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1. Headache in beta-thalassemia: An Italian multicenter clinical, conventional MRI and MR-angiography case-control study

Author

Tartaglione, Immacolata, Caiazza, Martina, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Maietta, Caterina, Valentino, Maria Sole, Russo, Camilla, Roberti, Domenico, Casale, Maddalena, Elefante, Andrea, Femina, Gianluca, Esposito, Fabrizio, Ponticorvo, Sara, Russo, Andrea G., Canna, Antonietta, Ermani, Mario, Cirillo, Mario, Perrotta, Silverio, and Manara, Renzo

Published
2020
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2. Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

Author

Manara, Renzo, Ponticorvo, Sara, Perrotta, Silverio, Barillari, Maria Rosaria, Costa, Giuseppe, Brotto, Davide, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Carafa, Pasquale Alessandro, Canna, Antonietta, Russo, Andrea Gerardo, Troisi, Donato, Caiazza, Martina, Ammendola, Federica, Roberti, Domenico, Santoro, Claudia, Picariello, Stefania, Valentino, Maria Sole, Inserra, Emanuela, Carfora, Roberta, Cirillo, Mario, Raimo, Simona, Santangelo, Gabriella, di Salle, Francesco, Esposito, Fabrizio, and Tartaglione, Immacolata

Published
2021
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7. Additional file 1 of Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

Author

Manara, Renzo, Ponticorvo, Sara, Perrotta, Silverio, Barillari, Maria Rosaria, Costa, Giuseppe, Brotto, Davide, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Carafa, Pasquale Alessandro, Canna, Antonietta, Russo, Andrea Gerardo, Troisi, Donato, Caiazza, Martina, Ammendola, Federica, Roberti, Domenico, Santoro, Claudia, Picariello, Stefania, Valentino, Maria Sole, Inserra, Emanuela, Carfora, Roberta, Cirillo, Mario, Raimo, Simona, Santangelo, Gabriella, di Salle, Francesco, Esposito, Fabrizio, and Tartaglione, Immacolata

Abstract

Additional file 1. Audiological, Cognitive functioning, MRI data evaluation. S. Fig.1. Relative auditory cortex perfusion values among patients with auditory evaluation. e-Table. Pearson’s correlations between cognitive scores derived by the WAIS and right and left auditory/visual cerebral area perfusion ratio in healthy controls and patients.

Published
2021
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8. Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort

Author

Casale, M, Forni, G, Cassinerio, E, Pasquali, D, Origa, R, Serra, M, Campisi, S, Peluso, A, Renni, R, Cattoni, A, De Michele, E, Allò, M, Poggi, M, Ferrara, F, Di Concilio, R, Sportelli, F, Quarta, A, Putti, M, Notarangelo, L, Sau, A, Ladogana, S, Tartaglione, I, Picariello, S, Marcon, A, Sturiale, P, Roberti, D, Lazzarino, A, Perrotta, S, Casale, Maddalena, Forni, Gian Luca, Cassinerio, Elena, Pasquali, Daniela, Origa, Raffaella, Serra, Marilena, Campisi, Saveria, Peluso, Angelo, Renni, Roberta, Cattoni, Alessandro, De Michele, Elisa, Allò, Massimo, Poggi, Maurizio, Ferrara, Francesca, Di Concilio, Rosanna, Sportelli, Filomena, Quarta, Antonella, Putti, Maria Caterina, Notarangelo, Lucia Dora, Sau, Antonella, Ladogana, Saverio, Tartaglione, Immacolata, Picariello, Stefania, Marcon, Alessia, Sturiale, Patrizia, Roberti, Domenico, Lazzarino, Antonio Ivan, Perrotta, Silverio, Casale, M, Forni, G, Cassinerio, E, Pasquali, D, Origa, R, Serra, M, Campisi, S, Peluso, A, Renni, R, Cattoni, A, De Michele, E, Allò, M, Poggi, M, Ferrara, F, Di Concilio, R, Sportelli, F, Quarta, A, Putti, M, Notarangelo, L, Sau, A, Ladogana, S, Tartaglione, I, Picariello, S, Marcon, A, Sturiale, P, Roberti, D, Lazzarino, A, Perrotta, S, Casale, Maddalena, Forni, Gian Luca, Cassinerio, Elena, Pasquali, Daniela, Origa, Raffaella, Serra, Marilena, Campisi, Saveria, Peluso, Angelo, Renni, Roberta, Cattoni, Alessandro, De Michele, Elisa, Allò, Massimo, Poggi, Maurizio, Ferrara, Francesca, Di Concilio, Rosanna, Sportelli, Filomena, Quarta, Antonella, Putti, Maria Caterina, Notarangelo, Lucia Dora, Sau, Antonella, Ladogana, Saverio, Tartaglione, Immacolata, Picariello, Stefania, Marcon, Alessia, Sturiale, Patrizia, Roberti, Domenico, Lazzarino, Antonio Ivan, and Perrotta, Silverio

