[Certification of health establishments: the changing perspective on transfusion risk]. / Certification des établissements de santé pour la qualité des soins : le regard évolue sur le risque transfusionnel en ES.

The HAS certification for healthcare organisation has gradually introduced the concepts of risk and relevance of care. Related to quality and safety of care, the transfusion act has early been part of the referential, and it seemed interesting to us to observe the changes in the requirements on this topic. After taking into account the regulations and the organization of haemovigilance in the establishment, it is now the search for the factual result for the patient which is the objective of the two main criteria devoted to transfusion. At the same time as the referential, the investigation methods have also evolved: the targeted tracer for Labile Blood Products and Blood-Derived Medicines allows a more detailed analysis geared towards the effective implementation of good transfusion practices. In conclusion, certification has moved from organizing and auditing the process to directly measuring transfusion safety for the patient.

Concerning one case of rupture of a flow regulator: How patient safety procedures contribute to the correct use of medical devices.

Flow regulators are widely used in hospitals to assist with intravenous (IV) infusion of medication. The rupture of a flow regulator at the base of the clamp was observed during parenteral nutrition. This rupture resulted in fluid leakage and an inlet of air, responsible for an air embolism in a fragile patient who had undergone a bilateral lung transplant. The patient's clinical condition required him to be transferred to a continuous monitoring unit. A serious Adverse Event in Healthcare (AEH) was reported, as well as a medical device vigilance report. A Feedback Committee (FC) was set up and it recommended an audit within the health care departments to study the conditions for use of flow regulators and to propose corrective actions. Despite the technical data sheet of the device not recommending the administration of lipid emulsions and glucose solutions above 10%, the manufacturer's expert report concluded that the mechanical failure could not be linked to the type of solution. However, the audit did reveal a lack of knowledge of certain rules for using this device. The analysis of this AEH is part of the establishment's patient safety procedure. The AEH highlighted a deviation in care concerning the conditions for use of flow regulators, thus resulting in misuse. The collaboration between the various actors involved in the analysis of this AEH led to the implementation of improvement actions on the root causes, related to the lack of information and of training for professionals on correct use of the medical device.

Hamstring grafts are tenogenic constructs for ACL reconstruction and Pulsed Electromagnetic Fields improve tendon specific markers expression. An in-vitro study.

Hamstring tendons represent one of the commonest autologous graft used during ACL reconstruction. The harvest of the tendon and the time of tendon processing on the operating table, together with the pretensioning maneuvers and the permanence out of the joint during the time of surgery, might impair tendon derived cells (TCs) viability. The aim of the study was: i) to assess the effective viability of the TCs at the end of the surgical procedure; ii) to investigate if TCs viability and the expression of tendon specific markers may be improved through exposure to prolonged pulsed electromagnetic fields (PEMF) similar to that of clinical practice. Remnants of semitendinosus and gracilis tendons (discarded at the end of the ACL reconstruction) were collected from 13 healthy donors. To isolate TCs, the tendon tissue was minced and digested enzymatically with 0.3% type I collagenase in DMEM with continuous agitation for 15 h at 37°C. The isolated nucleated cells were then plated at 5x103 cells/cm2 in a complete medium composed of DMEM, 10% fetal bovine serum, 50 U/ml Penicillin, 50 mg/ml Streptomycin, 2 mM L-glutamine, and supplemented with 5 ng/ml basic fibroblast growth factor (b-FGF). They were maintained at 37 °C in a humidified atmosphere with 5% CO2, changing culture medium every 3 days. When they reached 80-90% of confluence, the cells were detached by incubation with trypsin/EDTA and then cultured at a density of 5x103 cells/cm2. TCs were cultured in complete medium for 7, 14, 21 days (in chamber slides, to optimize the final immunofluorescence analysis). The following cell cultures were set up: i) TCs cultured with differentiation medium + exposure to PEMF 8 h/day; ii) TCs cultured with differentiation medium without exposure to PEMF. The stimulation with PEMF was generated by a pair of electrical coils, connected with the generator of pulsed electromagnetic fields (PEMF generator system IGEA, Carpi, Italy, intensity of magnetic field = 1.5 mT, frequency = 75 Hz). At day 0, day 7, day 14 and day 21 immunofluorescence analysis was performed to evaluate the expression of tendon specific markers (collagen type I, collagen type VI, scleraxis) and proliferative markers (PCNA, beta-catenin). The TCs from the hamstring tendon fragments at the end of the ACL reconstruction were alive and they expressed markers of proliferation and tendon phenotype at the end of the culture period. The TCs in the presence of PEMF 8h/day showed a greater production of collagen type I, collagen type VI and scleraxis than TCs cultured without PEMF (p<0.05). The expression of these markers increased from 7 to 21 days of culture. The expression of proliferative markers in the presence of PEMF stimulus was significantly lower (p<0.05) than that of TCs cultured without PEMF. Hamstring tendons are not simple "tenoconductive" scaffolds but biologic alive tenogenic constructs rich in cells that can sustain tenogenic behavior and tendon matrix synthesis. Prolonged exposure to PEMF improves their phenotype. Thus, from a clinical perspective, the use of PEMF may represent a possible future strategy to positively influence the early phase of graft remodeling and, ultimately, improve the ligamentization process. Following these concepts, further studies might also exploit the anabolic role of PEMF as an adjunctive postoperative strategy in different tendon pathologies.

