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OBJECTIVES: We sought to evaluate associations between Magnetic Resonance Imaging (MRI) findings, exocrine pancreatic insufficiency (EPI) and endocrine insufficiency (prediabetes or diabetes) in children. METHODS: This was a retrospective study that included patients<21 years of age who underwent MRI and endoscopic pancreatic function testing (ePFT; reference standard for pancreatic exocrine function) within 3 months. MRI variables included pancreas parenchymal volume, secreted fluid volume in response to secretin, and T1 relaxation time. Data were analyzed for the full sample as well as the subset without acute pancreatitis (AP) at the time of imaging. RESULTS: Of 72 patients, 56% (40/72) were female with median age 11.4 years. A 5 mL decrease in pancreas parenchymal volume was associated with increased odds of exocrine pancreatic dysfunction by both ePFT (OR = 1.16, p = 0.02 full sample; OR = 1.29, p = 0.01 no-AP subset), and fecal elastase (OR = 1.16, p = 0.04 full sample; OR = 1.23, p = 0.02 no-AP subset). Pancreas parenchymal volume had an AUC 0.71 (95% CI: 0.59, 0.83) for predicting exocrine pancreatic dysfunction by ePFT and when combined with sex and presence of AP had an AUC of 0.82 (95% CI: 0.72, 0.92). Regarding endocrine function, decreased pancreas parenchymal volume was associated with increased odds of diabetes (OR = 1.16, p = 0.03), and T1 relaxation time predicted glycemic outcomes with an AUC 0.78 (95% CI: 0.55-1), 91% specificity and 73% sensitivity. CONCLUSIONS: Pancreas parenchymal volume is an MRI marker of exocrine and endocrine pancreatic dysfunction in children. A model including sex, AP, and pancreas volume best predicted exocrine status. T1 relaxation time is also an MRI marker of endocrine insufficiency.
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Diabetes Mellitus , Insuficiencia Pancreática Exocrina , Pancreatitis , Humanos , Femenino , Niño , Masculino , Pancreatitis/complicaciones , Estudios Retrospectivos , Enfermedad Aguda , Insuficiencia Pancreática Exocrina/diagnóstico por imagen , Insuficiencia Pancreática Exocrina/complicaciones , Páncreas/diagnóstico por imagen , Páncreas/patología , Imagen por Resonancia Magnética/métodos , Diabetes Mellitus/patologíaRESUMEN
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.
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Enfermedades Gastrointestinales , Pancreatitis , Niño , Humanos , Calidad de Vida , Estudios de Seguimiento , Prevalencia , Enfermedad Aguda , Pancreatitis/epidemiología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Padres , Encuestas y CuestionariosRESUMEN
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.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatitis , Humanos , Adulto Joven , Niño , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Estudios Retrospectivos , Estudios Prospectivos , Pancreatitis/epidemiología , Pancreatitis/etiología , Pancreatitis/prevención & control , Factores de Riesgo , Stents/efectos adversosRESUMEN
Promotion of C-C bonds is one of the key fundamental questions in the field of CO2 electroreduction. Much progress has occurred in developing bulk-derived Cu-based electrodes for CO2-to-multicarbons (CO2-to-C2+), especially in the widely studied class of high-surface-area "oxide-derived" copper. However, fundamental understanding into the structural characteristics responsible for efficient C-C formation is restricted by the intrinsic activity of these catalysts often being comparable to polycrystalline copper foil. By closely probing a Cu nanoparticle (NP) ensemble catalyst active for CO2-to-C2+, we show that bias-induced rapid fusion or "electrochemical scrambling" of Cu NPs creates disordered structures intrinsically active for low overpotential C2+ formation, exhibiting around sevenfold enhancement in C2+ turnover over crystalline Cu. Integrating ex situ, passivated ex situ, and in situ analyses reveals that the scrambled state exhibits several structural signatures: a distinct transition to single-crystal Cu2O cubes upon air exposure, low crystallinity upon passivation, and high mobility under bias. These findings suggest that disordered copper structures facilitate C-C bond formation from CO2 and that electrochemical nanocrystal scrambling is an avenue toward creating such catalysts.
