H. Bittard

Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.

Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-β-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62Lhigh and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.

Accuracy of ultrasonography in diagnosis of testicular rupture after blunt scrotal trauma.

OBJECTIVES The aim of this study is to determine the accuracy of ultrasonography for the diagnosis of testis rupture after scrotal trauma and its sensitivity and specificity for testis rupture, tunica albuginea breach, testicular hematoma, testis avulsion, epididymis injuries, and hematocele. METHODS Between 1996 and 2006, 33 patients underwent surgical exploration for blunt scrotal trauma. All these patients had an emergency scrotal ultrasonography with the use of a 7.5 or 10 MHz linear transducer. Ultrasonographic findings were compared with surgical findings to calculate sensitivity and specificity of ultrasonography for each type of lesion. RESULTS Of 33 patients, 16 presented a testis rupture. Testis rupture was in all cases suspected ultrasonographically by the loss of contour of the testis and heterogeneous parenchyma. Tunica albuginea breach was visualized in only 8 patients. Sensitivity and specificity of ultrasound for testis rupture were 100% and 65%, respectively. Moreover, ultrasonography allowed diagnosis of hematocele (sensitivity: 87% and specificity: 89%), testicular hematoma (sensitivity: 71%, specificity: 77%), and testis avulsion (sensitivity: 100%, specificity: 97%). Ultrasonography results for epididymis injuries were poor. On 7 patients, 3 epididymis lesions were misdiagnosed by ultrasound examination. CONCLUSIONS Ultrasonography can distinguish various scrotal injuries. Testicular rupture is probably the most severe injury that needs early surgical treatment to improve testis salvage rate. In our work, ultrasonography is highly sensitive in the diagnosis of testis rupture and can provide information on the scrotal contents integrity that can help the physician to determine the optimal treatment.

Outcomes of renal transplantation in obese recipients.

PURPOSE Although obesity has been shown to paradoxically increase dialysis patient survival, its impact has not been clearly defined on renal transplantation. We assessed outcomes of obesity renal transplant patients by evaluating graft and patient survivals. PATIENTS AND METHODS A single-institution, retrospective study was performed on 202 renal transplant recipients from January 2004 to December 2008 excluding two combined kidney and liver transplantations. Recipients were classified based on body mass index (BMI) at the time of transplantation: obese (BMI ≥ 30 kg/m(2)) and nonobese recipients (BMI < 30 kg/m(2)). The comparative analysis included surgical complications, hospital stay, onset of delayed graft function (DGF), acute rejection episodes and graft patient survivals. RESULTS Twenty-one renal transplants were performed in obese recipients versus 179 in the control group. Obese patients were older (53.3 ± 11.2 versus 46.4 ± 14.4 years old; P = .035) and more often diabetic (29% ± 0.46 versus 60% ± 0.24, P = .001), but there were no differences among other combidities of high blood pressure, arteriopathy, thrombophilia, and smoking. Obesity did not appear to be a risk factor for urinary or vascular as well as parietal complications, but did tend to augment lymphatic complications (14.3% ± 0.36 versus 4.5% ± 0.21; P = .065). DGF occurred more frequently in obese patients (38% ± 0.50 versus 14% ± 0.34; P = .004) and hospital stays were therefore longer in this group (24.9 ± 23.53 days versus 15.6 ± 13.67 days; P = .008). Graft (hazard ratio [HR] 1.22; 95% confidence interval [CI] [0.25-6.0], P = .63) and patient survivals (HR:0,81; 95% CI [0.12- 5.3], P = .83) were comparable between the groups. CONCLUSION Obese patients seeking renal transplantation are usually older and more often diabetic compared with nonobese recipients. The higher rate of lymphatic complications and DGF lead to longer hospital stays among the group with BMI ≥ 30 kg/m(2). However, long-term results showed similar graft and patient survivals as nonobese patients. Consequently, there seemed to be no reason to avoid renal transplantation in obese recipients.

T‐cell flow‐cytometry crossmatch and long‐term renal graft survival

Abstract:  Flow cytometry crossmatch (FCXM) is a more sensitive technique than classical complement‐dependent cytotoxicity (CDC) for the detection of donor‐directed antibody before renal transplantation. Nevertheless, the role of FCXM in predicting long‐term survival of kidney grafts is still unclear. The purpose of our study was to evaluate the impact of a positive T‐cell FCXM (T‐FCXM) on long‐term kidney allografts outcome. Of the 184 consecutive kidney transplantations performed in our center between 1 January1991 and 15 November 1996 a FCXM, performed concurrently to the pre‐transplant CDCXM, was available for 170 patients. The CDCXM was negative in all recipients. Among these recipients, 12 (7.1%) had a positive T‐FCXM. These patients were not different from patients with a negative T‐FCXM for donor and recipient age, sex, frequency of second transplantation, number of human leukocyte antigen matches or mismatches. Frequency of immunized patients was higher in kidney recipients with a positive FCXM (58.3% vs. 24.7%; p = 0.02, chi‐square test). Survival analysis revealed that kidney graft outcome was better in negative T‐FCXM recipients (p = 0.03), while patient survival was not statistically different. Our results suggest that a positive pre‐transplant T‐FCXM despite a negative CDCXM is associated with an impaired long‐term graft survival in renal allotransplantation.

Risk Factors for Surgical Complications After Renal Transplantation and Impact on Patient and Graft Survival

PURPOSE We report herein the incidence of and factors predisposive to surgical complications (SC) after renal transplantation. METHODS Between 2004 and 2008, we performed 200 renal transplantation. We retrospectively studied recipient and donor characteristics, cold ischemia time, surgical revision in the month after transplantation, delayed graft function, surgical complications (vascular, urologic, wound, or bleeding), as well as graft and patient 5-year survival rates. RESULTS Sixty-six surgical complications were reported among 49 patients with a preponderance of urologic complications. We noted 6.1% Clavien I, 1.5% Clavien II, 30.3% Clavien IIIa, 53% Clavien IIIb, and 9.1% Clavien IVa SCs. Vascular complications showed a worse prognosis. Among recipients, dialysis duration before transplantation (40.3 ± 50.8 months in SCs versus 28 ± 26.5 months in the control unaffected group, P = .032) and anti-HLA immunization (34.7 ± 48% versus 21.2 ± 41%, P = .05) appeared to be risk factor. No significant factor was identified among donors, although patients with surgical complications received older transplants than the control popuation (49.7 ± 14.5 years versus 45.5 ± 15.1 years, P = .08). A greater percentage of delayed graft function (30.6 ± 46.6% versus 11.4 ± 31.9%; P = .001) and graft rejection episodes (34.7 ± 48.1% versus 17.9 ± 38.4%, P .013) were observed among the SC compared with the control group. No significant difference in patient (89.5% versus 95.6% confidence interval, CI 95% [0.7-10.0]; P = .14) or graft survival (88.7% versus 91.8%, CI 95% [0.4-3.9] P = .63) was observed between the groups. CONCLUSION Surgical complications, especially urologic complications appear frequently after renal transplantation. Dialysis duration and pre-transplant immunization were linked to the occurrence of a surgical complication, which did not affect graft or patient survival.

Prise en charge de la colique néphrétique chez la femme enceinte : à propos de 48 cas

INTRODUCTION Urinary stones are relatively frequent in pregnant women and raise specific diagnostic and therapeutic problems. The authors conducted a retrospective review of the management of this disease in their establishment. PATIENTS AND METHODS Between January 1999 and December 2003, out of a total of 10,398 parturients, 48 pregnant women were hospitalised for renal colic, that is, incidence of 0.04%. The medical records of these patients were retrospectively reviewed and clinical, laboratory, treatment and outcome data were analysed. RESULTS Standard analgesic treatment, comprising paracetamol and an antispasmodic, achieved pain relief in 84% of cases. A concomitant short course of corticosteroid therapy in cases of renal colic refractory to standard treatment was effective in 71% of patients and allowed deferral of surgical management in five out of seven cases. A double J stent was placed in all patients requiring urinary diversion, followed by closer ultrasound and bacteriological monitoring throughout pregnancy. Only two patients required surgical management of their stone after delivery. The only obstetric event related to renal colic was induction of labour at term in two cases because of foetal distress. CONCLUSION The authors propose a two-stage management plan for renal colic in pregnant women resulting in a low maternal and foetal complication rate.

