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To assess the accuracy of targeted and systematic biopsies for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in the everyday practice, evaluating the need for additional systematic biopsies at the time of targeted biopsy.From our multicentric database gathering data on 2,115 patients who underwent fusion biopsy with Koelis™ system between 2010 and 2017, we selected 1,119 patients who received targeted biopsies (a median of 3 for each target), followed by systematic sampling of the prostate (12 to 14 cores). Overall and clinically significant cancer detection rate (CDR) of Koelis™ fusion biopsies were assessed, comparing target and systematic biopsies. Secondary endpoint was the identification of predictors of PCa detection.The CDR of targeted biopsies only was 48% for all cancers and 33% for csPCa. The performance of additional, systematic prostate sampling improved the CDR of 15% for all cancers and of 12% for csPCa. PCa was detected in 35%, 69%, and 92% of patients with lesions scored as PI-RADS 3, 4 and 5, respectively. Elevated PI-RADS score and positive digital rectal examination were predictors of PCa, whereas biopsy-naïve status was associated with csPCa.In the everyday practice target biopsy with Koelis™ achieves a good CDR for all PCa and csPCa, which is significantly improved by subsequent systematic sampling of the prostate. The outstanding outcomes of fusion biopsy are confirmed also in biopsy-naïve patients. Elevated PI-RADS score and positive digital rectal examination are strongly associated with presence of PCa.

International audience; PURPOSE:Social Media (SoMe) have changed the face of modern medicine. Our purpose was to make an inventory on the use of SoMe within urologists members of the French Urological Association (AFU).MATERIAL AND METHODS:A 15 questions-survey was sent by email 2 months to urologists AFU members before the 108th French Congress of Urology (#CFU2014). At the same time, the activity of urologists using Twitter was analyzed over the period of the national conference with the symplur software (www.symplur.com).RESULTS:Overall, 270 (17.3%) surveys were completed. Only 50% of responders had an online SoMe account. The most commonly used social media platforms were: Facebook (36.1%) followed by LinkedIn (28.2%), Google+ (19.6%), YouTube (18.7%) and Twitter (17.4%). The use of SoMe was higher in the age groups 30-40 and 40-50 years than in older age groups (83% versus 36%). Only 38.7% of respondents reported using SoMe in a professional field. At the congress #CFU2014, there were over 1000 tweets generated by 173 different contributors.CONCLUSION:Only a minority of French urologists have reported to be connected to SoMe and a predominantly personal use. The emergence of Twitter in French urological conferences is very new but seems promising. Further studies are needed, especially within the members of the residents French urological association to better characterize the true impact of SoMe in urology.LEVEL OF EVIDENCE:4.

International audience; OBJECTIVE:To establish 18 fluorocholine-positron emission tomography/computed tomography (F-PET/CT) performances for the detection of local recurrence in a population of patients with biochemical failure after primary curative treatment for localized prostate carcinoma.MATERIAL AND METHOD:From February 2011 to February 2014, 55 patients underwent a F-PET/CT for biochemical relapse after primary radical therapy for prostate cancer localized or locally advanced. Primary therapies for prostate cancer were 19 radical prostatectomy, 18 radiotherapy, 13 radiotherapy with hormonal treatment, 3 brachytherapy. The median age was 65 years (50-79). The initial staging was 17 T1, 23 T2 and 15 T3, 52 were N0 and N1 3. The median PSA was 12 (3-127). The Gleason score was less than 7, equal to 7 and greater than 7 at 21, 25 and 9 patients respectively. The average time to recurrence was 69.5 months (8-147) with a median PSA of 2.9 ng/mL (0.48-41).RESULTS:In 42 cases, F-PET/CT showed uptake, suggesting a recurrence, metastatic (6), nodal (26) or local isolated (10). The focal uptake in PET commissioned in 5 cases prostate biopsy, confirming the histological recurrence of prostate cancer in 4 cases. Among the 10 patients with isolated local recurrence, 8 underwent salvage radiotherapy. Of the 13 cases where the (F-PET/CT) showed no recurrence, 7 multiparametric MRI were performed. The MRI showed a local recurrence in 3 patients, the diagnoses were confirmed with prostate biopsy for two of them.CONCLUSION:In our study, for the patients with biochemical relapse of prostate adenocarcinoma localized or locally advanced, (F-PET/CT) was able to detect local recurrence isolated in nearly half the cases but did not show sufficient sensitivity to exclude recurrence local if negative. It does not replace MRI or additional prostate biopsy.

