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Possibilities for personalised medicine in rheumatoid arthritis: Hype or hope
No full textKnowledge of pathophysiology of rheumatoid arthritis (RA) has improved over the past decades, which resulted in new treatment options and strategies that led to better clinical outcomes. At the same time, we have come to understand that RA is a heterogeneous disease on a clinical as well as a pathophysiological level. Despite this heterogeneity, current management recommendations still adopt a € one-size-fits-all' treatment approach, where ideally individualised treatment, or personalised medicine, is preferred. The first step towards personalised medicine in RA would be to designate different treatment strategies to distinct clinical or molecular phenotypes of patients. This viewpoint discusses current evidence and elaborates on future possibilities for personalised medicine in RA. </p
‘Met alles opnieuw starten’. Een onderzoek naar de werking van het programma van Stichting Nieuw Thuis Rotterdam
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The rise and fall of diseases: reflections on the history of population health in Europe since ca. 1700
Get PDFThis essay explores the amazing phenomenon that in Europe since ca. 1700 most diseases have shown a pattern of 'rise-and-fall'. It argues that the rise of so many diseases indicates that their ultimate cause is not to be sought within the body, but in the interaction between humans and their environment. In their tireless pursuit of a better life, Europeans have constantly engaged in new activities which exposed them to new health risks, at a pace that evolution could not keep up with. Fortunately, most diseases have also declined again, mainly as a result of human interventions, in the form of public health interventions or improvements in medical care. The virtually continuous succession of diseases starting to fall in the 18th, 19th and 20th centuries suggests that the concept of an “epidemiological transition” has limited usefulness
Determinants of educational inequalities in disability-free life expectancy between ages 35 and 80 in Europe
Get PDFSocioeconomic inequalities in disability-free life expectancy (DFLE) exist across all European countries, yet the driving determinants of these differences are not completely known. We calculated the impact on educational inequalities in DFLE of equalizing the distribution of eight risk factors for mortality and disability using register-based mortality data and survey data from 15 European countries for individuals between 35 and 80 years old. From the selected risk factors, the ones that contribute the most to the educational inequalities in DFLE are low income, high body-weight, smoking (for men), and manual occupation of the father. Potentially large reductions in inequalities can be achieved in Eastern European countries, where educational inequalities in DFLE are also the largest
Long-term morbidity and health after early menopause due to oophorectomy in women at increased risk of ovarian cancer: Protocol for a nationwide cross-sectional study with prospective follow-up (HARMOny Study)
Get PDFBackground: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO
The emerging role of nerves and glia in colorectal cancer
Get PDFThe role of the nervous system as a contributor in the tumor microenvironment has been recognized in different cancer types, including colorectal cancer (CRC). The gastrointestinal tract is a highly innervated organ system, which is not only innervated by the autonomic nervous system, but also contains an extensive nervous system of its own; the enteric nervous system (ENS). The ENS is important for gut function and homeostasis by regulating processes such as fluid absorption, blood flow, and gut motility. Dysfunction of the ENS has been linked with multiple gastrointestinal diseases, such as Hirschsprung disease and inflammatory bowel disease, and even with neurodegenerative disorders. How the extrinsic and intrinsic innervation of the gut contributes to CRC is not fully understood, although a mutual relationship between cancer cells and nerves has been described. Nerves enhance cancer progression through the secretion of neurotransmitters and neuropeptides, and cancer cells are capable of stimulating nerve growth. This review summarizes and discusses the nervous system innervation of the gastrointestinal tract and how it can influence carcinogenesis, and vice versa. Lastly, the therapeutic potential of these novel insights is discussed
Immune response to SARS-CoV-2 infection in obesity and T2D: Literature review
Get PDFIn December 2019, a novel coronavirus known as SARS-CoV-2 was first detected inWuhan, China, causing outbreaks of the coronavirus disease COVID-19 that has now spread globally. For this reason, The World Health Organization (WHO) declared COVID-19 a public health emergency in March 2020. People living with pre-existing conditions such as obesity, cardiovascular diseases, type 2 diabetes (T2D), and chronic kidney and lung diseases, are prone to develop severe forms of disease with fatal outcomes. Metabolic diseases such as obesity and T2D alter the balance of innate and adaptive responses. Both diseases share common features characterized by augmented adiposity associated with a chronic systemic low-grade inflammation, senescence, immunoglobulin glycation, and abnormalities in the number and function of adaptive immune cells. In obese and T2D patients infected by SARS-CoV-2, where immune cells are already hampered, this response appears to be stronger. In this review, we describe the abnormalities of the immune system, and summarize clinical findings of COVID-19 patients with pre-existing conditions such as obesity and T2D as this group is at greater risk of suffering severe and fatal clinical outcomes
The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche
Get PDFNotch and Wnt signaling are highly conserved intercellular communication pathways involved in developmental processes, such as hematopoiesis. Even though data from literature support a role for these two pathways in both physiological hematopoiesis and leukemia, there are still many controversies concerning the nature of their contribution. Early studies, strengthened by findings from T-cell acute lymphoblastic leukemia (T-ALL), have focused their investigation on the mutations in genes encoding for components of the pathways, with limited results except for B-cell chronic lymphocytic leukemia (CLL); in because in other leukemia the two pathways could be hyper-expressed without genetic abnormalities. As normal and malignant hematopoiesis require close and complex interactions between hematopoietic cells and specialized bone marrow (BM) niche cells, recent studies have focused on the role of Notch and Wnt signaling in the context of normal crosstalk between hematopoietic/leukemia cells and stromal components. Amongst the latter, mesenchymal stromal/stem cells (MSCs) play a pivotal role as multipotent non-hematopoietic cells capable of giving rise to most of the BM niche stromal cells, including fibroblasts, adipocytes, and osteocytes. Indeed, MSCs express and secrete a broad pattern of bioactive molecules, including Notch and Wnt molecules, that support all the phases of the hematopoiesis, including self-renewal, proliferation and differentiation. Herein, we provide an overview on recent advances on the contribution of MSC-derived Notch and Wnt signaling to hematopoiesis and leukemia development
Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: The PreCARA study
Get PDFObjectives: In patients with rheumatoid arthritis (RA), high disease activity impairs fertility outcomes and increases the risk of adverse pregnancy outcomes. The aim of this study was to determine the feasibility of a modern treatment approach, including treat-to-target (T2T) and the prescription of tumour necrosis factor (TNF) inhibitors, in patients with RA with a wish to conceive or who are pregnant. Methods: Patients were derived from the Preconception Counseling in Active RA (PreCARA) cohort. Patients with a wish to conceive or who are pregnant were treated according to a modified T2T approach, in which the obvious restrictions of pregnancy were taken into account. Results of the PreCARA study were compared with results of the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a historic reference cohort on RA during pregnancy. Patients in the PARA cohort were treated according to the standards of that time (2002-2010). Differences in disease activity over time between the two cohorts were tested using a linear mixed model. Results: 309 patients with RA were included in the PreCARA study, 188 children were born. 47.3% of the patients used a TNF inhibitor at any time during pregnancy. Mean disease activity over time in the PreCARA cohort was lower than in the reference cohort (p<0.001). In the PreCARA cohort, 75.4% of the patients were in low disease activity (LDA) or remission before pregnancy increasing to 90.4% in the third trimester, whereas in the PARA cohort, these percentages were 33.2% and 47.3%, respectively. Conclusions: This first study on a modern treatment approach in pregnant patients with RA shows that LDA and remission are an attainable goal during pregnancy, with 90.4% of patients achieving this in the third trimester