Renal function and safety in stable kidney transplant recipients converted from immediate-release to prolonged-release tacrolimus

This multicenter, open, phase IIIb study assessed short-term efficacy, safety and dose adjustments in adult stable renal transplant recipients converted from tacrolimus twice-daily (BID) to once-daily (QD). Patients receiving unchanged tacrolimus BID for ≥ 12 weeks were enrolled, and after 6-weeks, converted from tacrolimus BID to QD (morning dose) on a 1 : 1 (mg : mg) total daily dose basis, for a further 12 weeks. Primary endpoint: change in steady-state creatinine clearance between treatment phases. Secondary endpoints: biopsy-proven acute rejection (BPAR), patient and graft survival, safety. 128 patients enrolled (mean age 48.9 years; time post-transplant 48.9 months); 91 evaluated for the primary endpoint. Mean total daily dose was 0.06 mg/kg (BID) and 0.07 mg/kg (QD); 79.1% required one/no dose changes post-conversion to maintain recommended blood-trough levels; average dose increase was small (0.6-0.7 mg/day) with more dose increases in patients on the lowest tacrolimus BID doses. Renal function remained stable and non-inferiority of tacrolimus QD against tacrolimus BID was demonstrated. There were no BPAR episodes; patient and graft survival were 100%. Adverse events were few; none led to dose modifications/discontinuation. Tacrolimus BID to tacrolimus QD conversion is straightforward and does not compromise renal function in stable kidney transplant patients in the short term.     

Intraprostatic testosterone and dihydrotestosterone. Part I: concentrations and methods of determination in men with benign prostatic hyperplasia and prostate cancer

Owing to inconsistencies and methodological differences, the present peer-reviewed literature lacks conclusive data on the intraprostatic levels of androgens, in particular dihydrotestosterone (DHT), in untreated benign prostatic hyperplasia (BPH) and prostate cancer. To date, no difference has been shown between DHT concentrations in normal prostatic tissue and BPH, and nor has a difference been shown in DHT concentrations between the histologically distinct regions of the prostate. Recent literature has also failed to show a consistent difference in androgen level between BPH and prostate cancer. The role of intraprostatic DHT in the pathogenesis of BPH and in the initiation and progression of prostate cancer thus remains to be established. Increased knowledge of the mechanisms of the androgenic steroid pathways in prostatic diseases, with a special focus on intraprostatic androgen levels may lead to more optimized and more personalized forms of treatment, and probably new therapeutic targets as well.     

Posterior approach (Kraske procedure) for surgical treatment of presacral tumors

Presacral tumors are rare,but can comprise a great variety of histological types.Congenital tumors are the most common.Once the diagnosis is established,surgical resection is essential because of the potential for malignancy or infection.Previous biopsy is not necessary or may be even harmful.To decide the best surgical approach(abdominal,sacral or combined) an individual and multidisciplinary analysis must be carried out.We report three cases of cystic presacral masses in which a posterior approach(Kraske procedure) enabled complete resection,the only way to decrease local recurrence.All patients had a satisfactory recovery.A brief overview of retrorectal tumors is presented,focusing on classification,clinical presentation,diagnosis and surgical management.     

Traumatic Grief and Traumatic Stress in Survivors 12 Years after the Genocide in Rwanda

The relationship between exposure to traumatic events and traumatic grief and the role of mediating and moderating variables [peritraumatic distress, post traumatic stress disorder (PTSD) symptoms and symptoms of depression] were studied in survivors of the genocide of Batutsi in Rwanda in 1994. One hundred and two survivors (70 women, mean age 45 ± 7.53 years) participated in this retrospective study. All of them had lost a member of their family. The severity of traumatic exposure (Comprehensive Trauma Inventory), peritraumatic distress (Peritraumatic Distress Inventory), current PTSD symptoms (PTSD Checklist), depressive symptoms (Beck Depression Inventory) and traumatic grief symptoms (Inventory of Traumatic Grief) was evaluated. A hierarchical multiple regression analysis was then conducted to examine the relative contribution of each variable to the symptoms of traumatic grief. The severity of traumatic exposure was related to traumatic grief symptoms (B = 0.06, R = 0.6, R² = 0.36 and ß = 0.6, t = 7.54, p = 0.00). The Baron and Kenny procedure (1986) (including three separate regressions), along with the Sobel test, was used to test mediation effects. Peritraumatic distress and PTSD symptoms may be mediating variables between traumatic exposure and traumatic grief. Traumatic grief is a complex but assessable entity, where previous distress and suffering result from both psychological trauma and the loss of a loved one. Copyright © 2011 John Wiley & Sons, Ltd.     

