Is recipient's body mass index a determinant of short term complications in early renal transplantation?

OBJECTIVES: Obesity prevalence has increased over the past 20 years in the general population and among kidney transplant recipients. General surgical belief is that obesity increases surgical difficulty. The aim of this study was to assess the impact of Body Mass Index (BMI) on perioperative complications. METHODS: All kidney transplantations performed in adults in our centre from 2006 to 2011 were analysed. Data on patients' characteristics, surgical protocol, intra and postoperative complications and renal function were collected. Patients were divided into 4 groups as follows: underweight (BMI<18.5kg/m2), normal weight (18.5kg/m2≤BMI<25kg/m2), overweight (25kg/m2≤BMI<30kg/m2) and obese (BMI≥30kg/m2). We also studied the impact of BMI on complications using it as a continuous variable to identify potential threshold values. RESULTS: Among 694 patients included, 52% had normal BMI, 7%, 31% and 9% were underweight, overweight and obese, respectively. In multivariate analysis, overweight was significantly associated with longer operative time compared to normal-weight patients (estimated mean difference of 10,4min, 95% confidence interval (CI) [4.0; 16.9]) and obesity was associated with an increased risk of wound dehiscence (odds ratio 3.1, 95%CI [1.3; 7.3] compared with normal-weight patients). Considering BMI as a continuous variable, the risk of parietal dehiscence significantly increased beyond a BMI of 26kg/m2, intraoperative blood loss and the risk of ureteral stenosis beyond 32kg/m2 and the risk of abdominal wall hematoma beyond a BMI of 34kg/m2. CONCLUSIONS: We found BMI thresholds above which intraoperative blood loss and the risk of parietal dehiscence, ureteral stenosis, and parietal hematoma significantly increased. LEVEL OF EVIDENCE: 3.

In vitro biocompatibility of a dentine substitute cement on human MG63 osteoblasts cells: Biodentine™ versus MTA(®).

AIM: To compare the in vitro biocompatibility of Biodentine™ and White ProRoot(®) mineral trioxide aggregate (MTA(®) ) with MG63 osteoblast-like cells and to characterize the cement surface. METHODOLOGY: A direct contact model for MG63 osteoblast-like cells with cements was used for 1, 3 and 5 days. Four end-points were investigated: (i) cement surface characterization by atomic force microscopy (AFM), (ii) cell viability by MTT assay, (iii) protein amount quantification by Bradford assay and (iv) cell morphology by SEM. Statistical analyses were performed by analysis of variance (anova) with a repetition test method. RESULTS: The roughness of the cements was comparable as revealed by AFM analysis. The MTT test for Biodentine™ was similar to that of MTA(®) . Biodentine™ and MTA(®) induced a similar but slight decrease in metabolic activity. The amount of total protein was significantly enhanced at day three (P < 0.05) but slightly decreased at day five for both tested samples. Biodentine™ was tolerated as well as MTA(®) in all cytotoxicity assays. SEM observations showed improvement of cell attachment and proliferation on both material surfaces following the three incubation periods. CONCLUSION: The biocompatibility of Biodentine™ to bone cells was comparable to MTA(®) .

Hepatitis E virus infection as a new probable cause of de novo membranous nephropathy after kidney transplantation.

Hepatitis E virus (HEV) has been identified as a cause of chronic viral hepatitis in immunocompromised patients. Some glomerular diseases were found to be associated with this infection. We report the first case, to our knowledge, of a kidney transplant recipient who developed an HEV infection and de novo membranous nephropathy (MN) concomitantly. The patient displayed a hepatic cytolysis first and a nephrotic syndrome occurred 3 months later. HEV infection was diagnosed upon positive polymerase chain reaction on plasma and stool samples, and renal allograft biopsy revealed de novo MN. Typical causes of MN were definitively excluded. A 3-month course of ribavirin monotherapy allowed the patient to mount a sustained viral response that was rapidly followed by complete remission of the nephrotic syndrome. The chronology of the onset and remission of both diseases is highly suggestive of a causal relationship between hepatitis E and MN.

High incidence of anticytomegalovirus drug resistance among D+R- kidney transplant recipients receiving preemptive therapy.

