Effects of warm ischaemia combined with cold preservation on the hypoxia-inducible factor 1α pathway in an experimental renal autotransplantation model.

BACKGROUND: The increased use of marginal donors highlights the importance of organ quality in transplantation and the identification of prognostic biomarkers. This experimental study investigated modulation of the hypoxia-inducible factor (HIF) 1α pathway in kidney grafts in relation to different degrees of ischaemia. METHODS: In a porcine autotransplantation model, two different kidney graft protocols were compared: standard 24-h cold storage (CS) and 24-h CS preceded by 1 h warm ischaemia (WI + CS). The renal HIF-1α pathway and tubular dedifferentiation were analysed in the early phase of reperfusion and at 3 months. RESULTS: There was a relationship between the degree of ischaemic injury and the outcome of the kidney graft. During the first week of reperfusion, WI + CS grafts showed a higher degree of injury. The observed tubular dedifferentiation was associated with delayed HIF-1α expression, and with loss of its role in transcription. In highly injured kidneys, deregulation of the HIF-1α pathway was also observed in the chronic phase, with reduced production of vascular endothelial growth factor (VEGF) A, and upregulation of VEGF receptor 1 (Flt-1) and thrombospondin 1. In addition, these kidneys displayed altered kidney histology and decreased function. CONCLUSION: The HIF-1α pathway appears to be abolished early in response to severe ischaemia. A high degree of ischaemic injury also results in chronic activation of the HIF-1α pathway, diverting it away from the beneficial activation of angiogenesis. Further studies on the finely tuned balance of signals in this pathway may provide diagnostic biomarkers that can determine organ quality during kidney transplantation. Surgical relevance The increased use of marginal donors has highlighted the importance of organ quality in transplantation. Renal ischaemia-reperfusion injury following transplantation induces graft dysfunction. In a porcine model of renal autotransplantation, the induction of regenerative processes, in response to graded degrees of ischaemia, was studied in the post-transplantation phase. There was early abrogation of the hypoxia-inducible factor (HIF) 1α pathway in response to severe ischaemia. High degrees of ischaemic injury induced chronic activation of the HIF-1α pathway, diverting it from the beneficial activation of angiogenesis. Identification of the mechanisms involved in renal regeneration, such as those related to the HIF-1α pathway, are important as these mechanisms can be used to identify novel therapeutic targets or develop diagnostic biomarkers to determine organ quality early in the transplantation process.

[Reliability of imaging modalities for preoperative assessment of patients with endometrial carcinoma]. / Pertinence de l'imagerie dans l'évaluation préopératoire des patientes avec cancer endométrial.

OBJECTIVES: To investigate the value of transvaginal sonography, computed tomography and magnetic resonance imaging for the preoperative staging of endometrial cancer. PATIENTS AND METHODS: The patient group consisted of consecutive women undergoing surgery for endometrial cancer in our institution between January 2000, and September 2012. Clinical data included comorbidities, BMI (kg/m(2)), preoperative imaging findings, surgical procedures, surgical International Federation of Gynecology and Obstetrics stage, histological grade, relevant prognostic factors. The pathological data from surgical staging were compared with the preoperative imaging results. RESULTS: Two hundred and forty-four patients with the final diagnosis of endometrial cancer were enrolled. Hundred and ninety-six had preoperative transvaginal ultrasonography, 56 preoperative computed tomography and 158 preoperative MRI assessment. In our analysis, MRI had better sensitivity and specificity for all imaging criteria but lymph node assessment where MRI and CT-scan are equivalent (MRI: Se=45.45 %, Sp=79.52 %; CT: Se=50 %, Sp=80 %). DISCUSSION AND CONCLUSION: In patients with endometrial cancer, preoperative MRI may not accurately diagnose absence of myometrial invasion. This data should be kept in mind before planning the operative treatment modality and particularly before choosing patients for conservative endometrial carcinoma treatment.

[Cervical ripening with balloon catheter for scared uterus: a three-year retrospective study]. / Maturation cervicale par sonde à ballonnet sur utérus cicatriciel : étude rétrospective sur trois ans.

OBJECTIVES: To evaluate, for women with scared uterus, the mechanical cervical ripening with balloon catheter. METHODS: We conducted a retrospective study of our practice of ripening for scared uterus from january 2010 to august 2012. Feasibility, Bishop's score, birth modalities and complications for mothers and babies during this ripening were studied. RESULTS: Thirty-nine medical files were analysed. All patients could have mechanical ripening independently of the internal os status (open or not). The cervical ripening with balloon catheter improved Bishop's score before induction of labour, from 3.54 ± 1.23 to 5.38 ± 1.47 (p=0.02). 64.1% of women had a vaginal delivery. Concerning the predictive factors for vaginal delivery, we only found significant influence of a body mass index less than 30kg/m² (p=0.03). We didn't find any maternal or neonatal complications in our population. CONCLUSION: Mechanical ripening for scared uterus seems to be a useful option to improve vaginal delivery without increasing maternal and foetal morbidity. Anyway, these results have to be confirmed by a randomized controlled trial on a specific scared uterus population.

Evaluation of early regenerative processes in a preclinical pig model of acute kidney injury.

Renal failure due to ischemic injury is a common denominator of various clinical situations in critically ill patients. This study was designed to characterize the TPSO/Cholesterol synthesis and cell division pathways in response to different levels of ischemia. Porcine kidneys were subjected to either 60 min-warm ischemia (WI) or auto-transplanted after cold storage for 24 h at 4°C (CS), or both conditions (WI+CS), pathway activation and function were evaluated at 3 h, 3 and 7 days after reperfusion. CS combined to WI affects renal functions indicating a high degree of injury. During the first week of reperfusion, renal levels of free and esterified cholesterol, major cellular components, increased in CS group with an attenuated production when WI was associated. CS and WI+CS groups exhibited an elevated expression of cell cycle induction markers such as PCNA and stathmin. TSPO expression was highest in groups with the lowest injury, and correlated with kidney outcome, revealing its potential for diagnosis.

[Anal sphincter tears after vaginal delivery: risks factors and means of prevention]. / Lesions sphinctériennes anales après accouchement par voie vaginale: facteurs de risque et moyens de prévention.

To identify incidence and risks factors of obstetrical anal sphincter lacerations, we reviewed all cases of 3rd and 4th degree sphincter lacerations after vaginal deliveries (VD) occured in a tertiary maternity between 2005 and 2010. 78 anal sphincter lacerations were identified (3.8/1000 deliveries). 66 women (85%) were nulliparous. The mean age of women was of 29 +/- 5 years. The mean duration of the second stage of labour was of 3.4 +/- 1,7 hour. The birth weight of 12 newborns (15%) was greater than 4000 grams. Fourty-six women (2.5%) had sphincter lacerations after instrumental delivery and 32 after spontaneous vaginal delivery (0.2%). 51 patients out of 78 (65%) had a medio-lateral episiotomy, 82% occured after instrumental extraction and 43% after spontaneous delivery. A forceps of Tarnier was used in 18 cases, a Suzor forceps in 12 cases, spatula in 12 cases and vacuum in 4 cases. 76% of foetuses were in anterior presentation and 78% at the medium part of the pelvis. 2 patients experienced anal incontinence in early post-partum. Anal sphincter lacerations are relatively frequent after VD especially after instrumental delivery. Macrosomia, nulliparous women, prolonged second stage of labor were associated with anal sphincter tears. Medio-lateral episiotomy does not protect enough anal sphincters. Anal sphincter lacerations lead to anal incontinence in some cases.A long follow-up is useful for these patients.