Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score-matching analysis.

BACKGROUND: Portal vein tumor thrombosis (PVTT) signifies late-stage hepatocellular carcinoma (HCC) with high-risk progression and poor prognosis. As a standard treatment, sorafenib monotherapy has limited the efficacy in managing HCC with PVTT. Currently, both hepatic arterial infusion chemotherapy (HAIC) and the combination of camrelizumab and rivoceranib have shown favorable survival benefits for advanced HCC, surpassing the standard sorafenib treatment. In this study, we investigate the safety and efficacy of HAIC combined with camrelizumab and rivoceranib in treating HCC patients with PVTT. METHODS: From January 2020 to December 2021, HCC patients with PVTT, who received either a triple regime of HAIC combined with camrelizumab and rivoceranib or a dual regime of camrelizumab and rivoceranib as their first-line treatment, were reviewed for eligibility at four hospital centers in China. To balance any intergroup differences, propensity score matching (PSM) was applied. The aim of this study is to compare the efficacy of the dual and triple combination treatment regimens based on survival prognosis and tumor response and evaluate the safety based on the occurrence of adverse reactions. RESULT: In this study, a total of 411 patients who received either the triple treatment regime (HAIC combined with camrelizumab plus rivoceranib, referred to as the HAICCR group, n = 292) or the dual treatment regime (camrelizumab combined with rivoceranib, referred to as the CR group, n = 119) between January 2020 and December 2021 were included. The results showed that the HAICCR group exhibited significantly better overall survival (mOS: 19.60 months vs. 11.50 months, p < 0.0001) and progression-free survival (mPFS: 10.0 months vs. 5.6 months, p < 0.0001) compared to the CR group in the overall cohort. Moreover, the HAICCR group also had a significantly higher ORR (objective response rate, 55.5% vs. 42.0%, p = 0.013) and DCR (disease control rate, 89.0% vs. 79.0%) compared to the CR group. After PSM, a final matched cohort of 83 pairs was obtained, and the survival benefits were consistent in this cohort as well (mOS: 18.70 months vs. 11.0 months, p < 0.0001; mPFS: 10.0 months vs. 5.6 months, p < 0.0001). However, there was no significant difference in the ORR between the triple and dual combination regimes. Univariate and multivariate analysis showed that CTP (Child-Turcotte-Pugh) stage, ALBI (albumin-bilirubin index) grade, tumor number, and treatment regime were significant risk factors affecting overall survival, while AFP (α-fetoprotein) level, tumor number, metastasis, and treatment regime were significant risk factors affecting progression-free survival. As for safety, hypertension and hand-foot syndrome were the two most common adverse reactions in both groups, with no significant difference in the occurrence of adverse reactions between the two groups (p < 0.05). CONCLUSION: In the context of advanced HCC patients with PVTT, the combination regime of HAIC and camrelizumab plus rivoceranib demonstrates more excellent capacity for prolonging survival and offers a well-tolerated safety compared to the CR dual therapy approach. This triple regime represents a therapeutic modality of broad prospects and vast potential for HCC patients with PVTT.

Transarterial chemoembolization with/without immune checkpoint inhibitors plus tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a single center, propensity score matching real-world study.

OBJECTIVES: To explore the efficacy and safety of Transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: 456 patients with HCC receiving either TACE in combination with ICIs and TKIs (combination group, n = 139) or TACE monotherapy (monotherapy group, n = 317) were included from Apr 2016 to Dec 2021 in this retrospective study. We employed propensity score matching (PSM), performed 1:2 optimal pair matching, to balance potential bias. RESULTS: The mean follow-up time is 24.7 months (95% CI 22.6-26.8) for matched patients as of March 2022. After matching, the combination group achieved longer OS and PFS (median OS:21.9 vs. 16.3 months, P = 0.022; median PFS: 8.3 vs. 5.1 months, P < 0.0001) than TACE monotherapy group. The combination group had better objective response rate (ORR) and disease control rate (DCR) (ORR: 52.5% vs. 32.8%, P < 0.001; DCR: 82.7% vs. 59.6%, P < 0.001). Subgroup analysis showed that patients who received "TKIs + ICIs" after the first TACE procedure (after TACE group) achieved longer OS than those before the first TACE procedure (before TACE group) (26.8 vs. 19.2 months, P = 0.011). Adverse events were consistent with previous studies of TACE-related trials. CONCLUSIONS: TACE plus TKIs and ICIs appeared to deliver longer PFS and OS in HCC patients than TACE monotherapy. "TKIs + ICIs" co-treatment within 3 months after the first TACE procedure might be a better medication strategy.

Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis.

PURPOSE: To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between groups were compared. RESULTS: Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC-PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC-PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression-free survival (median progression-free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC-PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC-PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression-free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival. CONCLUSION: The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.

Prognosis prediction and risk stratification of transarterial chemoembolization or intraarterial chemotherapy for unresectable hepatocellular carcinoma based on machine learning.

OBJECTIVE: To develop and validate a risk scoring scale model (RSSM) for stratifying prognostic risk after intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC). METHODS: Between February 2014 and October 2022, 2338 patients with HCC who underwent initial IATs were consecutively enrolled. These patients were divided into training datasets (TD, n = 1700), internal validation datasets (ITD, n = 428), and external validation datasets (ETD, n = 200). Five-years death was used to predict outcome. Thirty-four clinical information were input and five supervised machine learning (ML) algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBT), and Random Forest (RF), were compared using the areas under the receiver operating characteristic (AUC) with DeLong test. The variables with top important ML scores were used to build the RSSM by stepwise Cox regression. RESULTS: The CatBoost model achieved the best discrimination when 12 top variables were input, with the AUC of 0.851 (95% confidence intervals (CI), 0.833-0.868) for TD, 0.817 (95%CI, 0.759-0.857) for ITD, and 0.791 (95%CI, 0.748-0.834) for ETD. The RSSM was developed based on the immune checkpoint inhibitors (ICI) (hazard ratios (HR), 0.678; 95%CI 0.549, 0.837), tyrosine kinase inhibitors (TKI) (HR, 0.702; 95%CI 0.605, 0.814), local therapy (HR, 0.104; 95%CI 0.014, 0.747), response to the first IAT (HR, 4.221; 95%CI 2.229, 7.994), tumor size (HR, 1.054; 95%CI 1.038, 1.070), and BCLC grade (HR, 2.375; 95%CI 1.950, 2.894). Kaplan-Meier analysis confirmed the role of RSSM in risk stratification (p < 0.001). CONCLUSIONS: The RSSM can stratify accurately prognostic risk for HCC patients received IAT. On the basis, an online calculator permits easy implementation of this model. CLINICAL RELEVANCE STATEMENT: The risk scoring scale model could be easily implemented for physicians to stratify risk and predict prognosis quickly and accurately, thereby serving as a more favorable tool to strengthen individualized intra-arterial therapies and management in patients with unresectable hepatocellular carcinoma. KEY POINTS: • The Categorical Gradient Boosting (CatBoost) algorithm achieved the optimal and robust predictive ability (AUC, 0.851 (95%CI, 0.833-0.868) in training datasets, 0.817 (95%CI, 0.759-0.857) in internal validation datasets, and 0.791 (95%CI, 0.748-0.834) in external validation datasets) for prediction of 5-years death of hepatocellular carcinoma (HCC) after intra-arterial therapies (IATs) among five machine learning models. • We used the SHapley Additive exPlanations algorithms to explain the CatBoost model so as to resolve the black boxes of machine learning principles. • A simpler restricted variable, risk scoring scale model (RSSM), derived by stepwise Cox regression for risk stratification after intra-arterial therapies for hepatocellular carcinoma, provides the potential forewarning to adopt combination strategies for high-risk patients.

