Studies of bone mineral density in children affected by dietary intolerances

The Pediatric Department of the University of Ferrara has developed a special expertise in the field of hemoglobinopathies and has also an interest in gastrointestinal diseases. It has a long standing collaboration with the Department of Genetics of the University of Verona. The main fields of interest are thalassemia, gluten intolerance, and osteoporosis in its various aspects. Using our previous research experience as a platform, we plan to study Vitamin D metabolism, bone mineral density, the FGF23 and Klotho axis in patients with thalassemia, in patients with adult type lactose intolerance, in patients treated with antiepileptic drugs and in those who suffer from gluten intolerance. Finally, we intend to cooperate with another group (PP9) of the Trans2Care project in order to clarify the role of tissue antitransglutaminases in seronegative patients with symptoms of gluten intolerance

Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children

Objective: The prevalence of coeliac disease (CD) inVietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi. Setting: The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam. Participants: Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years). Outcomes: Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG. Results: The IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative. Conclusions: Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings

Antibiotic Resistance in Paediatric Febrile Urinary Tract Infections

: Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard

Management of Pediatric Urinary Tract Infections: A Delphi Study

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis

A: Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging. Haematologica 2011; 96

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34±11ms) than in the deferasirox (21±12 ms) and the desferrioxamine groups (27±11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine. Key words: thalassemia, iron chelation therapy, cardiac magnetic resonance imaging. Citation: Pepe A, Meloni A, Capra M, Cianciulli P, Prossomariti L, Malaventura C, Putti MC, Lippi A, Romeo MA, Bisconte MG, Filosa A, Caruso V, Quarta A, Pitrolo L, Missere M, Midiri M, Rossi G, Positano V, Lombardi M, and Maggio A. Deferasirox, deferipron

Pregnancy in young adults treated for autoimmune hepatitis during childhood: A possible option?

We report on five pregnancies that occurred in four women who were followed up between 1990 and 2017 for autoimmune hepatitis (AIH). The median age at onset of AIH and pregnancy was 6 years (range 3–13 years) and 29 years (range 22–35 years) respectively. Two patients had AIH – autoimmune sclerosing cholangitis overlap syndrome (AOVLS) while the other two had AIH type 2. After diagnosis all patients received standard therapy with prednisone,azathioprine and ursodeoxycholic acid (UDCA) in case of AOVLS; one patient with AIH type 2 received cyclosporin after failure of first line therapy. At the beginning of pregnancy one woman had been off-therapy for 2.6 years while the other three were on azathioprine and UDCA. All patients were in complete remission. In a patient with AOVLS serum GGT were abnormal. Mean elastometry values was 6.9 kPa (range 4.8–10.3 kPa). No relapse was observed during pregnancies. In one patient a biochemical relapse occurred one year after delivery once azathioprine was discontinued. This relapse promptly responded to prednisone and azathioprine reintroduction. Three full-term healthy neonates were born without complications. The other two pregnancies are still ongoing at the 2nd and 6th months without complications. Pregnancy with good neonatal outcomes is a possible option for female patients with AIH even when treated with azathioprine. An early diagnosis and a tailored treatment during adolescence and early adulthood are the keys to increasing the success rate of pregnancy in these patients

Fecal calprotectin in Celiac children at diagnosis and on gluten-free diet: a pilot study

Introduction: Calprotectin is a neutrophil antimicrobial protein released during inflammation. Fecal calprotectin (FC) is an inflammatory mucosal biomarker used to distinguish between organic and functional gastrointestinal disease. The aim of this study was to estimate the prevalence of abnormal FC values in Celiac disease (CD). Methods: A stool sample was collected from 16 children (mean age: 5.8 years) at the time of diagnosis of CD and after 6 months of gluten free diet. Values for FC were considered abnormal when: >910 g/g of stool between 0–12 months of age; >286 g/g of stool between 1–4 years and >54 g/g of stool at age greater than 4 years (Roca, J Pediatr Gastroenterol Nutr 2017;65(4):394–8). Results: At diagnosis 3 patients were asymptomatic and 7 had gastrointestinal symptoms; 9 were diagnosed without small bowel biopsy according to ESPGHAN guidelines. Seven out of 16 patients had an abnormal value of FC (median of 75 g/g of stool, range 5–688); of these 4 had gastrointestinal symptoms. Two out of 7 children with small bowel lesions showed an abnormal value FC, both had a IIIc lesion according to Marsh. Patients with abnormal value FC had an anti-TTGA titre higher than patients with a normal FC level. After 6 months gluten free, all patient reduced FC levels (median FC value 28 g/g of stool, range 3.8–242) and the antibody titre. Only one patient had still abnormal FC value together with higher anti-transglutaminase titre when compared to the other patients. Conclusions: Increased fecal calprotectin concentration could be used as a non-invasive biomarker in the diagnosis of Celiac disease, especially in patients with gastrointestinal symptoms. Fecal calprotectin concentration returns to normal after a strict gluten- free diet. Fecal calprotectin might be used as a marker of diet adherence and improvement in gastrointestinal lesions in children with Celiac disease

