INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been sug... more INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared the efficacy and safety of these regimens in patients who previously failed conventional thiopurine treatment. METHODS: Children with IBD treated with split-dose thiopurine or low-dose thiopurine-allopurinol cotherapy were retrospectively identified. Medical records were reviewed for demographics, treatment regimen, reason for thiopurine failure, side effects, and discontinuation of treatment. Laboratory findings were evaluated at different time points. RESULTS: After prior therapeutic failure, 42 patients were on split-dose regimen (group A) and 20 patients were on thiopurine-allopurinol cotherapy (group B). Twelve patients crossed from group A to group B because of treatment failure, 1 patient was lost at follow-up, and 1 patient discontinued the treat...
Background: The most common cause of intestinal failure (IF) in childhood remains short bowel syn... more Background: The most common cause of intestinal failure (IF) in childhood remains short bowel syndrome (SBS), where bowel mass is significantly reduced due to a congenital atresia or resection and parenteral nutrition (PN) needed. Home PN has improved outcome and quality of life, but the long-term therapeutic goal is to achieve enteral autonomy whilst avoiding long term complications. This paper is aimed at discussing nutritional strategies available to clinicians caring for these patients. Methods: A literature search was performed from 1992 to 2022 using Pubmed, MEDLINE and Cochrane Database of Systematic Reviews, and recent guidelines were reviewed. In the absence of evidence, recommendations reflect the authors’ expert opinion. Results: Consensus on the best possible way of feeding children with IF-SBS is lacking and practice varies widely between centres. Feeding should commence as soon as possible following surgery. Oral feeding is the preferred route and breast milk (BM) the ...
Summary In the last few decades there has been a considerable increase in fructose and sweeteners... more Summary In the last few decades there has been a considerable increase in fructose and sweeteners consumption. At the same time, there has been an increase in childhood obesity and an ever more evident correlation between high fructose intake and obesity risk. Fructose, sucrose and sorbitol are toxic sugars for patients with Hereditary Fructose Intolerance (HFI), a rare disease in which early exposure to these carbohydrates can cause severe reactions, which are potentially lethal. The promotion of “fructose-free” diet before weaning could be a preventive measure for both childhood obesity and serious reactions due to early exposure to fructose in infants with HFI. On the other hand, it is not documented that an early introduction of fructose before weaning provides nutritional benefits for infants.
Coronavirus disease 2019 (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV... more Coronavirus disease 2019 (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is predominantly a respiratory disease. However, its significant impact on the gastrointestinal (GI) system is now well-known. SARS-CoV-2 enters cells via the angiotensin-converting enzyme-2 (ACE-2) receptor, which is abundantly expressed on lung cells, but also on enterocytes. Several etiopathogenetic mechanisms have been postulated to explain the GI involvement in COVID-19, including loss in intestinal absorption, microscopic mucosal inflammation and impaired ACE-2 function, which plays a significant role in maintaining gut homeostasis. In children the GI manifestations include anorexia, nausea, vomiting, diarrhea and abdominal pain, which may represent the earliest presenting symptoms of the disease. However, although rare, a significant GI mucosal inflammation, such as terminal ileitis mimicking an atypical appendicitis, and other GI manifestations have been reported. COVID-19 p...
ABSTRACT Introduction Irritable bowel syndrome is a common functional gastrointestinal disorder i... more ABSTRACT Introduction Irritable bowel syndrome is a common functional gastrointestinal disorder in children, characterized by recurrent abdominal pain associated with altered bowel habits in terms of both frequency and consistency. According to change in stool consistency it is categorized into 4 subtypes. From the etiological perspective, it is a combination of factors takes part in symptoms’ generation, the overall treatment response rate is often unsatisfactory if a multidisciplinary is not pursued. Areas covered The aim of this manuscript is to summarize the current pharmacotherapy in pediatric irritable bowel syndrome in order to aid clinicians in treating this challenging disorder. Expert opinion Most evidence involving pediatric populations rely on open label or retrospective studies and/or are not specifically designed for irritable bowel syndrome but tend to generalize their results to mixed populations of children with functional gastrointestinal disorders. A high placebo response rate combined with poor patients’ selection could account for the overall weak evidence supporting the use of pharmacological agents in pediatric irritable bowel syndrome. Given the multifaceted nature of the disorder, multidisciplinary approaches combining pharmacotherapy with alternative treatments is highly recommendable.
Background: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metaboli... more Background: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. Methods: Patients’ clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. Results: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransfer...