Tyrosine kinase inhibitors, immune checkpoint inhibitors combined with hepatic arterial infusion of oxaliplatin and raltitrexed versus oxaliplatin, 5-fluorouracil and leucovorin for intermediate and advanced hepatocellular carcinoma: A retrospective study.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated promising benefits in treating advanced hepatocellular carcinoma (HCC). In China, the most frequently used HAIC regimen is oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). However, arterial infusion of fluorouracil over 46 h was not convenient. Raltitrexed, another antimetabolic agent with a long plasma half-life, allows for shorter infusion durations. We aimed to compare the effectiveness and toxicity of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) combined with HAIC with raltitrexed plus oxaliplatin (RALOX) or FOLFOX in patients with intermediate and advanced HCC. METHODS: This retrospective study enrolled 82 eligible patients from February 2019 to December 2021. Forty patients were treated with FOLFOX HAIC (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 administered on day 1, and 5-fluorouracil 2400 mg/m2 infusion for 46 h, every 3 weeks) combined with TKIs and ICIs. Forty-two patients received RALOX HAIC (oxaliplatin 100 mg/m2 and raltitrexed 3 mg/m2 on day 1, every 3 weeks) combined with TKIs and ICIs. We compared the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile. RESULTS: ORR was similar between the FOLFOX HAIC and RALOX HAIC groups (42.5% vs 42.5%, P = 0.974). DCR also showed no significant difference between the two groups (87.5% vs 85.7%, P = 0.813). Median PFS was 10.7 months in the FOLFOX HAIC group versus 10.2 months in the RALOX HAIC group (P = 0.41). Median OS was 20.3 months in the FOLFOX HAIC group, compared to 17.7 months in the RALOX HAIC group (P = 0.50). Both groups had similar profiles of grade 3/4 treatment-related adverse events, including thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, and leukocytopenia. CONCLUSION: The effectiveness and safety of HAIC with RALOX were comparable to HAIC with FOLFOX in intermediate and advanced HCC patients.

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC.

BACKGROUND AND AIMS: Cancer stem cells (CSCs) contribute to therapy resistance in HCC. Linear ubiquitin chain assembly complex (LUBAC) has been reported to accelerate the progression of cancers, yet its role in the sorafenib response of HCC is poorly defined. Herein, we investigated the impact of LUBAC on sorafenib resistance and the CSC properties of HCC, and explored the potential targeted drugs. APPROACH AND RESULTS: We found that HOIL-1, but not the other components of LUBAC, played a contributing role in LUBAC-mediated HCC sorafenib resistance, independent of its ubiquitin ligase activity. Both in vitro and in vivo assays revealed that the upregulated HOIL-1 expression enhanced the CSC properties of HCC. Mechanistically, HOIL-1 promoted sorafenib resistance and the CSC properties of HCC through Notch1 signaling. Mass spectrometry, co-immunoprecipitation, western blot, and immunofluorescence were used to determine that the A64/Q65 residues of HOIL-1 bound with the K78 residue of Numb, resulting in impaired Numb-mediated Notch1 lysosomal degradation. Notably, pixantrone was screened out by Autodock Vina, which was validated to disrupt HOIL-1/Numb interaction to inhibit Notch1 signaling and CSC properties by targeting the Q65 residue of HOIL-1. Moreover, pixantrone exerted synergistic effects with sorafenib for the treatment of HCC in different HCC mouse models. CONCLUSIONS: HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.

Ozonated Water Inhibits Hepatocellular Carcinoma Invasion and Metastasis by Regulating the HMGB1/NF-κB/STAT3 Signaling Pathway.

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. High-mobility group box 1 (HMGB1), a highly conserved chromosome protein, is considered as a potential therapeutic target and novel biomarker because of its regulation in the proliferation and metastasis of HCC. Ozone has been shown to be beneficial in the treatment of cancer. The objective of this study was to explore the effects and molecular mechanism of ozonated water on the proliferation, migration, and invasion of BEL7402 HCC cells. Materials and Methods: We assessed cell proliferation using a CCK-8 assay kit and flow cytometry; we performed wound healing and transwell assays to evaluate the effects of ozonated water treatment on cell invasion and migration. We determined reactive oxygen species (ROS) values by flow cytometry and used ELISAs to detect cytokines HMGB1, IL-6, and TNF-α. In addition, we assessed mRNA and protein cytokine expressions using RT-qPCR and Western blot. Results: Ozonated water decreased the viability of the HCC cells; the IC50 of ozonated water at 24 h was approximately 1.5 µg/mL. Compared with control groups, ozone treated cells revealed reduced mobility on wound healing assays and decreased invasion in transwell assays. HMGB1, IL-6, and TNF-α cytokines were found at lower levels in ozone treated cells than in control cells. Ozonated water-induced ROS accumulation. Likewise, the expressions of phosphorylated nuclear factor Kappa B (NF-κB), p65, NF-κB, P-STAT3, IL-6, JAK2, Slug, Twist, vimentin, MMP-2, MMP-9, and HMGB1 were decreased in the treated cells. Conclusion: Our findings suggest that ozonated water inhibits the proliferation, invasion, and metastasis of HCC cells via regulation of the HMGB1/NF-κB/STAT3 signaling pathway.

