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1. Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study

Author

Civino, A, Alighieri, G, Prete, E, Caroleo, A, Magni-Manzoni, S, Vinti, L, Romano, M, Santoro, N, Filocamo, G, Belotti, T, Santarelli, F, Gorio, C, Ricci, F, Colombini, A, Pastore, S, Cesaro, S, Barone, P, Verzegnassi, F, Olivieri, A, Ficara, M, Miniaci, A, Russo, G, Gallizzi, R, Pericoli, R, Breda, L, Mura, R, Podda, R, Onofrillo, D, Lattanzi, B, Tirtei, E, Maggio, M, De Santis, R, Consolini, R, Arlotta, A, La Torre, F, Mainardi, C, Pelagatti, M, Coassin, E, Capolsini, I, Burnelli, R, Tornesello, A, Soscia, F, De Fanti, A, Rigante, D, Pizzato, C, De Fusco, C, Abate, M, Roncadori, A, Rossi, E, Stabile, G, Biondi, A, Lepore, L, Conter, V, Rondelli, R, Pession, A, Ravelli, A, Amatruda, M, Atzeni, C, Bertolini, P, Bigucci, B, Caniglia, M, Cappella, M, Cattalini, M, Cefalo, M, Cellini, M, Cortis, E, Davi, S, De Benedetti, F, Di Cataldo, A, Fabbri, E, Fagioli, F, Fontanili, I, Garaventa, A, Gicchino, M, Ladogana, S, Locatelli, F, Magnolato, A, Marsili, M, Martino, S, Mascarin, M, Messina, C, Micalizzi, C, Porta, F, Rizzari, C, Civino A., Alighieri G., Prete E., Caroleo A. M., Magni-Manzoni S., Vinti L., Romano M., Santoro N., Filocamo G., Belotti T., Santarelli F., Gorio C., Ricci F., Colombini A., Pastore S., Cesaro S., Barone P., Verzegnassi F., Olivieri A. N., Ficara M., Miniaci A., Russo G., Gallizzi R., Pericoli R., Breda L., Mura R., Podda R. A., Onofrillo D., Lattanzi B., Tirtei E., Maggio M. C., De Santis R., Consolini R., Arlotta A., La Torre F., Mainardi C., Pelagatti M. A., Coassin E., Capolsini I., Burnelli R., Tornesello A., Soscia F., De Fanti A., Rigante D., Pizzato C., De Fusco C., Abate M. E., Roncadori A., Rossi E., Stabile G., Biondi A., Lepore L., Conter V., Rondelli R., Pession A., Ravelli A., Amatruda M., Atzeni C., Bertolini P., Bigucci B., Caniglia M., Cappella M., Cattalini M., Cefalo M. G., Cellini M., Cortis E., Davi S., De Benedetti F., Di Cataldo A., Fabbri E., Fagioli F., Fontanili I., Garaventa A., Gicchino M. F., Ladogana S., Locatelli F., Magnolato A., Marsili M., Martino S., Mascarin M., Messina C., Micalizzi C., Porta F., Rizzari C., Civino, A, Alighieri, G, Prete, E, Caroleo, A, Magni-Manzoni, S, Vinti, L, Romano, M, Santoro, N, Filocamo, G, Belotti, T, Santarelli, F, Gorio, C, Ricci, F, Colombini, A, Pastore, S, Cesaro, S, Barone, P, Verzegnassi, F, Olivieri, A, Ficara, M, Miniaci, A, Russo, G, Gallizzi, R, Pericoli, R, Breda, L, Mura, R, Podda, R, Onofrillo, D, Lattanzi, B, Tirtei, E, Maggio, M, De Santis, R, Consolini, R, Arlotta, A, La Torre, F, Mainardi, C, Pelagatti, M, Coassin, E, Capolsini, I, Burnelli, R, Tornesello, A, Soscia, F, De Fanti, A, Rigante, D, Pizzato, C, De Fusco, C, Abate, M, Roncadori, A, Rossi, E, Stabile, G, Biondi, A, Lepore, L, Conter, V, Rondelli, R, Pession, A, Ravelli, A, Amatruda, M, Atzeni, C, Bertolini, P, Bigucci, B, Caniglia, M, Cappella, M, Cattalini, M, Cefalo, M, Cellini, M, Cortis, E, Davi, S, De Benedetti, F, Di Cataldo, A, Fabbri, E, Fagioli, F, Fontanili, I, Garaventa, A, Gicchino, M, Ladogana, S, Locatelli, F, Magnolato, A, Marsili, M, Martino, S, Mascarin, M, Messina, C, Micalizzi, C, Porta, F, Rizzari, C, Civino A., Alighieri G., Prete E., Caroleo A. M., Magni-Manzoni S., Vinti L., Romano M., Santoro N., Filocamo G., Belotti T., Santarelli F., Gorio C., Ricci F., Colombini A., Pastore S., Cesaro S., Barone P., Verzegnassi F., Olivieri A. N., Ficara M., Miniaci A., Russo G., Gallizzi R., Pericoli R., Breda L., Mura R., Podda R. A., Onofrillo D., Lattanzi B., Tirtei E., Maggio M. C., De Santis R., Consolini R., Arlotta A., La Torre F., Mainardi C., Pelagatti M. A., Coassin E., Capolsini I., Burnelli R., Tornesello A., Soscia F., De Fanti A., Rigante D., Pizzato C., De Fusco C., Abate M. E., Roncadori A., Rossi E., Stabile G., Biondi A., Lepore L., Conter V., Rondelli R., Pession A., Ravelli A., Amatruda M., Atzeni C., Bertolini P., Bigucci B., Caniglia M., Cappella M., Cattalini M., Cefalo M. G., Cellini M., Cortis E., Davi S., De Benedetti F., Di Cataldo A., Fabbri E., Fagioli F., Fontanili I., Garaventa A., Gicchino M. F., Ladogana S., Locatelli F., Magnolato A., Marsili M., Martino S., Mascarin M., Messina C., Micalizzi C., Porta F., and Rizzari C.

