FP045MATERNAL FOETAL OUTCOMES IN PREGNANT WOMEN WITH POLYCYSTIC KIDNEY DISEASE: HIGH RISK FOR HYPERTENSIVE DISORDERS OF PREGNANCY

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Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Dialysis or a Plant-Based Diet in Advanced CKD in Pregnancy? A Case Report and Critical Appraisal of the Literature

Pregnancy is increasingly reported in chronic kidney disease (CKD), reflecting higher awareness, improvements in materno-foetal care, and a more flexible attitude towards “allowing„ pregnancy in the advanced stages of CKD. Success is not devoid of problems and an important grey area regards the indications for starting dialysis (by urea level, clinical picture, and residual glomerular filtration rate) and for dietary management. The present case may highlight the role of plant-based diets in dietary management in pregnant CKD women, aimed at retarding dialysis needs. The case. A 28-year-old woman, affected by glomerulocystic disease and unilateral renal agenesis, in stage-4 CKD, was referred at the 6th week of amenorrhea: she weighed 40 kg (BMI 16.3), was normotensive, had no sign of oedema, her serum creatinine was 2.73 mg/dL, blood urea nitrogen (BUN) 35 mg/dL, and proteinuria 200 mg/24 h. She had been on a moderately protein-restricted diet (about 0.8 g/kg/real body weight, 0.6 per ideal body weight) since childhood. Low-dose acetylsalicylate was added, and a first attempt to switch to a protein-restricted supplemented plant-based diet was made and soon stopped, as she did not tolerate ketoacid and aminoacid supplementation. At 22 weeks of pregnancy, creatinine was increased (3.17 mg/dL, BUN 42 mg/dL), dietary management was re-discussed and a plant-based non-supplemented diet was started. The diet was associated with a rapid decrease in serum urea and creatinine; this favourable effect was maintained up to the 33rd gestational week when a new rise in urea and creatinine was observed, together with signs of cholestasis. After induction, at 33 weeks + 6 days, she delivered a healthy female baby, adequate for gestational age (39th centile). Urea levels decreased after delivery, but increased again when the mother resumed her usual mixed-protein diet. At the child’s most recent follow-up visit (age 4 months), development was normal, with normal weight and height (50th⁻75th centile). In summary, the present case confirms that a moderate protein-restricted diet can be prescribed in pregnancies in advanced CKD without negatively influencing foetal growth, supporting the importance of choosing a plant-based protein source, and suggests focusing on the diet’s effects on microcirculation to explain these favourable results

Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene

Shwachman-Diamond syndrome (SDS) (OMIM 260400) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, skeletal, and hematological abnormalities and bone marrow (BM) dysfunction. Mutations in the SBDS gene cause SDS. Clonal chromosome anomalies are often present in BM, i(7)(q10) and del(20q) being the most frequent ones. We collected 6 SDS cases with del(20q): a cluster of imprinted genes, including L3MBTL1 and SGK2 is present in the deleted region. Only the paternal allele is expressed for these genes. Based on these data, we made the hypothesis that the loss of this region, in relation to parental origin of deletion, may be of relevance for the hematological phenotype. By comparing hematological data of our 6 cases with a group of 20 SDS patients without evidence of del(20q) in BM, we observed a significant difference for Hb levels (P\u2009<\u20090.012), and a difference slightly above the significance level for RBC counts (P\u2009<\u20090.053): in both cases the values were higher in patients with del(20q). We also report preliminary evidence for an increased number of BFU-E colonies in cases with paternal deletion, data on the presence of the deletion in colonies and in mature circulating lymphocytes. \ua9 2016 Wiley Periodicals, Inc

Education as Risk Factor of Mild Cognitive Impairment: The Link to the Gut Microbiome

peer reviewedBackground: With differences apparent in the gut microbiome in mild cognitive impairment (MCI) and dementia, and risk factors of dementia linked to alterations of the gut microbiome, the question remains if gut microbiome characteristics may mediate associations of education with MCI. Objectives: We sought to examine potential mediation of the association of education and MCI by gut microbiome diversity or composition. Design: Cross-sectional study. Setting: Luxembourg, the Greater Region (surrounding areas in Belgium, France, Germany). Participants: Control participants of the Luxembourg Parkinson’s Study. Measurements: Gut microbiome composition, ascertained with 16S rRNA gene amplicon sequencing. Differential abundance, assessed across education groups (0–10, 11–16, 16+ years of education). Alpha diversity (Chao1, Shannon and inverse Simpson indices). Mediation analysis with effect decomposition was conducted with education as exposure, MCI as outcome and gut microbiome metrics as mediators. Results: After exclusion of participants below 50, or with missing data, n=258 participants (n=58 MCI) were included (M [SD] Age=64.6 [8.3] years). Higher education (16+ years) was associated with MCI (Odds ratio natural direct effect=0.35 [95% CI 0.15–0.81]. Streptococcus and Lachnospiraceae-UCG-001 genera were more abundant in higher education. Conclusions: Education is associated with gut microbiome composition and MCI risk without clear evidence for mediation. However, our results suggest signatures of the gut microbiome that have been identified previously in AD and MCI to be reflected in lower education and suggest education as important covariate in microbiome studies.MCI-BIOME_20193. Good health and well-bein

Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study

none331noneProietti, Marco; Nobili, Alessandro; Raparelli, Valeria; Napoleone, Laura; Mannucci, Pier Mannuccio; Lip, Gregory Y. H.; Pasina, Luca; Franchi, Carlotta; Marcucci, Maura; Eldin, Tarek Kamal; Di Blanca, Maria Pia Donatella; Perticone, Francesco; Salerno, Francesco; Corrao, Salvatore; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Guarnieri, Gianfranco; Zanetti, Michela; Fernandes, Giovanni; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Lupattelli, Graziana; Bianconi, Vanessa; Paciullo, Francesco; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Salvatore, Teresa; Sasso, Ferdinando Carlo; Girelli, Domenico; Olivieri, Oliviero; Matteazzi, Thomas; Barbagallo, Mario; Plances, Lidia; Alcamo, Roberta; Licata, Giuseppe; Calvo, Luigi; Valenti, Maria; Zoli, Marco; Arnò, Raffaella; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Palasciano, Giuseppe; Modeo, Maria Ester; Peragine, Maria; Pappagallo, Fabrizio; Di Gennaro, Carla; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Cappellini, Maria