International audience

This is the report of a workshop organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods that are of importance to the biosciences and which replace, reduce or refine the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organization of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (Anonymous, 1994). The workshop on "The use of in vitro systems for evaluating Immunotoxicity" was held at ECVAM (Ispra), Italy, on 24th-26th November 2003. The participants represented academia, national organizations, international regulatory bodies and industry. The aim of the workshop was to review the state-of-the-art in the field of in vitro immunotoxicology, and to develop strategies towards the replacement of in vivo testing. At the end of this report are listed the recommendations that should be considered for prevalidation and validation of relevant and reliable procedures, that could replace the use of animals in chemical and cosmetics toxicity testing.

To determine the optimal evaluation and management of renal injuries by review of the world's English-language literature on the subject.

Eczema is a skin inflammatory reaction mediated by antigen-specific T cells. Two main disorders belong to this group: contact dermatitis and atopic dermatitis. The pathophysiological mecanisms involved in both disorders are similar and include, at the cellular level, three elements: the antigen (hapten or environmental antigen), antigen-presenting cells belonging to the group of dendritic cells and antigen-specific T cells. The Langerhans cell responsible for antigen handling and presentation to specific T cells appears to play a central role for the generation of the inflammatory reaction.

Miconazole was found to exert a biphasic influence on both cellular immune response and hepatic drug metabolism in adult Swiss mice. Indeed, at the dose of 2.5 or 12.5 ma/kg/twice daily via intraperitoneal route, miconazole depressed delayed-type hypersensitivity (DTH) to sheep red blood cells and hepatic drug metabolism as determined from barbiturate sleeping time, following one-day treatment. By contrast, at the same dose level, miconazole enhanced DTH and hepatic drug metabolism after a five-day administration schedule. Primary humoral response and colloidal carbon clearance were not affected. Although the underlying mechanism remains to be fully elucidated, these findings clearly suggest a close relation between modulation of the cellular immune response and activity of liver drug metabolizing enzymes.

Experimental autogenous grafts were made on adult Wistar rats using microvascular techniques. 3 months postoperatively, the grafts were controlled by angiography and by histopathological examination. We obtained a total patency rate of 52.7% and we observed that failure of the grafting can be explained by progressive hypertrophy of the walls of the vessels inducing thrombosis.

In search for an effective treatment of human poisonings with ajmaline, a potent antiarrhythmic drug, the use of specific antibodies as neutralizing agents was explored in a preliminary animal model. For this purpose, New Zealand white rabbits were immunized with the antigen obtained after coupling the 17-hemisuccinate ester of ajmaline-21-acetate to bovine serum albumin, whereas other rabbits were immunized with the protein carrier only. While seven control rabbits receiving 0.625 mg/kg/min. ajmaline intravenously until death, died within 54.8 +/- 5.2 min. death was delayed until 137.7 +/- 15.5 min in seven ajmaline bovine serum albumin-immunized rabbits (p less than 0.001). Three bovine serum albumin-immunized rabbits behaved as controls. These results provide evidence that an immunological protection against ajmaline toxicity can be obtained in laboratory animals.

Summary Two cases of hypersensitivity reactions in the course of slow infusion of Althesin are reported. Serial examination of their complement system showed a marked activation of the alternate pathway which returned almost to normal within 24 hours.

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Propranolol pretreatment (0.1 mg X kg-1) significantly increased the lengthening induced by diltiazem (0.15 mg X kg-1 + 0.01 mg X kg-1 X min-1, 20 min) of the A-H interval of His bundle potential recordings in the dog. In the presence of propranolol, diltiazem also significantly increased the atrioventricular effective refractory period. The results suggest the possible occurrence of AV blocks as a result of the use of a diltiazem-beta blocker combination in clinical practice.