Abstract

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusiondependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3.13.1). Multiple Cox regression analysis identified three key predictors: Age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1.1.3, P=0.005), the serum concentration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1.1.4, P<0.001) regardless the kind of disease incident, while the number of previous endocrine diseases showed a negative linear effect: The higher the number of diseases at baseline the lower the chance of developing further diseasess (adjusted HR for unit increase 0.5, 95% CI: 0.4-0.7, P<0.001). Age and thyrotropin had similar effect sizes across the categories of baseline diseases. The administration of levothyroxine as a covariate did not change the estimates. Although in DFX-treated TDT patients the risk of developing an endocrine complication is generally lower than the previously reported risk, there is considerable risk variation and the burden of these complications remains high. We developed a simple risk score chart enabling clinicians to estimate their patients' risk. Future research will look at increasing the amount of variation explained from our model and testing further clinical and laboratory predictors, including the assessment of d

Published
2021

9. Non-transfusion-dependent thalassemia in Italy: less blues, no role of reds

Author

Tartaglione, Immacolata, primary, Manara, Renzo, additional, di Concilio, Rosanna, additional, Quarta, Antonella, additional, Ruffo, Giovan Battista, additional, De Michele, Elisa, additional, Ammendola, Federica, additional, Foderini, Maria Vittoria, additional, Raimo, Simona, additional, Santangelo, Gabriella, additional, and Perrotta, Silverio, additional

Published
2021
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10. Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort

Author

Casale, Maddalena, primary, Forni, Gian Luca, additional, Cassinerio, Elena, additional, Pasquali, Daniela, additional, Origa, Raffaella, additional, Serra, Marilena, additional, Campisi, Saveria, additional, Peluso, Angelo, additional, Renni, Roberta, additional, Cattoni, Alessandro, additional, De Michele, Elisa, additional, Allò, Massimo, additional, Poggi, Maurizio, additional, Ferrara, Francesca, additional, Di Concilio, Rosanna, additional, Sportelli, Filomena, additional, Quarta, Antonella, additional, Putti, Maria Caterina, additional, Notarangelo, Lucia Dora, additional, Sau, Antonella, additional, Ladogana, Saverio, additional, Tartaglione, Immacolata, additional, Picariello, Stefania, additional, Marcon, Alessia, additional, Sturiale, Patrizia, additional, Roberti, Domenico, additional, Lazzarino, Antonio Ivan, additional, and Perrotta, Silverio, additional

Published
2021
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11. Influenza Vaccination in Asplenia: Improving Quality of Care in Time of Coronavirus

Author

Di Maio, Nicoletta, primary, Russo, Giovanna, additional, Barella, Susanna, additional, Forni, Gian Luca, additional, Colombatti, Raffaella, additional, Notarangelo, Lucia, additional, Graziadei, Giovanna, additional, Sau, Antonella, additional, Rigoli, Luciana, additional, Farruggia, Piero, additional, Campisi, Saveria, additional, Casini, Tommaso, additional, Balocco, Manuela, additional, Boscarol, Gianluca, additional, Capolsini, Ilaria, additional, Grotto, Paolo, additional, Giona, Fiorina, additional, Lazzareschi, Ilaria, additional, Pugliese, Pellegrina, additional, Fioredda, Francesca, additional, Fasoli, Silvia, additional, Putti, Maria Caterina, additional, Migliavacca, Maddalena, additional, Paola, Corti, additional, Tripodi, Serena, additional, Saracco, Paola, additional, Ferrero, Simone, additional, Tornesello, Assunta, additional, Serra, Marilena, additional, Ladogana, Saverio, additional, Palazzi, Giovanni, additional, Verzegnassi, Federico, additional, Baronci, Carlo, additional, Palumbo, Giuseppe, additional, Cesaro, Simone, additional, Sainati, Laura, additional, Rivellini, Flavia, additional, Di Concilio, Rosanna, additional, Munaretto, Vania, additional, Facchini, Elena, additional, Giordano, Paola, additional, Sanna, Maria Grazia, additional, Perrotta, Silverio, additional, and Casale, Maddalena, additional

