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Subcutaneous bortezomib did not significantly reduce therapeutic efficacy but resulted in a lower incidence of peripheral neuropathy than intravenous bortezomib. Compared with intravenous bortezomib, subcutaneous bortezomib might reduce the incidence of thrombocytopenia and renal and urinary disorders, but this needs more clinical trials to confirm.
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STUDY OBJECTIVE To compare the efficacy and safety of once-weekly and twice-weekly bortezomib therapy in patients with hematologic malignancies. DESIGN Meta-analysis of 13 clinical or randomized controlled trials, with trial sequential analysis (TSA). PATIENTS A total of 1567 patients with hematologic malignancies who received either once-weekly or twice-weekly bortezomib therapy. MEASUREMENTS AND MAIN RESULTS We conducted a comprehensive literature search of the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis was conducted to calculate the pooled effect size; TSA was performed to assess the reliability of the pooled results. The pooled risk ratio (RR) for the overall response rate (ORR) was 1.00 (95% confidence interval [CI] 0.77-1.29, p=0.99), indicating no significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. TSA showed that the cumulative Z-curve of the ORR entered the futility area, implying that reliable evidence was obtained for this pooled result. The pooled RR for any grade of peripheral neuropathy was 0.48 (95% CI 0.26-0.88, p=0.02); however, the TSA plot revealed that there was insufficient evidence for this result. The pooled RR for peripheral neuropathy grade 3 or higher was 0.21 (95% CI 0.13-0.34, p<0.00001), and reliable evidence was obtained according to TSA. Regarding the other toxicities, including anemia, thrombocytopenia, neutropenia, infection, diarrhea, constipation, nausea, vomiting, and fatigue, we did not find any significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. CONCLUSION Compared with twice-weekly bortezomib, once-weekly bortezomib had a comparable ORR and a probable lower incidence of peripheral neuropathy. More clinical trials are needed to draw a conclusion regarding the difference in peripheral neuropathy between the two groups because of the insufficient evidence detected by TSA and the inconsistent results among subgroups.

Purpose Studies regarding death risk factors of disseminated intravascular coagulation (DIC) patients were limited. Therefore, we conducted this study to investigate whether the serum anion gap (AG) was independently related to all-cause mortality of DIC patients. Methods We used the data from Medical Information Mart for Intensive Care III version 1.4 (MIMIC-III v1.4). A total of 2,654 DIC patients were included. The main outcomes were in-hospital, 30-day, and 90-day all-cause mortality. The AG was measured upon ICU admission and its association with mortality was evaluated using the Cox proportional-hazards regression model. The generalized additive model and the smooth curve fitting were introduced to examine the non-linear association. Results After adjusting for potential covariates, the in-hospital, 30-day, and 90-day all-cause mortality were positively correlated with AG. The hazard ratio (HR), confidence intervals (CI), and P were 1.05 (1.04–1.07) <0.0001, 1.06 (1.04–1.07) <0.0001, and 1.05 (1.03–1.07) <0.0001, respectively. We did not find an obvious non-linear relationship between AG and in-hospital, 30-day, and 90-day mortality, which indicated that the association between AG and all-cause mortality of DIC patients was nearly linear. Conclusion Serum AG is positively related with all-cause mortality in DIC patients.