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101. Acute Hepatitis of Unknown Etiology Among Young Children

Author

Indolfi, Giuseppe, Czubkowski, Piotr, Fitzpatrick, Emer, Gonzales, Emmanuel, Gupte, Girish, Mancell, Sara, Mozer-Glassberg, Yael, Nicastro, Emanuele, Norman, Junge, Stephenne, Xavier, Zellos, Aglaia, and Samyn, Marianne

Abstract

In April 2022, an increased incidence of acute hepatitis cases of unknown etiology among previously healthy children across the United Kingdom was described. Since, more than 270 cases from the United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than 6 years of age. The clinical presentation was nonspecific with diarrhea and vomiting usually preceding the appearance of jaundice, abdominal pain, nausea, and malaise. Approximately 5% have required liver transplantation. An infectious etiology has been considered likely given the epidemiological and clinical features of the reported cases. Between 50 and 60% of the children tested were diagnosed with adenovirus infection although a clear etiological connection has still to be demonstrated. No link with SARS-CoV-2 infection and COVID-19 vaccine was found. What is not clear to date is whether the high number of acute hepatitis cases reported is related to a true increase in incidence or heightened awareness following on from the initial reports from the United Kingdom. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed a paper on the current outbreak of acute hepatitis of unknown etiology recognizing its importance and the need of approaching the current situation with a scientifically rigorous approach. The aims of the article are to summarize the current knowledge and to identify the most pertinent issues regarding the diagnosis and management of this condition and the research questions raised.

Published
2022
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107. Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy.

Author

Curcio, Antonio, Malovini, Alberto, Mazzanti, Andrea, Memmi, Mirella, Gambelli, Patrick, La Rosa, Francesca, Bloise, Raffaella, Indolfi, Ciro, Bellazzi, Riccardo, and Napolitano, Carlo

Abstract

Background: The genetic architecture of Brugada syndrome (BrS) is emerging as an increasingly complex area of investigation. The identification of genetically homogeneous populations can provide mechanistic insights and improve genotype-phenotype correlation.Objective: To characterize and define the clinical implications of a novel BrS founder mutation. Using a haplotype-based approach we investigated whether 2 SCN5A genetic variants could derive from founder events.Methods: Single nucleotide polymorphisms were genotyped in 201 subjects, haplotypes reconstructed, and mutational age estimated. Clinical phenotypes and historical records were collected.Results: A SCN5A variant (c.3352C>T; p.Gln1118Ter) was identified in 3 probands with BrS originating from south Italy. The same mutation was identified in a proband from central Italy and in 1 U.S. resident subject with Italian ancestry. The 5 individuals carried a common core haplotype, whose frequency was extremely low in local noncarrier probands and in population controls (0%-6.06%). The clinical presentation included multigenerational dominant transmission of Brugada electrocardiographic pattern, high incidence of sudden cardiac death (SCD), and cardiac conduction defects (CCD). We reconstructed 7-generation pedigrees with common geographic origin. Variant's age estimates suggested that origin of the p.Gln1118Ter dates back 76 generations (95% confidence interval: 28-200). A second SCN5A variant (c.5350G>A; p.Glu1784Lys) identified in the region did not show similar founder signal.Conclusion: p.Gln1118Ter is a novel BrS/CCD/SCD founder mutation. We illustrate how these findings provide insights on the inheritance patterns and phenotypes associated with SCN5A mutation. [ABSTRACT FROM AUTHOR]

Published
2021
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108. Appropriateness criteria for the use of cardiac computed tomography, SIC-SIRM part 2: acute chest pain evaluation; stent and coronary artery bypass graft patency evaluation; planning of coronary revascularization and transcatheter valve procedures; cardiomyopathies, electrophysiological applications, cardiac masses, cardio-oncology and pericardial diseases evaluation

Author

Carrabba, Nazario, Pontone, Gianluca, Andreini, Daniele, Buffa, Vitaliano, Cademartiri, Filippo, Carbone, Iacopo, Clemente, Alberto, Guaricci, Andrea Igoren, Guglielmo, Marco, Indolfi, Ciro, La Grutta, Ludovico, Ligabue, Guido, Liguori, Carlo, Mercuro, Giuseppe, Mushtaq, Saima, Neglia, Danilo, Palmisano, Anna, Sciagrà, Roberto, Seitun, Sara, Vignale, Davide, Francone, Marco, and Esposito, Antonio

Published
2022
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109. Recommendations in pre-procedural imaging assessment for transcatheter aortic valve implantation intervention: Italian Society of Cardiology (SIC)–Italian Society of Medical and Interventional Radiology (SIRM) position paper part 1 (Clinical Indication and Basic Technical Aspects, Heart Team, Role of Echocardiography)

Author

Pontone, Gianluca, Marano, Riccardo, Agricola, Eustachio, Alushi, Brunilda, Bartorelli, Antonio, Cameli, Matteo, Carrabba, Nazario, Esposito, Antonio, Faletti, Riccardo, Francone, Marco, Galea, Nicola, Golino, Paolo, Guglielmo, Marco, Palmisano, Anna, Petronio, Sonia, Petullà, Maria, Pradella, Silvia, Ribichini, Flavio, Romeo, Francesco, Russo, Vincenzo, Scandura, Salvatore, Schicchi, Nicolò, Spaccarotella, Carmen, Tomai, Fabrizio, Centonze, Maurizio, and indolfi, Ciro

Published
2022
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111. Effetti e meccanismi molecolari della Curcumina nelle leucemie linfoblasti che acute dell’età pediatrica

Author

D’Angelo, V., PICA, ALESSANDRA, Iannotta, A., Di Massa, L., Ramaglia, M., Tirino, V., Di Martino, M., Pota, E., Di Pinto, D., Boccieri, E., MANCA, ROSA, Perrotta, S., Indolfi, P., Casale, F. ., D’Angelo, V., Pica, Alessandra, Iannotta, A., Di Massa, L., Ramaglia, M., Tirino, V., Di Martino, M., Pota, E., Di Pinto, D., Boccieri, E., Manca, Rosa, Perrotta, S., Indolfi, P., and Casale, F. .

Subjects
curcumina, daunoblastina, linee cellulari leucemiche, SUP-B15, Jurkat
Abstract

La curcumina, componente della curcuma presente nei rizomi della Curcuma Longa, sembra avere effetti antineoplastici per cui è stata studiata quale potenziale agente per la prevenzione e il trattamento di varie neoplasie in quanto bloccherebbe la trasformazione cellulare, proliferazione delle cellule neoplastiche inducendo apoptosi. Ci proponiamo di studiare l’effetto della curcumina su cellule leucemiche della linea B e T, in singolo e combinato con farmaci convenzionali utilizzati nei protocolli delle leucemie e con DZnep inibitore indiretto del regolatore epigenetico EZH2. .METODI: Sono state utilizzate, come modelli in vitro, due linee cellulari (SuP B-15 e Jurkat) per verificare gli effetti della curcumina a concentrazioni scalari e in combinazione con diversi agenti chemioterapici (Daunoblastina, L-asparaginasi, metotrexate) e con l’ inibitore di EZH2 (DZnep). Abbiamo studiato l’apoptosi, il ciclo cellulare, la produzione cellulare di ROS prima e dopo trattamento e effettuato l’analisi al microscopio confocale. RISuLTATI: I risultati preliminari mostrano che la curcumina inibisce in maniera dose-dipendente la proliferazione delle cellule di entrambe le linee cellulari dopo 24 ore di trattamento (p

Published
2017

112. Enhancer Role of rMnSOD in apoptosis triggering by daunorubicin of pediatric B-ALL cells

Author

Casale, F., D’Angelo, V., PICA, ALESSANDRA, Iannotta, A., Ramaglia, M., Di Massa, L., POLLIO, MARIA LAURA, MANCA, ROSA, Di Martino, M., Oreste, M., Mancini, A, Borrelli, A, Indolfi, P., Casale, F., D’Angelo, V., Pica, Alessandra, Iannotta, A., Ramaglia, M., Di Massa, L., Pollio, MARIA LAURA, Manca, Rosa, Di Martino, M., Oreste, M., Mancini, A, Borrelli, A, and Indolfi, P.

Subjects
pediatric leukimia cells, chemioterapy enhancer, rMnSOD
Abstract

Background/Objectives Leukemic cells produce higher amounts of ROS than healthy cells and express low levels of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). Recently, it was demonstrated that rMnSOD, a recombinant new isoform of MnSOD, recently isolated from human liposarcoma cell line, is able to trigger apoptosis of human T-ALL cells (99%) without toxic effects on healthy cells. The present study was aimed to verify if rMnSOD is able to induce apoptosis and to stop in G0/G1 stage of the cell cycle in pediatric patients with B-cell acute lymphoblastic leukaemia (ALL) and if it displays synergic action with daunorubicin. Design and Methods Cells were collected from three patients diagnosed for B-cell ALL at the Pediatric Oncology of University “Luigi Vanvitelli”. Cell viability, apoptosis and cell cycle of lymphoblasts and SUP-B15 cell line (ATCC) were analyzed through “ Muse Kit” after rMnSOD treatment. ROS analysis was detected with NAC. Apoptotic fragmentations of SUP-B15 were demonstrated by confocal imaging. Results We observed that low concentrations of rMnSOD are able to trigger apoptosis of SUP-B15 cell line and B-ALL cells from pediatric patients. In detail, we observed an apoptosis rate from 30% to 46% in B-ALL pediatric patient cells and of 45% in SUP-B15 cell line. Instead, cell cycle analysis showed a cell fraction decrease in G0/G1 phase. Moreover, the synergic activity of rMnSOD and Daunorubicin induces apoptosis in 92% of cells, by comparing the treatment with the single substances, rMnSOD (64,7%) and Daunorubicin (23,9%). Confocal microscopy analysis revealed internalization of rMnSOD in SUP-B15 cells and evident apoptotic alterations, such as nuclear fragmentations and apoptotic-bodies. In conclusion, rMnSOD exerts toxic activity only against cancer cells, by enhancing drug effect, thus allowing to utilize lower concentration of standard chemotherapy to increase the apoptosis level.

