Edwin H.G. Oei

Bio: Edwin H.G. Oei is an academic researcher from Erasmus University Rotterdam. The author has contributed to research in topics: Osteoarthritis & Medicine. The author has an hindex of 34, co-authored 168 publications receiving 3940 citations. Previous affiliations of Edwin H.G. Oei include European Society of Radiology & Stanford University.

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Abstract: Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.

High Bone Mineral Density and Fracture Risk in Type 2 Diabetes as Skeletal Complications of Inadequate Glucose Control: The Rotterdam Study

Abstract: OBJECTIVEdIndividuals with type 2 diabetes have increased fracture risk despite higher bonemineraldensity(BMD).Ouraimwastoexaminetheinfluenceofglucosecontrolonskeletal complications. RESEARCH DESIGN AND METHODSdData of 4,135 participants of the Rotterdam Study, a prospective population-based cohort, were available (mean follow-up 12.2 years). At baseline, 420 participants with type 2 diabetes were classified by glucose control (according to HbA1c calculated from fructosamine), resulting in three comparison groups: adequately controlled diabetes (ACD; n = 203; HbA1c ,7.5%), inadequately controlled diabetes (ICD; n = 217; HbA1c $7.5%), and no diabetes (n = 3,715). Models adjusted for sex, age, height, and weight (and femoral neck BMD) were used to test for differences in bone parameters and fracture risk (hazard ratio [HR] [95% CI]).

Phenotypic spectrum of the SMAD3-related aneurysms–osteoarthritis syndrome

Abstract: Background Aneurysmseosteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence of arterial aneurysms and tortuosity, mild craniofacial, skeletal and cutaneous anomalies, and early-onset osteoarthritis. AOS is caused by mutations in the SMAD3 gene. Methods A cohort of 393 patients with aneurysms without mutation in FBN1, TGFBR1 and TGFBR2 was screened for mutations in SMAD3. The patients originated from The Netherlands, Belgium, Switzerland and USA. The clinical phenotype in a total of 45 patients from eight different AOS families with eight different SMAD3 mutations is described. In all patients with a SMAD3 mutation, clinical records were reviewed and extensive genetic, cardiovascular and orthopaedic examinations were performed. Results Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new AOS families. A follow-up description of the three families with a SMAD3 mutation previously described by the authors was included. In the majority of patients, early-onset joint abnormalities, including osteoarthritis and osteochondritis dissecans, were the initial symptom for which medical advice was sought. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. Aneurysms and tortuosity were found in the aorta and other arteries throughout the body, including intracranial arteries. Of the patients who first presented with joint abnormalities, 20% died suddenly from aortic dissection. The presence of mild craniofacial abnormalities including hypertelorism and abnormal uvula may aid the recognition of this syndrome. Conclusion The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up.

Factors that predict a poor outcome 5–8 years after the diagnosis of patellofemoral pain: a multicentre observational analysis

Abstract: Background Patellofemoral pain (PFP) has traditionally been viewed as self-limiting, but recent studies show that a large proportion of patients report chronic knee pain at long-term follow-up. We identified those patients with an unfavourable recovery (‘moderate improvement’ to ‘worse than ever’ measured on a Likert scale) and examined whether there is an association between PFP and osteoarthritis (OA) at 5–8-year follow-up. Methods Long-term follow-up data were derived from 2 randomised controlled trials (n=179, n=131). Patient-reported measures were obtained at baseline. Pain severity (100 mm visual analogue scale (VAS)), function (Anterior Knee Pain Scale (AKPS)) and self-reported recovery were measured 5–8 years later, along with knee radiographs. Multivariate backward stepwise linear regression analyses were used to evaluate the prognostic ability of baseline pain duration, pain VAS and AKPS on outcomes of pain VAS and AKPS at 5–8 years. Results 60 (19.3%) participants completed the questionnaires at 5–8-year follow-up (45 women, mean age at baseline 26 years) and 50 underwent knee radiographs. No differences were observed between responders and non-responders regarding baseline demographics, and 3-month and 12-month pain severity and recovery. 34 (57%) reported unfavourable recovery at 5–8 years. 48 out of 50 participants (98%) had no signs of radiographic knee OA. Multivariate models revealed that baseline PFP duration (>12 months; R 2 =0.22) and lower AKPS (R 2 =0.196) were significant predictors of poor prognosis at 5–8 years on measures of worst pain VAS and AKPS, respectively. Summary and conclusion More than half of participants with PFP reported an unfavourable recovery 5–8 years after recruitment, but did not have radiographic knee OA. Longer PFP duration and worse AKPS score at baseline predict poor PFP prognosis. Education of health practitioners and the general public will provide patients with more realistic expectations regarding prognosis.

