Nutritional parameters following first episode of pediatric acute pancreatitis.

BACKGROUND AND OBJECTIVES: Acute pancreatitis (AP) carries the risk of subsequent nutritional deficiencies. The prevalence of these deficiencies following a single episode of AP in children is unknown. We aimed to determine prevalence of anthropometric and laboratory-based measures of nutritional status in children following their first (index) admission for AP. METHODS: Prospective observational cohort study of patients ≤21 years of age with first episode of confirmed AP. Anthropometric and laboratory values were obtained at time of AP onset and at follow up time points of 3 and 12 months (m) post AP. AP attack was classified as either: mild, moderately severe or severe (which were combined in one group (SAP)). RESULTS: 181 patients met criteria and were followed prospectively with 52% male, a median age of 13.7 years (IQR 9.4-16.0) and median Body Mass Index (BMI) Z-score of 0.6 (IQR -0.5, 1.6). Most patients had mild AP (140, 77%), with 23% meeting criteria for moderate or severe (41/181). 6 (3%) had diabetes mellitus (DM) predating AP and were excluded from further analysis. BMI Z-score remained stable during the follow up period. 13% of patients developed pre-DM or DM at 3m or 12m. Nearly one third of patients had low ferritin at 3m (29%) or 12m (29%). At 12m, 8% of patients had Vitamin A deficiency. 6% of patients had low Vitamin E levels at 3m and 5% at 12m. Over half of patients at both 3m and 12m had 25 OH Vitamin D insufficiency or deficiency (56% and 56%). Prolonged International Normalized Ratio (INR) (>1.3) was seen in 9% of patients at 12m. Very low albumin (<3.5 g/dL) was found in 24% of patients at 3m and 18% at 12m (Table 1). Patients with very low albumin at 3m were younger (median 10.7 vs. 14.2 years, p = 0.04), however sex, BMI Z-score and AP severity were not associated with albumin level. Although BMI Z-score did not differ between the groups, those with SAP had a significant decrease in BMI Z-score from first attack compared to mild AP at 3m (-0.4 vs. 0.0, p = 0.0002, Figure 2). At 3m, Vitamin E deficiency in SAP versus mild AP was found in 20% vs 2% (p = 0.04) and SAP had a lower median hematocrit (35.8 vs. 37.6, p = 0.046). There were no other laboratory significant differences at 3m in mild versus SAP groups. At 12m, those with SAP were more likely to have pre-DM or DM compared to mild AP (31% vs. 7%, p = 0.002). No other significant laboratory differences occurred at 12m. CONCLUSIONS: After the first AP attack patients experience nutritional deficiencies, including ferritin, all fat-soluble vitamins, and low albumin. SAP is associated with a decrease in BMI Z-score, increased prevalence of vitamin E deficiency at 3m, and an increase in pre-diabetes and diabetes at 12m. Serial monitoring of vitamin and mineral values post AP is warranted and further prospective studies are needed.

Infrequent fractures and resilient bone mineral density: bone health in patients with Fanconi anemia.

Not available.

Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS. STUDY DESIGN: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C-reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP). RESULTS: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02). CONCLUSION: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.

Home Insulin Pump Use in Hospitalized Children With Type 1 Diabetes.

Importance: Pediatric data on inpatient home insulin pumps are absent in the literature. Understanding safety of home insulin pumps, managed by patients or caregivers, during times of illness will help diabetes technology securely move into pediatric hospitals. Objective: To examine whether insulin can be safely and accurately delivered to hospitalized children through home insulin pumps when managed by patients or caregivers. Design, Setting, and Participants: This single-center, retrospective, observational cohort study included children with insulin-dependent diabetes admitted to a tertiary children's hospital from January 1, 2016, to December 31, 2021. In all these patients, diabetes was the primary or secondary diagnosis on admission. Exposure: Insulin delivery via home insulin pump, hospital insulin pump, or subcutaneous injection. Main Outcomes and Measures: Hyperglycemia (glucose, >250 mg/dL) and hypoglycemia (glucose, <45 mg/dL) rates (quantified as the proportion of total insulin-days), glucose variability, and diabetic ketoacidosis (DKA) recurrences were compared for hospital pumps (manual mode), home pumps (manual mode), and subcutaneous injections using bivariate tests. Results: There were 18 096 insulin-days among 2738 patients aged 0.5 to 25 years (median age, 15.8 years [IQR, 12.3-18.3 years]). Overall, 990 (5.5%) of insulin-days involved hospital insulin pumps, and 775 (4.3%) involved home pumps. A total of 155 insulin-days (15.7%) involving hospital pumps were hyperglycemic, compared with 209 (27.0%) involving home pumps and 7374 (45.2%) involving injections (P < .001). Moderate hypoglycemia days comprised 31 insulin-days (3.1%) involving hospital pumps compared with 35 (4.5%) involving home pumps and 830 (5.1%) involving injections (P = .02). Severe hypoglycemia did not differ significantly according to insulin delivery method. Two patients using injections (0.01%) developed DKA; no patients using hospital or home pumps developed DKA. Conclusions and Relevance: In this cohort study, home insulin pump use was found to be safe in a children's hospital regarding hyperglycemia and hypoglycemia. These data support use of home insulin pumps during pediatric admissions in patients who do not require intensive care and without active DKA.

Endocrine Management and Clinical Outcomes in a Cohort of Pediatric Patients Undergoing Total Pancreatectomy with Islet Autotransplantation.

Objective: To describe management strategies that contributed to optimal outcomes in pediatric recipients of a total pancreatectomy with islet autotransplantation (TPIAT). Research Design and Methods: We provide a comprehensive report of the approach to endocrine management of the pediatric TPIAT recipient from initial evaluation through the first 4 years postsurgery. We performed a retrospective review of the endocrine outcomes of TPIAT recipients to describe the impact of this approach on post-TPIAT glycemic management. Results: Outcome data from 86 TPIAT recipients were reviewed. At 12 months post-TPIAT (n = 82), the median HbA1C was 6.0% (25-75th percentile 5.6-6.7), at 18 months (n = 56) HbA1C was 6.4% (5.6-7.5), at 2 years (n = 46) HbA1C was 6.4% (5.6-7.4), at 3 years (n = 31) HbA1C was 6.5% (5.5-8.1), and at 4 years (n = 16) HbA1C was 7.2% (6.2-8.3). Conclusions: Pediatric patients at our institution have favorable endocrine outcomes as evidenced by median HbA1C under the goal of 6.5% through the initial 3 years by following our modified management protocols.

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.

Total pancreatectomy with islet autotransplantation reduces opioid use and improves nutritional support in children with debilitating pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) can result in opioid dependence and nutritional challenges in children. Total pancreatectomy with islet autotransplantation (TPIAT) is a viable surgical option in appropriately selected patients. We examined differences between children who met criteria for TPIAT versus those who did not and continued with non-operative management. METHODS: Retrospective observational cohort study of patients evaluated for TPIAT between August 2014 and July 2020 was performed. Cohort-based analyses between TPIAT and non-TPIAT groups were performed. RESULTS: Analyses included 121 patients, 69 of whom underwent TPIAT. Demographics, genetic risk factors, and anatomic variants did not differ between groups. TPIAT patients were more likely to have CP (88% vs 71%; p = 0.02), had higher median number of endoscopic retrograde cholangiopancreatography procedures (2.0 vs 1.0; p = 0.0001), and had higher likelihood of opioid use (61% vs 42%; p = 0.04) and nutritional supplementation (23% vs 4%; p = 0.004), compared to non-TPIAT. At 6 months post-TPIAT, patients had lower use of any analgesic pain medications (39% vs 73%; p = 0.0002) and lower use of opioids (9% vs 39%; p = 0.0006), compared to non-TPIAT patients at 6 months after evaluation. At 6 months post-TPIAT, rate of exclusively oral nutrition increased from 77% to 86%, and total parenteral nutrition use decreased from 13% to 0% (p = 0.02). CONCLUSIONS: In children referred for TPIAT evaluation, there is greater burden of disease in those selected for operation, compared to patients who do not undergo operation. TPIAT achieves lower analgesic pain medication use compared to continuation with non-TPIAT management and achieves freedom from nutritional supplementation. Level of evidence: Retrospective comparative study, Level III.

