Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.

Bone health in children with recurrent and chronic pancreatitis: A multi-center cross sectional analysis.

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied. METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2. RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively). CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study.

BACKGROUND: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. METHODS AND FINDINGS: Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. CONCLUSIONS: Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. TRIAL REGISTRATION: ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258.

Gastrointestinal Features of 22q11.2 Deletion Syndrome Include Chronic Motility Problems From Childhood to Adulthood.

OBJECTIVES: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS. METHODS: All patients followed in the 22q and You Center at the Children's Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed. RESULTS: Included patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities ( P < 0.01) but not with deletion size or physiologic comorbidities ( P > 0.05). One exception was increased nausea/vomiting in hypothyroidism ( P = 0.002). CONCLUSIONS: Functional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.

Standardized Feeding Approach Mitigates Weight Loss in Infants with Congenital Heart Disease.

OBJECTIVE: To evaluate the effect of a standardized feeding approach using a clinical nutrition pathway on weight-for-age Z score (WAZ) over hospital length of stay (HLOS) for infants with congenital heart disease (CHD). STUDY DESIGN: A 10-year retrospective cohort study examined eligible infants who underwent neonatal cardiac surgery between July 2009 and December 2018 (n = 987). Eligibility criteria included infants born at least 37 weeks of gestation and a minimum birth weight of 2 kg who underwent cardiac surgery for CHD within the first 30 days of life. Using the best linear unbiased predictions from a linear mixed effects model, WAZ change over HLOS was estimated before and after January 2013, when the standardized feeding approach was initiated. The best linear unbiased predictions model included adjustment for patient characteristics including sex, race, HLOS, and class of cardiac defect. RESULTS: The change in WAZ over HLOS was significantly higher from 2013 to 2018 than from 2009 to 2012 (ß = 0.16; SE = 0.02; P < .001), after controlling for sex, race, HLOS, and CHD category, indicating that infants experienced a decreased WAZ loss over HLOS after the standardized feeding approach was initiated. Additionally, differences were found in WAZ loss over HLOS between infants with single ventricle CHD (ß = 0.26; SE = 0.04; P < .001) and 2 ventricle CHD (ß = 0.04; SE = 0.02; P = .04). CONCLUSIONS: These data suggest that an organized, focused approach for nutrition therapy using a standardized pathway improves weight change outcomes before hospital discharge for infants with single and 2 ventricle CHD who require neonatal cardiac surgery.

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

OBJECTIVES: The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). METHODS: Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. RESULTS: Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. CONCLUSIONS: In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study.

OBJECTIVE: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. STUDY DESIGN: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. RESULTS: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). CONCLUSIONS: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.

Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE.

INTRODUCTION: The significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact. PATIENTS AND METHODS: We compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ or Fisher exact test for categorical variables. RESULTS: PD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful). CONCLUSIONS: PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography.

Diabetes Mellitus in Children with Acute Recurrent and Chronic Pancreatitis: Data From the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort.

OBJECTIVES: Adults with chronic pancreatitis (CP) have a high risk for developing pancreatogenic diabetes mellitus (DM), but little is known regarding potential risk factors for DM in children with acute recurrent pancreatitis (ARP) or CP. We compared demographic and clinical features of children with ARP or CP, with and without DM, in the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE) registry. METHODS: We reviewed the INSPPIRE database for the presence or absence of physician-diagnosed DM in 397 children, excluding those with total pancreatectomy with islet autotransplantation, enrolled from August 2012 to August 2017. Patient demographics, BMI percentile, age at disease onset, disease risk factors, disease burden, and treatments were compared between children with DM (n = 24) and without DM (n = 373). RESULTS: Twenty-four children (6% of the cohort) had a diagnosis of DM. Five of 13 tested were positive for beta cell autoantibodies. The DM group was 4.2 years [95% confidence interval (CI) 3-5.4] older at first episode of acute pancreatitis, and tended to more often have hypertriglyceridemia [odds ratio (OR) 5.21 (1.33-17.05)], coexisting autoimmune disease [OR 3.94 (0.88-13.65)] or pancreatic atrophy [OR 3.64 (1.13, 11.59)]. CONCLUSION: Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.

Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE.

OBJECTIVE: The aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors. STUDY DESIGN: Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (nonprogression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% confidence interval [CI]) of progression for each risk variable. RESULTS: Of 442 children, 251 had ARP and 191 had CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those ages 6 years or older at the first episode of AP compared to those younger than 6 years (median time to CP: 2.91 vs 4.92 years; P = 0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003). Within 6 years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%). CONCLUSIONS: Children with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.

Chronic Pancreatitis: Pediatric and Adult Cohorts Show Similarities in Disease Progress Despite Different Risk Factors.

OBJECTIVES: The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. METHODS: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables. RESULTS: Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, P = 0.011). CONCLUSIONS: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

Adherence to Nutritional Supplementation in Cystic Fibrosis.

PURPOSE: The purpose of this study was to examine patterns of adherence to a novel dietary supplement in pediatric cystic fibrosis. Adherence to dietary supplementation in cystic fibrosis is challenging, and examination of patterns of adherence behavior over time is needed to better characterize subgroups of patients who need self-management support. DESIGN AND METHODS: We prospectively examined adherence to Lym-X-Sorb™ (LXS), an organized lipid matrix dietary supplementation for patients with cystic fibrosis (CF) and pancreatic insufficiency (PI), over a 12-month period. Adherence for participants aged 5-17 years with CF and PI (N = 109) was monitored monthly via supplement packet counts. Group-based trajectory modeling was employed to examine patterns in adherence behavior over time. RESULTS: Four distinct trajectories best characterized adherence in this sample, with 18% of participants demonstrating near perfect adherence, 42% demonstrating good adherence (at or above 80%), 16% demonstrating poor adherence that declined over time, and 24% demonstrating significant non-adherence (< 30%). CONCLUSIONS: Some patients with CF and PI who are prescribed nutritional supplements will require intensive, individualized behavioral intervention to enhance adherence. Identifying patients who will have difficulty adhering to dietary interventions may result in better treatment-to-patient matching and improved adherence promotion efforts. PRACTICE IMPLICATIONS: Assessment of adherence to dietary supplementation over time can identify patients at risk for continued difficulty with self-management and provide opportunities for early intervention.

Analysis of Jak2 signaling reveals resistance of mouse embryonic hematopoietic stem cells to myeloproliferative disease mutation.

The regulation of hematopoietic stem cell (HSC) emergence during development provides important information about the basic mechanisms of blood stem cell generation, expansion, and migration. We set out to investigate the role that cytokine signaling pathways play in these early processes and show here that the 2 cytokines interleukin 3 and thrombopoietin have the ability to expand hematopoietic stem and progenitor numbers by regulating their survival and proliferation. For this, they differentially use the Janus kinase (Jak2) and phosphatidylinositol 3-kinase (Pi3k) signaling pathways, with Jak2 mainly relaying the proproliferation signaling, whereas Pi3k mediates the survival signal. Furthermore, using Jak2-deficient embryos, we demonstrate that Jak2 is crucially required for the function of the first HSCs, whereas progenitors are less dependent on Jak2. The JAK2V617F mutation, which renders JAK2 constitutively active and has been linked to myeloproliferative neoplasms, was recently shown to compromise adult HSC function, negatively affecting their repopulation and self-renewal ability, partly through the accumulation of JAK2V617F-induced DNA damage. We report here that nascent HSCs are resistant to the JAK2V617F mutation and show no decrease in repopulation or self-renewal and no increase in DNA damage, even in the presence of 2 mutant copies. More importantly, this unique property of embryonic HSCs is stably maintained through ≥1 round of successive transplantations. In summary, our dissection of cytokine signaling in embryonic HSCs has uncovered unique properties of these cells that are of clinical importance.

What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia.

