Trout, Andrew T.

INTRODUCTION: Reliable biomarkers for the diagnosis of chronic pancreatitis (CP) and pancreatic fibrosis severity are lacking, hindering effective treatment and management. Histologic fibrosis is a hallmark of late-stage CP, but noninvasive methods to evaluate fibrosis progression are limited. We used urine proteomics to discover biomarkers that identify patients with CP and predict fibrosis severity. METHODS: We performed a cross-sectional study of 130 total subjects (CP n = 50) selected based on clinical criteria in a tertiary care setting. Urine proteomics samples were quantified using data-independent acquisition mass spectrometry. Differential biomarker candidates were identified with false discovery rate-corrected pairwise comparisons. These proteins were validated with an independent paired urine and plasma sample cohort (n = 36). Machine learning was used to develop a protein panel that predicted Ammann scores for patients with histologic fibrosis. RESULTS: We found 34 proteins consistently differentially expressed between CP and controls in pairwise false discovery rate-controlled tests. Of these, 25 urine proteins outperformed 19 previously suggested CP blood-based biomarkers in an independent validation cohort. Isocitrate dehydrogenase (IDH1), calcyphosin (CAPS), synuclein gamma (SNCG), and protein S100-P (S100P) all produced receiver operator curve area under the curve values >0.95, while the best plasma marker was interleukin 2 receptor subunit alpha (receiver operator curve area under the curve = 0.80). A 12-protein panel of identified markers predicted fibrosis severity with a linear correlation R 2 value of 0.61. DISCUSSION: We identified a panel of proteins that may diagnose CP in children and developed a model to predict pancreatic fibrosis severity, offering promising tools for improving diagnostics and patient care.

AbstractPrimary pancreatic tumors in children are rare with an overall age‐adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm, followed by pancreatoblastoma. This paper describes relevant imaging modalities and presents consensus‐based recommendations for imaging at diagnosis and follow‐up.

Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm followed by pancreatoblastoma. This manuscript describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow up.

PurposeChemical shift‐encoded MRI (CSE‐MRI) is well‐established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature‐controlled experiments, and a multi‐center, multi‐vendor phantom study.Theory and MethodsA technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude‐, complex‐, and hybrid‐based CSE‐MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine‐site multi‐vendor phantom study and compared to temperature‐corrected PDFF estimation using an a priori guess for ambient room temperature.ResultsSimulations and temperature‐controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude‐based CSE‐MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction.ConclusionCorrection for temperature reduces temperature‐related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude‐based CSE‐MRI, even without a priori information about the temperature.

Abstract Vertebroplasty alters spinal biomechanics and may lead to incident vertebral fractures. The endplate localization of prevalent and incident fractures was evaluated in 86 patients. In the absence of vertebroplasty, superior endplate fractures predominate. After the procedure, inferior endplate fractures are disproportionately common in adjacent vertebrae immediately above the treated level, potentially supporting a causative relationship between vertebroplasty and incident fractures. Introduction: To determine retrospectively whether new-onset fractures after vertebroplasty tend to cluster in the endplate immediately adjacent to the cemented vertebra. Materials and Methods: Institutional Review Board approval and patient consent for use the use of medical records were obtained for this study. We performed a retrospective review of patients with new (incident) vertebral fractures after vertebroplasty. The median age for these patients was 72.5 years, and 58 (67.4%) were women. Fractures were diagnosed on the basis of MRI or bone scan and were catalogued based on their location within the vertebral body (superior endplate, inferior endplate, or holo-vertebral). χ2 and generalized estimating equation (GEE) analyses were used to compare the distribution of fracture subtypes among pre-existing (prevalent) and incident fractures. Results: The patients had 313 prevalent osteoporotic vertebral fractures and were treated at 137 vertebral levels. Among prevalent fractures, superior endplate fractures predominated (57% superior, 11% inferior; p < 0.0001). After vertebroplasty, 186 incident fractures developed in these 86 patients. Seventy-seven (41%) of these incident fractures occurred adjacent to treated vertebrae. Nonadjacent, incident fractures, like prevalent fractures, occurred predominantly along superior endplate. Incident fractures immediately above treated levels, however, localized disproportionately to the inferior endplate (30% superior, 57% inferior; p < 0.0001). Conclusions: There are an increased number of inferior endplate fractures of the vertebral body immediately cephalad to the treated level.