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Cetica V.,Azienda Ospedaliero | Sieni E.,Azienda Ospedaliero | Pende D.,Istituto di Ricovero e Cura rattere Scientifico | Danesino C.,University of Pavia | And 10 more authors.
Journal of Allergy and Clinical Immunology | Year: 2016

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. Objective This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. Methods From our registry, we have analyzed a total of 500 unselected patients with HLH. Results Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. Conclusion We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL. © 2015 The Authors.

Ciprandi G.,Istituto di Ricovero e Cura rattere Scientifico | De Amici M.,Hospital Pediatric Clinic | Giunta V.,Hospital Pediatric Clinic | Marseglia A.,University of Pavia | Marseglia G.,University of Pavia
Pediatric Dermatology | Year: 2013

Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by impaired immune response. Th9 cells are a sub-population of T cells that release interleukin (IL)-9. No study has investigated the role of IL-9 in AD. This study compared 64 children with AD with 45 healthy children. Serum IL-9 levels were measured and clinical symptoms were assessed. Children with AD had higher serum IL-9 levels than controls (p = 0.01). Clinical severity was significantly related to IL-9 level, indicating that IL-9 might exert a pathogenic role in symptom occurrence in individuals with AD. Children with AD may have higher serum IL-9 levels than healthy children, and IL-9 levels are significantly related to symptom severity. © 2012 Wiley Periodicals, Inc.

Karkouti K.,University of Toronto | Von Heymann C.,Charite - Medical University of Berlin | Jespersen C.M.,Novo Nordisk AS | Korte W.,Center for Laboratory Medicine | And 4 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2013

Objectives: Cardiac surgery with cardiopulmonary bypass frequently leads to excessive bleeding, obligating blood product transfusions. Because low factor XIII (FXIII) levels have been associated with bleeding after cardiac surgery, we investigated whether administering recombinant FXIII after cardiopulmonary bypass would reduce transfusions. Methods: In this double-blinded, placebo-controlled, multicenter trial, 409 cardiac surgical patients at moderate risk for transfusion were randomized to receive an intravenous dose of recombinant FXIII, 17.5 IU/kg (n = 143), 35 IU/kg (n = 138), or placebo (n = 128) after cardiopulmonary bypass. Transfusion guidelines were standardized. The primary efficacy outcome was avoidance of allogeneic blood products for 7 days postsurgery. Secondary outcomes included amount of blood products transfused and reoperation rate. Serious adverse events were measured for 7 weeks. Results: Study groups had comparable baseline characteristics and an approximately 40% decrease in FXIII levels after cardiopulmonary bypass. Thirty minutes postdose, FXIII levels were restored to higher than the lower 2.5th percentile of preoperative activity in 49% of the placebo group, and 85% and 95% of the 17.5- and 35-IU/kg recombinant FXIII groups, respectively (P <.05 for both treatments vs placebo). Transfusion avoidance rates were 64.8%, 64.3%, and 65.9% with placebo, 17.5 IU/kg, and 35 IU/kg recombinant FXIII (respective odds ratios against placebo, 1.05 [95% confidence interval, 0.61-1.80] and 0.99 [95% confidence interval, 0.57-1.72]). Groups had comparable adverse event rates. Conclusions: Replenishment of FXIII levels after cardiopulmonary bypass had no effect on transfusion avoidance, transfusion requirements, or reoperation in moderate-risk cardiac surgery patients (ClinicalTrials.gov identifier: NCT00914589). Copyright © 2013 by The American Association for Thoracic Surgery.

Lambiase A.,Biomedical University of Rome | Micera A.,Istituto di Ricovero e Cura rattere Scientifico | Sacchetti M.,Biomedical University of Rome | Mantelli F.,Biomedical University of Rome | Bonini S.,Biomedical University of Rome
Clinical Science | Year: 2011

The ocular surface is the first line of defence in the eye against environmental microbes. The ocular innate immune system consists of a combination of anatomical, mechanical and immunological defence mechanisms. TLRs (Toll-like receptors), widely expressed by the ocular surface, are able to recognize microbial pathogens and to trigger the earliest immune response leading to inflammation. Increasing evidence highlights the crucial role of TLRs in regulating innate immune responses during ocular surface infective and non-infective inflammatory conditions. In addition, recent observations have shown that TLRs modulate the adaptive immune response, also playing an important role in ocular autoimmune and allergic diseases. One of the main goals of ocular surface treatment is to control the inflammatory reaction in order to preserve corneal integrity and transparency. Recent experimental evidence has shown that specific modulation of TLR pathways induces an improvement in several ocular inflammatory conditions, such as allergic conjunctivitis, suggesting new therapeutic anti-inflammatory strategies. The purpose of the present review is to summarize the current knowledge of TLRs at the ocular surface and to propose them as potential targets of therapy for ocular inflammatory conditions. © The Authors Journal compilation © 2011 Biochemical Society.

Parazzini F.,Gynecology and Neonatology | Cipriani S.,Gynecology and Neonatology | Bravi F.,Istituto di Ricovero e Cura rattere Scientifico | Bravi F.,University of Milan | And 4 more authors.
American Journal of Obstetrics and Gynecology | Year: 2013

Objective: To offer a general figure of the available data on the relation between alcohol intake and risk of endometriosis, we conducted a systematic review and a metaanalysis of studies published up to May 2012. Study Design: We carried out a literature search of all case-control and cohort studies published as original articles in English up to May 2012. Only those papers that were published as full-length articles were considered. Pooled estimates of the relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated using fixed or, when significant heterogeneity among estimates emerged, random effects models. A total of 15 studies were identified for the review. Results: The summary estimate was 1.24 (95% CI, 1.12-1.36) for any alcohol intake vs no alcohol intake. Considering the results of the analyses of infrequent, moderate/regular, and heavy alcohol intake vs no alcohol intake, the summary RR estimates were, respectively, 1.14 (95% CI, 0.86-1.52), 1.23 (95% CI, 1.08-1.40), and 1.19 (95% CI, 0.99-1.43). Three studies reported separate results for current and former drinkers, and the summary RR were 1.42 (95% CI, 1.14-1.76) and 1.09 (95% CI, 0.83-1.43), respectively. Conclusion: The present metaanalysis provides evidence for an association between alcohol consumption and endometriosis risk. Further studies are needed to clarify whether alcohol consumption may exacerbate an existing disease or could be related to the severity of the disease. © 2013 Mosby, Inc. All rights reserved.

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