Domenica; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Mari, Daniela; Rossi, Paolo Dionigi; Ottolini, Barbara Brignolo; Pugliese, Stefania; Lenti, Marco Vincenzo; Padula, Donatella; Murialdo, Giovanni; Marra, Alessio; Cattaneo, Federico; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Davì, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Meroni, Maria Rachele; Perin, Paolo Cavallo; Lorenzati, Bartolomeo; Gruden, Gabriella; Bruno, Graziella; Amione, Cristina; Fornengo, Paolo; Tassara, Rodolfo; Melis, Deborah; Rebella, Lara; Pretti, Vincenzo; Masala, Maristella Salvatora; Bolondi, Luigi; Rasciti, Leonardo; Serio, Ilaria; Fanelli, Filippo Rossi; Amoroso, Antonio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; Franceschi, Francesco; De Marco, Guido; Chiara, Cordischi; Marta, Sabbatini; Romanelli, Giuseppe; Delitala, Giuseppe; Chiesa, Deborah; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Annoni, Giorgio; Corsi, Maurizio; Zazzetta, Sara; Bellelli, Giuseppe; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Sesti, Giorgio; Loria, Paola; Becchi, Maria Angela; Martucci, Gianfranco; Fantuzzi, Alessandra; Maurantonio, Mauro; Carta, Stefano; Atzori, Sebastiana; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Agnelli, Giancarlo; Marchesini, Emanuela; Fabris, Fabrizio; Carlon, Michela; Baritusso, Aldo; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Valerio, Raffaella; Capobianco, Caterina; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Testa, Elisa; Serraino, Cristina; Fargion, Silvia; Bonara, Paola; Periti, Giulia; Porzio, Marianna; Peyvandi, Flora; Tedeschi, Alberto; Rossio, Raffaella; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Gobbo, Giulia; Balduini, Carlo L.; Bertolino, Giampiera; Provini, Stella; Quaglia, Federica; Dallegri, Franco; Ottonello, Luciano; Liberale, Luca; Chin, Wu Sheng; Carassale, Laura; Caporotundo, Silvia; Traisci, Giancarlo; De Feudis, Lucrezia; Di Carlo, Silvia; Liberato, Nicola Lucio; Buratti, Alberto; Tognin, Tiziana; Bianchi, Giovanni Battista; Giaquinto, Sabrina; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Rozzini, Renzo; Falanga, Lina; Montrucchio, Giuseppe; Greco, Elisabetta; Tizzani, Pietro; Petitti, Paolo; Perciccante, Antonio; Coralli, Alessia; Salmi, Raffaella; Gaudenzi, Piergiorgio; Gamberini, Susanna; Semplicini, Andrea; Gottardo, Lucia; Vendemiale, Gianluigi; Serviddio, Gaetano; Forlano, Roberta; Masala, Cesare; Mammarella, Antonio; Basili, Stefania; Perri, Ludovica; Landolfi, Raffaele; Montalto, Massimo; Mirijello, Antonio; Vallone, Carla; Bellusci, Martino; Setti, Donatella; Pedrazzoli, Filippo; Guasti, Luigina; Castiglioni, Luana; Maresca, Andrea; Squizzato, Alessandro; Molaro, Marta; Bertolotti, Marco; Mussi, Chiara; Libbra, Maria Vittoria; Miceli, Andrea; Pellegrini, Elisa; Carulli, Lucia; Sciacqua, Angela; Quero, Michele; Bagnato, Chiara; Corinaldesi, Roberto; De Giorgio, Roberto; Serra, Mauro; Grasso, Valentina; Ruggeri, Eugenio; Salvi, Andrea; Leonardi, Roberto; Grassini, Chiara; Mascherona, Ilenia; Minelli, Giorgio; Maltese, Francesca; Gabrielli, Armando; Mattioli, Massimo; Capeci, William; Martino, Giuseppe Pio; Messina, Silvia; Ghio, Riccardi; Favorini, Serena; Col, Anna Dal; Minisola, Salvatore; Colangelo, Luciano; Afeltra, Antonella; Alemanno, Pamela; Marigliano, Benedetta; Castellino, Pietro; Blanco, Julien; Zanoli, Luca; Cattaneo, Marco; Fracasso, Paola; Amoruso, Maria