The Impact of Teduglutide on Real-Life Health Care Costs in Children with Short Bowel Syndrome.

OBJECTIVES: To analyze the real-life health care costs of home parenteral nutrition (HPN) in children with short bowel syndrome with intestinal failure (SBS-IF) before and after treatment with teduglutide, and to compare those with costs of children with SBS-IF not treated with teduglutide. STUDY DESIGN: All consecutive children with SBS-IF on HPN treated with subcutaneous teduglutide starting from 2018 through 2020 in a tertiary French referral center were retrospectively included. These patients were matched to children with SBS-IF on HPN followed during the same 3-year period who were eligible for the teduglutide but were not treated. HPN direct medical costs included home-care charges, HPN bags, hospital admissions, and teduglutide. A comparison of costs before/after treatment and between patients treated/not treated was performed. RESULTS: Sixty children were included: 30 (50%) were treated with teduglutide and 30 (50%) were untreated. In the treated group, the median total costs of HPN significantly decreased after 1 (P < .001) and 2 years of treatment (P < .001) from 59 454 euros/year/patient to 43 885 euros/year/patient and 34 973 euros/year/patient, respectively. When we compared patients treated and not treated, the total HPN costs/year/patient were similar at baseline (P = .6) but were significantly lower in the teduglutide-treated group after 1 (P = .006) and 2 years of treatment (P < .001). When we added the cost of teduglutide into the analysis, the total cost increased significantly in the treated group and remained much greater even after modeling a reduction in the cost of the drug to one-third the present cost and PN weaning (P < .001). CONCLUSIONS: Treatment with teduglutide is associated with a significant reduction in the annual costs of HPN but still remains expensive because of the drug itself. Finding cost-saving strategies is essential.

A Systematic Review to Manage Avoidant/Restrictive Food Intake Disorders in Pediatric Gastroenterological Practice.

Avoidant/Restrictive food intake disorder (ARFID) is a feeding disorder characterized by persistent difficulty eating, such as limited choices of preferred foods, avoidance or restriction of certain foods or food groups, and negative emotions related to eating or meals. Although ARFID mainly affects children, it can also occur in adolescents and adults. ARFID can have serious physical and mental health consequences, including stunted growth, nutritional deficiencies, anxiety, and other psychiatric comorbidities. Despite its increasing importance, ARFID is relatively underrecognized and undertreated in clinical practice. Treatment consists of a multidisciplinary approach involving pediatric gastroenterologists, nutritionists, neuropsychiatrists, and psychologists. However, there are several gaps in the therapeutic approach for this condition, mainly due to the lack of interventional trials and the methodological variability of existing studies. Few studies have explored the nutritional management of ARFID, and no standardized guidelines exist to date. We performed a systematic literature review to describe the different nutritional interventions for children and adolescents diagnosed with ARFID and to assess their efficacy and tolerability. We identified seven retrospective cohort studies where patients with various eating and feeding disorders, including ARFID, underwent nutritional rehabilitation in hospital settings. In all studies, similar outcomes emerged in terms of efficacy and tolerability. According to our findings, the oral route should be the preferred way to start the refeeding protocol, and the enteral route should be generally considered a last resort for non-compliant patients or in cases of clinical instability. The initial caloric intake may be adapted to the initial nutritional status, but more aggressive refeeding regimens appear to be well tolerated and not associated with an increased risk of clinical refeeding syndrome (RS). In severely malnourished patients, however, phosphorus or magnesium supplementation may be considered to prevent the risk of electrolyte imbalance, or RS.

Early Tube Feeding Improves Nutritional Outcomes in Children with Neurological Disabilities: A Retrospective Cohort Study.

