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S. Peralta

Other affiliations: Queen Mary University of London
Bio: S. Peralta is an academic researcher from University of Palermo. The author has contributed to research in topics: Cirrhosis & Inflammation. The author has an hindex of 18, co-authored 31 publications receiving 1416 citations. Previous affiliations of S. Peralta include Queen Mary University of London.

Papers
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Journal ArticleDOI
TL;DR: Gut-derived IL-17+ and IL-22+ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.
Abstract: Background The aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS). Methods ILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed. Results ILC3 characterised as Lyn − RORc − Tbet + NKp44 + cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R + cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1. Conclusions Gut-derived IL-17 + and IL-22 + ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.

226 citations

Journal ArticleDOI
TL;DR: It is indicated that overexpression of IL-23, but not IL-17, is a pivotal feature of subclinical gut inflammation in AS, providing a pathophysiologic significance to the reported association between IL- 23 receptor polymorphisms and intestinal inflammation.
Abstract: Objective Subclinical gut inflammation is common in spondylarthritis, but the immunologic abnormalities underlying this process are undefined. Perturbation of the interleukin-23 (IL-23)/Th17 axis has emerged as a fundamental trigger of chronic inflammation. This study was undertaken to investigate the expression and tissue distribution of IL-23/Th17–related molecules in Crohn's disease (CD) and in subclinical gut inflammation in ankylosing spondylitis (AS). Methods Quantitative gene expression analysis of Th1/Th2 and IL-23/Th17 responses was performed in intestinal biopsy samples obtained from 12 patients with CD, 15 patients with AS, and 13 controls. IL-23 tissue distribution and identification of IL-23–producing cells were evaluated by immunohistochemistry. Results We demonstrated a strong and significant up-regulation of IL-23p19 transcripts in the terminal ileum in patients with AS and patients with CD. IL-23 was abundantly produced by infiltrating monocyte-like cells in inflamed mucosa from AS and CD patients. Notably, we also identified Paneth cells as a major source of IL-23 in patients with AS, patients with CD, and normal controls. Unlike CD, in AS patients, IL-23 was not associated with up-regulation of IL-17 and the IL-17–inducing cytokines IL-6 and IL-1β. Finally, while the Th1-related cytokines interferon-γ, IL-12p35, and IL-27p28 were overexpressed only in CD patients, IL-4, IL-5, and STAT-6 were also significantly increased in AS patients. Conclusion Our findings indicate that overexpression of IL-23, but not IL-17, is a pivotal feature of subclinical gut inflammation in AS. Identification of resident Paneth cells as a pivotal source of IL-23 in physiologic and pathologic conditions strongly suggests that IL-23 is a master regulator of gut mucosal immunity, providing a pathophysiologic significance to the reported association between IL-23 receptor polymorphisms and intestinal inflammation.

220 citations

Journal ArticleDOI
TL;DR: Severe ulcerative colitis is a life‐threatening disorder, despite i.v. glucocorticoids treatment, and infliximab has been proposed as a safe rescue therapy.
Abstract: Background Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. Aim To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. Methods Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. Results Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53). Seventy patients who survived colectomy and did not experience any fatal complications were followed-up for a median time of 23 months; 58 patients avoided colectomy during the follow-up. Forty-two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes. Conclusions Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long-term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.

161 citations

Journal ArticleDOI
TL;DR: In a prospective study of 444 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, HCC, and death, regardless of whether the patients had EVs.

128 citations

Journal ArticleDOI
TL;DR: The findings indicate that overexpression of IL-22, together with an increased number ofIL-22-producing NKp44+ NK cells, occurs in the gut of AS patients, where it appears to play a tissue-protective role.
Abstract: Objective The intestinal inflammation observed in patients with ankylosing spondylitis (AS) is characterized by an overexpression of interleukin-23 (IL-23). IL-23 is known to regulate IL-22 production through lamina propria NKp44+ natural killer (NK) cells, which are thought to be involved in protective mucosal mechanisms. This study was undertaken to evaluate the frequency of NKp44+ NK cells and the expression of IL-22 in the ileum of AS patients. Methods Tissue NKp44+ NK cells, NKp46+ NK cells, and IL-22–producing cells were analyzed by flow cytometry. Quantitative gene expression analysis of IL-22, IL-23, IL-17, STAT-3, and mucin 1 (MUC-1) was performed by reverse transcriptase–polymerase chain reaction on ileal samples from 15 patients with AS, 15 patients with Crohn's disease (CD), and 15 healthy controls. NKp44, pSTAT-3, and IL-22 expression was analyzed by immunohistochemistry. Results The frequency of NKp44+ but not NKp46+ NK cells was increased in the inflamed ileum of AS patients compared to CD patients and controls. The frequency of NKp46+ NK cells was significantly increased only in CD patients. Among CD4+ lymphocytes and NKp44+ NK cell subsets, the latter were the major source of IL-22 on lamina propria mononuclear cells from AS patients. Significant up-regulation of IL-22, IL-23p19, MUC-1, and STAT-3 transcripts in the terminal ileum of patients with AS was observed. Immunohistochemical analysis confirmed the increased IL-22 and pSTAT-3 expression in inflamed mucosa from AS and CD patients. Conclusion Our findings indicate that overexpression of IL-22, together with an increased number of IL-22–producing NKp44+ NK cells, occurs in the gut of AS patients, where it appears to play a tissue-protective role.

117 citations


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Journal ArticleDOI
TL;DR: Guidelines for clinical practice are aimed to indicate preferred approaches to medical problems as established by scientifically valid research, and are applicable to all physicians who address the subject regardless of specialty training or interests.

1,746 citations

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TL;DR: This guidance provides a data-supported approach to risk stratification, diagnosis, and management of patients with cirrhosis and portal hypertension (PH), varices, and variceal hemorrhage (VH), and statements are based on the following.

1,397 citations

Journal ArticleDOI
01 Feb 1932-Nature
TL;DR: It is scarcely an exaggeration to say that the recently issued preliminary report on the census of 1931 is one of the most sensational documents which has appeared for years, and that he who reads it intelligently will understand what is meant by saying that civilisation is in the melting pot.
Abstract: QUITE apart from the academic consideration that vital and medical statistics now form an obligatory part of the education of students seeking the University of London's diploma in public health, the demand for information about the methods of vital and medical statistics is increasing. The most casual reader of the newspapers is now aware that population problems are of serious practical importance and that the publications of the General Register Office cannot be ignored. It is scarcely an exaggeration to say that the recently issued preliminary report on the census of 1931 is one of the most sensational documents which has appeared for years, and that he who reads it intelligently will understand what is meant by saying that civilisation is in the melting pot. An Introduction to Medical Statistics. By Hilda M. Woods William T. Russell. Pp. x + 125. (London: P. S. King and Son, Ltd., 1931.) 7s. 6d.

1,329 citations

Journal ArticleDOI
TL;DR: The most widely used index for severe UC remains that of Truelove and Witts3: any patient who has a bloody stool frequency ≥ 6/day and a tachycardia (> 90 bpm), or temperature > 37.8 °C, or anaemia (haemoglobin 30 mm/h) has severe ulcerative colitis (Table 1.3) as mentioned in this paper.

1,318 citations