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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.

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022 by the American Diabetes Association.)

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., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: To assess the degree, duration, mean absolute relative difference (MARD), and error analysis of discrepant values per continuous glucose monitoring (CGM) systems after hydroxyurea (HU) administration. Research Design and Methods: Inpatient glucometer and CGM data from 16 total pancreatectomy/islet autotransplantation patients using Dexcom Professional G4 and 12 patients using Dexcom G6 were analyzed after daily dosing with HU. Timing of HU dosing and median of 9.5 days of sensor and glucometer values were assessed per patient. Results: A large positive elevation of sensor readings was identified after HU dosing. The greatest discrepancy between glucometer and sensor readings occurred 0.5-2 h after HU administration [G4 (mean 3.0 mmol/L, median 2.4 mmol/L, MARD 55%), G6 (mean 4.2 mmol/L, median 4.6 mmol/L, MARD 91%)]. The discrepancy was <1.1 mmol/L, mean (-0.5 mmol/L) and median (-0.5 mmol/L), MARD 14% (G4) and <1.1 mmol/L, mean (0.3 mmol/L) and median (0.3 mmol/L), MARD 17% (G6), by 6 h after administration. Error analysis with the G6 system found 94% of pairs in clinically acceptable range by 6-9 h after HU administration. Aspirin, also given once daily, did not result in glucose value discrepancy with the G6 system but variability was observed with the G4 system. Conclusions: There was marked elevation of sensor glucose readings compared with glucometer values [up to 13.9 mmol/L (G4), 13 mmol/L (G6)] from 0.5 to 6 h after HU administration. It is important to counsel a patient using a Dexcom CGM system and HU therapy on this finding and to advise reliance on glucometer testing for accurate glucose assessment up to 6-9 h after HU administration.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy ( n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44-6.66 mmol/L (80-120 mg/dL)), hypoglycemia (<3.33 mmol/L (<60 mg/dL)) and hyperglycemia (>7.77 mmol/L (>140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin ( p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay.

Hyperglycemia is detrimental to postoperative islet cell survival in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). This makes continuous glucose monitoring (CGM) a useful management tool. We evaluated the accuracy of the Dexcom G6 CGM in pediatric intensive care unit patients following TPIAT. Twenty-five patients who underwent TPIAT had Dexcom G6 glucose values compared to paired serum glucose values. All paired glucose samples were obtained within 5 minutes of each other during the first seven days post TPIAT. Data were evaluated using mean absolute difference (MAD), mean absolute relative difference (MARD), %20/20, %15/15 accuracy, and Clarke Error Grid analysis. Exclusions included analysis during the CGM "warm-up" period and hydroxyurea administration (known drug interference). A total of 183 time-matched samples were reviewed during postoperative days 2-7. MAD was 14.7 mg/dL and MARD was 13.4%, with values of 15.2%, 14.0%, 12.1%, 11.4%, 13.2% and 14.1% at days 2, 3, 4, 5, 6 and 7, respectively. Dexcom G6 had a %20/20 accuracy of 78%, and a %15/15 accuracy of 64%. Clarke Error Grid analysis showed that 77% of time-matched values were clinically accurate, and 100% were clinically acceptable. The Dexcom G6 CGM may be an accurate tool producing clinically acceptable values to make reliable clinical decisions in the immediate post-TPIAT period.