Anti-cytomegalovirus (CMV) prophylaxis is recommended in D+R- kidney transplant recipients (KTR), but is associated with a theoretical increased risk of developing anti-CMV drug resistance. This hypothesis was retested in this study by comparing 32 D+R- KTR who received 3 months prophylaxis (valganciclovir) with 80 D+R- KTR who received preemptive treatment. The incidence of CMV infections was higher in the preemptive group than in the prophylactic group (60% vs. 34%, respectively; p = 0.02). Treatment failure (i.e. a positive DNAemia 8 weeks after the initiation of anti-CMV treatment) was more frequent in the preemptive group (31% vs. 3% in the prophylactic group; p = 0.001). Similarly, anti-CMV drug resistance (UL97 or UL54 mutations) was also more frequent in the preemptive group (16% vs. 3% in the prophylactic group; p = 0.05). Antiviral treatment failures were associated with anti-CMV drug resistance (p = 0.0001). Patients with a CMV load over 5.25 log(10) copies/mL displayed the highest risk of developing anti-CMV drug resistance (OR = 16.91, p = 0.0008). Finally, the 1-year estimated glomerular filtration rate was reduced in patients with anti-CMV drug resistance (p = 0.02). In summary, preemptive therapy in D+R- KTR with high CMV loads and antiviral treatment failure was associated with a high incidence of anti-CMV drug resistance.

DTI-MR tractography of white matter damage in stroke patients with neglect.

Left visual neglect is a dramatic neurological condition that impairs awareness of left-sided events. Neglect has been classically reported after strokes in the territory of the right middle cerebral artery. However, the precise lesional correlates of neglect within this territory remain discussed. Recent evidence strongly suggests an implication of dysfunction of large-scale perisylvian networks in chronic neglect, but the quantitative relationships between neglect signs and damage to white matter (WM) tracts have never been explored. In this prospective study, we used diffusion tensor imaging (DTI) tractography in twelve patients with a vascular stroke in the right hemisphere. Six of these patients showed signs of neglect. Nonparametric voxel-based comparisons between neglect and controls on fractional anisotropy maps revealed clusters in the perisylvian WM and in the external capsule. Individual DTI tractography identified specific disconnections of the fronto-parietal and fronto-occipital pathways in the neglect group. Voxel-based correlation statistics highlighted correlations between patients' performance on two visual search tasks and damage to WM clusters. These clusters were located in the anterior limb of the internal capsule and in the WM underlying the inferior frontal gyrus, along the trajectory of the anterior segment of the arcuate fasciculus (asAF). These results indicate that chronic visual neglect can result from, and correlate with, damage to fronto-parietal connections in the right hemisphere, within large-scale cortical networks important for orienting of spatial attention, arousal and spatial working memory.

Noncoding RNA.

Regulatory RNAs, present in many bacterial genomes and particularly in pathogenic bacteria such as Staphylococcus aureus, control the expression of genes encoding virulence factors or metabolic proteins. They are extremely diverse and include noncoding RNAs (sRNA), antisense RNAs, and some 5' or 3' untranslated regions of messenger RNAs that act as sensors for metabolites, tRNAs, or environmental conditions (e.g., temperature, pH). In this review we focus on specific examples of sRNAs of S. aureus that illustrate how numerous sRNAs and associated proteins are embedded in complex networks of regulation. In addition, we discuss the CRISPR-Cas systems defined as an RNA-interference-like mechanism, which also exist in staphylococcal strains.

[Low protein diet supplemented with ketoanalogues of amino acids in patients with chronic renal insufficiency]. / Régime pauvre en protéines supplémentés par les céto-analogues des acides aminés chez le patient atteint d'insuffisance rénale : pour qui ? Comment ?

Restricted protein diets in patients with chronic kidney disease have been debated for several decades. In chronic kidney disease as in other chronic diseases, the modulation of the nutritional intake is the object of a certain renewal. It is supported by recent studies that highlight the importance of modulating nutrient intake by diets that are healthier, less rich in animal proteins and richer in plants. The recent reintroduction in France of amino acid supplements and ketoanalogs of amino acids allows the prescription of a very restricted diet. Historical studies have only focused on the relationship between protein intake and renal function degradation. Recent studies on acid loading, bone metabolism or potassium intake allow revisiting the interest of restricted diets. As with any change in eating habits, the selection of patients, information, education and monitoring during the diet are very important and help prevent undernutrition: this is the purpose of this short review.

Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons.

