Eight‐year results of the Spiesser study,a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation

We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death‐censored graft survival (log‐rank compared), de novo DSA appearance, risk of malignancy, post‐transplant diabetes mellitus (PTDM), and anemia. Intent‐to‐treat and on‐treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death‐censored graft survival (P = 0.858). In conditional intent‐to‐treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long‐term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.     

Is prenatal urethral descent a risk factor for urinary incontinence during pregnancy and the postpartum period?

Introduction and hypothesis

Obstetric trauma during childbirth is considered a major risk factor for postpartum urinary incontinence (UI), particularly stress urinary incontinence. Our aim was to investigate the relation between postpartum UI, mode of delivery, and urethral descent, and to define a group of women who are particularly at risk of postnatal UI.

Methods

A total of 186 women were included their first pregnancy. Validated questionnaires about urinary symptoms during pregnancy, 2 and 12 months after delivery, were administered. Urethral descent was assessed clinically and by ultrasound at inclusion. Multivariate logistic regression analysis was used to determine the risk factors for UI during pregnancy, at 2 months and 1 year after first delivery.

Results

The prevalence of UI was 38.6, 46.5, 35.6, and 34.4 % at inclusion, late pregnancy, 2 months postpartum, and 1 year postpartum respectively. No significant association was found between UI at late pregnancy and urethral descent assessed clinically or by ultrasound. The only risk factor for UI at 2 months postpartum was UI at inclusion (OR 6.27 [95 % CI 2.70–14.6]). The risk factors for UI at 1 year postpartum were UI at inclusion (6.14 [2.22–16.9]), body mass index (BMI), and urethral descent at inclusion, assessed clinically (7.21 [2.20–23.7]) or by ultrasound. The mode of delivery was not associated with urethral descent.

Conclusions

Prenatal urethral descent and UI during pregnancy are risk factors for UI at 1 year postpartum. These results indicate that postnatal UI is more strongly influenced by susceptibility factors existing before first delivery than by the mode of delivery.

     

Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies

We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler's encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C'-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.     

Kickstand rods and correction of coronal malalignment in patients with adult spinal deformity

Purpose

Coronal malalignment (CM) is a challenging spinal deformity to treat. The kickstand rod (KR) technique is powerful for correcting truncal shift. This study tested the hypothesis that the KR technique provides superior coronal alignment correction in adult deformity compared with traditional rod techniques.

Methods

A retrospective evaluation of a prospectively collected multicenter database was performed. A 2:1 matched cohort of non-KR accessory rod and KR patients was planned based on preoperative coronal balance distance (CBD) and a vector of global shift. Patients were subgrouped according to CM classification with a 30-mm CBD threshold defining CM, and comparisons of surgical and clinical outcomes among groups was performed.

Results

Twenty-one patients with preoperative CM treated with a KR were matched to 36 controls. KR-treated patients had improved CBD compared with controls (18 vs. 35 mm, P < 0.01). The postoperative CBD did not result in clinical differences between groups in patient-reported outcomes (P ≥ 0.09). Eight (38%) of 21 KR patients and 12 (33%) of 36 control patients with preoperative CM had persistent postoperative CM (P = 0.72). CM class did not significantly affect the likelihood of treatment failure (postoperative CBD > 30 mm) in the KR cohort (P = 0.70), the control cohort (P = 0.35), or the overall population (P = 0.31).

Conclusions

Application of the KR technique to coronal spinal deformity in adults allows for successful treatment of CM. Compared to traditional rod techniques, the use of KRs did not improve clinical outcome measures 1 year after spinal deformity surgery but was associated with better postoperative coronal alignment.

     

Trabecular Bone Score (TBS) Predicts Vertebral Fractures in Japanese Women Over 10 Years Independently of Bone Density and Prevalent Vertebral Deformity: The Japanese Population‐Based Osteoporosis (JPOS) Cohort Study

Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow‐up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual‐energy X‐ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey‐Kanis criteria or Genant's grade 2 fracture at follow‐up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/10³ person‐years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings. © 2014 American Society for Bone and Mineral Research.     

Normal serum and lipoprotein-deficient serum give different expressions of excitability, corresponding to different stages of differentiation, in chicken cardiac cells in culture.

Monolayers of cardiac cells from 11-day-old chicken hearts have different properties when maintained in fetal calf serum or in a lipoprotein-deficient serum (LPDS). Cells in fetal calf serum have a resting potential near -60 mV; the rate of rise of the action potential is low (less than 10 V/sec); the action potential and the contraction are essentially unaffected by tetrodotoxin (TTX); and the beating properties are unaffected by muscarinic agents. Cells in LPDS have a resting potential near -75 mV, and a fast rise of the action potential (approximately equal to 100 V/sec) that is drastically decreased by TTX with a parallel abolition of contraction, and the beat is blocked by very low concentrations of muscarinic agonists. Cells that are physiologically fully responsive to TTX and to muscarinic agents have receptors that remain stable 24 hr after protein synthesis is blocked, whereas cells that are physiologically unresponsive to TTX and muscarinic agents have receptors that are rapidly degraded with half-lives between 9 hr (TTX receptor) and 14 hr (muscarinic receptor). Differences in the physiological and biochemical properties are accompanied by changes in the cholesterol contents of the cell membranes. The properties of cardiac cells cultured in normal serum are similar to those found for cells of chicken hearts in the very early embryonic stage, whereas those of cardiac cells cultured in LPDS correspond to the late embryonic stage.     

Münchausen syndrome with forgery on biologic results. A case report

Münchausen syndrome is a disorder defined by the following: acute factitious symptoms leading to inappropriate investigation and therapy, a restless journey from hospital to hospital and autobiographical falsification. We report here a 20-year-old woman who presented at our hospital consultation of internal medicine with laboratory-test results suggesting the diagnosis of leukemia. A new complete blood cells count and a medullogram by sternal puncture did not show any abnormality. Comparative examination of laboratory-test sheets lead to the diagnosis of Münchausen syndrome as some results had been falsified. With unlimited access to information through internet and word or image processing softwares, laboratory results have become easy to falsify nowadays, particularly for patients with Münchausen syndrome, who may then be quite difficult to diagnose accurately in the context of medical consultation.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.