Background Sorafenib and lenvatinib remain important first-line therapies for unresectable hepatocellular carcinoma (uHCC), especially in patients unsuitable for immune checkpoint inhibitors. However, prospective real-world comparative data are limited. Methods This multicenter prospective observational study (KSCC HAMRET) enrolled 167 patients with uHCC at 20 Japanese institutions between February 2020 and October 2021. Patients received sorafenib (n = 32) or lenvatinib (n = 135) and were followed until October 2023. Outcomes included overall survival (OS), progression-free survival (PFS), tumor response, and safety. Inverse probability of treatment weighting (IPTW) adjusted for baseline imbalances. Results In the unadjusted cohort, sorafenib showed longer OS than lenvatinib (median 35.1 vs. 15.7 months; hazard ratio [HR], 0.49; p = 0.0088). After IPTW adjustment, OS was similar (HR, 1.13; 95% confidence interval, 0.68–1.88). Median PFS was 4.8 months for sorafenib and 5.4 months for lenvatinib, with IPTW analysis favoring lenvatinib (HR, 1.50; p = 0.047). Weighted objective response rates were higher with lenvatinib by RECIST v1.1 (30.7% vs. 7.8%; p = 0.045) and mRECIST (43.3% vs. 14.7%; p = 0.036). Disease control rates were also greater with lenvatinib. Grade ≥ 3 adverse events occurred in 31.3% of sorafenib-treated and 45.2% of lenvatinib-treated patients, with hand–foot syndrome and proteinuria being the most common severe toxicities. Conclusions This prospective real-world study showed comparable OS between sorafenib and lenvatinib in first-line uHCC. Lenvatinib demonstrated superior PFS and tumor response, whereas sorafenib had a more favorable tolerability profile. These findings support individualized treatment selection based on tumor burden, biomarkers, and patient factors.
Background: This nationwide survey investigated new heart failure drug prescriptions by Japanese pediatric cardiologists. Methods and Results: Among 97 responding institutions, 357 patients received sodium-glucose cotransporter-2 inhibitors (SGLT-2i; n=189), angiotensin receptor-neprilysin inhibitors (ARNI; n=89), selective hyperpolarization-activated cyclic nucleotide-gated channel (HCN) blockers (n=76), or soluble guanylate cyclase (sGC) stimulators (n=3). SGLT-2i were predominantly prescribed in post-Fontan patients (45%), with one-third being children under 18 years. ARNI were commonly used for biventricular congenital heart disease (CHD) and cardiomyopathy (47% and 29%), with 40% under 18 years. Conclusions: Pediatric-specific clinical trials and appropriate usage guidelines are urgently needed.
ABCC6 pathogenic variants affect ischemic and hemorrhagic lesions in multiple organs and represent the third most common cause of hereditary cerebral small vessel diseases (CSVD) in Japan, yet their CSVD phenotypes remains unclear. We conducted a multicenter, cross-sectional study of 158 consecutive Japanese adults with severe CSVD. Genetic analysis was performed, and clinical and brain MRI findings were compared among ABCC6-related CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and genetically undetermined CSVD. Univariate and multivariate analyses assessed the association between ABCC6 pathogenic variants and hemorrhagic stroke, adjusting for age and hypertension. Nine patients (5.7