22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by recurrent, chromosome-specific, low copy repeat (LCR)-mediated copy-number losses of chromosome 22q11. The Children's Hospital of Philadelphia has been involved in the clinical care of individuals with what is now known as 22q11.2DS since our initial report of the association with DiGeorge syndrome in 1982. We reviewed the medical records on our continuously growing longitudinal cohort of 1,421 patients with molecularly confirmed 22q11.2DS from 1992 to 2018. Most individuals are Caucasian and older than 8 years. The mean age at diagnosis was 3.9 years. The majority of patients (85%) had typical LCR22A-LCR22D deletions, and only 7% of these typical deletions were inherited from a parent harboring the deletion constitutionally. However, 6% of individuals harbored other nested deletions that would not be identified by traditional 22q11.2 FISH, thus requiring an orthogonal technology to diagnose. Major medical problems included immune dysfunction or allergies (77%), palatal abnormalities (67%), congenital heart disease (64%), gastrointestinal difficulties (65%), endocrine dysfunction (>50%), scoliosis (50%), renal anomalies (16%), and airway abnormalities. Median full-scale intelligence quotient was 76, with no significant difference between individuals with and without congenital heart disease or hypocalcemia. Characteristic dysmorphic facial features were present in most individuals, but dermatoglyphic patterns of our cohort are similar to normal controls. This is the largest longitudinal study of patients with 22q11.2DS, helping to further describe the condition and aid in diagnosis and management. Further surveillance will likely elucidate additional clinically relevant findings as they age.

Recommendations for Diagnosis and Management of Autoimmune Pancreatitis in Childhood: Consensus From INSPPIRE.

OBJECTIVES: Autoimmune pancreatitis (AIP) represents a complex immune-mediated pancreas disorder. Pediatric AIP (P-AIP) is rare. We have recently summarized the characteristic features of P-AIP. We now aim to develop recommendation statements to standardize the diagnostic and therapeutic approach to P-AIP and facilitate future research in the field. METHODS: A panel of pediatric gastroenterologists participating in the International Study Group of Pediatric Pancreatitis: In search for a cuRE was formed to discuss and then vote on 15 recommendation statements. A consensus of at least 80% was obtained following 3 voting rounds and revision of the statements. RESULTS: We have now generated 15 statements to help standardize the approach to diagnosis and management of P-AIP. CONCLUSIONS: The first P-AIP recommendation statements developed by the International Study Group of Pediatric Pancreatitis: In search for a cuRE group are intended to bring standardization to the diagnosis and treatment of this rare childhood disorder. These statements may help guide a uniform approach to patient care and facilitate future research studies.

Autoimmune Pancreatitis in Children: Characteristic Features, Diagnosis, and Management.

OBJECTIVES: Autoimmune pancreatitis (AIP) is an increasingly recognized disease entity, but data in children are limited. AIP presentation and outcome in children might differ from the adult experience. We aim to determine the characteristic features of AIP in children. METHODS: Data about clinical symptoms, imaging, histology, and treatment were collected using two sources: (i) a systematic literature search and (ii) the INSPPIRE database, the largest international multicenter study of pancreatitis in children and the Cliniques Universitaires St-Luc (CUSL) registry. RESULTS: We identified 48 AIP cases: 30 from literature review, 14 from INSPPIRE, and 4 from CUSL. The median age at diagnosis was 13 years (range 2-17 years). Abdominal pain (43/47, 91%) and/or obstructive jaundice (20/47, 42%) were the most common symptoms at diagnosis. Elevated serum IgG4 levels were only observed in 9/40 (22%) children. Cross-sectional imaging studies were abnormal in all children including hypointense global or focal gland enlargement (39/47, 83%), main pancreatic duct irregularity (30/47, 64%), and common bile duct stricture (26/47, 55%). A combination of lymphoplasmacytic inflammation, pancreatic fibrosis, and ductal granulocyte infiltration were the main histological findings (18/25, 72%). Children with AIP had a prompt clinical response to steroids. Complications of AIP included failure of exocrine (4/25, 16%) and endocrine (3/27, 11%) pancreas function. CONCLUSIONS: Pediatric AIP has a distinct presentation with features similar to type 2 AIP in adults. This comprehensive report on the largest group of children with AIP to date is expected to help with the diagnosis and management of this disease and pave the way for future research studies.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.