Aim: This study aimed to systematically characterize transplant rejection after immune checkpoint inhibitors (ICIs) initiation in solid organ transplant recipients (SOTRs).Methods: Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database and case reports in the literature. Disproportionality analysis including information component and reported odds ratio (ROR) was performed to access potential risk signals.Results: A total of 168 patients with transplant rejection after ICIs usage were identified in the FAERS database, and 89 cases were identified in the literature review. ICIs were significantly associated with transplant rejection (ROR₀₂₅: 2.2). A strong risk signal was found for combination therapy with pembrolizumab and ipilimumab compared to monotherapy.Conclusion: Immune checkpoint inhibitors were significantly associated with transplant rejection in SOTRs.

Objective: To evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhotic PVT, and compare differences in efficacy and safety among different anticoagulants. Methods: We comprehensively searched Pubmed, Cochrane Library, EMBASE, and ClinicalTrials.gov from inception to April 2022 for studies using anticoagulants for cirrhotic PVT. Meta-analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results: 3 RCTs and 14 cohort studies involving 1270 patients were included. Anticoagulant therapy can increase the recanalization rate compared with non-anticoagulation therapy (OR 4.44, 95% CI 3.11-6.32, I² = 2.5%) and can decrease the extension rate of cirrhotic PVT (OR 0.33, 95% CI 0.18-0.62, I² = 41.0%), without increasing the incidence of total bleeding (OR 1.21, 95% CI 0.75-1.97, I² = 9.8%), major bleeding (OR 0.98, 95% CI 0.49-1.95, I² = 19.7%), and variceal bleeding (OR 0.35, 95% CI 0.12-1.01, I² = 39.9%). Subgroup analysis showed that VKA, LMWH, and DOACs could increase the recanalization rate of PVT and were not associated with the risk of bleeding. Studies that compared direct oral anticoagulants (DOACs) with warfarin directly showed that the recanalization rate of PVT in the DOACs group might be higher than that in the warfarin group (OR 30.99, 95% CI 7.39-129.87, I² = 0.0%), and there was no difference in the rate of total bleeding (OR 0.30, 95% CI 0.01-8.65, I² = 79.6%). Conclusions: Anticoagulants are safe and effective in patients with cirrhotic PVT. The rate of PVT recanalization associated with DOACs may be higher than warfarin.

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m²) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients. To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations. A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers. A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m²), and standard dosing of edoxaban may be effective and safe for AF patients. Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.

Background: The role of anticoagulants in the treatment of cirrhotic PVT remains controversial. This study aimed to analyze the safety and efficacy of anticoagulant therapy in patients with cirrhotic portal vein thrombosis (PVT) and its impact on prognosis. Methods: A retrospective cohort study was conducted for PVT patients with liver cirrhosis in our hospital. The primary outcome of the study was the PVT recanalization rate. Other outcomes included bleeding rate, liver function, and mortality. Cox and Logistic regression were used to explore the risk factors of outcomes. Results: This study included 77 patients that 27 patients in the anticoagulant group and 50 in the non-anticoagulant group. Anticoagulant therapy was associated with higher rate of PVT recanalization (44.4% vs 20.0%, log-rank P = 0.016) and lower rate of PVT progression (7.4% vs 30.0%, log-rank P = 0.026), and without increasing the rate of total bleeding (14.8% vs 24%, P = 0.343), major bleeding (3.7% vs 6%, P = 0.665) and variceal bleeding (3.7% vs 16%, P = 0.109). The safety and efficacy of different anticoagulants were similar. The Child-Pugh grade of the anticoagulant therapy group was better than that of the non-anticoagulant therapy group (P = 0.030). There was no significant difference in the 2-year survival rate of the two groups. Conclusion: Anticoagulants could increase the PVT recanalization rate and reduce the PVT progression rate without increasing the rate of bleeding. Anticoagulants may be beneficial to improving the liver function of patients with cirrhotic PVT. There was no significant difference in the safety and efficacy of different anticoagulants in the treatment of cirrhotic PVT.