Metabolic Outcomes in Pediatric Patients One-Year Post-Total Pancreatectomy with Islet Autotransplantation after Early Pump Initiation.

We previously published that insulin pump initiation immediately after IV insulin therapy was associated with improved post-surgical glycemic outcomes compared to multiple daily injections (MDI) in pediatric patients following a total pancreatectomy with islet autotransplantation (TPIAT). We investigated metabolic outcomes of this population at one-year post-TPIAT to assess if the improved outcomes in the early pump group were sustained over time. We retrospectively reviewed 40 patients post-TPIAT previously studied at 10-days post-surgery (15 used MDI and 25 used pump therapy immediately post-ICU, and all were discharged on pump therapy). Data analyzed included: demographics, islet equivalents per kilogram (IEQ/kg) transplanted, exogenous insulin use, and baseline vs. one-year (via mixed meal testing) HbA1c, fasting glucose, insulinogenic index, and the area under the curve (AUC) for insulin and c-peptide. More patients were off insulin at one year in the early pump group compared to the MDI group (45% vs. 13%, p = 0.07). Of all patients off insulin, 100% of the early pump users weaned off by six months post-TPIAT compared to 30% of the MDI users. Two known variables associated with favorable insulin outcomes, lower age and higher IEQ/kg, were not significantly different between groups. Fasting glucose was lower in the early pump group compared to the MDI group (median 97 vs. 122 mg/dL, p = 0.003), while AUC c-peptide was greater in early pump users at one-year post-TPIAT but did not reach significance (median 57.0 vs. 50.3 ng/mL × minutes, p = 0.14). Other metabolic outcomes did not differ between groups. Despite lower median age and higher IEQ/kg in the MDI group, the early pump group had a lower fasting glucose. Younger TPIAT age (p = 0.02) and early pump users (p = 0.04) were significantly associated with insulin independence at one year. This study was limited by sample size. Early pump use may have long-term benefits in post-TPIAT endogenous insulin secretion.

Age-related trajectory of bone density in children with intestinal failure: A longitudinal retrospective cohort study.

BACKGROUND: Longitudinal changes in bone health in children with intestinal failure (IF) are unclear. We aimed to better understand the trajectory of bone mineral status over time in children with IF and identify clinical factors that influence the trajectory. METHODS: Clinical records of patients attending the Intestinal Rehabilitation Center of Cincinnati Children's Hospital Medical Center between 2012 and 2021 were reviewed. Children diagnosed with IF before age 3 years with at least two lumbar spine dual-energy x-ray absorptiometry scans were included. We abstracted information on medical history, parenteral nutrition, bone density, and growth. We calculated bone density z scores with and without adjustment for height z scores. RESULTS: Thirty-four children with IF met inclusion criteria. Children were shorter than average with a mean height z score of -1.5 ± 1.3. The mean bone density z score was -1.5 ± 1.3 with 25 of the cohort having a z score < -2.0. After height adjustment, the mean bone density z score was -0.42 ± 1.4 with 11% below -2.0. Most dual-energy x-ray absorptiometry scans (60%) had a feeding tube artifact. Bone density z scores increased slightly with age and lower parenteral nutrition dependency and were higher in scans without an artifact. Etiologies of IF, line infections, prematurity, and vitamin D status were not associated with height-adjusted bone density z scores. CONCLUSION: Children with IF were shorter than expected for age. Deficits in bone mineral status were less common when adjusting for short stature. Etiologies of IF, prematurity, and vitamin D deficiency were not associated with bone density.