Valentina; Saracco, Valter; Fogliati, Marisa; Bussolino, Carlo; Durante, Vittorio; Eusebi, Giovanna; Tirotta, Daniela; Mete, Francesca; Gino, Miriam; Cittadini, Antonio; Arcopinto, Michele; Salzano, Andrea; Bobbio, Emanuele; Marra, Alberto Maria; Sirico, Domenico; Moreo, Guido; Scopelliti, Francesco; Gasparini, Francesca; Cocca, Melissa; Nieves, Ramirez Duque; Alberto, Muela Molinero; Pedro, Abad Requejo; Vanessa, Lopez Pelaez; Lara, Tamargo; Xavier, Corbella Viros; Francesc, Formiga; Jesus, Diez Manglano; Esperanza, Bejarano Tello; Behamonte Esther, Del Corral; Maria, Sevil Puras; Romero, Manuel; Blanca, Pinilla Llorente; Cristina, Lopez Gonzalez-Cobos; Victoria, Villalba Garcia M.; Saez, Lopez; Bosco, Juan; Susana, Sanz Baena; Marta, Arroyo Gallego; Concepcion, Gonzalez Becerra; Antonio, Fernandez Moyano; Hernandez, Mercedes Gomez; Borrego, Manuel Poyato; Raquel, Pacheco Cuadros; Florencia, Perez Rojas; Beatriz, Garcia Olid; Sara, Carrascosa Garcia; Cervellera Alfonso, Gonzalez-Cruz; Marta, Peinado Martinez; Alberto, Ruiz Cantero; Antonio, Albarracín Arraigosa; Montserrat, Godoy Guerrero; Miguel Ángel, Barón Ramos; Manuel, Machin Jose; Ignacio, Novo Veleiro; Lucía, Alvela Suarez; Alfonso, Lopez; David, Rubal Bran; Iria, Iñiguez Vazquez; Monica, Rios Prego; On behalf of REPOSI investigators, nullProietti, Marco; Nobili, Alessandro; Raparelli, Valeria; Napoleone, Laura; Mannucci, Pier Mannuccio; Lip, Gregory Y. H.; Pasina, Luca; Franchi, Carlotta; Marcucci, Maura; Eldin, Tarek Kamal; Di Blanca, Maria Pia Donatella; Perticone, Francesco; Salerno, Francesco; Corrao, Salvatore; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Guarnieri, Gianfranco; Zanetti, Michela; Fernandes, Giovanni; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Lupattelli, Graziana; Bianconi, Vanessa; Paciullo, Francesco; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Salvatore, Teresa; Sasso, Ferdinando Carlo; Girelli, Domenico; Olivieri, Oliviero; Matteazzi, Thomas; Barbagallo, Mario; Plances, Lidia; Alcamo, Roberta; Licata, Giuseppe; Calvo, Luigi; Valenti, Maria; Zoli, Marco; Arnò, Raffaella; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Palasciano, Giuseppe; Modeo, Maria Ester; Peragine, Maria; Pappagallo, Fabrizio; Di Gennaro, Carla; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Cappellini, Maria Domenica; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Mari, Daniela; Rossi, Paolo Dionigi; Ottolini, Barbara Brignolo; Pugliese, Stefania; Lenti, Marco Vincenzo; Padula, Donatella; Murialdo, Giovanni; Marra, Alessio; Cattaneo, Federico; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Davì, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Meroni, Maria Rachele; Perin, Paolo Cavallo; Lorenzati, Bartolomeo; Gruden, Gabriella; Bruno, Graziella; Amione, Cristina; Fornengo, Paolo; Tassara, Rodolfo; Melis, Deborah; Rebella, Lara; Pretti, Vincenzo; Masala, Maristella Salvatora; Bolondi, Luigi; Rasciti, Leonardo; Serio, Ilaria; Fanelli, Filippo Rossi; Amoroso, Antonio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; Franceschi, Francesco; De Marco, Guido; Chiara, Cordischi; Marta, Sabbatini; Romanelli, Giuseppe; Delitala, Giuseppe; Chiesa, Deborah; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Annoni, Giorgio; Corsi, Maurizio; Zazzetta, Sara; Bellelli, Giuseppe; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Sesti, Giorgio; Loria, Paola; Becchi, Maria