Objectives: Pancreas divisum (PD) is a risk factor in children for the development of acute pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (mPES) may be of clinical benefit, however, the clinical outcomes from endotherapy remain unclear. We sought to review the outcomes and safety of therapeutic ERCP in children with PD., Methods: We performed a retrospective chart of children with PD who underwent an ERCP between February 2012 and December 2018. Pertinent patient, clinical and procedure information was collected including procedure-related adverse events. A follow-up questionnaire of the parent was conducted to determine the clinical impact from endotherapy., Results: Fifty-eight ERCPs were performed in 27 patients (14 boys; mean age: 9.7 years, range 2-19) with PD. All patients underwent a successful mPES. A genetic variant was identified in 19/26 (73%) tested patients. Post-ERCP pancreatitis (PEP) was the only observed adverse event; 21% (12/58). Median follow-up interval from first ERCP intervention to questionnaire completion was 31.5 months (range: 4--72 months). Of the 20 questionnaire responders, 13 reported clinical improvement from endotherapy., Conclusions: The majority of children from our PD cohort possessed at least 1 genetic variant. Most questionnaire responders had a favorable response to endotherapy. PEP rate was comparable with that of prior reports in adult patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The aim of the study was to determine whether patients with eosinophilic esophagitis (EoE) have lower bone mineral density (BMD) than expected and if bone deficits are more pronounced in subgroups of patients according to comorbidities (atopic disease and joint hypermobility) or treatments (dietary restriction, medication exposure)., Study Design: Retrospective chart review was performed to obtain clinical data, including length of diagnosis, comorbidities, and methods of treatment for patients with EoE ages 3 to 21 years who had a lumbar spine dual-energy x-ray absorptiometry scan performed between 2014 and 2017. BMD was standardized by calculation of age, sex, and race-specific z scores., Results: A total of 269 patients met study criteria. The mean BMD z score (-0.55, 95% confidence interval: -0.68, -0.42) was lower than expected (P < 0.0001), and the prevalence of low BMD z score (≤-2.0) was higher than expected (8.5%, 95% confidence interval: 5.2%-11.9%, P < 0.0001). In multivariable regression models, BMD z scores were -0.27 lower among those following an elimination diet and -0.65 lower among those with any lifetime use of a proton pump inhibitor (93% of the sample). There was no association with swallowed steroid use., Conclusions: In our sample, pediatric patients with EoE had a slightly lower BMD z score compared to peers, and the prevalence of low BMD was higher than expected. Taken cautiously given the limitations of our sample, risk factors for bone deficits included any lifetime use of proton pump inhibitor and a restrictive elimination diet, but not swallowed steroid use. Larger prospective studies are needed to better characterize risk factors for low BMD to help inform screening, selection of therapies, and provide appropriate anticipatory guidance for patients with EoE.

This is the first report on safety and efficacy of intravenous bisphosphonates (IV BP) for treatment of disuse osteoporosis and low bone mineral density (BMD) in children with spinal muscular atrophy (SMA). IV BP appears to be safe and effective in fracture rate reduction. However, caution is necessary given the occurrence of an atypical femur fracture., Introduction: Children with SMA are at high risk for fragility fractures and low BMD. IV BP have been used for treatment of disuse osteoporosis in pediatrics. However, safety and efficacy of IV BP in the SMA population has not been reported., Methods: Retrospective chart review of IV BP for treatment of disuse osteoporosis and low BMD in children with SMA at a tertiary pediatric center from 2010 to 2018 RESULTS: Eight patients (50% female; 75% SMA type 1; median age at first infusion 6.7 years) receiving a total of 39 infusions (54% pamidronate, 46% zoledronic acid) were included in this report. Acute phase reactions occurred following 38% and 3% of initial and subsequent infusions, respectively. BMD trended toward improvement at 1 year post-treatment. Among six patients who had > 2 years of follow-up, fracture rate decreased from 1.4 to 0.1 fracture/year. An atypical femur fracture was observed in one patient., Conclusion: These findings suggest that in children with SMA, IV BP therapy appears to be safe with minimal acute side effects and effective to reduce fracture rate. Caution is still needed given the occurrence of an atypical femur fracture in SMA population.

