INTRODUCTION: Overt hepatic encephalopathy (HE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to develop and validate prognostic models to identify patients at different risks of overt HE within 3 months after TIPS. METHODS: Two cohorts of patients with cirrhosis undergoing TIPS insertion were retrospectively included. In the derivation cohort of 276 patients, 3 models were established in increasing order of complexity: core model (age + Child-Pugh class), sarcopenia model (core model + sarcopenia), and full model (sarcopenia model + post-TIPS portal pressure gradient). All models were internally validated for discrimination and calibration and externally validated in an independent cohort of 182 patients. RESULTS: During a 3-month follow-up period, 61 (22.1%) and 33 patients (18.1%) developed overt HE in the derivation and validation cohort, and sarcopenia was associated with increased risk of the outcome. In the derivation cohort, the core model showed a c-statistic of 0.68 (95% confidence interval [CI] 0.61–0.75), and discrimination improved in the sarcopenia model (c-statistic 0.73; 95% CI 0.66–0.80). The full model that extended the core model with inclusion of sarcopenia and post-TIPS portal pressure gradient showed a significant improvement in discriminative ability (0.77; 95% CI 0.71–0.83; P = 0.001). Both sarcopenia and full model yielded comparable performances in the validation cohort. DISCUSSION: We developed and externally validated 2 prediction models applied before (sarcopenia model) and after TIPS (full model) to estimate the risk of post-TIPS overt HE. These tools could aid to select appropriate candidates for TIPS and guide postoperative management.

The emergence of effective immunotherapies has revolutionized therapies for many types of cancer. However, current immunotherapy has limited efficacy in certain patient populations and displays therapeutic resistance after a period of treatment. To address these challenges, a growing number of immunotherapy drugs have been investigated in clinical and preclinical applications. The diverse functionality of peptides has made them attractive as a therapeutic modality, and the global market for peptide-based therapeutics is witnessing significant growth. Peptides can act as immunotherapeutic agents for the treatment of many malignant cancers. However, a systematic understanding of the interactions between different peptides and the host’s immune system remains unclear. This review describes in detail the roles of peptides in regulating the function of the immune system for cancer immunotherapy. Initially, we systematically elaborate on the relevant mechanisms of cancer immunotherapy. Subsequently, we categorize peptide-based nanomaterials into the following three categories: peptide-based vaccines, anti-cancer peptides, and peptide-based delivery systems. We carefully analyzed the roles of these peptides in overcoming the current barriers in immunotherapy, including multiple strategies to enhance the immunogenicity of peptide vaccines, the synergistic effect of anti-cancer peptides in combination with other immune agents, and peptide assemblies functioning as immune stimulators or vehicles to deliver immune agents. Furthermore, we introduce the current status of peptide-based immunotherapy in clinical applications and discuss the weaknesses and future prospects of peptide-based materials for cancer immunotherapy. Overall, this review aims to enhance comprehension of the potential applications of peptide-based materials in cancer immunotherapy and lay the groundwork for future research and clinical applications.

Objective: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. Methods: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. Results: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8–30.5 months) and the median PFS was 15.7 months (95% CI: 14.7–16.6 months). The ORR was 58.8% (95% CI: 47.2–69.6) and DCR reached 81.2% (95% CI: 71.0–89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060–0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184–0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. Conclusion: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.

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.