Quantitative MRI techniques of cartilage composition.

Abstract: Due to aging populations and increasing rates of obesity in the developed world, the prevalence of osteoarthritis (OA) is continually increasing. Decreasing the societal and patient burden of this disease motivates research in prevention, early detection of OA, and novel treatment strategies against OA. One key facet of this effort is the need to track the degradation of tissues within joints, especially cartilage. Currently, conventional imaging techniques provide accurate means to detect morphological deterioration of cartilage in the later stages of OA, but these methods are not sensitive to the subtle biochemical changes during early disease stages. Novel quantitative techniques with magnetic resonance imaging (MRI) provide direct and indirect assessments of cartilage composition, and thus allow for earlier detection and tracking of OA. This review describes the most prominent quantitative MRI techniques to date—dGEMRIC, T2 mapping, T1rho mapping, and sodium imaging. Other, less-validated methods for quantifying cartilage composition are also described—Ultrashort echo time (UTE), gagCEST, and diffusion-weighted imaging (DWI). For each technique, this article discusses the proposed biochemical correlates, as well its advantages and limitations for clinical and research use. The article concludes with a detailed discussion of how the field of quantitative MRI has progressed to provide information regarding two specific patient populations through clinical research—patients with anterior cruciate ligament rupture and patients with impingement in the hip. While quantitative imaging techniques continue to rapidly evolve, specific challenges for each technique as well as challenges to clinical applications remain.

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC).

Abstract: Table 1. Classes of recommendation Table 2. Levels of evidence Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study Table 6. Modified WHO classification of maternal cardiovascular risk: principles Table 7. Modified WHO classification of maternal cardiovascular risk: application Table 8. Maternal predictors of neonatal events in women with heart disease Table 9. General recommendations Table 10. Recommendations for the management of congenital heart disease Table 11. Recommendations for the management of aortic disease Table 12. Recommendations for the management of valvular heart disease Table 13. Recommendations for the management of coronary artery disease Table 14. Recommendations for the management of cardiomyopathies and heart failure Table 15. Recommendations for the management of arrhythmias Table 16. Recommendations for the management of hypertension Table 17. Check list for risk factors for venous thrombo-embolism Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy Table 19. Risk groups according to risk factors: definition and preventive measures Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium Table 21. Recommendations for drug use ABPM : ambulatory blood pressure monitoring ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AHA : American Heart Association aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker AS : aortic stenosis ASD : atrial septal defect AV : atrioventricular AVSD : atrioventricular septal defect BMI : body mass index BNP : B-type natriuretic peptide BP : blood pressure CDC : Centers for Disease Control CHADS : congestive heart failure, hypertension, age (>75 years), diabetes, stroke CI : confidence interval CO : cardiac output CoA : coarction of the aorta CT : computed tomography CVD : cardiovascular disease DBP : diastolic blood pressure DCM : dilated cardiomyopathy DVT : deep venous thrombosis ECG : electrocardiogram EF : ejection fraction ESC : European Society of Cardiology ESH : European Society of Hypertension ESICM : European Society of Intensive Care Medicine FDA : Food and Drug Administration HCM : hypertrophic cardiomyopathy ICD : implantable cardioverter-defibrillator INR : international normalized ratio i.v. : intravenous LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVOTO : left ventricular outflow tract obstruction MRI : magnetic resonance imaging MS : mitral stenosis NT-proBNP : N-terminal pro B-type natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulant PAH : pulmonary arterial hypertension PAP : pulmonary artery pressure PCI : percutaneous coronary intervention PPCM : peripartum cardiomyopathy PS : pulmonary valve stenosis RV : right ventricular SBP : systolic blood pressure SVT : supraventricular tachycardia TGA : complete transposition of the great arteries TR : tricuspid regurgitation UFH : unfractionated heparin VSD : ventricular septal defect VT : ventricular tachycardia VTE : venous thrombo-embolism WHO : World Health Organization Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …