Papers by Emanuele Nicastro
2022 IEEE 9th International Conference on Computational Intelligence and Virtual Environments for Measurement Systems and Applications (CIVEMSA)
Objective E-learning is a candidate tool for clinical practice guidelines (CPG) implementation du... more Objective E-learning is a candidate tool for clinical practice guidelines (CPG) implementation due to its versatility, universal access and low costs. We aimed to assess the impact of a five-mod-ule e-learning course about CPG for acute gastroenteritis (AGE) on physicians ’ knowledge and clinical practice. Study design This work was conceived as a pre/post single-arm intervention study. Physicians from 11 European countries registered for the online course. Personal data, pre- and post-course questionnaires and clinical data about 3 to 5 children with AGEmanaged by each physician before and after the course were collected. Primary outcomemeasures included the propor-tion of participants fully adherent to CPG and number of patients managed with full adherence.
Journal of Pediatric Gastroenterology & Nutrition, 2020
Objectives: The aim of the study was to assess changes in clinical phenotype, and identify determ... more Objectives: The aim of the study was to assess changes in clinical phenotype, and identify determinants of outcome in children with chronic hepatitis B virus (HBV) infection born in HBV-endemic countries followed in 2 Italian tertiary care centers after immigration or adoption. Methods: A prospective observational study on hepatitis B e-antibodies–negative chronic hepatitis B children started on 2002. Patients with liver fibrosis, or those needing antiviral treatment were excluded. Immune active patients were defined those with raised transaminases (alanine aminotransferase > 40 IU/L), immune tolerants those having normal alanine aminotransferase, both exhibiting substantial viral replication (HBV DNA >2000 IU/mL). Results: Sixty-nine patients (44 boys, median age 4.7 years) had a median follow-up of 53 months. At entry, 18 (26%) children were immune tolerant, 47 (68%) immune active, and 4 had indeterminant immune status. At last follow-up, 14 (78%) of the immune-tolerant pati...
Pediatric Hepatology and Liver Transplantation, 2019
The knowledge of the underlying aetiology of neonatal idiopathic hepatitis and the so-called “int... more The knowledge of the underlying aetiology of neonatal idiopathic hepatitis and the so-called “intrahepatic” cholestasis has been rapidly expanding in the last decade, and great advances in genetic testing have clarified that the vast majority of these conditions are monogenic liver disorders. Among those referred to as progressive familial intrahepatic cholestases (PFICs), the level of serum GGT is a good discriminant to guide the initial evaluation, being low/normal in Byler disease, BSEP deficiency, TJP2 deficiency, FXR deficiency and MYO5B deficiency, and increased only in MDR3 deficiency; however genetic testing is needed to reach a definite categorisation. In bile acid synthesis defects, normal serum bile acid is a clue to the diagnosis, although mass spectrometry is required to characterise the type of defect. Other well-known conditions such as Alagille syndrome and alpha-1 antitrypsin deficiency are more common and less challenging to recognise. In this chapter we discuss th...
Children, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Digestive and Liver Disease, 2021
Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable dise... more Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.
