A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial.

We aimed to compare the efficacy and safety of maintaining or withdrawing abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer who had experienced cancer progression to this treatment and were beginning a docetaxel-based therapy. Phase II, randomised, open-label study conducted in patients with metastatic castration-resistant prostate cancer who were asymptomatic or mildly symptomatic. After open-label treatment with AAP, patients who had experienced cancer progression to AAP were randomised to 75 mg/m2 of docetaxel plus AAP or to receive 75 mg/m2 of docetaxel plus 10 mg of prednisone orally daily. The primary outcome was the radiographic progression-free survival rate at 12 months as evaluated by the investigators in all randomised patients. A total of 148 patients were included in open-label treatment with AAP, and of them, 94 patients were randomised to receive either docetaxel plus AAP (intervention group; n = 47) or docetaxel plus prednisone (control group; n = 47). The 12-month radiographic progression-free survival rates did not differ between the intervention group (34.9%; 95% CI 20.7-49.2) and the control group (33.9%; 95% CI 19.5-48.3). There were no significant differences in the time to radiographic progression and the overall survival between the intervention and control groups. Grade 3-5 neutropenia with the combination of docetaxel plus prednisone and AA was more frequent than with docetaxel plus prednisone (59.6% versus 27.7%). Our results indicate that the therapeutic strategy of maintaining AAP added to docetaxel in chemotherapy-naïve patients who have experienced cancer progression to AAP treatment should not be further evaluated and should be avoided in clinical practice. NCT02036060 https://clinicaltrials.gov/ct2/show/NCT02036060

Niraparib for Advanced Breast Cancer with Germline and Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPurpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer. Patients and methods: BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician's choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor-positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety. Results: After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n = 141) versus 3.1 months in the PC arm [n = 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65-1.44; P = 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63-1.42) and 0.65 (95% CI, 0.46-0.93), respectively. ORR was 35% (95% CI, 26-45) with niraparib and 31% (95% CI, 19-46) in the PC arm. Conclusions: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.TESARO United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

PURPOSE:: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS:: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS:: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION:: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders. © 2011 Lippincott Williams & Wilkins

Infective Endocarditis in Patients on Chronic Hemodialysis

International audienceInfective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD)

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients

Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement

Abstract Background Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. Methods Data were collected from the “Infectious Endocarditis after TAVR International” (enrollment from 2005 to 2020) and the “International Collaboration on Endocarditis” (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. Results A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P &lt; .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P &lt; .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P &lt; .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P &lt; .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). Conclusions Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective