Cardiovascular risk independently predicts small functional bladder storage capacity

International Urology and Nephrology - We aimed to determine the potential relationship between atherosclerotic cardiovascular disease (ASCVD) score, which equates to 10-year risk of...     

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.     

Can Machine Learning Methods Produce Accurate and Easy-to-Use Preoperative Prediction Models of One-Year Improvements in Pain and Functioning After Knee Arthroplasty?

BackgroundApproximately 15%-20% of total knee arthroplasty (TKA) patients do not experience clinically meaningful improvements. We sought to compare the accuracy and parsimony of several machine learning strategies for developing predictive models of failing to experience minimal clinically important differences in patient-reported outcome measures (PROMs) 1 year after TKA.MethodsPatients (N = 587) in 3 large Veteran Health Administration facilities completed PROMs before and 1 year after TKA (92% follow-up). Preoperative PROMs and electronic health record data were used to develop and validate models to predict failing to experience at least a minimal clinically important difference in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total, KOOS JR, and KOOS subscales (Pain, Symptoms, Activities of Daily Living, Quality of Life, and recreation). Several machine learning strategies were used for model development. Ten-fold cross-validation and bootstrapping were used to produce measures of overall accuracy (C-statistic, Brier Score). The sensitivity and specificity of various predicted probability cut-points were examined.ResultsThe most accurate models produced were for the Activities of Daily Living, Pain, Symptoms, and Quality of Life subscales of the KOOS (C-statistics 0.76, 0.72, 0.72, and 0.71, respectively). Strategies varied substantially in terms of the numbers of inputs required to achieve similar accuracy, with none being superior for all outcomes.ConclusionModels produced in this project provide estimates of patient-specific improvements in major outcomes 1 year after TKA. Integrating these models into clinical decision support, informed consent and shared decision making could improve patient selection, education, and satisfaction.Level of EvidenceLevel III, diagnostic study.     

Capsular Management in Direct Anterior Total Hip Arthroplasty: A Randomized,Single-Blind,Controlled Trial

BackgroundThe direct anterior approach (DAA) is a popular approach to total hip arthroplasty (THA). Unlike the posterior approach, the importance of anterior capsular management is unknown. This randomized controlled trial compares capsular repair versus capsulectomy.MethodsThis single-surgeon, single-blinded, parallel-group randomized controlled trial occurred between 2013 and 2016. Patients undergoing unilateral, primary THA for osteoarthritis consented to undergo blinded, simple randomization to anterior capsulotomy with repair or anterior capsulectomy. Primary outcome measures included hip range of motion, hip flexion strength, and pain with seated hip flexion. Secondary outcome measures included surgical time, estimated blood loss, postoperative complications, and hip disability and osteoarthritis outcome score. Data were prospectively collected intraoperatively, six weeks, six months, an average of over 5 years postoperatively.ResultsNinety-eight patients were ultimately enrolled in the trial; 50 received capsulectomy and 48 received capsulotomy. No significant differences were seen in preoperative demographics or in primary or secondary outcomes during this study. No difference was seen in pain at final follow-up at average > 5 years postoperatively.ConclusionThis study demonstrates that capsular management in DAA THA does not affect postoperative pain or range of motion. The anterior capsule’s role in prosthetic stability after DAA THA remains uncertain, but it does not currently appear that repair provides benefit and may lead to increased surgical time and blood loss. As such, capsular management in DAA THA is at surgeon discretion.     

Periprosthetic Tissue Reaction Independent of LTT Result and Implanted Materials in Total Knee Arthroplasty

BackgroundAn allergic reaction may rarely cause a painful or stiff total knee arthroplasty (TKA). However, no consensus diagnostic criteria for TKA immune failure exist. Lymphocyte transformation testing (LTT) measures immune sensitivity to various materials, but its role in diagnosing an allergic reaction to a TKA has not been established. This study compares TKA periprosthetic tissues in a) LTT-positive versus -negative patients and b) patients with conventional CoCrNi versus hypoallergenic implants.MethodsPeriprosthetic tissues from 26 revision cases of well-fixed, aseptic, but painful or stiff TKAs were analyzed. Twelve patients LTT positive for nickel (Ni) were matched as a cohort to 6 LTT-negative patients. In 4 patients LTT positive for Ni, tissue from first revision of CoCrNi implants was compared with tissue from subsequent revision of hypoallergenic implants. Histology was evaluated using the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) score.ResultsNo correlation was found between LTT and any ALVAL score component. The mean total ALVAL score was 3.8 ± 1.5 for LTT-negative patients and 3.3 ± 1.2 for LTT-positive patients (P = .44). The mean total ALVAL score at revision of CoCrNi implants was 3.0 ± 1.8 compared with 5.8 ± 0.5 at rerevision of hypoallergenic implants (P = .053).ConclusionPeriprosthetic TKA tissue reactions were indistinguishable between LTT-positive and -negative patients. LTT does not predict the periprosthetic tissue response. ALVAL scores of hypoallergenic revision implant tissue trended higher than primary CoCrNi implant tissue. A positive LTT may not indicate that a periprosthetic immune reaction is the cause of pain and stiffness after TKA.Level of Evidence3, retrospective cohort study.     

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.