Left Ventricular Systolic Dysfunction in Rheumatoid Disease An Unrecognized Burden?

ObjectivesThis study sought to ascertain whether left ventricular systolic dysfunction (LVSD) is more common among clinic patients with rheumatoid disease (RD) compared with the general population, and to assess the diagnostic utility of brain natriuretic peptide (BNP).BackgroundPatients with RD are at increased risk of ischemic heart disease. However, there are few large echocardiographic studies identifying cardiac dysfunction in RD. We hypothesized that LVSD would be more prevalent in RD patients than in the general population.MethodsA total of 226 hospital out-patients with RD (65% women) underwent clinical evaluation, electrocardiography (ECG), echocardiography, and plasma BNP assay (218 patients). Prevalence of LVSD was compared with local population estimates.ResultsDefinite LVSD (left ventricular ejection fraction <40%) occurred in 5.3% of the RD group: standardized prevalence ratio, 3.20; 95% confidence interval, 1.65 to 5.59. Median BNP values were higher in patients with LVSD compared with those without: 16.6 pmol/l versus 8.5 pmol/l, p < 0.005, although values between the two groups overlapped. One in nine patients with an abnormal ECG had definite LVSD.ConclusionsDefinite LVSD was three times more common in RD patients than in the general population. Given the prognostic benefits of treating LVSD, echocardiographic screening of RD patients with an abnormal ECG may be worthwhile

Simulated Anthrax Attacks and Syndromic Surveillance

Bioterrorism surveillance systems can be assessed using modeling to simulate real-world attacks

Contribution of NOTCH1 genetic variants to bicuspid aortic valve and other congenital lesions

INTRODUCTION: Bicuspid aortic valve (BAV) affects 1% of the general population. NOTCH1 was the first gene associated with BAV. The proportion of familial and sporadic BAV disease attributed to NOTCH1 mutations has not been estimated. AIM: The aim of our study was to provide an estimate of familial and sporadic BAV disease attributable to NOTCH1 mutations. METHODS: The population of our study consisted of participants of the University of Leicester Bicuspid aoRtic vAlVe gEnetic research-8 pedigrees with multiple affected family members and 381 sporadic patients. All subjects underwent NOTCH1 sequencing. A systematic literature search was performed in the NCBI PubMed database to identify publications reporting NOTCH1 sequencing in context of congenital heart disease. RESULTS: NOTCH1 sequencing in 36 subjects from 8 pedigrees identified one variant c.873C>G/p.Tyr291* meeting the American College of Medical Genetics and Genomics criteria for pathogenicity. No pathogenic or likely pathogenic NOTCH1 variants were identified in 381 sporadic patients. Literature review identified 64 relevant publication reporting NOTCH1 sequencing in 528 pedigrees and 9449 sporadic subjects. After excluding families with syndromic disease pathogenic and likely pathogenic NOTCH1 variants were detected in 9/435 (2.1%; 95% CI: 0.7% to 3.4%) of pedigrees and between 0.05% (95% CI: 0.005% to 0.10%) and 0.08% (95% CI: 0.02% to 0.13%) of sporadic patients. Incomplete penetrance of definitely pathogenic NOTCH1 mutations was observed in almost half of reported pedigrees. CONCLUSIONS: Pathogenic and likely pathogenic NOTCH1 genetic variants explain 2% of familial and <0.1% of sporadic BAV disease and are more likely to associate with tetralogy of Fallot and hypoplastic left heart

Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation

Immune responses to tissue-engineered grafts made of xenogeneic materials remain poorly studied. The scope of current investigations is limited by the lack of information on orthotopically implanted grafts. A deeper understanding of these processes is of great importance since innovative surgical approaches include the implantation of xenogeneic decellularized scaffolds seeded by cells. The purpose of our work is to study the immunological features of tracheal repair during the implantation of tissue-engineered constructs based on human xenogeneic scaffolds modified via laser radiation in rabbits. The samples were stained with hematoxylin and Safranin O, and they were immunostained with antibodies against tryptase, collagen II, vimentin, and CD34. Immunological and inflammatory responses were studied by counting immune cells and evaluating blood vessels and collagen. Leukocyte-based inflammation prevailed during the implantation of decellularized unseeded scaffolds; meanwhile, plasma cells were significantly more abundant in tissue-engineered constructs. Mast cells were insignificantly more abundant in tissue-engineered construct samples. Conclusions: The seeding of decellularized xenogeneic cartilage with chondrocytes resulted in a change in immunological reactions upon implantation, and it was associated with plasma cell infiltration. Tissue-engineered grafts widely differed in design, including the type of used cells. The question of immunological response depending on the tissue-engineered graft composition requires further investigation