Association of pancreatic fat on imaging with pediatric metabolic co-morbidities.

BACKGROUND: The relationship between pancreatic fat on imaging and metabolic co-morbidities has not been established in pediatrics. We sought to investigate the relationship between pancreatic fat measured by MRI and endocrine/exocrine dysfunctions along with the metabolic co-morbidities in a cohort of children. OBJECTIVE: To investigate relationships between pancreatic fat quantified by MRI and endocrine and exocrine conditions and metabolic co-morbidities in a cohort of children. MATERIALS AND METHODS: This was a retrospective review of pediatric patients (n = 187) who had a clinically indicated MRI examination between May 2018 and February 2020. After 51 patients without useable imaging data were excluded, the remaining 136 subjects comprised the study sample. Laboratory studies were assessed if collected within 6 months of MRI and patient charts were reviewed for demographic and clinical information. MRI proton density fat fraction (PDFF) sequence had been acquired according to manufacturer's specified parameters at a slice thickness of 3 mm. Two blinded radiologists independently collected PDFF data. RESULTS: The median age at MRI was 12.1 (IQR: 9.0-14.8) years and the majority of patients were Caucasian (79%), followed by African American and Hispanic at 12% and 11% respectively. There was a higher median pancreas fat fraction in patients with exocrine conditions (chronic pancreatitis or exocrine insufficiency) compared to those without (3.5% vs 2.2%, p = 0.03). There was also a higher median fat fraction in the head of pancreas in patients with endocrine insufficient conditions (insulin resistance, pre-diabetes, type 1 and type 2 diabetes) compared to those without endocrine insufficiency when excluding patients with active acute pancreatitis (3.5% vs 2.0%, p = 0.04). Patients with BMI > 85% had higher mean fat fraction compared to patients with BMI ≤ 85% (head: 3.8 vs 2.4%, p = 0.01; body: 3.8 vs 2.5%, p = 0.005; tail: 3.7 vs 2.7%, p = 0.049; overall pancreas fat fraction: 3.8 vs 2.6%, p = 0.002). CONCLUSION: Pancreas fat is elevated in patients with BMI > 85% and in those with exocrine and endocrine insufficiencies.

Risk Factors for Post-ERCP Pancreatitis in Pediatric and Young Adult Patients.

OBJECTIVES: Post-ERCP pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Limited existing data suggest that prophylactic pancreatic duct (PD) stenting in pediatric patients may increase the risk of PEP. The aim of this study is to identify factors associated with PEP in pediatric patients. METHODS: Patients at a single institution who underwent ERCP between 2012 and 2020 were retrospectively reviewed. Patient and procedure-related factors were collected. Data were analyzed using Chi-square or Fisher exact tests as appropriate and Mann-Whitney-Wilcoxon tests. RESULTS: Seven hundred thirty-six ERCPs were performed for 402 unique patients. Ninety-four cases were complicated by PEP (12.8%), of which 91 were mild and 3 were moderately severe. Pancreatic indication, native major papilla, PD cannulation and injection, and higher American Society for Gastrointestinal Endoscopy (ASGE) complexity were associated with PEP. A higher proportion of patients who received rectal indomethacin (65% vs 47%, P = 0.002), or who had placement of a prophylactic (31% vs 20%, P = 0.01) or therapeutic PD stent (37% vs 27%, P = 0.04) developed PEP; however, in a subgroup analysis of high-risk patients, this association was not persistent. A smaller proportion of PEP patients had PRSS1 mutation compared to non-PEP patients (22% vs 40%, P = 0.04). CONCLUSIONS: This study evaluates factors associated with developing PEP in a large pediatric cohort. A high rate of PEP was observed, likely secondary to higher rates of pancreatic indication and higher ASGE complexity scores compared to previously reported literature. Randomized prospective trials are needed to better define the utility of various interventions.