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OBJECTIVE: To compare the efficacy of magnetic resonance cholangiopancreatography (MRCP) with endoscopy retrograde cholangiopancreatography (ERCP) in children for the identification of pancreatic duct variants. STUDY DESIGN: We identified children with a pancreatic duct variant by ERCP and separately queried our MRCP database for similar variants. Patients with a paired ERCP-MRCP were reviewed. Three radiologists blinded to the ERCP and MRCP findings were asked to independently review the MRCP studies and define the pancreatic duct anatomy. These blinded reviewers also graded the magnetic resonance imaging examination quality. RESULTS: Seventy-four pairs of ERCP-MRCP examinations were identified. Pancreas divisum was the most frequent ductal variant encountered (73%). There was fair agreement between the radiology reviewers as to the quality of the magnetic resonance imaging studies (Fleiss Kappa agreement). Concordance of the reviewers with that of the ERCP was moderate for the exact diagnosis, moderate for the presence of pancreas divisum, and fair for agreement on the presence of any duct variant. Concordance among reviewers was moderate for the exact diagnosis, moderate for normal vs abnormal, and substantial for the presence of pancreas divisum. CONCLUSIONS: Diagnostic limitations exist when comparing MRCP with the gold reference standard of ERCP, specifically when assessing for pancreatic duct variants in children.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Niño , Humanos , Imagen por Resonancia Magnética , Páncreas/diagnóstico por imagen , Conductos Pancreáticos/diagnóstico por imagen , Conductos Pancreáticos/patologíaRESUMEN
BACKGROUND: Hepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents. OBJECTIVES: To define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT. METHODS: In this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis. RESULTS: A total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2-25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2-40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96). CONCLUSION: Our study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.
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Hígado Graso , Trasplante de Islotes Pancreáticos , Adulto , Humanos , Niño , Adolescente , Femenino , Pancreatectomía/efectos adversos , Trasplante Autólogo , Estudios Prospectivos , Hígado Graso/diagnóstico por imagen , Hígado Graso/epidemiología , Hígado Graso/etiología , Imagen por Resonancia Magnética , Trasplante de Islotes Pancreáticos/efectos adversosRESUMEN
OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. CONCLUSIONS: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.
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Insuficiencia Pancreática Exocrina , Pancreatitis Crónica , Masculino , Niño , Humanos , Femenino , Enfermedad Aguda , Estudios Prospectivos , Recurrencia , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/epidemiología , Factores de Riesgo , Costo de Enfermedad , Insuficiencia Pancreática Exocrina/complicaciones , Dolor Abdominal/etiología , Dolor Abdominal/complicacionesRESUMEN
OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. RESULTS: The sample included 368 children (54.3% girls, mean ageâ=â12.7years, standard deviation [SD]â=â3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (Mâ=â38.5, SDâ=â16.0) was demonstrated while psychosocial HRQOL (Mâ=â49.5, SDâ=â10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (Bâ=â-10.28, Pâ <â0.001), episodic and constant abdominal pain (Bâ=â04.66, Pâ=â0.03; Bâ=â-13.25, Pâ<â0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271]â=â8.34, Pâ<â0.001). Borderline and clinical levels of emotional and behavioral problems (Bâ=â-10.18, Pâ<â0.001; Bâ=â-15.98, Pâ<â0.001), and constant pain (Bâ=â-4.46, Pâ<â0.001) were associated with low psychosocial HRQOL (F [9, 271]â=â17.18, Pâ<â0.001). CONCLUSIONS: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.
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Pancreatitis Crónica , Calidad de Vida , Dolor Abdominal/complicaciones , Niño , Femenino , Humanos , Masculino , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/terapia , Recurrencia , Factores de RiesgoRESUMEN
BACKGROUND: Studies systematically documenting US findings in children with acute pancreatitis are limited. Pancreas duct dilation is described as the most reliable finding of acute pancreatitis but this has not been rigorously examined in children. OBJECTIVE: To systematically document US findings in children with acute pancreatitis and to define interobserver agreement on those findings. MATERIALS AND METHODS: In this cross-sectional study we retrospectively reviewed images for all pediatric patients <18 years of age who had been prospectively enrolled in a registry of patients with index admissions for acute pancreatitis between March 2013 and July 2020. Two blinded observers (R1, R2) reviewed the first transabdominal US examination performed within 2 weeks of the pancreatitis attack for each patient. RESULTS: In 141 children, US was performed at a median of 1 day (interquartile range [IQR]: 0, 1) following acute attack. Thirty-three (23%, R1) and 38 (27%, R2) children had no abnormal findings on US. Peripancreatic edema was the most frequent finding documented by both reviewers (63% R1, 54% R2). The pancreatic duct was visible in only 35% of the children and was dilated in only 12% (R1) and 14% (R2). There was substantial to almost-perfect agreement between reviewers on findings of acute pancreatitis (κ=0.62-1), including duct visibility. CONCLUSION: Peripancreatic edema was the most frequently identified finding in children with acute pancreatitis, present in up to 63%, with almost perfect interobserver agreement. Duct dilation, cited in the literature as a reliable finding of acute pancreatitis, was rarely identified in our sample.
