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Objective This study aims to identify predictors of severe paediatric AP based on laboratory trends and peak/trough values on day 2 (D2) after presentation. The performance of identified predictors was first assessed and then combined with the previously validated sensitive predictor serum lipase ≥7 times the upper limit of normal (× ULN) on day 1 (D1). Methods A retrospective review of children with AP (January 2000–July 2011) was performed at three tertiary referral hospitals (two in Australia, one in the Netherlands). Trends of candidate predictors were analysed using the percentage change from D1 to D2 or peak/trough values within 48 h after presentation. Results 175 AP episodes (including 50 severe episodes [29%]) were identified. Serum lipase ≥50% decrease on D2 (sensitivity 73%, specificity 54%) and calcium trough ≤2.15 mmol/L within 48 h (sensitivity 59%, specificity 81%) were identified as statistically significant predictors for severe AP. By combining the newly identified predictors with the previously validated predictor serum lipase ≥7× ULN on D1 (sensitivity 82%, specificity 53%), specificity improved to predict severe AP on D2 with the addition of: (i) serum lipase ≥50% decrease (sensitivity 67%, specificity 79%), or (ii) trough calcium ≤2.15 mmol/L (sensitivity 46%, specificity 89%). Conclusions Serum lipase and calcium, may be helpful in predicting severity of paediatric AP. There may be a clinical role on D1 for using serum lipase ≥7× ULN (high sensitivity), and on D2 for combining D1 serum lipase ≥7× ULN with calcium trough ≤2.15 mmol/L within 48 h (high specificity) to help predict severe paediatric AP. [ABSTRACT FROM AUTHOR]

Objective Faecal elastase-1 (FE1) is a sensitive marker for exocrine pancreatic enzyme insufficiency. Pancreatic insufficiency (EPI) leads to maldigestion and subsequent poor weight gain. Thus, FE1 is performed as work-up for children with failure to thrive (FTT). However, EPI in the paediatric population outside of cystic fibrosis (CF) is rare. This study aimed to identify the indications for FE1 testing and their diagnostic yield in children. The secondary aim was to evaluate the cost per case of EPI detected for the various indications. Design All FE1 tests performed on children (0–18 years) at a tertiary paediatric hospital in Sydney, Australia between 2010 and 2013 (inclusive) were identified. A retrospective chart audit was performed to identify the indication for testing FE1. The diagnostic yield based on FE1 cut-offs <200 and < 100 μg/g were assessed. Results The most common indication for testing FE1 was “FTT only” (71/216, 32.9%), however, in this cohort of patients, FE1 was least likely to be positive with only 2 out of the 71 (2.8%) patients returning a positive result. In comparison, CF was the second most common indication for testing (60/216, 27.8%), but nearly half (48.8%) of tests returned a positive result in this cohort. The cost per case detected (FE1 <200 μg/g) reflected the test yield with an average cost per positive test of $262.50 (AUD2015) for FTT with short-gut syndrome and $420.00 (AUD2015) for CF-related indications. Conclusion Our study shows that for patients with isolated failure to thrive, FE1 testing is low yield and costly. [ABSTRACT FROM AUTHOR]

Aim Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). Methods A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. Results and conclusions Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the ‘unlikely’ PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000–40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by severe abdominal pain, elevated pancreatic enzymes, and pancreatic changes on abdominal imaging. AP is, by nature, an inflammatory process that leads to protein catabolism and an increased metabolic rate, highlighting the strong need for early nutritional support in the initial management of the disease process. The goal of nutritional support in acute pancreatitis is to correct the negative nitrogen balance to reduce inflammation and improve outcomes. Many trials and multiple systemic reviews and meta-analyses have examined the best modality, timing, and composition of nutritional support for acute pancreatitis. Early enteral nutrition has emerged as an important aspect of the clinical management of AP. This narrative review aimed to provide an overview of the clinical management of nutrition in acute pancreatitis based on the currently available data. [ABSTRACT FROM AUTHOR]

Intestinal dysbiosis has been observed in children with cystic fibrosis (CF), yet the functional consequences are poorly understood. We investigated the functional capacity of intestinal microbiota and inflammation in children with CF. Stool samples were collected from 27 children with CF and 27 age and gender matched healthy controls (HC) (aged 0.8–18 years). Microbial communities were investigated by iTag sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun. Inflammation was measured by faecal calprotectin and M2-pyruvate kinase. Paediatric CF gastrointestinal microbiota demonstrated lower richness and diversity compared to HC. CF samples exhibited a marked taxonomic and inferred functional dysbiosis when compared to HC. In children with CF, we predicted an enrichment of genes involved in short-chain fatty acid (SCFA), antioxidant and nutrient metabolism (relevant for growth and nutrition) in CF. The notion of pro-inflammatory GI microbiota in children with CF is supported by positive correlations between intestinal inflammatory markers and both genera and functional pathways. We also observed an association between intestinal genera and both growth z-scores and FEV1%. These taxonomic and functional changes provide insights into gastrointestinal disease in children with CF and future gastrointestinal therapeutics for CF should explore the aforementioned pathways and microbial changes. [ABSTRACT FROM AUTHOR]

To support investigation of the etiology and psychophysiology of medical traumatic stress, we developed a standardized set of emotionally-salient medical images, called the 'MEDical Image Collection' (MEDIC), for use in neuroimaging or psychological research. This study aimed to establish internal consistency, test re-test reliability, and congruent validity of the image set. A representative sample of 300 adults in the United States were recruited via research recruitment platform, Prolific. Participants rated 124 images depicting medical stimuli on one of two dimensions: emotional arousal (i.e., how strongly an evoked emotion is felt) or affective valence (i.e., how positive or negative the evoked emotion is). Sociodemographic and health-related characteristics, including experiences during the COVID-19 pandemic, were also assessed. To assess test re-test reliability, a subset (n = 200) rated the images on the same dimension a second time, 3 months later. The MEDIC image set was found to: (a) elicit a range of emotional arousal and valence ratings, (b) have excellent inter-rater reliability, (c) moderate test-retest reliability, and (d) good face validity. Results indicate the new MEDIC 124-image set is a reliable and valid instrument, enabling researchers to provide context-specific and emotionally-salient stimuli to individuals when studying affective responses in relation to health and medicine. • MEDIC is a newly developed image set (124 images) of medical stimuli for research into medical traumatic stress and anxiety. • MEDIC elicited a wide range of emotional arousal and valence ratings in a sample of 300 adults. • The MEDIC image set was found to have excellent inter-rater reliability and moderate test-retest reliability. • We demonstrated the sensitivity of the MEDIC image set to medical experiences. • MEDIC can be accessed for use by contacting the study team. [ABSTRACT FROM AUTHOR]

Background: Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF.Methods: In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016.Results: Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8-206.2) vs. 75.0 (61.0-105.9); P < 0.0001). Infants with CRMS/CFSPID→CF (n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3-126.8) vs. 73.7(60.0-96.0); P = 0.02).Conclusions: Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID. [ABSTRACT FROM AUTHOR]

The article present a case study of a 1-week-old boy with neonatal jaundice underwent work-up for conjugated hyperbilirubinemia; at 3 weeks of age liver histopathology revealed prominent cholestasis, focal bile duct plugging, and bile duct proliferation; at 4 months of age, the patient presented with upper gastrointestinal tract bleeding; and at 8 months of age, the AV fistula was suspected; and mentions that the fistula was embolized with placement of a 3- and 2-mm Hydrasoft hydrocoils.