Abstract

Background: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed b

Published
2021

4. Studio Multicentrico prospettico osserva zionale sui sintomi muscolo scheletrici all’esordio in oncologia pediatrica e i fattori predittivi nella diagnosi differenziale con l’atrite idiopatica giovanile. Analisi preliminare

Author

Civino, A., Alighieri, G., Davi, S., Pession, A., Ravelli, A., Santoro, N., Belotti, T, Martino, S., Cesaro, Simone, Filocamo, G., Marino, S., Magnolato, A., Colombini, A., Ricci, F., Suffia, C., Galizzi, R., Palmisani, E., Verzegnassi, F., Olivieri, A. N., Tirtei, E., Gerloni, V, Gorio, C., Lattanzi, B., Pizzati, C., Soscia, F., Vinti, L., De Fanti, A., Ficara, M., Magni Manzoni, S., Boaro, M. P., Prete, E., Quartulli, L., La Torre, F., Onofrillo, D., Rigante, D., Capolsini, I., Maggio, C., Ladogana, S., Marsali, M., Burnelli, R., Coassin, E., Pelegatti, M. A., Arlotta, A., Lepore, L., Conter, V., Biondi, A., Fagioli, F., and Rondelli, R.

Subjects
diagnosi, leucemia acuta, sintomi, diagnosi, sintomi, leucemia acuta
Published
2016

6. Antimicrobial stewardship in newborns and young infants: Why and how to do it,Stewardship antimicrobica nel neonato e nel piccolo lattante: Perché e come praticarla