The Journal of Pediatrics, 2020
Hepatology International, 2019
Objectives and study Various degrees of biliary changes are considered to be part of the histolog... more Objectives and study Various degrees of biliary changes are considered to be part of the histological picture of children with pediatrics autoimmune liver disease (AILD), but the literature is scarce and confusing. We aimed to describe the characteristics of children with AILD (autoimmune hepatitis, AIH, and autoimmune sclerosing cholangitis, ASC) focusing on the prevalence and type of biliary abnormalities on initial biopsy to see whether ASC was predictable on histological ground. Methods The files of children diagnosed with AILD were reviewed. The Ishak score was used to grade inflammation and fibrosis on biopsy; a biliary score was built to grade bile duct injury. Demographic, laboratory and histological features at diagnosis were reported and compared between the two groups (AIH vs ASC). Results Forty-one patients were diagnosed with AIH (n = 24), ASC (n = 13) and PSC (n = 4) between 2009 and 2018. Twentynine patients [F = 76%, AIH = 20, ASC = 9, median age at diagnosis 11.7 (range 2.2-17.8)] were included in the study; 12 (4 with PSC) were excluded. Prevalence of inflammatory bowel disease was higher in ASC group (56% vs 10% in AIH, p < 0.05). On histology 17% had cirrhosis. The grade of biliopathy with AILD was moderate in 72% and severe in 31%, and overall more prominent in ASC (p = 0.031). The inflammation of the bile ducts was classified as "multifocal" or "diffuse" mainly in ASC patients (89% vs 45% in AIH, p = 0.043). Periductular fibrosis was reported in 52% of AILD patients, with a higher mean score in ASC group (p < 0.05). However, ductular reaction, biliary metaplasia and granulomatous cholangitis were equally reported in AIH and ASC, providing no clear-cut for the distinction of the two entities in the global histological evaluation. Conclusions Majority of patients with pediatrics AILD have "moderate" or "severe" features of biliopathy; AIH and ASC are not easily distinguishable on histological ground at diagnosis, and therefore, the cholangiogram remains the only effective tool to differentiate patients with AIH from those with ASC. Further prospective studies are needed to better define histological biliary features in AILD, assess if the biliopathy responds to immunosuppressive treatment and evaluate its impact on long-term outcome.
Journal of Hepatology, 2019
Transplantation, 2017
Background. Most pediatric liver transplantation (LT) centers administer long courses of prophyla... more Background. Most pediatric liver transplantation (LT) centers administer long courses of prophylaxis against cytomegalovirus (CMV) without evidence of benefit and with significant drug exposure and costs. We aimed at evaluating overall outcomes, direct and putative indirect effects of CMV, possible impact of viremia and risk factors for CMV infection in pediatric LTrecipients managed with ganciclovir-based preemptive therapy (PET). Methods. The records of all the children who underwent LT between 2008 and 2014 were retrospectively analyzed. Results. One hundred children were included. Three children had CMV disease; no CMV-related death or graft loss was recorded. The only identified risk factor for CMV infection was the donor/recipient serostatus (odds ratio, 17.23; 95% confidence interval, 1.88-157.87; P = 0.012), while viremia per se did not worsen LT outcomes, such as the incidence of acute rejection, Epstein-Barr virus infection, sepsis, biliary and vascular complications, nor graft dysfunction/loss or death at 3 and 5 years after LT. When compared with a historical cohort of children receiving ganciclovir prophylaxis, PET did not differ from prophylaxis for any of the selected outcomes, but was rather associated with lower antiviral drug exposure (6.4 ± 13 days vs 38.6 ± 14 days, P < 0.0001) and cost per patient (2.2 ± 3.9 k€ vs 6.6 ± 8.2 k€, P = 0.001). Conclusions. PET is effective in controlling CMV in children receiving LT, with lower costs and lower exposure to antivirals.
Advances in experimental medicine and biology, Jan 28, 2016
Tuberculosis is a major problem in children depending on their families for management and a re-e... more Tuberculosis is a major problem in children depending on their families for management and a re-emerging disease in low incidence countries, where foreign-born cases account for a large proportion of cases. We investigated socioeconomic features of families and their impact on management and outcome of children with tuberculosis disease seen at a tertiary care centre for paediatric infectious diseases in Italy. Forty-nine Italian and 30 foreign-origin children were included. Children from foreign families had more complicated diseases (20 % vs 0 %; P = 0.002), harbored more drug resistant strains (20 % vs 2 %; P = 0.011), showed longer hospital stay (12 ± 13.1 vs 5.1 ± 6.5 days; P = 0.012) and higher proportion of missed medical visits (15.7 ± 16 vs 8.6 ± 9.6; P ≤ 0.042) than those from Italian families. Harboring drug resistant strains was an independent risk factor for complicated disease course (OR: 72.98; 95 %CI: 1.54-3468.58; P = 0.029), and this risk is higher in children from...
World Review of Nutrition and Dietetics, 2013
Culture-independent strategies such as high-throughput parallel sequencing and comparative genomi... more Culture-independent strategies such as high-throughput parallel sequencing and comparative genomics, metabolic profiling and functional genomics, fluorescence in situ hybridization, and phylogenetic microarray are providing new insights into the composition, determinants, and functional roles of human microbiota. The initial colonization and subsequent development of the intestinal microbiota in early life is a key step for the composition of the human microbiota throughout one's life. An increasing body of evidence highlights the role of nutrition both in early infancy and childhood in the age-related development of the microflora, but other factors significantly contribute to the final composition in the adult age, such as antibiotics and/or functional foods, both of which are widely used in children. The microflora in children is plastic and susceptible to changes in response to diet modifications, antibiotic treatment, and other events. In contrast, the microbiota in adults is relatively stable, reflecting the resilience of the microbiome to external perturbations, such as antibiotic therapies. Eubiosis, i.e. a normal microflora structure, provides protection against infections, educates the immune system, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. However, changes in the microflora, i.e. the presence of too many harmful species or not enough commensal species, called dysbiosis, produce dysfunctions such as intestinal inflammation. It is becoming clear that dysbiosis plays a role in a broad range of important intestinal and extraintestinal diseases such as inflammatory bowel diseases, atopy, and obesity. Moreover, abnormal patterns of microflora have been consistently detected in specific diseases and may provide biomarkers to monitor their course.
PLOS ONE, 2015
Objective E-learning is a candidate tool for clinical practice guidelines (CPG) implementation du... more Objective E-learning is a candidate tool for clinical practice guidelines (CPG) implementation due to its versatility, universal access and low costs. We aimed to assess the impact of a five-module e-learning course about CPG for acute gastroenteritis (AGE) on physicians' knowledge and clinical practice. Study design This work was conceived as a pre/post single-arm intervention study. Physicians from 11 European countries registered for the online course. Personal data, pre-and post-course questionnaires and clinical data about 3 to 5 children with AGE managed by each physician before and after the course were collected. Primary outcome measures included the proportion of participants fully adherent to CPG and number of patients managed with full adherence. Results Among the 149 physicians who signed up for the e-learning course, 59 took the course and reported on their case management of 519 children <5 years of age who were referred to their practice because of AGE (281 and 264 children seen before and after the course, respectively). The course improved knowledge scores (pre-course 8.6 ± 2.7 versus post-PLOS ONE |
PLoS ONE, 2011
The intestinal mucosa is an important target of human immunodeficiency virus (HIV) infection. HIV... more The intestinal mucosa is an important target of human immunodeficiency virus (HIV) infection. HIV virus induces CD4+ T cell loss and epithelial damage which results in increased intestinal permeability. The mechanisms involved in nutrient malabsorption and alterations of intestinal mucosal architecture are unknown. We previously demonstrated that HIV-1 transactivator factor (Tat) induces an enterotoxic effect on intestinal epithelial cells that could be responsible for HIVassociated diarrhea. Since oxidative stress is implicated in the pathogenesis and morbidity of HIV infection, we evaluated whether Tat induces apoptosis of human enterocytes through oxidative stress, and whether the antioxidant Nacetylcysteine (NAC) could prevent it. Caco-2 and HT29 cells or human intestinal mucosa specimens were exposed to Tat alone or combined with NAC. In an in-vitro cell model, Tat increased the generation of reactive oxygen species and decreased antioxidant defenses as judged by a reduction in catalase activity and a reduced (GSH)/oxidized (GSSG) glutathione ratio. Tat also induced cytochrome c release from mitochondria to cytosol, and caspase-3 activation. Rectal dialysis samples from HIV-infected patients were positive for the oxidative stress marker 8-hydroxy-29-deoxyguanosine. GSH/GSSG imbalance and apoptosis occurred in jejunal specimens from HIV-positive patients at baseline and from HIVnegative specimens exposed to Tat. Experiments with neutralizing anti-Tat antibodies showed that these effects were direct and specific. Pre-treatment with NAC prevented Tat-induced apoptosis and restored the glutathione balance in both the invitro and the ex-vivo model. These findings indicate that oxidative stress is one of the mechanism involved in HIV-intestinal disease.
Pediatric Transplantation, 2011
Nicastro E, Stephenne X, Smets F, Fusaro F, de Magnée C, Reding R, Sokal EM. Recovery of graft st... more Nicastro E, Stephenne X, Smets F, Fusaro F, de Magnée C, Reding R, Sokal EM. Recovery of graft steatosis and protein‐losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child.: PFIC 1 is a genetic disorder characterized by hepatic and gastrointestinal disease, often requiring LT during childhood. Extrahepatic symptoms, such as diarrhea and malabsorption, do not improve or may be aggravated after LT, as graft steatosis or steatohepatitis as consequences of the interaction between transplanted liver and native bowel. We describe a patient with PFIC 1 who presented with cholestasis in infancy, who developed intractable pruritus and liver fibrosis. The child underwent living donor LT at 3.6 yr of age, and he early developed severe refractory diarrhea, secondary malabsorption with protein‐losing enteropathy, and an early fatty liver disease trough graft steatohepatitis. As the response to cholestyramine was unsatisfactory, we decided to perform an EBD by using the ...
Journal of Pediatric Gastroenterology & Nutrition, 2010
Journal of Pediatric Gastroenterology & Nutrition, 2013
Objectives: The aim of the present study was to investigate the segment-and time-related changes ... more Objectives: The aim of the present study was to investigate the segment-and time-related changes in rat short bowel syndrome and construct a 4-dimensional (4D) geometrical model of intestinal adaptation. Methods: Sprague-Dawley rats were divided into 3 groups: 2-day, 7-day, and 15-day postresection groups in which 75% of the jejunoileum was removed. Histological and morphometrical parameters in the remaining proximal to distal intestinal segments, from the jejunum to the distal colon, were comparatively evaluated in the groups. The data were used to construct a 4D geometric model in which villi were considered as cylinders, and their surface area was expressed as cylinder lateral area. Results: Major adaptive changes were observed in the ileum consisting of an increase in both the diameter of base and the height of villi. A parallel reduction in their number/mm 2 was observed. The resulting ileal architecture was characterized by a limited number of large villi. An opposite pattern was observed in the jejunum whose postresection structure consisted of an increased number of villi. No changes were observed in the colon. Postresection restructuring was early and faster in the ileum than in the jejunum resulting in an increase in absorptive area of 81.5% and 22.5% in the ileum and jejunum, respectively. Conclusions: Postresection adaptation is intestinal segment-specific because all of the major changes occur in the ileum rather than in the jejunum. Sparing ileal segments during resection may improve the outcome of patients undergoing extensive intestinal resection. Our 4D model can be used to test interventions aimed at optimizing postresection intestinal adaptation.
Journal of Hepatology, 2007
Neonatal hemochromatosis is a rare congenital disorder of the liver associated to a poor prognosi... more Neonatal hemochromatosis is a rare congenital disorder of the liver associated to a poor prognosis. Liver transplantation is often required, since no effective medical treatment has been found. Despite mounting evidence of an alloimmune etiology of this condition, exchange transfusion has never been proposed as a specific treatment for neonatal hemochromatosis. Here we describe two siblings affected by neonatal hemochromatosis. The first, a female, died at 18 days of severe coagulopathy and acute renal failure, diagnosed as affected by neonatal hemochromatosis only when the second sibling was suspected as being affected by the same disease. The second child showed a rapidly worsening coagulopathy which was treated with two exchange transfusions, followed by rapid clinical and laboratory improvement, before reaching a definite diagnosis of neonatal hemochromatosis. He is healthy at present after a follow-up of 12 months. Although exchange transfusion has never been considered as treatment for neonatal hemochromatosis, this case suggests that it could be a feasible treatment option for children affected by this disease, as for other alloimmune conditions.
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Papers by Emanuele Nicastro