Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma.

BACKGROUND: Recently, combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma (HCC). However, research on triple therapy [lenvatinib + sintilimab + transarterial chemoembolization (TACE)] as a first-line treatment for advanced HCC is limited. AIM: To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC. METHODS: HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled. All patients were treated with lenvatinib every day and sintilimab once every 3 wk. Moreover, TACE was performed every 4-6 wk if necessary. The primary outcome of the study was overall survival (OS). The secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. RESULTS: Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022. With a median follow-up of 8.5 months, the 3-, 6-, and 12-mo OS rates were 100%, 88.5%, and 22.5%, respectively. The ORR and DCR were 45% and 90%, respectively. The median progressive free survival and median OS were not reached. Common complications were observed in 76% of the patients (grade 3, 15%; grade 4, 2.5%). CONCLUSION: Combination therapy comprising lenvatinib, sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

Incidence and impact of antiplatelet therapy cessation among very older patients with stable coronary artery disease.

Objectives: Long-term use of evidence-based antiplatelet therapy is recommended for management of stable coronary artery disease (SCAD). However, non-adherence to antiplatelet drugs is common in older patients. This study aimed to evaluate the incidence and impact of antiplatelet therapy cessation on clinical outcomes of older patients with SCAD. Methods: A total of 351 consecutive eligible very older patients (≥80 years) with SCAD from the PLA General Hospital were included. Baseline demographics, clinical characteristics, and clinical outcomes were collected during follow-up. Patients were divided into cessation group and standard group based on whether discontinuing of antiplatelet drugs. The primary outcome was major adverse cardiovascular events (MACE) and secondary outcomes were minor bleeding and all-cause mortality. Results: A total of 351 participants, with a mean age of 91.76 ± 5.01 years old (range 80-106 years) were included in statistical analysis. The antiplatelet drug cessation rate was 60.1%. There were 211 patients in cessation group and 140 patients in standard group. During a median follow-up of 98.6 months, the primary outcome of MACE occurred in 155 patients (73.5%) in the cessation group and 84 patients (60.0%) in the standard group (HR = 1.476, 95% CI:1.124-1.938, p = 0.005). Cessation of antiplatelet drugs increased the rates of angina (HR = 1.724, 95% CI:1.211-2.453, p = 0.002) and non-fatal MI (HR = 1.569, 95% CI:1.093-2.251, p = 0.014). The secondary outcomes of minor bleeding and all-cause mortality were similar between the two groups. Conclusion: Among very older patients with SCAD, antiplatelet therapy cessation significantly increased the risk of MACE, and continuous antiplatelet drug therapy didn't increase the risk of minor bleeding.

Influence of Calcineurin Inhibitors and Genetic Polymorphism of Transporters on Enterohepatic Circulation and Exposure of Mycophenolic Acid in Chinese Adult Renal Allograft Recipients.

There is significant enterohepatic circulation (EHC) during the disposition of mycophenolic acid (MPA). The aim of this study was to elucidate factors influencing the EHC of MPA in Chinese adult renal allograft recipients. After 2 weeks of therapy with mycophenolate mofetil or enteric-coated mycophenolate sodium, blood samples were collected from 125 patients at 0 to 12 hours post-administration and MPA concentrations were determined. The influence of calcineurin inhibitors (CNIs) and genetic polymorphisms on MPA exposure and EHC was studied. The Shapley additive explanations method was used to estimate the impact of various factors on the area under the plasma drug concentration-time curve (AUC0-12h ) for MPA. An extreme gradient boosting (XGboost) machine learning-based model was established to predict AUC0-12h . Results showed that the dose-normalized AUC6-12h (dn-AUC6-12h ) of MPA was significantly lower in patients co-administered with cyclosporine (CsA) than in patients co-administered with tacrolimus (TAC) (P < .05). For patients co-administered with TAC, patients with ABCC2 C-24T CC or SLCO1B1 T521C TT genotypes had significantly higher values of dn-AUC6-12h (P < .05). Patients with SLCO1B3 334T/699G alleles had significantly lower dn-AUC6-12h values than homozygotes (P < .05). By introducing body weight, age, and EHC-related factors, including co-administered CNIs and genetic polymorphism of drug transporters, as covariates in the XGboost machine learning model, the prediction performance of AUC0-12h for MPA in Chinese adult renal allograft recipients can be improved.

Transarterial chemoembolization combined with radiofrequency ablation in the treatment of large hepatocellular carcinoma with stage C.

BACKGROUND: The combination therapy of transarterial chemoembolization and radiofrequency ablation (TACE-RFA) shows promising efficacy in large hepatocellular carcinoma (HCC). Data on the clinical efficacy and safety of TACE-RFA for large HCC with barcelona clinic liver cancer (BCLC) stage C are lacking in China. AIM: To determine the safety and efficacy of TACE-RFA for large, advanced HCC. METHODS: Patients of HCC with BCLC stage C who were treated with TACE-RFA or TACE alone at our institute from August 2008 to January 2017 were retrospectively reviewed. The complications were observed. The associations between overall survival (OS) and treatment method were analysed. RESULTS: Data were collected from 102 HCC patients. Among them, 64 underwent TACE-RFA and 38 underwent TACE. The combination of TACE and RFA was safe. All complications were controllable. The median OS in the TACE-RFA group was significantly longer than that in the TACE group (8.0 mo vs 4.0 mo, P = 0.000). The 6-, 12- and 24-mo survival rates of the combination group were 68.8%, 34.4%, and 10.9%, respectively, while those of the TACE group were 36.8%, 7.9%, and 0% (P < 0.05). CONCLUSION: TACE-RFA has an advantage over TACE alone in improving OS in large HCC patients with BCLC stage C.