Published
2020
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12. White matter volume changes in adult beta‐thalassemia: Negligible and unrelated to anemia and cognitive performances

Author

Manara, Renzo, primary, Canna, Antonietta, additional, Caiazza, Martina, additional, Ponticorvo, Sara, additional, Russo, Andrea G., additional, Di Concilio, Rosanna, additional, Ciancio, Angela, additional, De Michele, Elisa, additional, Carafa, Pasquale Alessandro, additional, Ammendola, Federica, additional, Roberti, Domenico, additional, Casale, Maddalena, additional, Elefante, Andrea, additional, Cirillo, Mario, additional, Salle, Francesco, additional, Esposito, Fabrizio, additional, Perrotta, Silverio, additional, and Tartaglione, Immacolata, additional

Published
2020
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15. Vaccinazione Antinfluenzale in soggetti con Asplenia: warning in tempo di Coronavirus

Author

Di Maio Nicoletta, Barella, Susanna, Graziadei, Giovanna, Forni, Gianluca, Perrotta, Silverio, Allò, Massimo, Sau, Antonella, Balocco, Manuela, Di Concilio Rosanna, Rivellini, Flavia, Facchini, Elena, Peluso, Angelo, Russo, Giovanna, Rigoli, Luciana, Farruggia, Piero, Campisi, Saveria, Casini, Tommaso, Boscarol, Gianluca, Capolsini, Ilaria, Colombatti, Raffaella, Grotto, Paolo, Giona, Fiorina, Lazzareschi, Ilaria, Pugliese, Pellegrina, Fioredda, Francesca, Notarangelo Lucia Dora, Fasoli, Silvia, Putti Maria Caterina, Casciana Maria Luisa, Migliavacca, Maddalena, Corti, Paola, Tripodi, Serena, Saracco, Paola, Ferrero, Simone, Tornesello, Assunta, Serra, Marilena, Ladogana, Saverio, Palazzi, Giovanni, Verzegnassi, Federico, Baronci, Carlo, Palumbo, Giuseppe, Cesaro, Simone, and Casale, Maddalena

Published
2020

17. Brain functional impairment in beta‐thalassaemia: the cognitive profile in Italian neurologically asymptomatic adult patients in comparison to the reported literature

Author

Tartaglione, Immacolata, primary, Manara, Renzo, additional, Caiazza, Martina, additional, Carafa, Pasquale Alessandro, additional, Caserta, Violetta, additional, Ferrantino, Teresa, additional, Granato, Ilaria, additional, Ippolito, Noemi, additional, Maietta, Caterina, additional, Oliveto, Tiziana, additional, Casale, Maddalena, additional, Di Concilio, Rosanna, additional, Ciancio, Angela, additional, De Michele, Elisa, additional, Russo, Camilla, additional, Elefante, Andrea, additional, Ponticorvo, Sara, additional, Russo, Andrea Gerardo, additional, Femina, Gianluca, additional, Canna, Antonietta, additional, Ermani, Mario, additional, Cirillo, Mario, additional, Esposito, Fabrizio, additional, Centanni, Antonella, additional, Gritti, Paolo, additional, and Perrotta, Silverio, additional

Published
2019
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18. No evidence of increased cerebrovascular involvement in adult neurologically‐asymptomatic β‐Thalassaemia. A multicentre multimodal magnetic resonance study

Author

Tartaglione, Immacolata, primary, Russo, Camilla, additional, Elefante, Andrea, additional, Caiazza, Martina, additional, Casale, Maddalena, additional, Di Concilio, Rosanna, additional, Ciancio, Angela, additional, De Michele, Elisa, additional, Amendola, Giovanni, additional, Gritti, Paolo, additional, Carafa, Pasquale A., additional, Ferrantino, Teresa, additional, Centanni, Antonella, additional, Ippolito, Noemi, additional, Caserta, Violetta, additional, Oliveto, Tiziana, additional, Granato, Ilaria, additional, Femina, Gianluca, additional, Esposito, Fabrizio, additional, Ponticorvo, Sara, additional, Russo, Andrea G., additional, Canna, Antonietta, additional, Ermani, Mario, additional, Cirillo, Mario, additional, Perrotta, Silverio, additional, and Manara, Renzo, additional

