Reactome pathway analysis from whole-blood transcriptome reveals unique characteristics of systemic sclerosis patients at the preclinical stage

ObjectiveThis study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.MethodsWhole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.ResultsAt 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate <0.05, differentiating PreSSc versus HC with an AUROC = 0.792 ± 0.242 in regression models. Four clinical groups were identified via unsupervised clustering (HC, HC and PreSSc with HC-like features, PreSSc and HC with PreSSc-like features, and PreSSc). Biological signatures changed with disease progression while remaining unchanged in stable subjects. The magnitude of change was related to the baseline cluster, yet no DEP at baseline was predictive of progression. Disease progression was mostly related to changes in signal transduction pathways especially linked to calcium-related events and inositol 1,4,5-triphosphate metabolism.ConclusionPreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy

IMPORTANCE Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. OBJECTIVE To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. EXPOSURES COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). MAIN OUTCOMES AND MEASURES The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. RESULTS Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] agewas 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dosewas 0.03 (95% CI, 0.03-0.04; P <.001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P <.001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P <.001), primarily male individuals (110 patients [ 79.1%] vs 252 patients [60.9%]; P <.001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P <.001) and had higher ratio of arterial partial pressure of oxygen (PaO2) and fraction of inspiratory oxygen (FiO(2)) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P =.007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower PaO2/FiO(2) at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. CONCLUSIONS AND RELEVANCE In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status.These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations

EFAS upgrade for the extended model domain

This publication is a Technical report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policymaking process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of this publication.JRC.E.1-Disaster Risk Managemen

EFAS upgrade for the extended model domain

This publication is a Technical report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policymaking process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of this publication.JRC.E.1-Disaster Risk Managemen

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Nationwide cross-sectional survey of 3560 children and adolescents with diabetes in Italy.

none6VANELLI M; CERUTTI F; CHIARELLI F; R. LORINI; MESCHI F; MCDC-ITALY GROUP.Vanelli, M; Cerutti, F; Chiarelli, F; Lorini, RENATA GIUSEPPINA; Meschi, F; MCDC ITALY, Grou

Enhanced tissue factor expression by blood eosinophils from patients with hypereosinophilia: a possible link with thrombosis.

Thrombotic risk is increased in eosinophil-mediated disorders, and several hypotheses have been proposed to link eosinophilia and thrombosis. In particular, eosinophils have been described as source of tissue factor (TF), the main initiator of blood coagulation; however, this aspect is still controversial. This study was aimed to evaluate whether TF expression varies in eosinophils isolated from normal subjects and patients with different hypereosinophilic conditions. Eosinophils were immunologically purified from peripheral blood samples of 9 patients with different hypereosinophilic conditions and 9 normal subjects. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were performed to test eosinophil TF expression. For comparison, TF expression was evaluated in monocytes from blood donors and in human endothelial (ECV304) and fibroblast (IMR90) cell lines. Western blot analysis revealed a major band of 47,000 corresponding to native TF in homogenates of purified eosinophils with a higher intensity in the 9 patients than in the 9 controls (p<0.0001). According to RT-PCR cycle threshold (Ct), TF gene expression was higher in eosinophils from patients than in those from controls, median (range) 35.10 (19.45-36.50) vs 37.17 (35.33-37.87) (p = 0.002), and was particularly abundant in one patient with idiopathic hypereosinophilic syndrome and ischemic heart attacks (Ct: 19.45). TF gene expression was moderate in monocytes, Ct: 31.32 (29.82-33.49) and abundant in endothelial cells, Ct: 28.70 (27.79-29.57) and fibroblasts, Ct: 22.77 (19.22-25.05). Our results indicate that human blood eosinophils contain variable amounts of TF. The higher TF expression in patients with hypereosinophilic disorders may contribute to increase the thrombotic risk

Demographic and clinical characteristics of patients with hypereosinophilia.

<p>Demographic and clinical characteristics of patients with hypereosinophilia.</p