Intervertebral disc and endplate cell characterisation highlights annulus fibrosus cells as the most promising for tissue-specific disc degeneration therapy.

Degenerative processes of the intervertebral disc (IVD) and cartilaginous endplate lead to chronic spine pathologies. Several studies speculated on the intrinsic regenerative capacity of degenerated IVD related to the presence of local mesenchymal progenitors. However, a complete characterisation of the resident IVD cell populations, particularly that isolated from the endplate, is lacking. The purpose of the present study was to characterise the gene expression profiles of human nucleus pulposus (NPCs), annulus fibrosus (AFCs) and endplate (EPCs) cells, setting the basis for future studies aimed at identifying the most promising cells for regenerative purposes. Cells isolated from NP, AF and EP were analysed after in vitro expansion for their stemness ability, immunophenotype and gene profiles by large-scale microarray analysis. The three cell populations shared a similar clonogenic, adipogenic and osteogenic potential, as well as an immunophenotype with a pattern resembling that of mesenchymal stem cells. NPCs maintained the greatest chondrogenic potential and shared with EPCs the loss of proliferation capability during expansion. The largest number of selectively highly expressed stemness, chondrogenic/tissue-specific and surface genes was found in AFCs, thus representing the most promising source of tissue-specific expanded cells for the treatment of IVD degeneration.

[Laparoscopic sacrocolpopexy for pelvic organ prolapse: guidelines for clinical practice]. / Traitement du prolapsus génital par promontofixation laparoscopique : recommandations pour la pratique clinique.