Published
2019
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19. Treatment of childhood chronic idiopathic thrombocytopenic purpura with ascorbate

Author

Amendola, Giovanni, Cirillo, Giuseppe, Spiezie, Massimo, Di Concilio, Rosanna, and Rolando, Paolo

Subjects
Thrombocytopenic purpura -- Drug therapy, Vitamin C -- Evaluation, Health
Abstract

Ascorbic acid does not seem to be effective in treating chronic idiopathic thrombocytopenic purpura (ITP) in children. Chronic ITP causes small hemorrhaging in the skin and mucous membranes because of a deficiency in the number of blood platelets. A daily dose of 2 g of ascorbic acid was given to 8 patients aged 4 to 16 years. All of the patients had thrombocytopenia, a low platelet count, for at least 6 months before treatment. The average duration of treatment was 17 months, and a complete blood cell count was done every 4 weeks. The ascorbic acid was only effective in treating 2 patients, whose platelet count rose to normal after several months of treatment.

Published
1995

20. Cognitive, Brain and Intracranial Artery Involvement in Beta Thalassemia

Author

Tartaglione, Immacolata, Perrotta, Silverio, Caiazza, Martina, Casale, Maddalena, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Amendola, Giovanni, Gritti, Paolo, Carafa, Pasquale Alessandro, Ferrantino, Teresa, Centanni, Antonella, Ippolito, Noemi, Caserta, Violetta, Oliveto, Tiziana, Granato, Ilaria, Femina, Gianluca, Esposito, Fabrizio, Ponticorvo, Sara, Russo, Andrea, Russo, Camilla, Cirillo, Mario, Elefante, Andrea, and Manara, Renzo

Published
2017
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21. Structural and Functional Characterization of Csda Protein Complexes Involved In Modulation of Fetal Globin Gene Expression

Author

Gaudino, Sara, primary, Petruzzelli, Raffaella, additional, Amendola, Giovanni, additional, Sessa, Raffaele, additional, Puzone, Stella, additional, Risitano, Antonio M., additional, Storino, Maria Rosaria, additional, Di Concilio, Rosanna, additional, D’Urzo, Giovanna, additional, Amendolara, Maria, additional, Aurino, Annamaria, additional, Izzo, Paola, additional, and Grosso, Michela, additional

Published
2010
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25. Identification of a Transcription Factor Potentially Involved in ?-Globin Gene Expression.

Author

Grosso, Michela, Amendola, Giovanni, Petruzzelli, Raffaella, Puzone, Stella, Sessa, Raffaele, Di Concilio, Rosanna, D’Urzo, Giovanna, and Izzo, Paola

Abstract

The switch from fetal to adult globin gene expression occurs around birth when fetal hemoglobin (HbF) production gradually declines within a few months. Much effort is underway to clarify the molecular basis of this mechanism, since impaired hemoglobin switching leading to persistent expression of fetal globin genes in adults (HPFH) offers therapeutic potential for hemoglobinopathies (S.L. Thein. Br. J. Haematol2004; 124: 264–74). In order to identify and study regulatory factors putatively involved in ?-globin gene expression, we examined the reticulocyte mRNAs differently expressed in three siblings (one brother, 54 years-old and two sisters 35- and 37-years old, respectively). The eldest brother had been referred to Umberto I Hospital for evaluation of a severe condition of ß-thalassemia intermedia on chronic transfusion therapy since 1990. Both of his sisters resulted clinically affected by a milder form of thalassemia intermedia, non-transfusion dependent, showing Hb values around 8.4 g/dL, Hb A2 levels from 6.0 to 7.9% and HbF ranging from 14.5 to 27.6%, values higher than those resulted in their brother (5.9% Hb A2 and 7.2% HbF). Molecular analysis was performed on DNA extracted from peripheral leucocytes and revealed the same ß-globin gene cluster genotype for all these subjects who resulted homozygous for the ß+ IVSI-6 (C?T) mutation associated to haplotype VI chromosomes. Different levels of HbF were thus presumably responsible of different clinical phenotypes. To investigate the possible causes of the variations in ?-globin gene expression, extensive sequence analysis was performed on putative regulatory regions within the ß-globin gene cluster (Zhi-Hong Lu et al., Blood1996; 87: 1604–11). Results showed the same genetic background in all the siblings. It was thus supposed that genetic determinants external to the ß-globin gene cluster were responsible of the different ?-globin gene expression. To explore this hypothesis, the reticulocyte transcriptome was analyzed by a differential mRNA display approach. Reticulocytes were isolated from peripheral blood and total RNA extracted for all family members. Our study revealed several bands differentially displayed in the sample from the more severely affected sibling respect to his sisters. Selected bands were cloned in a pGEM T-vector (Promega, WI) and sequenced. Comparative sequence searches were performed using the BLAST algorithm. Preliminary data gave, for two of the clones originated from bands with increased expression in the brother, a complete homology (greater than 95%) with the cDNA sequence of a cold shock domain protein, displaying features of a repressor factor for several hematopoietic genes (Horwitz M. et al. JBC1994; 269: 14130–39; P. Coles et al. Nucleic Acids Res1996; 12: 2311–17).

Published
2005
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26. Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

Author

Claudia Santoro, Sara Ponticorvo, Giuseppe Costa, Elisa De Michele, Rosanna Di Concilio, Maria Rosaria Barillari, Simona Raimo, Maria Sole Valentino, Mario Cirillo, Emanuela Inserra, Renzo Manara, Donato Troisi, Angela Ciancio, Roberta Carfora, Martina Caiazza, Antonietta Canna, Francesco Di Salle, Pasquale Alessandro Carafa, Domenico Roberti, Andrea G. Russo, Federica Ammendola, Davide Brotto, Immacolata Tartaglione, Stefania Picariello, Fabrizio Esposito, Silverio Perrotta, Gabriella Santangelo, Manara, Renzo, Ponticorvo, Sara, Perrotta, Silverio, Barillari, Maria Rosaria, Costa, Giuseppe, Brotto, Davide, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Carafa, Pasquale Alessandro, Canna, Antonietta, Russo, Andrea Gerardo, Troisi, Donato, Caiazza, Martina, Ammendola, Federica, Roberti, Domenico, Santoro, Claudia, Picariello, Stefania, Valentino, Maria Sole, Inserra, Emanuela, Carfora, Roberta, Cirillo, Mario, Raimo, Simona, Santangelo, Gabriella, di Salle, Francesco, Esposito, Fabrizio, and Tartaglione, Immacolata

Subjects
medicine.medical_specialty, Hearing loss, Hearing Loss, Sensorineural, Thalassemia, Auditory area, Perfusion scanning, Sensorineural, Auditory cortex, Audiometry, Internal medicine, Humans, Medicine, Pharmacology (medical), Genetics (clinical), Auditory Cortex, Brain, Perfusion, Transfusion medicine, Audiometry, Pure-Tone, Cross-Sectional Studies, beta-Thalassemia, medicine.diagnostic_test, business.industry, Research, General Medicine, medicine.disease, Cardiology, Sensorineural hearing loss, Pure tone audiometry, medicine.symptom, business, Pure-Tone
Abstract

Background Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded. Results Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemia patients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemia patients. Audiometric test results did not correlate to cognitive test scores in any subgroup. Conclusions In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations.

Published
2021
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27. Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort

Author

Raffaella Origa, Antonella Sau, Maria Caterina Putti, Maurizio Poggi, Gian Luca Forni, Antonella Quarta, Alessandro Cattoni, Marilena Serra, Immacolata Tartaglione, Domenico Roberti, Elena Cassinerio, Elisa De Michele, Patrizia Sturiale, Filomena Sportelli, Saveria Campisi, Antonio Ivan Lazzarino, Massimo Allò, Silverio Perrotta, Rosanna Di Concilio, Daniela Pasquali, Alessia Marcon, Angelo Peluso, Stefania Picariello, Maddalena Casale, Francesca Ferrara, Roberta Renni, Saverio Ladogana, Lucia Dora Notarangelo, Casale, Maddalena, Luca Forni, Gian, Cassinerio, Elena, Pasquali, Daniela, Origa, Raffaella, Serra, Marilena, Campisi, Saveria, Peluso, Angelo, Renni, Roberta, Cattoni, Alessandro, De Michele, Elisa, Allò, Massimo, Poggi, Maurizio, Ferrara, Francesca, Di Concilio, Rosanna, Sportelli, Filomena, Quarta, Antonella, Caterina Putti, Maria, Dora Notarangelo, Lucia, Sau, Antonella, Ladogana, Saverio, Tartaglione, Immacolata, Picariello, Stefania, Marcon, Alessia, Sturiale, Patrizia, Roberti, Domenico, Ivan Lazzarino, Antonio, Perrotta, Silverio, Casale, M, Forni, G, Cassinerio, E, Pasquali, D, Origa, R, Serra, M, Campisi, S, Peluso, A, Renni, R, Cattoni, A, De Michele, E, Allò, M, Poggi, M, Ferrara, F, Di Concilio, R, Sportelli, F, Quarta, A, Putti, M, Notarangelo, L, Sau, A, Ladogana, S, Tartaglione, I, Picariello, S, Marcon, A, Sturiale, P, Roberti, D, Lazzarino, A, and Perrotta, S

Subjects
medicine.medical_specialty, Iron Overload, Thalassemia, blood transfusion, Iron Chelating Agents, Benzoates, Risk Assessment, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Endocrine system, Humans, Chelation therapy, iron chelation, business.industry, Incidence (epidemiology), Deferasirox, beta-Thalassemia, Hematology, Triazoles, medicine.disease, Chelation Therapy, 030220 oncology & carcinogenesis, Cohort, business, Complication, Thalassemia, endocrine complications, iron chelation, deferasirox, endocrine function, 030215 immunology, medicine.drug, Follow-Up Studies
Abstract

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusiondependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3–13.1). Multiple Cox regression analysis identified three key predictors: age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1–1.3, P=0.005), the serum concentration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1–1.4, P

Published
2020

28. White matter volume changes in adult beta‐thalassemia: Negligible and unrelated to anemia and cognitive performances

Author

Sara Ponticorvo, Mario Cirillo, Andrea G. Russo, Federica Ammendola, Renzo Manara, Rosanna Di Concilio, Silverio Perrotta, Andrea Elefante, Francesco Di Salle, Domenico Roberti, Angela Ciancio, Martina Caiazza, Pasquale Alessandro Carafa, Antonietta Canna, Maddalena Casale, Elisa De Michele, Immacolata Tartaglione, Fabrizio Esposito, Manara, Renzo, Canna, Antonietta, Caiazza, Martina, Ponticorvo, Sara, Russo, Andrea G, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Carafa, Pasquale Alessandro, Ammendola, Federica, Roberti, Domenico, Casale, Maddalena, Elefante, Andrea, Cirillo, Mario, Di Salle, Francesco, Esposito, Fabrizio, Perrotta, Silverio, Tartaglione, Immacolata, Manara, R., Canna, A., Caiazza, M., Ponticorvo, S., Russo, A. G., Di Concilio, R., Ciancio, A., De Michele, E., Carafa, P. A., Ammendola, F., Roberti, D., Casale, M., Elefante, A., Cirillo, M., Di Salle, F., Esposito, F., Perrotta, S., and Tartaglione, I.

Subjects
Adult, Anemia, business.industry, beta-Thalassemia, Physiology, Beta thalassemia, Cognition, Syndrome, Anemia, Sickle Cell, Hematology, medicine.disease, White Matter, White matter, medicine.anatomical_structure, Volume (thermodynamics), medicine, business, Human
Published
2020
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29. No evidence of increased cerebrovascular involvement in adult neurologically-asymptomatic β-Thalassaemia. A multicentre multimodal magnetic resonance study