Published
2017

113. Late mortality and causes of death among 5-year survivors of childhood cancer diagnosed in the period 1960–1999 and registered in the Italian Off-Therapy Registry

Author

Bagnasco, F., Caruso, S., Andreano, A., Valsecchi, M. G., Jankovic, M., Biondi, A., Miligi, L., Casella, C., Terenziani, M., Massimino, M., Sacerdote, C., Morsellino, V., Erminio, G., Garaventa, A., Faraci, M., Micalizzi, C., Garre, M. L., Pillon, M., Basso, G., Biasin, E., Fagioli, F., Rondelli, R., Pession, A., Locatelli, Franco, Santoro, N., Indolfi, P., Palumbo, G., Russo, G., Verzegnassi, F., Favre, C., Zecca, M., Mura, R., D'Angelo, P., Cano, C., Byrne, J., Haupt, R., Pierani, P., Porta, F., Consarino, C., Burnelli, R., Fedeli, F., Cellini, M., Casale, F., Menna, G., Bertolini, P., Caniglia, M., Cecinati, V., Casazza, G., Foa, R., Clerico, A., Ladogana, S., Galimberti, D., Rabusin, M., Nespoli, L., Cesaro, S., Locatelli F. (ORCID:0000-0002-7976-3654), Bagnasco, F., Caruso, S., Andreano, A., Valsecchi, M. G., Jankovic, M., Biondi, A., Miligi, L., Casella, C., Terenziani, M., Massimino, M., Sacerdote, C., Morsellino, V., Erminio, G., Garaventa, A., Faraci, M., Micalizzi, C., Garre, M. L., Pillon, M., Basso, G., Biasin, E., Fagioli, F., Rondelli, R., Pession, A., Locatelli, Franco, Santoro, N., Indolfi, P., Palumbo, G., Russo, G., Verzegnassi, F., Favre, C., Zecca, M., Mura, R., D'Angelo, P., Cano, C., Byrne, J., Haupt, R., Pierani, P., Porta, F., Consarino, C., Burnelli, R., Fedeli, F., Cellini, M., Casale, F., Menna, G., Bertolini, P., Caniglia, M., Cecinati, V., Casazza, G., Foa, R., Clerico, A., Ladogana, S., Galimberti, D., Rabusin, M., Nespoli, L., Cesaro, S., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Introduction: Advances in paediatric oncology led to the increase in long-term survival, revealing the burden of therapy-related long-term side effects. We evaluated overall and cause-specific mortality in a large cohort of Italian childhood cancer survivors (CCSs) and adolescent cancer survivors identified through the off-therapy registry. Materials and methods: CCSs alive 5 years after cancer diagnosis occurring between 1960 and 1999 were eligible; the last follow-up was between 2011 and 2014. Outcomes were reported as standardised mortality ratios (SMRs) and absolute excess risks (AERs). Results: Among 12,214 CCSs, 1113 (9.1%) deaths occurred. Survival at 35 years since diagnosis was 87% (95% confidence interval [CI]: 86–88) and at 45 years was 81% (95% CI: 77–84). CCSs had an 11-fold increased risk of death (SMR 95% CI: 10.7–12), corresponding to an AER of 48 (95% CI: 45–51). Mortality decreased by 60% for survivors treated most recently (1990–1999). The most frequent causes of death were recurrence of the original cancer (56%), a subsequent neoplasm (19%) and cardiovascular diseases (5.8%). Among those who survived at least 15 years after diagnosis, a secondary malignancy was the leading cause of death. Conclusions: This study confirms the impact of recent advances in anticancer therapy in reducing mortality, mainly attributable to recurrence but also to other causes. However, overall mortality continues to be higher than in the general population. A long-term follow-up is needed to prevent late mortality due to secondary neoplasms and non-neoplastic causes in CCSs.

Published
2019

114. Late mortality and causes of death among 5-year survivors of childhood cancer diagnosed in the period 1960–1999 and registered in the Italian Off-Therapy Registry

Author

Bagnasco, F, Caruso, S, Andreano, A, Valsecchi, M, Jankovic, M, Biondi, A, Miligi, L, Casella, C, Terenziani, M, Massimino, M, Sacerdote, C, Morsellino, V, Erminio, G, Garaventa, A, Faraci, M, Micalizzi, C, Garrè, M, Pillon, M, Basso, G, Biasin, E, Fagioli, F, Rondelli, R, Pession, A, Locatelli, F, Santoro, N, Indolfi, P, Palumbo, G, Russo, G, Verzegnassi, F, Favre, C, Zecca, M, Mura, R, D'Angelo, P, Cano, C, Byrne, J, Haupt, R, Pierani, P, Porta, F, Consarino, C, Burnelli, R, Fedeli, F, Cellini, M, Casale, F, Menna, G, Bertolini, P, Caniglia, M, Cecinati, V, Casazza, G, Foà, R, Clerico, A, Ladogana, S, Galimberti, D, Rabusin, M, Nespoli, L, Cesaro, S, Bagnasco, Francesca, Caruso, Silvia, Andreano, Anita, Valsecchi, Maria Grazia, Jankovic, Momcilo, Biondi, Andrea, Miligi, Lucia, Casella, Claudia, Terenziani, Monica, Massimino, Maura, Sacerdote, Carlotta, Morsellino, Vera, Erminio, Giovanni, Garaventa, Alberto, Faraci, Maura, Micalizzi, Concetta, Garrè, Maria Luisa, Pillon, Marta, Basso, Giuseppe, Biasin, Eleonora, Fagioli, Franca, Rondelli, Roberto, Pession, Andrea, Locatelli, Franco, Santoro, Nicola, Indolfi, Paolo, Palumbo, Giovanna, Russo, Giovanna, Verzegnassi, Federico, Favre, Claudio, Zecca, Marco, Mura, Rossella, D'Angelo, Paolo, Cano, Carmen, Byrne, Julianne, Haupt, Riccardo, Pierani, Paolo, Pession, Andreea, Porta, Fulvio, Consarino, Caterina, Burnelli, Roberta, Fedeli, Fausto, Cellini, Monica, Casale, Fiorina, Menna, Giuseppe, Bertolini, Patrizia, Caniglia, Maurizio, Cecinati, Valerio, Casazza, Gabriella, Foà, Roberto, Clerico, Anna, Ladogana, Saverio, Galimberti, Daniela, Rabusin, Marco, Nespoli, Luigi, Cesaro, Simone, Bagnasco, F, Caruso, S, Andreano, A, Valsecchi, M, Jankovic, M, Biondi, A, Miligi, L, Casella, C, Terenziani, M, Massimino, M, Sacerdote, C, Morsellino, V, Erminio, G, Garaventa, A, Faraci, M, Micalizzi, C, Garrè, M, Pillon, M, Basso, G, Biasin, E, Fagioli, F, Rondelli, R, Pession, A, Locatelli, F, Santoro, N, Indolfi, P, Palumbo, G, Russo, G, Verzegnassi, F, Favre, C, Zecca, M, Mura, R, D'Angelo, P, Cano, C, Byrne, J, Haupt, R, Pierani, P, Porta, F, Consarino, C, Burnelli, R, Fedeli, F, Cellini, M, Casale, F, Menna, G, Bertolini, P, Caniglia, M, Cecinati, V, Casazza, G, Foà, R, Clerico, A, Ladogana, S, Galimberti, D, Rabusin, M, Nespoli, L, Cesaro, S, Bagnasco, Francesca, Caruso, Silvia, Andreano, Anita, Valsecchi, Maria Grazia, Jankovic, Momcilo, Biondi, Andrea, Miligi, Lucia, Casella, Claudia, Terenziani, Monica, Massimino, Maura, Sacerdote, Carlotta, Morsellino, Vera, Erminio, Giovanni, Garaventa, Alberto, Faraci, Maura, Micalizzi, Concetta, Garrè, Maria Luisa, Pillon, Marta, Basso, Giuseppe, Biasin, Eleonora, Fagioli, Franca, Rondelli, Roberto, Pession, Andrea, Locatelli, Franco, Santoro, Nicola, Indolfi, Paolo, Palumbo, Giovanna, Russo, Giovanna, Verzegnassi, Federico, Favre, Claudio, Zecca, Marco, Mura, Rossella, D'Angelo, Paolo, Cano, Carmen, Byrne, Julianne, Haupt, Riccardo, Pierani, Paolo, Pession, Andreea, Porta, Fulvio, Consarino, Caterina, Burnelli, Roberta, Fedeli, Fausto, Cellini, Monica, Casale, Fiorina, Menna, Giuseppe, Bertolini, Patrizia, Caniglia, Maurizio, Cecinati, Valerio, Casazza, Gabriella, Foà, Roberto, Clerico, Anna, Ladogana, Saverio, Galimberti, Daniela, Rabusin, Marco, Nespoli, Luigi, and Cesaro, Simone

Abstract

Introduction: Advances in paediatric oncology led to the increase in long-term survival, revealing the burden of therapy-related long-term side effects. We evaluated overall and cause-specific mortality in a large cohort of Italian childhood cancer survivors (CCSs) and adolescent cancer survivors identified through the off-therapy registry. Materials and methods: CCSs alive 5 years after cancer diagnosis occurring between 1960 and 1999 were eligible; the last follow-up was between 2011 and 2014. Outcomes were reported as standardised mortality ratios (SMRs) and absolute excess risks (AERs). Results: Among 12,214 CCSs, 1113 (9.1%) deaths occurred. Survival at 35 years since diagnosis was 87% (95% confidence interval [CI]: 86–88) and at 45 years was 81% (95% CI: 77–84). CCSs had an 11-fold increased risk of death (SMR 95% CI: 10.7–12), corresponding to an AER of 48 (95% CI: 45–51). Mortality decreased by 60% for survivors treated most recently (1990–1999). The most frequent causes of death were recurrence of the original cancer (56%), a subsequent neoplasm (19%) and cardiovascular diseases (5.8%). Among those who survived at least 15 years after diagnosis, a secondary malignancy was the leading cause of death. Conclusions: This study confirms the impact of recent advances in anticancer therapy in reducing mortality, mainly attributable to recurrence but also to other causes. However, overall mortality continues to be higher than in the general population. A long-term follow-up is needed to prevent late mortality due to secondary neoplasms and non-neoplastic causes in CCSs.

Published
2019

115. Loss of Heterozygosity Analysis at Different Chromosome Regions in Wilms Tumor Confirms 1p Allelic Loss as a Marker of Worse Prognosis: A Study from the Italian Association of Pediatric Hematology and Oncology

Author

Spreafico F, Gamba B, Mariani L, Collini P, D'Angelo P, Di Cataldo A, Indolfi P, Nantron M, Terenziani M, Morosi C, Radice P, Perotti D, AIEOP Wilms Tumor Working Group, PESSION, ANDREA, Spreafico F, Gamba B, Mariani L, Collini P, D'Angelo P, Pession A, Di Cataldo A, Indolfi P, Nantron M, Terenziani M, Morosi C, Radice P, Perotti D, and AIEOP Wilms Tumor Working Group

Subjects
Genetic Markers, Male, Oncology, medicine.medical_specialty, Vincristine, Multivariate analysis, Adolescent, pediatrics, kidney neoplasms, loss of heterozygosity, pediatrics, Wilms tumor, Urology, STAGE-I, CHILDRENS-CANCER, RENAL TUMORS, SHORT ARM, 16Q, ANAPLASIA, RELAPSE, GENE, 11Q, AGE, Loss of heterozygosity, Chromosome regions, Internal medicine, medicine, Overall survival, Humans, kidney neoplasms, Prospective Studies, Child, loss of heterozygosity, Wilms tumor, business.industry, Infant, Wilms' tumor, Prognosis, medicine.disease, Child, Preschool, Microsatellite, Female, business, Allelic loss, medicine.drug
Abstract

PURPOSE: The specific aims of the AIEOP-TW-2003 protocol included prospectively investigating a possible association of tumor loss of heterozygosity with outcomes in children treated for Wilms tumor. MATERIALS AND METHODS: We analyzed 125 unilateral favorable histology Wilms tumors registered between 2003 and 2008 in the Italian cooperative protocol for microsatellite markers mapped to chromosomes 1p, 7p, 11q, 16q and 22q. RESULTS: The 3-year disease-free survival and overall survival probabilities were 0.87 (95% CI 0.81-0.93) and 0.98 (95% CI 0.96-1.0), respectively. Loss of heterozygosity at 1p was significantly associated with a worse disease-free survival (probability 0.67 for patients with and 0.92 for those without 1p loss of heterozygosity, p = 0.0009), as confirmed also by multivariate analysis adjusting for tumor stage and patient age at diagnosis. There was no difference in disease-free survival probability among children with loss of heterozygosity in the other chromosomal regions tested. The worse outlook for children older than 2 years at diagnosis did not seem to be influenced by the loss of heterozygosity patterns considered. CONCLUSIONS: Chromosome 1p loss of heterozygosity seems to be a risk factor for nonanaplastic Wilms tumor, possibly regardless of other clinical factors. Our findings were uninformative regarding loss of heterozygosity in the other chromosomal regions tested.

