Histopathology of thymectomy specimens from the MGTX-trial: Entropy analysis as strategy to quantify spatial heterogeneity of lymphoid follicle and fat distribution.

The thymectomy specimens from the "thymectomy trial in non-thymomatous myasthenia gravis patients receiving prednisone therapy" (MGTX) underwent rigid and comprehensive work-up, which permits analysis of the spatial distribution of histological and immunohistological features. This analysis revealed strong intra- and inter-case variability. While many histological features (e.g. median percent fat content among different specimens) can easily be correlated with clinical parameters, intra-case spatial variability of histological features has yet defied quantification and statistical evaluation. To overcome this gap in digital pathology, we here propose intra-case entropy of measured histological features in all available slides of a given thymectomy specimen as a quantitative marker of spatial histological heterogeneity. Calculation of entropy led to one value per specimen and histological feature. Through these 'entropy values' the so far neglected degree of spatial histological heterogeneity could be fed into statistical analyses, extending the scope of clinico-pathological correlations.

DuraGraft vascular conduit preservation solution in patients undergoing coronary artery bypass grafting: rationale and design of a within-patient randomised multicentre trial.

Introduction: Saphenous vein grafts (SVGs) remain the most often used conduits in coronary artery bypass grafting (CABG). However, they are prone to vein graft disease (VGD) during follow-up, which may compromise clinical outcomes. Injury to the SVG endothelium during harvesting and storage promotes neointimal hyperplasia that can advance to atherosclerosis characterised by SVG failure. This trial investigates the potential benefit of DuraGraft, a novel, one-time intraoperative graft treatment developed to efficiently protect the structural and functional integrity of the vascular endothelium, on the development and progression of VGD in CABG patients. Methods and analysis: This ongoing prospective randomised, double-blinded multicentre trial (NCT02272582/NCT02774824) includes patients undergoing isolated CABG requiring at least two SVGs. It compares the impact of DuraGraft, a novel treatment against VGD versus the standard-of-care (SOC; heparinised saline) using a within-patient randomisation (with one SVG treated with DuraGraft and the other treated with SOC). Besides clinical assessments, patients undergo longitudinal 64-slice or better multidetector CT (MDCT) angiography of paired grafts (within each patient) at 4-6 weeks, 3 months and 12 months. Primary endpoints will be the magnitude of change in mean wall thickness and lumen diameter (stenosis) of paired grafts, at 3 and 12 months, respectively. Besides the evaluation of overall safety, longitudinal assessment of each graft (secondary endpoint) is performed in order to obtain insight into graft behaviour after CABG. Enrolment of 119 patients was successfully completed, and analysis of MDCT angiography follow-up is ongoing with the completed analysis becoming available by end of first quarter of 2018. Ethics and dissemination: The regional ethics committees have approved the trial. Results will be submitted for publication. Clinical trial identifier: NCT02272582 and NCT02774824.

Bifactor structure of clinical disability in relapsing multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) can affect virtually every neurological function which complicates the conceptualization and assessment of disability. Similar challenges are encountered in other medical fields including child cognitive development and psychiatry, for instance. In these disciplines progress in diagnosis and outcome measurement has been recently achieved by capitalizing on the concept of bifactor model. OBJECTIVE: To present in accessible terms an application of bifactor confirmatory factor analysis to study the clinical disability outcomes in MS. METHODS: Data included 480 assessments on 301 patients with relapsing-remitting MS who participated in the North American interferon beta-1a clinical trial (Avonex). Measures consisted of the Expanded Disability Status Scale (EDSS), the three components of the Multiple Sclerosis Functional Composite (MSFC), and five other clinical measures of neurological functions. We determined which of three confirmatory factor analysis models (unidimensional, multidimensional, and bifactor) best described the structure of the data. RESULTS: EDSS scores ranged from 0 to 8 (94% between 0 and 4). The final bifactor model fitted the data well, explained 59.4% of total variance, and provided the most useful representation of the data. In this model, the nine measures defined a scoring dimension of global neurological function (63.1% of total composite score variance) and two auxiliary dimensions of extra variability in leg and cognitive function (17.1% and 9% of total composite score variance). CONCLUSION: Bifactor modeling is a promising approach to further understanding of the structure of disability in MS and for refining composite measures of global disability.