Phosphotungstate Acid Doped Polyanilines Nanorods for in situ NIR-II Photothermal Therapy of Orthotopic Hepatocellular Carcinoma in Rabbit.

Introduction: Second near-infrared photothermal therapy (NIR-II PTT) has become a promising strategy for treating cancer in terms of safety and potency. However, the application of NIR-II PTT was limited in the treatment of deep-buried solid tumors due to the low dose of NIR-II absorption nanomaterials and the inadequate laser energy in the deep tumor. Methods: Herein, the authors report the engineering of NIR-II absorbing polyaniline nanorods, termed HPW@PANI Nanorods, for in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial infusion for the treatment of orthotopic hepatocellular carcinoma in the rabbit. HPW@PANI Nanorods were prepared via chemical oxidant polymerization of aniline under phosphotungstic acid, which exhibited effective NIR-II absorption for hyperthermia ablation cells. Results: HPW@PANI Nanorods were fast and efficiently deposited into primary orthotopic transplantation VX2 tumor in rabbits via transarterial infusion. Furthermore, an optical fiber was interventionally inserted into the primary VX2 tumor to transmit 1064nm laser energy for in situ NIR-II PTT, which could ablate primary tumor, inhibit distant tumor, and suppress peritoneal metastasis. Conclusion: This study provides new insights into the application of in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial injection of NIR-II absorption nanomaterials to treat deep-buried tumors.

Tumor-feeding artery diameter reduction is associated with improved short-term effect of hepatic arterial infusion chemotherapy plus lenvatinib treatment.

BACKGROUND: Recently, hepatic arterial infusion chemotherapy (HAIC) plus lenvatinib has been frequently used to treat unresectable hepatocellular carcinoma (uHCC) in China. In the clinic, the hepatic arteries of some patients shrink significantly during this treatment, leading to improved short-term efficacy. AIM: To investigate the relationship between the shrinkage of hepatic arteries and the short-term effect of HAIC plus lenvatinib treatment. METHODS: Sixty-seven participants with uHCC were enrolled in this retrospective study. The patients received HAIC every 3 wk, followed by oral lenvatinib after the first HAIC course. Hepatic artery diameters were measured on CT before treatment and after 1 and 2 mo of treatment. Meanwhile, the changes in tumor capillaries were also examined on pathological specimens before and after 1 mo of treatment. The antitumor response after 1, 3, and 6 mo of treatment was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The relationship between the changes in vessel diameters and the short-term effect of the combination treatment was evaluated by receiver-operating characteristic and logistic regression analyses. RESULTS: The hepatic artery diameters were all significantly decreased after 1 and 2 mo of treatment (P < 0.001), but there was no difference in the vessel diameters between 1 and 2 mo (P > 0.05). The microvessel density in the tumor lesions decreased significantly after 1 mo of combination treatment (P < 0.001). According to mRECIST, 46, 41, and 24 patients had complete or partial responses after 1, 3, and 6 mo of treatment, respectively, whereas 21, 21, and 32 patients had a stable or progressive disease at these times, respectively. Shrinkage of the tumor-feeding artery was significantly associated with the tumor response after 1, 3, and 6 mo of treatment (P < 0.001, P = 0.004, and P = 0.023, respectively); however, changes in other hepatic arteries were not significantly associated with the tumor response. Furthermore, shrinkage of the tumor-feeding artery was an independent factor for treatment efficacy (P = 0.001, P = 0.001, and P = 0.002 and 1, 3, and 6 mo, respectively). CONCLUSION: The hepatic arteries shrank rapidly after treatment with HAIC plus lenvatinib, and shrinkage of the tumor-feeding artery diameter was closely related to improved short-term efficacy.