Published
2013
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116. Proceedings of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition Monothematic Conference, 2020

Author

Zellos, Aglaia, Debray, Dominique, Indolfi, Giuseppe, Czubkowski, Piotr, Samyn, Marianne, Hadzic, Nedim, Gupte, Girish, Fischler, Björn, Smets, Françoise, Clément de Cléty, Stéphan, Grenda, Ryszard, Mozer, Yael, Mancell, Sara, Jahnel, Jörg, Auzinger, Georg, Worth, Austen, Lisman, Ton, Staufner, Christian, Baumann, Ulrich, Dhawan, Anil, Alonso, Estelle, Squires, Robert H., and Verkade, Henkjan J.

Abstract

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled “ Acute Liver Failure” (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF. We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points. The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research.

Published
2022
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117. Proceedings of ESPGHAN Monothematic Conference 2020

Author

Zellos, Aglaia, Debray, Dominique, Indolfi, Giuseppe, Czubkowski, Piotr, Samyn, Marianne, Hadzic, Nedim, Gupte, Girish, Fischler, Björn, Smets, Françoise, Cléty, Stéphan Clément, Grenda, Ryszard, Mozer, Yael, Mancell, Sara, Jahnel, Jörg, Auzinger, Georg, Worth, Austen, Lisman, Ton, Staufner, Christian, Baumann, Ulrich, Dhawan, Anil, Alonso, Estelle, Squires, Robert H., and Verkade, Henkjan J.

Abstract

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children. The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled “acute liver failure” (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups. In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points. The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.

Published
2022
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119. The Impact of Severe Acute Respiratory Syndrome Coronavirus Type 2 on Children With Liver Diseases

Author

Nicastro, Emanuele, Ebel, Noelle H., Kehar, Mohit, Czubkowski, Piotr, Ng, Vicky L., Michaels, Marian G., Lobritto, Steven J., Martinez, Mercedes, and Indolfi, Giuseppe

Abstract

Children are seldom affected by severe forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) infection; however, the impact of comorbidities in the clinical presentation and outcome of SARS-CoV2 in children is poorly characterized including that of chronic liver disease (CLD) and those taking immunosuppressive medications for autoimmune liver disease or following liver transplantation (LT). Although not the main target organ, a spectrum of liver involvement has been described in children infected with SARS-CoV2 and those presenting with Multisystem Inflammatory Syndrome in Children (MIS-C). The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the Society of Pediatric Liver Transplantation (SPLIT) present an evidence-based position paper on liver involvement in children with SARS-CoV2 infection and its impact on those with CLD as well as LT recipients. All children may exhibit acute liver injury from SARS-CoV2 infection, and those with CLD and may experience hepatic decompensation. Preventative and therapeutic measures are discussed.

Published
2022
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120. Cardiovascular risk management in type 2 diabetes mellitus: A joint position paper of the Italian Cardiology (SIC) and Italian Diabetes (SID) Societies.

Author

Avogaro, Angelo, Barillà, Francesco, Cavalot, Franco, Consoli, Agostino, Federici, Massimo, Mancone, Massimo, Paolillo, Stefania, Pedrinelli, Roberto, Perseghin, Gianluca, Perrone Filardi, Pasquale, Scicali, Roberto, Sinagra, Gianfranco, Spaccarotella, Carmen, Indolfi, Ciro, and Purrello, Francesco

Abstract

Aim: This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus.Data Synthesis: Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing.Conclusions: The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration. [ABSTRACT FROM AUTHOR]

Published
2021
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121. Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Author

Di Giorgio, A., Bartolini, E., Calvo, P.L., Cananzi, M., Cirillo, F., Della Corte, C., Dionisi-Vici, C., Indolfi, G., Iorio, R., Maggiore, G., Mandato, C., Nebbia, G., Nicastro, E., Pinon, M., Ranucci, G., Sciveres, M., Vajro, P., and D'Antiga, L.

Abstract

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference. [ABSTRACT FROM AUTHOR]

Published
2021
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122. Molecular typing of group B Neisseria meningitidis'subcapsular antigens directly on biological samples demonstrates epidemiological congruence between culture-positive and -negative cases: A surveillance study of invasive disease over a 13-year period.

Author

Lodi, Lorenzo, Moriondo, Maria, Nieddu, Francesco, Ricci, Silvia, Guiducci, Sara, Lippi, Francesca, Canessa, Clementina, Calistri, Elisa, Citera, Francesco, Giovannini, Mattia, Indolfi, Giuseppe, Resti, Massimo, and Azzari, Chiara

Abstract

Background: Surveillance of serogroup B Neisseria meningitidis (MenB) subcapsular antigen variant distribution in invasive disease (IMD) is fundamental for multicomponent vaccine coverage prediction. IMD incidence in Tuscany in 2018 was 0.37/100,000 inhabitants, with MenB representing 57% of cases. More than 50% of MenB responsible for IMD cannot be grown in culture, and molecular characterization of these cases is often lacking. The aim of the present study was to describe the distribution of MenB subcapsular antigens, comparing their distribution in culture-positive and culture-negative cases.Methods: Molecular data regarding clonal complexes and subcapsular antigen variants of the 55 MenB-IMD occurring in Tuscany from 2007 to 2019 were made available, and their distribution between culture-positive and culture-negative cases was compared. Genetic-MATS and MenDeVAR prediction systems were used to assess multicomponent vaccine coverage predictions.Results: Culture-positive and culture-negative cases presented a similar percentage representation of fHbp subfamilies. Clonal complex 162 was almost constantly associated with fHbp B231/v1.390, Neisserial-heparin-binding-antigen (NHBA) peptide 20, and PorinA P1.22,14 (BAST-3033): these were the most represented antigenic variants, both in culture-positive and culture-negative groups. Point-estimate 4CMenB coverage prediction was 88.5% (84.6%-92.3%).Conclusions: Our data demonstrate that non-cultivable meningococci, responsible for IMD, possess genetic variants of subcapsular antigens that are representative of what has been observed in culture. The vaccine-related antigenic epidemiology of MenB is thus similar in both groups. One of the first on-field applications of gMATS and MenDeVAR identifies their major advantage in their accessibility and in the possibility of dynamic data implementation that must be pursued continuously in the future. [ABSTRACT FROM AUTHOR]

Published
2021
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126. Vernal keratoconjunctivitis: An update

Author

Ghiglioni, Daniele Giovanni, Zicari, Anna Maria, Parisi, Giuseppe Fabio, Marchese, Giuseppe, Indolfi, Cristiana, Diaferio, Lucia, Brindisi, Giulia, Ciprandi, Giorgio, Marseglia, Gian Luigi, and Miraglia del Giudice, Michele

Abstract

Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are potentially severe and complex disease in its management among the various allergic eye diseases. In this regard, studies clarified the etiopathogenetic mechanisms. The workup should be multidisciplinary. The treatment includes topical and systemic medications with anti-inflammatory and immunosuppressant activity. However, a definition of nationally- and internationally-shared diagnostic protocols would also be needed and validated access to therapeutic options of proven safety and efficacy to avoid the use of galenic preparations, up to now still essential in the management of moderate-severe VKC. Finally, recognizing VKC and AKC, among rare diseases, at a national and international level would be an essential step to allow the management of VKC with adequate timings and settings within the National Health System.

Published
2021
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127. Prognostic value of implantable defibrillator-computed respiratory disturbance index: The DASAP-HF study.

Author

Boriani, Giuseppe, Pisanò, Ennio C.L., Pieragnoli, Paolo, Locatelli, Alessandro, Capucci, Alessandro, Talarico, Antonello, Zecchin, Massimo, Rapacciuolo, Antonio, Piacenti, Marcello, Indolfi, Ciro, Arias, Miguel Angel, Diemberger, Igor, Checchinato, Catia, La Rovere, Maria Teresa, Sinagra, Gianfranco, Emdin, Michele, Ricci, Renato Pietro, and D'Onofrio, Antonio

Abstract

Background: Sleep apnea, as measured by polysomnography, is associated with adverse outcomes in heart failure. The DASAP-HF (Diagnosis and Treatment of Sleep Apnea in Patient With Heart Failure) study previously demonstrated that the respiratory disturbance index (RDI) computed by the ApneaScan algorithm (Boston Scientific) accurately identifies severe sleep apnea in implantable cardioverter-defibrillator (ICD) patients.Objective: The purpose of the long-term study phase was to assess the incidence of clinical events after 24 months and investigate the association with RDI values.Methods: Patients with left ventricular ejection fraction ≤35% implanted with an ICD were enrolled and followed-up for 24 months. The RDI calculated at 1 month after implantation was used to stratify patients (below or above 30 episodes/h). The endpoints were all-cause death and a combination of all-cause death or cardiovascular hospitalization.Results: Of the 265 enrolled patients, 224 had usable RDI values. Severe sleep apnea (RDI ≥30 episodes/h) was diagnosed in 115 patients (51%). These patients were more frequently male (84% vs 72%; P = .030) and had higher creatinine levels. During median follow-up of 25 months, 19 patients (8%) died. Cardiovascular hospitalizations were reported in 19 patients (8%). The risk of all-cause death was higher in patients with RDI ≥30 episodes/h (hazard ratio [HR] 3.33; 95% confidence interval [CI] 1.35-8.21; P = .023), as well as the risk of all-cause death or cardiovascular hospitalization (HR 1.94; 95% CI 1.01-3.76; P = .048). At multivariate analysis, independent predictors of death were RDI ≥30 episodes/h (HR 4.02; 95% CI 1.16-13.97; P = .029) and creatinine levels (HR 2.36; 95% CI 1.26-4.42; P = .008).Conclusion: In heart failure patients implanted with an ICD, higher RDI values are associated with death and cardiovascular hospitalizations. Device-detected severe sleep apnea independently predicts death. [ABSTRACT FROM AUTHOR]

Published
2021
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129. Evolution, Predictors, and Neurocognitive Effects of Silent Cerebral Embolism During Transcatheter Aortic Valve Replacement.