Prevalence of Gastrointestinal Symptoms and Impact on Quality of Life at 1-Year Follow-Up of Initial Attack of Acute Pancreatitis.

OBJECTIVES: This study aims to describe the prevalence of gastrointestinal (GI) symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents. METHODS: Questionnaires regarding GI symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy-matched healthy controls. RESULTS: Children with a standalone occurrence of AP experienced a similar rate of GI symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within 1 year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains. CONCLUSIONS: Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.

Histologic Severity of Nonalcoholic Fatty Liver Disease Associates with Reduced Bone Mineral Density in Children.

BACKGROUND: Lower whole body bone mineral density (BMD) has been reported in children with nonalcoholic fatty liver disease (NAFLD), but potential mediators remain uncertain. AIMS: To assess BMD at multiple skeletal sites in children with confirmed NAFLD and controls with obesity, adjusting for known determinants of BMD, and examine potential mediators. METHODS: We assessed age-, sex-, and race-specific, and height-adjusted BMD z-scores of whole body, lumbar spine, hip, femoral neck and forearm by dual-energy-x-ray absorptiometry in 79 children, 8-19 years old: 46 with biopsy-confirmed NAFLD [29 steatohepatitis (NASH)/17 fatty liver (NAFL)] and 33 controls without liver disease. We compared BMD z-scores by multivariable regression, adjusting for known BMD determinants and potential mediators (inflammatory and insulin resistance measures). RESULTS: Unadjusted mean BMD z-scores in NAFLD were similar to controls, but significantly lower in NASH vs. NAFL at all sites. After covariate adjustment, mean forearm BMD z-score was higher in NAFL (ß 0.60 ± SE 0.30, p < 0.05) and lower in NASH (ß - 0.49 ± SE 0.26, p = 0.06) vs. controls (p = 0.002 for group), with similar trends at whole body and total hip; hs-CRP negatively associated with whole body and forearm BMD z-scores (p < 0.05), while visceral fat area negatively associated with femoral neck (p < 0.05). Only three children had clinically low whole body BMD z-scores (< - 2), one per group (control, NAFL and NASH). CONCLUSIONS: NASH, but not NAFL, may be associated with increased risk of reduced BMD in children. Systemic inflammation, independent of body composition and load bearing, may mediate reduction in BMD in NASH.

Prevalence of delayed puberty and low bone density in patients with epidermolysis bullosa: Insight from a large single center's experience.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare genetic skin conditions that result in skin fragility. EB can be quite severe with chronic inflammation and malnutrition impairing growth and pubertal development. These factors have potential consequences for skeletal health. We aimed to determine the prevalence of delayed puberty and low bone mineral density (BMD) for age in children and young adults with EB. METHODS: Electronic medical records (EMR) of patients with confirmed EB <30 years of age at time of initial encounter at Cincinnati Children's Hospital Medical Center between January 1, 2010 and September 30, 2020 were reviewed. Natural language processing software was used to categorize pubertal status of patients with EB as early, normal or delayed. BMD was measured by dual energy x-ray absorptiometry and categorized as low if height adjusted Z-score was <-2.0 using age, sex and race specific reference ranges. RESULTS: 29% of individuals with EB had low BMD with most cases occurring prior to 10 years of age. Of patients who reached adolescence, 23% failed to develop any signs of puberty in the normal range (before age 13 in females or 14 in males) and BMD Z-scores further declined in these individuals. CONCLUSION: Delayed puberty is an under-recognized comorbidity of individuals with EB, especially in those with recessive dystrophic EB, and can have a significant impact on BMD.

Pancreatitis in the Complex Care Population: Presentation, Incidence, and Severity.

