Morbidity and mortality in premature or low birth weight patients with congenital heart disease in three European pediatric heart centers between 2016 and 2020

Background: The treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group. Methods: A retrospective cohort study was conducted of preterm [<37 weeks gestational age (GA)] and/or LBW neonates (<2,500 g) born with a diagnosis of CHD, which requires invasive cardiac intervention (surgery or catheter) within their first year of life. Patients born between 2016 and 2020 and treated in three European pediatric heart centers were included.ResultsA total of 308 neonates (51% male) with CHD were included. Of those, 237 (77%) were born preterm, 259 (84%) were LBW, and 188 (61%) were both. The median GA was 35.4 weeks (interquartile range 33.3–36.9) and the mean birth weight was 2,016 ± 580 g. CHD was categorized as simple (12%), moderate (64%), or severe (24%). The overall complication rate was 45% and was highest in patients with severe CHD (p = 0.002). One-year mortality (19%) was associated with severe CHD, low relative birth weight in patients with genetic diagnoses, and low GA at birth, whereas GA at birth significantly impacted survival only after 3 months of life. Conclusions: The high morbidity and mortality in preterm and LBW neonates with CHD reflect their complexity and consequent limited treatment feasibility

Maternal microchimerism in the livers of patients with Biliary atresia

BACKGROUND: Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA. METHODS: Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM. RESULTS: By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2–4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1–142 copies of maternal DNA per 25,000 copies of patients DNA was found. CONCLUSIONS: Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA

Electrospun nanofibrous meshes cultured with Wharton’s Jelly Stem Cell: an alternative for cartilage regeneration, without the need of growth factors

Many efforts are being directed worldwide to the treatment of OA-focal lesions. The majority of those efforts comprise either the refinement of surgical techniques or combinations of biomaterials with various autologous cells. Herein, we tested electrospun polycaprolactone (PCL) nanofibrous meshes for cartilage tissue engineering. For that, articular chondrocytes (hACs) isolated from human osteoarthritic joints and Whartonâ s Jelly Stem Cells (hWJSCs) are cultured on electrospun nanofiber meshes, without adding external growth factors. We observed higher glycosaminoglycans production and higher overexpression of cartilage-related genes from hWJSCs cultured with basal medium, when compared to hACs isolated from osteoarthritic joints. Moreover, the presence of sulfated proteoglycans and collagen type II is observed on both types of cell cultures. We believe that this effect is due to either the electrospun nanofibers topography or the intrinsic chondrogenic differentiation potential of hWJSCs. Therefore, we propose the electrospun nanofibrous scaffolds in combination with hWJSCs as a viable alternative to the commercial membranes used in autologous chondrogenic regeneration approaches.The authors thank the Portuguese Foundation for Science and Technology for the Post-Doc grant of Marta Alves da Silva (SFRH/BPD/73322/2010, financed by POPH QREN Tipologia 4.1 – Advanced Formation, co-financed by Fundo Social Europeu and MEC national funds). This work was supported by the project SPARTAN (PTDC/CTM-BIO/4388/2014) FCT/MEC with PIDDAC funds. It was also partly supported by the POLARIS (FP7-REGPOT-2012-2013-1) and the Project “New methodologies for the isolation and control of stem cells differentiation using advanced culturing conditions and/or nanomaterials” (RL2 SCN NORTE-01-0124-FEDER-000018), co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

The role of pulmonary arterial stiffness in COPD

AbstractCOPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests.The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2

Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients with Acute Myocardial Infarction or Stable Angina Pectoris

Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of two invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. 54 patients (61±10 years) undergoing cardiac catheterization, for stable coronary artery disease (n=10) or acute myocardial infarction (AMI, n=44), had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and hyperemia. Three independent measures of microvascular function were assessed, using predefined dichotomous thresholds: i) CFR, the average value of Doppler- and thermodilution-derived coronary flow reserve (CFR), and cardiovascular magnetic resonance derived: ii) Myocardial Perfusion Reserve Index (MPRI) and iii) Microvascular Obstruction (MVO). hMR correlated with IMR (rho = 0.41, p<0.0001). hMR had better diagnostic accuracy than IMR to predict CFR (area under curve, (AUC) 0.82 versus 0.58, p<0.001, sensitivity/specificity 77/77% versus 51/71%) and MPRI (AUC 0.85 versus 0.72, p=0.19, sensitivity/specificity 82/80% versus 64/75%). In AMI patients, the AUCs of hMR and IMR at predicting extensive MVO were 0.83 and 0.72 respectively (p=0.22, sensitivity/specificity 78/74% versus 44/91%). We measured two invasive indices of coronary microvascular resistance to predict multiple distinct measures of microvascular dysfunction. We found these two invasive indices only correlate modestly and so cannot be considered equivalent. In our study, the correlation between independent invasive and non-invasive measures of microvascular function was better with hMR than with IMR

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe