Targeting CD20 in the treatment of interstitial lung diseases related to connective tissue diseases: A systematic review

INTRODUCTION: The effectiveness of CD20 targeting in connective tissue diseases (CTD) with lung involvement is controversial. This paper aims to review the current evidence about rituximab (RTX) use in CTD-related interstitial lung disease (ILD). METHODS: We performed a systematic review of papers published between January 2009 and May 2019. We included clinical trials, case/control studies and cohort studies. We excluded letters, case reports, case series, reviews, and full articles when not in English. The selected studies listed as primary or secondary outcome a variation in pulmonary function tests or in the scores used to radiologically stage lung involvement, in CTD-related ILD patients after RTX. RESULTS: Out of 1206 potentially eligible articles, 24 papers were selected: 3 retrospectively described cohorts of patients with different CTD, 14 dealt with systemic sclerosis (SSc)-related ILD, 5 with idiopathic inflammatory myopathies (IIMs)-related ILD, and 2 with Sjögren's Syndrome-related ILD. A direct comparison of the selected studies was hampered by their heterogeneity for outcomes, follow-up duration, the severity of lung involvement, and clinical features of study populations. However, an overall agreement existed concerning the effectiveness of RTX in the stabilization of lung disease, with some studies reporting an improvement of functional parameters from baseline. IIM-related ILD appeared more responsive than other CTD-related ILD to CD20 targeting. CONCLUSION: RTX is a promising therapeutic tool in CTD-related ILD. This systematic review remarks the unmet need of multicenter prospective studies aiming to evaluate the effectiveness of RTX with adequate sample size and study design

Gas6/TAM system: A key modulator of the interplay between inflammation and fibrosis

Fibrosis is the result of an overly abundant deposition of extracellular matrix (ECM) due to the fact of repetitive tissue injuries and/or dysregulation of the repair process. Fibrogenesis is a pathogenetic phenomenon which is involved in different chronic human diseases, accounting for a high burden of morbidity and mortality. Despite being triggered by different causative factors, fibrogenesis follows common pathways, the knowledge of which is, however, still unsatisfactory. This represents a significant limit for the development of effective antifibrotic drugs. In the present paper, we aimed to review the current evidence regarding the potential role played in fibrogenesis by growth arrest-specific 6 (Gas6) and its receptors Tyro3 protein tyrosine kinase (Tyro3), Axl receptor tyrosine kinase (Axl), and Mer tyrosine kinase protooncogene (MerTK) (TAM). Moreover, we aimed to review data about the pathogenetic role of this system in the development of different human diseases characterized by fibrosis. Finally, we aimed to explore the potential implications of these findings in diagnosis and treatment

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We reanalyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7-and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1–17.8] vs. 7.9 [3.8–12.9] ng/mL and 34.8 [26.4–47.5] vs. 29.8 [22.1–41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00–1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00–1.02] and 1.04 [1.02–1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00–1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02–1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage

Change over time of COVID-19 hospital presentation in Northern Italy

none40After the first autochthonous case described on February 19, also in Italy the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARSCoV-2) infection rapidly circulated, mainly in the Northern regions of the country. The earliest reports on Coronavirus disease-19 (COVID-19) have described worldwide a high prevalence of severe respiratory illness [1]. A suggestive feature of COVID-19 has been a rapid progression of the respiratory impairment, leading to acute respiratory distress syndrome (ARDS) and often requiring ventilation support [2]. To date, whether clinical features at hospital presentation and outcome of COVID-19 have changed over the outbreak course is unknown. We explored this issue in a multicenter cohort of patients hospitalized for COVID-19 in Northern Italy.mixedPatti G.; Mennuni M.; Della Corte F.; Spinoni E.; Sainaghi P. P.; COVID-UPO Clinical Team; Azzolina D; Hayden E; Rognon A; Grisafi L; Colombo C; Lio V; Pirisi M; Vaschetto R; Aimaretti G; Krengli M; Avanzi GC; Balbo PE; Capponi A; Castello LM; Bellan M; Malerba M; Garavelli PL; Zeppegno P; Savoia P; Chichino G; Olivieri C; Re R; Maconi A; Comi C; Roveta A; Bertolotti M; Carriero A; Betti M; Mussa M; Borrè S; Cantaluppi V; Cantello R; Bobbio F; GavellI F.Patti, G.; Mennuni, M.; Della Corte, F.; Spinoni, E.; Sainaghi, P. P.; COVID-UPO Clinical, Team; Azzolina, D; Hayden, E; Rognon, A; Grisafi, L; Colombo, C; Lio, V; Pirisi, M; Vaschetto, R; Aimaretti, G; Krengli, M; Avanzi, Gc; Balbo, Pe; Capponi, A; Castello, Lm; Bellan, M; Malerba, M; Garavelli, Pl; Zeppegno, P; Savoia, P; Chichino, G; Olivieri, C; Re, R; Maconi, A; Comi, C; Roveta, A; Bertolotti, M; Carriero, A; Betti, M; Mussa, M; Borrè, S; Cantaluppi, V; Cantello, R; Bobbio, F; Gavelli, F

Simple Parameters from Complete Blood Count Predict In-Hospital Mortality in COVID-19

The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions

Where to Begin –A Parametric Study for Vapor Barriers at LNG Export Facilities

PresentationVapor barriers are widely used to contain the release of flammable mixtures in LNG facilities in the United States. The computational fluid dynamics (CFD) modeling tool FLACS has been validated and accepted for detailed consequence modeling of flammable vapor dispersion scenarios and includes capabilities to assess the impact of vapor barriers at varying heights and locations. While every plant design is unique and the optimization of vapor barriers often requires several iterations, guidance on where to begin is often limited. This paper will detail a parametric study on vapor barrier height and placement for different release rates to establish a basis for beginning a vapor barrier design

La casa di rieducazione professionale per mutilati e storpi di guerra di Bologna (9 aprile 1916-3 gennaio 1922)

Il saggio, approfondimento di quello pubblicato nel volume Una regione ospedale, analizza in particolare la ricca raccolta fotografica conservata presso il Museo del Risorgimento di Bologna, parte integrante dell\u2019archivio dell\u2019istituto riabilitativo. In particolare l\u2019attenzione \ue8 rivolta agli interventi di recupero lavorativo (le scuole e i laboratori attivati), letti attraverso le immagini che lo documentano

La casa di rieducazione professionale per mutilati e storpi di guerra di Bologna (9 aprile 1916-3 gennaio 1922)

Il saggio analizza, utilizzando fonti d\u2019archivio, le vicende di enti e istituzioni volte alla rieducazione fisica e morale di quanti la guerra aveva colpito e resi inabili. L\u2019attenzione \ue8 rivolta sia alla vita e all\u2019organizzazione di queste istituzioni, sia a quanti ne furono in diversa misura protagonisti: i dirigenti, i medici, gli educatori e i malati ospiti della struttura, seguiti dal loro arrivo fino al momento della loro restituzione alla normale quotidianit\ue0