Introduction: Intravenous bisphosphonates (IV BP) have been used to treat children with osteoporosis for many years. Favorable side effect profile and improvements in bone mineral density (BMD) have been demonstrated in patients with osteogenesis imperfecta (OI), a primary form of osteoporosis in pediatrics. Less is known about the safety of IV BP in children with secondary osteoporosis or glucocorticoid-induced osteoporosis (GIO). We aimed to determine the prevalence of both acute and long-term side effects and assess the efficacy of IV BP treatment to increase bone mineral density in pediatric patients with varying presentations of compromised bone health., Methods: We conducted a retrospective chart review of pediatric patients (<21 years old) treated for osteoporosis with intravenous pamidronate (PAM) or zoledronic acid (ZA) at Cincinnati Children's Hospital Medical Center from 2010 to 2017. Patient demographics, diagnosis, infusion type and dose, acute phase reactions (APR), electrolyte abnormalities, and bone density measurements were collected from the electronic medical records. Diagnoses were grouped into 3 categories: primary osteoporosis, secondary osteoporosis, and GIO. Descriptive characteristics and adverse events were compared among categories. Change in bone mineral density (BMD) over time was compared among groups., Results: 123 patients (56% male) received 942 infusions (83% PAM and 17% ZA). APR was reported in 7% of all infusions and more common in secondary osteoporosis (16%, p < 0.0001). There was a higher percentage of acute adverse events after the first infusion (27% vs 5%, p < 0.0001). Hypocalcemia following IV BP infusions occurred in 7% (27/379) of infusions and was significantly associated with ZA use (p = 0.04). Severity of hypocalcemia was generally mild, requiring intravenous calcium in 3% (13/379) of infusions. Hypophosphatemia occurred frequently, however rarely required intravenous supplementation. In 468 patient years of IV BP exposure, there were no reports of osteonecrosis of the jaw (ONJ) nor atypical femoral fracture (AFF). Lumbar spine (LS) aBMD Z-score 1 year after IV BP initiation increased overall for all groups (p < 0.0001) but did not significantly differ for those who did or did not fracture following IV BP treatment., Conclusions: APR due to intravenous BP treatment for pediatric osteoporosis were infrequent and generally mild. APR were more likely to occur in patients with secondary osteoporosis, a group who may require closer monitoring. A higher proportion of hypophosphatemia occurred in the patients with GIO. Long-term serious adverse events including ONJ and AFF were not identified in our patient population. LS aBMD Z-score increased following initiation of IV BP. However, the change in BMD was not associated with risk of fracture during the follow-up interval. These data provide reassurance and suggest that IV BP can be safely used in pediatric patients with osteoporosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The progression of β-cell function in newly diagnosed adolescents with type 2 diabetes mellitus (T2DM) is not well documented. We hypothesized that at the time of diagnosis with T2DM, adolescents would have impaired β-cell function as demonstrated by the disposition index (calculated as: insulin secretion adjusted for insulin sensitivity), and this would be followed by a rapid decline of function despite standard medical management., Methods: Thirty-nine adolescents with recently diagnosed T2DM and 32 obese adolescent controls with normal glucose tolerance had acute insulin response to glucose, homeostatic model assessment of insulin resistance, and disposition index measured serially over 2 years., Results: In the adolescent T2DM group, fasting glucose increased over 2 years (p = .04), while DI was impaired at baseline and showed an overall relative decline of 25% per year. The mean Hemoglobin A 1c remained below 8% (64 mmol/mol). Differences were observed between the T2DM and control adolescents in the way DI changed over time (p = .02)., Conclusions: β-cell function in adolescents with recently diagnosed T2DM was impaired with no improvement of β-cell function over the 2 years of study despite stable Hemoglobin A 1c , body mass index markers of insulin sensitivity, and standard treatment of hyperglycemia., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Aim was to determine whether CGM could accurately monitor blood glucose concentration in the immediate postoperative period following pancreatectomy with IAT in children. CGM was used in nine patients undergoing IAT at our institution between April 2015 and September 2016 (eight total pancreatectomy and one subtotal pancreatectomy). MAD and MARD of CGM values compared to time-matched serum blood glucose were calculated during the first 5 days of ICU admission. Goal range was defined as 70-140 mg/dL and out-of-range was >140 mg/dL or <70 mg/dL. Of 89 time-matched measures found, 75% of CGM values were within 15 mg/dL, and 51% were within 10 mg/dL, compared to serum glucose. MAD was 11.6 mg/dL, and MARD was 10.6%. CGM values did not differ from serum glucose (P=.74). By Clarke error grid analysis, 100% of paired values were in clinically acceptable zones. By surveillance error grid analysis, 96% of paired values were within clinically acceptable agreement. CGM is a reliable tool in monitoring glycemic control in the immediate postoperative period following pancreatectomy with IAT in children., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients with Spinal Muscular Atrophy (SMA) are at risk for poor bone health. The prevalence of fractures, low areal bone mineral density (aBMD; Z-score ≤-2.0) of the lateral distal femur and of osteoporosis by SMA subtype is not known. We aimed to describe the natural history of bone health in patients with SMA prior to bisphosphonate treatment. We reviewed data from 85 eligible patients with SMA ages 12 months to 18 years, seen at a single institution between January 2005 and July 2016. Fracture history was reported at annual clinic visits. aBMD was obtained from dual energy x-ray absorptiometry scans of the lumbar spine, total body, and lateral distal femur. 85% of patients had aBMD Z-scores ≤-2.0 SD and were progressively lower with worsening SMA severity. Longitudinal aBMD Z-scores of the lateral distal femur decreased with age. Fractures occurred in 38% (32/85) of patients with the femur being the most common location (25 of 57 fractures). Thirteen percent of patients fulfilled criteria for osteoporosis. Low aBMD and femur fractures are highly prevalent in all SMA subtypes from a young age; however, few patients met the criteria for osteoporosis. Poor bone health may be an under-recognized comorbidity of SMA., (Copyright © 2017. Published by Elsevier B.V.)