Background: Cholecystoduodenostomy is a surgical procedure that bypasses the extrahepatic biliary tree and connects the gallbladder directly to the duodenum. This case describes the successful use of this procedure in a novel situation.Case Presentation: A premature (34 weeks gestation) female infant with cystic fibrosis required a laparotomy on day 1 of life due to an intrauterine small bowel perforation. Resection of small bowel and ileostomy formation resulted in short gut syndrome, with 82 cm residual small bowel and intact ileocaecal valve. Post-ileostomy reversal at 2 months old, she developed conjugated hyperbilirubinaemia. Despite conservative management including increased enteral feeding, ursodeoxycholic acid, cholecystostomy drain insertion and flushes, her cholestatic jaundice persisted. A liver biopsy revealed an "obstructive/cholestatic" picture with fibrosis. To avoid further shortening her gut with an hepatoportoenterostomy, cholecystoduodenostomy was performed at 3 months of age with subsequent post-operative improvement and eventual normalisation of her clinical jaundice and liver biochemistry.Conclusions: This is the first reported case of a cholecystoduodenostomy being used successfully to treat an infant with persistent conjugated hyperbilirubinemia, cystic fibrosis and short gut syndrome. Cholecystoduodenostomy is a treatment option that with further study, may be considered for obstruction of the common bile duct in patients with short gut and/or where a shorter operating time with minimal intervention is preferred. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Next to progressive airway disease, CF is also associated with intestinal inflammation and dysbiosis. Ivacaftor, a CFTR potentiator, has improved pulmonary and nutritional status but its effects on the intestinal microbiota and inflammation are unclear. Hence, we assessed the changes on the intestinal microbial communities (16S rRNA variable 3 gene region) and inflammatory markers (calprotectin and M2-pyruvate kinase [M2-PK]) in 16 CF individuals (8 children and 8 adults) before and after (median 6.1 months) ivacaftor. Stool calprotectin significantly decreased following ivacaftor (median [IQR]: 154.4 [102.1-284.2] vs. 87.5 [19.5-190.2] mg/kg, P = 0.03). There was a significant increase in Akkermansia with ivacaftor. Increased abundance of Akkermansia was associated with normal stool M2-PK concentrations, and decreased abundances of Enterobacteriaceae correlated with decreased stool calprotectin concentrations. In summary, changes in the gut microbiome and decrease in intestinal inflammation was associated with Ivacaftor treatment among individuals with CF carrying at least one gating CFTR mutation. Thus, CFTR-modifying therapy may adequately improve the aberrant pathophysiology and milieu of the CF gut to favor a more healthy microbiota, which in turn reduces intestinal inflammation. [ABSTRACT FROM AUTHOR]

Screening for Cystic Fibrosis-related diabetes is recommended in patients with CF <10 years old when there are concerns about growth and lung function. The Oral Glucose Tolerance Test (OGTT) is recommended but has not been validated in this cohort. We sought to determine whether the 2-h OGTT, the gold standard diagnostic test for CFRD, detects clinical decline in children with CF <10 years old. We analysed blood glucose(BG) levels collected every 30 min during OGTT in 27 children with CF < 10 years old, comparing the 2-hour BG (BG 120min), peak BG (BG max) and Area Under the Curve(AUC) for glucose and the association with lung function and nutritional status. We also compared the OGTT results with results from Continuous Glucose Monitoring (CGM) performed in 11 participants. The BG max was higher than the BG 120min in 25/27 (93%) participants. There was a significant inverse correlation between BG max and weight z-score (r s = −0.56, p =.002) and between BG max and FEV 1 (r s = −0.54, p =.014) that was not present for BG 120min. A significant inverse correlation was also identified between fasting insulin level and elevated glucose on CGM, defined as AUC >7.8 mmol/L (r s = − 0.69, p =.027) or as % time > 7.8 (r s = − 0.76, p =.011). Children with CF < 10 years of age with higher BG max on OGTT have lower lung function and weight z- scores that may not be identified using the 2 h OGTT BG 120min. CGM also identifies glucose excursions in young children with CF. • Higher BG max on 30-minutely OGTT is associated with lower lung function and weight z-scores in young children with CF. • Elevated 2 h glucose level on OGTT may not capture early clinical decline • Low fasting insulin levels are associated with elevated glucose levels on CGM [ABSTRACT FROM AUTHOR]