NIR-absorbing Prussian blue nanoparticles for transarterial infusion photothermal therapy of VX2 tumors implanted in rabbits.

Nanomaterial-related photothermal therapy has been intensively investigated for treatment of hepatocellular carcinoma (HCC). However, owing to the low specificity to tumors and easy excretion from the systemic circulation, the low dose of photoactive nanomaterials in solid tumors severely hinders the photothermal therapy applications for HCC. Herein, an innovative strategy for transarterial infusion photothermal therapy (TAIPPT) of VX2 tumors implanted in rabbits is reported. NIR-absorbing Prussian blue nanoparticles were prepared by microemulsion methods, which demonstrate excellent photothermal therapy capacity and satisfactory biocompatibility. Prussian blue nanoparticles are transarterially infused into VX2 tumors and irradiated for photothermal therapy. TAIPPT achieves fast and efficient delivery of nanoparticles into tumors and complete ablation by one-time transarterial infusion treatment. Furthermore, TAIPPT could activate the immune cells in rabbits and inhibit distant tumors. Our findings describe a promising strategy for tumor eradication and may benefit future clinical HCC patients.

Twelve-Month Computed Tomography Follow-Up after Thoracic Endovascular Repair for Acute Complicated Aortic Dissection.

BACKGROUND: To explore the impact of thoracic endovascular aortic repair (TEVAR) on aortic remodeling (AR) and the relationship between AR and complications after TEVAR. METHODS: A total of 56 patients (2 type IIIA aortic dissection [AD] and 54 type IIIB AD) with complicated acute type B aortic dissection suitable for TEVAR were prospectively enrolled. There were 44 men (78%) and 12 women (22%) with an average age of 54 ± 13.8 years. Aortic enhanced computed tomography (CT) was performed pre-TEVAR and 3, 6, and 12 months postoperatively. The morphological changes in AR, namely aortic volume and false lumen thrombosis, were obtained by analyzing the CT data. The effect of TEVAR on AR was determined by the morphological changes in the aorta. The relationship between AR index, false lumen thrombosis, and complications was analyzed. RESULTS: The volume of the thoracic aortic true lumen gradually increased post-TEVAR, whereas the volume of the thoracic aortic false lumen gradually decreased. The volume of abdominal aortic total lumen and false lumen increased 6 months postoperatively. The AR index increased significantly 3 months postoperatively, which was negatively correlated with complications and mortality. The thoracic and abdominal aortic false lumen thrombosis developed gradually after TEVAR, and the degree of thoracic aortic false lumen thrombosis was negatively correlated with complications and mortality. CONCLUSIONS: TEVAR promotes AR. AR index and the degree of thoracic aortic false lumen thrombosis can serve as predictors of complications and mortality.

Percutaneous Treatment of Benign Biliary Anastomotic Strictures: Retrievable Covered Self-Expandable Metal Stent with Fixation String Versus Large-Bore Catheters.

