Thrombospondin-1 and VEGF in inflammatory bowel disease

Background and aim: Angiogenesis is an important process in the pathogenesis of chronic inflammation. We aimed to study the angiogeneic balance in inflammatory bowel disease (IBD) by evaluating the expression of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) on colonic epithelial cells, together with the expression of inducible nitric oxide synthase (iNOS). Methods: Twenty-one ulcerative colitis (UC), 14 Crohn’s disease (CD), 11 colorectal cancer patients, and 11 healthy controls colonic biopsy samples were evaluated immunohistochemically. Results: The expressions of TSP-1, VEGF, and iNOS in UC and CD groups were higher than expression in healthy control group, all with statistical significance. However, in colorectal cancer group, VEGF and iNOS expressions were increased importantly, but TSP-1 expression was not statistically different from healthy control group’s expression. Both TSP-1 and VEGF expressions were correlated with iNOS expression distinctly but did not correlate with each other. Conclusions: Both pro-angiogeneic VEGF and antiangiogeneic TSP-1 expressions were found increased in our IBD groups, but in colorectal cancer group, only VEGF expression was increased. TSP-1 increases in IBD patients as a response to inflammatory condition, but this increase was not enough to suppress pathologic angiogenesis and inflammation in IBD.Keywords: inflammatory bowel disease; thrombospondin-1; VEGF; iNOS; colon cance

Assessing the outcomes and experiences of care from the perspective of people living with chronic conditions, to support countries in developing people-centred policies and practices: study protocol of the International Survey of People Living with Chronic Conditions (PaRIS survey).

This is the final version. Available from BMJ Publishing via the DOI in this record. INTRODUCTION: In view of growing populations with chronic conditions, many countries are redesigning their health systems. However, little information is available about how health systems perform from the perspective of people living with chronic conditions. The Organisation for Economic Co-operation and Development (OECD) Member States therefore mandated the OECD to initiate the International Survey of People Living with Chronic Conditions (PaRIS survey), which aims to provide insight in outcomes and experiences of care as reported by people living with chronic conditions. The PaRIS-SUR consortium has been tasked by the OECD to support the development and implementation of the survey. METHODS AND ANALYSIS: As primary care services play a pivotal role in the management of chronic conditions, the PaRIS survey will be implemented in the primary care setting. Data will be collected with a survey among users of primary care services aged 45 years or older, of whom many have chronic conditions. An additional survey is conducted among their primary care providers. The nested study design will allow analysis of the patient-reported data in relation to characteristics of and care provided by primary care providers within and across countries. In 2022, the survey will be tested in a Field Trial in participating countries. Data for cross-country comparison will be collected by the Main Survey in 2023. ETHICS AND DISSEMINATION: Informed consent will be obtained from primary care providers and service users. National Project Managers search ethical approval of the survey in their country, if required. Reporting by the OECD will focus on questions for international comparison. A secured information technology platform will be developed for participants and stakeholders in countries to receive feedback and answer their own questions. Findings will also be disseminated through an international OECD flagship report, conferences, scientific papers and policy briefs, to inform strategies to improve care for people living with chronic conditions throughout the world.Organisation for Economic Co-operation and Development (OECD

Cardiovascular disease patients have increased risk for comorbidity: A cross-sectional study in the Netherlands

textabstractBackground: Comorbidity is a cause of increased mortality, decreased quality of life and increased use of healthcare services. It is important particularly for physicians and other healthcare providers in primary care settings to evaluate these patients properly. Cardiovascular diseases (CVD) are the most common cause of death from non-communicable diseases worldwide and are characterized by a high level of comorbidities. Objectives: To address the distribution of CVDs and comorbidities across sociodemographic groups and associations between CVDs and comorbidities. Methods: A cross-sectional study was conducted using data of 67 786 patients. Data were collected by the Registration Network Family Practices (RegistratieNet Huisartspraktijken, RNH). Comorbidities were analysed using chi-square and logistic regression analyses. Results: At the time of study, 26.5% of the patients had at least one CVD and 10.5% of patients had two or more CVD diagnoses. The strongest association within cardiovascular diseases were between health failure and arrhythmias (OR: 9.20; 95%CI: 7.78–10.89). Coronary artery disease and hypertension had strong relationship with diabetes (OR: 2.22; 95%CI: 2.02–2.45, OR: 2.22; 95%CI: 2.02–2.45 respectively) and lipid metabolism disorders (OR: 2.04; 95%CI: 1.87–2.23, OR: 2.04; 95%CI: 1.87–2.23, respectively). The strongest associations for cerebrovascular diseases were with epilepsy (OR: 4.09; 95%CI: 3.29–5.10) and arrhythmias (OR: 2.23; 95%CI: 1.99–2.50). Conclusion: One out of every four patients suffered from at least one CVD. Having one CVD increased the risk of another, co-occurring CVD and a higher number of other chronic diseases

Expanding the clinical and immunological phenotypes and natural history of MALT1 deficiency.

Purpose: MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. Methods: The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. Results: The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). Conclusion: This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life

Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability

Pathogenic variants in genes encoding subunits of the spliceosome are the cause of several human diseases, such as neurodegenerative diseases. The RNA splicing process is facilitated by the spliceosome, a large RNA-protein complex consisting of small nuclear ribonucleoproteins (snRNPs), and many other proteins, such as heterogeneous nuclear ribonucleoproteins (hnRNPs). The HNRNPU gene (OMIM *602869) encodes the heterogeneous nuclear ribonucleoprotein U, which plays a crucial role in mammalian development. HNRNPU is expressed in the fetal brain and adult heart, kidney, liver, brain, and cerebellum. Microdeletions in the 1q44 region encompassing HNRNPU have been described in patients with intellectual disability (ID) and other clinical features, such as seizures, corpus callosum abnormalities (CCA), and microcephaly. Recently, pathogenic HNRNPU variants were identified in large ID and epileptic encephalopathy cohorts. In this study, we provide detailed clinical information of five novels and review two of the previously published individuals with (likely) pathogenic de novo variants in the HNRNPU gene including three non-sense and two missense variants, one small intragenic deletion, and one duplication. The phenotype in individuals with variants in HNRNPU is characterized by early onset seizures (6/7), severe ID (6/6), severe speech impairment (6/6), hypotonia (6/7), and central nervous system (CNS) (5/6), cardiac (4/6), and renal abnormalities (3/4). In this study, we broaden the clinical and mutational HNRNPU-associated spectrum, and demonstrate that heterozygous HNRNPU variants cause epilepsy, severe ID with striking speech impairment and variable CNS, cardiac, and renal anomalies