Aim: This study addresses the absence of a definition of care for children with feeding disorders, limited agreement on key performance indicators (KPIs), and the lack of data linked to those KPIs. Methods: Clinicians, consumers and researchers involved in outpatient feeding care in New South Wales (NSW), Australia were invited to participate in a two‐Phase study. In Phase 1, a modified Delphi method was used. Two rounds of voting resulted in a new consensus definition of a multidisciplinary paediatric feeding clinic. Three further rounds voting determined relevant KPIs. In Phase 2, the KPIs were piloted prospectively in 10 clinics. Results: Twenty‐six clinicians, consumers and researchers participated in Phase 1. Participation across five voting rounds declined from 92% to 60% and a valid definition and KPI set were created. In Phase 2, the definition and KPIs were piloted in 10 clinics over 6 weeks. Data for 110 patients were collected. The final KPI set of 28 measures proposed covers clinical features, patient demographics and medical issues, parent–child interaction and outcome measures. Conclusions: A new definition of a multidisciplinary paediatric feeding clinic is now available, linked to a standardised KPI set covering relevant performance measures. These proved viable in baseline data collection for 10 clinics across NSW. This sets a foundation for further data collection, systematic measurement of care provision and outcomes, and research needed to deliver care improvement for children with paediatric feeding disorder. [ABSTRACT FROM AUTHOR]

The pathologic effects of an altered cystic fibrosis transmembrane receptor (CFTR) protein on the exocrine pancreas is ubiquitous and of varying severity. In this section, pancreatitis and pancreatic cystosis are covered. [ABSTRACT FROM AUTHOR]

• MI patients had lower FEV1 percentage predicted over time • MI patients had lower BMI Z-scores over time • Both groups had similar P. aeruginosa isolation and chronic colonisation rates • Increased nutritional interventions in MI group • Increased hospitalisations (gastrointestinal/respiratory) and mortality in MI group Meconium ileus (MI) affects up to 20% of newborns with cystic fibrosis (CF). We compared clinical outcomes between Australian paediatric CF patients with and without meconium ileus (non-MI). This was a retrospective case-control study of MI and non-MI patients in New South Wales, Australia, from 1988 to 2010. MI patients were matched 1:1 with pancreatic insufficient non-MI patients for age, sex and CF clinic. Clinical measurements, nutrition and gastrointestinal outcomes over this period were compared between groups using linear mixed models for continuous variables to account for age. There were 162 matched pairs (N=324, 52% female) with mean (SD) age of 15.3 (8.2) and 14.9 (7.9) years for MI and non-MI patients respectively (P=0.6). MI patients aged 5-23 had poorer FEV1% compared to non-MI patients (estimate -0.070 SE [0.02], P=0.003). There were no significant differences in P. aeruginosa isolation rates; however S. aureus isolation rates were lower in MI patients (72%) compared to non-MI (82%) (OR 0.6 [0.3-1.0], P=0.03). Chronic colonisation rates for P. aeruginosa and S. aureus were not significantly different between groups. MI patients aged 2-20 had significantly lower BMI Z-scores over time (estimate -0.25 SE [0.1], P=0.02). MI patients were more likely to receive oral feed supplements (OR 2.8 [1.4-6.1], P=0.003) and gastrostomy formation (OR 4.4 [1.1-24.6], P=0.02). CF patients with MI may have worse lung function, growth and nutrition than non-MI patients over time. Meconium ileus may be an early poor prognostic factor for CF. [ABSTRACT FROM AUTHOR]

Background & Aims Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been characterized fully. Methods We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013. Results Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 y; P = .01). Splenomegaly was observed in 99% of patients and varices in 71%. Levels of liver enzymes were near normal in most patients. Thrombocytopenia affected 70% of patients and was more severe in patients with varices (88 × 10 9 /L vs 145 × 10 9 /L; P < .0001). Ninety-one patients received liver transplants (16%), at a median age of 13.9 years. Compared with patients who did not receive liver transplants, patients who received liver transplants had lower platelet counts (78 × 10 9 /L vs 113 × 10 9 /L; P < .0001), higher international normalized ratios ( P < .0001), and lower levels of albumin ( P = .0002). The aminotransferase to platelet ratio index (APRi) and fibrosis index based on 4 factor (FIB-4) values were higher than the diagnostic thresholds for CF liver disease in 96% and in 90% of patients, respectively. Patients who received liver transplants or who had varices had higher APRi and FIB-4 values than patients who did not. Conclusions In patients with CF, severe liver disease develops early in childhood (approximately 10 years of age), and is more common in boys than in girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores. [ABSTRACT FROM AUTHOR]

• Among 171 patients with severe CFLD, 19 (11.1%) were not eligible for CFTR modulators. • All ineligible patients carried at least one mutation leading to complete loss of CFTR function. • There remains an unmet therapy need for ineligible patients with CFLD. Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. The severe CFLD variant with cirrhosis or portal hypertension has a poor prognosis and life expectancy. CFTR modulator therapies are now available for people with CF and eligibility for such treatment is based on their CFTR genotype. We evaluated the genetic eligibility for elexacaftor, tezacaftor, ivacaftor (ETI), and ivacaftor (IVA) monotherapy in a previously reported CF cohort of 1591 people with CF of whom 171 with severe CFLD. Based on their CFTR mutations, 13% (N=184/1420) of subjects without CFLD and 11% (N=19/171) of those with severe CFLD are not eligible for either ETI or IVA therapy. The non-eligible patients without CFLD or with severe CFLD can currently not take advantage of the potential benefits of these new treatments. Although this study cannot provide any data regarding the effect of ETI or IVA on the progression of severe CFLD, the consequences for ineligibility of patients with extreme liver phenotype may be even more significant because of their poorer disease risk profile. [Display omitted] [ABSTRACT FROM AUTHOR]

• Incidence of liver outcome evaluated in UDCA prescribing vs. non-prescribing centers. • No significant difference in cumulative incidence of portal hypertension was identified. • No significant differences in liver-related and other-cause mortality were found. The efficacy and safety of ursodeoxycholic acid (UDCA) for the treatment of liver disease associated with cystic fibrosis (CF) are under discussion, and clinical practice varies among centers. The study aimed at evaluating if the incidence of severe liver disease differs between CF centers routinely prescribing or not prescribing UDCA. We carried out a retrospective multicenter cohort study including 1591 CF patients (1192 patients from UDCA-prescribing centers and 399 from non-prescribing centers) born between 1990 and 2007 and followed from birth up to 31 December 2016. We computed the crude cumulative incidence (CCI) of portal hypertension (PH) at the age of 20 years in the two groups and estimated the subdistribution hazard ratio (HR) through a Fine and Gray model. Over the observation period, 114 patients developed PH: 90 (7.6%) patients followed-up in UDCA prescribing centers and 24 (6.0%) in non-prescribing centers. The CCI of PH at 20 years was 10.1% (95% CI: 7.9-12.3) in UDCA-prescribing and 7.7% (95% CI: 4.6-10.7) in non-prescribing centers. The HR among patients followed in prescribing centers indicated no significant difference in the rate of PH either in the unadjusted model (HR: 1.21, 95% CI: 0.69-2.11) or in the model adjusted for pancreatic insufficiency (HR: 1.28, 95% CI: 0.77-2.12). CF patients followed-up in UDCA prescribing centers did not show a lower incidence of PH as compared to those followed in centers not prescribing UDCA. These results question the utility of UDCA in reducing the occurrence of severe liver disease in CF. [ABSTRACT FROM AUTHOR]