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Pancreatitis , Humanos , Niño , Pancreatitis/diagnóstico por imagen , Enfermedad Aguda , Estudios Retrospectivos , Estudios Transversales , Variaciones Dependientes del Observador , Páncreas/diagnóstico por imagenRESUMEN
OBJECTIVES: To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. STUDY DESIGN: Patients (<19 years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48 hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing. RESULTS: The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P = .02) and monocyte chemotactic protein-1 (MCP-1) (P = .02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P = .02) and MCP-1 (P = .007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CONCLUSIONS: This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis.
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Quimiocina CCL2/sangre , Interleucina-6/sangre , Pancreatitis/sangre , Receptores Inmunológicos/sangre , Adolescente , Biomarcadores/sangre , Nitrógeno de la Urea Sanguínea , Niño , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pancreatitis/diagnóstico , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: Predicting post-operative glycemic control in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) remains difficult. The purpose of our study was to explore preoperative imaging as a marker for islet yield and insulin need in pediatric patients undergoing TPIAT. METHODS: This was a retrospective study of children (≤18 years) who had undergone TPIAT between April 2015 and December 2018 and had 6 or more months of post-TPIAT follow-up. Patient specific factors (height, weight, body mass index [BMI], body surface area [BSA]) and pancreas volume segmented from the most recent pre-operative cross-sectional imaging were explored as predictors of islet yield (total islet counts [TIC], total islet equivalents [TIE], islet equivalents per kilogram body weight [IEQ/kg]) and glycemic control (total daily dose of insulin per kilogram body weight [TDD/kg], insulin independence) using Pearson correlation and univariate and multiple regression. RESULTS: Thirty-three patients, median age 13 years (IQR: 10-15 years), 64% female (21/33) met inclusion criteria. Nine patients (27%) achieved insulin independence at six months. Median TIE isolated was 310,000 (IQR: 200,000-460,000). Segmented pancreas volume was moderately associated with TIE (coefficient estimate = 0.34, p = 0.034). On multiple regression analysis, there was no significant predictor of insulin independence but number of attacks of pancreatitis (estimate = 0.024; p = 0.018) and segmented pancreas volume by body weight (estimate = -0.71; p < 0.001) were significant predictors of insulin TDD/kg. CONCLUSION: Pancreas volume segmented from pre-TPIAT imaging has predictive performance for post-TPIAT insulin need in children.
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Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/diagnóstico por imagen , Pancreatectomía , Adolescente , Peso Corporal , Niño , Femenino , Control Glucémico , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Páncreas/diagnóstico por imagen , Pancreatitis/etiología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Trasplante AutólogoRESUMEN
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.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatitis , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Humanos , Masculino , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Pancreatitis/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Drug induced acute pancreatitis (DIAP) as one of the acute pancreatitis (AP) risks factors is a poorly understood entity. The aim of the current study was to compare the characteristics and course of DIAP cases in children presenting with a first attack of AP. METHODS: Patients presenting with AP were included in a prospective database. We enrolled 165 AP patients that met criteria for inclusion. DIAP patients were included in that group if they were exposed to a drug known to be associated with AP and the rest were included in the non-drug induced-acute pancreatitis (non-DIAP) group. RESULTS: DIAP was observed in 40/165 (24%) of cases, 24 cases had drug-induced as the sole risk factor, and 16 had DIAP with another risk factor(s). The two groups were similar in intravenous fluid and feeding managements, but ERCP was more commonly performed in the non- DIAP group, 14 (11%), vs 0% in the DIAP group, p = 0.02. Moderately severe [9 (23%) vs 11 (9%)] and severe AP [7 (18%) vs 6 (5%)] were more commonly associated with DIAP than non- DIAP, p = 0.001. DIAP was more commonly associated with ICU stay, 10 (25%), vs 12 (10%), p = 0.01, hospital stay was longer in DIAP median (IQR) of 6 (3.9-11) days vs 3.3 (2-5.7) days in non- DIAP, p = 0.001. The DIAP group had a significantly higher proportion of comorbidities (p < 0.0001). CONCLUSIONS: DIAP is a leading risk factor for a first attack of AP in children and is associated with increased morbidity and severity of the pancreatitis course. DIAP warrants further investigation in future studies.
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Pancreatitis/inducido químicamente , Pancreatitis/epidemiología , Enfermedad Aguda , Adolescente , Niño , Colangiopancreatografia Retrógrada Endoscópica/estadística & datos numéricos , Comorbilidad , Cuidados Críticos , Estudios Transversales , Bases de Datos Factuales , Femenino , Humanos , Tiempo de Internación , Masculino , Pancreatitis/terapia , Factores de RiesgoRESUMEN
OBJECTIVES: The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor. STUDY DESIGN: Patients from 2 hospitals were included for the validation model (Children's Hospital of the King's Daughters and Children's National Hospital). Children's Hospital of the King's Daughters and Cincinnati Children's Hospital Medical Center data were used for analysis of BUN at 24 to 48âhours. RESULTS: The validation cohort included 73 patients; 22 (30%) with either severe or moderately severe AP, combined into the all severe AP (SAP) group. Patients with SAP had higher BUN (Pâ=â0.002) and lower albumin (Pâ=â0.005). Admission BUN was confirmed as a significant predictor (Pâ=â0.005) of SAP (area under the receiver operating characteristic [AUROC] 0.73, 95% confidence interval [CI] 0.60-0.86). Combining BUN (Pâ=â0.005) and albumin (Pâ=â0.004) resulted in better prediction for SAP (AUROC 0.83, 95% CI 0.72-0.94). A total of 176 AP patients were analyzed at 24-48âhours; 39 (22%) met criteria for SAP. Patients who developed SAP had a significantly higher BUN (Pâ<â0.001) after 24âhours. Elevated BUN levels within 24 to 48âhours were independently predictive of developing SAP (AUROC: 0.76, 95% CI: 0.66-0.85). Patients who developed SAP had a significantly smaller percentage decrease in BUN from admission to 24 to 48âhours (Pâ=â0.002). CONCLUSION: We externally validated the prior model with admission BUN levels and further optimized it by incorporating albumin. We also found that persistent elevation of BUN is associated with development of SAP. Our model can be used to risk stratify patients with AP on admission and again at 24 to 48âhours.
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Pancreatitis , Enfermedad Aguda , Biomarcadores , Nitrógeno de la Urea Sanguínea , Niño , Humanos , Pancreatitis/diagnóstico , Pronóstico , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
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%, Pâ=â0.0002). 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, Pâ=â0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, Pâ=â0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, Pâ<â0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, Pâ<â0.0001). 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 (Pâ<â0.0002 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.
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Dolor Abdominal/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Manejo del Dolor/estadística & datos numéricos , Pancreatitis/complicaciones , Aceptación de la Atención de Salud/estadística & datos numéricos , Dolor Abdominal/etiología , Enfermedad Aguda , Adolescente , Niño , Enfermedad Crónica , Estudios Transversales , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Oportunidad Relativa , Fenotipo , RecurrenciaRESUMEN
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 (Pâ<â0.0001); white race in Northeast (Pâ=â0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (Pâ=â0.0002 and Pâ=â0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (Pâ=â0.002). Gallstones were more frequent in South (Pâ=â0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (Pâ<â0.0001), 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 (Pâ<â0.0001). 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.
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Pancreatitis Crónica , Enfermedad Aguda , Niño , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/epidemiología , Pancreatitis Crónica/terapia , RecurrenciaRESUMEN
Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children's hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.