Author

Berardi, A., Ficara, M., Pietrella, E., Boncompagni, A., Toffoli, C., Bianchini, A., Della Casa, E., Spada, C., Spaggiari, E., Ciccia, M., Gargano, G., Rizzo, V., Azzalli, M., Biasucci, G., Gambini, L., Bolognesi, S., Piccinini, G., Ferrari, F., Memo, L., Nicolini, G., Bastelli, A., Sandri, F., Ambretti, S., Capretti, M. G., Corvaglia, L., Dondi, A., Lanari, M., Pasini, L., Ragni, L., Albarelli, A., Fiorini, V., Giugno, C., Lanzoni, P., Di Grande, E., Polese, A., China, M. C., Stella, M., Zucchini, A., Malaguti, L., Garani, G., Lama, C., Nasi, S., Bacchini, P., Fragni, G., Baldassarri, P., Pulvirenti, R. M., Valletta, E., Venturoli, V., Alessandrini, C., Bidetti, M. L., Incerti, S. S., Di Carlo, C., Lanzoni, A., Serra, L., Silvestrini, D., Facchinetti, F., licia lugli, Venturelli, C., Sarti, M., Volta, A., Dodi, I., Magnani, C., Guidi, B., Bertelli, M., Chiarabini, R., Paulis, N., Padrini, D., Riboni, S., Pedna, M. F., Sambri, V., Casadio, L., Marchetti, F., Muratori, C., Renzelli, C., Amarri, S., Baroni, L., Carretto, E., Fornaciari, S., Pedori, S., Riva, M., Zuelli, C., Ancona, G., Papa, I., Vergine, G., Viola, L., Chiossi, C., Pagano, R., Rivi, C., Zanacca, C., Bonvicini, C., and Palmieri, R.

7. Antimicrobial stewardship in newborns and young infants: Why and how to do it,Stewardship antimicrobica nel neonato e nel piccolo lattante: Perché e come praticarla

Author

Berardi, A., Ficara, M., Pietrella, E., Boncompagni, A., Toffoli, C., Bianchini, A., Della Casa, E., Spada, C., Spaggiari, E., Ciccia, M., Gargano, G., Rizzo, V., Azzalli, M., Biasucci, G., Gambini, L., Bolognesi, S., Piccinini, G., Ferrari, F., Memo, L., Nicolini, G., Bastelli, A., Sandri, F., Ambretti, S., Capretti, M. G., Corvaglia, L., Dondi, A., Lanari, M., Pasini, L., Ragni, L., Albarelli, A., Fiorini, V., Giugno, C., Lanzoni, P., Di Grande, E., Polese, A., China, M. C., Stella, M., Zucchini, A., Malaguti, L., Garani, G., Lama, C., Nasi, S., Bacchini, P., Fragni, G., Baldassarri, P., Pulvirenti, R. M., Valletta, E., Venturoli, V., Alessandrini, C., Bidetti, M. L., Incerti, S. S., Di Carlo, C., Lanzoni, A., Serra, L., Silvestrini, D., Facchinetti, F., Lugli, L., Venturelli, C., Sarti, M., Volta, A., Dodi, I., Magnani, C., Guidi, B., Bertelli, M., Chiarabini, R., Paulis, N., Padrini, D., Riboni, S., Pedna, M. F., Sambri, V., Casadio, L., Marchetti, F., Muratori, C., Renzelli, C., Amarri, S., Baroni, L., Edoardo Carretto, Fornaciari, S., Pedori, S., Riva, M., Zuelli, C., Ancona, G., Papa, I., Vergine, G., Viola, L., Chiossi, C., Pagano, R., Rivi, C., Zanacca, C., Bonvicini, C., and Palmieri, R.

8. Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study

Author

Giovanna Russo, Valentino Conter, M Caniglia, A Garaventa, Giulia Stabile, MF Gicchino, Elisa Rossi, Annalisa Arlotta, S Ladogana, C Atzeni, Rita Consolini, Luciana Vinti, Daniela Onofrillo, Roberto Rondelli, Nicola Santoro, Loredana Lepore, F Locatelli, Elisa Coassin, Monica Ficara, Micol Romano, S Martino, Roberta Burnelli, I Fontanili, Francesca Soscia, Eleonora Prete, Francesca Santarelli, Romina Gallizzi, Patrizia Barone, MG Cefalo, E Cortis, Giovanni Filocamo, M Amatruda, Angela Miniaci, Anna Maria Caroleo, Massimo Eraldo Abate, Maria Cristina Maggio, M Mascarin, Simone Cesaro, E Fabbri, F De Benedetti, Angelo Ravelli, Alma Nunzia Olivieri, C Micalizzi, A Magnolato, B Bigucci, Francesca Ricci, Elisa Tirtei, Antonella Colombini, Luciana Breda, Tamara Belotti, Raffaela De Santis, Roberta Pericoli, Serena Pastore, Silvia Magni-Manzoni, Rosa Anna Podda, Chiara Mainardi, Donato Rigante, Federico Verzegnassi, C Messina, Adele Civino, Cristina Pizzato, M Marsili, Chiara Gorio, Rossella Mura, M Cattalini, Andrea Pession, M Cappella, A Di Cataldo, Francesco La Torre, Assunta Tornesello, Andrea Roncadori, F Porta, Maria Antonietta Pelagatti, F Fagioli, P Bertolini, Ilaria Capolsini, C Rizzari, M Cellini, Bianca Lattanzi, Alessandro De Fanti, S Davì, Carmela De Fusco, Giovanni Alighieri, Andrea Biondi, Civino, Adele, Alighieri, Giovanni, Prete, Eleonora, Maria Caroleo, Anna, SilviaMagni-Manzoni, Vinti, Luciana, Romano, Micol, Santoro, Nicola, Filocamo, Giovanni, Belotti, Tamara, Santarelli, Francesca, Gorio, Chiara, Ricci, Francesca, Colombini, Antonella, Pastore, Serena, Cesaro, Simone, Barone, Patrizia, Verzegnassi, Federico, Olivieri, Alma Nunzia, Ficara, Monica, Miniaci, Angela, Russo, Giovanna, Gallizzi, Romina, Pericoli, Roberta, Breda, Luciana, Mura, Rossella, Annapodda, Rosa, Onofrillo, Daniela, Lattanzi, Bianca, Elisatirtei, Cristina Maggio, Maria, De Santis, Raffaela, Ritaconsolini, Arlotta, Annalisa, La Torre, Francesco, Mainardi, Chiara, Antonietta Pelagatti, Maria, Coassin, Elisa, Capolsini, Ilaria, Burnelli, Roberta, Tornesello, Assunta, Soscia, Francesca, De Fanti, Alessandro, Donatorigante, Pizzato, Cristina, De Fusco, Carmela, Eraldo Abate, Massimo, Roncadori, Andrea, Rossi, Elisa, Stabile, Giulia, Biondi, Andrea, Lepore, Loredana, Conter, Valentino, Rondelli, Roberto, Pession, Andrea, Ravelli, Angelo, Association of Paediatric Haematology and Oncology†and the Italian Paediatric Rheumatology Study Group†, Italian, Amatruda, M, Atzeni, C, Pbertolini, Bigucci, B, Caniglia, M, Cappella, M, Cattalini, M, Cefalo, Mg, Cellini, M, Cortis, E, Davì, S, De Benedetti, F, Di Cataldo, A, Fabbri, E, Fagioli, F, Fontanili, I, Garaventa, A, Gicchino, MARIA FRANCESCA, Ladogana, S, Locatelli, F, Magnolato, A, Marsili, M, Martino, S, Mascarin, M, Messina, C, Micalizzi, C, Porta, F, Rizzari, C, Civino A., Alighieri G., Prete E., Caroleo A.M., Magni-Manzoni S., Vinti L., Romano M., Santoro N., Filocamo G., Belotti T., Santarelli F., Gorio C., Ricci F., Colombini A., Pastore S., Cesaro S., Barone P., Verzegnassi F., Olivieri A.N., Ficara M., Miniaci A., Russo G., Gallizzi R., Pericoli R., Breda L., Mura R., Podda R.A., Onofrillo D., Lattanzi B., Tirtei E., Maggio M.C., De Santis R., Consolini R., Arlotta A., La Torre F., Mainardi C., Pelagatti M.A., Coassin E., Capolsini I., Burnelli R., Tornesello A., Soscia F., De Fanti A., Rigante D., Pizzato C., De Fusco C., Abate M.E., Roncadori A., Rossi E., Stabile G., Biondi A., Lepore L., Conter V., Rondelli R., Pession A., Ravelli A., Amatruda M., Atzeni C., Bertolini P., Bigucci B., Caniglia M., Cappella M., Cattalini M., Cefalo M.G., Cellini M., Cortis E., Davi S., De Benedetti F., Di Cataldo A., Fabbri E., Fagioli F., Fontanili I., Garaventa A., Gicchino M.F., Ladogana S., Locatelli F., Magnolato A., Marsili M., Martino S., Mascarin M., Messina C., Micalizzi C., Porta F., Rizzari C., Civino, A, Alighieri, G, Prete, E, Caroleo, A, Magni-Manzoni, S, Vinti, L, Romano, M, Santoro, N, Filocamo, G, Belotti, T, Santarelli, F, Gorio, C, Ricci, F, Colombini, A, Pastore, S, Cesaro, S, Barone, P, Verzegnassi, F, Olivieri, A, Ficara, M, Miniaci, A, Russo, G, Gallizzi, R, Pericoli, R, Breda, L, Mura, R, Podda, R, Onofrillo, D, Lattanzi, B, Tirtei, E, Maggio, M, De Santis, R, Consolini, R, Arlotta, A, La Torre, F, Mainardi, C, Pelagatti, M, Coassin, E, Capolsini, I, Burnelli, R, Tornesello, A, Soscia, F, De Fanti, A, Rigante, D, Pizzato, C, De Fusco, C, Abate, M, Roncadori, A, Rossi, E, Stabile, G, Biondi, A, Lepore, L, Conter, V, Rondelli, R, Pession, A, Ravelli, A, Bertolini, P, Cefalo, M, Davi, S, and Gicchino, M

