Ramucirumab has shown efficacy in combination with paclitaxel in the second-line treatment of advanced gastric cancer (AGC). The efficacy and safety regarding the combination therapy of ramucirumab and docetaxel have not been reported. This treatment could reduce the incidence of neuropathy and patients’ hospital visits. This was a multicenter, single-arm phase II trial. Patients with AGC who were refractory or intolerant to primary treatment were eligible. Patients received ramucirumab at a dose of 8 mg/kg on day1 and 15, and docetaxel at a dose of 60 mg/m2 on day1 of a 28-day cycle. The primary endpoint was overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), relative dose intensity, and safety. A final analysis of efficacy and safety was performed in 35 patients. ORR was 25.7
In April 2023, the Japan Society of Hepatology published its official guidelines on liver rehabilitation for chronic liver disease. In this article, we summarize the current evidence on the role of liver rehabilitation in slowing the progression of chronic liver disease, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), liver cirrhosis, and hepatocellular carcinoma (HCC). Specifically, we outline the following: (1) the definition of liver rehabilitation and its target population; (2) exercise therapy in liver rehabilitation according to disease state; (3) considerations for patients with complications; (4) nutritional therapy in liver rehabilitation; and (5) potential economic benefits. Liver rehabilitation represents a novel therapeutic approach for patients with chronic liver disease, and this guidance aims to promote high-quality clinical research and strengthen the evidence base for its application.
Introduction Guideline-directed medical therapy (GDMT) has been demonstrated to reduce morbidity and mortality in patients with heart failure (HF). In addition to the need for GDMT, a large number of cardiovascular and non-cardiovascular medications are prescribed to patients with HF, especially the elderly, due to multiple comorbidities and chronic health conditions, such as chronic pain, musculoskeletal problems, insomnia or gastrointestinal issues. Polypharmacy may reduce adherence to GDMT and compromise its optimisation, potentially leading to worse clinical outcomes in patients with HF.Methods and analysis The Polypharmacy Evaluation for improving adherence, Regimen Simplification, Enhancement and Utilization of Standard therapy in Heart Failure (PERSEUS-HF) trial is a prospective, multicentre, randomised, open-label trial testing whether a comprehensive medication management programme (CMMP) improves medication adherence at 6 months compared with standard of care in patients with HF and polypharmacy (≥ five regular oral medications). Three hundred patients are randomly assigned to receive either a CMMP or standard of care in a 1:1 ratio. The CMMP incorporates deprescribing potentially inappropriate medications based on the established Beers Criteria, structured medication education and counselling, optimising GDMT, reducing dosing frequency, using polypill, transitioning to as-needed medication and using unit-dose packaging. The primary endpoint is the change in total Adherence Starts with Knowledge 20 score from baseline to 6 months. The PERSEUS-HF trial will evaluate the efficacy of CMMP in improving medication adherence in patients with HF and polypharmacy.Ethics and dissemination This study was approved by the Institutional Review Board of the Gunma University Hospital, with the participants’ hospitals approving the execution of the study (IRB2025-070).Clinical trial registration jRCT1030250606
BACKGROUND AND AIMS:This multicenter retrospective study in Japan aimed to investigate the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in patients with unresectable hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). METHODS:A total of 377 patients with HCC and treated with Dur/Tre across 30 institutions in Japan were included in this multicenter study. Time-dependent receiver operating characteristic (ROC) analysis was performed to determine the optimal LMR cut-off value. Hazard ratio (HR) spline curve analysis was used to identify the optimal LMR range for predicting progression-free survival (PFS) and overall survival (OS). RESULTS:Time-dependent ROC analysis identified an optimal LMR cut-off value of 2.52 for predicting median OS. Multivariate analysis demonstrated that an LMR of ≥ 2.52 was independently associated with superior PFS (HR: 0.777) and OS (HR: 0.657). The median PFS was 2.6 months in patients with an LMR of < 2.52, compared with 3.5 months in those with an LMR of ≥ 2.52 (p = 0.022). The median OS was 12.8 months in patients with an LMR of < 2.52, compared with 23.4 months in those with an LMR of ≥ 2.52 (p < 0.001). The disease control rate was significantly higher in the high LMR group (p = 0.032). The HR spline curve analysis revealed that an LMR range of approximately 1.8-2.6 represents an optimal cut-off for predicting both PFS and OS. CONCLUSIONS:LMR is a readily accessible prognostic biomarker for both PFS and OS in patients with unresectable HCC treated with Dur/Tre, and may serve as a practical tool for risk stratification in clinical practice.
BACKGROUND:Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor prognosis, but the impact relative to de novo AML remains controversial. We investigated clinical and genetic features in a multicenter Japanese cohort before CPX-351 approval. METHODS:We retrospectively analyzed 294 patients with newly diagnosed AML registered in the Hokkaido Leukemia Net between 2022 and 2023. Propensity score matching was used to adjust baseline variables. Genetic profiles were assessed in 160 matched patients. RESULTS:In the matched cohort, sAML/AML-MRC did not show inferior overall survival compared with non-sAML/non-AML-MRC (P = 0.90). Adverse karyotypes were the predominant determinant among sAML/AML-MRC. Among sAML/AML-MRC patients, adverse karyotypes were associated with poorer survival than those without adverse karyotypes (P = 0.0075). In contrast, non-sAML/non-AML-MRC groups did not affect survival regardless of adverse karyotypes (P = 0.51). Among 65 patients with ELN 2017 adverse-risk, those with TP53 mutations had markedly shorter survival than those with TP53 wild-type (P = 0.018). CONCLUSIONS:sAML/AML-MRC with an adverse karyotype had a dismal outcome. These findings provide a benchmark for risk stratification in the pre- CPX-351 era.
