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Author

Barbara Ruaro

Other affiliations: University of Trieste
Bio: Barbara Ruaro is an academic researcher from University of Genoa. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 22, co-authored 88 publications receiving 1249 citations. Previous affiliations of Barbara Ruaro include University of Trieste.

Papers published on a yearly basis

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Journal ArticleDOI
TL;DR: It is shown for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement.
Abstract: Systemic sclerosis (SSc) is a disorder characterized by immune system alterations, vasculopathy and fibrosis. SSc-related interstitial lung disease (ILD) represents a common and early complication, being the leading cause of mortality. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be used as biomarker for lung involvement in SSc. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and we evaluated possible relations with lung involvement parameter values. A single centre cross-sectional study was performed in fifty-five consecutive SSc patients, during the year 2017. All clinical and instrumental tests requested for SSc follow up and in particular, lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide (pro-BNP) evaluation, were performed in each patient in a maximum one-month period. Flow cytometry characterization of circulating cells belonging to the monocyte/macrophage lineage was performed using specific M1 (CD80, CD86, TLR2 and TLR4) and M2 surface markers (CD204, CD163 and CD206). Non-parametric tests were used for statistical analysis. A higher percentage of circulating CD204+CD163+CD206+TLR4+CD80+CD86+ and CD14+CD206+CD163+CD204+TLR4+CD80+CD86+ mixed M1/M2 monocyte/macrophage subsets, was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Mixed M1/M2 monocyte/macrophage subset showed higher percentages in patients positive for anti-topoisomerase antibody, a known lung involvement predictor. The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement.

118 citations

Journal ArticleDOI
TL;DR: In patients with severe COVID-19 pneumonia, early administration of prolonged, low dose MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence and treatment was safe and did not impact viral clearance.
Abstract: Background In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. Methods We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. Results Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). Conclusion In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.

101 citations

Journal ArticleDOI
01 Jan 2019-RMD Open
TL;DR: There is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications, and patients with SSc experience significant uncertainty concerning S Sc-related taxonomy, management, management and education.
Abstract: Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains 'Vascular & Ulcers' (ie, non-pharmacological approach to digital ulcer), 'PAH' (ie, screening and treatment), 'Treatment' and 'Juveniles' (ie, evaluation of juveniles with Raynaud's phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation.

96 citations

Journal ArticleDOI
TL;DR: A review of the role of alveolar type II (ATII) cells in pulmonary diseases can be found in this paper, where the origin, phenotypic regulation and crosstalk of these cells still remain a mystery.
Abstract: Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.

94 citations

Journal ArticleDOI
09 Jun 2017-PLOS ONE
TL;DR: Serum 25(OH)D deficiency was found to correlate with lung involvement, peripheral vascular, kidney and gastrointestinal Medsger’s DSS parameters and with seasonality In SSc patients, and Supplementation with oral colecalciferol was found not effective in increasing 25( OH)D serum concentrations.
Abstract: Objective : Assessment of serum 25-hydroxyvitamin D (25(OH) D) correlations with clinical parameters and evaluation of the efficacy of standard oral supplementation in systemic sclerosis (SSc) patients. Methods : 154 SSc patients were recruited, in all seasons. Serum 25(OH) D concentrations were evaluated using LIAISON 25-OH (Diasorin, Italy). Medsger disease severity scale (DSS), nailfold videocapillaroscopy (NVC) and all instrumental exam contemplated by international guidelines were performed. Drug assumption, including oral colecalciferol, was evaluated. Nonparametric tests were used for statistical analysis. Results : Average 25(OH) D serum concentration was 18.7 +/- 9 ng/ml (<20 classified as deficiency). A significant correlation was found with presence/absence of lung bi-basal fibrotic changes (16.1 +/- 8 ng/ml and 20 +/- 10 ng/ml, respectively; p = 0.04). Peripheral vascular (p = 0.03), kidney (p = 0.02), gastrointestinal (p = 0.05) Medsger's DSS parameters were found to correlate with 25(OH) D serum concentrations. No significant correlations were observed with digital ulcers incidence, strictly correlated to patterns of microangiopathy, defined at NVC analysis (p<0.0001). Interestingly, no effects of treatment with oral colecalciferol (Dibase 1,000 IU daily for at least 6 months) were found on 25(OH) D serum concentrations in treated (18.8 +/- 10 ng/ml) or untreated (18.7 +/- 9 ng/ml) SSc patients (p = 0.81). A significant difference was observed among seasonal 25(OH) D serum concentrations (winter: 14.6 +/- 7.8 ng/ml, spring: 17.2 +/- 7.9 ng/ml, summer: 21.43 +/- 10 ng/ml, autumn: 20.2 +/- 10 ng/ml; p = 0.032) in all patients. Conclusion : Serum 25(OH) D deficiency was found to correlate with lung involvement, peripheral vascular, kidney and gastrointestinal Medsger's DSS parameters and with seasonality In SSc patients. Supplementation with oral colecalciferol was found not effective in increasing 25 (OH) D serum concentrations. Therefore, for successful replacement, supra-physiological vitamin D3 doses or programmed UVB light exposure should be tested.

