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Sickle cell anemia (SCA) is a genetic hemoglobinopathy associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes and increase intramuscular acidosis. These alterations have been already reported in the Townes mouse model of SCA but the corresponding changes in humans have not been documented. In the present study, we used 31-phosphorus magnetic resonance spectroscopy to investigate in vivo the metabolic changes induced by a moderate-intensity exercise in twelve SCA patients, eight sickle cell trait (SCT) carriers, and twelve controls women. The rest-exercise-recovery protocol disclosed slight differences regarding phosphocreatine (PCr) consumption and lactate accumulation between SCA patients and controls but these differences did not reach a statistical significance. On that basis, the in vivo metabolic changes associated with a moderate-intensity muscle exercise were slightly altered in SCA patients and SCT carriers but within a normal range. The present results strongly support the fact that a moderate-intensity exercise is safe and could be recommended in stable SCA patients and SCT subjects.

Background: Knee osteoarthritis–related pain limits physical function and leads to functional disability. Physical activity is one of the central recommendations for the management of knee osteoarthritis. Although concentric muscle activities are often preferred to eccentric ones, the corresponding rationale remains controversial. Objective: To explore the effect of a 6-week exercise program on function, pain, and performance in patients with symptomatic knee osteoarthritis. Methods: Patients with symptomatic knee osteoarthritis were included in the prospective EX-ART project (Walking performance in osteoARThritic subjects: effect of an ECCentric muscle strengthening program) and randomized in a 6-week rehabilitation program including either eccentric or concentric activities. Metrics of interest chosen as end points measured before and after the rehabilitation were WOMAC score, pain, and muscular performance (quadriceps power PMAX and contraction strength MMAX). MRI was also used to assess muscle volume and fat infiltration changes. Results: 30 patients were included in each group; mean age was 74 (±7.6); 69% were women. At week 6, both groups showed a significant improvement in the WOMAC without difference between the two groups ( p = 0.7). No difference between the two groups was identified for the pain reduction ( p = 0.7). A significant improvement in the change in PMAX and MMAX at high velocity ( p = 0.001 and p = 0.002) was observed in the eccentric group only. A vastus medialis hypertrophy was quantified in the eccentric group only ( p = 0.002), whereas fat infiltration in the quadriceps muscles was unchanged. Conclusion: Physical activity, whether eccentric or concentric, has a benefit on function and pain in patients with symptomatic knee osteoarthritis. A few differences have been identified between the two types of rehabilitation. More particularly, a gain in muscle performance and vastus medialis volume was found with eccentric rehabilitation only. Registration: www.ClinicalTrials.gov , registration number NCT03167502.

Resume Le developpement de l’immunotherapie dans les cancers de la prostate est en plein essor. Le vaccin autologue, sipuleucel-T, est le premier vaccin approuve par la Food and Drug Administration (FDA) dans le cancer de la prostate. Les premiers resultats avec les vaccins ou molecules de type GVAX, tasquinimob ou anti-PD-1 sont plutot decevants. L’ipilimumab semble interessant a un stade precoce de la maladie metastatique. Les progres viendront de la meilleure comprehension du profil patient pouvant beneficier de ces immunomodulateurs. Les essais d’associations entre traitements immunomodulateurs et hormonotherapie ou traitements cibles osseux sont en plein developpement.

The incidence of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1 g intravenous (i.v.) dose of ertapenem 1 h (n = 10, group A) or 12 h (n = 9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3 mg/L (95% CI 126.5-157.9) in group A and 30.7 mg/L (95% CI 22.9-36.4) in group B (P

ImportanceThe role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain.ObjectiveTo establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer.Design, Setting, and ParticipantsSingle-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months.InterventionsPatients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression.Main Outcomes and MeasuresThe primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis.ResultsOf 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n=13) and patient choice (n=9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS, 5.7 [95% CI, 2.6-10.8] and 3.9 [95% CI, 0.5-9.1] months, respectively). Surgical complications were observed in 14 (22%) of the nephrectomies. Biomarker analysis from sequential tissue samples revealed a decrease in CD8 expression (20.00 vs 13.75; P=.05) and significant reduction in expression of von Hippel–Lindau tumor suppressor (100 vs 40; PConclusions and RelevanceNephrectomy after upfront pazopanib therapy could be performed safely and was associated with good outcomes in patients with intermediate-risk metastatic clear cell renal cancer.

Objectifs L’incidence des infections urinaires a germes producteurs de betalactamase a spectre etendu (BLSE) est en augmentation. Elles sont associees a une hospitalisation prolongee pour les patients (Pts) necessitant des interventions chirurgicales urologiques. L’objectif de cette etude etait de demontrer qu’une diffusion intra-prostatique significative d’ertapeneme etait obtenue apres une seule administration intraveineuse (IV) avant chirurgie prostatique. Methodes Vingt Pts avec indication de chirurgie pour hyperplasie benigne de prostate etaient inclus prospectivement et divises en 2 groupes ; 19 Pts etaient analyses. Les Pts recevaient une dose d’1 gramme IV d’ertapeneme 1 heure ( n = 10, groupe A) ou 12 heures ( n = 9, groupe B) avant prelevements sanguins et prostatiques (copeaux de resection) ( Fig. 1 ). Les concentrations plasmatiques et intra-prostatiques d’ertapeneme etaient mesurees par chromatographie en phase liquide couplee a la spectrometrie de masse tandem (LC-MS/MS). Les concentrations intra-prostatiques etaient considerees comme satisfaisantes si elles etaient superieures aux concentrations minimales inhibitrices90 (CMI90) des pathogenes cibles urinaires. Un test de Wilcoxon et un modele predictif pharmacocinetique etaient utilises. Resultats Les concentrations plasmatiques medianes d’ertapeneme etaient de 144,3 mg/L (IC95 % ; 126,5–157,9) dans le groupe A et de 30,7 mg/L (IC95 % ; 22,9–36,4) dans le groupe B ( p p P. vulgaris ) et 1 mg/L (contre Enterobacter spp) ( Fig. 2 ). Le rapport concentration plasmatique sur concentration intra-prostatique n’etait pas significativement different entre les groupes ( p = 0,97), en faveur d’une diffusion intra-prostatique similaire independamment de l’intervalle de temps entre administration et chirurgie. Les analyses pharmacocinetiques retrouvaient une demi-vie de 4,8 h pour l’ertapeneme comparable a la litterature. Conclusion Une seule dose d’ertapeneme administree en preoperatoire 1 heure avant l’intervention en IV permet d’obtenir des concentrations plasmatiques et intra-prostatiques satisfaisantes. Ces resultats suggerent qu’il pourrait s’agit d’une strategie prophylactique interessante pour les Pts porteurs de BLSE necessitant des interventions sur les voies urinaires. Ces resultats necessitent d’etre confirmes dans de futurs essais prospectifs.