Subjects
medicine.medical_specialty, business.industry, Immunology, Arthritis, Cancer, Odds ratio, Musculoskeletal manifestation, Juvenile idiopathic arthritis, medicine.disease, Histiocytosis, Rheumatology, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Prednisone, Internal medicine, Joint pain, Arthropathy, Musculoskeletal manifestations, childhood cancer, juvenile idiopathic arthritis, medicine, childhood cancer, Immunology and Allergy, Differential diagnosis, medicine.symptom, business, medicine.drug
Abstract

Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding Associazione Lorenzo Risolo.

Published
2021

9. Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus.

Author

Tincati C, Ficara M, Ferrari F, Augello M, Dotta L, Tagliabue C, Diana A, Camelli V, Iughetti L, Badolato R, Cellini M, and Marchetti G

Subjects
Child, Pregnancy, Female, Humans, Cross-Sectional Studies, Pilot Projects, Inflammation, Biomarkers, Gastrointestinal Microbiome, HIV Infections drug therapy
Abstract

Objective: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown., Design: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother., Methods: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA., Results: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU., Conclusion: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2022
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10. Ecthyma Gangrenosum in Children With Cancer: Diagnosis at a Glance: A Retrospective Study From the Infection Working Group of Italian Pediatric Hematology Oncology Association.

Author

Muggeo P, Zama D, Decembrino N, Onofrillo D, Frenos S, Colombini A, Perruccio K, Calore E, Giurici N, Ficara M, La Spina M, Mura R, De Santis R, Santoro N, and Cesaro S

Subjects
Adolescent, Anti-Bacterial Agents therapeutic use, Bacteremia microbiology, Child, Child, Preschool, Ecthyma complications, Ecthyma microbiology, Escherichia coli isolation & purification, Escherichia coli Infections drug therapy, Female, Humans, Infant, Italy, Male, Neoplasm Recurrence, Local complications, Neutropenia complications, Pseudomonas Infections, Pseudomonas aeruginosa isolation & purification, Retrospective Studies, Stenotrophomonas maltophilia isolation & purification, Ecthyma diagnosis, Ecthyma drug therapy, Hematology methods, Neoplasms complications
Abstract

Background: To depict ecthyma gangrenosum (EG) clinical presentation and evolution in a large multicenter pediatric retrospective collection of children with malignancies or bone marrow failure syndromes, to facilitate early diagnosis., Methods: EG episodes diagnosed in the period 2009-2019 were identified by a retrospective review of clinical charts at centers belonging to the Italian Pediatric Hematology Oncology Association., Results: Thirty-eight cases of EG occurring in children (male/female 16/22; median age 5.2 years) with hematologic malignancy (29), allogeneic stem cell transplantation (2) or relapsed/refractory solid tumor (3) were collected. The involved sites were: perineal region (19), limbs (10), trunk (6), head and the iliac crest (3). Bacteremia was present in 22 patients. Overall, the germs isolated were Pseudomonas aeruginosa (30), Stenotrophomonas maltophilia (3) and Escherichia coli (1); 31% of them were multidrug-resistant. All patients received antibacterial treatment, while surgery was performed in 24 patients (63.1%). Predisposing underlying conditions for EG were severe neutropenia (97.3%), corticosteroid treatment (71%) and iatrogenic diabetes (23.7%). All patients recovered, but EG recurred in 5 patients. Nine patients (24%) showed sequelae (deep scars, with muscle atrophy in 2). Four patients (10.5%) died, 1 due to relapse of EG with Carbapenem-resistant Enterobacteriaceae co-infection and 3 due to the progression of the underlying disease., Conclusions: EG requires early recognition and a proper and timely treatment to obtain the recovery and to avoid larger necrotic lesions, eventually evolving in scarring sequelae., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2022
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11. Antibiotic Exposure, Common Morbidities and Main Intestinal Microbial Groups in Very Preterm Neonates: A Pilot Study.

Author

Bozzi Cionci N, Lucaccioni L, Pietrella E, Ficara M, Spada C, Torelli P, Bedetti L, Lugli L, Di Gioia D, and Berardi A

Abstract

Prematurity exposes newborns to increased risks of infections and it is associated with critical morbidities. Preterm infants often require antibiotic therapies that can affect the correct establishment of gut microbiota. The aim of this study was to investigate targeted intestinal bacteria in preterm neonates with common morbidities and receiving antibiotic treatments of variable duration. Stool samples were collected after birth, at 15, 30 and 90 days of life. qPCR quantification of selected microbial groups ( Bifidobacterium spp., Bacteroides fragilis group, Enterobacteriaceae, Clostridium cluster I and total bacteria) was performed and correlation between their levels, the duration of antibiotic treatment and different clinical conditions was studied. An increasing trend over time was observed for all microbial groups, especially for Bifdobacterium spp. Prolonged exposure to antibiotics in the first weeks of life affected Clostridium and B. fragilis levels, but these changes no longer persisted at 90 days of life. Variations of bacterial counts were associated with the length of hospital stay, feeding and mechanical ventilation. Late-onset sepsis and patent ductus arteriosus reduced the counts of Bifidobacterium , whereas B. fragilis was influenced by compromised respiratory conditions. This study can be a start point for the identification of microbial biomarkers associated with some common morbidities and tailored strategies for a healthy microbial development.

Published
2022
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12. Complementary Feeding in Italy: From Tradition to Innovation.

Author

Alvisi P, Congiu M, Ficara M, De Gregorio P, Ghio R, Spisni E, Di Saverio P, Labriola F, Lacorte D, and Lionetti P

Abstract

Complementary feeding (CF) is a pivotal phase of the individual's growth, during which children develops their future dietary habits. To date, only few studies investigated and compared weaning modalities between different geographical areas. The aim of this article is to describe the current Italian practice for CF in healthy term infants among different areas (North, Center, South) of Italy. Two different multiple-choice questionnaires were produced and sent to 665 Italian primary care pediatricians (PCP) and 2023 families with children under 1 year of age. As emerged from our investigation, in Italy CF is usually started between the 5th and 6th month of life. The preferred approach (chosen by 77% of families) involves the use of home-cooked liquid or semi-liquid ailments, or industrial baby foods. A new CF modality is emerging, consisting of traditional complementary foods with adult food tastings (10% of families). Approximately 91% of pediatricians give written dietary suggestions, and 83% of families follow their advice. We found significantly divergent weaning habits among different areas of Italy. PCP have a key role in guiding parents during the introduction of new foods in their infant's diet and should take this as an opportunity to educate the whole family to healthy dietary habits.