BACKGROUND: Undernutrition is a main cause of immunodeficiency. Many confounding factors limit the interpretation of immune function in hospitalized elderly patients. OBJECTIVE: We compared the effects of short-term fasting and refeeding on lymphocyte subset distribution and neutrophil function in healthy subjects. DESIGN: Seven young adult (x +/- SE age: 24 +/- 2 y) and 8 elderly (71 +/- 3 y) subjects were fed standardized diets (1.6 x predicted resting energy expenditure; 16% protein) for 7 d. They then fasted for 36 h and were refed for 4 h (42 kJ/kg). Lymphocyte subsets were quantified by using fluorochrome-conjugated monoclonal antibodies. Neutrophil chemotactic migration was evaluated by using a 2-compartment chamber. Neutrophil reactive oxygen species production was measured by using a luminol-amplified chemiluminescence assay and oxidation of 2'7'-dichlorofluorescein diacetate. RESULTS: Baseline total and cytotoxic T lymphocyte subpopulations were lower in elderly than in adult subjects (P < 0.01). Nutritional state had a significant effect (P < 0.05) on total, helper, and cytotoxic T and B lymphocyte counts in all subjects, and the response of lymphocyte subpopulations to nutritional fluctuations was significantly affected by age. The chemotactic index was lowered by fasting in both groups (P < 0.05 compared with basal values). After refeeding, neutrophil migration was restored in adult but not elderly subjects. The superoxide anion production rate increased with fasting and reverted to prefasting values with refeeding in both groups (P < 0.05). Fasting induced a significant decrease in hydrogen peroxide production in stimulated neutrophils that was reversed by refeeding in adult but not elderly subjects. CONCLUSION: The lack of response of lymphocyte subpopulation counts and neutrophil function to nutritional changes may help to explain the proneness of elderly persons to infection.

Noninvasive assessment of left ventricular performance in patients with ischemic heart disease: ear densitographic study during uninterrupted treadmill exercise.

Among 738 consecutive patients with chest pain referred for exercise testing, only 17 men fulfilled strict criteria for this pilot study: (1) achievement of at least 90 percent of age-predicted maximal heart rate or electrocardiographic criteria for a positive test; (2) subsequent coronary angiography; (3) exclusion of prior heart disease; and (4) absence of medication. Measurements of systolic time intervals obtained with ear densitography during early exercise differentiated 10 patients with coronary artery disease (Group 1) from 17 men (7 patients plus 10 normal volunteers) with normal coronary arteries (Group 2). Despite nearly identical heart rate and blood pressure responses in both groups, men in Group 1 had a significantly greater reduction of preejection period (PEP) at 1 minute and 4 minutes as well as a greater decrease in PEP/LVET (left ventricular ejection time) ratio. Differences were most significant when expressed as percent change of PEP/LVET ratio from control value (p less than 0.001 at both 1 minute and 4 minutes). After 4 minutes, men in Group 1 had no further decrease in PEP/LVET ratio and in 8 of the 10 men PEP/LVET ratio then increased to peak exercise. By contrast, PEP/LVET ratio continued to decrease to peak exercise in men in Group 2. The early floor in PEP/LVET ratio in Group 1 represents limited functional reserve and the subsequent increase suggests functional deterioration. Thus, densitographic systolic time interval measurements during uninterrupted exercise in unmedicated subjects appear to improve the sensitivity and specificity of the conventional treadmill test.

Cardiac response during uninterrupted treadmill exercise and recovery: measurement by systolic time intervals.

In 12 normal subjects, use of ear densitography permitted measurement of systolic time intervals (STI) during uninterrupted treadmill exercise to over 90 percent maximal heart rate on a modified Bruce protocol. Results for control (sitting leads to standing) leads to end-exercise at 18 minutes leads to 10 minutes' sitting recovery were--heart rate (HR): (77 leads to 861 leads to 171 leads to 98 beats per minute; preejection period (PEP): (106 leads to 111) leads to 49 leads to 110 msec; ejection time index (ETI) (351 leads to 330) leads to 380 leads to 366 msec; PEP/LVET (0.42 leads to 0.49) leads to 0.29 leads to 0.45. Heart rate increased steadily to 18 minutes. In contrast, the PEP/LVET decrease was almost complete by three minutes and both ETI and PEP responses were bimodal with respective plateaus between three and six minutes and three and nine minutes. All STI and HR curves showed rapid restitution during early recovery. The changes during treadmill exercise were numerically comparable to those during bicycle exercise at a common heart rate. The results indicate that it is technically feasible to measure systolic time intervals with precision during uninterrupted treadmill exercise; responses to treadmill exercise were in the direction expected and quantitatively comparable to bicycle exercise at comparable stress level. These obervations provide the technical and physiologic bases for applying this method in clinical treadmill exercise testing.

Increasing daily walking lowers blood pressure in postmenopausal women.

