BACKGROUND:Neoadjuvant chemotherapy (NAC) may improve outcomes in perihilar cholangiocarcinoma (PHC); however, its efficacy compared with upfront surgery (US) for resectable PHC remains unclear. We compared survival and clinicopathological characteristics between NAC and US in patients with technically resectable PHC, using propensity score matching (PSM). METHODS:We retrospectively analyzed 261 patients with resectable PHC who underwent surgical treatment (2016-2024) across multiple institutions. Among them, 50 received NAC and 199 underwent US. The 38 patients receiving NAC were matched 1:1 with patients undergoing US using PSM. Overall survival (OS) and progression-free survival (PFS) were compared between groups. Pathological response to NAC and its association with chemotherapy doses were also evaluated. RESULTS:Before PSM, OS and PFS did not differ significantly between the US and NAC groups. After PSM, OS did not differ significantly between groups, but PFS was significantly longer in the NAC group, where patients with a therapeutic-effect grade ≥1b had better PFS than those with US. Grade ≥1b response was associated with receiving ≥7 NAC doses. DISCUSSION:NAC may improve PFS in selected patients with resectable PHC, especially those showing major pathological responses. Prospective studies should validate these findings and define optimal selection criteria and regimens.
Backgrounds: The AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease) trial demonstrated that rivaroxaban monotherapy was non-inferior in efficacy and superior in safety compared to rivaroxaban plus single antiplatelet therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). This study examined whether systolic blood pressure (SBP) affects clinical outcomes and modifies the impact of antithrombotic therapy. Methods: In this post hoc analysis, participants were stratified based on median SBP at baseline: >126 mmHg (High SBP group, n = 1042) and ≤126 mmHg (Low SBP group, n = 1093). The primary efficacy endpoint was a composite of cardiovascular events and all-cause death. The primary safety endpoint was major bleeding. Results: The mean SBP was 139 mmHg and 114 mmHg in the High and Low SBP groups, respectively. In the propensity score-matched cohort (n = 1684), the Low SBP group had a significantly higher incidence of the primary efficacy endpoint (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.01–1.88; p = 0.039), while the primary safety endpoint was comparable between groups. In the Low SBP group, rivaroxaban monotherapy was associated with lower risks of both the primary efficacy (HR, 0.60; 95% CI, 0.41–0.86; p = 0.006) and safety endpoints (HR, 0.40; 95% CI, 0.22–0.74; p = 0.003) compared with combination therapy, whereas no significant differences were observed in the High SBP group. Conclusions: Lower SBP was associated with increased risk of cardiovascular events and all-cause death. Rivaroxaban monotherapy demonstrated more favorable efficacy and safety outcomes particularly patients with lower SBP.
BACKGROUND:Introduction of guideline-directed medical therapy (GDMT) has transformed the care of heart failure (HF) with reduced ejection fraction, establishing four foundational drug classes. Yet, in clinical practice, many patients cannot initiate or maintain all four, and clinicians must pragmatically prioritise agents such as angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter-2 inhibitor, whose comparative impacts are still explored. Moreover, the optimal loop diuretic to pair with modern GDMT, which enhances natriuresis, remains uncertain. METHODS:Between January 2022 and February 2024, we conducted a multicentre, open-label, randomised, 2×2 factorial design trial for ambulatory patients with symptomatic HF, elevated natriuretic peptide levels and left ventricular ejection fraction (LVEF) <50%, despite conventional therapies (eg, renin-angiotensin-aldosterone system inhibitors and beta-blockers). The patients were assigned to receive either sacubitril/valsartan or dapagliflozin, and torsemide or furosemide. The primary endpoint was the change in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) over 6 months; a prespecified secondary endpoint was a hierarchical clinical outcome. RESULTS:Of 231 randomised patients (median age 73 years; median LVEF 36%; 84.0% New York Heart Association class II), changes in KCCQ-OSS did not differ between sacubitril/valsartan and dapagliflozin (adjusted mean difference 2.53 points; 95% confidence interval (CI) -1.81 to 6.88; p=0.25) or between torsemide and furosemide (0.25 points; 95% CI -4.10 to 4.59; p=0.91). Hierarchical composite outcome analyses also showed no significant differences between sacubitril/valsartan and dapagliflozin (win ratio, 1.15; 95% CI 0.71 to 1.88), or between torsemide and furosemide (win ratio, 1.15; 95% CI 0.70 to 1.85). CONCLUSIONS:This trial found no evidence of benefit of one treatment over another for health status over 6 months. Given the sample size and predefined power, modest differences between treatments cannot be excluded. TRIAL REGISTRATION NUMBER:UMIN000045229.
BACKGROUND:Prognostic models for oldest old patients with colorectal cancer (CRC) are needed to inform treatment decision-making. We aimed to develop a conditional survival (CS) nomogram tailored specifically to this patient population. METHODS:We examined 594 patients from the Keio Surveillance, Epidemiology, and End Results database who were aged over 80 years and underwent curative surgery for CRC. Overall survival (OS) was analyzed using the Kaplan-Meier method. CS was calculated using the following formula: CS (y|x) = OS (y + x)/OS (x). Least absolute shrinkage and selection operator regression and multivariate Cox regression were used to identify risk factors. A CS nomogram was constructed based on the prognostic factors identified. The performance of the nomogram was assessed using the concordance index, calibration curves, and time-dependent area under curve (AUC). Internal validation was performed using the bootstrap method. RESULTS:CS analysis showed gradual improvement in real-time survival over time after surgery. Age, pT stage, pN stage, pM stage, R status, and CEA value were predictors of CS. The CS nomogram demonstrated a concordance index of 0.718 (95% confidence interval (CI), 0.625-0.810). Calibration curves and time-dependent AUCs provided evidence of the model's stability and reliability. After internal validation via bootstrapping, the model still had a high discriminative ability (a concordance index of 0.716 [95% CI, 0.695-0.729]), and its predicted calibration curve and time-dependent AUC also demonstrated good performance. CONCLUSIONS:The nomogram developed in this study accurately predicted postoperative CS in oldest old patients with CRC.
