Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Topical Vancomycin Powder and Dilute Povidone-Iodine Lavage Reduce the Rate of Early Periprosthetic Joint Infection After Primary Total Knee Arthroplasty

BackgroundVancomycin powder and dilute povidone-iodine lavage (VIP) was introduced to reduce the incidence of periprosthetic joint infection (PJI) in high-risk total knee arthroplasty (TKA) patients. We hypothesize that VIP can reduce the incidence of early PJI in all primary TKA patients, regardless of preoperative risk.MethodsAn infection database of primary TKAs performed before a VIP protocol was implemented (January 2012-December 2013), during a time when only high-risk TKAs received VIP (January 2014-December 2015), and when all TKAs received VIP (January 2016-September 2019) at an urban, university-affiliated, not-for-profit orthopedic hospital was retrospectively reviewed to identify patients with PJI. Criteria used for diagnosis of PJI were the National Healthcare Safety Network and Musculoskeletal Infection Society guidelines.ResultsVIP reduced early primary TKA PJI incidence in both the high-risk and all-risk cohorts compared with the pre-VIP cohort by 44.6% and 56.4%, respectively (1.01% vs 0.56% vs 0.44%, P = .0088). In addition, after introducing VIP to all-risk TKA patients, compared with high-risk TKA patients, the relative risk of PJI dropped an additional 21.4%, but this finding did not reach statistical significance (0.56% vs 0.44%, P = .4212). There were no demographic differences between the 3 VIP PJI cohorts.ConclusionVIP is associated with a reduced early PJI incidence after primary TKA, regardless of preoperative risk. With the literature supporting its safety and cost-effectiveness, VIP is a value-based intervention, but given the nature of this historical cohort study, a multicenter randomized controlled trial is underway to definitively confirm its efficacy.     

Protection From the Second Warm Ischemic Injury in Kidney Transplantation Using an Ex Vivo Porcine Model and Thermally Insulating Jackets

BackgroundKidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury.MethodsA novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation.ResultsIn both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P < .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants.ConclusionProtection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.     

Assessment of the Long-Term Impact of Pancreatoduodenectomy on Health-Related Quality of Life Using the EORTC QLQ-PAN26 Module

Annals of Surgical Oncology - Long-term pancreatoduodenectomy (PD) survivors have previously reported favorable quality of life (QoL). However, there has been a paucity of studies utilizing...