Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Summary

Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

Introduction

Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.

Methods

VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.

Results

Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), ?0.5?±?1.1; p?=?0.001) and at 3 months (?0.6?±?1.1; p?<?0.001), but not at 6 months (?0.3?±?1.3; p?=?0.066) or 12 months (?0.3?±?1.2; p?=?0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p?=?0.003). A subgroup (N?=?16; 25 %) had LS BMD Z-scores that were ≤?1.0 at 12 months. In these children, each additional 1,000 mg/m² of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, ?0.71 to ?0.07; p?=?0.017).

Conclusions

The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤?1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.     

Trunk exercise training improves muscle size,strength, and function in older adults: A randomized controlled trial

The aim of this study was to assess the effectiveness of a multimodal exercise program to increase trunk muscle morphology and strength in older individuals, and their associated changes in functional ability. Using a single‐blinded parallel‐group randomized controlled trial design, 64 older adults (≥60 years) were randomly allocated to a 12‐week exercise program comprising walking and balance exercises with or without trunk strengthening/motor control exercises; followed by a 6‐week walking‐only program (detraining; 32 per group). Trunk muscle morphology (ultrasound imaging), strength (isokinetic dynamometer), and functional ability and balance (6‐Minute Walk Test; 30 second Chair Stand Test; Sitting and Rising Test; Berg Balance Scale, Multi‐Directional Reach Test; Timed Up and Go; Four Step Square Test) were the primary outcome measures. Sixty‐four older adults (mean [SD]; age: 69.8 [7.5] years; 59.4% female) were randomized into two exercise groups. Trunk training relative to walking‐balance training increased (mean difference [95% CI]) the size of the rectus abdominis (2.08 [1.29, 2.89] cm²), lumbar multifidus (L4/L5:0.39 [0.16, 0.61] cm; L5/S1:0.31 [0.07, 0.55] cm), and the lateral abdominal musculature (0.63 [0.40, 0.85] cm); and increased trunk flexion (29.8 [4.40, 55.31] N), extension (37.71 [15.17, 60.25] N), and lateral flexion (52.30 [36.57, 68.02] N) strength. Trunk training relative to walking‐balance training improved 30‐second Chair Stand Test (5.90 [3.39, 8.42] repetitions), Sitting and Rising Test (1.23 [0.24, 2.23] points), Forward Reach Test (4.20 [1.89, 6.51] cm), Backward Reach Test (2.42 [0.33, 4.52] cm), and Timed Up and Go Test (?0.76 [?1.40, ?0.13] seconds). Detraining led to some declines but all outcomes remained significantly improved when compared to pre‐training. These findings support the inclusion of trunk strengthening/motor control exercises as part of a multimodal exercise program for older adults.     

Virtual Reality Exposure Therapy for PTSD Vietnam Veterans: A Case Study

Virtual reality (VR) integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment that changes in a natural way with head and body motion. VR exposure (VRE) is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with posttraumatic stress disorder (PTSD). This report presents the results of the first Vietnam combat veteran with PTSD to have been treated with VRE. The patient was exposed to two virtual environments, a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by jungle. The patient experienced a 34% decrease on clinician-rated PTSD and a 45% decrease on self-rated PTSD. Treatment gains were maintained at 6-month follow-up.     

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

Objective

To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer.

Methods and materials

Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (_maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADC_mean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS.

Results

Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADC_mean, SUV_max, MTV and TLG according to FIGO stage (p < 0.001–0.025). There were significant correlations between ADC_mean, MTV, TLG and LN metastasis (p = 0.017–0.032). SUV_max was not associated with LN metastasis. FIGO stage (p = 0.017/0.033), LN metastases (p = 0.001/0.020), ADC_mean (p = 0.007/0.020) and MTV (p = 0.014/0.026) were adverse predictors of both DFS/OS. _maxTD (p = 0.005) and TLG (p = 0.024) were adverse predictors of DFS. PE and SUV_max did not correlate with DFS or OS (p = 0.18–0.72).

Conclusions

Quantitative parameters derived from pre-treatment DW-MRI (ADC_mean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.     

Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing

Nuclear inclusions formed by proteins with expanded polyglutamine tracts are found in several neurodegenerative diseases. The effect of nuclear inclusions formed by these disease proteins on the functional organization of the nucleus is only partially understood. In particular, it is not known whether polyglutamine disease proteins disrupt the function of Cajal bodies, which are subnuclear domains that play a role in the biogenesis of small nuclear ribonucleoproteins (snRNPs). snRNPs are an integral part of the pre-mRNA splicing machinery, so it is possible that mutant proteins that alter Cajal body activity indirectly affect pre-mRNA splicing. Here, we evaluate three different polyglutamine disease proteins--ataxin-1, ataxin-3, and huntingtin--for their ability to disrupt Cajal body localization and reduce the splicing of an artificial reporter in HeLa cells. Consistent with previous observations, ataxin-1 inclusions do not drastically alter the localization of Cajal bodies. In contrast, ataxin-3 inclusions associate with this structure. Inclusions formed by a fragment of the huntingtin protein do not associate with Cajal bodies or PML bodies, another subnuclear domain. Among the three disease proteins, only ataxin-3 significantly decreases the splicing of an artificial reporter. These results support the hypothesis that different mutant proteins vary in their ability to disrupt nuclear organization and function.     

Caudal-posteroanterior view in coronary arteriography

Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography.