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Basal-cell carcinoma with matrical differentiation (BCC-MD) is one of the rarest pathologic variants of basal-cell carcinoma, of which 41 cases have been so far reported in detail. One of them developed in a heart-transplant recipient. We report a new case of BCC-MD occurring in a renal-transplant recipient and review the relevant literature. A 75-year-old white man who had received a renal allograft 7 years ago developed a tumor on the left temple clinically suggestive of basal-cell carcinoma. Microscopically, the tumor associated features typical of basal-cell carcinoma (basaloid lobules with peripheral palisading and clefting) and pilomatricoma (presence of shadow/ghost cells). The 2 tumor components expressed variably beta-catenin, HEA/Ber-EP4, CD10, PHLDA-1, MIB-1/Ki67, calretinin, and bcl-2. BCC-MD has no distinctive clinical features. It affects predominantly male patients with a mean age of 69 years. More than half of cases appear on the head/neck area. Some cases harbor CTNNB1 mutations. Differential diagnosis includes tumors with matrical differentiation, namely pilomatrix carcinoma. The outcome is usually favorable after surgical excision, although regional lymph node metastases developed in 2 patients.

Background Enhancing vaccine immunogenicity in kidney transplant recipients, particularly against influenza, is required since the immunosuppression used to prevent graft rejection limits vaccine immunogenicity. We therefore investigated the immunogenicity and safety of a double dose non-adjuvanted vaccination regimen against influenza H1N1pdm2009 in kidney transplant adult recipients. Methods A prospective single-arm study was conducted including 121 renal transplant recipients under triple immunosuppressive regimen. Patients received 2 injections (day 0, day 21) of an inactivated, non-adjuvanted H1N1pdm2009 vaccine. Immunogenicity (hemagglutination-inhibition [HI] antibodies and anti-hemagglutin [HA] specific T cells) was evaluated after one and two injections (day 21, day 42) and at 6 months (day 182). Results The seroprotection rate (HI antibody titer ≥ 1/40) was 19% at day 0 (n = 119), 53% at day 21 (n = 118), 60% at day 42 (n = 116) (p = 0.013; day 42 vs. day 21) and 56% at day 182 (n = 113). The seroconversion rate was 24% and 32%, the geometric mean fold rise was 3.7 and 4.6 after the first and second injections, respectively. T-cell immunity to the H1N1pdm2009 vaccine showed a two-fold increase from baseline, though not statistically significant, in H1N1pdm2009-HA-specific CD4+ and CD8+ T cells in 34% and 48% of cases, respectively. No rejection episodes related to vaccination were observed while the donor-specific antibodies and creatinine clearance remained unchanged throughout the study. Conclusion Administration of two doses of the non-adjuvanted influenza H1N1pdm2009 vaccine in renal transplant patients is safe and induces a significant seroprotection, not strong enough yet to meet European or US requirements for adults below 60 years, but comparable to seroprotection levels usually observed in the non immunosuppressed elderly population or conferred by a single dose of adjuvanted vaccine in solid organ transplant recipients. These results provide useful indications for future strategies required to improve immunogenicity of vaccines against influenza in transplanted patients.

Summary Use of high dose intravenous immunoglobulin (IVIg) has been associated with necrotizing enterocolitis in late-preterm and term infants treated for severe isoimmune hemolytic jaundice. We present the first adult case of reversible ileitis related to high dose IVIg that occurred during the treatment of acute humoral rejection in a kidney transplant recipient (original nephropathy: lupus). At the third of the 5 days of a 0.4 g/kg/day IVIg infusion, he had periumbilical pain and nausea. Non-iodine injected abdominal computed tomography (CT) demonstrated a major proximal ileitis that was absent 1 month earlier on a previous CT. After the fourth injection, IVIg therapy was discontinued. Clinical and radiological signs disappeared, respectively, 5 and 7 days after IVIg discontinuation. No other causes of ileitis were diagnosed (especially infectious, vascular, or lupus-related bowel disease causes). Usual abdominal pain and nausea during IVIg therapy may be related to sub-clinical ileitis and/or enteritis. As in newborn, such complication has to be diagnosed and IVIg infusion discontinued because of potential evolution to intestinal necrosis.