PURPOSE: To retrospectively compare the safety and efficacy of a covered self-expandable metal stent (CSEMS) with a transhepatic fixation string and a large-bore catheter for benign biliary anastomotic stricture after hepatobiliary surgery. MATERIALS AND METHODS: From March 2012 to June 2017, 49 patients with benign biliary anastomotic strictures, untreatable with endoscopy, were included. Twenty-three patients (catheter group) were treated with a large-bore catheter (with progressive catheter upsizing to 16-18 Fr), whereas 26 patients (stent group) were treated by CSEMS (10-mm stent) placement. Technical success, clinical success, primary patency, recurrent strictures, complication rate, and catheter or stent indwelling time were compared between the groups. RESULTS: Technical success and clinical success were achieved in all patients. In the stent group, stent retrieval was successful in all patients. The overall complication rate was 24.5% (catheter group vs. stent group, 30.4% vs. 19.2%; P = .363). Stent migration occurred in 1 patient during follow-up (1/26, 3.8%). The mean indwelling time was 10.3 ± 3.0 months (range, 8-16 months; median, 10 months) in the catheter group and 4.0 ± 1.2 months (range, 3-7 months; median, 4 months) in the stent group (P < .001). Recurrent strictures occurred in 10 (43.5%) patients in the catheter group and 4 (15.4%) patients in the stent group (P = .030). The 1- and 3-year primary patency rates were 82.6% and 69.3% in the catheter group and 92.3% and 84.4% in the stent group (P = .042). CONCLUSIONS: Percutaneous placement of a retrievable CSEMS showed superior intermediate-term outcomes over a large-bore catheter in patients with benign biliary anastomotic strictures.

A model to predict early hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND/AIMS: Early hepatic encephalopathy (HE) is one of the most common complications developed after undergoing transjugular intrahepatic portosystemic shunt (TIPS). Hence, its early prevention and treatment are important. This study aimed at establishing a model to predict early post-TIPS HE. MATERIALS AND METHODS: Clinical data of 262 patients who underwent TIPS procedure was analyzed retrospectively. Patients were divided into early post-TIPS HE and non-early post-TIPS HE groups, based on the presence of HE within 3 months after TIPS. About 70% of the patients were randomly selected as the model group to establish a prediction model, and the remaining 30% were used as the validation group to test the model. The independent risk factors for early HE post-TIPS were identified and selected using single factor analysis and multi-factor logistic regression analysis. Subsequently the prediction model was established and validated. RESULTS: Age, Child-Pugh classification, and fibrinogen were found to be the independent risk factors for early post-TIPS HE., The logistic regression model was established based on these factors and their regression coefficients: p=1/{1+exp[4.829-1.975*age-1.110*(Child-Pugh classification)+1.724*loge (fibrinogen in g/L)]}. Finally, the model was validated among a set of 79 patients from the validation group. CONCLUSION: The logistic regression model based on age, Child-Pugh classification, and fibrinogen for early post-TIPS HE can effectively predict the risk of early HE after TIPS.

A Randomized Trial of Ultrasound- versus. Fluoroscopy-Guided Subclavian Vein Catheterization in Children with Hematologic Disease.

OBJECTIVE: To compare the ultrasound- and fluoroscopy-guided subclavian vein catheterization in pediatric population with hematologic diseases. METHODS: A randomized prospective study of subclavian vein catheterization in pediatric population with hematologic diseases was performed. After randomization, the patients were assigned to either ultrasound- or fluoroscopy-guided subclavian vein catheterization. The primary outcome was number of attempts at venous cannulation. Secondary outcomes included: catheterization success rate, fluoroscopy time, operation time, and surgical complications. RESULTS: There were 170 children enrolled between February 2017 and July 2018. There was no difference between the two groups with regard to the demographic data. Success within 3 attempts was achieved in 82 cases (82/87, 92.0%) in the ultrasound (US) group vs. 65 cases (65/83, 78.3%) in the fluoroscopy group (P = 0.002). The average operation time was 10(7) min in US group vs. 10(6) min in fluoroscopy group (P = 0.722). There were 3 complications in the US group, while there were 6 complications in the fluoroscopy group (P = 0.321). There were 4 catheter-related thrombosis (CRTs) found in the US group during follow-up, however there was no CRT in the fluoroscopy group (P = 0.121). CONCLUSIONS: Ultrasound-guided venous puncture is a more accurate method of subclavian vein catheterization. However, the catheter tip can be placed more precisely by fluoroscopy. Thus, combined ultrasound-and fluoroscopy-guided technology is more efficient in subclavian vein catheterization of children with hematologic disease.

Selection of Stents by Calculation of Arterial Cross-sectional Area in Modified Sandwich Technique for Complex Aortoiliac Arterial Lesions.

