{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T19:40:32Z","timestamp":1772134832851,"version":"3.50.1"},"reference-count":24,"publisher":"BMJ","issue":"4","funder":[{"DOI":"10.13039\/100010898","name":"Edinburgh and Lothians Health Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010898","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2018,3,23]]},"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To obtain pilot data to evaluate the discriminatory power of biomarkers microRNA-122 (miR-122), high-mobility group box 1 (HMGB1), full-length keratin-18 (flk-18) and caspase-cleaved keratin-18 (cck-18) in plasma to identify potential biliary complications that may require acute intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>An observational biomarker cohort pilot study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>In a Scottish University teaching hospital for 12 months beginning on 3 September 2014.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Blood samples were collected from adults (\u226516 years old) referred with acute biliary-type symptoms who have presented to hospital within 24\u2009hours prior were recruited. Patients unable or refused to give informed consent or were transferred from a hospital outside the National Health Service regional trust were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary outcome measures<\/jats:title>\n                    <jats:p>To evaluate whether circulating miR-122, HMGB1, flk-18 and cck-18 can discriminate between people with and without gallstone disease and uncomplicated from complicated gallstone disease during the first 24\u2009hours of hospital admission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      300 patients were screened of which 285 patients were included. Plasma miR-122, cck-18 and flk-18 concentrations were increased in patients with gallstones compared with those without (miR-122: median: 2.89\u00d710\n                      <jats:sup>4<\/jats:sup>\n                      \u2009copies\/mL vs 0.90\u00d710\n                      <jats:sup>4<\/jats:sup>\n                      \u2009copies\/mL (p&lt;0.001); cck-18: 121.2\u2009U\/L vs 103.5\u2009U\/L (p=0.031); flk-18: 252.4\u2009U\/L vs 145.1\u2009U\/L (p&lt;0.001)). Uncomplicated gallstone disease was associated with higher miR-122 and cck-18 concentrations than complicated disease (miR-122: 5.72\u00d710\n                      <jats:sup>4<\/jats:sup>\n                      \u2009copies\/mL vs 2.26\u00d710\n                      <jats:sup>4<\/jats:sup>\n                      \u2009copies\/mL (p=0.023); cck-18: 139.7\u2009U\/L vs 113.6\u2009U\/L (p=0.047)). There was no significant difference in HMGB1 concentration between patients with and without gallstones (p=0.559). Separation between groups for all biomarkers was modest.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>miR-122 and keratin-18 plasma concentrations are elevated in patients with gallstones. However, this result is confounded by the association between biomarker concentrations, age and gender. In this pilot study, miR-122 and keratin-18 were not sufficiently discriminatory to be progressed as clinically useful biomarkers in this context.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-020061","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T09:20:21Z","timestamp":1524820821000},"page":"e020061","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of plasma microRNA-122, high-mobility group box 1 and keratin-18 concentrations to stratify acute gallstone disease: a pilot observational cohort study in an emergency general surgery unit"],"prefix":"10.1136","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-6532","authenticated-orcid":false,"given":"Francesca","family":"Th\u2019ng","sequence":"first","affiliation":[{"name":"Clinical Surgery, School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastiaan","family":"Vliegenthart","sequence":"additional","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D","family":"Lea","sequence":"additional","affiliation":[{"name":"MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J","family":"Antoine","sequence":"additional","affiliation":[{"name":"MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W","family":"Dear","sequence":"additional","affiliation":[{"name":"BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian J","family":"Mole","sequence":"additional","affiliation":[{"name":"Clinical Surgery, School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, UK"},{"name":"MRC Centre for Inflammation Research, Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh, UK"},{"name":"General Surgery, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"2025121601584370000_8.4.e020061.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69044-2"},{"key":"2025121601584370000_8.4.e020061.2","unstructured":"NHS Digital. Hospital Episode Statistics, Admitted Patient Care \u2013 England, 2011-12 [NS]. http:\/\/content.digital.nhs.uk\/searchcatalogue?productid=9161&q=gallbladder&infotype=0%2fOfficial+statistics&sort=Relevance&size=50&page=1#top (assessed 15 Jun 2017)."