Hemodialysis (HD) has been associated with higher 1-year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1-year and ≥1-year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (

Background/Aims: In diabetics with end-stage renal disease (ESRD), risk of death has been reported to be non-constant after the first dialysis, and different outcomes have been observed between genders. We assessed the impact of type 2 diabetes (T2DM) on mortality in dialysis regarding its differential effect by gender using time-dependent analyses. Methods: All T2DM and non-diabetic (no-DM) patients who started dialysis in two renal units in Lyon, France, between January 1, 1995, and December 31, 2007, were included. In multivariate analyses, the Cox model and Shoenfeld residual approach were used to assess the effect of T2DM on dialysis mortality by gender. Results: We included 235 T2DM (males: 57.9%) and 480 no-DM (males: 65.6%) patients. In males, the adjusted hazard ratio (aHR) for death in T2DM versus no-DM was 0.83 (p = 0.20) and was constant over time after the first renal replacement therapy (RRT) (p = 0.88). In females, aHR for death in T2DM versus no-DM patients was not constant over time (p = 0.002). It was 0.64 (p = 0.13) within the first year after the first RRT and 2.10 (p = 0.002) after the first year. Evolutions with time of these aHR by gender were significantly different (p = 0.009). Conclusions: T2DM was associated with death only in females. This association was not constant over time after the first dialysis.

Human cytomegalovirus (HCMV) resistance to antiviral drugs is a major drawback of repeated or long-duration treatment in immunocompromised patients. Resistance testing is usually performed by genotypic assays. For accurate interpretation of these assays, the role of new mutations in HCMV resistance has to be assessed. Two previously unknown UL54 single point mutations (D515Y and V787A) were characterized for phenotypic drug-resistance by marker transfer analysis using bacterial artificial chromosome (BAC) mutagenesis. Increases in 50% inhibitory concentrations of ganciclovir and foscarnet were found for both mutated recombinant strains showing that mutations D515Y and V787A induce resistance to both antivirals. Importantly, none of those impacted the viral growth kinetics. For a better understanding of their molecular resistance mechanisms, a 3D homology model was used to localize the mutated amino-acids in functional domains of UL54 and predict their impact on UL54 function and resistance. However, 3D homology model analysis has limits and phenotypic characterization using BAC-HCMV is still essential to measure the role of unknown mutations.

Background. The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. Methods. This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mglkg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. Results. At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001)). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P

To evaluate the influence of various parameters on peak systolic velocity in the transplanted renal artery and to define the normal range of peak systolic velocity.Color Doppler ultrasonographic (US) findings in 105 patients were reviewed. There were no clinical or biologic findings suggestive of a stenosis in the transplanted renal artery in these patients. The peak systolic velocity in the transplanted renal and external iliac arteries and the renal resistive index were measured.A large range of peak systolic velocities was noted in the transplanted renal artery. Peak systolic velocity in the renal artery was statistically significantly correlated with that in the external iliac artery when there was no pronounced vessel curvature. There was no relationship between peak systolic velocity and resistive index or time between transplantation and US. High peak systolic velocity was associated with a pronounced vessel curvature.The normal range of peak systolic velocity in the transplanted renal artery has considerable variability. Because of the strong correlation, the ratio of velocity in the renal artery to that in the external iliac artery may be useful in detection of stenosis.

It has been reported and also has been our preliminary experience that many false ostial stenoses are attributable to a loss of signal intensity at the origin of the renal arteries when three-dimensional (3D) phase-contrast MR angiography is used. Our objective was to add a 3D time-of-flight MR angiography sequence to the 3D phase-contrast MR angiography sequence to better analyze the origin of the main renal arteries. We assessed the value of the combination of these two MR angiography sequences for the depiction of renal artery stenosis.Forty-six patients suspected of having renal artery stenosis on the basis of clinical history, physical examination, and laboratory data were prospectively enrolled. Intraarterial digital subtraction angiography findings were available for all patients. Using intraarterial digital subtraction angiography, we considered stenosis to be significant when the vessel was narrowed more than 50%. During MR angiography, half of the data were reconstructed by interpolation to avoid long acquisition times. Total acquisition times were less than 15 min. MR angiography findings were interpreted independently by two radiologists who were unaware of the findings of intraarterial digital subtraction angiography. With 3D phase-contrast MR angiography, any cutoff in signal intensity or any narrowing of the vessel diameter of more than 50% from the renal ostium to the renal hilum was considered to represent significant stenosis. With 3D time-of-flight MR angiography, our image analysis was focused on the origin of the arteries. Any cutoff in signal intensity in the first centimeter of the renal artery was considered to represent significant stenosis.Intraarterial digital subtraction angiography showed 105 renal arteries, including 15 supernumerary renal arteries. Eleven stenoses were localized to the main hilar renal arteries. Using time-of-flight MR angiography, we found that polar supernumerary renal arteries of small caliber and intrarenal branches of renal arteries were not adequately displayed. Using phase-contrast MR angiography to evaluate only whether the main hilar renal arteries were stenotic, we calculated the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to be 100%, 65%, 28%, 100%, and 69%, respectively. Using a combination of the two imaging sequences, we found that the specificity, positive predictive value, and accuracy were increased to 90%, 58%, and 92%, respectively.For detecting stenoses of the main renal arteries but not for visualizing small accessory renal arteries or distal branches, our results support the use of a combination of the two MR angiography sequences. For now, this combination of sequences should be viewed primarily as a technique for screening patients.