Published
2021
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13. Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study.

Author

Civino A, Alighieri G, Prete E, Caroleo AM, Magni-Manzoni S, Vinti L, Romano M, Santoro N, Filocamo G, Belotti T, Santarelli F, Gorio C, Ricci F, Colombini A, Pastore S, Cesaro S, Barone P, Verzegnassi F, Olivieri AN, Ficara M, Miniaci A, Russo G, Gallizzi R, Pericoli R, Breda L, Mura R, Podda RA, Onofrillo D, Lattanzi B, Tirtei E, Maggio MC, De Santis R, Consolini R, Arlotta A, La Torre F, Mainardi C, Pelagatti MA, Coassin E, Capolsini I, Burnelli R, Tornesello A, Soscia F, De Fanti A, Rigante D, Pizzato C, De Fusco C, Abate ME, Roncadori A, Rossi E, Stabile G, Biondi A, Lepore L, Conter V, Rondelli R, Pession A, and Ravelli A

Abstract

Background: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis., Methods: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis., Findings: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0-27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2-4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89-408·12]), followed by weight loss (59·88 [6·34-565·53]), thrombocytopenia (12·67 [2·40-66·92]), monoarticular involvement (11·30 [4·09-31·19]), hip involvement (3·30 [1·13-9·61]), and male sex (2·40 [1·03-5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01-0·20]), joint swelling (0·03 [0·01-0·09]), and involvement of the small hand joints (0·02 [0-1·05])., Interpretation: Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis., Funding: Associazione Lorenzo Risolo., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Published
2021
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14. Long term outcomes of infants born by mothers with thyroid dysfunction during pregnancy.

Author

Lucaccioni L, Ficara M, Cenciarelli V, Berardi A, Predieri B, and Iughetti L

Subjects
Adult, Child, Diabetes Mellitus, Type 2, Female, Humans, Infant, Infant, Newborn, Mothers, Pregnancy, Hypothyroidism epidemiology, Pregnancy Complications, Thyroid Diseases epidemiology
Abstract

According to Barker's hypothesis, sub-optimal conditions during gestation might affect the predisposition for diseases in adulthood. Alteration in endocrine functions during pregnancy, such us thyroid function or glucose metabolism, are not exempt. It is well known that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism during early pregnancy are associated with increased risk of gestational diabetes mellitus and both conditions influence pregnancy outcome and newborn development and metabolism at short and long terms. Fetal production of thyroid hormones starts from the 12th week of gestational age. The transplacental passage of maternal thyroxine (T4) is therefore essential for the fetal neurological development, especially during the first half of pregnancy.  If this passage is interrupted, such as in premature birth, neonates are more susceptible to develop impaired thyroid function, because of physiological immaturity of their hypothalamic-pituitary-thyroid axis, acute illnesses and stressful events (sepsis, invasive procedures, drugs). The aim of this review is to investigate the short and long term effects of maternal dysthyroidisms on term and preterm newborns, with particular attention to the metabolic and thyroid consequences. Metabolic syndrome, higher body mass index and greater waist circumference, seem to be more prevalent in children of TPO-Ab-positive mothers. Maternal hypothyroidism may be associated with higher risk of gestational diabetes and adverse birth outcomes, such as preeclampsia, preterm delivery, fetal death and low birth weight offspring.  In adulthood, preterm (< 37 weeks of gestational age) or low birth weight (<2.500 g) newborns  seem to be more susceptible to develop gestational diabetes, preeclampsia, type 2 diabetes mellitus and behavioral alterations.

