Clinically Relevant Laboratory Monitoring of Gender-Affirming Hormone Therapy in Transgender People-Experiences from a Teaching Hospital in the Netherlands.

Background: Transgender care is shifting from academic to nonacademic settings leading to use of common (immunoassay) compared to sophisticated (mass spectrometry) methods to monitor estradiol and testosterone during gender-affirming hormone therapy (GAHT). The type of assay can influence results and have significant implications for clinical decision making. An evidence gap is present in recommendations regarding the assay needed to monitor GAHT.

The alternative Thomas-plot: A new tool for effective anemia diagnostics.

Introduction: The Thomas-plot has proven to be a helpful tool to discriminate between different types of anemia. This plot combines the reticulocyte hemoglobin content (Ret-He) with the soluble transferrin receptor (sTfR)/log ferritin (fer) ratio. In this study, we designed an alternative Thomas-plot in which Ret-He is combined with the transferrin (Tf)/log ferritin ratio.

Assessment of Comorbidity in Bariatric Patients through a Biomarker-Based Model-A Multicenter Validation of the Metabolic Health Index.

Background: The metabolic health index (MHI) is a biomarker-based model that objectively assesses the cumulative impact of comorbidities type 2 diabetes mellitus, hypertension and dyslipidemia on the health state of bariatric patients. The MHI was developed on a single-center cohort using a fully laboratory data-driven approach, resulting in a MHI score on a range from 1 to 6. To show universal applicability in clinical care, the MHI was validated externally and potential laboratory-related shortcomings were evaluated.

Cardiovascular Biomarker Profiles in Obesity and Relation to Normalization of Subclinical Cardiac Dysfunction after Bariatric Surgery.

Aims: We aimed to gain insight into the underlying pathophysiology of cardiac dysfunction in obesity patients and the improvement of cardiac function after weight loss.

Methods: This is a longitudinal study in which 92 cardiovascular biomarkers were measured by multiplex immunoassays in obesity patients without known cardiovascular disease, before and one year after bariatric surgery.

Results: Out of 100 eligible patients, 72 patients completed the follow-up.

Biomarker profiles in obesity patients and their relation to cardiac dysfunction.

Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient. Several biomarkers reflecting biological processes that may play a role in the occurrence of cardiac dysfunction in obesity patients are available. To compare cardiovascular biomarker profiles between obesity patients and nonobese controls, and between obesity patients with and without cardiac dysfunction, in order to better understand the underlying pathophysiology of cardiac dysfunction in obesity patients.

Analyses of abdominal adiposity and metabolic syndrome as risk factors for respiratory distress in COVID-19.

Background: Several characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19.

Subclinical cardiac dysfunction in obesity patients is linked to autonomic dysfunction: findings from the CARDIOBESE study.

Aims: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology.

A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus.

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear.

Effect of Vitamin D on the Postprandial Lipid Profile in Obese Patients: A Non-Targeted Lipidomics Study.

: Postprandial lipemia can lead to an accumulation of atherogenic lipoproteins in the circulation associated with systemic low-grade inflammation and an increased risk of cardiovascular disease. Lifestyle and pharmacological treatments are usually prescribed for prevention. Vitamin D (cholecalciferol), as an anti-atherogenic agent, is being taken into consideration due to its potential beneficial effects in lipid metabolism and its anti-inflammatory potency.

Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of Cancer Immunotherapies.

Cellular immunotherapy targeting human tumor antigens is a promising strategy to treat solid tumors. Yet clinical results of cellular immunotherapy are disappointing. Moreover, the currently available in vitro human tumor models are not designed to study the optimization of T-cell therapies of solid tumors.

Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy.

The transfer of T cell receptor (TCR) genes can be used to induce immune reactivity toward defined antigens to which endogenous T cells are insufficiently reactive. This approach, which is called TCR gene therapy, is being developed to target tumors and pathogens, and its clinical testing has commenced in patients with cancer. In this study we show that lethal cytokine-driven autoimmune pathology can occur in mouse models of TCR gene therapy under conditions that closely mimic the clinical setting.

TCR gene-engineered T cell: limited T cell activation and combined use of IL-15 and IL-21 ensure minimal differentiation and maximal antigen-specificity.

Clinical TCR gene therapy of melanoma represents a feasible and promising treatment rationale yet is currently challenged by objective response rates that stay behind those observed with conventional adoptive T cell therapy. Here, the phenotype and function of TCR-transduced T cells, considered to determine the efficacy of TCR gene therapy, were studied in relation to T cell activation and cytokine treatments. We observed that the lectin Concanavalin A (ConA), and to a lesser extent anti-CD3 and CD28 mAbs (soluble CD3/CD28), resulted in functional surface expression of the TCRalphabeta transgenes and enhanced fractions of CD62L(hi), CD44(lo) naive T cells.

Combination of IL-21 and IL-15 enhances tumour-specific cytotoxicity and cytokine production of TCR-transduced primary T cells.

IL-21, and to a lesser extent IL-15, inhibits differentiation of antigen-primed CD8 T cells and promotes their homeostasis and anti-tumour activity. Here, we investigated molecular mechanisms behind tumour-specific responses of primary murine T lymphocytes engineered to express a TCR directed against human gp100/HLA-A2 following short-term exposure to IL-15 and/or IL-21. We demonstrated that IL-15 + IL-21, and to a lesser extent IL-21, enhanced antigen-specific T-cell cytotoxicity, which was related to enhanced expression of granzymes A and B, and perforin 1.

Gene transfer of human TCR in primary murine T cells is improved by pseudo-typing with amphotropic and ecotropic envelopes.

Background: T cell receptor (TCR) gene therapy represents an attractive anti-cancer treatment but requires further optimization of its efficacy and safety in clinically relevant models, such as those using a tumor antigen and TCR of human origin. Currently, however, there is no consensus as to what protocol is most optimal for retroviral human TCR gene transfer into primary murine T cells, most notably with respect to virus pseudo-type.

Methods: Primary murine T cells were transduced, expanded and subsequently tested for transgene expression, proliferation and antigen-specific function.