Relationship between conventional sperm parameters and motile sperm organelle morphology examination (MSOME)

With the motile sperm organelle morphology examination (MSOME), spermatozoa morphology may be assessed directly on motile spermatozoa at high magnification (up to 6600×). This procedure describes more precisely spermatozoa abnormalities, especially head vacuoles. However, no consensus has been established concerning normal or abnormal MSOME criteria. The aim of our study was to define MSOME vacuole criteria assessed objectively with a digital imaging system software to establish a potential relationship between conventional semen parameters. A total of 440 semen samples were obtained from males consulting in Rouen University Hospital Reproductive Biology Laboratory. Conventional semen analysis (volume, sperm concentration, progressive motility, vitality and morphology) and MSOME assessment {sperm head length, width and area as well as vacuole number, vacuole area and relative vacuole area to sperm head [RVA (%) = [vacuole area (μm(2))/head area (μm(2))] × 100)]} were performed for each semen sample. Among our 440 males, 109 presented normal conventional semen parameters and 331 abnormal ones. Sperm head vacuoles were significantly larger in abnormal semen samples (p < 0.0001). RVA was the most discriminative MSOME criterion between normal and abnormal semen samples according to ROC curves analysis, and was negatively correlated with poor sperm morphology (r = -0.53, p < 0.0001). We concluded to (i) the normal occurrence of vacuoles in sperm head whatever the normality or abnormality of semen parameters, (ii) the discriminative function of the RVA to distinguish semen samples with normal and abnormal parameters, and (iii) the strong correlation between high RVA and poor sperm morphology.     

CT colonography: Why? When? How?

Although optical colonoscopy is still the gold standard for diseases of the colon, radiologic examination of the colon is now being performed by CT scan. Evaluation of the colon is enhanced by distension, which "de-folds" the intestinal wall, thus facilitating its examination for abnormalities of the mucosa, the wall as a whole, and the diameter of the bowel lumen. Water or gas (CO(2)) may be used for the distension, depending on the suspected lesions. The water enema method of colonography combines filling the bowel lumen with water and intravenous injection of a contrast medium. It is indicated when there is a clinical suspicion of colon cancer, or for initial discovery of liver metastases, and for staging of colon tumors. This technique, which requires little or no colon cleansing preparation, can be performed with no special equipment and has a short learning curve. The gas enema method of colonography, or virtual colonoscopy, is performed by distending the colon with CO(2), without any intravenous injection of contrast medium. Its purpose is to detect polyps as part of a screening for precancerous growths. This technique, which does require bowel cleansing preparation, uses a dedicated console for reading and requires specific training.     

Salvage of failed trochanteric and subtrochanteric fractures using a distally fixed, modular, uncemented hip revision stem: 30 patients followed for a mean of 4 years

Background and purpose

Treatment options for failed internal fixation of hip fractures include prosthetic replacement. We evaluated survival, complications, and radiographic outcome in 30 patients who were operated with a specific modular, uncemented hip reconstruction prosthesis as a salvage procedure after failed treatment of trochanteric and subtrochanteric fractures.

Patients and methods

We used data from the Swedish Hip Arthroplasty Register and journal files to analyze complications and survival. Initially, a high proportion of trochanteric fractures (7/10) were classified as unstable and 12 of 20 subtrochanteric fractures had an extension through the greater trochanter. Modes of failure after primary internal fixation were cutout (n = 12), migration of the femoral neck screw (n = 9), and other (n = 9).

Results

Mean age at the index operation with the modular prosthesis was 77 (52–93) years and the mean follow-up was 4 (1–9) years. Union of the remaining fracture fragments was observed in 26 hips, restoration of proximal bone defects in 16 hips, and bone ingrowth of the stem in 25 hips. Subsidence was evident in 4 cases. 1 patient was revised by component exchange because of recurrent dislocation, and another 6 patients were reoperated: 5 because of deep infections and 1 because of periprosthetic fracture. The cumulative 3-year survival for revision was 96% (95% CI: 89–100) and for any reoperation it was 83% (68–93).

Interpretation

The modular stem allowed fixation distal to the fracture system. Radiographic outcome was good. The rate of complications, however—especially infections—was high. We believe that preoperative laboratory screening for low-grade infection and synovial cultures could contribute to better treatment in some of these patients.The failure rate after surgery for extracapsular hip fractures is low. Occasionally, cutout and migration of the femoral neck screw occur regardless of whether a sliding hip screw or an intramedullary nail is used (Stern 2007). Implant failure after open or closed reduction and internal fixation is mostly seen in patients with unstable fracture patterns, poor bone quality, or poor positioning of the internal fixation device (Haidukewych et al. 2001).It is often difficult to find straightforward solutions. For younger patients, a second attempt at osteosynthesis with or without bone grafting may be favored. For elderly patients, prosthetic replacement is attractive, allowing immediate ambulation without fear of further fracture complications (Stern 2007).A salvage procedure converting failed internal fixation to a cemented primary total hip arthroplasty (THA) is challenging due to pre-existing and acquired osteoporosis, deformation of the trochanteric region, and difficulties in obtaining cement pressurization because of cortical screw holes (Zhang et al. 2004). Thus, an uncemented hip revision arthroplasty in these cases would appear attractive. These implants are designed to bypass regions of proximally deficient bone and to obtain stability and fixation in the distal femoral bone where there is good bone stock.There have been few reports on salvage THA with modular revision implants, and the numbers of patients have been limited (n = 10–23) (Laffosse et al. 2007, Talmo and Bono 2008, D’Arrigo et al. 2010, Abouelela 2011, Thakur et al. 2011). We reviewed a series of patients who had been operated with a specific modular, uncemented hip revision arthroplasty for failure of internal fixation of trochanteric and subtrochanteric fractures.     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.