BACKGROUND: We prospectively evaluated the modified sandwich technique for treatment of complex aortoiliac arterial lesions using commercial stent grafts selected according to the arterial cross-sectional area. The primary outcomes were technical feasibility and mid-term follow-up results. METHODS: We prospectively enrolled 13 patients (mean age 63.85 ± 6.12 years) with aortoiliac arterial lesions (5 infrarenal abdominal aortic dissections, 1 lower abdominal aortic occlusion, 5 iliac artery aneurysms, 1 external iliac arterial pseudoaneurysm, and 1 type IB endoleak following endovascular aneurysm repair) for endovascular repair with the modified sandwich technique. All lesions were complex and unsuitable for routine endovascular treatment. The bifurcated stent-graft diameters were determined by calculating the arterial cross-sectional area. Success and complication rates were recorded. Patients were followed for 20.69 ± 6.51 (range 6-31) months and stent patency determined by contrast-enhanced ultrasound and computed tomography 1, 3, and 6 months post-operatively and every 12 months thereafter. RESULTS: The initial technical success rate was 100%, and no surgical complications occurred. The primary patency of the stent grafts was 100% during follow-up. Post-procedural type I "gutter" endoleaks occurred in 4 patients (30.8%) after 1 month. At 3 months, the endoleaks in 3 of the 4 patients had disappeared without treatment, and the remaining endoleak resolved after coil embolization. CONCLUSIONS: The sandwich technique is a safe and effective therapy for complex aortoiliac arterial lesions. Stent-graft sizes based on the arterial cross-sectional area can ensure technical success and reduce the rate of "gutter" endoleaks.

Fluoroscopy-guided subclavian vein catheterization in 203 children with hematologic disease.

Subclavian vein catheterization plays an important role in the treatment of children with hematologic disease. However, catheter placement is a difficult and high-risk procedure in children.Fluoroscopy-guided subclavian vein catheterization was used in 203 children (mean age, 6.99 years ±â€Š3.722 years; range, 1-16 years) with hematologic disease. The number of vein punctures, catheterization success rate, fluoroscopy time, operation time, and surgical complications were recorded.There was a 100% success rate for fluoroscopy-guided subclavian vein catheterization. A total of 124 cases (61.1%) were successful on the first venipuncture attempt; 171 cases (84.2%) achieved success within 3 attempts. Twenty-five cases had 4 to 6 time venipunctures and the remaining 7 cases underwent ≥7 time venipunctures. All catheter tips were successfully placed at the junction of the superior vena cava and the right atrium. Fluoroscopy times ranged from 16 to 607 seconds (mean, 65.46 ±â€Š85.864 seconds). Operation time ranged between 5 and 25 minutes (mean, 10.38 ±â€Š4.036 minutes). Arterial punctured was happened during surgery in 2 cases. There were 2 cases of catheter-related infection, but no other complications. The mean follow-up time was 35 days; range 20 to 50 days.Fluoroscopy-guided subclavian vein catheterization in children is a safe procedure, with a high success rate, resulting in a reduced number of venipunctures, optimal catheter placement, and reduced complications.

VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often arises in the setting of chronic inflammation with multiple inhibitory immune signals. V-domain Ig suppressor of T cell activation (VISTA) is identified as a novel negative checkpoint regulator. This study sought to determine the expression and prognostic value of VISTA in HCC and classify tumor microenvironments (TMEs) based on VISTA and CD8+ tumor-infiltrating lymphocytes (TILs). METHODS: The expression of VISTA and CD8 proteins was assessed in 183 HCC tissue microarrays (TMAs) by immunohistochemistry (IHC). VISTA and CD8A mRNA extracted from 372 patients with HCC in The Cancer Genome Atlas (TCGA) database was included as a validation cohort. Associations between the VISTA, clinicopathological variables, and survival were analyzed. RESULTS: VISTA expression was detected in 29.5% HCC tissues, among which 16.4% tissues were positive for tumor cells (TCs), and 16.9% tissues were positive for immune cells (ICs). VISTA expression was significantly associated with tissues with a high pathological grading (p = 0.038), without liver cirrhosis (p = 0.011), and with a high density of CD8 + TILs (p < 0.001). Kaplan-Meier curves demonstrated that patients with VISTA-positive staining in TCs (p = 0.037), but not in ICs, (p = 0.779) showed significantly prolonged overall survival (OS) than those with VISTA-negative expression. Classification of HCC TME-based VISTA and CD8 + TILs showed 4 immune subtypes: VISTA+/CD8+ (16.9%), VISTA+/CD8- (12.6%), VISTA-/CD8+ (16.4%), and VISTA-/CD8+ (54.1%). The dual positive VISTA+/CD8+ subtype showed significantly prolonged OS than other subtypes (p = 0.023). CONCLUSIONS: VISTA protein expression in HCC showed cell specific and displayed different prognosis. VISTA expression was significantly associated with CD8 + TILs, Dual positive VISTA+/CD8+ showed favorable TME and better OS.