Textbook of Pediatric Gastroenterology, Hepatology and Nutrition, 2015
Gastrointestinal (GI) disorders are present in 5–50 % of patients with primary immunodeficiencies... more Gastrointestinal (GI) disorders are present in 5–50 % of patients with primary immunodeficiencies. These manifestations mimic classic forms of disease (in the absence of immunodeficiency) such as celiac disease, food allergy, or inflammatory bowel disease, but they are often unresponsive to conventional therapies. Because GI disease may be the first presentation of an underlying immunodeficiency, it is crucial to consider immunodeficiency in any child with recurrent or chronic severe diarrhea, malabsorption, and failure to thrive resistant to conventional treatments. At the same time, routine evaluation of GI tract is useful for children with immunodeficiency, given the high incidence of GI disorders in these patients and considering that early evaluation and diagnosis can prevent potentially irreversible tissue damage. Primary immunodeficiencies are relatively common but likely underdiagnosed. A clinical history of recurrent, opportunistic, or unusual infections; histological features that do not fit the usual pattern of disease; and a poor response to conventional therapy should prompt the pediatrician to pursue further immunologic evaluation in collaboration with the immunologist.
Objective: Hereditary Fructose Intolerance (HFI) is an inborn error of fructose metabolism, respo... more Objective: Hereditary Fructose Intolerance (HFI) is an inborn error of fructose metabolism, responsible for severe liver disease, if untreated. Currently, treatment only relies on strict fructose-free diet. It is not clear if continued daily intake of small amounts of fructose is associated with chronic liver damage. The aim of this study was to analyze the possible correlation between fructose intake and presence of liver disease signs in HFI patients and the role of genotype-phenotype correlation. Methods: Forty-four patients (22 males; mean age at diagnosis 5.8 ± 3.1 months) with HFI were enrolled. At diagnosis, in all patients a fructose-free diet was prescribed. According to liver function tests and hepatic ultrasound evaluation, patients were divided in two groups: the first with liver disease signs and the second without. The daily fructose intake was calculated using a food diary. Results: During a mean follow-up of 13.5 ± 6.6 years, 25 (56.8%) patients presented liver disease signs. These patients did not differ from those without liver disease signs with regard to the daily fructose intake (67 ± 156 versus 138 ± 150 mg/day, p = 0.391). No significant correlation between dietary fructose intake and hypertransaminasemia was found. The two groups did not differ in relation to the type of mutation (missense, nonsense or frameshift). Analyzing the specific types of mutation, homozigosity for A149P type was present in 12% of patients with liver disease and 36.8% of those without liver disease (p = 0.0187). Conclusions: There is a subset of HFI patients that continue to have liver disease signs despite an appropriate fructose-free diet. It is likely that factors other than dietary fructose intake affect the liver disease.
Journal of Pediatric Gastroenterology & Nutrition
Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic propert... more Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication (“off label”) for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an “off label/on evidence” prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an o...
INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been sug... more INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared the efficacy and safety of these regimens in patients who previously failed conventional thiopurine treatment. METHODS: Children with IBD treated with split-dose thiopurine or low-dose thiopurine-allopurinol cotherapy were retrospectively identified. Medical records were reviewed for demographics, treatment regimen, reason for thiopurine failure, side effects, and discontinuation of treatment. Laboratory findings were evaluated at different time points. RESULTS: After prior therapeutic failure, 42 patients were on split-dose regimen (group A) and 20 patients were on thiopurine-allopurinol cotherapy (group B). Twelve patients crossed from group A to group B because of treatment failure, 1 patient was lost at follow-up, and 1 patient discontinued the treat...
Background: The most common cause of intestinal failure (IF) in childhood remains short bowel syn... more Background: The most common cause of intestinal failure (IF) in childhood remains short bowel syndrome (SBS), where bowel mass is significantly reduced due to a congenital atresia or resection and parenteral nutrition (PN) needed. Home PN has improved outcome and quality of life, but the long-term therapeutic goal is to achieve enteral autonomy whilst avoiding long term complications. This paper is aimed at discussing nutritional strategies available to clinicians caring for these patients. Methods: A literature search was performed from 1992 to 2022 using Pubmed, MEDLINE and Cochrane Database of Systematic Reviews, and recent guidelines were reviewed. In the absence of evidence, recommendations reflect the authors’ expert opinion. Results: Consensus on the best possible way of feeding children with IF-SBS is lacking and practice varies widely between centres. Feeding should commence as soon as possible following surgery. Oral feeding is the preferred route and breast milk (BM) the ...
Summary In the last few decades there has been a considerable increase in fructose and sweeteners... more Summary In the last few decades there has been a considerable increase in fructose and sweeteners consumption. At the same time, there has been an increase in childhood obesity and an ever more evident correlation between high fructose intake and obesity risk. Fructose, sucrose and sorbitol are toxic sugars for patients with Hereditary Fructose Intolerance (HFI), a rare disease in which early exposure to these carbohydrates can cause severe reactions, which are potentially lethal. The promotion of “fructose-free” diet before weaning could be a preventive measure for both childhood obesity and serious reactions due to early exposure to fructose in infants with HFI. On the other hand, it is not documented that an early introduction of fructose before weaning provides nutritional benefits for infants.
