158 research outputs found

    Cardiopulmonary exercise testing in a combined screening approach to individuate pulmonary arterial hypertension in systemic sclerosis

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    Objectives The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy. Methods Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates. Results Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714\u20130.846), positive predictive value 0.636 (0.556\u20130.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636\u20130.8) and positive predictive value of 0.714 (0.636\u20130.8). Conclusion In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension

    Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

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    Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.This work was supported by EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS grant No. 115565

    First trimester PTX3 levels in women who subsequently develop preeclampsia and fetal growth restriction

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    Pentraxin 3 (PTX3) and C-reactive protein (CRP) levels were measured in the first trimester of pregnancy in women who subsequently developed preeclampsia (PE, n 16) and fetal growth restriction (FGR, n 12) requiring iatrogenic delivery before 37 weeks, and those who had uncomplicated pregnancies delivering at term (n 60). Mean PTX3 levels were significantly higher in women who subsequently developed PE (7.31 ng/ml, SD 4.12) when compared to those with normal pregnancy outcome (4.92 ng/ml, SD 1.94, p 0.0046). There were no significant differences between PTX3 levels in women with FGR (4.82 ng/ml, SD 2.35) compared to normal pregnancy outcome (p 0.88). The median CRP levels did not vary significantly between the three groups (p 0.26). PTX3 levels in women who subsequently develop PE are already elevated in the first trimester, but not in those that develop FGR. This supports the hypothesis of an excessive maternal inflammatory response to pregnancy in the etiology of PE

    A framework to assess welfare mix and service provision models in health care and social welfare: case studies of two prominent Italian regions

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    BACKGROUND: The mechanisms through which the relationships among public institutions, private providers and families affect care and service provision systems are puzzling. How can we understand the mechanisms in these contexts? Which elements should we explore to capture the complexity of care provision? The aim of our study is to provide a framework that can help read and reframe these puzzling care provision mechanisms in a welfare mix context. METHODS: First, we develop a theoretical framework for understanding how service provision occurs in care systems that are characterised by a variety of relationships between multiple actors, using an evidence-based approach that looks at both public and private expenditures and the number of users relative to the level of needs coverage and compared with declared values and political rhetoric. Second, we test this framework in two case studies built on data from two prominent Italian regions, Lombardy and Emilia-Romagna. We argue that service provision models depend on the interplay among six conceptual elements: policy values, governance rules, resources, nature of the providers, service standards and eligibility criteria. RESULTS: Our empirical study shows that beneath the relevant differences in values and political rhetoric between the case studies of the two Italian regions, there is a surprising isomorphism in service standards and the levels of covering the population’s needs. CONCLUSION: The suggested framework appears to be effective and feasible; it fosters interdisciplinary approaches and supports policy-making discussions. This study may contribute to deepening knowledge about public care service provision and institutional arrangements, which can be used to promote more effective reforms and may advance future research. Although the framework was tested on the Italian welfare system, it can be used to assess many different systems
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