We report on a 28-year-old AIDS patient who developed a rapidly progressive glomerulonephritis while being treated with foscarnet for cytomegalovirus retinitis. Renal biopsy showed crescentic proliferation related to crystals within the glomerular capillaries. The role of foscarnet in this unusual renal syndrome is discussed.

Wegener granulomatosis (WG) is an uncommon systemic necrotizing vasculitis that demonstrates renal and respiratory tropism. While the pathogenesis of WG remains controversial, autoimmune and inflammatory mechanisms are likely to be involved. The nervous system could be affected in up to 54% of cases. Although central nervous system involvement has been reported in 7-11% of cases, aneurysmal subarachnoid hemorrhage (SAH) occurrence is exceptional.We describe the third reported case of WG-related aneurysmal SAH and then discuss the diagnosis and pathogenesis of WG along with the physiopathology of intracranial aneurysm in light of recent data reported in the literature.A 63-year-old woman with WG was referred to our neurosurgical department for aneurysmal SAH. The vasculitis diagnosis had been established 4 years earlier when she presented with chronic sinusitis, recurrent cystitis, and renal failure. The cerebral angiography revealed an anterior communicating artery dysplastic aneurysm. The neurosurgical management of the aneurysm was scheduled but delayed because the patient was experiencing a vasculitis flare-up. Immunosuppressive therapy and intravenous corticotherapy were given, with the patient's improvement, allowing neurosurgical clipping of the aneurysm.Wegener granulomatosis-related aneurysmal SAH is an exceptional condition in neurovascular pathology. As inflammatory mechanisms are involved in the pathogenesis of aneurysm, the vasculitis flare-up could account for this SAH. The management of WG could benefit from anti-inflammatory therapy, as could the vasculitis-related SAH. SAH occurrence in patients with systemic vasculitis could indicate a vasculitis flare-up.

Background The increased incidence of skin cancers in transplant patients is well documented; however, few data exist on the risk of subsequent skin tumors in a given patient after the first skin cancer. The aim of this study was to compare the individual rate of subsequent skin cancers in kidney (KTR) and heart transplant recipients (HTR) after the first squamous cell carcinoma (SCC) and to assess risk factors for tumor multiplicity. Methods In all, 188 patients (121 KTR/67 HTR) were studied for up to 5 years. The cumulative number of SCC, basal cell carcinomas, Bowen's diseases, premalignant keratoses, and keratoacanthomas was recorded yearly after the first SCC. Results Overall, 71% of patients developed 757 new skin tumors. At 5 years, 100% of HTR and 88% of KTR had presented new tumors. However, the mean number of all tumors was significantly higher in KTR (3.4 vs. 2.0, 4.8 vs. 2.6, 6.6 vs. 2.9, 8.5 vs. 3.5, and 9.7 vs. 4.6 at 1, 2, 3, 4, and 5 years, respectively). Transplantation before 1984, multiple tumors at first consultation, eye and hair color, and skin type were predictive of multiple tumors. Early minimization of immunosuppression and of sun exposure tended to be associated with a reduced rate of all tumors and of SCC, respectively. Conclusions Although the proportion of HTR developing new tumors is greater as compared with KTR, the mean number of tumors per patient is higher in KTR. This could be due to a longer immunosuppression in patients younger at transplantation.

Introduction Pour faciliter l’acces a la Tx apres debut de HD, nous evaluons apres 9 mois un chemin clinique (CC). Apres information sur la Tx, un bilan de pre-Tx (BPT) est debute sauf refus du pat ou contre-indication medicale (CIM) evidente et un expert du CHU est consulte pour les cas complexes. L’impact du CC est presente en termes d’etat sur liste d’attente par modalite d’HD : avant (Av) et apres (Ap) CC. Patients et methodes Avec le CC, 10 % des patients refusent le BPT pour âge ou comorbidite. Il y a beaucoup plus de BPT en cours, souvent finalises, surtout en UDM et centre, par moins de CIM, mais pas plus d’inscrits malgre avec equipe de Tx realisees. Les Tx sur periode ne sont pas prises en compte ( Tableau 1 ). Discussion et conclusion La proposition et l’evaluation systematisees de la possibilite de Tx des l’arrivee en dialyse peuvent etre efficaces pour reduire le delai d’attente de Tx, qui reste neanmoins conditionne par l’inscription sur liste d’attente en CHU, parfois retardee.

The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients.This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day.At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction).Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

THE MECHANISMS of chronic cyclosporine (CyA) toxicity are not well established. CyA impairs cytosolic calcium singling.1 Calcium modulates the activity of a calmodulin-dependent protein kinase, which phosphorylates a sialytransferase.2 The CyA-cyclophilin complex inhibits the phosphatase activity.3 The fixation of sialic acid on glycoconjugates is regulated by sialytransferase phosphorylation,2 thus we looked for an effect of CyA on the enzymatic glycosylation processes.

The goal of this study was to assess the value of a three-dimensional phase contrast magnetic resonance angiography (3D PC MRA) for diagnosing transplant renal artery stenosis (TRAS). Twelve consecutive patients clinically suspected of having TRAS were prospectively enrolled during a period of 18 months. Delays from transplantation varied from 3 months to 4 years (mean: 18.3 months). Patients first had color Doppler sonography, then MRA-and, on the following day, intraarterial digital subtraction angiography (IADSA). The site of the maximum peak systolic velocity was noted when doing the report of each color Doppler sonogram. On MRA images, any signal cutoff or any vascular narrowing of more than 50% of the diameter of the vessel was considered to be a significant stenosis. Eight patients were considered to have TRAS on MRA, but only two stenoses were noted on IADSA. The six false-positive results of MRA (due to major intravoxel phase dispersion) were observed when elevated peak systolic velocities were noted on doppler sonograms (mean: 214 cm/sec). These elevated peak systolic velocities were noted in the proximal part of the renal artery when there was a tortuous vessel or a sharp angle between the renal artery and the parent vessel. It is our opinion that 3D PC MRA is of limited value for the diagnosis of renal transplant artery stenosis because of a high number of false-positive results.

Hodgkin's disease (HD) has seldom been reported after transplantation. Epstein-Barr virus (EBV) is present in about 50% of Reed-Sternberg cells in HD developing in immunocompetent individuals, but is more frequently found in HD of acquired immune deficiency syndrome patients. We report 7 cases of HD that occurred in transplant recipients. Clinical and pathological data and studies of EBV reveal specific features of HD after transplantation. Six patients received kidney transplants and 1 patient received combined kidney and pancreas transplantation. Immunosuppressive therapy consisted of cyclosporine, steroids, azathioprine, and antilymphocyte globulins. One patient received, in addition, anti-CD3 mAb therapy and an EBV+ B cell lymphoma developed. Retrospective EBV serological data from patients were collected. Tumors were classified according to pathology. EBV studies were conducted by immunohistochemical methods with monoclonal antibodies to EBV-latent membrane protein (LMP) or EBV-nuclear antigen 2 (EBNA2), and by in situ hybridization for latent nuclear EBV-early RNAs (EBERs). The mean lapse of time between transplantation and HD was 49 months. Six patients presented with enlarged lymph nodes and 1 patient presented with liver involvement. HD was classified as IA in 2 patients, IIA in 3 patients, IIIB in 1 patient, and IVB in 1 patient. Four patients had primary EBV infection after graft, before HD, and the others reactivated latent EBV infection. Histological subtypes were mixed cellularity in 6 cases and lymphocytic depletion in 1 case. Latent EBV infection was detected with EBERs in all tumors. Reed-Sternberg cells expressed LMP, and were negative for EBNA2 expression. Six patients were treated: 2 patients at stage I received radiotherapy, and relapsed within 1 year with a more advanced stage of HD; chemotherapy was indicated as primary therapy in 5 patients, and as salvage therapy in 2 patients; it was associated with radiotherapy in 4 patients. Immunosuppressive therapy was reduced in all patients. Four patients were alive and in complete remission 18, 25, 31, and 67 months after chemotherapy, with a functioning graft in 3 patients. Two patients died of infection. Mixed cellularity is the most frequent histological subtype observed in HD occurring in transplant patients. EBV is present in all Reed-Sternberg cells. Posttransplant HD shows similarities with human immunodeficiency virus-associated HD. These facts argue for a role of EBV infection and immunosuppression in the progression of HD after transplantation.