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Death most often results from human acute poisonings due to paraquat, a widely used herbicide. It causes a quick and insidious accumulation in lungs. It was proposed to study the effects of the administration of antiparaquat F(ab')2 fragments in mice intoxicated with paraquat. Antisera against a paraquat acid derivative coupled to bovine serum albumin were prepared in rabbits, then purified using immunoaffinity chromatography columns and fragmented by pepsin. Antiparaquat F(ab')2 antibodies obtained were preventively injected to mice. After intravenous paraquat injection of 8 mg/kg, plasma paraquat levels were measured from 0.25 to 48 hours. Plasma from antiparaquat F(ab')2 pretreated mice as compared with non-specific immunoglobulin pretreated control mice showed a significant increase (p less than 0.001) of the paraquat concentrations from the 4th (1.17 +/- 0.06 versus 0.20 +/- 0.01 microgram/ml) to the 48th hour (0.47 +/- 0.08 versus 0.02 +/- 0.01 microgram/ml). Although pulmonary paraquat concentrations presented no modification, it could be considered that these preliminary results would have to be studied thoroughly with a view to finding an efficient treatment in human acute poisoning with paraquat.

The assessment of risks following drug exposure during pregnancy is of major concern to Drug-Information Centers. A computer-based management is helpful. The authors describe a computerized system to follow pregnancy outcomes and discuss their first results, stressing the merits of automatized recalls.

A wide variety of agents have been associated with erythema multiforme, particularly drugs and infectious agents. We describe a typical Stevens-Johnson's syndrome developing 15 days after initiation of propranolol and maprotiline therapy. Other etiologies have been excluded by appropriate investigations and the responsibility of each drug is discussed.

5-fluorouracil (5-FU), a fluoropyrimidine antimetabolite, is widely used in the treatment of cancers of the digestive tract and breast. The clinical cardiotoxicity of 5-FU was first reported in 1975. Adverse cardiac effects include coronary disorders, heart failure and sudden death of suspected cardiac origin. Six new cases are reported, including 5 cases of angina and one of heart failure. The patients, 4 males and 2 females, were 26 to 71 years of age (mean: 56.2). They had no medical history of heart failure, myocardial ischemia or electrocardiographic anomalies prior to 5-FU treatment. Three patients had hypertension of whom one had had type-II diabetes mellitus for the past 20 years. Clinical symptoms included chest pain in 4 patients and heart failure in one, whereas the last patient had ECG changes with no associated clinical symptoms. Clinical symptoms of angina totally disappeared after the cessation of 5-FU administration, but heart failure was alleviated only after the introduction of digitalis, a converting-enzyme inhibitor and a diuretic. It has been estimated that 1.6% of patients treated with 5-FU develop adverse cardiac effects. Patients at greater risk are those with a history of ischemic cardiac disease, thoracic radiotherapy or high-dose 5-FU therapy. The mechanism involved is not clearly elucidated. Spasms of the coronary arteries or toxic inflammation of the myocardium have been suspected. These 6 new cases confirm the potential for cardiotoxicity of 5-FU and the need for careful cardiac monitoring of treated patients.

A careful diagnosis and the identification of the causative drug after a cutaneous adverse reaction can avoid relapses. Skin tests facilitate the identification of the causative molecule by producing a hypersensitivity reaction at the application site. Adverse drug reactions are reported to Pharmacovigilance Centres who determine the imputation score of the suspected drugs. The aim of this study was to assess to what extent skin testing after a suspected allergic drug reaction can be helpful to identify the causative drug and whether an impact on the final imputation score could be evidenced.A 18-month prospective study was performed. All patients with a history of cutaneous adverse drug reaction of suspected immunoallergic origin were included provided skin tests could be performed within 6 to 12 weeks after the adverse drug reaction. The imputation score was determined using the French imputation method prior to and after skin testing.Thirthy-nine patients were included in the study. Positive skin tests were observed in 11 of 20 patients with a C2S2 (I2: plausible) initial imputation score and in 6 of 15 patients with a C2S1 (I1: doubtful) initial imputation score. One patient with a C1S1 (I1: doubtful) initial imputation score had positive skin tests.The results of skin tests helped change the imputation score of the suspected drug in 18 patients out of 39. In 55 p. 100 of cases, the imputation score was increased from C2S2 (I2) to C2S3 (I3: likely) and from C2S1 (I1) to C2S3 (I3) in 40 p. 100 of cases. The increase in imputation scores was helpful to improve warning signals after an immunoallergic reaction. Skin tests led to a more accurate diagnosis in 50 p. 100 of cases. Thus, more adequate advices for further drug treatment were possible, particularly in avoiding the irrelevant prohibition of innocent drugs.

The incidence of neuropsychiatric complications is very low in patients receiving conventional doses of cimetidine or ranitidine. In this case report, the same patient presented with psychiatric symptoms successively following treatment with both histamine H2-receptor antagonists, suggesting the involvement of histamine-mediated CNS modulation.