Published
2020
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15. Changes of intestinal microbiota in early life.

Author

Ficara M, Pietrella E, Spada C, Della Casa Muttini E, Lucaccioni L, Iughetti L, and Berardi A

Subjects
Anti-Bacterial Agents, Breast Feeding, Cesarean Section adverse effects, Child, Child, Preschool, Dermatitis, Atopic microbiology, Dermatitis, Atopic prevention & control, Enterocolitis, Necrotizing microbiology, Enterocolitis, Necrotizing prevention & control, Gestational Age, Health Promotion, Hospitalization, Humans, Infant, Infant, Newborn, Inflammatory Bowel Diseases microbiology, Inflammatory Bowel Diseases prevention & control, Obesity microbiology, Obesity prevention & control, Protective Factors, Risk Factors, Sepsis microbiology, Sepsis prevention & control, Child Health, Gastrointestinal Microbiome drug effects, Gastrointestinal Microbiome immunology, Gastrointestinal Microbiome physiology, Infant Health
Abstract

There is an increasing evidence that the intestinal microbiota plays a pivotal role in the maturation of the immune system and in the prevention of diseases occurring during the neonatal period, childhood, and adulthood. A number of nonphysiological conditions during the perinatal period (i.e. caesarean section, prolonged hospitalization, formula feeding, low gestational age) may negatively affect the normal development of the microbiota, leading to decreased amounts of lactobacilli and bifidobacteria and increased amounts of Clostridia. In addition, perinatal antibiotics can cause intestinal dysbiosis that has been associated with short- and long-term diseases. For example, prolonged early empiric antibiotics increase the risk of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm neonates, whereas the administration of intrapartum antibiotic prophylaxis (IAP) has been associated with inflammatory bowel diseases, obesity, and atopic conditions, such as eczema and wheezing. Promoting breastfeeding, reducing the length of hospital stay, and reducing unnecessary antibiotic therapies are useful strategies to counterbalance unintended effects of these conditions.

Published
2020
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16. Unusual meningitis caused by non-typhoid Salmonella in an Italian infant: a case report.

Author

Ficara M, Cenciarelli V, Montanari L, Righi B, Fontjin S, Cingolani G, Predieri B, Berardi A, Lucaccioni L, and Iughetti L

Subjects
Follow-Up Studies, Humans, Infant, Italy, Magnetic Resonance Imaging methods, Male, Meningitis, Bacterial diagnosis, Rare Diseases, Risk Assessment, Salmonella Infections diagnosis, Salmonella Infections drug therapy, Tomography, X-Ray Computed methods, Treatment Outcome, Cefotaxime therapeutic use, Meningitis, Bacterial drug therapy, Meningitis, Bacterial microbiology, Salmonella enteritidis isolation & purification
Abstract

Background: Non-typhoid Salmonella (NTS) is an important cause of bacterial meningitis in newborn and infants in developing countries, but rarely in industrialized ones. We describe an unusual presentation of bacterial meningitis in an infant, focusing on his diagnostic and therapeutic management., Case Report: An Italian two-month old male presented high fever and diarrhea with blood, associated with irritability. Inflammatory markers were high, cerebrospinal fluid analysis was compatible with bacterial meningitides but microbiological investigations were negative. Salmonella enteritidis was isolated from blood. Cerebral ultrasound and MRI showed periencephalic collection of purulent material. Specific antibiotic therapy with cefotaxime was initiated with improvement of clinical conditions and blood tests. Brain MRI follow up improved progressively., Conclusions: Most of pediatric patients with NTS infection develop self-limited gastroenteritis, but in 3-8% of the cases complications such as bacteremia and meningitis may occur, especially in weak patients. Cerebral imaging can be useful to identify neurological findings. Although there is no standardized treatment for this condition, specific antibiotic therapy for at least four weeks is recommended. Neuroimaging follow up is required due to high risk of relapse.

Published
2019
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