Author

Gianluca Femina, Antonietta Canna, Sara Ponticorvo, Renzo Manara, Violetta Caserta, Maddalena Casale, Paolo Gritti, Elisa De Michele, Silverio Perrotta, Andrea G. Russo, Teresa Ferrantino, Camilla Russo, Martina Caiazza, Mario Cirillo, Giovanni Amendola, Antonella Centanni, Noemi Ippolito, Fabrizio Esposito, Angela Ciancio, Rosanna Di Concilio, Andrea Elefante, Ilaria Granato, Mario Ermani, Tiziana Oliveto, Pasquale Alessandro Carafa, Immacolata Tartaglione, Tartaglione, Immacolata, Russo, Camilla, Elefante, Andrea, Caiazza, Martina, Casale, Maddalena, Di Concilio, Rosanna, Ciancio, Angela, De Michele, Elisa, Amendola, Giovanni, Gritti, Paolo, Carafa, Pasquale A, Ferrantino, Teresa, Centanni, Antonella, Ippolito, Noemi, Caserta, Violetta, Oliveto, Tiziana, Granato, Ilaria, Femina, Gianluca, Esposito, Fabrizio, Ponticorvo, Sara, Russo, Andrea G, Canna, Antonietta, Ermani, Mario, Cirillo, Mario, Perrotta, Silverio, Manara, Renzo, Tartaglione, I., Russo, C., Elefante, A., Caiazza, M., Casale, M., Di Concilio, R., Ciancio, A., De Michele, E., Amendola, G., Gritti, P., Carafa, P. A., Ferrantino, T., Centanni, A., Ippolito, N., Caserta, V., Oliveto, T., Granato, I., Femina, G., Esposito, F., Ponticorvo, S., Russo, A. G., Canna, A., Ermani, M., Cirillo, M., Perrotta, S., and Manara, R.

Subjects
Adult, medicine.medical_specialty, brain MRI, Adolescent, transfusion medicine, Venography, thalassaemia, Asymptomatic, Magnetic resonance angiography, Brain Ischemia, White matter, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Leukoencephalopathies, medicine, Humans, thrombosi, Prospective Studies, vascular malformations, thrombosis, Aged, medicine.diagnostic_test, business.industry, beta-Thalassemia, Brain, Intracranial Aneurysm, Magnetic resonance imaging, Intracranial Artery, Hematology, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, Thrombosis, Hyperintensity, medicine.anatomical_structure, Case-Control Studies, 030220 oncology & carcinogenesis, Radiology, Nervous System Diseases, medicine.symptom, business, Magnetic Resonance Angiography, 030215 immunology
Abstract

Multi-factorial causes jeopardize brain integrity in β-thalassaemia. Intracranial parenchymal and vascular changes have been reported among young β-thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic β-thalassaemia patients (mean-age 35·2±10·7years; 52/75 transfusion-dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic-like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean-age 33·9±10·8years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0±10·6 vs. 4·6±9·1, P=0·63), size and Fazekas' Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic β-thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring.

Published
2019

30. Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort.

Author

Casale M, Forni GL, Cassinerio E, Pasquali D, Origa R, Serra M, Campisi S, Peluso A, Renni R, Cattoni A, De Michele E, Allò M, Poggi M, Ferrara F, Di Concilio R, Sportelli F, Quarta A, Putti MC, Notarangelo LD, Sau A, Ladogana S, Tartaglione I, Picariello S, Marcon A, Sturiale P, Roberti D, Lazzarino AI, and Perrotta S

Subjects
Benzoates adverse effects, Chelation Therapy adverse effects, Deferasirox adverse effects, Follow-Up Studies, Humans, Iron Chelating Agents adverse effects, Risk Assessment, Risk Factors, Triazoles adverse effects, Iron Overload drug therapy, Iron Overload epidemiology, Iron Overload etiology, Thalassemia complications, Thalassemia epidemiology, Thalassemia therapy, beta-Thalassemia complications
Abstract

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusiondependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3-13.1). Multiple Cox regression analysis identified three key predictors: age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1-1.3, P=0.005), the serum concentration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1-1.4, P<0.001) regardless the kind of disease incident, while the number of previous endocrine diseases showed a negative linear effect: the higher the number of diseases at baseline the lower the chance of developing further diseasess (adjusted HR for unit increase 0.5, 95% CI: 0.4-0.7, P<0.001). Age and thyrotropin had similar effect sizes across the categories of baseline diseases. The administration of levothyroxine as a covariate did not change the estimates. Although in DFX-treated TDT patients the risk of developing an endocrine complication is generally lower than the previously reported risk, there is considerable risk variation and the burden of these complications remains high. We developed a simple risk score chart enabling clinicians to estimate their patients' risk. Future research will look at increasing the amount of variation explained from our model and testing further clinical and laboratory predictors, including the assessment of direct endocrine magnetic resonance imaging.

Published
2022
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