Objectives: Exocrine pancreatic insufficiency (EPI) can have a significant impact on a child's growth and nutrition. Our aim was to evaluate the utility of direct endoscopic pancreatic function testing (ePFT) in pediatrics., Methods: A single-center retrospective chart review was performed of children who underwent ePFT from December 2007 through February 2015. Endoscopic pancreatic function testings were performed by 1 of 2 methods: (1) intravenous cholecystokinin, followed by the collection of a single duodenal aspirate at 10 minutes, or (2) intravenous cholecystokinin or secretin, followed by the collection of 3 duodenal aspirates at a 5, 10, and 15 minutes. Samples were tested for pH and enzyme activities., Results: A total of 508 ePFTs were performed (481 single-sample tests, 27 multiple-sample tests). Based on the multiple-sample group, enzyme levels for chymotrypsin, amylase, and lipase peaked at 5 minutes, followed by a decrease in activity over time. Exocrine pancreatic sufficiency was identified in 373 (73.4%) and EPI in 93 (18.3%). Exocrine pancreatic sufficiency analysis found all pancreatic enzyme activities significantly increase with age: trypsin, chymotrypsin, amylase, and lipase, (P < 0.05)., Conclusions: Endoscopic pancreatic function testing can be used in the evaluation of EPI in children. Normative data suggest that pancreatic enzyme activities mature with age.

Objective: To establish the prevalence of adrenal insufficiency (AI) in children with eosinophilic esophagitis treated with swallowed fluticasone propionate (FP) or budesonide., Study Design: Children treated with FP or budesonide for ≥ 6 months underwent a low-dose adrenocorticotropin stimulation test. Patients using systemic, inhaled, intranasal, or topical glucocorticoids were excluded. The primary outcome is AI, defined as peak serum cortisol <18 μg/dL (≤ 495 nmol/L)., Results: Of 58 patients (81% male), 67% were on FP (median age 13.7 years [range 4.3-19.1], dose 1320 μg/d [440-1760], treatment duration 4.0 years [0.6-13.5]). Thirty-three percent were on budesonide (median age 10.7 years [range 3.2-17.2], dose 1000 μg/d [500-2000], treatment duration 3.4 years [0.6-7.7]). The overall prevalence of abnormal peak cortisol response (≤ 20 μg/dL) was 15% (95% CI 6%-25%) (indeterminate [18-20 μg/dL] 5% [n = 3] vs AI [<18 μg/dL] 10% [n = 6]). All patients on budesonide had a normal response vs only 77% of patients on FP (P = .02), all of whom were taking FP at a dose >440 μg/d., Conclusions: AI was present in 10% of children treated with swallowed glucocorticoids for ≥ 6 months and was found only in those treated with FP >440 μg/d. We recommend low-dose adrenocorticotropin stimulation testing in children treated long term with high dose FP to allow early detection of AI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Biliary pancreatitis (BP) is common in adults and children. Current standard of care is to perform a cholecystectomy (CCE) to decrease the recurrence risk of pancreatitis. Controversy exists as to the timing of surgery, early versus delayed surgical intervention. Adult literature suggests a greater benefit of early CCE. Comparatively, there is limited pediatric literature as to the optimal timing of a CCE in children. We report a retrospective case series of children with BP who underwent early versus late CCE., Methods: A retrospective chart review was performed of children with BP for a period of 45 months. Reviewed information included patient demographics, timing of CCE, and the occurrence of adverse events preceding or following surgical intervention. Early CCE was defined as surgery during the index admission; late CCE was defined as surgery during a subsequent admission., Results: Nineteen children and adolescents (17 girls) were identified to have had BP with a subsequent CCE. Cholecystectomy was performed early in 9 patients with no adverse events. Ten patients had delayed surgery with 4 occurrences of adverse clinical events (recurrence of pancreatitis or biliary colic abdominal pain) while awaiting their CCE., Conclusions: Adverse biliary-related events occur at a higher rate in children with mild BP who undergo a delayed CCE when compared to early CCE performance. Early CCE is safe to perform in children with mild BP.

Objective: To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents., Study Design: Obese adolescents with normal glucose tolerance (n = 41) were studied longitudinally over the course of 4 years with serial measure of the acute insulin response to glucose (AIRg) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with the homeostatic model assessment of insulin resistance (HOMA-IR), the disposition index (DI) computed as AIRg × 1/HOMA-IR, and intravenous glucose tolerance estimated as the glucose disappearance constant., Results: Four adolescents developed diabetes mellitus (DM) during the study, and the rest of the cohort remained nondiabetic. Baseline PI exceeded the IQR of the nondiabetic group in 3 of 4 subjects with DM, and all had >85% reduction from baseline AIRg, and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study, but these changes paralleled those for the nondiabetic group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis but was comparable with baseline in the other 3. The DI and glucose disappearance constant of the subjects with DM was less than the 10th percentile of the nondiabetic group before and after diagnosis., Conclusion: Conversion from normal glucose tolerance to T2DM in adolescents can occur rapidly, and the onset of T2DM is heralded by a substantial decrease in AIRg and DI, as well as increased release of PI. These results support loss of β-cell function as the proximate step in the development of T2DM in this age group., (Copyright © 2015 Elsevier Inc. All rights reserved.)