François Desgrandchamps

BACKGROUND: Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure. METHODS: We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed. RESULTS: The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97). CONCLUSIONS: Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

PURPOSE: To describe the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer as assessed in a Phase II/III prospective multicentric clinical trial. PATIENTS AND METHODS: Patients (N = 402) presenting with localized (stage T(1-2)N(0-x)M(0)) prostate cancer between 1995 and 1999 at six European sites who were not candidates for radical prostatectomy were treated with HIFU under general or spinal anesthesia. Their mean age was 69.3 +/- 7.1 (SD) years, the mean prostate volume 28.0 +/- 13.8 cc, and the mean serum prostate specific antigen (PSA) concentration 10.9 +/- 8.7 ng/mL. Nearly all (92.2%) of the patients had one to four positive biopsy samples at baseline. The Gleason scores were 2 to 4 for 13.2% of the patients, 5 to 7 for 77.5%, and 8 to 10 for 9.3%. During the follow-up, random sextant biopsies and serum PSA measurements were performed. Any positive sample in biopsies performed after the last treatment session resulted in a "HIFU failure" classification. RESULTS: The patients received a mean of 1.4 HIFU sessions. The mean follow-up duration was 407 days (quartile 1 135 days, median 321 days, quartile 3 598 days). The negative biopsy rate observed in the T1-2 primary-care population was 87.2%. These results were also stratified according to the usual disease-related risk classification, and as much as a 92.1% negative biopsy rate was observed in low-risk patients. Nadir PSA results correlated with prostate size and the clinical procedure. CONCLUSION: These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for the primary treatment of localized prostate cancer.

Study Type – Therapy (symptom prevalence) Level of Evidence 2a What's known on the subject? and What does the study add? Largest survey ever conducted evaluating the management of AUR in real life practice in a wide range of health care systems. It shows that urethral catheterization followed by a TWOC has become a standard worldwide and that α 1 ‐blockade prior to TWOC doubles the chances of success. It also evidences important differences (hospitalization rate, duration of catheterization ...) between countries/regions reflecting lack of guidelines. This large survey also clearly identifies predictors of TWOC failure. OBJECTIVES To evaluate the management of acute urinary retention (AUR) associated with benign prostatic hyperplasia (BPH) in real‐life practice. To identify predictors of successful trial without catheter (TWOC). MATERIALS AND METHODS In all, 6074 men catheterized for painful AUR were enrolled in a prospective, cross‐sectional survey conducted in public and private urology practices in France, Asia, Latin America, Algeria and the Middle East. Patient clinical characteristics, type of AUR and its management (type of catheterization, hospitalization, TWOC, use of α 1 ‐blockers, immediate or elective surgery) and adverse events observed during the catheterization period were recorded. Predictors of TWOC success were also analysed by multivariate regression analysis with stepwise procedure. RESULTS Of the 6074 men, 4289 (71%) had a spontaneous AUR and 1785 (29%) had a precipitated AUR, mainly as the result of loco‐regional/general anaesthesia (28.5%) and excessive alcohol intake (18.2%). Presence of BPH was revealed by AUR in 44% of men. Hospitalization for AUR varied between countries, ranging from 1.7% in Algeria to 100% in France. A urethral catheter was inserted in most cases (89.8%) usually followed by a TWOC (78.0%) after a median of 5 days. Overall TWOC success rate was 61%. Most men (86%) received an α 1 ‐blocker (mainly alfuzosin) before catheter removal with consistently higher TWOC success rates, regardless of age and type of AUR. Multivariate regression analysis confirmed that α 1 ‐blocker before TWOC doubled the chances of success (odds ratio 1.92, 95% CI 1.52–2.42, P &lt; 0.001). Age ≥70 years, prostate size ≥50 g, severe lower urinary tract symptoms, drained volume at catheterization ≥1000 mL and spontaneous AUR favoured TWOC failure. Catheterization &gt;3 days did not influence TWOC success but was associated with increased morbidity and prolonged hospitalization for adverse events. In the case of TWOC failure, 49% of men were recatheterized and had BPH surgery and 43.5% tried another TWOC with a success rate of 29.5%. Elective surgery was preferred to immediate surgery. CONCLUSIONS TWOC has become a standard practice worldwide for men with BPH and AUR. In most cases, an α 1 ‐blocker is prescribed before TWOC and significantly increases the chance of success. Prolonged catheterization is associated with an increased morbidity.