BACKGROUND/AIM:Radiofrequency ablation (RFA) is a mainstay curative treatment for unresectable hepatocellular carcinoma (HCC). Despite the success of RFA, however, some patients with HCC continue to experience local recurrence (LR). The aim of the present study was to identify risk factors for LR post-RFA, considering cases of repeated RFA for LR-HCC separately. PATIENTS AND METHODS:This study initially included 829 patients who underwent RFA for HCC at our institution between January 2013 and December 2022. From these, 447 patients with single HCC were selected based on the selection criteria, and they were further classified into a new HCC lesion group (n=400, NL group) and repeated RFA for LR-HCC post-first RFA group (n=47, LR group). The two groups were retrospectively analyzed to identify factors related to LR post-RFA. RESULTS:In the NL and LR groups, the median observation period after treatment was 36.9 months and 33.7 months, respectively. The cumulative LR rates were 5.1%, 11.0%, and 14.2% in the NL group, and 12.8%, 34.2%, and 40.8% in LR group at 1, 3, and 5 years post-RFA, respectively. The Cox proportional hazard test showed that HCC tumors >1.5 cm [hazard ratio (HR)=3.606; p=0.001] and tumor site (adjacent to blood vessels) (HR=1.932; p=0.035) were identified as independent risk factors for LR post-RFA in the NL group, while only TACE prior to RFA was identified in the LR group. CONCLUSION:Tumor size and site of HCC were independent risk factors for LR post-RFA. Moreover, repeated RFA for LR-HCC post-first RFA had quite a high rate of LR post-RFA. For these cases, the selection of modalities other than RFA should be considered.
Introduction Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening event with high mortality. While systemic corticosteroids are commonly used in clinical practice for AE-IPF despite the absence of randomised evidence, the optimal tapering strategy is uncertain. Early corticosteroid tapering reduces adverse events in other inflammatory diseases. However, the efficacy and safety of this approach in AE-IPF have not been established. This study aims to determine if an early corticosteroid tapering regimen is non-inferior to a conventional regimen for 90-day mortality in patients with AE-IPF.Methods and analysis The RApid PrednIsolone Dose reduction for acute exacerbation of Idiopathic Pulmonary Fibrosis (RAPID-IPF) trial is a multicentre, parallel-group, open-label, randomised controlled non-inferiority trial conducted in Japan. A total of 70 patients (up to 130) hospitalised for AE-IPF will be randomly assigned in a 1:1 ratio to either an accelerated 6-week prednisolone tapering regimen (early tapering group) or a conventional 12-week tapering regimen (standard tapering group). The primary outcome is all-cause mortality at 90 days. The non-inferiority margin is set at a 10% risk difference. Key secondary outcomes include 28-day mortality, mortality due to respiratory causes, time to respiratory worsening or death, protocol adherence and the proportion of patients lost to follow-up. The trial incorporates two interim analyses for feasibility and sample size re-estimation.Ethics and dissemination This study will be conducted in compliance with the Declaration of Helsinki and Japanese ethical guidelines. The protocol was approved by the institutional review boards of all participating hospitals (lead approval: Saiseikai Kumamoto Hospital, #1367). Written informed consent will be obtained from all participants or their legally acceptable representatives. Findings will be disseminated through scientific conferences and publication in a peer-reviewed journal.Trial registration number Japan Registry of Clinical Trials (jRCT1071250015).
BACKGROUND/AIM:Immune checkpoint inhibitor-based combination therapies are standard treatment options for unresectable hepatocellular carcinoma (HCC). However, conventional endpoints such as objective response rate, progression-free survival, and overall survival may not fully capture response dynamics, including depth of response (DpR), time to response, and duration of response. This study descriptively evaluated response dynamics in patients with unresectable HCC treated with durvalumab plus tremelimumab or atezolizumab plus bevacizumab. PATIENTS AND METHODS:This retrospective single-center study included 148 patients with unresectable HCC who received durvalumab-tremelimumab (n=53) or atezolizumab-bevacizumab (n=95). A reduction of ≥50% in target lesion diameter was defined as DpR50. Because of baseline imbalances and differences in observation period, the analysis was only descriptive and hypothesis-generating. RESULTS:Fifty-three patients received durvalumab-tremelimumab and 95 received atezolizumab-bevacizumab. The overall response rate was 35.8% for the durvalumab-tremelimumab group and 27.4% for the atezolizumab-bevacizumab group, whereas the disease control rates were 54.7% and 71.6%, respectively. DpR50 was observed in 26.4% and 11.6% of patients, respectively. The median times to response were 2.3 and 3.3 months, and the median durations of response were 22.3 and 10.0 months, respectively. Durable response lasting ≥6 months occurred in 24.5% and 15.8% of all treated patients, respectively. The median PFS was 5.2 and 7.0 months, and median OS was 17.0 and 22.0 months, respectively. CONCLUSION:Therapy with durvalumab-tremelimumab was associated with deeper and more durable tumor shrinkage in selected responders, whereas atezolizumab-bevacizumab provided broader disease control mainly through stable disease. These findings should be interpreted as hypothesis-generating.
Abstract Background Decreased serum sodium (Na) and chloride (Cl) concentrations are each known independent predictors of poor prognosis in patients with heart failure (HF). However, their impact on the effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2i) and other guideline-directed HF medications remains unclear. Purpose This study aimed to evaluate whether the prognostic effects of SGLT2i and other major HF medications differ according to serum Na and Cl levels at discharge. Methods Quality of HEart Failure CARe and OuTcomes (QHEART) Registry Retrospective Cohort (QHEART-R) Study included patients hospitalized for worsening HF from October 2020 through December 2024 at six institutions in Japan. Low Na and Low Cl at discharge were defined as serum Na <135 mmol/L and Cl <97 mmol/L, respectively. Patients were stratified according to use of SGLT2i, β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and renin–angiotensin system (RAS) inhibitors (ACEi/ARB/ARNI) at discharge. The primary endpoint was a composite of all-cause death or HF rehospitalization within 3 months after discharge. Results A total of 2,613 patients were analyzed (mean age 77 years, 55% male, mean LVEF 44%). Low Na and low Cl were observed in 11% and 7% of patients, respectively. As shown in Figure1, both low Na and low Cl were associated with worse 3-month prognosis compared with normal Na or Cl values (Low Na: HR 1.75 [1.31–2.33], Low Cl: HR 1.91 [1.37–2.65]). SGLT2i use was associated with favorable outcomes in patients with normal Na and Cl (Normal Na: HR 0.52 [0.40-0.68], Normal Cl: HR 0.50 [0.39-0.65]), and also in low Na patients (HR 0.56 [0.31-0.98]), but no prognostic benefit was observed in low Cl patients (HR 0.92 [0.48-1.75]) (Figure 2). No significant differences in effect across Na or Cl strata were observed for BB, MRA, or RAS inhibitors. Conclusions In HF patients with low Cl at discharge, the prognostic benefit of SGLT2i may be attenuated. In contrast, BB, MRA, and RAS inhibitors showed no significant differences in effect across Na or Cl strata. These findings provide novel insights into the mechanisms of SGLT2i and guide drug selection in patients with electrolyte abnormalities.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.
