PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.
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Auteurs : Ray Y. Chen [États-Unis] ; Lori E. Dodd [États-Unis] ; Myungsun Lee [Corée du Sud] ; Praveen Paripati [États-Unis] ; Dima A. Hammoud [États-Unis] ; James M. Mountz [États-Unis] ; Doosoo Jeon [Corée du Sud] ; Nadeem Zia [États-Unis] ; Homeira Zahiri [États-Unis] ; M Teresa Coleman [États-Unis] ; Matthew W. Carroll [États-Unis] ; Jong Doo Lee [Corée du Sud] ; Yeon Joo Jeong [Corée du Sud] ; Peter Herscovitch [États-Unis] ; Saher Lahouar [États-Unis] ; Michael Tartakovsky [États-Unis] ; Alexander Rosenthal [États-Unis] ; Sandeep Somaiyya [États-Unis] ; Soyoung Lee [Corée du Sud] ; Lisa C. Goldfeder [États-Unis] ; Ying Cai [États-Unis] ; Laura E. Via [États-Unis] ; Seung-Kyu Park [Corée du Sud] ; Sang-Nae Cho [Corée du Sud] ; Clifton E. Barry [Afrique du Sud]Source :
- Science translational medicine [ 1946-6242 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Algorithmes, Biais de l'observateur, Courbe ROC, Expectoration (microbiologie), Femelle, Fluorodésoxyglucose F18, Humains, Imagerie multimodale, Interprétation de radiographie assistée par ordinateur, Logiciel, Mâle, Méthode en double aveugle, Métronidazole (usage thérapeutique), Poumon (imagerie diagnostique), Résultat thérapeutique, Sensibilité et spécificité, Tomodensitométrie, Tomographie par émission de positons, Tuberculose multirésistante (), Tuberculose multirésistante (imagerie diagnostique), Études prospectives.
- MESH :
- imagerie diagnostique : Poumon, Tuberculose multirésistante.
- microbiologie : Expectoration.
- usage thérapeutique : Métronidazole.
- Adulte, Algorithmes, Biais de l'observateur, Courbe ROC, Femelle, Fluorodésoxyglucose F18, Humains, Imagerie multimodale, Interprétation de radiographie assistée par ordinateur, Logiciel, Mâle, Méthode en double aveugle, Résultat thérapeutique, Sensibilité et spécificité, Tomodensitométrie, Tomographie par émission de positons, Tuberculose multirésistante, Études prospectives.
English descriptors
- KwdEn :
- Adult, Algorithms, Double-Blind Method, Female, Fluorodeoxyglucose F18, Humans, Lung (diagnostic imaging), Male, Metronidazole (therapeutic use), Multimodal Imaging, Observer Variation, Positron-Emission Tomography, Prospective Studies, ROC Curve, Radiographic Image Interpretation, Computer-Assisted, Sensitivity and Specificity, Software, Sputum (microbiology), Tomography, X-Ray Computed, Treatment Outcome, Tuberculosis, Multidrug-Resistant (diagnostic imaging), Tuberculosis, Multidrug-Resistant (therapy).
- MESH :
- chemical , therapeutic use : Metronidazole.
- chemical : Fluorodeoxyglucose F18.
- diagnostic imaging : Lung, Tuberculosis, Multidrug-Resistant.
- microbiology : Sputum.
- therapy : Tuberculosis, Multidrug-Resistant.
- Adult, Algorithms, Double-Blind Method, Female, Humans, Male, Multimodal Imaging, Observer Variation, Positron-Emission Tomography, Prospective Studies, ROC Curve, Radiographic Image Interpretation, Computer-Assisted, Sensitivity and Specificity, Software, Tomography, X-Ray Computed, Treatment Outcome.
Abstract
Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.
DOI: 10.1126/scitranslmed.3009501
PubMed: 25473034
Affiliations:
- Afrique du Sud, Corée du Sud, États-Unis
- Maryland, Pennsylvanie, Région capitale de Séoul, Virginie
- Pittsburgh, Séoul
- Université de Pittsburgh
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Le document en format XML
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Sandeep" sort="Somaiyya, Sandeep" uniqKey="Somaiyya S" first="Sandeep" last="Somaiyya">Sandeep Somaiyya</name><affiliation wicri:level="2"><nlm:affiliation>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Lee, Soyoung" sort="Lee, Soyoung" uniqKey="Lee S" first="Soyoung" last="Lee">Soyoung Lee</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Goldfeder, Lisa C" sort="Goldfeder, Lisa C" uniqKey="Goldfeder L" first="Lisa C" last="Goldfeder">Lisa C. Goldfeder</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Cai, Ying" sort="Cai, Ying" uniqKey="Cai Y" first="Ying" last="Cai">Ying Cai</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Via, Laura E" sort="Via, Laura E" uniqKey="Via L" first="Laura E" last="Via">Laura E. Via</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Park, Seung Kyu" sort="Park, Seung Kyu" uniqKey="Park S" first="Seung-Kyu" last="Park">Seung-Kyu Park</name><affiliation wicri:level="1"><nlm:affiliation>National Masan Hospital, Changwon 631-710, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>National Masan Hospital, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Sang Nae" sort="Cho, Sang Nae" uniqKey="Cho S" first="Sang-Nae" last="Cho">Sang-Nae Cho</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, South Korea. Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 120-752, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710, South Korea. Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 120-752</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Barry, Clifton E" sort="Barry, Clifton E" uniqKey="Barry C" first="Clifton E" last="Barry">Clifton E. Barry</name><affiliation wicri:level="1"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701, South Africa. cbarry@niaid.nih.gov.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701</wicri:regionArea><wicri:noRegion>Rondebosch 7701</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25473034</idno><idno type="pmid">25473034</idno><idno type="doi">10.1126/scitranslmed.3009501</idno><idno type="wicri:Area/PubMed/Corpus">000D96</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000D96</idno><idno type="wicri:Area/PubMed/Curation">000D93</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000D93</idno><idno type="wicri:Area/PubMed/Checkpoint">000D93</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000D93</idno><idno type="wicri:Area/Ncbi/Merge">004265</idno><idno type="wicri:Area/Ncbi/Curation">004265</idno><idno type="wicri:Area/Ncbi/Checkpoint">004265</idno><idno type="wicri:Area/Main/Merge">001D57</idno><idno type="wicri:Area/Main/Curation">001C81</idno><idno type="wicri:Area/Main/Exploration">001C81</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.</title><author><name sortKey="Chen, Ray Y" sort="Chen, Ray Y" uniqKey="Chen R" first="Ray Y" last="Chen">Ray Y. Chen</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Dodd, Lori E" sort="Dodd, Lori E" uniqKey="Dodd L" first="Lori E" last="Dodd">Lori E. Dodd</name><affiliation wicri:level="2"><nlm:affiliation>Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lee, Myungsun" sort="Lee, Myungsun" uniqKey="Lee M" first="Myungsun" last="Lee">Myungsun Lee</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Paripati, Praveen" sort="Paripati, Praveen" uniqKey="Paripati P" first="Praveen" last="Paripati">Praveen Paripati</name><affiliation wicri:level="2"><nlm:affiliation>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Hammoud, Dima A" sort="Hammoud, Dima A" uniqKey="Hammoud D" first="Dima A" last="Hammoud">Dima A. Hammoud</name><affiliation wicri:level="2"><nlm:affiliation>Division of Diagnostic Radiology, Clinical Center, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Diagnostic