Over the past two decades there has been considerable progress with the evaluation and management of infants with an inconclusive diagnosis following Newborn Screening (NBS) for cystic Fibrosis (CF). In addition, we have an increasing amount of evidence on which to base guidance on the management of these infants and, importantly, we have a consistent designation being used across the globe of CRMS/CFSPID. There is still work to be undertaken and research questions to answer, but these infants now receive more consistent and appropriate care pathways than previously. It is clear that the majority of these infants remain healthy, do not convert to a diagnosis of CF in childhood, and advice on management should reflect this. However, it is also clear that some will convert to a CF diagnosis and monitoring of these infants should facilitate their early recognition. Those infants that do not convert to a CF diagnosis have some potential of developing a CFTR-RD later in life. At present, it is not possible to quantify this risk, but families need to be provided with clear information of what to look out for. This paper contains a number of changes from previous guidance in light of developing evidence, but the major change is the recommendation of a detailed assessment of the child with CRMS/CFSPID in the sixth year of age, including respiratory function assessment and imaging. With these data, the CF team can discuss future care arrangements with the family and come to a shared decision on the best way forward, which may include discharge to primary care with appropriate information. Information is key for these families, and we recommend consideration of a further appointment when the individual is a young adult to directly communicate the implications of the CRMS/CFSPID designation. [ABSTRACT FROM AUTHOR]

Children with CF have been reported to consume significantly more energy-dense, nutrient-poor foods than controls where there are now concerns of inadequate micronutrient intake. There are no current or comprehensive dietary studies assessing micronutrient intake in CF children. To evaluate micronutrient intake in children with CF compared to recommended dietary intakes (RDIs). Dietary intake of 13 micronutrients was measured in CF children aged 2–18 years and age- and sex-matched controls using a validated food frequency questionnaire (The Australian Child and Adolescent Eating Survey). CF children (n = 82) consumed significantly more energy than controls (n = 82) [3142(2531–3822) kcal vs 2216(1660–2941) kcal; p <.001]. Absolute intake in CF children was significantly higher in all micronutrients except vitamin C and folate, however energy-adjusted intake was significantly lower for all micronutrients except vitamin A, sodium, calcium and phosphorous. Energy-adjusted intake in primary school CF children was significantly less than controls in 8/13 micronutrients. Overall, median intakes exceeded the RDIs for all micronutrients however CF children fell short of the RDIs for folate (26.8%), iron (15.9%) and calcium (9.8%). In pre-school, 50% of CF children and 91.7% of controls did not meet the iron RDI. High school CF and control children failed to meet RDIs for 7/13 and 9/13 micronutrients respectively. Increased intake of most micronutrients in CF children was largely attributed to higher energy consumption. However, micronutrient density of the diet declined with increasing age, where high school children failed to meet RDIs for most key micronutrients. • CF children consumed significantly more total energy than controls. • CF children had significantly higher intake in most micronutrients than controls. • Energy-adjusted micronutrient intake decreased as CF children reached school age. • CF children failed to meet RDIs for key micronutrients such as folate and iron. • High school CF children are most at risk of overall inadequate micronutrient intake. [ABSTRACT FROM AUTHOR]

Abstract Background Prescription of a high-energy, high-fat diet is a mainstay of nutrition management in cystic fibrosis (CF). However, families may be relying on energy-dense, nutrient-poor (EDNP) foods rather than nutrient-dense (ND) foods to meet dietary targets. We aimed to evaluate the relative contribution of EDNP and ND foods to the usual diets of children with CF and identify sociodemographic factors associated with higher EDNP intakes. Methods This is a cross-sectional comparison of children with CF aged 2–18 years and age- and gender-matched controls. Dietary intake was assessed using the Australian Child and Adolescent Eating Survey (ACAES) food frequency questionnaire. Results Children with CF (n = 80: 37 males; mean age 9.3 years) consumed significantly more EDNP foods than controls (mean age 9.8 years) in terms of both total energy (median [IQR]: 1301 kcal/day (843–1860) vs. 686 kcal/day (480–1032); p < 0.0001), and as a proportion of energy intake (median [IQR]: 44% (34–51) vs. 31% (24–43); p < 0.0001). Although children with CF met their estimated energy requirements (median [IQR]: 158% (124–187) vs. 112% (90–137); p < 0.0001) and their diets were high in fat (median [IQR]: 38% (35–41) vs. 34% (32–36); p < 0.0001), this was largely attributable to EDNP foods. High EDNP intakes (≥10 serves/day) were associated with socioeconomic disadvantage (p = 0.01) and rural residential location (p = 0.03). Discussion The energy- and fat-dense CF diet is primarily achieved by overconsumption of EDNP foods, rather than ND sources. This dietary pattern may not be optimal for the future health of children with CF, who are now expected to survive well into adulthood. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. Methods M2-PK was measured in stools collected from patients with CF and HC (0–10 years). Linear mixed model analysis was used. Results M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) ( P = 0.998) or HC (45 patients, 45 samples) ( P = 0.21), over the age range 0–10 years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7–28.6; 1.0–239.1] (n = 77) vs. 1.0 [1.0–1.0; 1.0–50.0] (n = 45) U/mL, respectively; P = 0.001). Conclusions Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life. [ABSTRACT FROM AUTHOR]