PURPOSE: The American College of Sports Medicine and the Centers for Disease Control and Prevention (ACSM-CDC) recommend 30 min of daily moderate-intensity physical activity for health; however, the effectiveness of this recommendation in lowering blood pressure (BP) in hypertensives is unclear. The present study tested the hypothesis that walking activity following the ACSM-CDC physical activity recommendation would lower BP in postmenopausal women with high BP. METHODS: Resting BP was measured in 24 postmenopausal women with borderline to stage 1 hypertension at baseline, 12 wk, and 24 wk. Fifteen women in the exercise (EX) group walked 3 km.d-1 above their daily lifestyle walking, whereas 9 women in the control (CON) group did not change their activity. Walking activity was self-measured with a pedometer in both groups. RESULTS: Resting systolic BP was reduced in the EX group after 12 wk by 6 mm Hg (P < 0.005) and was further reduced by 5 mm Hg at the end of 24 wk (P < 0.005). There was no change in diastolic BP with walking. The CON group experienced no change in BP at either 12 or 24 wk. Body mass was modestly reduced by 1.3 kg in the EX group after 24 wk (P < 0.05); however, it was not correlated with the change in BP. There were no changes in selected variables known to impact BP including percent body fat, fasting plasma insulin, or dietary intake. CONCLUSION: In conclusion, a 24-wk walking program meeting the ACSM-CDC physical activity recommendation is effective in lowering systolic BP in postmenopausal women with borderline to stage 1 hypertension.

Long-term follow-up of surgically treated AIS patients.

The aim of this study was to determine the long-term changes in spine and trunk alignment in patients who have undergone scoliosis surgery. Twenty-three (16F; 7M; at age of surgery 15.7 +/- 4.9 years) patients with adolescent idiopathic scoliosis agreed to participate and had posterior-anterior radiographs and surface topography prior to derotation surgery, within 6 months of surgery, at 2 years post-operatively and 5-10 years (mean follow-up period 6.11 +/- 1.6 years) after surgery. Cobb angles, surface trunk rotations, and cosmetic scores were measured at each visit. A questionnaire assessed back appearance and pain at the 5-10 year follow-up. The results of the questionnaire were compared to 25 patients with idiopathic scoliosis who had recently undergone surgery. A paired two-tailed Student's t-test with p=0.05 was used to compare the deformity between visits. The Cobb angle and cosmetic score improved after surgery while the change in trunk rotation was insignificant (p=0.37). Between the two-year and 5-10 year review, the Cobb angle, cosmetic score, and surface trunk rotation significantly increased. Self-perception of appearance and pain were similar to the control group. Surgical correction of scoliosis is not completely maintained during adulthood although the radiographic and surface deterioration does not appear to be clinically significant.

Assessing the impact of pelvic obliquity in post-operative neuromuscular scoliosis.

The goal of this pilot study was to explore the relationship between pelvic obliquity and patient pain, sitting tolerance, pressure sores, and function. Five neuromuscular patients who underwent spinal surgery 6-26 weeks prior to assessment took part in this on-going study (4F; 1M); age at surgery (14.6 +/- 2.6 years). Pelvic obliquity was measured from pre- and post-operative anterior-posterior radiographs. A force-sensing pad with a grid of sensors was placed on a flat surface and the weight distribution pattern was recorded. The pressures were divided into left and right sides and peak levels were noted on each side. The parents or caregivers completed a questionnaire on their child's pain, sitting tolerance, pressure sores, and functional abilities. Pelvic obliquity was reduced after surgery by approximately 50% depending on the method used to assess pelvic obliquity. The major curve was reduced from 64 degrees(10 degrees) to 39 degrees (10 degrees). Post operatively, the average pressure (left/right side) ranged from 1.2 to 2.0 (average 1.6). The peak pressure ratio ranged from 1.1 to 1.9 (average 1.4). The ratio of left/right pressure correlated with improvement in pelvic obliquity (r2=0.9). Pain was moderate/severe in the 2 patients with the least correction as measured with the Cobb angle from surgery; both improved following surgery. Two patients suffered pressure sores pre-operatively and one post-operatively. Only 3/5 felt sitting endurance had increased. All parents felt their child sat straighter after surgery. The outcome measures of pain, pressure sores, sitting tolerance, and function were not well related to the amount of pelvic obliquity. More candidates and a longer follow-up may shed light on the many relationships.

Examining the effects of a targeted noise reduction program in a neonatal intensive care unit.