Variants of Renal Angiomyolipoma Closely Simulating Renal Cell Carcinoma: Difficulties in the Histological Diagnosis

Renal angiomyolipoma is considered to be a benign renal tumor composed of atypical blood vessels, smooth muscles and fat cells. We report 2 cases of unilateral renal angiomyolipoma. In both cases, our preoperative diagnosis was renal cell carcinoma, because no low density area compatible with fat tissue was noted in the tumors on radiographic evaluation. Through histological examination, both tumors proved to be angiomyolipomas mainly composed of epithelioid cells in 1 case, and spindle-shaped smooth muscle cells mimicking a leiomyoma in the other case. Both patients are well showing no evidence of metastases 16 and 14 months after nephrectomy, respectively.

Lymphocyte Subsets in Renal Transplant Recipients with de novo Genitourinary Malignancies

Introduction: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence. Patients and Methods: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry. Results and Conclusion: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR.

Hospital Costs of Renal Transplant Management

Renal transplantation is considered to be a cost-effective therapy, but hospital medical costs are not accurately known. The aim of this work was to evaluate the costs of hospital stay for renal transplantation. This retrospective study included all patients who underwent renal transplantation between January 1, 2004, and December 31, 2005, in our University hospital. The incurred costs were determined using our centers analytical accounting (AA). The mean local cost was then compared with the median national cost of hospitalization for renal transplantation, based on a sample of participating centers contributing to the National Cost Scale (NCS) per homogenous diagnosis-related group (DRG). These mean costs were weighed against the financing obtained by national rates of the case-mix based payment system (termed T2A). Data were collected from 77 patients. Their mean length of stay was 19.4 days. AA determined the cost of management to be euro14,100 per patient. National economic approaches were significantly higher: euro16,389 for NCS and euro17,369 for national rates. Thus, the specific DRG rate (case mix index) of renal transplantation covers the expenses incurred by our center. These results are rather interesting; however, it is unlike those obtained for the management of other diseases such as acute myeloid leukemia, where T2A underestimates the actual cost by 2-4 times. Last, the hospital budget and T2A must be considered as a whole. The fact that DRGs with favorable and unfavorable pricing balance out should be taken into account.

The PPARβ agonist L-165041 promotes VEGF mRNA stabilization in HPV18-harboring HeLa cells through a receptor-independent mechanism

Peroxisome Proliferator-Activated Receptor-β (PPARβ) is a ligand-inducible transcription factor activated by both natural (fatty acids and derivatives) and high affinity synthetic agonists. It is thought to play a role in angiogenesis development and Vascular Endothelial Growth Factor (VEGF) regulation but its contribution remains unclear. Until now, the PPARβ agonism effect on VEGF expression in cervical cancer cells was unknown. This led to our interest in assessing the effect of PPARβ activation on the regulation of different VEGF isoforms mRNA expression and the impact of E6 viral oncoprotein and its target p53 on this regulation in cervical cancer cells. Here, we showed that the PPARβ agonist L-165041 induces VEGF(121), VEGF(165) and VEGF(189) expression in HPV (Human Papillomavirus) positive HeLa cells but not in HPV negative cells. The underlying mechanisms did involve neither E6 oncoprotein nor p53. We highlighted a novel mode of PPARβ ligand action including a post-transcriptional regulation of VEGF mRNA expression through the p38 MAPK signaling pathway and the activation of the mRNA-stabilizing factor HuR. But most importantly, we clearly demonstrated that L-165041 acts independently of PPARβ since its effect was not reversed by a chemical inhibition with a specific antagonist and the siRNA-mediated knockdown of the nuclear receptor. As VEGF is crucial for cancer development, the impact of PPARβ ligands on VEGF production is of high importance. Thus, the molecular mechanism of their action has to be elucidated and as a result, PPARβ agonists currently in clinical trials should be carefully monitored.