INTRODUCTION: Open sacrocolpopexy have demonstrated its efficiency in surgical treatment of pelvic organ prolapse with an important backward on a large number of patients. Laparoscopic sacrocolpopexy reproduced the same surgical technique with reduced morbidity and may benefits from the recent development of robotic. Numerous technical variants have been developped around the original procedure but results seems not ever equivalent. Our objectives are to establish practical recommendations issues from the data of the litterature on the various technical aspects of this technique. METHODS: This work leans on an exhaustive lecture of the literature concerning meta analyses, randomized tries, registers, controlled studies and the largest non controlled studies published on the subject. Recommendations were developed by a multidisciplinary workgroup then reread and amended by an also multidisciplinary group of proofreaders (urologists, gynecologists, gastroenterologists and surgeons). The methodology follows at best the recommendations of the HAS with a scientific argument for every question (accompanied with the level of proof, NP) and the recommendations, the officers (In, B, C and agreement of experts) and validated at the end of the phase of review. RESULTS: Surgical treatment of uro-genital prolapse by abdominal route classically associated hystero and anterior vaginopexy on the sacral ligament with a synthethic mesh. There are no argument to systematically associated a posterior vaginopexy to prevent secondary rectocele (level C). The consensual indication of laparoscopic rectopexy is represented by symptomatic rectal prolapse, the anatomical and functional results of which are the best estimated (level C). The surgical treatment of rectocele, elytrocele and enterocele with a posterior vaginopexy is not well estimated (level 3). Thus, it is not possible to conclude on the results of a posterior vaginal fixation with a mesh in these indications (AP). In the absence of colpocèle, the interest brought by the posterior vaginal mesh is not established (level 3). There is no comparative studies which allows to conclude on the type and mode of fixation of the prostheses of sacrocolpopexy. We would only report the most common practices without other conclusion. The anterior mesh is usually fixed upper on the anterior part of uterus cervix and lower on the anterior vaginal wall. These fixations are most of the time made by suture and on the promontory with non absorbable suture. The great majority of the authors recommend to make a peritonisation of prostheses to limit the risk of post-operative occlusion. It is now recommended to use only 2 kind of not absorbable prostheses: type I (macroporous polypropylene) or type III (polyester) and not to use any more prostheses type II (PTFE, Silicone) (level C) because of a high rate of mesh erosion: PTFE (9 %) or Silicone (19%) (level 3). Biological prostheses are no more recommended, because of short and medium-term lower anatomical results (level B). Anatomical and functional results are not stastistically differents between laparotomy and coelioscopy (NP1) but the comparison of tong-term results between both ways is not yet established. Coelioscopy allows significant reduction of blood losses, hospital stay and return to normal activity (level 1). Furthemore, there is a higher level of post-operative complications in laparotomy (level 1). When sacrocolpopexy is indicated, coelioscopy is thus recommended (level B). During coelioscopic sacrocolpopexy, anatomical and functional result have not shown any significance difference when using or no a robotics assistance but real randomised studies does not exist (level 2). In comparison to coelioscopy, robotic seems not to improve post-operative consequences and not to decrease the rate of complications of sacrocolpopexy (level 3). Robotic assistance cannot be yet recommended when a coelioscopic sacrocolpopexy is indicated (rank B). CONCUSION: Sacrocolpopexy using not absorbable meshes allows to cure pelvic organ prolapses with very good results with few complications in terms of prothetic exposure and infection and thus is now considered as the referent prothetic surgical technique in this indication. Thus, it seems very important to establish clear recommendations on the numerous operating technical variants which developed around the original technique. © 2016 Published by Elsevier Masson SAS.

Protein O-mannosylation is crucial for human mesencyhmal stem cells fate.

Human mesenchymal stem cells (MSC) are promising cell types in the field of regenerative medicine. Although many pathways have been dissected in the effort to better understand and characterize MSC potential, the impact of protein N- or O-glycosylation has been neglected. Deficient protein O-mannosylation is a pathomechanism underlying severe congenital muscular dystrophies (CMD) that start to develop at the embryonic developmental stage and progress in the adult, often in tissues where MSC exert their function. Here we show that O-mannosylation genes, many of which are putative or verified glycosyltransferases (GTs), are expressed in a similar pattern in MSC from adipose tissue, bone marrow, and umbilical cord blood and that their expression levels are retained constant during mesengenic differentiation. Inhibition of the first players of the enzymatic cascade, POMT1/2, resulted in complete abolishment of chondrogenesis and alterations of adipogenic and osteogenic potential together with a lethal effect during myogenic induction. Since to date, no therapy for CMD is available, we explored the possibility of using MSC extracellular vesicles (EVs) as molecular source of functional GTs mRNA. All MSC secrete POMT1 mRNA-containing EVs that are able to efficiently fuse with myoblasts which are among the most affected cells by CMD. Intriguingly, in a pomt1 patient myoblast line EVs were able to partially revert O-mannosylation deficiency and contribute to a morphology recovery. Altogether, these results emphasize the crucial role of protein O-mannosylation in stem cell fate and properties and open the possibility of using MSC vesicles as a novel therapeutic approach to CMD.

[Radical cystectomy for urothelial bladder cancer: prognostic impact of lymph node metastasis and soft tissue surgical margins]. / Cystectomie totale pour cancer urothélial : impact pronostique de l'atteinte ganglionnaire et des marges chirurgicales positives.