Author

De Carlo, Marco, Liga, Riccardo, Migaleddu, Gianmichele, Scatturin, Melania, Spaccarotella, Carmen, Fiorina, Claudia, Orlandi, Giovanni, De Caro, Francesco, Rossi, Marco L., Chieffo, Alaide, Indolfi, Ciro, Reimers, Bernhard, Cosottini, Mirco, and Petronio, A. Sonia

Abstract

The aim of this study was to assess the characteristics, predictors, evolution, and neurocognitive effects of silent cerebral ischemic lesions (SCILs). Most patients undergoing transcatheter aortic valve replacement (TAVR) develop SCILs detectable on magnetic resonance imaging (MRI). The natural history and clinical relevance of SCILs are not well established. Cerebral MRI was performed within 7 days before TAVR to assess baseline status and age-related white matter change score. MRI was repeated post-operatively to assess the occurrence, location, number, and dimensions of SCILs. Patients developing SCILs underwent a third MRI examination at 3- to 5-month follow-up. A neurocognitive evaluation was performed before TAVR, at discharge, and at 3-month follow-up. Of the 117 patients enrolled, 96 underwent post-procedural MRI; SCILs were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, a median diameter of 4.5 mm, and a median total volume of 140 mm3. Independent predictors of SCIL occurrence were higher baseline age-related white matter change score and the use of self-expanding or mechanically expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of post-procedural SCILs evolved into gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVR and with lower recovery at follow-up. SCILs occur in the vast majority of patients undergoing TAVR and are predicted by more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCILs disappear within months, their occurrence has a limited but significant impact on neurocognitive function. [ABSTRACT FROM AUTHOR]

Published
2020
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130. Long-term results of the AIEOP MH’96 childhood Hodgkin’s lymphoma trial and focus on significance of response to chemotherapy and its implication in low risk patients to avoid radiotherapy

Author

Burnelli, R., Rinieri, S., Rondelli, R., Todesco, A., Bianchi, M., Garaventa, A., Zecca, M., Indolfi, P., Conter, V., Santoro, N., Arico, M., Cesaro, S., D'Amico, S., Farruggia, P., De Santis, R., Locatelli, Franco, Pileri, S. A., Scarzello, G., Mascarin, M., Vecchi, V., Locatelli F. (ORCID:0000-0002-7976-3654), Burnelli, R., Rinieri, S., Rondelli, R., Todesco, A., Bianchi, M., Garaventa, A., Zecca, M., Indolfi, P., Conter, V., Santoro, N., Arico, M., Cesaro, S., D'Amico, S., Farruggia, P., De Santis, R., Locatelli, Franco, Pileri, S. A., Scarzello, G., Mascarin, M., Vecchi, V., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Identify a subset of early-stage HL children (GR1) curable with limited chemotherapy+/-radiotherapy; improve outcome of intermediate (GR2) and high-risk (GR3) patients; establish impact of response to chemotherapy evaluated with conventional imaging (CI). One hundred and sixty GR1-patients received 3ABVD + involved-field (IF) low-dose (LD) (20 Gy) irradiation if mediastinal mass or partial response (PR) after chemotherapy. Eighty-five GR2- and 315 GR3-patients received 4 and 6 COPP/ABV + IFRT, respectively. The 63 GR1 patients spared from radiotherapy had 15-year survival and EFS of 100 and 84.5%, respectively. The GR2 and GR3 15-year FFP were 84.7 and 78.6%, respectively. No different prognosis for patients in CR or PR evaluated during and after chemotherapy was observed. In conclusion, low-risk patients in CR may be successfully treated with radiation-free, low-intensity chemotherapy. Good, but less satisfactory, results were registered in GR2 and GR3. Response evaluated with CI is not a prognostic factor, but permits identification of low-risk patients who can avoid radiotherapy.

Published
2018

132. Mature and immature teratoma: A report from the second Italian pediatric study

Author

Terenziani, M., D'Angelo, P., Inserra, A., Boldrini, R., Bisogno, G., Babbo, G., Conte, M., Dall' Igna, P., De Pasquale, M., Indolfi, P., Piva, L., Riccipetitoni, G., Siracusa, F., Spreafico, L., Tamaro, P., Cecchetto, G., Terenziani, M, D'Angelo, P, Inserra, A, Boldrini, R, Bisogno, G, Babbo, GL, Conte, M, Dall' Igna, P, De Pasquale, MD, Indolfi, P, Piva, L, Riccipetitoni,G, Siracusa, F, Spreafico, L, Tamaro, P, and Cecchetto, G

Subjects
immature teratoma, Settore MED/20 - Chirurgia Pediatrica E Infantile, Settore MED/20, germ cell tumor, mature teratoma, germ cell tumors, childhood
Abstract

Background. Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the ®rst Italian study, we collected cases of teratoma, alongside the protocol for malignant germ cell tumors. Procedure. Patients with teratoma were collected from 2004 to 2014. Teratomas were classi®ed according to the WHO classi®cations, as mature and immature. Patients with pathological aFP and/or bHCG, and those with a malignant germ cell component were not included. Results. The study enrolled 219 patients (150 mature, 69 immature teratomas) with a median age at diagnosis of 42 months. The primary sites involved were: 118 gonadal and 101 extragonadal teratomas. Two females with ovarian teratoma had a positive family history. Complete and incomplete surgeries were performed in 85% and 9% of cases. Seventeen events occurred: six females had a second metachronous tumor (5 contralateral ovarian teratoma, 1 adrenal neuroblastoma) and 11 teratomas relapsed/progressed (3 mature, 8 immature teratomas). Two patients died, one of progressive immature teratoma and one of surgical complications. At a median follow up of 68 months, the event-free, relapse-free, and overall survival rates were 90.6%, 94.3%, 98.6%, respectively. Conclusions. Teratomas show a good prognosis, especially the mature ones: surgery and follow-up remain the standard approach. Incomplete surgery in immature teratoma is the group at greatest risk of relapse. Bilateral ovarian tumors are a possibility, and the rare family predisposition to ovarian mature teratoma warrants further analyses.

Published
2015

133. Rischio di recidiva nel linfoma di Hodgkin pediatrico: dalla esperienza AIEOP ad una strategia europea

Author

Mascarin, M., Bernasconi, S., Bertolini, P., Bianchi, M., Buffardi, S., Casale, F., Casini, T., Cellini, M., Cesaro, S., Civino, A., Consarino, C., Cosmi, C., D’Amico, S., De Santis, R., Facchini, E., Fagioli, F., Farruggia, P., Favre, C., Felici, L., Galimberti, D., Garaventa, A., Iaria, G., Indolfi, P., Locatelli, F., Moleti, M. L., Muggeo, P., Mura, R. M., Pericoli, R., Perruccio, K., Pierani, P., Pillon, M., Porta, F., Provenzi, M., Rinieri, S., Rondelli, R., Russo, G., Sala, A., Santoro, N., Sau, A., Sperli, D., Todesco, A., Tolva, A., Varasso, G., Verzegnassi, F., Vinti, L., Zecca, M., Lopci, E., Elia, C., Birri, S., Sabattini, E., D’Amore, E., and Burnelli, R.

Subjects
pediatria, linfoma hodgkin, risultati, linfoma hodgkin, pediatria, risultati
Published
2017

134. Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis

Author

Guedeney, Paul, Sorrentino, Sabato, Giustino, Gennaro, Chapelle, Celine, Laporte, Silvy, Claessen, Bimmer E, Ollier, Edouard, Camaj, Anton, Kalkman, Deborah N, Vogel, Birgit, De Rosa, Salvatore, Indolfi, Ciro, Lattuca, Benoit, Zeitouni, Michel, Kerneis, Mathieu, Silvain, Johanne, Collet, Jean-Philippe, Mehran, Roxana, and Montalescot, Gilles

Published
2021
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135. Il linfoma di Hodgkin in età pediatrica: risultati a lungo termine del protocollo AIEOP-MH’89

Author

Robazza, M., Mascarin, M., Elia, C., Barra, S., Bianchi, M., Buffardi, S., Bunkheila, F., Caniglia, M., Casini, T., Cellini, M., Cesaro, Simone, Consarino, C., D’Amico, S., De Santis, R., Farruggia, P., Guerrini, G., Garaventa, A., Indolfi, P., Locatelli, F., Moleti, M. L., Nardi, M., Pession, A., Pierani, P., Porta, F., Provenzi, M., Riccardi, U., Rondelli, R., Sala, A., Santoro, N., Sau, A., Scarzello, G., Todesco, A., Zanazzo, G. A., Zecca, M., and Brunelli, R.

Subjects
chemioterapia, protocollo MH 89, Linfoma di Hodgkin, Linfoma di Hodgkin, protocollo MH 89, chemioterapia
Published
2016

