Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

Utilization and Complications of Central Venous Access Devices in Oncology Patients

Purpose: To describe how central venous access devices (CVADs) are utilized for ambulatory oncology patients and to evaluate the rate of complications. Method: Single institution retrospective study of oncology patients with CVADs who received systemic treatment at the Walker Family Cancer Centre (WFCC) between 1 January and 31 December 2018. Results: A total of 480 CVADS were placed in 305 patients, of which 408 (85%) were peripherally inserted central catheters (PICCs) and 72 (15%) were implanted vascular access devices (PORTs). The incidence of early and late complications was 9% and 24%, respectively. For the entire cohort, the rate of venous thromboembolism (VTE) was 16%, of which 9% were CVAD-related thrombosis (CRTs) and 7% were distant VTE. The CRT rates were similar for PICCs and PORTs (9% vs. 7%). A total of 6% of CVADs were complicated by infection (i.e., localized infections and bacteremia), with a total infection rate of 0.43 and 0.26 per 1000 indwelling days for PICCs and PORTs, respectively. The incidence of central line associated bloodstream infections (CLABSI) was greater for PICCs than PORTs, at a rate of 0.22 compared with 0.08 per 1000 indwelling days, respectively. The premature catheter removal rate was 26% for PICCs and 18% for PORTs. PORTs required more additional hospital visits. Conclusions: PICCs were utilized more frequently than PORTs and had a higher rate of premature removal. The rates of VTE and CRT were similar for both CVAD types. PORTs had a lower rate of infection per 1000 indwelling days. However, the management of PORT related complications required more visits to the hospital and oncology clinic.     

Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

非那雄胺在慢性中心性浆液性脉络膜视网膜病变患者中的应用

目的评估非那雄胺治疗慢性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的有效性及安全性。方法选取2017年3月至2019年6月在本院确诊的慢性CSC患者31例40眼,采用单臂试验对患者进行非那雄胺治疗。使用非那雄胺治疗后6个月,对患者的视网膜神经上皮层(retinal neuroepithelial layer,RNL)下积液状况,ETDRS视力以及黄斑中心凹视网膜厚度(central foveal thickness,CFT)进行检查。结果非那雄胺治疗后1个月,有10眼(25.0%)RNL下积液完全消退。持续治疗2个月、3个月、4个月、5个月、6个月,分别有7眼(17.5%)、6眼(15.0%)、7眼(17.5%)、3眼(7.5%)及3眼(7.5%)RNL下积液消退,仅有4眼(10.0%)在治疗后6个月RNL下积液仍存在。患眼EDTRS视力非那雄胺治疗后1个月为(50.00±16.11)个字母,与治疗前(46.16±16.67)个字母差异无统计学意义(P=0.2213);治疗后2个月(53.39±14.67)个字母,较治疗前显著升高(P=0.0003);治疗后3个月、4个月、5个月、6个月,分别为(57.39±12.76)个字母、(58.52±12.39)个字母、(59.13±10.76)个字母及(60.42±10.96)个字母,与治疗前相比差异均有统计学意义(均为P<0.0001)。而患眼CFT自治疗后1个月、2个月、3个月、4个月、5个月、6个月分别为(274.10±22.74)μm、(273.00±17.22)μm、(263.50±12.81)μm、(263.90±10.62)μm、(259.70±12.48)μm及(252.60±11.00)μm,与治疗前(296.60±35.41)μm相比,差异均有统计学意义(均为P<0.05)。所有患者均无服药后身体不适或并发症发生。结论非那雄胺对于慢性CSC的治疗安全且有效,有望成为慢性CSC的治疗选择。     

Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

A peripherally inserted central catheter misplacement into lateral thoracic vein: A case report

IntroductionCentral venous catheter applications and complications are closely related to the tip position. Previous studies have reported some rare cases of catheter misplacement. Here, we report a case of misplacement of a peripherally inserted central catheter into the lateral thoracic vein.Case reportA 56-year-old cancer patient underwent placement of a peripherally inserted central catheter through the left basilic vein under ultrasound-guided puncture. The catheterisation procedure was uneventful, so the catheter was believed to be in the superior vena cava. However, the post-anterior chest X-ray image revealed that after the catheter advanced towards the axilla, it turned downwards and outwards in the direction of the left lateral thoracic region, with the projection of the catheter tip giving the appearance of termination in the subcutaneous tissue of the lateral thoracic wall on the two-dimensional image. The catheter was then repositioned in the distal superior vena cava.DiscussionPeripherally inserted central catheters can be potentially misplaced into the lateral thoracic vein because these catheters can pass through the orifice of the lateral thoracic vein which flows into the axillary vein. Some pathological cases and clinical conditions can cause dilatation of the lateral thoracic vein, which increases the probability of catheter misplacement. Three principles were proposed to avoid this rare complication: a comprehensive review of the patients’ medical history, real-time image-guided catheterisation and routine radiographic identification of the tip position.     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.