Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE.

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

OBJECTIVE: To determine if mild-moderate hypertriglyceridemia is associated with increased development of chronic pancreatitis or pancreatitis-associated complications in children with acute recurrent or chronic pancreatitis. STUDY DESIGN: Longitudinal data from the INSPPIRE-2 (INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort of children with acute recurrent or chronic pancreatitis (n=559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any hypertriglyceridemia (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate hypertriglyceridemia (150-499 mg/dL; 1.7-5.6 mmol/L), moderate hypertriglyceridemia (500-999 mg/dL; 5.6-11.3 mmol/L), and severe hypertriglyceridemia groups (≥1,000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed. RESULTS: In children with acute recurrent or chronic pancreatitis and hypertriglyceridemia, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in chronic pancreatitis prevalence. However, hypertriglyceridemia severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days. CONCLUSIONS: Mild-moderate hypertriglyceridemia in children with acute recurrent or chronic pancreatitis was not associated with increased pancreatitis frequency, nor increased development of chronic pancreatitis, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate hypertriglyceridemia may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or chronic pancreatitis.

A novel nutritional approach to infants and children with congenital diarrhea due to homozygous DGAT1 mutations.

OBJECTIVES: Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 deficiency often presents with severe diarrhea and protein-losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN. METHODS: From 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life. RESULTS: All patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN. CONCLUSIONS: Children with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency.

Evolution of nutritional management in children with cystic fibrosis - a narrative review.

Nutrition has played a central role in the management and outcomes of people with cystic fibrosis (pwCF) since the 1970s. Advances in therapies and practices in recent decades have led to a significant change in the patient landscape with dramatic improvements in life expectancy, as well as quality of life, bringing with it new issues. Historically, cystic fibrosis was a condition associated with childhood and malnutrition; however, changes in patient demographics, nutritional assessment and fundamental nutritional management have evolved, and it has become an increasingly prevalent adult disease with new nutritional challenges, including obesity. This paper aims to describe these changes and the impact and challenges they bring for those working in this field. Nutritional professionals will need to evolve, adapt and remain agile to the wider range of situations and support required for a new generation of pwCF. Specialised nutrition support will continue to be required, and it will be additionally important to improve and optimise quality of life and long-term health.

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE.

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. RESULTS: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. CONCLUSIONS: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.

The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial.

BACKGROUND: Around 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes - abstinence for alcoholic and cholecystectomy for biliary pancreatitis - the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended. Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. METHODS, DESIGN: Participants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a 'reduced fat diet' (15% fat, 65% carbohydrate, 20% protein) and a 'standard healthy diet' (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DISCUSSION: This study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.

Nutritional and metabolic management for cystic fibrosis in a post-cystic fibrosis transmembrane conductance modulator era.

PURPOSE OF REVIEW: The introduction of highly effective cystic fibrosis transmembrane conductance regulator modulators has resulted in a paradigm shift towards treating underlying cause of cystic fibrosis (CF) rather than the ensuing complications. In this review, we will describe the impact of these small molecules on growth, nutrition, and metabolic status in people with CF (pwCF). RECENT FINDING: Results of clinical trials and real world data demonstrate that these small molecules are having a significant impact of on augmenting body weight, improving nutritional status and reducing gastrointestinal symptom burden. Early treatment can also positively impact on pancreatic endocrine and exocrine function. SUMMARY: Nutritional and metabolic management of pwCF needs to change in order to maximize long term health and avoid future complications relating to obesity and increased cardiovascular risk. Longitudinal registry studies will be key to improve our understanding of the longer-term outcome of these new therapies.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. CONCLUSIONS: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Training in Paediatric Clinical Nutrition Across Europe: A Survey of the National Societies Network (2016-2019) of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition.

OBJECTIVES/BACKGROUND: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. METHODS: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. RESULTS: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) andhome parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of <5 annually are reported by 13% and 43% of centres, respectively. CONCLUSIONS: The survey shows clear differences and deficits in Clinical Nutrition training infrastructure, including staff and patient volumes, in European PGHN training centres, leading to large differences and limitations in training opportunities in Clinical Nutrition.

Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors.

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. RESULTS: The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P  < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001). CONCLUSIONS: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.