OBJECTIVES: To describe the incidence and presentation of pancreatitis in Children with Medical Complexity (CMC) while evaluating severity of disease and outlining risk factors. METHODS: This was a retrospective chart review between January 2010 and December 2019 of patients seen in the complex care clinic at Nationwide Children's Hospital (NCH) and Cincinnati Children's Hospital Medical Center (CCHMC). Data collected included sex, underlying diagnosis, family history of pancreatitis, type of pancreatitis, signs/symptoms, abdominal imaging, severity of attack, and presence of various risk factors associated with pancreatitis. Severity and diagnosis of pancreatitis was determined based on North American Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria. RESULTS: One hundred and twelve patients from both institutions were included, 62% from NCH, median age 11.5 [interquartile range (IQR): 5-16 years], 50% male. Most patients were less than 18 years of age with a median age of 8 years (IQR: 4-13 years). Underlying diagnoses included seizures (67%), cerebral palsy/spastic quadriplegia (65%), diabetes (3.6%), and mitochondrial disease (3%). Majority of patients were found to have multiple underlying diagnoses (88%). Incidence of pancreatitis for both institutions was 336 of 100,000 patients/year which is significantly higher than the general pediatric population ( P < 0.0001). Majority of first episodes of pancreatitis were mild (82%) with abdominal pain as the predominant symptom (50%). Adult patients were more likely to have pancreatitis related to medication use than pediatric patients (70% vs 38%, respectively P = 0.007). CONCLUSIONS: Individuals in the CMC population at our institutions have a high incidence of pancreatitis with unique risk factors compared to the general pediatric/young adult populations.

An Initiative to Reduce Insulin-Related Adverse Drug Events in a Children's Hospital.

OBJECTIVES: Adverse drug events (ADEs) during hospitalization are common. Insulin-related events, specifically, are frequent and preventable. At a tertiary children's hospital, we sought to reduce insulin-related ADEs by decreasing the median event rate of hyper- and hypoglycemia over a 12-month period. METHODS: Using Lean 6 σ methodology, we instituted a house-wide process change from a single-order ordering process to a pro re nata (PRN) standing order process. The standardized process included parameters for administration and intervention, enabling physician and nursing providers to practice at top of licensure. Automated technology during dose calculation promoted patient safety during dual verification processes. Control charts tracked rates of insulin-related ADEs, defined as hyperglycemia (glucose level >250 mg/dL) or hypoglycemia (glucose level <65 mg/dL). Events were standardized according to use rates of insulin on each nursing unit. The rates of appropriately timed insulin doses (within 30 minutes of a blood sugar check) were assessed. RESULTS: Baseline median house-wide frequencies of hyperglycemic and hypoglycemic episodes were 55 and 6.9 events (per 100 rapid-acting insulin days), respectively. The median time to insulin administration was 32 minutes. The implementation of the PRN process reduced the median frequencies of hyperglycemic and hypoglycemic episodes to 45 and 3.8 events, respectively. The median time to insulin administration decreased to 18 minutes. CONCLUSIONS: A PRN ordering process and education decreased insulin-associated ADEs and the time to insulin dosing compared with single-entry processes. Engaging bedside providers was instrumental in reducing insulin-related ADEs. Strategies that decrease the time from patient assessment to drug administration should be studied for other high-risk drugs.

Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and health system cost. Matrix metalloproteinases (MMPs) are endopeptidases which degrade extracellular matrix proteins and increase activity of pro-inflammatory cytokines. Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity. Prior limited studies of MMPs and TIMPs have found some to be associated with development of SAP. The aim of this study was to further investigate the role of MMPs and TIMPs in detecting pediatric patients at risk for developing moderately severe AP or SAP. METHODS: Plasma samples were prospectively collected for patients <21 years of age presenting with AP between November 2015 and October 2019, along with healthy controls. Bead-based multiplex assays were utilized to test levels of 12 MMPs and TIMPs. RESULTS: Samples were collected from 7 subjects who developed SAP, 7 with moderately severe AP, 45 with mild AP and 44 healthy controls. MMP-9 (p = 0.04) and TIMP-1 (p = 0.01) levels were significantly higher in SAP patients. A multivariable logistic regression model using MMP-9 and TIMP-1 predicted SAP (AUROC 0.87, 95% CI 0.76-0.98). CONCLUSION: We have demonstrated that MMP9 and TIMP1 levels are increased at AP presentation in pediatric patients who developed SAP during the course of illness. Further studies are needed to validate the use of MMPs and TIMPs as predictive tools for development of SAP in pediatric pancreatitis.

