Thrombomodulin as a regulator of the anticoagulant pathway: implication in the development of thrombosis

Thrombomodulin is a cell surface-expressed glycoprotein that serves as a cofactor for thrombin-mediated activation of protein C (PC), an event further amplified by the endothelial cell PC receptor. The PC pathway is a major anticoagulant mechanism that downregulates thrombin formation and hedges thrombus formation. The objectives of this review were to review recent findings regarding thrombomodulin structure, its involvement in the regulation of hemostasis and further discuss the implication, if any, of the genetic polymorphisms in the thrombomodulin gene in the risk of development of thrombosis. We performed a literature search by using electronic bibliographic databases. Although the direct evaluation of risk situations associated with thrombomodulin mutations/polymorphisms could be of clinical significance, it appears that mutations that affect the function of thrombomodulin are rarely associated with venous thromboembolism. However, several polymorphisms are reported to be associated with increased risk for arterial thrombosis. Additionally studies on knock out mice as well studies on humans bearing rare mutations suggest that thrombomodulin dysfunction may be implicated in the pathogenesis of myocardial infraction.     

Single-catheter radiofrequency ablation of a permanent junctional reciprocating tachycardia in a premature neonate

A 34-week premature neonate presented with drug-refractory permanent junctional incessant tachycardia and haemodynamic compromise. The patient underwent successful radiofrequency catheter ablation using a single-catheter approach. The child remains in sinus rhythm, without pharmacological treatment, 2 years after the procedure.     

Determinants of change in self-rated health among older adults in Europe: a longitudinal perspective based on SHARE data

The present study aims at detecting factors which may predict a decline or an improvement in self-rated health (SRH) of older adults (persons aged 50 or higher) among socio-demographic characteristics, physical and mental health indicators and risky health behaviours. In the analysis, multinomial logistic regression models are applied to data from waves 1 and 2 of the Survey of Health Ageing and Retirement in Europe (carried out about 3 years apart); persons who report a decline or an improvement in SRH at wave 2 are compared to those who report no change while controlling for SRH at baseline and country of residence. The analysis was carried out for the whole sample and two subgroups, persons aged 50–64 and 65 or higher. The results indicate that female sex and higher educational attainment have a strong protective effect against decline in SRH. Worse health at baseline is an important predictor of subsequent decline but changes occurring between the waves have a more pronounced effect, implying that SRH is influenced more by recent developments. The findings also indicate that improvement in SRH is a more complex concept than decline and is strongly affected by factors other than health. Among behavioural risk factors, low levels of physical activity and a decrease in the levels of activity between the waves are significantly related to decline while frequent drinking seems associated with improvement. Differentiations by age are modest and probably suggest that advancing age is related to a milder view of one’s health.     

Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.     

Waterproof cast liners in paediatric forearm fractures: a randomized trial

Purpose

Waterproof casts have been shown to provide adequate support and immobilization in fractures. This study evaluated two waterproof cast liners, namely, Wet or Dry^® and Delta Dry^®, in terms of ease of application/removal, durability, longevity, and patient satisfaction using patient- and technician-reported outcome measures.

Methods

A total of 105 children were enrolled in a randomized trial and received a below-elbow synthetic cast with either of the two cast liners.

Results

The two groups were comparable with regards to age, gender, side of cast, and hand dominance. Assessment was carried out at application and removal. In the patient-reported outcomes, the Wet or Dry^® group was rated significantly better in the odor and water resistance categories. In the technician-reported application and removal outcome measures, the Delta Dry^® group was rated significantly higher.

Conclusions

The use of waterproof cast liners appears to be safe in children with forearm fractures, with some differences in outcome between the two products trialed.     

Executive functions in borderline personality disorder

Different domains of executive function such as working memory and response inhibition were investigated together with elementary cognitive processes in borderline personality disorder (BPD). Patients with BPD (N=28) were compared to nonpatient controls (NP, N=28) on eight tasks (e.g. n-back, Go/NoGo, CPT-AX). In order to separate impairments in different cognitive domains and to assess the influence of more elementary cognitive processes on executive functioning, tasks were embedded in a reaction-time-decomposition approach. BPD patients solved tasks with accuracies comparable to those of nonpatients. The only exception was the n-back task, for which working memory is required: here, error rates were higher and increased more prominently in BPD patients depending on working memory load. In most tasks, movement times were shorter for BPD patients than for nonpatients, while the quality of task-solving was comparable. The faster processing in the BPD group was observable starting with the simplest task, i.e. a simple reaction-time task. These findings suggest that domains of executive functioning are differentially affected in BPD. In contrast to load-dependent deficits in working memory, response inhibition processes were unimpaired. Faster action-related processes could be observed in BPD patients in a variety of tasks; however, these did not influence executive functioning.