[Transjugular intrahepatic portosystemic shunt with Viatorr stent grafting: report of 3 cases].

We here report 3 cases successfully treated with transjugular intrahepatic portosystemic shunt using Viatorr stent. The 3 patients were had a diagnosis of liver cirrhosis with portal vein hypertension, and presented with black stool and hematemesis. After the treatment, the patients' portal vein pressures were decreased without black stool or hematemesis. Our success demonstrate the feasibility of using Viatorr stent in transjugular intrahepatic portosystemic shunt.

Ozone promotes regeneration by regulating the inflammatory response in zebrafish.

Ozone is thought to advance wound healing by inhibiting inflammation, but the mechanism of this phenomenon has not been determined. Although the zebrafish is often used in regeneration experiments, there has been no report of zebrafish treated with ozonated water. We successfully established a zebrafish model of ozonated water treatment and demonstrate that ozonated water stimulates the regeneration of the zebrafish caudal fin, its mechanism, and time dependence. The growth rate of the caudal fin and the number of neutrophils migrating to the caudal fin wound after resection were higher in the experimental (ozonated) group than in the control group, preliminarily confirming that ozone-promoted regeneration is related to the stimulation of an early inflammatory response by ozone. Ozone modulated the expression of tumor necrosis factor-α (TNF-α) in two ways by regulating interleukin 10 (IL-10) expression. Therefore, ozone promotes tissue regeneration by regulating the inflammatory pathways. This effect of ozone in an experimental zebrafish model is demonstrated for the first time, confirming its promotion of wound healing and the mechanism of its effect in tissue regeneration. These results will open up new directions for ozone and regeneration research.

Iodine based radiopacity of experimental blood clots for testing of mechanical thrombectomy devices.

BACKGROUND: Barium sulfate powder used for radiopacity of experimental blood clots (EBCs) for testing mechanical thrombectomy devices (MTD) has negative effects on EBCs mechanical properties. In vitro and in vivo exploration was performed to determine if the iodine based contrast medium will have less negative effects on the EBCs than barium. MATERIALS AND METHODS: Fresh blood from 2 swine was used to create fibrinogen enhanced and thrombin initiated EBC in tubes. Iodine radiopacity was achieved by mixing the blood with 65% Iohexol or by soaking the EBCs for 2 or 24 hours in Iohexol. The EBCs opacified with barium served as controls. In vitro study: The EBCs were subjected to four tests, manual elongation, catheter injection, radiopacity and contrast wash out tests. In vivo study: The common carotid arteries of 2 swine were embolized by either barium EBC or EBC soaked for 24 hours in Iohexol. The duration of radiopacity of the different EBCs was compared. RESULTS: The EBCs opacified with Iohexol initially had higher radiopacity than the barium opacified EBCs. However, their opacity rapidly decreased with saline soaking and, particularly, after they were embolized in live animals. The mechanical properties of Iohexol opacified EBCs were inferior to barium opacified EBCs. The Iohexol mixed EBCs were less firm and elastic and half of them fragmented during catheter injection. The Iohexol soaked EBCs exhibited decreased tensile strength and elasticity compared to the barium EBCs. CONCLUSIONS: Compared to barium, iodine based contrast medium does not offer any advantage for opacifying EBCs.