137. Global multi-stakeholder endorsement of the MAFLD definition

Author

Méndez-Sánchez, Nahum, Bugianesi, Elisabetta, Gish, Robert G, Lammert, Frank, Tilg, Herbert, Nguyen, Mindie H, Sarin, Shiv K, Fabrellas, Núria, Zelber-Sagi, Shira, Fan, Jian-Gao, Shiha, Gamal, Targher, Giovanni, Zheng, Ming-Hua, Chan, Wah-Kheong, Vinker, Shlomo, Kawaguchi, Takumi, Castera, Laurent, Yilmaz, Yusuf, Korenjak, Marko, Spearman, C Wendy, Ungan, Mehmet, Palmer, Melissa, El-Shabrawi, Mortada, Gruss, Hans-Juergen, Dufour, Jean-François, Dhawan, Anil, Wedemeyer, Heiner, George, Jacob, Valenti, Luca, Fouad, Yasser, Romero‐Gomez, Manuel, Eslam, Mohammed, Abate, Maria Lorena, Abbas, Bahaa, Abbassy, Ahmed Amr, Abd El Ghany, Waleed, Abd Elkhalek, Amira, Abd ElMajeed, Emad, Abdalgaber, Mohammad, AbdAllah, Mohamed, Abdallah, Marwa, Abdallah, Nourhan, Abdelaleem, Shereen, Abdelghani, Yasser, Abdelghany, Wael, Abdelhalim, Safaa Mohamed, Abdelhamid, Wafaa, Abdelhamid, Nehal, Abdelkader, Nadia A., Abdelkreem, Elsayed, Abdelmohsen, Aly Mohamed, Abdelrahman, Awny Ali, Abd-elsalam, Sherief M, Abdeltawab, Doaa, Abduh, Abdulbaset, Abdulhakam, Nada, Abdulla, Maheeba, Abedpoor, Navid, Abenavoli, Ludovico, Åberg, Fredrik, Ablack, Omala, Abo elftouh, Mostafa, Abo-Amer, Yousry Esam-Eldin, Aboubkr, Ashraf, Aboud, Alaa, Abouelnaga, Amr M., Aboufarrag, Galal A., Aboutaleb, Ashraf, Abundis, Leticia, Adalı, Gupse, Adames, Enrique, Adams, Leon, Adda, Danjuma, Adel, Noor, Adel, Nada, Adel Sayed, Muhammad, Afaa, Taiba Jibril, Afredj, Nawal, Aghayeva, Gulnara, Aghemo, Alessio, Aguilar-Salinas, Carlos A., Ahlenstiel, Golo, Ahmady, Walid, Ahmed, Wafaa, Ahmed, Amira, Ahmed, Samah Nasser, Ahmed, Heba Mostafa, Ahmed, Rasha, Aigner, Elmar, Akarsu, Mesut, Akroush, Maisam, Akyuz, Umit, Al Mahtab, Mamun, Al Qadiri, Tahani, Al Rawahi, Yusriya, AL rubaee, Razzaq, Al Saffar, Muna, Alam, Shahinul, Al-Ani, Zaid, Albillos, Agustín, Alboraie, Mohamed, Al-Busafi, Said, Al-Emam, Mohamed, Alharthi, Jawaher, Ali, Kareem, Ali, Basma Abdelmoez, Ali, Mohammad, Ali, Raja Affendi Raja, Alisi, Anna, AL-Khafaji, Ali Raad, Alkhatry, Maryam, Aller, Rocio, Almansoury, Yahya, Al-Naamani, Khalid, Alnakeeb, Alaa, Alonso, Anna, Alqahtani, Saleh A., Alrabadi, Leina, Alswat, Khalid, Altaher, Mahir, Altamimi, Turki, Altamirano, Jose, Alvares-da-Silva, Mario R., Aly, Elsragy Adel M., Alzahaby, Amgad, Alzamzamy, Ahmed, Amano, Keisuke, Amer, Maysa A., Amin, Mona A., Amin, Sayed A., Amir, Ashraf A., Ampuero, Javier, Anas, Noha, Andreone, Pietro, Andriamandimby, Soa Fy, Anees, Mahmoud, Angela, Peltec, Antonios, Manal, Arafat, Wael, Araya, Jose Moreno, Armendariz-Borunda, Juan, Armstrong, Matthew J., Ashktorab, Hassan, Aspichueta, Patricia, Assal, Fathia, Atef, Mira, Attia, Dina, Atwa, Hoda, Awad, Reham, Awad, Mohyeldeen Abd Elaziz, Awny, Sally, Awolowo, Obafemi, Awuku, Yaw Asante, Ayada, Ibrahim, Aye, Than Than, Ayman, Sherif, Ayman, Hedy, Ayoub, Hesham, Azmy, Hosny M., Babaran, Romiro P., Badreldin, Omneya, Badry, Ahmed, Bahçecioğlu, İbrahim Halil, Bahour, Amira, Bai, Jiajia, Balaban, Yasemin, Balasubramanyam, Muthuswamy, Bamakhrama, Khaled, Banales, Jesus M, Bangaru, Babu, Bao, Jianfeng, Barahona, Jorge Suazo, Barakat, Salma, Barbalho, Sandra Maria, Barbra, Bikwa, Barranco, Beatriz, Barrera, Francisco, Baumann, Ulrich, Bazeed, Shamardan, Bech, Eva, Benayad, Aourarh, Benesic, Andreas, Bernstein, David, Bessone, Fernando, Birney, Susie, Bisseye, Cyrille, Blake, Martin, Bobat, Bilal, Bonfrate, Leonilde, Bordin, Dmitry S, Bosques-Padilla, Francisco, Boursier, Jerome, Boushab, Boushab Mohamed, Bowen, David, Bravo, Patricia Medina, Brennan, Paul N, Bright, Bisi, Broekaert, Ilse, Buque, Xabier, Burgos-Santamaría, Diego, Burman, Julio, Busetto, Luca, Byrne, Chris D., Cabral-Prodigalidad, Patricia Anne I., Cabrera-Alvarez, Guillermo, Cai, Wei, Cainelli, Francesca, Caliskan, Ali Riza, Canbay, Ali, Cano-Contreras, Ana, Cao, Hai-Xia, Cao, Zhujun, Carrion, Andres, Carubbi, Francesca, Casanovas, Teresa, Castellanos Fernández, Marlen Ivón, Chai, Jin, Chan, Siew Pheng, Charatcharoenwitthaya, Phunchai, Chavez-Tapia, Norberto, Chayama, Kazuaki, Chen, Jinjun, Chen, Lin, Chen, Zhong-Wei, Chen, Huiting, Chen, Sui-Dan, Chen, Qiang, Chen, Yaxi, Chen, Gang, Chen, En-Quang, Chen, Fei, Chen, Fei, Chen, Pei-Jer, Cheng, Robert, Cheng, Wendy, Chieh, Jack Tan Wei, Chokr, Imad, Cholongitas, Evangelos, Choudhury, Ashok, Chowdhury, Abhijit, Chukwudike, Evaristus Sunday, Ciardullo, Stefano, Clayton, Michelle, Clement, Karine, Cloa, Marie Michelle, Coccia, Cecilia, Collazos, Cristina, Colombo, Massimo, Cosar, Arif Mansur, Cotrim, Helma Pinchemel, Couillerot, Joris, Coulibaly, Alioune, Crespo, Gonzalo, Crespo, Javier, Cruells, Maria, Cua, Ian Homer Y., Dabbous, Hesham K., Dalekos, George N, D'Alia, Patricia, Dan, Li, Dao, Viet Hang, Darwish, Mostafa, Datz, Christian, Davalos-Moscol, Milagros B, Dawoud, Heba, de Careaga, Blanca Olaechea, de Knegt, Robert, de Ledinghen, Victor, de Silva, Janaka, Debzi, Nabil, Decraecker, Marie, Del Pozo, Elvira, Delgado, Teresa C, Delgado-Blanco, Manuel, Dembiński, Łukasz, Depina, Adilson, Derbala, Moutaz, Desalegn, Hailemichael, Desbois-Mouthon, Christèle, Desoky, Mahmoud, Dev, Anouk, Di Ciaula, Agostino, Diago, Moisés, Diallo, Ibrahima, Díaz, Luis Antonio, Dirchwolf, Melisa, Dongiovanni, Paola, Dorofeyev, Andrriy, Dou, Xiaoguang, Douglas, Mark W., Doulberis, Michael, Dovia, Cecil K., Doyle, Adam, Dragojević, Ivana, Drenth, Joost PH, Duan, Xuefei, Dulskas, Audrius, Dumitrascu, Dan L, Duncan, Oliver, Dusabejambo, Vincent, Dwawhi, Rev. Shem N.A., Eiketsu, Sho, El Amrousy, Doaa, El Deeb, Ahmed, El Deriny, Ghada, El Din, Hesham Salah, El Kamshishy, Salwa, El Kassas, Mohamed, El Raziky, Maissa, Elagamy, Osama A, Elakel, Wafaa, Elalfy, Dina, Elaraby, Hanaa, ElAwady, Heba, Elbadawy, Reda, Eldash, Hanaa Hassan, Eldefrawy, Manal S., Elecharri, Carol Lezama, Elfaramawy, Amel, Elfatih, Mohammed, Elfiky, Mahmoud, Elgamsy, Mohamed, Elgendy, Mohamed, El-Guindi, Mohamed A., Elhussieny, Nagi, Eliwa, Ahmed Maher, Elkabbany, Zeineb, El-Khayat, Hesham, El-Koofy, Nehal M., Elmetwalli, Alaa, Elrabat, Amr, El-Raey, Fathiya, Elrashdy, Fatma, Elsahhar, Medhat, Elsaid, Esraa M., Elsayed, Shimaa, Elsayed, Hany, Elsayed, Aly, Elsayed, Amr M., Elsayed, Hamdy, El-Serafy, Magdy, Elsharkawy, Ahmed M., Elsheemy, Reem Yehia, Elshemy, Eman Elsayed, Elsherbini, Sara, Eltoukhy, Naglaa, Elwakil, Reda, Emad, Ola, Emad, Shaimaa, Embabi, Mohamed, Ergenç, Ilkay, Ermolova, Tatiana, Esmat, Gamal, Esmat, Doaa M., Estupiñan, Enrique Carrera, Ettair, Said, Eugen, Tcaciuc, Ezz-Eldin, Mohammed, Falcón, Lidia Patricia Valdivieso, Fan, Yu-Chen, Fandari, Samah, Farag, Mahmoud, Farahat, Taghreed Mohamed, Fares, Eman M., Fares, Michael, Fassio, Eduardo, Fathy, Hayam, Fathy, Dina, Fathy, Wael, Fayed, Soheir, Feng, Dan, Feng, Gong, Fernández-Bermejo, Miguel, Ferreira, Cristina Targa, Ferrer, Javier Díaz, Forbes, Alastair, Fouad, Rabab, Fouad, Hanan M., Frisch, Tove, Fujii, Hideki, Fukunaga, Shuhei, Fukunishi, Shinya, Fulya, Hacer, Furuhashi, Masato, Gaber, Yasmine, Galang, Augusto Jose G., Gallardo, Jacqueline Cordova, Galloso, Rocío, Gamal, Mahmoud, Gamal, Reham, Gamal, Hadeel, Gan, Jian, Ganbold, Anar, Gao, Xin, Garas, George, Garba, Tony, García-Cortes, Miren, García-Monzón, Carmelo, García-Samaniego, Javier, Gastaldelli, Amalia, Gatica, Manuel, Gatley, Elizabeth, Gegeshidze, Tamar, Geng, Bin, Ghazinyan, Hasmik, Ghoneem, Salma, Giacomelli, Luca, Giannelli, Gianluigi, Giannini, Edoardo G., Giefer, Matthew, Ginès, Pere, Girala, Marcos, Giraudi, Pablo J, Goh, George Boon-Bee, Gomaa, Ahmed Ali, Gong, Benbingdi, Gonzales, Dina Hilda C., Gonzalez, Humberto C., Gonzalez-Huezo, Maria Saraí, Graupera, Isabel, Grgurevic, Ivica, Grønbæk, Henning, Gu, Xuelian, Guan, Lin, Gueye, Ibrahima, Guingané, Alice Nanelin, Gul, Ozen Oz, Gul, Cuma Bulent, Guo, Qing, Gupta, Pramendra Prasad, Gurakar, Ahmet, Gutierrez, Juan Carlos Restrepo, Habib, Ghada, Hafez, Azaa, Hagman, Emilia, Halawa, Eman, Hamdy, Osama, Hamed, Abd Elkhalek, Hamed, Dina H., Hamid, Saeed, Hamoudi, Waseem, Han, Yu, Haridy, James, Haridy, Hanan, Harris, David C H Harris, Hart, Michael, Hasan, Fuad, Hashim, Almoutaz, Hassan, Israa, Hassan, Ayman, Hassan, Essam Ali, Hassan, Adel Ahmed, Hassan, Magda Shehata, Hassanin, Fetouh, Hassnine, Alshymaa, Haukeland, John Willy, Hawal, Amr Ismael M., He, Jinfan, He, Qiong, He, Yong, He, Fang-Ping, Hegazy, Mona, Hegazy, Adham, Henegil, Osama, Hernández, Nelia, Hernández-Guerra, Manuel, Higuera-de-la-Tijera, Fatima, Hindy, Ibrahim, Hirota, Keisuke, Ho, Lee Chi, Hodge, Alexander, Hosny, Mohamed, Hou, Xin, Huang, Jiao-Feng, Huang, Yan, Huang, Zhifeng, Huang, Yuan, Huang, Ang, Huang, Yuan, Huang, Xiao-Ping, Hui-ping, Sheng, Hunyady, Bela, Hussein, Mennatallah A., Hussein, Osama, Hussien, Shahinaz Mahmoud, Ibáñez-Samaniego, Luis, Ibdah, Jamal, Ibrahim, Luqman, Ibrahim, Miada, Ibrahim, Ibrahim, Icaza-Chávez, Maria E., Idelbi, Sahar, Idilman, Ramazan Idilman, Ikeda, Mayumi, Indolfi, Giuseppe, Invernizzi, Federica, Irshad, Iram, Isa, Hasan Mohamed Ali, Iskandar, Natacha Jreige, Ismaiel, Abdulrahman, Ismail, Mariam, Ismail, Zulkifli, Ismail, Faisal, Iwamoto, Hideki, Jack, Kathryn, Jacob, Rachael, Jafarov, Fuad, Jafri, Wasim, Jahshan, Helen, Jalal, Prasun