Tube feeding is a life-saving treatment for children with neurological disabilities (ND), who often suffer from malnutrition and feeding disorders. Nonetheless, it is still not widely used. Our aim was to evaluate the outcomes of exclusive tube feeding in a cohort of ND children. All consecutive ND children who started tube feeding at our center within the last 5 years were included in this retrospective study. Weight-for-age, body mass index (BMI), mid-upper arm circumference (MUAC) Z-scores, and symptoms were collected at baseline (V0), 6 (V1), and 12 months (V2) after gastrostomy placement. Fifty children (62% males) were included. The ND-underlying disease was genetic (n = 29, 58%), hypoxic-ischemic encephalopathy (n = 17, 34%), or metabolic (n = 4, 8%). Indications for tube feeding were malnutrition (n = 35, 70%), recurrent respiratory infections (n = 11, 22%), or both (n = 4, 8%). Enteral formulae were polymeric (n = 29, 58%), semi-elemental (n = 17, 34%), hypercaloric (n = 3, 6%), or elemental (n = 1, 2%). Homemade blended feed was offered to three children (6%) in addition to the formula. Weight and BMI increased over the study period. Except for constipation, all symptoms (cough, vomiting, and diarrhea) improved at 6 and 12 months (p < 0.05). Non-serious complications (n = 8; track disruption, granuloma, and skin infection) were observed. Longer disease duration (p < 0.001) at the start of tube feeding was associated with the absence of normalization of nutritional status (BMI Z-score > 2 SD) at 12 months. Tube feeding with commercially available enteral formulae should be started as early as possible for better outcomes.

Clinical Course of Very Early-Onset Inflammatory Bowel Disease.

OBJECTIVES: Data on the phenotypes and disease outcomes of very early-onset inflammatory bowel disease (VEO-IBD) are limited. The aims of this study were to describe the clinical features, outcomes, and treatment response of VEO-IBD patients and to compare them with later-onset pediatric inflammatory bowel disease (P-IBD) patients. METHODS: All consecutive patients aged 0-6 years who were diagnosed with Crohn disease (CD), ulcerative colitis, or IBD unclassified (IBD-U) at 2 academic hospitals from 2010 to March 2021 were included. They were compared to sex-matched IBD patients aged 6-17 years. RESULTS: Two hundred thirty-two patients were included, 78 (34%) with VEO-IBD and 154 (66%) with P-IBD. IBD-U was the most common diagnosis in the VEO-IBD group compared to P-IBD (28% vs 3%, P < 0.001), while CD was predominant in older children (27% vs 52%, P < 0.001). The VEO-IBD group showed lower rates of clinical remission after induction with steroids compared to older children (82% vs 93%, P = 0.01), higher rates of steroid resistance (14% vs 5%, P = 0.02), and steroid dependence (27% vs 8%, P < 0.001). The number of patients who started anti-tumor necrosis factor (TNF)-α agents was similar between the groups. Anti-TNF-α retention was lower in the VEO-IBD group at 1 and 2 years (59% vs 85%, P = 0.003; 16% vs 55%, P < 0.001, respectively). Surgical risk appeared to be higher for VEO-IBD (32% vs 14%, P < 0.001). CONCLUSIONS: When compared to P-IBD patients, patients with VEO-IBD may have a more severe disease course, a poorer response to steroids and anti-TNF-α agents, and require more frequent surgical procedures.

Severe Activity of Inflammatory Bowel Disease is a Risk Factor for Severe COVID-19.

BACKGROUND: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids. METHODS: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes. RESULTS: Data on 122 patients (mean age, 43.9 ±â€…16.7 years; males, 50.0%; Crohn's disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006-1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104-164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320-178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076). CONCLUSIONS: In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19.

This retrospective, observational study on patients with inflammatory bowel disease and severe acute respiratory syndrome coronavirus 2 infection showed that severe inflammatory bowel disease activity was the only independent risk factor for severe coronavirus disease 2019.

Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy.

WHAT IS KNOWN AND OBJECTIVE: Onasemnogene abeparvovec (OA) is the first gene replacement therapy for the treatment of paediatric patients with bi-allelic mutations in the SMN1 gene. Efficacy and safety of OA have been assessed in several studies with promising results, despite rare side effects have been described. CASE SUMMARY: A 3-year-old child with spinal muscular atrophy was treated with OA and subsequently developed fever, widespread erythematous skin lesions and hepatosplenomegaly. Laboratory tests were suggestive for Hemophagocytic lymphohistiocytosis (HLH). WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case of HLH following gene replacement therapy with OA, described in literature.

Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease.

OBJECTIVE: To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD). METHODS: A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes. RESULTS: Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027). CONCLUSION: This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.

Biosimilars in Pediatric IBD: Updated Considerations for Disease Management.

Biologic drugs have significantly modified the pharmacological management of several chronic conditions, including inflammatory bowel diseases (IBD). By contrast, in the last two decades, biologics have been associated with increased direct medical costs. As patents for the reference drugs have expired, the development and commercialization of biosimilars through abbreviated licensing pathways represented an affordable alternative in patients fulfilling the indication for biologics. A growing body of evidence, first in adults and then in the pediatric age group too, has provided reassuring data in terms of efficacy and safety of biosimilars both in naïve patients and in those previously on reference drugs who had to switch to the biosimilar. This review summarizes the currently available evidence for biosimilar use in IBD, with a focus on pediatric IBD. The most common practical approaches to biosimilar use in the pediatric clinical settings are also discussed.

Vedolizumab-associated pulmonary manifestations in children with ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: The off-label use of vedolizumab (VDZ) for inflammatory bowel disease in children is increasing. We report on possibly the first case of VDZ-associated pulmonary manifestations in paediatrics. CASE SUMMARY: This report details the case of a 13-year-old child with ulcerative colitis who was initiated on VDZ due to persistent active disease. After the first three doses, he developed a persistent and productive cough. Microbiological work-up was normal. VDZ discontinuation led to the resolution of symptoms. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case report of VDZ-associated pulmonary manifestations in paediatrics. A direct, pro-inflammatory effect of VDZ has been hypothesized, but further studies are warranted.

Pancreatic Associated Manifestations in Pediatric Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBDs) are chronic relapsing inflammatory conditions of the gastrointestinal tract, encompassing Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U). They are currently considered as systemic disorders determined by a set of genetic predispositions, individual susceptibility and environmental triggers, potentially able to involve other organs and systems than the gastrointestinal tract. A large number of patients experiences one or more extraintestinal manifestations (EIMs), whose sites affected are mostly represented by the joints, skin, bones, liver, eyes, and pancreas. Pancreatic abnormalities are not uncommon and are often underestimated, encompassing acute and chronic pancreatitis, autoimmune pancreatitis, exocrine pancreatic insufficiency and asymptomatic elevation of pancreatic enzymes. In most cases they are the result of environmental triggers. However, several genetic polymorphisms may play a role as precipitating factors or contributing to a more severe course. The aim of this paper is to provide an updated overview on the available evidence concerning the etiology, pathogenesis and clinical presentation of pancreatic diseases in IBD pediatric patients.

Implications of SARS-COV-2 infection in the diagnosis and management of the pediatric gastrointestinal disease.

Gastrointestinal diseases such as celiac disease, functional gastrointestinal disorders (FGIDs), inflammatory bowel disease (IBDs) and acute or chronic diarrhea are quite frequent in the pediatric population. The approach, the diagnosis and management can be changed in the 2019 coronavirus disease (COVID-19) pandemic era. This review has focused on: i) the current understanding of digestive involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected children and adolescents and the clinical implications of COVID-19 for pediatric gastroenterologists, ii) the impact of COVID-19 on the clinical approach to patients with pre-existing or onset diseases, including diagnosis and treatment, and iii) the role and limited access to the instrumental diagnosis such as digestive endoscopy. To date, it is unclear if immunosuppression in patients with IBD and chronic liver disease represents a risk factor for adverse outcomes. Scheduled outpatient follow-up visits may be postponed, especially in patients in remission. Conversely, telemedicine services are strongly recommended. The introduction of new therapeutic regimens should be made on an individual basis, discussing the benefits and risks with each patient. Furthermore, psychological care in all children with chronic disease and their parents should be ensured. All non-urgent and elective endoscopic procedures may be postponed as they must be considered at high risk of viral transmission. Finally, until SARS-CoV-2 vaccination is not available, strict adherence to standard social distancing protocols and the use of personal protective equipment should continue to be recommended.