PURPOSE: To assess the association of soft tissue surgical margins (STSM) and/or lymph node metatstasis (pN+) with characteristics and outcomes of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We retrospectively collected the data of 242 patients treated with RC and pelvic lymphadenectomy for UCB between January 2005 and June 2009. Different parameters were studied: age, PSAt, pathological stage of cystectomy specimen (pT and pN), tumor grade, number (nb) of nodes (N) in lymphadenectomy, nb of metastatic nodes (nb N+), bigger diameter of N+, ganglionic density, nb of N with capsular ruptur, associated CIS, associated prostate cancer, follow-up, global and specific survival, date and etiology of death. RESULTS: Positive STSM were identified in 22 patients (9.1%) and lymph node metastasis in 59 (24.4%). pN+ status was significantly associated with lower global (GS) and specific survival (SS) (P<0.003). So was it for patients with positive STSM R+ with actuarial 3-year GS and SS respectively of 5% and 25% versus 35% and 43.9% no STSM (P<0.001). CONCLUSIONS: Positive soft tissue surgical margin and/or lymph node metatstasis on cystectomy specimen is a strong predictor of GS and SS from urothelial carcinoma of the bladder. So it is for capsular rupture, ganglionic density greater or equal to 0.10 and nb of N in lymphadenectomy less than 14 for pN+ patients.

[Role of surgery (cytoreductive nephrectomy and metastasectomy) in the management of metastatic renal cell carcinoma: a literature review]. / Place de la chirurgie (néphrectomie cytoréductrice et métastasectomie) dans la prise en charge du cancer du rein métastatique: revue de la littérature.

Cytoreductive nephrectomy is an established treatment option prior immunotherapy in well-selected patients with metastatic renal cell carcinoma. With the recent introduction of new targeted agents, the role of surgery has been source of controversy. This review examines the role of cytoreductive nephrectomy during the immunotherapy era, then in the new targeted therapies era. This review also summarizes the optimal timing of these treatments, the prognostic factors predicting outcome following cytoreductive nephrectomy, the role of metastasectomy, partial and laparoscopic cytoreductive nephrectomy.

[Renal artery pseudoaneurysm following partial nephrectomy: a case report with a current literature review]. / Faux anévrisme rénal après chirurgie conservatrice du rein pour cancer : à propos d'un cas et revue de la littérature.

Renal artery pseudoaneurysm (RAP) is a well-documented complication of percutaneous urologic procedures (biopsy, nephrostomy, nephrolithotomy) and renal trauma. Only few cases occurring after partial nephrectomy for cancer have been reported in the literature. We describe the case of one patient who presented with postoperative haemorrhage due to a RAP after partial nephrectomy. He has been successfully treated by angiographic selective embolization. This complication is rare but potentially life threatening. We describe its clinical and radiological diagnosis, and its management along with the current medical literature.

[Carcinologic outcomes after radical prostatectomy in 81 high-risk patients]. / Résultats carcinologiques de la prostatectomie totale chez 81 patients à haut risque.

OBJECTIVES: To evaluate carcinologic outcomes and biologic recurrence (BR) factor after radical prostatectomy (RP) for high-risk (HR) prostate cancer. MATERIAL AND METHODS: Between 1996 and 2006, 81 consecutives RP (65 with standard lymphadenectomy) have been done by a single surgeon for HR cancer according to d'Amico classification. No patient received neo-adjuvant therapy. Minimum follow-up required was 2 years. The BR was defined by two consecutives PSA greater than 0.2 ng/ml. Forty patients required immediate adjuvant therapy. Thirty for patients required secondary therapy. A multivariate analysis have been done for the following factors: age at RP, TNM stage, pre- and postoperative PSA, Gleason score, number of positive core biopsy, number of HR factor, positive surgical margin and immediate adjuvant therapy. RESULTS: Mean age was 64 years. Median follow-up was 71 month. Forty-nine patients was pT3 (60.5 %), seven was pN+(8.7 %) and 40 had positive surgical margin (49.4 %). The 5 years biological recurrence free survival rate was 42 %. The Gleason score (p=0.003, RR=1.688, IC=1.193-2.387), the preoperative PSA (p=0.001, RR=1.06, IC=1.032-1.089) and the number of positive core biopsy (p=0.006, RR=5.316, IC=1.605-17.607) were significant independent prognostic factors for the BR. The number of HR factor, positive surgical margin and immediate adjuvant therapy were not significant independent prognostic factors for the BR. CONCLUSIONS: At 5 years, RP in HR prostate cancer allowed carcinologic control without BR in 34 patients (42 %). This result was not influenced by the number of HR factor, surgical positive margin and immediate adjuvant therapy.

[Guidelines for treatment of urinary incontinence in women due to refractory idiopathic vesical hyperactivity with botulinum toxin A]. / Recommandations pour le traitement de l'incontinence urinaire féminine par hyperactivité vésicale idiopathique réfractaire par la toxine botulique A.

The data reported in the literature today show that botulinum toxin A may have a certain value in the therapeutic arsenal for non-neurological vesical hyperactivity. However, the use of botulinum toxin cannot be recommended in daily practice of non-neurological vesical hyperactivity incontinence treatment. In patients presenting non-neurological vesical hyperactivity, the use of botulinum toxin A (which in 2009 did not have market authorization for this indication, even in neurological patients) should be reserved for highly targeted, second- and third-line indications (failure or intolerance of recommended treatments), and certainly at first within clinical research or in specialized units.

[Synthesis of the guidelines for the treatment of non-neurological urinary incontinence in women]. / Synthèse des recommandations pour le traitement de l'incontinence urinaire féminine non neurologique.

The last two decades have brought about new medical and surgical treatments revolutionizing care for non-neurological urinary incontinence in women. Many studies, often randomized prospective studies with sufficient follow-up, have validated the therapeutic choices and shown them not to be part of a fad or marketing pressures. The French Association of Urology (L'Association Française d'Urologie), through its Committee on Women's Urology and Pelviperineology (Comité d'Urologie et de Pelvipérinéologie de la Femme), proposes its recommendations. These were established by an expert group of specialists (urologists, gynecologists, and physical therapists), based on a review of the literature but taking into account the daily practices in academic and private practice settings. Between evidence-based medicine and reality in the field, these recommendations attempt to propose realistic and applicable strategies.

[Physiopathology of genitourinary prolapse]. / Physiopathologie des prolapsus génito-urinaires.

The physiopathology of urogenital prolapse is multifactorial, a combination of the interaction between constitutional and acquired factors resulting in the weakening of perineal support. Genetic modifications contribute to the occurrence of prolapse (proof level 2). Differences relating to types of collagen and their proportions, the construction of smooth muscle fibres and nervous structures, have been described between women with and without prolapse. But the relationship of cause and effect is not always clear. It would appear that the reduction in the expression of the elastine gene and the perturbation of metabolism may be at the origin of the cause of a prolapse. However, the intense activity of tissue remodeling is probably the consequence of biomechanical pressure born by the prolapse. Muscular or neuropathic lesions of the levator ani have been widely researched and documented. In the case of prolapse, these were isolated exceptions and most often associated with dehiscence of support tissue.

[Risk factors and prevention of genitourinary prolapse]. / Facteurs de risque et prévention des prolapsus génito-urinaires.

Numerous epidemiological studies in recent years have involved the search for the principal risk factors of genitourinary prolapse. Although it has been agreed for a long time that vaginal delivery increases the risk of prolapse (proof level 1), on the other hand, the Cesarian section cannot be considered a completely effective preventative method (proof level 2). The pregnancy itself is a risk factor for prolapse (proof level 2). Certain obstetrical conditions contribute to the alterations of the perineal floor muscle: a foetus weighing more than four kilos, the use of instruments at birth (proof level 3). If the risk of prolapse increases with age, intrication with hormonal factors is important (proof level 2). The role of hormonal replacement therapy remains controversial. Antecedent pelvic surgery has also been identified as a risk factor (proof level 2). Other varying acquired factors have been documented. Obesity (BMI and abdominal perimeter), professional activity and intense physical activity (proof level 3), as well as constipation, increase the risk of prolapse. More thorough research into these varying factors is necessary in order to be able to argue for measures of prevention, obstetrical techniques having already evolved to ensure minimal damage to the perineal structure.

[Conservative surgery for kidney cancer: Indications and results based on a review of 40 patients]. / Chirurgie conservatrice du rein pour cancer : indications et résultats. A propos d'une revue de 40 patients.