K, Jancoriene, Ligita, Janicko, Martin, Jayasena, Hiruni, Jefferies, Meryem, Jha, Vivekanand, Ji, Fanpu, Ji, Yaqiu, Jia, Jidong, Jiang, Changtao, Jiang, Ni, Jiang, Zong-zhe, Jin, Xing, Jin, Yi, Jing, Xu, Jingyu, Qian, Jinjolava, Maia, Jong, FX Himawan Haryanto, Jucov, Alina, Julius, Ibecheole, Kaddah, Mona, Kamada, Yoshihiro, kamal, Abobakr, Kamal, Enas Mohamed, Kamel, Ashraf Sayed, Kao, Jia-Horng, Karin, Maja, Karlas, Thomas, Kashwaa, Mohammad, Katsidzira, Leolin, Kaya, Eda, Kayasseh, M.Azzam, Keenan, Bernadette, Keklikkiran, Caglayan, Keml, William, Khalaf, Deia K., Khalefa, Rofida, Khamis, Sherin, Khater, Doaa, khattab, Hamed, Khavkin, Anatoly, Khlynova, Olga, Khmis, Nabil, Kobyliak, Nazarii, Koffas, Apostolos, Koike, Kazuhiko, Kok, Kenneth Y.Y., Koller, Tomas, Komas, Narcisse Patrice, Korochanskaya, Nataliya V., Koulla, Yannoula, Koya, Shunji, Kraft, Colleen, Kraja, Bledar, Krawczyk, Marcin, Kuchay, Mohammad Shafi, Kulkarni, Anand V, Kumar, Ashish, Kumar, Manoj, Lakoh, Sulaiman, Lam, Philip, Lan, Ling, Lange, Naomi F., Lankarani, Kamran Bagheri, Lanthier, Nicolas, Lapshyna, Kateryna, Lashen, Sameh A., Laure, Konang Nguieguia Justine, Lazebnik, Leonid, Lebrec, Didier, Lee, Samuel S., Lee, Way Seah, Lee, Yeong Yeh, Leeming, Diana Julie, Leite, Nathalie Carvalho, Leon, Roberto, Lesmana, Cosmas Rinaldi Adithya, Li, Junfeng, Li, Qiong, Li, Jun, Li, Yang-Yang, Li, Yufang, Li, Lei, Li, Min, li, Yiling, Liang, Huiqing, Lijuan, Tang, Lim, Seng Gee, Lim, Lee-Ling, Lin, Shumei, Lin, Han-Chieh, Lin, Rita, Lithy, Rania, Liu, Yaru, Liu, Yuanyuan, Liu, Xin, Liu, Wen-Yue, Liu, Shourong, Liu, Ken, Liu, Tian, Lonardo, Amedeo, López, Mariana Bravo, López-Benages, Eva, Lopez-Jaramillo, Patricio, Lu, Huimin, Lu, Lun Gen, Lu, Yan, Lubel, John, Lui, Rashid, Lupasco, Iulianna, Luzina, Elena, Lv, Xiao-Hui, Lynch, Kate, Ma, Hong-Lei, Machado, Mariana Verdelho, Maduka, Nonso, Madzharova, Katerina, Magdaong, Russellini, Mahadeva, Sanjiv, Mahfouz, Amel, Mahmood, Nik Ritza Kosai Nik, Mahmoud, Eman, Mahrous, Mohamed, Maiwall, Rakhi, Majeed, Ammar, Majumdar, Avik, Mak, Loey, Maklouf, Madiha M, Malekzadeh, Reza, Mandato, Claudia, Mangia, Alessandra, Mann, Jake, Mansour, Hala Hussien, Mansouri, Abdellah, Mantovani, Alessandro, Mao, Jun qian, Maramag, Flor, Marchesini, Giulio, Marcus, Claude, Marinho, Rui António Rocha Tato, Martinez-Chantar, Maria L, Martins, Antonieta A. Soares, Marwan, Rana, Mason, Karen Frances, Masoud, Ghadeer, Massoud, Mohamed Naguib, Matamoros, Maria Amalia, Mateos, Rosa Martín, Mawed, Asmaa, Mbanya, Jean Claude, Mbendi, Charles, McColaugh, Lone, McLeod, Duncan, Medina, Juan Francisco Rivera, Megahed, Ahmed, Mehrez, Mai, Memon, Iqbal, Merat, Shahin, Mercado, Randy, Mesbah, Ahmed, Meskini, Taoufik, Metwally, Mayada, Metwaly, Rasha, Miao, Lei, Micah, Eileen, Miele, Luca, Milivojevic, Vladimir, Milovanovic, Tamara, Mina, Yvonne L., Mishkovik, Milan, Mishriki, Amal, Mitchell, Tim, Mohamed, Alshaimaa, Mohamed, Mona, Mohamed, Sofain, Mohammed, Shady, Mohammed, Ahmed, Mohan, Viswanathan, Mohie, Sara, Mokhtar, Aalaa, Moniem, Reham, Montilla, Mabel Segura, Morales, Jose Antonio Orozco, Morata, María María Sánchez, Moreno-Planas, Jose Maria, Morise, Silvia, Mosaad, Sherif, Moselhy, Mohamed, Mostafa, Alaa Mohamed, Mostafa, Ebraheem, Mouane, Nezha, Mousa, Nasser, Moustafa, Hamdy Mahfouz, Msherif, Abeer, Muller, Kate, Munoz, Christopher, Muñoz-Urribarri, Ana Beatriz, Murillo, Omar Alfaro, Mustapha, Feisul Idzwan, Muzurović, Emir, Nabil, Yehia, Nafady, Shaymaa, Nagamatsu, Ayu, Nakajima, Atsushi, Nakano, Dan, Nan, Yuemin, Nascimbeni, Fabio, Naseef, Mirella S., Nashat, Nagwa, Natalia, Taran, Negro, Francesco, Nersesov, Alexander V., Neuman, Manuela, Ng'wanasayi, Masolwa, Ni, Yan, Nicoll, Amanda, Niizeki, Takashi, Nikolova, Dafina, Ningning, Wang, Niriella, Madunil, Nogoibaeva, K.A, Nordien, Rozeena, O Sullivan, Catherine, O'Beirne, James, Obekpa, Solomon, Ocama, Ponsiano, Ochwoto, Missiani, Ogolodom, Michael Promise, Ojo, Olusegun, Okrostsvaridze, Nana, Oliveira, Claudia P., Omaña, Raul Contreras, Omar, Omneya M., Omar, Hanaa, Omar, Mabroka, Omran, Salma, Omran, Reham, Osman, Marian Muse, Owise, Nevin, Owusu-Ansah, Theobald, Padilla- Machaca, P. Martín, Palle, Sirish, Pan, Ziyan, Pan, Xiao-Yan, Pan, Qiuwei, Papaefthymiou, Apostolis, Paquissi, Feliciano Chanana, Par, Gabriella, Parkash, Arit, Payawal, Diana, Peltekian, Kevork M., Peng, Xuebin, Peng, Liang, Peng, Ying, Pengoria, Rahul, Perez, Martina, Pérez, José Luis, Pérez, Norma Marlene, Persico, Marcello, Pessoa, Mário Guimarães, Petta, Salvatore, Philip, Mathew, Plaz Torres, Maria Corina, Polavarapu, Naveen, Poniachik, Jaime, Portincasa, Piero, Pu, Chunwen, Pürnak, Tuğrul, Purwanto, Edhie, Qi, Xiaolong, Qi, Xingshun, Qian, Zibing, Qiang, Zhao, Qiao, Zengpei, Qiao, Liang, Queiroz, Alberto, Rabiee, Atoosa, Radwan, Manal, Rahetilahy, Alain Marcel, Ramadan, Yasmin, Ramadan, Dina, Ramli, Anis Safura, Ramm, Grant A., Ran, Ao, Rankovic, Ivan, RAO, Huiying, Raouf, Sara, Ray, Sayantan, Reau, Nancy, Refaat, Ahmed, Reiberger, Thomas, Remes-Troche, Jose M, Reyes, Eira Cerda, Richardson, Ben, Ridruejo, Ezequiel, Riestra Jimenez, Sergio, Rizk, Ibrahim, Roberts, Stuart, Roblero, Juan Pablo, Robles, Jorge Alberto Prado, Rockey, Don, Rodríguez, Manuel, Rodríguez Hernández, Heriberto, Román, Eva, Romeiro, Fernando Gomes, Romeo, Stefano, Rosales-Zabal, Jose Miguel, Roshdi, Georgina R., Rosso, Natalia, Ruf, Andres, Ruiz, Patricia Cordero, Runes, Nelia R., Ruzzenente, Andrea, Ryan, Marno, Saad, Ahmed, Sabbagh, Eman BE, Sabbah, Meriam, Saber, Shimaa, Sabrey, Reham, Sabry, Ramy, Saeed, Maysaa Abdallah, Said, Dina, Said, Ebada M, Sakr, Mohammad Amin, Salah, Yara, Salama, Rabab Maamoun, Salama, Asmaa, Saleh, Hussein, Saleh, Ahmed, Salem, Ahmed, Salem, Ahmed Thabet, Salifou, Alkassoum, Salih, Aso Faeq, Salman, Abdallah, Samouda, Hanen, Sanai, Faisal, Sánchez-Ávila, Juan Francisco, Sanker, Lakshumanan, Sano, Tomoya, Sanz, Miquel, Saparbu, Tobokalova, Sawhney, Rohit, Sayed, Fatma, Sayed, Sayed A., Sayed, Ashraf Othman, Sayed, Manar, Sebastiani, Giada, Secadas, Laura, Sediqi, Khawaja Qamaruddin, Seif, Sameh, Semida, Nady, Şenateş, Ebubekir, Serban, Elena Daniela, Serfaty, Lawrence, Seto, Wai-Kay, Sghaier, Ikram, Sha, Min, Shabaan, Hamada M., Shalaby, Lobna, Shaltout, Inass, Sharara, Ala I., Sharma, Vishal, Shawa, Isaac Thom, Shawkat, Ahmed, Shawky, Nehal, Shehata, Osama, Sheils, Sinead, Shewaye, Abate Bane, Shi, Guojun, Shi, Junping, Shimose, Shigeo, Shirono, Tomotake, Shou, Lan, Shrestha, Ananta, Shui, Guanghou, Sievert, William, Sigurdardottir, Solveig, Sira, Mostafa Mohamed, Siradj, Riyadh, Sison, Cecilia, Smyth, Linda, Soliman, Reham, Sollano, Jose D, Sombie, Roger, Sonderup, Mark, Sood, Siddharth, Soriano, German, Stedman, Catherine A M, Stefanyuk, Oksana, Štimac, Davor, Strasser, Simone, Strnad, Pavel, Stuart, Katherine, Su, Wen, Su, Minghua, Sumida, Yoshio, Sumie, Shuji, Sun, Dan-Qin, Sun, Jing, Suzuki, Hiroyuki, Svegliati-Baroni, Gianluca, Swar, Mohamed Osman, TAHARBOUCHT, S., Taher, Zenab, Takamura, Saori, Tan, Lin, Tan, Soek-Siam, Tanwandee, Tawesak, Tarek, Sara, Tatiana, Ghelimici, Tavaglione, Federica, Tecson, Gina Y., Tee, Hoi-Poh, Teschke, Rolf, Tharwat, Mostafa, Thong, Vo Duy, Thursz, Mark, Tine, Tulari, Tiribelli, Claudio, Tolmane, Ieva, Tong, Jing, Tongo, Marco, Torkie, Mamdouh, Torre, Aldo, Torres, Esther A, Trajkovska, Meri, Treeprasertsuk, Sombat, Tsutsumi, Tsubasa, Tu, Thomas, Tur, Josep A., Turan, Dilara, Turcan, Svetlana, Turkina, Svetlana, Tutar, Engin, Tzeuton, Christian, Ugiagbe, Rose, Uygun, Ahmet, Vacca, Michele, Vajro, Pietro, Van der Poorten, David, Van Kleef, Laurens A., Vashakidze, Eliza, Velazquez, Carlos Moctezuma, Velazquez, Mirtha Infante, Vento, Sandro, Verhoeven, Veronique, Vespasiani-Gentilucci, Umberto, Vethakkan, Shireene Ratna, Vilaseca, Josep, Vítek, Libor, Volkanovska, Ance, Wallace, Michael, Wan, Wang, Wang, Yan, Wang, Ying, Wang, Xiaolin, Wang, Xuemei, Wang, Chengyan, Wang, Chunjiong, Wang, Mingjie, Wangchuk, Pelden, Weltman, Martin, White, MaryFrances, Wiegand, Johannes, Wifi, Mohamed-Naguib, Wigg, Alan, Wilhelmi, Markus, William, Remon, Wittenburg, Henning, Wu, Shengjie, Wubeneh, Abdu Mohammed, Xia, Hongping, Xiao, Jian, Xiao, Xiao, Xiaofeng, Wang, Xiong, Wanyuan, Xu, Liang, Xu, Jie, Xu, Weiguo, Xu, Jing-Hang, Xu, Keshu, Xu, Yumin, Xu, Shi-Hao, Xu, Meng, Xu, Aimin, Xu, Chengfu, Yan, Hongmei, Yang, Jingyi, Yang, Rui-Xu, Yang, Yating, Yang, Qinhe, Yang, Naibin, Yao, Jia, Yara, Justine, Yaraş, Serkan, Yılmaz, Nimet, Younes, Ramy, younes, Huda, Young, Sona, Youssef, Farah, Yu, Yanyan, Yu, Ming-Lung, Yuan, Jing, Yue, Zhang, Yuen, Man-Fung, Yun, Wang, Yurukova, Nonka, Zakaria, Serag, Zaky, Samy, Zaldastanishvili, Maia, Zapata, Rodrigo, Zare, Nazanin, Zerem, Enver, Zeriban, Nema, Zeshuai, Xu, Zhang, Huijie, Zhang, Xuemei, Zhang, Yupei, Zhang, Wen-Hua, Zhang, Xuchen, Zhang, Yon-ping, Zhang, Yuexin, Zhang, Zhan-qing, Zhao, Jingmin, Zhao, Rong-Rong, Zhao, Hongwei, Zheng, Chao, Zheng, Yijie, Zheng, Ruidan, Zheng, Tian-Lei, Zheng, Kenneth, Zhou, Xi Qiao, Zhou, Yongjian, Zhou, Yu-Jie, Zhou, Hong, Zhou, Ling, Zhou, Yongning, Zhu, Long dong, Zhu, Yong Fen, Zhu, Yueyong, Zhu, Pei-Wu, Ziada, Ebtesam, Ziring, David, Ziyi, Li, Zou, Shanshan, Zou, Zhengsheng, Zou, Huaibin, and Zuart Ruiz, Roberto