CT-guided percutaneous chemical ablation combined with radiofrequency ablation for hepatocellular carcinomas in high-risk locations: lobaplatin vs. ethanol.

To retrospectively compare the clinical efficacy and safety of CT-guided percutaneous injection of lobaplatin vs. ethanol for chemical ablation combined with radiofrequency ablation (RFA) in patients with hepatocellular carcinomas (HCCs) in high-risk locations. From January 2017 to June 2018, a total of 41 patients with HCCs in high-risk locations were enrolled and divided into two groups: percutaneous lobaplatin injection (PLI+RFA) group and percutaneous ethanol injection (PEI+RFA) group. The mixture of lobaplatin or ethanol was accurately injected into the high-risk part of the tumors, while RFA ablated the non-high-risk part. The efficacy and safety were compared between the two groups. 41 patients had 51 lesions in high-risk locations, including 24 cases with 30 lesions in PLI+RFA group and 17 cases with 21 lesions in PEI+RFA group. The complete ablation rate was 93.3% (28/30) in PLI+RFA group and 90.5% (19/21) in PEI+RFA group (P=1.000). The 2-year local tumor progression rate of PLI+RFA group and PEI+RFA group was 20.0% (6/30) and 19.0% (4/21), respectively (P=1.000). No significant differences were found in time to progression and overall survival between the two groups (P=0.501 and P=0.424, respectively). The incidence and severity of adverse events between the two groups were similar (P > 0.05). No severe complications were observed in both groups. Percutaneous lobaplatin injection combined with RFA in the treatment of HCC in high-risk locations may achieve the complete ablation rate similar to percutaneous ethanol injection combined with RFA, but further research is needed to confirm.

Serum Lipid Profiles and All-Cause Mortality: A Retrospective Single Center Study on Chinese Inpatient Centenarians.

Objectives: To analyze the serum lipid profiles and investigate the relationship between the lipoprotein cholesterol levels and all-cause mortality in Chinese inpatient centenarians. Design: Retrospective study. Methods: Centenarians aged 100 years and older were admitted from January 2010 to January 2021 in our hospital. All centenarians completed a follow up visit till April 2021 of all-cause mortality and serum lipid profiles, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels. Cox proportional hazard models were used to assess the association between lipid profiles and all-cause mortality. Results: (1) These 121 centenarians on average were 100.85 ± 1.37 years old (100~107 years), including 114 males and 7 females. (2) The rate of treatment with lipid-lowering drugs was 69.4%, and the lipid-lowering drugs were mainly statins (63.6%). (3) The results of serum lipid profiles were as follows: TC 3.90 ± 0.69 mmol/L, TG 1.36 ± 0.55 mmol/L, HDL-C 1.14 ± 0.24 mmol/L, and LDL-C 2.05 ± 0.46 mmol/L. (4) The median follow-up time was 589 days (95% CI: 475, 703), and the all-cause mortality rate was 66.1%. (5) Multivariable analysis showed that higher TC level (HR = 1.968, 95% CI = 1.191-3.253, P = 0.008), lower LDL-C level (HR = 0.379, 95% CI = 0.212-0.677, P = 0.001) was independent factors contributed to all-cause mortality. Sensitivity analysis showed that the above results were stable. The therapy and complication morbidity did not present significant publication bias. Conclusions: The serum lipid profiles of Chinese inpatient centenarians were lower than those of the previous studies. Low LDL-C level was associated with an increased risk of all-cause mortality, which may indicate that more intensive lowering of LDL-C had a potential adverse effect on all-cause mortality for centenarians.

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'Jinyan No. 4'cucumber was used as experimental material. The growth of cucumber radicles treated with different concentrations of p-hydroxybenzoic acid (0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5 and 20 mmol·L-1) was investigated firstly, and 10 mmol·L-1 p-hydroxybenzoic acid was chosen for the further experiment. To investigate if melatonin alleviate p-hydroxybenzoic acid stress on cucumber radical elongation, 0, 1, 10, 25, 50, 75 and 100 µmol·L-1 melatonin were used to pretreat cucumber seeds for 24 h before 10 mmol·L-1 p-hydroxybenzoic acid treatment. The results suggested that exogenous melatonin could alleviate the radicle growth inhibition induced by p-hydroxybenzoic acid, and 75 µmol·L-1 melatonin showed the best effect. The growth of cucumber radical was significantly inhibited with an increase in p-hydroxybenzoic acid concentration, which was accompanied with lower activity of amylase. The melatonin pretreatment could significantly increase the activities of amylase and antioxidant enzymes in cucumber seeds resulting in lower accumulation of O2-·, H2O2 and MDA. Exogenous melatonin effectively reduced the PHBA stress on cucumber germination, which might be due to its function in decreasing oxidative stress and promoting starch catabolism.