Radiology, Clinical Center, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mountz, James M" sort="Mountz, James M" uniqKey="Mountz J" first="James M" last="Mountz">James M. Mountz</name><affiliation wicri:level="4"><nlm:affiliation>Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Jeon, Doosoo" sort="Jeon, Doosoo" uniqKey="Jeon D" first="Doosoo" last="Jeon">Doosoo Jeon</name><affiliation wicri:level="1"><nlm:affiliation>National Masan Hospital, Changwon 631-710, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>National Masan Hospital, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Zia, Nadeem" sort="Zia, Nadeem" uniqKey="Zia N" first="Nadeem" last="Zia">Nadeem Zia</name><affiliation wicri:level="4"><nlm:affiliation>Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Zahiri, Homeira" sort="Zahiri, Homeira" uniqKey="Zahiri H" first="Homeira" last="Zahiri">Homeira Zahiri</name><affiliation wicri:level="2"><nlm:affiliation>Division of Diagnostic Radiology, Clinical Center, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Diagnostic Radiology, Clinical Center, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Coleman, M Teresa" sort="Coleman, M Teresa" uniqKey="Coleman M" first="M Teresa" last="Coleman">M Teresa Coleman</name><affiliation wicri:level="4"><nlm:affiliation>Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Carroll, Matthew W" sort="Carroll, Matthew W" uniqKey="Carroll M" first="Matthew W" last="Carroll">Matthew W. Carroll</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lee, Jong Doo" sort="Lee, Jong Doo" uniqKey="Lee J" first="Jong Doo" last="Lee">Jong Doo Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul 120-752</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Jeong, Yeon Joo" sort="Jeong, Yeon Joo" uniqKey="Jeong Y" first="Yeon Joo" last="Jeong">Yeon Joo Jeong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Diagnostic Radiology, Pusan National University School of Medicine, Busan 609-735, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Diagnostic Radiology, Pusan National University School of Medicine, Busan 609-735</wicri:regionArea><wicri:noRegion>Busan 609-735</wicri:noRegion></affiliation></author><author><name sortKey="Herscovitch, Peter" sort="Herscovitch, Peter" uniqKey="Herscovitch P" first="Peter" last="Herscovitch">Peter Herscovitch</name><affiliation wicri:level="2"><nlm:affiliation>PET Department, Clinical Center, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>PET Department, Clinical Center, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lahouar, Saher" sort="Lahouar, Saher" uniqKey="Lahouar S" first="Saher" last="Lahouar">Saher Lahouar</name><affiliation wicri:level="2"><nlm:affiliation>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Tartakovsky, Michael" sort="Tartakovsky, Michael" uniqKey="Tartakovsky M" first="Michael" last="Tartakovsky">Michael Tartakovsky</name><affiliation wicri:level="2"><nlm:affiliation>Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Rosenthal, Alexander" sort="Rosenthal, Alexander" uniqKey="Rosenthal A" first="Alexander" last="Rosenthal">Alexander Rosenthal</name><affiliation wicri:level="2"><nlm:affiliation>Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Somaiyya, Sandeep" sort="Somaiyya, Sandeep" uniqKey="Somaiyya S" first="Sandeep" last="Somaiyya">Sandeep Somaiyya</name><affiliation wicri:level="2"><nlm:affiliation>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Lee, Soyoung" sort="Lee, Soyoung" uniqKey="Lee S" first="Soyoung" last="Lee">Soyoung Lee</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Goldfeder, Lisa C" sort="Goldfeder, Lisa C" uniqKey="Goldfeder L" first="Lisa C" last="Goldfeder">Lisa C. Goldfeder</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Cai, Ying" sort="Cai, Ying" uniqKey="Cai Y" first="Ying" last="Cai">Ying Cai</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Via, Laura E" sort="Via, Laura E" uniqKey="Via L" first="Laura E" last="Via">Laura E. Via</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Park, Seung Kyu" sort="Park, Seung Kyu" uniqKey="Park S" first="Seung-Kyu" last="Park">Seung-Kyu Park</name><affiliation wicri:level="1"><nlm:affiliation>National Masan Hospital, Changwon 631-710, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>National Masan Hospital, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Sang Nae" sort="Cho, Sang Nae" uniqKey="Cho S" first="Sang-Nae" last="Cho">Sang-Nae Cho</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, South Korea. Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 120-752, South Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710, South Korea. Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 120-752</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Barry, Clifton E" sort="Barry, Clifton E" uniqKey="Barry C" first="Clifton E" last="Barry">Clifton E. Barry</name><affiliation wicri:level="1"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701, South Africa. cbarry@niaid.nih.gov.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701</wicri:regionArea><wicri:noRegion>Rondebosch 7701</wicri:noRegion></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Algorithms</term><term>Double-Blind Method</term><term>Female</term><term>Fluorodeoxyglucose F18</term><term>Humans</term><term>Lung (diagnostic imaging)</term><term>Male</term><term>Metronidazole (therapeutic use)</term><term>Multimodal Imaging</term><term>Observer Variation</term><term>Positron-Emission Tomography</term><term>Prospective Studies</term><term>ROC Curve</term><term>Radiographic Image Interpretation, Computer-Assisted</term><term>Sensitivity and Specificity</term><term>Software</term><term>Sputum (microbiology)</term><term>Tomography, X-Ray Computed</term><term>Treatment Outcome</term><term>Tuberculosis, Multidrug-Resistant (diagnostic imaging)</term><term>Tuberculosis, Multidrug-Resistant (therapy)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Algorithmes</term><term>Biais de l'observateur</term><term>Courbe ROC</term><term>Expectoration (microbiologie)</term><term>Femelle</term><term>Fluorodésoxyglucose F18</term><term>Humains</term><term>Imagerie multimodale</term><term>Interprétation de radiographie assistée par ordinateur</term><term>Logiciel</term><term>Mâle</term><term>Méthode en double aveugle</term><term>Métronidazole (usage thérapeutique)</term><term>Poumon (imagerie diagnostique)</term><term>Résultat thérapeutique</term><term>Sensibilité et spécificité</term><term>Tomodensitométrie</term><term>Tomographie par émission de positons</term><term>Tuberculose multirésistante ()</term><term>Tuberculose multirésistante (imagerie diagnostique)</term><term>Études prospectives</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Metronidazole</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Fluorodeoxyglucose F18</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Lung</term><term>Tuberculosis, Multidrug-Resistant</term></keywords><keywords scheme="MESH" qualifier="imagerie diagnostique" xml:lang="fr"><term>Poumon</term><term>Tuberculose multirésistante</term></keywords><keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Expectoration</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Sputum</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Tuberculosis, Multidrug-Resistant</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Métronidazole</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Algorithms</term><term>Double-Blind Method</term><term>Female</term><term>Humans</term><term>Male</term><term>Multimodal Imaging</term><term>Observer Variation</term><term>Positron-Emission Tomography</term><term>Prospective Studies</term><term>ROC Curve</term><term>Radiographic Image Interpretation, Computer-Assisted</term><term>Sensitivity and Specificity</term><term>Software</term><term>Tomography, X-Ray Computed</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Algorithmes</term><term>Biais de l'observateur</term><term>Courbe ROC</term><term>Femelle</term><term>Fluorodésoxyglucose F18</term><term>Humains</term><term>Imagerie multimodale</term><term>Interprétation de radiographie assistée par ordinateur</term><term>Logiciel</term><term>Mâle</term><term>Méthode en double aveugle</term><term>Résultat thérapeutique</term><term>Sensibilité et spécificité</term><term>Tomodensitométrie</term><term>Tomographie par émission de positons</term><term>Tuberculose multirésistante</term><term>Études prospectives</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.