Dalla nefrolitiasi alla malattia metabolica: un caso di iperossaluria primitiva in eterozigosi composta

Una bambina di 3 anni, con anamnesi patologica silente, giunge in Pronto Soccorso per stranguria e dolore al fianco sinistro. Lo stick urine risulta negativo. L’ecografia documenta “reni in sede, regolari per dimensioni ed ecostruttura e presenza di immagini iperecogene multiple di tipo litiasico bilaterali con diametro massimo a sinistra di 5,3 millimetri e a destra di 3,5 millimetri in assenza di dilatazioni calico-pieliche.” In anamnesi familiare risulta il nonno materno con nefrolitiasi in età giovanile, mai indagata. In considerazione delle buone condizioni cliniche si dimette con indicazione ad eseguire terapia idrica e paracetamolo. Al controllo ambulatoriale dopo 3 settimane viene riferito benessere, negati sintomi urinari. All'esame urine sono presenti emazie (PS 1009, PH 7, eritrociti 255 /mmc) e l’urinocoltura è negativa. I valori di creatinina e pressione arteriosa sono normali. Esegue screening metabolico completo per nefrolitiasi con riscontro isolato, su due raccolte urine consecutive, di iperossaluria severa (400 mg/1,73 mq/die, valore normale A che comporta la sostituzione dell’aminoacido glicina in posizione 41 con una Arginina. L’analisi quantitativa MLPA evidenzia invece, in eterozigosi, una delezione a livello dell'esone 1-2 di circa 507 bp. Si formula diagnosi di iperossaluria primitiva di tipo I AR in eterozigosi composta. La madre, asintomatica, risulta portatrice della mutazione c.121G>A in eterozigosi. Attualmente la bambina mantiene un alto intake di fluidi, assume citrato di magnesio e potassio alla dose di 0,1 g/kg/die e terapia con piridossina alla dose di 5 mg/kg/ die. Tale terapia ha consentito una decisa riduzione dell’escrezione urinaria di ossalati superiore al 50%. La nefrolitiasi in età infantile è spesso associata a disordini metabolici (>75% casi) anche severi, tra cui l’iperossaluria primitiva (IP) di tipo I. Il difetto dell’enzima epatico AGXT conduce ad una iperproduzione ed eccessiva escrezione urinaria di ossalati responsabile di calcolosi severa e precoce con progressivo declino della funzione renale sino all’ossalosi sistemica. Nelle forme non responsive alla piridossina il trapianto fegato-rene rappresenta al momento l’unica opzione terapeutica. La diagnosi precoce a funzione renale conservata e l’ottima risposta alla terapia con vitamina B6, osservate nella nostra paziente, ci fanno sperare in un outcome favorevole. Pertanto di fronte ad una nefrolitiasi pediatrica, specie se bilaterale e precoce, lo screening metabolico non può essere trascurato

Trattamento della epatite autoimmune giovanile Management of juvenile autoimmune hepatitis

Juvenile autoimmune hepatitis characteristically progresses to cirrhosis and organ failure if untreated. Treatment consists of immunosuppressive drugs, mainly prednisone and azathioprine, except in cases presenting with fulminant hepatic failure in which liver transplant may be immediately necessary. The majority of patients respond to imunosuppression. However, this needs to be prolonged, at the lowest possible dose, due to the substantial risk of relapse

Pseudoxanthoma Elasticum-Like in β-Thalassemia Major, a matter of α-Klotho and Parathyroid Hormone?

Pseudoxanthoma elasticum-like (PXL) condition is one of the complications faced by patients with β-thalassemia major (β-TM). Histopathological features include abnormal, mineralized and fragmented elastic fibers in skin, eyes and arterial blood vessels (elastorrhexia). The pathogenesis of PXL lesions in β-TM is not yet completely understood. This study was aimed at analyzing a possible implication of α-Klotho in the clinical manifestation of PXL in patients with β-TM (30 with and 78 without PXL). A significant correlation was observed between Klotho, parathyroid hormone (PTH) and serum calcium (Ca). Our analysis seems to indicate α-Klotho and PTH as factors that can affect the development of PXL