OBJECTIVES: To determine whether implementation of a noise reduction policy followed by the addition of direct audit and feedback reduces noise levels in a tertiary-level neonatal intensive care unit (NICU). STUDY DESIGN: Noise level data was collected in three phases: (1) baseline (preintervention), (2) immediately postimplementation of our noise reduction policy, (3) postunveiling of direct audit and feedback mechanism. SETTING: A level 3 NICU in Ontario, Canada. INTERVENTIONS: Noise reduction policy and a direct audit and feedback mechanism. MAIN OUTCOME MEASURES: Average noise level. RESULTS: The baseline level of noise in our unit consistently exceeds guidelines with an average baseline noise of 49 dB (±1.4). Our intervention resulted in a significant reduction in noise levels for one of the four areas in our NICU [-1.06 dB (-1.52, -0.6)], with a trend towards reduction in a second area (-0.21 dB (-0.6, 0.18)). Unexpectedly, two other areas experienced a significant increase in noise (2.05 dB (1.18, 2.94); 0.85 dB (0.11, 1.59)). CONCLUSIONS: The baseline noise in the NICU consistently exceeds guidelines, but reductions in noise levels are achievable. Nonetheless, more work is needed to find the optimal NICU design and noise reduction strategy.

Reduction of noise in the neonatal intensive care unit using sound-activated noise meters.

OBJECTIVES: To determine if sound-activated noise meters providing direct audit and visual feedback can reduce sound levels in a level 3 neonatal intensive care unit (NICU). DESIGN/METHODS: Sound levels (in dB) were compared between a 2-month period with noise meters present but without visual signal fluctuation and a subsequent 2 months with the noise meters providing direct audit and visual feedback. RESULTS: There was a significant increase in the percentage of time the sound level in the NICU was below 50 dB across all patient care areas (9.9%, 8.9% and 7.3%). This improvement was not observed in the desk area where there are no admitted patients. There was no change in the percentage of time the NICU was below 45 or 55 dB. CONCLUSIONS: Sound-activated noise meters seem effective in reducing sound levels in patient care areas. Conversations may have moved to non-patient care areas preventing a similar change there.

Preemptive therapy versus valgancyclovir prophylaxis in cytomegalovirus-positive kidney transplant recipients receiving antithymocyte globulin induction.

International consensus guidelines on the management of cytomegalovirus (CMV) infections in kidney transplantation recommend the use of universal prophylaxis over preemptive therapy for the highest risk kidney transplant recipients (KTR), namely donor+/recipient - CMV serostatus. However, no universal recommendations have been made for R+ KTR undergoing antithymocyte globulin (ATG) induction. In this retrospective study, we compared 1-year outcomes among 24 R+ KTR who received 3 months of valgancyclovir prophylaxis with 72 R+ KTR who were subjected to a preemptive strategy. All subjects received ATG induction. The incidence of CMV infection was significantly higher among the preemptive subjects versus the prophylaxis group (78% versus 38%, respectively; P = .0003), whereas the incidence of CMV disease was low and did not differ significantly between the cohorts (8% versus 7% respectively, P = .8). Late-onset CMV infections were only observed in the prophylaxis group (25% versus 0%, P = .0001). Finally, the rate of opportunistic infections, acute rejection episodes, and graft/patient survivals at 1 year were also similar between the two groups. In light of this study, preemptive therapy and universal prophylaxis were almost equally effective to prevent CMV infection among R+ KTR receiving ATG induction.

Suppression substractive hybridisation (SSH) and real time PCR reveal differential gene expression in the Pacific cupped oyster, Crassostrea gigas, challenged with Ostreid herpesvirus 1.

Virus-induced genes were identified using suppression subtractive hybridisation (SSH) from Pacific cupped oyster, Crassostrea gigas, haemocytes challenged by OsHV-1. A total of 304 clones from SSH forward library were sequenced. Among these sequences, some homologues corresponded to (i) immune related genes (macrophage express protein, IK cytokine, interferon-induced protein 44 or multicopper oxidase), (ii) apoptosis related genes (Bcl-2) and (iii) cell signalling and virus receptor genes (glypican). Molecular characterization and phylogenic analysis of 3 immune-related genes (macrophage expressed protein, multicopper oxidase and immunoglobulin domain cell adhesion molecule) were performed. Finally, quantitative PCR revealed significant changes in the expression of immune related genes (multicopper oxidase, macrophage expressed protein, myeloid differentiation factor 88 and interferon-induced protein 44) in oysters experimentally challenged with OsHV-1. These findings provide a first basis for studying the role of innate immunity in response to viruses in bivalves and identified genes may serve as markers of interest in breeding programs in order to obtain selected oysters presenting OsHV-1 resistance.