Background Fecal calprotectin may be used as a non-invasive method to assess the effect of novel therapies on the gut in cystic fibrosis (CF). Method Stools from CF patients and healthy controls (HC) (0–10 years old) were prospectively collected for evaluation of temporal trends. Results 130 CF samples (64 subjects) and 114 HC samples (101 subjects) were collected. Overall, fecal calprotectin levels were different in CF patients and HC from 0 to 10 years ( P = 0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to 1 years ( P = 0.03) and demonstrated an upward trajectory until 4 years. From > 4 to 10 years calprotectin was consistently higher in CF patients compared with HC ( P = 0.007). Conclusions Fecal calprotectin levels in children with CF and HC were age-dependent and had distinct trajectories. Careful interpretation of calprotectin is required if used in drug trials for CF, particularly in children less than 4 years old. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 by The American College of Gastroenterology.)

Highly effective modulator therapy (HEMT), particularly the triple combination elexacaftor-tezacaftor-ivacaftor (ETI), significantly improved clinical outcomes and quality of life in people with Cystic Fibrosis (pwCF). This review analyzes current knowledge on the impact of HEMTs on gastrointestinal (GI) symptoms and features in pwCF. A descriptive review of English literature until February 29, 2024, was conducted using medical databases. Observational studies and clinical trials addressing GI reflux disease (GERD), lower GI symptoms and pancreatic disease were considered. Studies report positive effects of HEMTs on pH levels and bicarbonate secretion as well as improvement on intestinal inflammation. HEMTs also demonstrated positive effects on GERD and lower GI symptoms or conditions CF related such as dysbiosis. Taking ETI during pregnancy could also allow resolution of meconium ileus in fetuses with CF. The best benefits were observed in pancreatic function, potentially delaying CF-related diabetes and recovering pancreatic function in some children on ETI. Larger trials, particularly in pediatric populations, need to confirm these findings and explore long-term effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP., Study Design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 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 CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days., Conclusions: Mild-moderate HTG in children with acute recurrent or CP was not associated with increased pancreatitis frequency, nor increased development of CP, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate HTG may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or CP., Competing Interests: Declaration of Competing Interest Z.M.S. is currently an employee of 4D Molecular Therapeutics Inc and a consultant for BridgeBio Pharma and Renexxion. M.A.H. is the president of CAPER, a board member of CAPER, and a board member of the National Pancreas Foundation. T.G. received a research grant from Vertex Pharmaceuticals, and she is a consultant for Cystic Fibrosis Foundation (CFF). C.Y.O. is a consultant for and has received research grant from Vertex Pharmaceuticals. E.R.P. is a consultant for BridgeBio and Ultragenyx. S.J.S. is a consultant for UpToDate, Nestle, Abbvie, Renexxion, and the CFF. A.J.F. is a consultant for Takeda and AbbVie, CFF, and is a member of the CAPER board. V.D.M. is an Associate Editor for JPGN Reports. D.M.T. is an Associate Editor for JPGN. M.W. is a consultant for and has received research grants from Vertex Pharmaceuticals. M.E.L. receives royalties from Millipore Inc and UpToDate and consults for CFF. A.U. is a consultant for CFF and Abbvie Inc. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)