Coronavirus disease 2019 (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV... more Coronavirus disease 2019 (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is predominantly a respiratory disease. However, its significant impact on the gastrointestinal (GI) system is now well-known. SARS-CoV-2 enters cells via the angiotensin-converting enzyme-2 (ACE-2) receptor, which is abundantly expressed on lung cells, but also on enterocytes. Several etiopathogenetic mechanisms have been postulated to explain the GI involvement in COVID-19, including loss in intestinal absorption, microscopic mucosal inflammation and impaired ACE-2 function, which plays a significant role in maintaining gut homeostasis. In children the GI manifestations include anorexia, nausea, vomiting, diarrhea and abdominal pain, which may represent the earliest presenting symptoms of the disease. However, although rare, a significant GI mucosal inflammation, such as terminal ileitis mimicking an atypical appendicitis, and other GI manifestations have been reported. COVID-19 p...
ABSTRACT Introduction Irritable bowel syndrome is a common functional gastrointestinal disorder i... more ABSTRACT Introduction Irritable bowel syndrome is a common functional gastrointestinal disorder in children, characterized by recurrent abdominal pain associated with altered bowel habits in terms of both frequency and consistency. According to change in stool consistency it is categorized into 4 subtypes. From the etiological perspective, it is a combination of factors takes part in symptoms’ generation, the overall treatment response rate is often unsatisfactory if a multidisciplinary is not pursued. Areas covered The aim of this manuscript is to summarize the current pharmacotherapy in pediatric irritable bowel syndrome in order to aid clinicians in treating this challenging disorder. Expert opinion Most evidence involving pediatric populations rely on open label or retrospective studies and/or are not specifically designed for irritable bowel syndrome but tend to generalize their results to mixed populations of children with functional gastrointestinal disorders. A high placebo response rate combined with poor patients’ selection could account for the overall weak evidence supporting the use of pharmacological agents in pediatric irritable bowel syndrome. Given the multifaceted nature of the disorder, multidisciplinary approaches combining pharmacotherapy with alternative treatments is highly recommendable.
Background: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metaboli... more Background: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. Methods: Patients’ clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. Results: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransfer...
Textbook of Pediatric Gastroenterology, Hepatology and Nutrition, 2015
Gastrointestinal (GI) disorders are present in 5–50 % of patients with primary immunodeficiencies... more Gastrointestinal (GI) disorders are present in 5–50 % of patients with primary immunodeficiencies. These manifestations mimic classic forms of disease (in the absence of immunodeficiency) such as celiac disease, food allergy, or inflammatory bowel disease, but they are often unresponsive to conventional therapies. Because GI disease may be the first presentation of an underlying immunodeficiency, it is crucial to consider immunodeficiency in any child with recurrent or chronic severe diarrhea, malabsorption, and failure to thrive resistant to conventional treatments. At the same time, routine evaluation of GI tract is useful for children with immunodeficiency, given the high incidence of GI disorders in these patients and considering that early evaluation and diagnosis can prevent potentially irreversible tissue damage. Primary immunodeficiencies are relatively common but likely underdiagnosed. A clinical history of recurrent, opportunistic, or unusual infections; histological features that do not fit the usual pattern of disease; and a poor response to conventional therapy should prompt the pediatrician to pursue further immunologic evaluation in collaboration with the immunologist.
Objective: Hereditary Fructose Intolerance (HFI) is an inborn error of fructose metabolism, respo... more Objective: Hereditary Fructose Intolerance (HFI) is an inborn error of fructose metabolism, responsible for severe liver disease, if untreated. Currently, treatment only relies on strict fructose-free diet. It is not clear if continued daily intake of small amounts of fructose is associated with chronic liver damage. The aim of this study was to analyze the possible correlation between fructose intake and presence of liver disease signs in HFI patients and the role of genotype-phenotype correlation. Methods: Forty-four patients (22 males; mean age at diagnosis 5.8 ± 3.1 months) with HFI were enrolled. At diagnosis, in all patients a fructose-free diet was prescribed. According to liver function tests and hepatic ultrasound evaluation, patients were divided in two groups: the first with liver disease signs and the second without. The daily fructose intake was calculated using a food diary. Results: During a mean follow-up of 13.5 ± 6.6 years, 25 (56.8%) patients presented liver disease signs. These patients did not differ from those without liver disease signs with regard to the daily fructose intake (67 ± 156 versus 138 ± 150 mg/day, p = 0.391). No significant correlation between dietary fructose intake and hypertransaminasemia was found. The two groups did not differ in relation to the type of mutation (missense, nonsense or frameshift). Analyzing the specific types of mutation, homozigosity for A149P type was present in 12% of patients with liver disease and 36.8% of those without liver disease (p = 0.0187). Conclusions: There is a subset of HFI patients that continue to have liver disease signs despite an appropriate fructose-free diet. It is likely that factors other than dietary fructose intake affect the liver disease.
Journal of Pediatric Gastroenterology & Nutrition
Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic propert... more Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication (“off label”) for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an “off label/on evidence” prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an o...
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