Adoptive Transfer and Bone Marrow Chimera Models to Analyze Treg Function and Differentiation.

Cellular adoptive transfer and mixed bone marrow chimera are cornerstone experimental tools for immuno-biology. Here we describe protocols for adoptive transfer and bone marrow chimera to address the effect of a specific mutation on T regulatory cell (Treg) function and differentiation, respectively. Treg function can be quantitatively measured by analyzing the expansion of conventional CD4 T cells and their differentiation into helper cells. The quantitative measure of Treg differentiation is addressed by analyzing the number and phenotype of Foxp3-expressing cells. The use of congenic markers is instrumental for these approaches.

Planning a Collection of Virtual Patients to Train Clinical Reasoning: A Blueprint Representative of the European Population.

BACKGROUND: Virtual patients (VPs) are a suitable method for students to train their clinical reasoning abilities. We describe a process of developing a blueprint for a diverse and realistic VP collection (prior to VP creation) that facilitates deliberate practice of clinical reasoning and meets educational requirements of medical schools. METHODS: An international and interdisciplinary partnership of five European countries developed a blueprint for a collection of 200 VPs in four steps: (1) Defining the criteria (e.g., key symptoms, age, sex) and categorizing them into disease-, patient-, encounter- and learner-related, (2) Identifying data sources for assessing the representativeness of the collection, (3) Populating the blueprint, and (4) Refining and reaching consensus. RESULTS: The blueprint is publicly available and covers 29 key symptoms and 176 final diagnoses including the most prevalent medical conditions in Europe. Moreover, our analyses showed that the blueprint appears to be representative of the European population. CONCLUSIONS: The development of the blueprint required a stepwise approach, which can be replicated for the creation of other VP or case collections. We consider the blueprint an appropriate starting point for the actual creation of the VPs, but constant updating and refining is needed.

Increased short-term risk of cardiovascular events in inflammatory rheumatic diseases: results from a population-based cohort.

Cardiovascular diseases represent the first cause of death globally. Inflammatory rheumatic disease (IRMD) patients, due to their lifelong inflammatory status, are at increased risk of developing premature cardiovascular disease. We aimed to assess the risk for cardiovascular events (CVE) in a population-based study. We followed 10,153 adults from the EpiDoC Cohort, a large Portuguese population-based prospective study (2011-2016). IRMD patients were identified at baseline and followed during 5 years. CVE were defined as a composite of self-reported myocardial infarction or angina pectoris, arrhythmias, valvular disease, stroke or transient ischemic attack and peripheral artery disease. Statistical analysis was performed by utilizing multivariate logistic regression and goodness-of-fit and area under ROC curve. At baseline, IRMD patients had similar age as the non-IRMD participants (mean age 55 vs 53 years-old; 72.1% female); dyslipidaemia and sedentary lifestyle were more common (40.7% vs 31.4%, p = 0.033; 87.3% vs 67%, p = 0.016, respectively). During an average follow-up of 2.6 years, 26 CVE were reported among IRMD patients. IRMD patients had higher odd of CVE (OR 1.64, 95% CI 1.04-2.58; p = 0.03), despite comparable mortality rates (1.7% vs 0.7%, p = 0.806). A stepwise approach attained that gender, age, history of hypertension, body mass index, IRMD and follow-up time are the most important predictive variables of CVE (AUC 0.80). IRMD patients, at community level, have an increased short-term risk of major CVE when compared to non-IRMD, and that highlights the potential benefit of a systematic screening and more aggressive cardiovascular risk assessment and management of these patients.