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVE: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS: This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (<0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS: At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

Bone Health Outcomes at 1 Year after Hematopoietic Stem Cell Transplantation in a Heterogeneous Pediatric Population.

Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Less is known in children about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. In this study, we evaluated the incidence of fragility fractures in a large diverse pediatric HSCT recipient population and identified risk factors for both fracture and impaired BMD. We reviewed the records of 237 patients age ≤21 years at the time of transplantation who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was the incidence of fragility fractures, and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). DXA studies were available for analysis in 79 of 206 patients who were alive at 1 year after HSCT, and the median height-for-age adjusted z-score for spine BMD was 0.15. Among the 237 patients in this study, 25 (10.5%) had evidence of at least 1 fragility fracture on imaging. In the patients with at least 1 fragility fracture, 18 (72%) sustained spine fractures. The median time to fracture was 5.9 months after HSCT. Mortality at 1 year was proportionally higher, although not statistically significantly so (P = .11) in patients who had at least 1 fragility fracture (24%; 6 of 25) compared with patients without a fragility fracture (12%; 25 of 212). Vitamin D status at 1 year post-HSCT was sufficient (>20 ng/mL) in 94% of the patients assessed (160 of 171). There was no difference in the incidence of fracture between vitamin D-sufficient patients and vitamin D-insufficient patients (P = 1.0). The incidence of fracture was significantly higher in patients with graft-versus-host disease (GVHD) compared with those without GVHD (15% vs 6%; P = .02). There was no significant difference in fracture occurrence between patients who received reduced-intensity conditioning and those who received myeloablative conditioning. The cumulative glucocorticoid dose was significantly associated with fracture in patients exposed to glucocorticoids for >3 months (P = .03). The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking. Furthermore, there may have been additional, asymptomatic patients in our cohort with undetected, occult fractures. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention to spinal imaging in pediatric patients undergoing HSCT.

The effect of oral bisphosphonate therapy on vertebral morphometry and fractures in patients with Duchenne muscular dystrophy and glucocorticoid-induced osteoporosis.

INTRODUCTION/AIMS: Glucocorticoid-induced osteoporosis with vertebral fractures is frequent in patients with Duchenne muscular dystrophy (DMD). In this study, we evaluated the effects of oral bisphosphonate (BP) therapy on the prevalence and severity of vertebral fractures by vertebral morphometry assessment. METHODS: We reviewed the records and radiographs of patients with DMD who had been treated with oral BP (weekly alendronate) and had undergone routine spine radiographic monitoring for glucocorticoid-induced osteoporosis at Cincinnati Children's Hospital Medical Center between 2010 and 2017. Study outcomes were thoracic and lumbar vertebral fracture prevalence and severity, assessed by Genant semiquantitative grading of vertebral morphometry, for up to 5 years of treatment. RESULTS: Fifty-two patients (median age, 11.8 years; 88% prepubertal; 31% nonambulatory) had been treated with long-term glucocorticoids (median duration, 4.7 years at BP start). Most patients (75%) had mild vertebral height loss or fractures (Genant grade = 0 or 1) at baseline. The prevalence of vertebral fractures at each year of treatment was not statistically different from that at baseline (P = .08-1.00). Serial radiographs showed no longitudinal change in severity by Genant grade in most vertebrae (64%-80%). Improvement in vertebral fracture grade was observed in some patients. DISCUSSION: We observed stable prevalence of vertebral fractures and no change in severity by Genant grade in most vertebrae for up to 5 years of treatment. Oral BP may mitigate development or progression of vertebral fractures and be beneficial for secondary prevention of glucocorticoid-induced osteoporosis in this population.