Tu1482 Common genetic susceptibility factors for recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in white patients are rare in black patients

Background: RAP and CP affects individuals of all demographics and geographic regions. Genetic factors increasing the susceptibility to pancreatitis in PRSS1, SPINK1, CFTR, and CTRC genes have been reported in many populations. Variations between people of European ancestry and populations from South or East Asia are known. Genetic testing for pancreatitis risks factors is now routinely performed in clinical practice, especially in patients with no obvious cause of pancreatitis. In the North American Pancreatitis Study (NAPS2), ~33% white CP patients were noted to have at least one, and ~10% had more than one variant in these genes. However there are no data on the prevalence of genetic mutations in black patients with pancreatitis. We tested the hypothesis that the genetic risk factors for pancreatitis are similar between black and white patients in the United States. Methods: Controls (n= 253) and subjects with RAP (n=45) or CP (n=230), who identified themselves as AfricanAmerican, enrolled prospectively in the multicenter NAPS2 studies from 2000-2014 were studied. Demographic and phenotypic information was obtained from structured questionnaires completed by the study subjects and the enrolling physician. A blood sample was obtained from each subject, and peripheral blood leukocyte DNA was isolated and purified for analysis. Genotyping for known variants in pancreatitis risk genes PRSS1, SPINK1, CFTR and CTRC was performed by a combination of direct sequencing, restriction fragment length polymorphism (RFLP), multiplex SNP genotyping assays and individual taqman genotyping assays. Results: Mean age of black controls, RAP and CP patients was 47.3±13.4, 45.7±13.6, and 51.9±10.6 years, and 38%, 38% and 63% of them were male, respectively. Physiciandefined alcohol etiology was present in 33% RAP and 77% CP patients. Of all the variants tested, only SPINK1 N34S was overrepresented in CP when compared with controls with borderline significance (CP 1.8%, controls 0%, p=0.051) (Table 1). Two CP patients had a CF mutation found to be specific for blacks with cystic fibrosis (3120+GtoA), one of whom was a compound heterozygote with a CF bicarbonate specific mutation (L967S) on the other allele. None of the pancreatitis patients had disease causing CTRC mutations. One CP patient was found to be carrying deleterious mutations in PRSS1 (R122H). Interestingly, 10/12 CP patients with CF mutations, and all 4 with SPINK1 mutation had physician-defined alcohol etiology. Discussion: Prevalence of mutations in susceptibility genes reported in Caucasians is infrequent among black patients. Genetic sequencing of known susceptibility genes and regulatory elements, plus appropriately powered genetic association studies are needed to understand the risks and mechanisms of pancreatitis in black patients

Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort studyResearch in context

Summary: Background: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort. Methods: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 μg/g; severe FE-1 level ≤100 μg/g; mild FE-1 101–200 μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398. Findings: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%). Interpretation: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening. Funding: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc

Polarimetric detection of non-radial oscillation modes in the β Cephei star β Crucis

Here we report the detection of polarization variations due to non-radial modes in the β Cephei star β Crucis. In so doing we confirm 40-year-old predictions of pulsation-induced polarization variability and its utility in asteroseismology for mode identification. In an approach suited to other β Cephei stars, we combine polarimetry with space-based photometry and archival spectroscopy to identify the dominant non-radial mode in polarimetry, f2, as mode degree ℓ = 3, azimuthal order m = −3 (in the m-convention of Dziembowski) and determine the stellar axis position angle as 25 (or 205) ± 8°. The rotation axis inclination to the line of sight was derived as ~46° from combined polarimetry and spectroscopy, facilitating identification of additional modes and allowing for asteroseismic modelling. This reveals a star of 14.5 ± 0.5 M⊙ and a convective core containing ~28% of its mass—making β Crucis the most massive star with an asteroseismic age

Serum biomarkers for chronic pancreatitis pain patterns

Objectives: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. Methods: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. Results: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. Discussion: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis