Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein
Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute ne...
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| Veröffentlicht in: | PloS one 2016-04, Vol.11 (4), p.e0153645-e0153645 |
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| creator | Alqahtani, Mashael F Smith, Craig M Weiss, Scott L Dawson, Susan Ralay Ranaivo, Hantamalala Wainwright, Mark S |
| description | Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p |
| doi_str_mv | 10.1371/journal.pone.0153645 |
| format | Article |
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We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were significantly lower, while A-FaBP and mrProANP were higher in septic patients compared to the control groups. Each biomarker was associated with hospital morbidity and length of stay. These results suggest that these biomarkers merit further prospective study for the early identification of children with sepsis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0153645</identifier><identifier>PMID: 27089280</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adipocytes - metabolism ; Adolescent ; Adult ; Adults ; Analysis ; Atrial Natriuretic Factor - blood ; Atrial natriuretic peptide ; Bacterial infections ; Biological Assay ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Biomarkers - blood ; Case-Control Studies ; Child ; Child, Preschool ; Children ; Complications ; Diagnosis ; Diagnostic systems ; Fatty acid-binding protein ; Fatty Acid-Binding Proteins - blood ; Fatty acids ; Female ; Follow-Up Studies ; Gelatinase B ; Health aspects ; Humans ; Infant ; Infant, Newborn ; Inhibitors ; Innovations ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 9 - blood ; Medical diagnosis ; Medicine and Health Sciences ; Metal concentrations ; Metalloproteinase ; Morbidity ; Mortality ; Nervous System Diseases - blood ; Nervous System Diseases - diagnosis ; Neurological complications ; Observational studies ; Patient outcomes ; Patients ; Pediatrics ; Powder injection molding ; Prognosis ; Prospective Studies ; Protein binding ; Proteins ; Research and Analysis Methods ; Rodents ; Sepsis ; Sepsis - blood ; Sepsis - diagnosis ; Septic shock ; Severity of Illness Index ; Systematic review ; Tissue inhibitor of metalloproteinase 1 ; Tissue Inhibitor of Metalloproteinase-1 - blood</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0153645-e0153645</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Alqahtani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Alqahtani et al 2016 Alqahtani et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-cc9f4b602f4afe25d28ad07c5aa6afb0af8a71eafcc6a0846b3b141d7c3890d73</citedby><cites>FETCH-LOGICAL-c725t-cc9f4b602f4afe25d28ad07c5aa6afb0af8a71eafcc6a0846b3b141d7c3890d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835068/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835068/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27089280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ricci, Zaccaria</contributor><creatorcontrib>Alqahtani, Mashael F</creatorcontrib><creatorcontrib>Smith, Craig M</creatorcontrib><creatorcontrib>Weiss, Scott L</creatorcontrib><creatorcontrib>Dawson, Susan</creatorcontrib><creatorcontrib>Ralay Ranaivo, Hantamalala</creatorcontrib><creatorcontrib>Wainwright, Mark S</creatorcontrib><title>Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were significantly lower, while A-FaBP and mrProANP were higher in septic patients compared to the control groups. Each biomarker was associated with hospital morbidity and length of stay. These results suggest that these biomarkers merit further prospective study for the early identification of children with sepsis.</description><subject>Acids</subject><subject>Adipocytes - metabolism</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Adults</subject><subject>Analysis</subject><subject>Atrial Natriuretic Factor - blood</subject><subject>Atrial natriuretic peptide</subject><subject>Bacterial infections</subject><subject>Biological Assay</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Complications</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Fatty acid-binding protein</subject><subject>Fatty Acid-Binding Proteins - blood</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gelatinase B</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Inhibitors</subject><subject>Innovations</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 9 - blood</subject><subject>Medical diagnosis</subject><subject>Medicine and Health Sciences</subject><subject>Metal concentrations</subject><subject>Metalloproteinase</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Nervous System Diseases - blood</subject><subject>Nervous System Diseases - diagnosis</subject><subject>Neurological complications</subject><subject>Observational studies</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Powder injection molding</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Sepsis</subject><subject>Sepsis - blood</subject><subject>Sepsis - diagnosis</subject><subject>Septic shock</subject><subject>Severity of Illness Index</subject><subject>Systematic review</subject><subject>Tissue inhibitor of metalloproteinase 1</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - 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blood</topic><topic>Medical diagnosis</topic><topic>Medicine and Health Sciences</topic><topic>Metal concentrations</topic><topic>Metalloproteinase</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Nervous System Diseases - blood</topic><topic>Nervous System Diseases - diagnosis</topic><topic>Neurological complications</topic><topic>Observational studies</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Powder injection molding</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Protein binding</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Rodents</topic><topic>Sepsis</topic><topic>Sepsis - blood</topic><topic>Sepsis - diagnosis</topic><topic>Septic shock</topic><topic>Severity of Illness Index</topic><topic>Systematic review</topic><topic>Tissue inhibitor of metalloproteinase 1</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alqahtani, Mashael F</creatorcontrib><creatorcontrib>Smith, Craig M</creatorcontrib><creatorcontrib>Weiss, Scott L</creatorcontrib><creatorcontrib>Dawson, Susan</creatorcontrib><creatorcontrib>Ralay Ranaivo, Hantamalala</creatorcontrib><creatorcontrib>Wainwright, Mark S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alqahtani, Mashael F</au><au>Smith, Craig M</au><au>Weiss, Scott L</au><au>Dawson, Susan</au><au>Ralay Ranaivo, Hantamalala</au><au>Wainwright, Mark S</au><au>Ricci, Zaccaria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-18</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0153645</spage><epage>e0153645</epage><pages>e0153645-e0153645</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were significantly lower, while A-FaBP and mrProANP were higher in septic patients compared to the control groups. Each biomarker was associated with hospital morbidity and length of stay. These results suggest that these biomarkers merit further prospective study for the early identification of children with sepsis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27089280</pmid><doi>10.1371/journal.pone.0153645</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-04, Vol.11 (4), p.e0153645-e0153645 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1781800010 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Adipocytes - metabolism Adolescent Adult Adults Analysis Atrial Natriuretic Factor - blood Atrial natriuretic peptide Bacterial infections Biological Assay Biological markers Biology and Life Sciences Biomarkers Biomarkers - blood Case-Control Studies Child Child, Preschool Children Complications Diagnosis Diagnostic systems Fatty acid-binding protein Fatty Acid-Binding Proteins - blood Fatty acids Female Follow-Up Studies Gelatinase B Health aspects Humans Infant Infant, Newborn Inhibitors Innovations Male Matrix metalloproteinase Matrix Metalloproteinase 9 - blood Medical diagnosis Medicine and Health Sciences Metal concentrations Metalloproteinase Morbidity Mortality Nervous System Diseases - blood Nervous System Diseases - diagnosis Neurological complications Observational studies Patient outcomes Patients Pediatrics Powder injection molding Prognosis Prospective Studies Protein binding Proteins Research and Analysis Methods Rodents Sepsis Sepsis - blood Sepsis - diagnosis Septic shock Severity of Illness Index Systematic review Tissue inhibitor of metalloproteinase 1 Tissue Inhibitor of Metalloproteinase-1 - blood |
| title | Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein |
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