Asunto(s)
Hospitalización , Trasplante de Islotes Pancreáticos , Pancreatectomía , Resultado del Tratamiento , Enfermedad Aguda , Adolescente , Niño , Enfermedad Crónica , Femenino , Humanos , Masculino , Calidad de Vida , Recurrencia , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
OBJECTIVE: To determine the diagnostic sensitivity of serum biomarkers and imaging in the diagnosis of acute pancreatitis in children. STUDY DESIGN: This was a cross-sectional analysis of prospective registry data for children (age <21 years) whose first documented attack of acute pancreatitis occurred between March 2013 and October 2016 at a single-institution, tertiary care center. Main outcome was sensitivity of serum biomarkers and of imaging modalities, measured via descriptive statistics. RESULTS: In total, 112 children met the criteria for acute pancreatitis; 57 (51%) were male with a median age of 13.4 years (IQR 9.3-15.8 years). Serum amylase and lipase levels were obtained in 85 (76%) and 112 (100%) patients, respectively. Imaging was performed in 98 (88%) patients, with abdominal ultrasound (US) performed in 84 (75%) and computed tomography and/or magnetic resonance imaging performed in 46 (41%) patients. Fifty-three (47%) patients met all 3 diagnostic criteria (clinical, biochemical, and imaging) for acute pancreatitis. Laboratory testing had a 5.4% false-negative rate for acute pancreatitis. Serum lipase alone and amylase alone were 95% (95% CI 89%-98%) and 39% (95% CI 28%-50%) sensitive for acute pancreatitis, respectively. Imaging (any modality) was 61% sensitive (95% CI 51%-71%) for acute pancreatitis with a 34% false-negative rate. US alone was 52% (95% CI 41%-63%) sensitive for acute pancreatitis and computed tomography/magnetic resonance imaging was 78% (95% CI 63%-89%) sensitive. Combinations of diagnostic criteria performed no better than laboratory testing alone. CONCLUSIONS: The majority of children coming to medical attention with their first documented occurrence of acute pancreatitis have characteristic symptoms. Serum lipase is highly sensitive for the diagnosis of acute pancreatitis, and serum amylase is moderately sensitive. Imaging, particularly US, is only moderately sensitive, and cross-sectional imaging provides greater sensitivity for diagnosing acute pancreatitis.
Asunto(s)
Pancreatitis/sangre , Pancreatitis/diagnóstico por imagen , Enfermedad Aguda , Adolescente , Amilasas/sangre , Biomarcadores/metabolismo , Niño , Estudios Transversales , Reacciones Falso Negativas , Femenino , Estudios de Seguimiento , Humanos , Lipasa/sangre , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Sensibilidad y Especificidad , Atención Terciaria de Salud , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
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 (â¼7%). 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.
Asunto(s)
Páncreas/anomalías , Pancreatitis Crónica/fisiopatología , Pancreatitis/fisiopatología , Adolescente , Niño , Preescolar , Colangiopancreatografia Retrógrada Endoscópica , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Mutación , Conductos Pancreáticos/fisiopatología , Pancreatitis/genética , Pancreatitis/terapia , Pancreatitis Crónica/genética , Pancreatitis Crónica/terapia , Prevalencia , Recurrencia , Factores de Riesgo , Factores SexualesRESUMEN
OBJECTIVE: Functional pancreatic sphincter dysfunction (FPSD), previously characterized as pancreatic sphincter of Oddi dysfunction, is a rarely described cause of pancreatitis. Most studies are reported in adults with alcohol or smoking as confounders, which are uncommon risk factors in children. There are no tests to reliably diagnose FPSD in pediatrics and it is unclear to what degree this disorder contributes to childhood pancreatitis. METHODS: We conducted a literature review of the diagnostic and treatment approaches for FPSD, including unique challenges applicable to pediatrics. We identified best practices in the management of children with suspected FPSD and formed a consensus expert opinion. RESULTS: In children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), we recommend that other risk factors, specifically obstructive factors, be ruled out before considering FPSD as the underlying etiology. In children with ARP/CP, FPSD may be the etiology behind a persistently dilated pancreatic duct in the absence of an alternative obstructive process. Endoscopic retrograde cholangiopancreatography with sphincterotomy should be considered in a select group of children with ARP/CP when FPSD is highly suspected and other etiologies have been effectively ruled out. The family and patient should be thoroughly counseled regarding the risks and advantages of endoscopic intervention. Endoscopic retrograde cholangiopancreatography for suspected FPSD should be considered with caution in children with ARP/CP when pancreatic ductal dilatation is absent. CONCLUSIONS: Our consensus expert guidelines provide a uniform approach to the diagnosis and treatment of pediatric FPSD. Further research is necessary to determine the full contribution of FPSD to pediatric pancreatitis.