Impact of pneumococcal conjugate vaccination: a retrospective study of hospitalization for pneumonia in North-East Italy

Introduction. Pneumonia remains a common reason for hospitalizing infants and the elderly worldwide, and streptococcal infection is often responsible. The aim of this study was to assess the burden of pneumonia in a large general population. Methods. All pneumonia-related hospitalizations from 2004 to 2013 in north-east Italy were identified from the hospital records with a first-listed diagnosis on discharge of bacterial pneumonia, or a first-listed diagnosis on discharge of meningitis, septicemia or empyema associated with a secondary diagnosis of bacterial pneumonia. We identified major comorbidities, calculated agespecific case-fatality rates (CFR), and estimated the related cost to the health care system. Results. Of the 125,722 hospitalizations identified, 96.9% were cases of pneumonia, 2.4% of septicemia, 0.4% of meningitis, and 0.3% of empyema; 75.3% of hospitalizations involved 65 65-yearolds. The overall CFR was 12.4%, and it increased with age, peaking in people over 80 (19.6%). The mean annual pneumonia-associated hospitalization rate was 204.6 per 100,000 population, and it peaked in 0- to 4-year-old children (325.6 per 100,000 in males, 288.9 per 100,000 in females), and adults over 65 (844.9 per 100,000 in males, 605.7 per 100,000 in females). Hospitalization rates dropped over the years for the 0-4 year-olds, and rose for people over 80. The estimated overall annual cost of these pneumonia-related hospitalizations was approximately \u20ac 41 million. Conclusions. This study shows that the burden on resources for pneumonia-related hospitalization is an important public health issue. Prevention remains the most valuable tool for containing pneumonia, and vaccination strategies can help in the primary prevention of infection, possibly reducing the number of cases in all age groups

Assessment of Natural Resources Use for Sustainable Development - DPSIR Framework for Case Studies in Portsmouth and Thames Gateway, U.K.

This chapter reports on the uses of the DPSIR framework to assess the sustainability of the intertidal environments within the two UK case study areas, Portsmouth and Thames Gateway. It focuses on statutory conservation areas dominated by intertidal habitats. Two are located in Portsmouth (Portsmouth and Langstone Harbours) and four in the Thames Gateway (Benfleet Marshes, South Thames Estuary, Medway Estuary and the Swale in the Thames Gateway). Based on the reduction of a number of pressures and impacts observed in recent decades and the improvement of overall environmental quality, all six SSSIs are considered to be sustainable in the short and medium term. In the future, it is possible that the impacts of climate change, especially sea-level rise, might result in further reduction in the area and/or quality of intertidal habitats. Further integration between conservation and planning objectives (both for urban development and management of flood risk) at local level is needed to support the long-term sustainability of intertidal habitats

Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy

open116noBACKGROUND: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. METHODS: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). CONCLUSIONS: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.openTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Sarah Shalaby, Raffaella Petrara, Patrizia Burra, Giacomo Zanus, Stefano Zanini,Paolo Rigotti; Maria Rendina, AlfredoDi Leo, Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, Augusto Lauro, Antonio Daniele Pinna, PaoloDi Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, PaolaTodeschini, Laura Panicali, Chiara Valentini, Umberto Baccarani, Andrea Risaliti, Gian Luigi Adani, Dario Lorenzin, Giuseppe Maria Ettorre, Giovanni Vennarecci,Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, LuciaMiglioresi, Francesco Nudo, Massimo Rossi,Gianluca Mennini, Luca Toti, GiuseppeTisone, Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria,Carlo Gazia, Chiara Belardi, ClaudiaCimaglia, Alessandro Agresta, Gianpiero D’Offizi, Ubaldo Visco Comandini,Raffaella Lionetti, Marzia Montalbano, Chiara Taibi, Giovanni Fantola, Fausto Zamboni, Gian Benedetto Piredda,Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano, Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi,Emanuela Vaccher, Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, LindaDe Luca, Maurizio Iaria, Enzo Capocasale,Elena Cremaschi, Silvio Sandrini, Francesca Valerio,Valentina Mazzucotelli, Nicola Bossini, Gisella Setti, Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida,Alessia Giaquinta, Domenico Zerbo, GhilBusnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, ValerianaColombo, Maria Chiara Sghirlanzoni , Piergiorgio Messa, Antonio Leoni , Laura Galatioto, Salvatore Gruttadauria, Vito Sparacino, FlaviaCaputo, Barbara Buscemi ,Franco Cit-terio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi Giuseppe Paolo Segoloni, Luigi Biancone, AntonioLavacca, Maria Cristina Maresca, CarmeloCascone, Bice Virgilio, Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di CiccoTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Shalaby, Sarah; Petrara, MARIA RAFFAELLA; Burra, Patrizia; Zanus, Giacomo; Zanini, Stefano; Rigotti, Paolo; Maria, Rendina; Alfredodi, Leo; Francesco Paolo Schena, ; Giuseppe, Grandaliano; Marco, Fiorentino; Augusto, Lauro; Antonio Daniele Pinna, ; Paolodi, Gioia; Sara, Pellegrini; Chiara, Zanfi; Maria Piera Scolari, ; Sergio, Stefoni; Paolatodeschini, ; Laura, Panicali; Chiara, Valentini; Umberto, Baccarani; Andrea, Risaliti; Gian Luigi Adani, ; Dario, Lorenzin; Giuseppe Maria Ettorre, ; Giovanni, Vennarecci; Marco, Colasanti; Manuela, Coco; Fabrizio, Ettorre; Roberto, Santoro; Luciamiglioresi, ; Francesco, Nudo; Massimo, Rossi; Gianluca, Mennini; Luca, Toti; Giuseppetisone, ; Annachiara, Casella; Laura, Fazzolari; Daniele, Sforza; Giuseppe, Iaria; Carlo, Gazia; Chiara, Belardi; Claudiacimaglia, ; Alessandro, Agresta; Gianpiero, D’Offizi; Ubaldo Visco Comandini, ; Raffaella, Lionetti; Marzia, Montalbano; Chiara, Taibi; Giovanni, Fantola; Fausto, Zamboni; Gian Benedetto Piredda, ; Maria Benigna Michittu, ; Maria Gavina Murgia, ; Bruno, Onano; Lucia, Fratino; Luigino Dal Maso, ; Paolo De Paoli, ; Diana, Verdirosi; Emanuela, Vaccher; Francesco, Pisani; Antonio, Famulari; Federica, Delreno; Samuele, Iesari; Lindade, Luca; Maurizio, Iaria; Enzo, Capocasale; Elena, Cremaschi; Silvio, Sandrini; Francesca, Valerio; Valentina, Mazzucotelli; Nicola, Bossini; Gisella, Setti; Massimiliano, Veroux; Pierfrancesco, Veroux; Giuseppe, Giuffrida; Alessia, Giaquinta; Domenico, Zerbo; Ghilbusnach, ; Laura Di Leo, ; Maria Luisa Perrino, ; Marialuisa, Querques; Valerianacolombo, ; Maria Chiara Sghirlanzoni, ; Piergiorgio, Messa; Antonio, Leoni; Laura, Galatioto; Salvatore, Gruttadauria; Vito, Sparacino; Flaviacaputo, ; Barbara, Buscemi; Franco, Cit-terio; Gionata, Spagnoletti; Maria Paola Salerno, ; Evaldo Favi Giuseppe Paolo Segoloni, ; Luigi, Biancone; Antoniolavacca, ; Maria Cristina Maresca, ; Carmelocascone, ; Bice, Virgilio; Donato, Donati; Fiorella, Dossi; Andrea, Fontanella; Andrea, Ambrosini; Marco Di Cicco

Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect.