Angela; Martucci, Gianfranco; Fantuzzi, Alessandra; Maurantonio, Mauro; Carta, Stefano; Atzori, Sebastiana; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Agnelli, Giancarlo; Marchesini, Emanuela; Fabris, Fabrizio; Carlon, Michela; Baritusso, Aldo; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Valerio, Raffaella; Capobianco, Caterina; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Testa, Elisa; Serraino, Cristina; Fargion, Silvia; Bonara, Paola; Periti, Giulia; Porzio, Marianna; Peyvandi, Flora; Tedeschi, Alberto; Rossio, Raffaella; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Gobbo, Giulia; Balduini, Carlo L.; Bertolino, Giampiera; Provini, Stella; Quaglia, Federica; Dallegri, Franco; Ottonello, Luciano; Liberale, Luca; Chin, Wu Sheng; Carassale, Laura; Caporotundo, Silvia; Traisci, Giancarlo; De Feudis, Lucrezia; Di Carlo, Silvia; Liberato, Nicola Lucio; Buratti, Alberto; Tognin, Tiziana; Bianchi, Giovanni Battista; Giaquinto, Sabrina; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Rozzini, Renzo; Falanga, Lina; Montrucchio, Giuseppe; Greco, Elisabetta; Tizzani, Pietro; Petitti, Paolo; Perciccante, Antonio; Coralli, Alessia; Salmi, Raffaella; Gaudenzi, Piergiorgio; Gamberini, Susanna; Semplicini, Andrea; Gottardo, Lucia; Vendemiale, Gianluigi; Serviddio, Gaetano; Forlano, Roberta; Masala, Cesare; Mammarella, Antonio; Basili, Stefania; Perri, Ludovica; Landolfi, Raffaele; Montalto, Massimo; Mirijello, Antonio; Vallone, Carla; Bellusci, Martino; Setti, Donatella; Pedrazzoli, Filippo; Guasti, Luigina; Castiglioni, Luana; Maresca, Andrea; Squizzato, Alessandro; Molaro, Marta; Bertolotti, Marco; Mussi, Chiara; Libbra, Maria Vittoria; Miceli, Andrea; Pellegrini, Elisa; Carulli, Lucia; Sciacqua, Angela; Quero, Michele; Bagnato, Chiara; Corinaldesi, Roberto; De Giorgio, Roberto; Serra, Mauro; Grasso, Valentina; Ruggeri, Eugenio; Salvi, Andrea; Leonardi, Roberto; Grassini, Chiara; Mascherona, Ilenia; Minelli, Giorgio; Maltese, Francesca; Gabrielli, Armando; Mattioli, Massimo; Capeci, William; Martino, Giuseppe Pio; Messina, Silvia; Ghio, Riccardi; Favorini, Serena; Col, Anna Dal; Minisola, Salvatore; Colangelo, Luciano; Afeltra, Antonella; Alemanno, Pamela; Marigliano, Benedetta; Castellino, Pietro; Blanco, Julien; Zanoli, Luca; Cattaneo, Marco; Fracasso, Paola; Amoruso, Maria Valentina; Saracco, Valter; Fogliati, Marisa; Bussolino, Carlo; Durante, Vittorio; Eusebi, Giovanna; Tirotta, Daniela; Mete, Francesca; Gino, Miriam; Cittadini, Antonio; Arcopinto, Michele; Salzano, Andrea; Bobbio, Emanuele; Marra, Alberto Maria; Sirico, Domenico; Moreo, Guido; Scopelliti, Francesco; Gasparini, Francesca; Cocca, Melissa; Nieves, Ramirez Duque; Alberto, Muela Molinero; Pedro, Abad Requejo; Vanessa, Lopez Pelaez; Lara, Tamargo; Xavier, Corbella Viros; Francesc, Formiga; Jesus, Diez Manglano; Esperanza, Bejarano Tello; Behamonte Esther, Del Corral; Maria, Sevil Puras; Romero, Manuel; Blanca, Pinilla Llorente; Cristina, Lopez Gonzalez-Cobos; Victoria, Villalba Garcia M.; Saez, Lopez; Bosco, Juan; Susana, Sanz Baena; Marta, Arroyo Gallego; Concepcion, Gonzalez Becerra; Antonio, Fernandez Moyano; Hernandez, Mercedes Gomez; Borrego, Manuel Poyato; Raquel, Pacheco Cuadros; Florencia, Perez Rojas; Beatriz, Garcia Olid; Sara, Carrascosa Garcia; Cervellera Alfonso, Gonzalez-Cruz; Marta, Peinado Martinez; Alberto, Ruiz Cantero; Antonio, Albarracín Arraigosa; Montserrat, Godoy Guerrero; Miguel Ángel, Barón Ramos; Manuel, Machin Jose; Ignacio, Novo Veleiro; Lucía, Alvela Suarez; Alfonso, Lopez; David, Rubal Bran; Iria, Iñiguez Vazquez; Monica, Rios Prego; On behalf of REPOSI investigators, Nul