.3%, p < 0.001), while no difference was found in overall survival between the two groups. In Cox regression analysis, only higher age was independently associated with worse survival. CONCLUSIONS: Type II Endoleak was significantly associated with aneurysm sac growth and no association with survival was observed.