OBJECTIVES: To evaluate the oncological and functional results in patients treated by conservative surgery for kidney cancer and to study the intraoperative and postoperative morbidity. MATERIAL AND METHODS: Retrospective, single-centre study based on 40 consecutive patients undergoing a conservative surgery for kidney cancer between March 1997 and July 2006. Patients had a mean age of 60 years (range: 26-81 years) and the surgical indication was elective in 75% of cases (n=30) and mandatory in 25% of cases (n=10). Preoperative mean creatinine and creatinine clearance were 101mol/l (53-237mol/l) and 80ml/min (35-147ml/min), respectively. Tumours were classified according to the TNM 2002 classification as stage T1a (75%), T1b (20%) and T2 (5%). Guided kidney aspiration biopsy was performed in 80% of patients. The main endpoints were positive surgical margins, local recurrence, intraoperative complications and postoperative renal function. Secondary endpoints were postoperative complications, need for blood transfusion, surgical revision, operating time and hospital stay, metastatic disease and overall and specific survival. Statistical analysis was performed with SPSS 13.0.1 software. RESULTS: With a mean follow-up of 44 months (range: 15-134 months), one patient (2.5%) presented local recurrence. The positive surgical margin rate was 5% and overall and specific survivals were 97.5%. No metastases have been observed. Serum creatinine was increased and creatinine clearance was significantly decreased (P<0.05) after the operation, with no clinical consequences. The urinary fistula rate was 5%, blood transfusion and surgical revision were required in 5% of cases respectively, the mean operating time was 128minutes and the mean hospital stay was 8.1 days. CONCLUSION: Mandatory, relative or elective conservative kidney surgery gives functional and oncological results at least equivalent to those of radical nephrectomy, with the advantage of nephron-sparing surgery. It should be suggested as first-line procedure whenever possible, even when the contralateral kidney is healthy.

[Value of percutaneous kidney biopsy in the management of solid renal tumours less or equal to 4 cm]. / Intérêts des ponctions biopsies rénales percutanées dans la prise en charge des tumeurs solides du rein inférieures ou égales à 4 cm.

OBJECTIVE: To assess the value of diagnostic percutaneous kidney biopsy of solid renal tumours less or equal to 4 cm and its impact on management. MATERIALS AND METHOD: From January 2001 to October 2006, all solid renal tumours less or equal to 4 cm were systematically assessed by CT-guided percutaneous biopsy: 66 tumours were biopsied in 65 patients (one bilateral tumour) and four patients had a second biopsy. A total of 70 biopsies were performed. RESULTS: Among the biopsies, 18% (12/66) were not contributive. Four were repeated and provided a diagnosis in 50% of cases. Two patients with non contributive biopsies were lost to follow-up. Seven benign tumours (10.9%) and 54 malignant tumours were diagnosed. The kidney biopsy diagnosed 91% (52/57) of malignant tumours and 57% (4/7) of benign tumours. The concordance between biopsy results and pathology results was 90.7% for histological type of tumour and 64% for Fuhrman nuclear grade. Histological type and tumour grade had no impact on the type of surgery performed (51 patients operated, 29 kidney-preserving procedures, by necessity in seven cases). Four patients (6.3%) in whom a benign tumour was diagnosed on biopsy were simply followed, thereby avoiding surgery. CONCLUSION: This series revealed 10.9% of benign tumours, only 57% of which were diagnosed by biopsy. Management was modified for only four patients (6.3%). Kidney biopsy remains an option in the pretreatment assessment of renal tumours less or equal to 4 cm, but cannot be proposed systematically.

Histologic evaluation of radiofrequency ablation in renal cancer.

AIM: To report on the histologic evaluation of renal tumors after intraoperative radiofrequency ablation (RFA) performed immediately before surgical nephrectomy. MATERIALS AND METHODS: Ten patients with renal tumors were studied. All tumors were confirmed to be renal cell carcinoma before radio frequency ablation treatment. All specimens were stained with hematoxylin and eosin and nicotinamide adenine dinucleotide (NADH). RESULTS: Mean tumor size was 29 mm (range 14 to 48 mm). Of the 10 tumors 5 were completely devitalized with a treatment margin ranged from 1 to 20mm. One tumor needed two treatment sessions. No complication related to radiofrequency treatment was recorded. CONCLUSIONS: Our data indicate that RFA can completely destroy renal tumors. However, in our study, complete tumor cell death was obtained only in 50% of cases. More studies are needed to ensure that is technique is an effective and reproducible treatment.