Published
2022
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138. Neumonía por COVID-19 en niños: De su etiología a su manejo

Author

Parisi, Giuseppe Fabio, Indolfi, Cristiana, Decimo, Fabio, Leonardi, Salvatore, and Miraglia del Giudice, Michele

Abstract

El COVID-19 es menos serio en niños que en adultos. Sin embargo, las afecciones respiratorias dominan el cuadro clínico de pacientes hospitalizados por COVID-19, aun en niños. En algunas series de casos, el deterioro del estado clínico, donde la disnea, la cianosis y el inicio del síndrome de dificultad respiratoria aguda (SDRA) emergieron ∼8–10 días después del inicio de la infección por SARS-CoV-2, pudo progresar rápidamente hasta la falla multiorgánica y la muerte. Esta revisión tiene como objetivo evaluar las características de la neumonía por COVID-19 en poblaciones pediátricas, comenzando con su etiología y sus mecanismos patológicos, para cerrar con su manejo clínico.

Published
2021
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139. Efficacy of Sofosbuvir/Ledipasvir in Adolescents With Chronic Hepatitis C Genotypes 1, 3, and 4

Author

Serranti, Daniele, Nebbia, Gabriella, Cananzi, Mara, Nicastro, Emanuele, Di Dato, Fabiola, Nuti, Federica, Garazzino, Silvia, Silvestro, Erika, Giacomet, Vania, Forlanini, Federica, Pinon, Michele, Calvo, Pier Luigi, Riva, Silvia, Dodi, Icilio, Cangelosi, Antonina Marta, Antonucci, Roberto, Ricci, Silvia, Bartolini, Elisa, Mastrangelo, Greta, Trapani, Sandra, Lenge, Matteo, Gaio, Paola, Vajro, Pietro, Iorio, Raffaele, D’Antiga, Lorenzo, and Indolfi, Giuseppe

Abstract

Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to <18 years old) with CHC in the real-world setting. Prospective, open-label, multicentre study involving 12 Italian centres. Patients received the fixed-dose combination of SOF/LDV (400/90?mg) once daily ± ribavirin as per EMA approval and recommendations. The key efficacy endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) as per intention-to-treat analysis. Safety was assessed by adverse events and clinical/laboratory data. Seventy-eight consecutive adolescents (median age 15.2 years, range 12–17.9; girls 53.8%) were enrolled and treated between June 2018 and December 2019. Genotype distribution was as follows: genotype 1 (82.1%), 3 (2.5%), and 4 (15.4%). Seventy-six (97.4%) patients completed treatment and follow-up. Overall, SVR12 was 98.7%. One patient was lost to follow-up after 4 weeks of treatment; 1 patient completed treatment and missed the follow-up visit. No virological breakthrough or relapse were observed. No patient experienced grade 3 to 4 adverse event or serious adverse event. The results of this real-world study confirmed the high efficacy and the optimal safety profile of SOF/LDV for treatment of CHC in adolescents.

Published
2021
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140. Old unsolved problems: when and how to treat silent ischaemia

Author

Indolfi, Ciro, Polimeni, Alberto, Mongiardo, Annalisa, De Rosa, Salvatore, and Spaccarotella, Carmen

Abstract

Silent myocardial ischaemia (SMI) is defined as objective evidence of ischaemia without angina (or equivalent symptoms) in the presence of coronary artery disease, differing from silent coronary artery disease. Silent myocardial ischaemia represents the majority of episodes of myocardial ischaemia at Holter monitoring. During transient myocardial ischaemia, the symptoms appear after the contraction anomalies of the left ventricle and after the ECG changes. The cause of silent myocardial ischaemia is still not well established. The severity and duration of ischaemia have been theorized as important elements in the SMI mechanism. Another possible mechanism responsible for SMI is represented by changes in the perception of painful stimuli with an increased pain threshold. Finally, a neuronal dysfunction of the diabetic, in post-infarction or a cardiac neuronal ‘stunning’ could play a role in SMI. In the pre-stent era, the SMI was associated with a worse prognosis. In patients with diabetes mellitus, SMI seems to be more represented because autonomic dysfunction is present in this category of patients. In conclusion, SMI is more frequent than symptomatic ischaemia. However, despite the presence of countless studies on the subject, it is not clear today whether medical therapy has equalized the risk and what the real prognosis of SMI is.

Published
2020
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141. Stent Thrombosis After Percutaneous Coronary Intervention

Author

Polimeni, Alberto, Sorrentino, Sabato, Spaccarotella, Carmen, Mongiardo, Annalisa, Sabatino, Jolanda, De Rosa, Salvatore, Gori, Tommaso, and Indolfi, Ciro

Abstract

Since their introduction in clinical practice in 1986, different types of coronary stents have been developed and become available for the treatment of coronary artery disease. Stent thrombosis (ST) is an uncommon but harmful complication after percutaneous coronary implantation, with a high occurrence of acute myocardial infarction and risk of mortality. Among several procedural and clinical predictors, the type of coronary stent is a strong determinant of ST. This article reviews the available evidence on the most used coronary stent types in the modern era and the related risk of ST.

Published
2020
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142. Multichannel Electrocardiograms Obtained by a Smartwatch for the Diagnosis of ST-Segment Changes

Author

Spaccarotella, Carmen Anna Maria, Polimeni, Alberto, Migliarino, Serena, Principe, Elisa, Curcio, Antonio, Mongiardo, Annalisa, Sorrentino, Sabato, De Rosa, Salvatore, and Indolfi, Ciro

Abstract

IMPORTANCE: Acute coronary syndromes are the leading cause of death worldwide and the leading cause of disease burden in high-income countries. Quick and accurate diagnosis of acute coronary syndromes is essential to avoid fatal events, for timely intervention, and to improve the prognosis. OBJECTIVE: To prospectively investigate the feasibility and accuracy of a smartwatch in recording multiple electrocardiographic (ECG) leads and detecting ST-segment changes associated with acute coronary syndromes compared with a standard 12-lead ECG. DESIGN, SETTING, AND PARTICIPANTS: A commercially available smartwatch was used in 100 participants to obtain multiple-channel ECGs. The study was conducted from April 19, 2019, to January 23, 2020. Fifty-four patients with ST elevation myocardial infarction, 27 patients with non-ST elevation myocardial infarction, and 19 healthy individuals were included in the study. The watch was placed in different body positions to obtain 9 bipolar ECG tracings (corresponding to Einthoven leads I, II, and III and precordial leads V1-V6) that were compared with a simultaneous standard 12-lead ECG. MAIN OUTCOMES AND MEASURES: The concordance among the results of the smartwatch and standard ECG recordings was assessed using the Cohen κ coefficient and Bland-Altman analysis. RESULTS: Of the 100 participants in the study, 67 were men (67%); mean (SD) age was 61 (16) years. Agreement was found between the smartwatch and standard ECG for the identification of a normal ECG (Cohen κ coefficient, 0.90; 95% CI, 0.78-1.00), ST-segment elevation changes (Cohen κ coefficient, 0.88; 95% CI, 0.78-0.97), and non–ST-segment elevation changes (Cohen κ coefficient, 0.85; 95% CI, 0.74-0.96). In addition, the Bland-Altman analysis demonstrated agreement between the smartwatch and standard ECG to detect the amplitude of ST-segment changes (bias, −0.003; SD, 0.18; lower limit, −0.36; and upper limit, 0.36). Use of the smartwatch ECG for the diagnosis of normal ECG showed a sensitivity of 84% (95% CI, 60%-97%) and specificity of 100% (95% CI, 95%-100%); for ST elevation, sensitivity was 93% (95% CI, 82%-99%) and specificity was 95% (95% CI, 85%-99%); and for NSTE ECG alterations, sensitivity was 94% (95% CI, 81%-99%) and specificity was 92% (95% CI, 83%-97%). CONCLUSIONS AND RELEVANCE: The findings of this study suggest agreement between the multichannel smartwatch ECG and standard ECG for the identification of ST-segment changes in patients with acute coronary syndromes.

Published
2020
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143. Nasal Swab as Preferred Clinical Specimen for COVID-19 Testing in Children

Author

Palmas, Giordano, Moriondo, Maria, Trapani, Sandra, Ricci, Silvia, Calistri, Elisa, Pisano, Laura, Perferi, Giancarlo, Galli, Luisa, Venturini, Elisabetta, Indolfi, Giuseppe, and Azzari, Chiara

Abstract

The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014–0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.

