Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn's disease through IFNα pathway.

Introduction: Crohn's disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, the disease pathogenesis remains elusive, and the therapeutic options are limited. Here, we investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis, a disease mechanism predisposing to inflammatory and fibrotic complications.

Evaluation of the current guidelines for the management of haemorrhoidal disease using the Appraisal of Guidelines Research and Evaluation II instrument.

Background: Haemorrhoids are a very common disease and many professional societies have produced guidelines for their treatment. The aim of this study is to appraise the quality of the existing guidelines in the management of haemorrhoids.

Methods: A systematic search of the literature was conducted in the EMBASE, Google Scholar, Cochrane library, and PubMed databases.

Down-regulation of KLF2 in lung fibroblasts is linked with COVID-19 immunofibrosis and restored by combined inhibition of NETs, JAK-1/2 and IL-6 signaling.

Kruppel-like factor 2 (KLF2) has been linked with fibrosis and neutrophil-associated thromboinflammation; however, its role in COVID-19 remains elusive. We investigated the effect of disease microenvironment on the fibrotic potential of human lung fibroblasts (LFs) and its association with KLF2 expression. LFs stimulated with plasma from severe COVID-19 patients down-regulated KLF2 expression at mRNA/protein and functional level acquiring a pre-fibrotic phenotype, as indicated by increased CCN2/collagen levels.

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 ( = 16) or placebo ( = 15) in addition to standard of care.

Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure.

Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. Patients with PaO2/FiO2 < 100 mmHg were analysed. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n = 26) or SOC plus monotherapy with either IL-1-receptor antagonist anakinra (n = 19) or tocilizumab (n = 11).

Appraisal of the current guidelines for the management of diverticular disease using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument.

Introduction: Diverticular disease is one of the most frequent reasons for attending emergency departments and surgical causes of hospital admission. In the past decade, many surgical and gastroenterological societies have published guidelines for the management of diverticular disease. The aim of the present study was to appraise the methodological quality of these guidelines using the Appraisal of Guidelines Research and Evaluation II (AGREE II) tool.

Appraisal of the Current Guidelines for Management of Malignant Left-Sided Colonic Obstruction Using the Appraisal of Guidelines Research and Evaluation II Instrument.

Introduction: Colorectal cancer (CRC) is the fourth leading cause of death with 1.4 million new cases occurring annually worldwide. High-quality clinical practice guidelines are needed to tailor high-quality individualized treatment.

The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality.

Background: Activins are members of the transforming growth factor-β superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (COVID-19), we hypothesized that activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology.

Methods: Activin-A, activin-B, and follistatin were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters.