Radiological and clinical outcome of selective thoracic fusion for patients with Lenke 1C and 2C adolescent idiopathic scoliosis with a minimum follow-up of 2 years

Background Context

In Lenke 1C and 2C curves, the choice between selective thoracic fusion (STF) versus non-selective thoracic fusion as the optimal surgical treatment is controversial.

Amikacin population pharmacokinetics among paediatric burn patients

Introduction

The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.

Methods

Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10–20 mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.

Results

The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean C_max was 33.2 ± 9.4 μg/mL and the mean C_min was 3.8 ± 4.6 μg/mL. The final covariate model estimated clearance as 5.98 L/h/70 kg (4.97–6.99, 95% CI), the volume of distribution in the central compartment as 16.7 L/70 kg (14.0–19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1 L/70 kg (15.0–80.4, 95% CI), and the inter-compartmental clearance as 3.38 L/h/70 kg (2.44–4.32, 95% CI). In multivariate analyses, current weight (P < 0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.

Discussion

Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.     

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.     

Microstructural white matter changes in carriers of the DYT1 gene mutation

We tested the hypothesis that the DYT1 genotype is associated with a disorder of anatomical connectivity involving primarily the sensorimotor cortex. We used diffusion tensor magnetic resonance imaging (DTI) to assess the microstructure of white matter pathways in mutation carriers and control subjects. Fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of DYT1 carriers. Abnormal anatomical connectivity of the supplementary motor area may contribute to the susceptibility of DYT1 carriers to develop clinical manifestations of dystonia.     

Brain dynamics of post‐task resting state are influenced by expertise: Insights from baseball players

Post‐task resting state dynamics can be viewed as a task‐driven state where behavioral performance is improved through endogenous, non‐explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post‐task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division‐1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No‐Go task before a resting state scan, and we compared post‐task resting state connectivity using a seed‐based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post‐task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA–L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD‐alpha oscillation correlations between groups suggests variability in modulatory attention in the post‐task state, and (3) group differences between BOLD‐beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post‐task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454–4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

An MDM2 antagonist (MI-319) restores p53 functions and increases the life span of orally treated follicular lymphoma bearing animals

Background  

MI-319 is a synthetic small molecule designed to target the MDM2-P53 interaction. It is closely related to MDM2 antagonists MI-219 and Nutlin-3 in terms of the expected working mechanisms. The purpose of this study was to evaluate anti-lymphoma activity of MI-319 in WSU-FSCCL, a B-cell follicular lymphoma line. For comparison purpose, MI-319, MI-219 and Nutlin-3 were assessed side by side against FSCCL and three other B-cell hematological tumor cell lines in growth inhibition and gene expression profiling experiments.     

糖稳态调节细胞定向分化的基因改造方案探讨

目的:探索糖稳态调节细胞定向分化的基因改造方案思路.方法:①研究构建的解除干细胞分化抑制状态的信号传导与转录激活因子-3(STAT-3)基因载体,检测其介导目的基因感染ARIP等细胞基因表达;②研究构建的活化配体DL诱导N信号、在"旁侧抑制"过程中扮演重要角色的Kuzbanian(KUZ)基因载体在转基因小鼠表达后糖稳态调节细胞的分化.结果:在完成的STAT-3腺病毒基因载体生产了腺病毒,用带有目的基因的腺病毒对ARIP靶细胞进行感染,3 d后,荧光显微镜观察时,活细胞、固定液固定细胞均看到了构建基因中绿色荧光蛋白成功、高效的阳性表达报告.在完成的Kuzbanian(KUZ)基因载体构建、转基因、动物模型、小鼠品系鉴定后,用非放射性原位杂交实验对胰腺靶细胞的mRNA进行检测,获得了预期的阳性结果.结论:通过用某些分化抑制性基因的显性失活形式(DN)竞争性预先解除干细胞分化的抑制状态,然后再定向分化诱导使之朝向期望的目标细胞方向分化,可能是糖稳态细胞定向分化的可行途径之一.     

Modeling the effect of progressive endotracheal tube occlusion on tidal volume in pressure-control mode

A recognized hazard of prolonged endotracheal intubation is progressive airway occlusion resulting from deposition of secretions on the inner surface of the endotracheal tube (ETT). When volume-controlled ventilation is used, progressive ETT occlusion may be detected by monitoring the difference between peak and plateau airway pressures. In pressure-controlled modes, however, inspiratory airway pressures are preset and thus cannot act as a warning indicator. Instead, changes in delivered tidal volumes may aid the diagnosis of ETT occlusion. To determine whether tidal volume monitoring effectively detects progressive ETT occlusion, we mathematically modeled the response of a ventilator operating in pressure-controlled mode to increasing airway resistance. To corroborate our model, we then bench-tested the Siemens 300 and Puritan-Bennett 7200 ventilators by using a test lung and a series of ETTs ranging in size from 9.0 to 3.5 mm inner diameter to simulate progressive occlusion. We found that when pressure-controlled mode was used, progressive ETT occlusion did not reduce delivered tidal volumes until occlusion was nearly complete. We conclude that prolonged use of pressure-controlled mode may allow significant ETT obstruction to build up undetected, risking complete ETT occlusion and complicating the perioperative care of patients ventilated with this mode. IMPLICATIONS: Although increasing airway pressures during volume-controlled ventilation allow early recognition of endotracheal tube (ETT) obstruction, airway pressures with pressure-controlled ventilation are fixed. We found during tests of two intensive care unit ventilators that although ETT obstruction reduces delivered tidal volumes during pressure-controlled ventilation, reductions do not occur until occlusion is advanced.