87 citations


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Journal ArticleDOI
TL;DR: The beneficial and harmful effects of vitamin D supplementation on the prevention of mortality in healthy adults and in adults with a stable form of disease are assessed.
Abstract: Relevance to nursing care The evidence available regarding vitamin D on mortality has been inconclusive. Vitamin D can be obtained from sun exposure on skin, dietary intake, or supplementation as vitamin D3 or D2. Proper balance of vitamin D and calcium levels are important for healthy bones. Past studies have indicated that vitamin D supplementation prevents osteoporosis, osteomalacia, and fractures. Contradictory studies suggest that vitamin D may prevent cancer, cardiovascular disease, and affect mortality; and observational research has indicated a relationship of low vitamin D levels and risk of mortality. Evidence related to vitamin D is important for nurses working with patients with and without vitamin D insufficiency. The value of vitamin D needs clarification, and health information about risk factors, common problems with deficiency, as well as the benefits and proper use of vitamin D supplementation are needed by patients and caregivers. The purpose of this systematic review was to assess the beneficial and harmful effects of vitamin D supplementation on the prevention of mortality in healthy adults and in adults with a stable form of disease.

323 citations

Journal ArticleDOI
TL;DR: Compared with never smokers, current smokers appear to be at reduced risk of SARS‐CoV‐2 infection while former smokers appearTo be at increased risk of hospitalisation, increased disease severity and mortality from COVID‐19, however, it is uncertain whether these associations are causal.
Abstract: AIMS: To estimate the association of smoking status with rates of (i) infection, (ii) hospitalization, (iii) disease severity and (iv) mortality from SARS-CoV-2/COVID-19 disease. DESIGN: Living rapid review of observational and experimental studies with random-effects hierarchical Bayesian meta-analyses. Published articles and pre-prints were identified via MEDLINE and medRxiv. SETTING: Community or hospital, no restrictions on location. PARTICIPANTS: Adults who received a SARS-CoV-2 test or a COVID-19 diagnosis. MEASUREMENTS: Outcomes were SARS-CoV-2 infection, hospitalization, disease severity and mortality stratified by smoking status. Study quality was assessed (i.e. 'good', 'fair' and 'poor'). FINDINGS: Version 7 (searches up to 25 August 2020) included 233 studies with 32 'good' and 'fair' quality studies included in meta-analyses. Fifty-seven studies (24.5%) reported current, former and never smoking status. Recorded smoking prevalence among people with COVID-19 was generally lower than national prevalence. Current compared with never smokers were at reduced risk of SARS-CoV-2 infection [relative risk (RR) = 0.74, 95% credible interval (CrI) = 0.58-0.93, τ = 0.41]. Data for former smokers were inconclusive (RR = 1.05, 95% CrI = 0.95-1.17, τ = 0.17), but favoured there being no important association (21% probability of RR ≥ 1.1). Former compared with never smokers were at somewhat increased risk of hospitalization (RR = 1.20, CrI = 1.03-1.44, τ = 0.17), greater disease severity (RR = 1.52, CrI = 1.13-2.07, τ = 0.29) and mortality (RR = 1.39, 95% CrI = 1.09-1.87, τ = 0.27). Data for current smokers were inconclusive (RR = 1.06, CrI = 0.82-1.35, τ = 0.27; RR = 1.25, CrI = 0.85-1.93, τ = 0.34; RR = 1.22, 95% CrI = 0.78-1.94, τ = 0.49, respectively), but favoured there being no important associations with hospitalization and mortality (35% and 70% probability of RR ≥ 1.1, respectively) and a small but important association with disease severity (79% probability of RR ≥ 1.1). CONCLUSIONS: Compared with never smokers, current smokers appear to be at reduced risk of SARS-CoV-2 infection, while former smokers appear to be at increased risk of hospitalization, increased disease severity and mortality from COVID-19. However, it is uncertain whether these associations are causal.

241 citations

Journal ArticleDOI
01 Aug 2017-BioDrugs
TL;DR: Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab.
Abstract: A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety. Literature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn’s disease, and ulcerative colitis. Of >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0–83%), adalimumab (0–54%), and infliximab biosimilar CT-P13 (21–52%), and the lowest with secukinumab (0–1%), ustekinumab (1–11%), etanercept (0–13%), and golimumab (0–19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb− patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases. Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.

236 citations

Journal ArticleDOI
TL;DR: In this paper, a systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines.
Abstract: In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19. A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections. Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57–0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present. Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.

230 citations