Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database

ObjectivesThe relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP.MethodsSubjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features.ResultsWe included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]).ConclusionIn this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.     

Surface-active phospholipid as the lubricating component of lubricin

To resolve the apparent conflict between a lubricating glycoprotein, 'lubricin', as the active ingredient in synovial fluid (SF) and surface- active phospholipid (SAPL) present in SF (and adsorbed to articular cartilage) as the boundary lubricant reducing friction to such low physiological levels, lubricin was isolated from bovine SF following the original procedure of Swann et al. (Arthritis Rheum 1981;24:22-30). Analysis of the lipid extract by thin-layer chromatography and phosphorus determination demonstrated a phospholipid component of 11.1 +/- 1.7% (N = 5) which corresponds very closely to the 9.2-13.0% of lubricin which had hitherto remained unidentified and which has previously been shown to be transferable to the articular surface to impart lubrication. These results would appear to resolve any theoretical conflict in that lubricin is, indeed, an active ingredient within SF. Yet, as a large water-soluble molecule, it really functions as a carrier for the highly insoluble SAPL which it deposits on the articular surface as the oligolamellar layer visualized in previous studies. However, it is this deposited SAPL, rather than lubricin, which actually lubricates.      

大学生饮酒模式调查分析

目的分析影响大学生饮酒模式的因素,针对饮酒教育及酒精政策提出建议。方法采用整群抽样方法,选择来自北京和郑州的530名大学生完成有效问卷调查。采用 Epidata 录入数据,SAS 12.0和 R 2.7.2进行数据描述和分析。结果74.5%的大学生在过去1年内饮过酒,啤酒是饮酒者的主要选择（85.9%）,餐馆和家里是饮酒比较频繁的场所,饮用酒多来自同学/朋友及家庭成员提供,25.3%饮酒者并无特别原因饮酒,各有约1/5的饮酒者是出于社交目的或喜欢饮酒的感觉。认为“饮酒有助于社交暠或“饮酒促进交流暠者、父母及同学/朋友饮酒者、来自农村地区或小城镇者及吸烟者更容易发生饮酒行为（均 P 〈0.05）,男生大学生、规律饮酒者更容易遭遇强迫劝酒场面、更易发生醉酒（均 P 〈0.05）。超过一半饮酒者出现酒后脸红、肌肉软弱无力等生理反应,饮酒对被调查大学生产生的社会心理影响依次是记忆丧失（23.9%）、宿醉（14.6%）、做了后悔的事（低于10%）等。结论目前大学生仍保持着一种低风险饮酒模式。大学生饮酒教育应提供关于饮酒利弊的科学信息,使其对饮酒保持一种现实的期望。应制定针对性酒精政策和教育鼓励和支持低风险且满足社交功能的饮酒模式,控制高风险饮酒模式。     

Tumor mutational burden and purity adjustment before and after treatment with temozolomide in 27 paired samples of glioblastoma: a prospective study

Treatment of glioblastoma (GBM) remains a challenging task, with limited treatment options, none offering a cure. Immune therapy has proven effective across different cancers with remarkable response rates. Tumor mutational burden (TMB) is a marker of response, but technical and methodological differences in TMB estimates have made a proper assessment and comparison challenging. Here, we analyzed a prospective collection of paired samples from 35 patients with newly diagnosed GBM, all of whom were wild‐type (WT) for isocitrate dehydrogenase, before and after treatment with radiotherapy and temozolomide. Seven patients (20%) had O6‐methylguanine‐DNA methyltransferase‐methylated tumors. Six patients (17%) had two relapse surgeries, and tissue from all three surgeries was collected. We found that accurate evaluation of TMB was confounded by high variability in the cancer cell fraction of relapse samples. To ameliorate this, we developed a model to adjust for tumor purity based on the relative density distribution of variant allele frequencies in each primary–relapse pair. Additionally, we examined the mutation spectra of shared and private mutations. After tumor purity adjustment, we found TMB comparison reliable in tumors with tumor purity between 15% and 40%, resulting in 27/35 patients (77.1%). TMB remained unchanged from 0.65 mutations per megabase (Mb) to 0.67/Mb before and after treatment, respectively. Examination of the mutation spectra revealed a dominance of C > T transitions at CpG sites in both shared and relapse‐private mutations, consistent with cytosine deamination and the clock‐like mutational signature 1. We present and apply a cellularity correction approach that enables more accurate assessment of TMB in paired tumor samples. We did not find a significant increase in TMB after correcting for cancer cell fraction. Our study raises significant concerns when determining TMB. Although a small sample size, corrected TMB can have a clinical significance when stratifying patients to experimental treatment, for example, immune checkpoint therapy.     

Glycine‐modified growth hormone secretagogues identified in seized doping material

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography–high resolution mass spectrometry (LC–HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP‐2 (Pralmorelin), GHRP‐6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1–29), which can be used as performance‐enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N‐terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.