Citations

Abstract Background Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. Methods Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. Results Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. Conclusions BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Objective: Using a triage algorithm for primary cytoreductive surgery (PCS) reduces perioperative mortality, however, nonlethal complications are common. This study identified procedures associated with postoperative complications in triage-appropriate women, with the aim of guiding the next steps to foster surgical quality improvement. Materials and Methods: Consecutive triage-appropriate women with stage IIIC/IV ovarian cancer undergoing PCS, from January 2012 to April 2018, were included. The expanded Accordion scale was used to grade complications. Adjusted risk ratios ( RRs ) were calculated to quantify the association between concomitant procedures and risk of 30-day grade 3+ (G3+) complications by fitting Poisson regression models adjusted for performance status and age. Population-attributable risk (PAR) was calculated based on the adjusted RR s and prevalence of each procedure. Results: Of 214 women, 82.7% had intermediate- or high-complexity surgery, 68.7% had complete gross resection, 3.7% had residual disease >1 cm, and 18.7% experienced G3+ complications. In univariate analysis, operative time, surgical complexity, splenectomy, and bowel resection (any and extent of) were associated with G3+ complications. Operative time, bowel resection (any, extent of, and large) were associated with G4+ complications. In the adjusted analysis for G4+ complications, bowel resection (any, extent of, and large) had statistically significant PAR values of 60.7%, 54.7%, and 50.8%, respectively. PAR values associated with G3+ complications were 27.4% and 26.8% for any and multiple bowel resections, respectively. Conclusions: Bowel resection, upper abdominal procedures, and longer operative times are essential for PCS, but each contributes to the relatively constant rates of postoperative morbidity despite triage to prevent frail patients from undergoing PCS. Surgical-improvement research should focus on improving the safety of these procedures. (J GYNECOL SURG 39:123)

AbstractClinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p < .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.