Diet and Nutrition in Pediatric Inflammatory Bowel Diseases.

Both genetic and environmental factors are involved in the onset of inflammatory bowel disease (IBD). In particular, diet composition is suspected to significantly contribute to IBD risk. In recent years, major interest has raised about the role of nutrition in disease pathogenesis and course, and many studies have shown a clear link between diet composition and intestinal permeability impairment. Moreover, many IBD-related factors, such as poor dietary intake, nutrients loss and drugs interact with nutritional status, thus paving the way for the development of many therapeutic strategies in which nutrition represents the cornerstone, either as first-line therapy or as reversing nutritional deficiencies and malnutrition in IBD patients. Exclusive enteral nutrition (EEN) is the most rigorously supported dietary intervention for the treatment of Crohn's Disease (CD), but is burdened by a low tolerability, especially in pediatric patients. Promising alternative regimens are represented by Crohn's Disease Exclusion Diet (CDED), and other elimination diets, whose use is gradually spreading. The aim of the current paper is to provide a comprehensive and updated overview on the latest evidence about the role of nutrition and diet in pediatric IBD, focusing on the different nutritional interventions available for the management of the disease.

Fibers in pediatric functional gastrointestinal disorders. Practical considerations from clinical cases.

Introduction: Functional gastrointestinal disorders (FGIDs) are common in children and incur high direct and indirect social costs. Partially hydrolyzed guar gum (PHGG) is a natural and water-soluble dietary fiber that is derived from guar gum. It has been proposed as complementary therapy in pediatric FGIDs, especially in chronic functional constipation and irritable bowel syndrome.Areas covered: By focusing on four clinical cases, this article illustrates the use of PHGG fiber as sole supplement ingredient or as a formula component in orally- and tube-fed children suffering from malnutrition due to FGIDs, with or without special medical conditions such as neurological disability. The formula used was a whey peptide-based nutritionally complete formula containing PHGG as a source of soluble dietary fiber. It was offered under medical supervision and after full consideration of all feeding options.Expert opinion: Implementing appropriate feeding behaviors, adapted to age and potential comorbidities, is an essential requisite for therapeutic management of FGIDs. The use of a PHGG supplement or a nutritionally complete formula containing PHGG as a source of soluble dietary fiber can be helpful to manage pediatric FGIDs.

Acute haemorrhagic oedema of infancy: a condition that is not always benign.

Acute haemorrhagic oedema of infancy (AHOI) is a rare condition and an unusual diagnosis for the paediatrician, as approximately 300 cases have been reported in literature so far. Although it was considered for years a less serious variant of Henoch-Schönlein purpura, nowadays it is thought to be a different entity, with his own characteristics and clinical outcome. In literature it is described as a benign condition, self-limiting and without any systemic involvement in most of the cases. We present an atypical case of AHOI with a severe presentation and which needed an aggressive and prolonged steroid therapy.

Acute Malnutrition in Children: Pathophysiology, Clinical Effects and Treatment.

Acute malnutrition is a nutritional deficiency resulting from either inadequate energy or protein intake. Children with primary acute malnutrition are common in developing countries as a result of inadequate food supply caused by social, economic, and environmental factors. Secondary acute malnutrition is usually due to an underlying disease causing abnormal nutrient loss, increased energy expenditure, or decreased food intake. Acute malnutrition leads to biochemical changes based on metabolic, hormonal, and glucoregulatory mechanisms. Most children with primary acute malnutrition can be managed at home with nutrition-specific interventions (i.e., counseling of parents, ensuring household food security, etc.). In case of severe acute malnutrition and complications, inpatient treatment is recommended. Secondary acute malnutrition should be managed by treating the underlying cause.