BACKGROUND AND PURPOSE: The objective was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis and in the migraine-ischemic stroke pathway. METHODS: A first genotype-migraine association study was conducted on 100 patients with migraine with aura (MA), 106 with migraine without aura (MO), and 105 subjects without migraine, which provided evidence in favor of association of the TT677 MTHFR genotype with increased risk of MA compared with both control subjects (OR, 2.48; 95% CI, 1.11 to 5.58) and patients with MO (OR, 2.21; 95% CI, 1.01 to 4.82). Based on these findings, mediational models of the genotype-migraine-stroke pathway were fitted on a group of 106 patients with spontaneous cervical artery dissection, 227 young patients whose ischemic stroke was unrelated to a spontaneous cervical artery dissection (noncervical artery dissection), and 187 control subjects, and a genotype-migraine partial mediation model was selected. RESULTS: Both migraine and the TT genotype were more strongly associated to the subgroup of patients with spontaneous cervical artery dissection (OR, 4.06; 95% CI, 1.63 to 10.02 for MA; OR, 5.45; 95% CI, 3.03 to 9.79 for MO; OR, 2.87; 95% CI, 1.45 to 5.68 for TT genotype) than to the subgroup of patients with noncervical artery dissection ischemic stroke (OR, 2.22; 95% CI, 1.00 to 4.96 for MA; OR, 1.81; 95% CI, 1.02 to 3.22 for TT genotype) as compared with controls. CONCLUSIONS: Migraine may act as mediator in the methylenetetrahydrofolate reductase-ischemic stroke pathway with a more prominent effect in the subgroup of patients with spontaneous artery dissection

Killer Ig-like receptors (kirs). their role in nk cell modulation and developments leading to their clinical exploitation

Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell function and the molecular mechanisms of tumor cell killing. Stemmed from the seminal discoveries in early ‘90s, in which Alessandro Moretta was the major actor, an extraordinary amount of research on KIR specificity, genetics, polymorphism, and repertoire has followed. These basic notions on NK cells and their receptors have been successfully translated to clinical applications, primarily to the haploidentical hematopoietic stem cell transplantation to cure otherwise fatal leukemia in patients with no HLA compatible donors. The finding that NK cells may express the PD-1 inhibitory checkpoint, particularly in cancer patients, may allow understanding how anti-PD-1 therapy could function also in case of HLA class Ineg tumors, usually susceptible to NK-mediated killing. This, together with the synergy of therapeutic anti-checkpoint monoclonal antibodies, including those directed against NKG2A or KIRs, emerging in recent or ongoing studies, opened new solid perspectives in cancer therapy

General Argyres-Douglas Theory

We construct a large class of Argyres-Douglas type theories by compactifying six dimensional (2,0) A_N theory on a Riemann surface with irregular singularities. We give a complete classification for the choices of Riemann surface and the singularities. The Seiberg-Witten curve and scaling dimensions of the operator spectrum are worked out. Three dimensional mirror theory and the central charges a and c are also calculated for some subsets, etc. Our results greatly enlarge the landscape of N=2 superconformal field theory and in fact also include previous theories constructed using regular singularity on the sphere.Comment: 55 pages, 20 figures, minor revision and typos correcte

Connective tissue anomalies in patients with spontaneous cervical artery dissection.

OBJECTIVE: To investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD). METHODS: We systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD. RESULTS: The study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045). CONCLUSIONS: Connective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease

P2X7 receptor antagonist reduces fibrosis and inflammation in a mouse model of alpha-sarcoglycan muscular dystrophy

Limb-girdle muscular dystrophy R3, a rare genetic disorder affecting the limb proximal muscles, is caused by mutations in the α-sarcoglycan gene (Sgca) and aggravated by an immune-mediated damage, finely modulated by the extracellular (e)ATP/purinoceptors axis. Currently, no specific drugs are available. The aim of this study was to evaluate the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079. Sgca knockout mice were treated with A438079 every two days at 3 mg/Kg for 24 weeks. The P2X7 antagonist improved clinical parameters by ameliorating mice motor function and decreasing serum creatine kinase levels. Histological analysis of muscle morphology indicated a significant reduction of the percentage of central nuclei, of fiber size variability and of the extent of local fibrosis and inflammation. A cytometric characterization of the muscle inflammatory infiltrates showed that A438079 significantly decreased innate immune cells and upregulated the immunosuppressive regulatory T cell subpopulation. In α-sarcoglycan null mice, the selective P2X7 antagonist A438079 has been shown to be effective to counteract the progression of the dystrophic phenotype and to reduce the inflammatory response. P2X7 antagonism via selective inhibitors could be included in the immunosuppressant strategies aimed to dampen the basal immune-mediated damage and to favor a better engraftment of gene-cell therapies