The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach

Background and objectives: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphomas, characterized by mature, skin-tropic CD4+ T-helper cells. In order to study the immune tumor microenvironment in MF patients, we performed immunohistochemical stains on MF biopsies, digitized whole-slide tissue sections, and performed quantitative analysis of the different immune cell subsets to correlate tissue parameters with the clinical data of patients, such as progression-free survival or overall survival. Patients and methods: Overall, 35 patients who were treated between 2009 and 2019 and for whom one or more paraffin tissue blocks were available have been included in the present study (58 tissue specimens in total). Conventional immunohistochemistry stains for CD3, CD4, CD8, CD20 and CD30 were used for the analysis of the immune phenotype, and quantitative analysis was performed using QuPath as a quantitative digital pathology tool for bioimage analysis of whole slides. Results: Analysis of tissue parameters for prognostic significance revealed that patients with a stronger infiltration by CD8+ lymphocytes within the tumor cell compartment had a higher risk of disease progression (p = 0.031) and showed a shorter progress-free survival (p = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression (p = 0.023) and progression-free survival (p = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression (p = 0.015) and a shorter progression-free survival (p = 0.032) for older patients (>61 years) were observed. Conclusions: Our results demonstrated the prognostic relevance of large-cell transformation in mycosis fungoides and its strong association with the presence of CD30+ lymphocytes. Unlike previous reports, our study suggests an adverse prognostic role for CD8+ T cells in patients with mycosis fungoides. Moreover, our data indicate that the immune phenotype within the tumor microenvironment shows strong temporal heterogeneity and is altered in the course of tumor progression

The influence of micronutrients on oral and general health

<p>Abstract</p> <p>Objective</p> <p>The aim of the present clinical pilot study was to examine the influence of a combination of micronutrients on individuals with high stress experience.</p> <p>Methods</p> <p>40 healthy students (28 female, 12 male) with a mean age of 27.1 ± 3.0 years, experiencing high examination stress, were chosen. After approval of the ethics commission, one group of students (n = 19) took a combination of micronutrients (Orthomol vital m/f) for three months, whereas other students (n = 21) served as control group. All participants underwent at the beginning and at the end of the trial a dental examination, a determination of 10 periodontal pathogens, a salivary and a blood analysis. In addition, the participants filled in a questionnaire on nutrition, quality of life and degree of stress experienced during their final examinations.</p> <p>Results</p> <p>The evaluation of the results, obtained at the end of the trial period, showed that for all students a slight worsening of oral hygiene and an increased consumption of unhealthy food could be observed. The intake of the micronutrients led to a slight improvement of the degree of gingival inflammation in comparison to the control group. The blood analysis showed an increase in vitamin (vitamin C, vitamin E) and zinc concentrations, and a lower increase in CRP. In the male subjects, a decrease in the serum concentrations of triglycerides (p = 0.073) and LDL (p = 0.048) was observed.</p> <p>Conclusions</p> <p>This pilot study shows that micronutrients, taken during periods of high stress experience, had a beneficial effect on inflammatory processes and helped reduce the level of some of the plasma lipids in males, and thus can be recommended for supplementing the diet. However, additional studies with a higher number of subjects, also suffering from periodontal disease, are necessary to show the effect of a micronutrient supplementation more clearly.</p

A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study

Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions