Maastricht University

About: Maastricht University is a education organization based out in Maastricht, Limburg, Netherlands. It is known for research contribution in the topics: Population & Health care. The organization has 19263 authors who have published 53291 publications receiving 2266866 citations. The organization is also known as: Universiteit Maastricht & UM.

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Abstract: Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Chronic obstructive pulmonary disease phenotypes: the future of COPD.

Abstract: Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.

C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction

Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P = 20%) (P = 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma.

Abstract: Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands ljschouten@epidunimaasnl BACKGROUND: The objective of this study was to report on the incidence of and factors related to the occurrence of central nervous system metastases in a cohort of patients who were diagnosed with colorectal, lung, breast, or kidney carcinoma or melanoma METHODS: Using the population-based Maastricht Cancer Registry (MCR), a cohort was created of patients with colorectal carcinoma (n = 720 patients), lung carcinoma (n = 938 patients), breast carcinoma (n = 802 patients), renal carcinoma (n = 114 patients), and melanoma (n = 150 patients) The patients had to live in the catchment area of the University Hospital Maastricht (UHM) and had to have been diagnosed at the UHM during the period 1986-1995 Patients with brain metastases were searched for by linking the MCR to the Neuro-Oncology Registry of the UHM Radiology files were checked as well Follow-up lasted until December 31, 1998 RESULTS: Brain metastases were diagnosed in 232 patients (85%) in the cohort (n = 2724 patients) Of these patients, 84 patients were diagnosed with brain metastases within 1 month after their primary diagnosis, 82 patients were diagnosed with brain metastases within 1 year of their primary diagnosis, and 66 patients were diagnosed with brain metastases more than 1 year after their primary diagnosis The cumulative incidence after 5 years was estimated at 163% in patients with lung carcinoma, 98% in patients with renal carcinoma, 74% in patients with melanoma, 50% in patients with breast carcinoma, and 12% in patients with colorectal carcinoma The incidence was lower in patients age > or = 70 years compared with younger patients (breast and lung carcinoma), lower in patients who were diagnosed before 1991 compared with patients who were diagnosed after 1991 (breast and lung carcinoma), and lower in patients who had nonsmall cell lung carcinoma compared with patients who had small cell lung carcinoma CONCLUSIONS: The frequency of brain metastases in this cohort was highest in patients with lung carcinoma, followed by patients with renal carcinoma There was no evidence of an increasing incidence of brain metastasis in patients with carcinoma of the breast or lung

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease

Abstract: There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.