</div></front></TEI><affiliations><list><country><li>Afrique du Sud</li><li>Corée du Sud</li><li>États-Unis</li></country><region><li>Maryland</li><li>Pennsylvanie</li><li>Région capitale de Séoul</li><li>Virginie</li></region><settlement><li>Pittsburgh</li><li>Séoul</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Chen, Ray Y" sort="Chen, Ray Y" uniqKey="Chen R" first="Ray Y" last="Chen">Ray Y. Chen</name></region><name sortKey="Cai, Ying" sort="Cai, Ying" uniqKey="Cai Y" first="Ying" last="Cai">Ying Cai</name><name sortKey="Carroll, Matthew W" sort="Carroll, Matthew W" uniqKey="Carroll M" first="Matthew W" last="Carroll">Matthew W. Carroll</name><name sortKey="Coleman, M Teresa" sort="Coleman, M Teresa" uniqKey="Coleman M" first="M Teresa" last="Coleman">M Teresa Coleman</name><name sortKey="Dodd, Lori E" sort="Dodd, Lori E" uniqKey="Dodd L" first="Lori E" last="Dodd">Lori E. Dodd</name><name sortKey="Goldfeder, Lisa C" sort="Goldfeder, Lisa C" uniqKey="Goldfeder L" first="Lisa C" last="Goldfeder">Lisa C. Goldfeder</name><name sortKey="Hammoud, Dima A" sort="Hammoud, Dima A" uniqKey="Hammoud D" first="Dima A" last="Hammoud">Dima A. Hammoud</name><name sortKey="Herscovitch, Peter" sort="Herscovitch, Peter" uniqKey="Herscovitch P" first="Peter" last="Herscovitch">Peter Herscovitch</name><name sortKey="Lahouar, Saher" sort="Lahouar, Saher" uniqKey="Lahouar S" first="Saher" last="Lahouar">Saher Lahouar</name><name sortKey="Mountz, James M" sort="Mountz, James M" uniqKey="Mountz J" first="James M" last="Mountz">James M. Mountz</name><name sortKey="Paripati, Praveen" sort="Paripati, Praveen" uniqKey="Paripati P" first="Praveen" last="Paripati">Praveen Paripati</name><name sortKey="Rosenthal, Alexander" sort="Rosenthal, Alexander" uniqKey="Rosenthal A" first="Alexander" last="Rosenthal">Alexander Rosenthal</name><name sortKey="Somaiyya, Sandeep" sort="Somaiyya, Sandeep" uniqKey="Somaiyya S" first="Sandeep" last="Somaiyya">Sandeep Somaiyya</name><name sortKey="Tartakovsky, Michael" sort="Tartakovsky, Michael" uniqKey="Tartakovsky M" first="Michael" last="Tartakovsky">Michael Tartakovsky</name><name sortKey="Via, Laura E" sort="Via, Laura E" uniqKey="Via L" first="Laura E" last="Via">Laura E. Via</name><name sortKey="Zahiri, Homeira" sort="Zahiri, Homeira" uniqKey="Zahiri H" first="Homeira" last="Zahiri">Homeira Zahiri</name><name sortKey="Zia, Nadeem" sort="Zia, Nadeem" uniqKey="Zia N" first="Nadeem" last="Zia">Nadeem Zia</name></country><country name="Corée du Sud"><noRegion><name sortKey="Lee, Myungsun" sort="Lee, Myungsun" uniqKey="Lee M" first="Myungsun" last="Lee">Myungsun Lee</name></noRegion><name sortKey="Cho, Sang Nae" sort="Cho, Sang Nae" uniqKey="Cho S" first="Sang-Nae" last="Cho">Sang-Nae Cho</name><name sortKey="Jeon, Doosoo" sort="Jeon, Doosoo" uniqKey="Jeon D" first="Doosoo" last="Jeon">Doosoo Jeon</name><name sortKey="Jeong, Yeon Joo" sort="Jeong, Yeon Joo" uniqKey="Jeong Y" first="Yeon Joo" last="Jeong">Yeon Joo Jeong</name><name sortKey="Lee, Jong Doo" sort="Lee, Jong Doo" uniqKey="Lee J" first="Jong Doo" last="Lee">Jong Doo Lee</name><name sortKey="Lee, Soyoung" sort="Lee, Soyoung" uniqKey="Lee S" first="Soyoung" last="Lee">Soyoung Lee</name><name sortKey="Park, Seung Kyu" sort="Park, Seung Kyu" uniqKey="Park S" first="Seung-Kyu" last="Park">Seung-Kyu Park</name></country><country name="Afrique du Sud"><noRegion><name sortKey="Barry, Clifton E" sort="Barry, Clifton E" uniqKey="Barry C" first="Clifton E" last="Barry">Clifton E. 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