Post-transplant lymphoproliferative disorders (PTLD) represent a dreaded complication in transplant patients. Early recognition and treatment is critical in reversing the disease. We report on 2 cases of PTLD in renal transplant recipients in whom plasmacytoid cells could be detected in peripheral blood several days before the clinical onset of the disease.

A prospective study was undertaken to determine the incidence of preexisting lesions in renal grafts and their possible influence on renal function after transplantation.

PUBMED database in March 2012 with the following keywords: barefoot running. We retained 40 articles that focus on medical aspects of this practice. Results.–Many articles focus on the biomechanical and physiological aspects of barefoot running. Aspects of injury, studies are few and contradictory. The studies focus on long distance race, there are very few studies on the sprint barefoot. The distal lower limb injuries in running are common with an overall prevalence of 30 to 60% in athletes. It is not possible to compare their prevalence in the runner without shoes for which no studies exist to date. Injuries specific to practice barefoot are yet to be described.Onewonders about the long-termdamage such as osteoarthritis. No studies about the sprained ankle in runners barefoot. Discussion.– Theories to explain different injuries and even less in with or without shoes, will be discussed. Conclusion.– Comparative and prospective studies on large cohorts are needed to see if running barefoot reduces or increases the risk of injury in the short or long term.

Intravenous pyelography and cystography may fail to localize the origin of haematuria. Microhaematuria is known to be present in 2 to 10 percent of the general population, usually without pathological consequences. Study of red cell morphology by phase contrast microscopy is effective in distinguishing between "glomerular" (from renal tissue) and "non-glomerular" (from urinary tract) erythrocytes, but this technique is not currently available in all laboratories. Urinary blood cell volume analysis has been presented as a simple and automatic alternative method. We compared these two techniques in 100 cases of haematuria of various origins. The cut-off point between glomerular and non-glomerular erythrocytes was set at 71 fl. Phase contrast microscopy always confirmed the clinical and/or histological diagnosis, but volume analysis did not: mean erythrocyte volume of glomerular origin was 66.6 +/- 10.4 fl, while non-glomerular volume was 94.5 +/- 17 fl (P0.001); cell volume analysis was confirmative in only 72 percent of all diagnoses (65 percent of microhaematurias, 83 percent of macrohaematurias); sensitivity was 65 percent and specificity 85 percent for glomerular erythrocytes. Due to poor performance, urinary red volume analysis is not an acceptable alternative method to phase contrast microscopy when searching for the site of bleeding.

26 cases of multiple cholesterol emboli syndrome were investigated to loo for a trigger factor : endoarterial catheterism, vascular surgery or anticoagulant/fibrinolytic therapy. One at least was present in 21 cases (81 %) and we discuss these physiopathologic conditions.

The excretion of four inhibitors of urinary stone formation (zinc, magnesium, citrates and glycosaminoglycans (GAG) was studied in 20 normal controls and 40 recurrent calcium stone formers who were placed on a fixed diet restricted in calcium, oxalates and purines. We were unable to show any abnormality in the excretion of Zn, Mg or GAG. In 11 patients, a low level of urinary citrate was a significant feature that was associated in most cases with a urinary pH value above 6. Citrate concentration (per litre) and output (per 24 h) were found to be lower than in the controls in 19 and 33% respectively of the determinations. The overall ratio of average urinary citrate concentration in patients and controls was 0.56, a figure in agreement with previous data.