},{"key":"2025121601584370000_8.4.e020061.3","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1007\/s00464-013-2921-8","article-title":"Predictive factors for the diagnosis of severe acute cholecystitis in an emergency setting","volume":"27","author":"Borzellino","year":"2013","journal-title":"Surg Endosc"},{"key":"2025121601584370000_8.4.e020061.4","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12214"},{"key":"2025121601584370000_8.4.e020061.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.12.019"},{"key":"2025121601584370000_8.4.e020061.6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0073133","article-title":"Circulating liver-specific miR-122 as a novel potential biomarker for diagnosis of cholestatic liver injury","volume":"8","author":"Shifeng","year":"2013","journal-title":"PLoS One"},{"key":"2025121601584370000_8.4.e020061.7","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M004531"},{"key":"2025121601584370000_8.4.e020061.8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26427"},{"key":"2025121601584370000_8.4.e020061.9","unstructured":"Shi Z , Huang Q , Chen J , et al . Correlation of HMGB1 expression to progression and poor prognosis of adenocarcinoma and squamous cell\/adenosquamous carcinoma of gallbladder. Am J Transl Res 2015;7."},{"key":"2025121601584370000_8.4.e020061.10","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfp235"},{"key":"2025121601584370000_8.4.e020061.11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2002.01387.x"},{"key":"2025121601584370000_8.4.e020061.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2013.12.002"},{"key":"2025121601584370000_8.4.e020061.13","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.6.1379"},{"key":"2025121601584370000_8.4.e020061.14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0109618","article-title":"Serum levels of caspase-cleaved cytokeratin-18 and mortality are associated in severe septic patients: pilot study","volume":"9","author":"Lorente","year":"2014","journal-title":"PLoS One"},{"key":"2025121601584370000_8.4.e020061.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.09.023"},{"key":"2025121601584370000_8.4.e020061.16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1471-230X-8-14","article-title":"Total and caspase-cleaved cytokeratin 18 in chronic cholecystitis: a prospective study","volume":"8","author":"Simopoulos","year":"2008","journal-title":"BMC Gastroenterol"},{"key":"2025121601584370000_8.4.e020061.17","unstructured":"Qiagen. miRNeasy Serum\/Plasma Handbook: miRNeasy Serum\/Plasma Kit For purification of total RNA, including miRNA, from animal and human plasma and serum; miRNeasy Serum\/Plasma Spike-In Control; For normalization of miRNA purification from serum or plasma. Qiagen: Sample and Assay Technologies. 2012 http:\/\/www.qiagen.com\/aw\/resources\/download.aspx?id=710c0168-e408-408b-95af-91df5b5b1dd6&lang=en (assessed 15 Jun 2017)."},{"key":"2025121601584370000_8.4.e020061.18","unstructured":"Applied Biosystems. TaqMan Small RNA Assays (TaqMan microRNA assays; TaqMan siRNA assays; Custom TaqMan small RNA assays) Protocol. Applied Biosystems by Life Technologies. [Online]. 2011 https:\/\/tools.lifetechnologies.com\/content\/sfs\/manuals\/cms_042167.pdf (assessed 15 Jun 2017)."},{"key":"2025121601584370000_8.4.e020061.19","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"2025121601584370000_8.4.e020061.20","unstructured":"SHINO-TEST Corporation. HMGB1 ELISA Kit: Assay Principle. [Online]. 2017 http:\/\/www.hmgb1.net\/en\/products\/elisa.html (assessed 15 Jun 2017)."},{"key":"2025121601584370000_8.4.e020061.21","unstructured":"IBL International. HMGB1 ELISA. [Online]. 2011 http:\/\/novamedline.com\/downloads\/instructions\/en\/ST51011.pdf (assessed 15 Jun 2017)."},{"key":"2025121601584370000_8.4.e020061.22","unstructured":"PEVIVA Products. M65 ELISA. [Online]. 2014 http:\/\/diapharma.com\/wp-content\/uploads\/2017\/03\/P10020_Peviva_M65_ELISA_2014-12-19_Rev90097_insert.pdf (assessed 15 Jun 2017)."},{"key":"2025121601584370000_8.4.e020061.23","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26294"},{"key":"2025121601584370000_8.4.e020061.24","first-page":"241","article-title":"Cytokeratin 8 and 18 tissue expression in gallbladder mucosa of patients with cholelithiasis","volume":"62","author":"Kasprzak","year":"2011","journal-title":"Pol J Pathol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2017-020061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:58:57Z","timestamp":1765879137000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2017-020061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":24,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,27]]},"published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1136\/bmjopen-2017-020061"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2017-020061","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]}}}