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Background@#Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab. @*Methods@#A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin’s lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups. @*Results@#In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41–12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4–16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99–26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4–33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999). @*Conclusion@#Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.Trial Registration: ClinicalTrials.gov Identifier: NCT02585947
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Background/Aims@#Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients. @*Methods@#Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias. @*Results@#Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04). @*Conclusions@#After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.
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BACKGROUND: Heart rate (HR) is an essential vital sign based on the finding that HR beyond its normal range is associated with several conditions or diseases, including high mortality in several clinical settings. Nevertheless, the clinical implications of HR remain unresolved in patients undergoing continuous renal replacement therapy (CRRT). METHODS: This retrospective cohort study included 828 patients who underwent CRRT due to acute kidney injury between 2010 and 2014. HR and other baseline parameters at the time of CRRT initiation were retrieved. The odds ratio (OR) of 30-day mortality was calculated using a multivariate logistic model. RESULTS: CRRT significantly lowered the HR of patients such that the pre- and post-CRRT HRs (average 6 hours) were 107 beats/min and 103 beats/min, respectively (P < 0.001). When we explored the relationship with 30-day mortality, only HR at the time of CRRT initiation, but not pre- or post-CRRT HR, had a significant relationship with mortality outcome. Based on this result, we divided patients into quartiles of HR at the time of CRRT initiation. Mortality OR in the 4th quartile HR group was 2.6 (1.78–3.92) compared with the 1st quartile HR group. This relationship remained consistent despite adjusting for 28 baseline covariates: OR, 1.7 (1.09–2.76); P = 0.020. However, HR was not associated with the weaning rate from CRRT. CONCLUSION: High HR at the time of CRRT initiation is subsequently related with high mortality. These results can be a basis for a future predictive model of CRRT-related mortality.