Published
2020
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144. Comparison of Recommendations for Treatment of Chronic Hepatitis C Virus Infection in Children and Adolescents

Author

Indolfi, Giuseppe, Fischler, Björn, Gonzalez-Peralta, Regino P., Ciocca, Mirta, Porta, Gilda, Neelam, Mohan, El-Guindi, Mohamed, Kelly, Deirdre, Ni, Yen-Hsuan, Sibal, Anupan, Leung, Daniel H., and Chang, Mei Hwei

Abstract

This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus, and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement. MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019. A total of 5 documents were analysed: 3 CPGs, 1 medical consensus, and 1 position paper. All publications were consistent in recommending DAA treatment for adolescents (12–17 years old) with chronic HCV infection. Similarly, all of these publications consistently recommended deferring therapy for children between 3 and 11 years of age until DAA became available as standard of care. Finally, none of the included publications recommended treating children younger than 3 years old. By contrast, there was significant discrepancy across the retrieved documents regarding specific DAA regimens and treatment strategies. There is strong consensus on treating all adolescents with chronic HCV infection with DAA and on delaying therapy in younger children until these agents are approved for them. Interferon-based therapies should be avoided. Specific recommendations regarding which DAA regimen to use and treatment duration varied significantly. Key stakeholders need to convene to standardize therapeutic strategies at a global level if we are to eradicate HCV in children.

Published
2020
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145. Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies

Author

Indolfi, Giuseppe, Abdel-Hady, Mona, Bansal, Sanjay, Debray, Dominique, Smets, Françoise, Czubkowski, Piotr, Woerd, Wendy, Samyn, Marianne, Jahnel, Jörg, Gupte, Girish, Zellos, Aglaia, Mozer-Glassberg, Yael, Verkade, Henkjan J., Sokal, Etienne, and Fischler, Björn

Abstract

Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.

Published
2020
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146. Postchemotherapy PET evaluation correlates with patient outcome in paediatric Hodgkin's disease

Author

Lopci, E, Burnelli, R, Guerra, L, Cistaro, A, Piccardo, A, Zucchetta, P, Derenzini, E, Todesco, A, Garaventa, A, Schumacher, F, Farruggia, P, Buffardi, S, Sala, A, Casale, F, Indolfi, P, Biondi, S, Pession, A, Fanti, S, Lopci E., Burnelli R., Guerra L., Cistaro A., Piccardo A., Zucchetta P., Derenzini E., Todesco A., Garaventa A., Schumacher F., Farruggia P., Buffardi S., Sala A., Casale F., Indolfi P., Biondi S., Pession A., Fanti S., Lopci, E, Burnelli, R, Guerra, L, Cistaro, A, Piccardo, A, Zucchetta, P, Derenzini, E, Todesco, A, Garaventa, A, Schumacher, F, Farruggia, P, Buffardi, S, Sala, A, Casale, F, Indolfi, P, Biondi, S, Pession, A, Fanti, S, Lopci E., Burnelli R., Guerra L., Cistaro A., Piccardo A., Zucchetta P., Derenzini E., Todesco A., Garaventa A., Schumacher F., Farruggia P., Buffardi S., Sala A., Casale F., Indolfi P., Biondi S., Pession A., and Fanti S.

Abstract

Aim: To evaluate the role of postchemotherapy FDG PET and compare it with other predictive factors in paediatric Hodgkin's disease (HD). Materials and methods: In this retrospective study, 98 paediatric patients with HD (enrolled in eight Italian centres) were analysed. Their mean age was 13.8 years (range 5-19 years). A PET scan was performed at the end of chemotherapy and reported as positive or negative on the basis of visual and/or semiquantitative analysis. True outcome was defined as remission or disease on the basis of combined criteria (clinical, instrumental and/or histological) with a mean follow-up period of 25 months. Statistical analyses were performed for the postchemotherapy PET results and other potential predictive factors (age cut-off, stage, presence of bulky masses and therapeutic group) with respect to patient outcome and progression-free survival (PFS). Results: Overall the patients had a mean PFS of 23.5 months (range 4-46 months): 87 achieved remission (88.8%) and 11 showed disease. Of the 98 patients, 17 were positive on postchemotherapy PET. Seven patients (41%) showed disease during follow-up, and relapse occurred in only four out of the 81 patients who were negative on PET (p=0.0001). Kaplan-Meier analysis demonstrated significant correlations between PFS and the postchemotherapy PET result (p=0.0001) and a cut-off age at diagnosis of 13.3 years (p=0.0337), whereas disease stage (p=0.7404), therapeutic group (p=0.5240) and presence of bulky masses (p=0.2208) were not significantly correlated with PFS. Multivariate analysis confirmed a statistically significant correlation with PFS only for the postchemotherapy PET findings (p=0.0009). Conclusion: In paediatric HD, age at diagnosis and postchemotherapy PET results are the main predictors of patient outcome and PFS, with FDG PET being the only independent predictive factor for PFS. © Springer-Verlag 2011

Published
2011

147. Childhood Head and Neck Lymphadenopathy: A Report by a Single Institution (2003-2017)

Author

Indolfi, Paolo, Perrotta, Silverio, Rossi, Francesca, Di Martino, Martina, Pota, Elvira, Di Pinto, Daniela, Gualdiero, Giovanna, Boccieri, Emilia, Indolfi, Cristiana, and Casale, Fiorina

Abstract

Actually, there is still no consensus related to diagnostic and management algorithms in case of head and neck lymphadenopathy in children. The aim of our study was to analyze the causes of head and neck lymphadenopathy in children to determine a systematic diagnostic approach. We enrolled all cases of head and neck lymphadenopathy in children under the age of 18 diagnosed at the Unit of Hemato-Oncology, Pediatric Department of University “Luigi Vanvitelli,” Naples, over a 15-year period (January 2003-December 2017). In total, 405 patients (271 males) were enrolled in the study. Thirteen cases due to other causes, were left off the study. Therefore, the study was performed on 392 cases. A total of 220 patients (56.1%) had a history of infection, 66 cases (16.8%) a diagnosis of neoplasia, and 101 (24.9%) cases a diagnosis of reactive inflammatory changes of nonspecific origin. We have observed the following from our study: (1) the acute infections are the most common causes of head and neck lymphadenopathy in the pediatric population; (2) in about a quarter of patients, the lymphadenopathy resulted by nonspecific origin; (3) the supraclavicular nodes should be regarded with a high index of suspicion of malignancy.

Published
2019
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148. Delayed Flow-Mediated Vasodilation and Critical Coronary Stenosis

Author

Irace, Concetta, De Rosa, Salvatore, Tripolino, Cesare, Ambrosio, Giuseppe, Covello, Caterina, Abramo, Ennio, Carallo, Claudio, Mongiardo, Annalisa, Spaccarotella, Carmen, Torella, Daniele, Gnasso, Agostino, Indolfi, Ciro, De Rosa, Salvatore, Tripolino, Cesare, Ambrosio, Giuseppe, Covello, Caterina, Abramo, Ennio, Carallo, Claudio, Mongiardo, Annalisa, Spaccarotella, Carmen, Torella, Daniele, Gnasso, Agostino, and Indolfi, Ciro

Abstract

Endothelial dysfunction, wall thickening and plaque are progressive manifestations of atherosclerosis. Delayed or absent brachial artery dilation after ischemic stimulus has been associated with severity of extracoronary and coronary atherosclerosis. In the current study, we aimed to verify if delayed or absent dilation associates with critical coronary stenosis. We also evaluated the association between coronary stenosis, carotid artery wall thickness and peripheral artery disease. Endothelial function was investigated by flow-mediated dilation of the brachial artery up to 3?min after ischemia, and patients classified as early, late or no dilators. Coronary angiography was performed through transradial or femoral artery approach. Computerized quantitative angiography was used to obtain percent stenosis of all lesions, while the Gensini score was used to evaluate the severity of coronary atherosclerosis. Seventy-four patients were enrolled. Carotid wall thickness and plaque, and peripheral artery disease were detected by ultrasound. Subjects with critical coronary stenosis showed a higher prevalence of delayed or absent dilation (coronary stenosis =70 per cent: late dilators 50 per cent, no dilators 35 per cent; coronary stenosis =70 per cent: late dilators 27 per cent, no dilators 6 per cent). The Gensini score was progressively higher in late dilators and no dilators compared with early dilators (early: 4.5±13.5; late 17.5±27.1; no 39.7±55.0; P<0.02). Carotid atherosclerosis and peripheral artery disease were more prevalent in subjects with critical coronary stenosis. Delayed or absent dilation associates with coronary stenosis and different degree of coronary atherosclerosis. The kinetic of arterial dilation seems to be relevant as the magnitude of dilation.

Published
2018
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149. Etiology, presenting features and outcome of children with non-cirrhotic portal vein thrombosis: A multicentre national study.

Author

Di Giorgio, Angelo, De Angelis, Paola, Cheli, Maurizio, Vajro, Pietro, Iorio, Raffaele, Cananzi, Mara, Riva, Silvia, Maggiore, Giuseppe, Indolfi, Giuseppe, Calvo, Pier Luigi, Nicastro, Emanuele, and D'Antiga, Lorenzo

Abstract

Non-cirrhotic portal vein thrombosis (PVT) is a main cause of portal hypertension in children. We describe the characteristics at presentation and outcome of a cohort of patients with PVT to determine clinical features and predictors of outcome. We recorded: (1) Associated factors: prematurity, congenital malformations, neonatal illnesses, umbilical vein catheterization (UVC), deep infections, surgery; (2) congenital and acquired prothrombotic disorders; (3) features at last follow up including survival rate and need for surgery. 187 patients, mean age at diagnosis 4 ± 3.7 years, had a history of prematurity (61%); UVC (65%); neonatal illnesses (79%). The diagnosis followed the detection of splenomegaly (40%), gastrointestinal bleeding (36%), hypersplenism (6%), or was incidental (18%). Of 71 patients who had endoscopy at presentation 62 (87%) had oesophageal varices. After 11.3 years' follow up 63 (34%) required surgery or TIPS. Ten-year survival rate was 98%, with 90% shunt patency. Spleen size, variceal bleeding and hypersplenism at presentation were predictors of surgery or TIPS (p < 0.05). PVT is associated with congenital and acquired co-morbidities. History of prematurity, neonatal illnesses and UVC should lead to rule out PVT. Large spleen, variceal bleeding and hypersplenism at presentation predict the need for eventual surgery in a third of cases. [ABSTRACT FROM AUTHOR]

Published
2019
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150. Rabdomiosarcoma (RMS) of the biliary tract (VB): clinical suspicion, diagnostic, treatment, prognosis in the series of group AIEOP

Author

Provenzi, M, Giraldi, E, Foglia, C, Cavalieri, L, Morali, L, Conter, V, Alberti, D, Colledan, M, Prete, A, Castello, M, Ferrari, A, Indolfi, P, Dall'Orso, S, Garaventa, A, Carli, M, Bisogno, G, Provenzi M, Giraldi E, Foglia C, Cavalieri L, Morali L, Conter V, Alberti D, Colledan M, Prete A, Castello MA, Ferrari A, Indolfi P, Dall'Orso S, Garaventa A, Carli M, Bisogno G, Provenzi, M, Giraldi, E, Foglia, C, Cavalieri, L, Morali, L, Conter, V, Alberti, D, Colledan, M, Prete, A, Castello, M, Ferrari, A, Indolfi, P, Dall'Orso, S, Garaventa, A, Carli, M, Bisogno, G, Provenzi M, Giraldi E, Foglia C, Cavalieri L, Morali L, Conter V, Alberti D, Colledan M, Prete A, Castello MA, Ferrari A, Indolfi P, Dall'Orso S, Garaventa A, Carli M, and Bisogno G

Published
2010

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