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      Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: a computerized tomography study with history length matched cases

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          Abstract

          Background

          There have been concerns that literature described radiological feature differences between drug-sensitive pulmonary tuberculosis (DS-PTB) and multidrug-resistant (MDR)-PTB were confounded by that MDR-PTB cases tend to have a longer history. Using history length matched DS-PTB and MDR-PTB cases from a well-defined urban region in Dalian, we retrospectively analysed the CT feature differences of these paired cases with a focus on pulmonary nodular (PN) consolidation and pulmonary cavity (PC).

          Methods

          There were 33 consecutive MDR-PTB cases [inclusive of rifampicin-resistant (RR) cases, 27 males and 6 females, mean age: 49.2 years], with 19 cases had a history of <1 month and 8 and 6 cases had a history of 1–6 and >6 months respectively. To pair the MDR-PTB cases with history length, matched 33 cases of DS-PTB patients (21 males and 12 females, mean age: 56.5 years) were included. All patients were new PTB without HIV infection. The first CT exams prior to treatment were analysed.

          Results

          Compared with DS cases, MDR cases had a much higher prevalence of PN (75.76% vs. 45.45%) and a higher number of PN per positive case for PN (6.2 vs.1.53). For the cases >1 month history, MDR-PTB had a higher number of PC per positive case than that of DS-PTB cases (7.18 vs. 2.36). To differentiate DS-PTB from MDR-PTB, receiver operating characteristic (ROC) analysis showed a cutoff PN number of ≥3 had 48.5% sensitivity and 93.9% specificity, and a cutoff PC number of ≥4 had 39.4% sensitivity and 84.9% specificity. The lung field distribution of all lesions tended to be wider for MDR-PTB cases. MDR-PTB cases appeared to be associated with a faster progression in the absence of treatment.

          Conclusions

          MDR-TB is likely intrinsically more invasive than DS-TB. Multiple PN and Multiple PC are promising signs for the suspicion of MDR-PTB on chest imaging.

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          Most cited references26

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          Fleischner Society: glossary of terms for thoracic imaging.

          Members of the Fleischner Society compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984 and 1996 for thoracic radiography and computed tomography (CT), respectively. The need to update the previous versions came from the recognition that new words have emerged, others have become obsolete, and the meaning of some terms has changed. Brief descriptions of some diseases are included, and pictorial examples (chest radiographs and CT scans) are provided for the majority of terms. (c) RSNA, 2008.
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            Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis.

            The burden of tuberculosis is compounded by drug-resistant forms of the disease. This study aimed to analyse data on antituberculosis drug resistance gathered by the WHO and International Union Against Tuberculosis and Lung Disease Global Project on Anti-tuberculosis Drug Resistance Surveillance. Data on drug susceptibility testing for four antituberculosis drugs--isoniazid, rifampicin, ethambutol, and streptomycin--were gathered in the third round of the Global Project (1999-2002) from surveys or ongoing surveillance in 79 countries or geographical settings. These data were combined with those from the first two rounds of the project and analyses were done. Countries that participated followed a standardised set of guidelines to ensure comparability both between and within countries. The median prevalence of resistance to any of the four antituberculosis drugs in new cases of tuberculosis identified in 76 countries or geographical settings was 10.2% (range 0.0-57.1). The median prevalence of multidrug resistance in new cases was 1.0% (range 0.0-14.2). Kazakhstan, Tomsk Oblast (Russia), Karakalpakstan (Uzbekistan), Estonia, Israel, the Chinese provinces Liaoning and Henan, Lithuania, and Latvia reported prevalence of multidrug resistance above 6.5%. Trend analysis showed a significant increase in the prevalence of multidrug resistance in new cases in Tomsk Oblast (p<0.0001). Hong Kong (p=0.01) and the USA (p=0.0002) reported significant decreasing trends in multidrug resistance in new cases of tuberculosis. Multidrug resistance represents a serious challenge for tuberculosis control in countries of the former Soviet Union and in some provinces of China. Gaps in coverage of the Global Project are substantial, and baseline information is urgently required from several countries with high tuberculosis burden to develop appropriate control interventions.
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              Totally drug-resistant tuberculosis and adjunct therapies

              The first cases of totally drug-resistant (TDR) tuberculosis (TB) were reported in Italy 10 years ago; more recently, cases have also been reported in Iran, India and South Africa. Although there is no consensus on terminology, it is most commonly described as 'resistance to all first- and second-line drugs used to treat TB'. Mycobacterium tuberculosis (M.tb) acquires drug resistance mutations in a sequential fashion under suboptimal drug pressure due to monotherapy, inadequate dosing, treatment interruptions and drug interactions. The treatment of TDR-TB includes antibiotics with disputed or minimal effectiveness against M.tb, and the fatality rate is high. Comorbidities such as diabetes and infection with human immunodeficiency virus further impact on TB treatment options and survival rates. Several new drug candidates with novel modes of action are under late-stage clinical evaluation (e.g., delamanid, bedaquiline, SQ109 and sutezolid). 'Repurposed' antibiotics have also recently been included in the treatment of extensively drug resistant TB. However, because of mutations in M.tb, drugs will not provide a cure for TB in the long term. Adjunct TB therapies, including therapeutic vaccines, vitamin supplementation and/or repurposing of drugs targeting biologically and clinically relevant molecular pathways, may achieve better clinical outcomes in combination with standard chemotherapy. Here, we review broader perspectives of drug resistance in TB and potential adjunct treatment options.
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                Author and article information

                Journal
                J Thorac Dis
                J Thorac Dis
                JTD
                Journal of Thoracic Disease
                AME Publishing Company
                2072-1439
                2077-6624
                July 2022
                July 2022
                : 14
                : 7
                : 2522-2531
                Affiliations
                [1 ]deptDepartment of Internal Medicine , Dalian Public Health Clinical Center , Dalian, China;
                [2 ]Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong , China;
                [3 ]deptDepartment of Radiology , Dalian Public Health Clinical Center , Dalian, China;
                [4 ]deptDepartment of Ultrasonic Medicine , West China Second University Hospital of Sichuan University , Chengdu, China;
                [5 ]Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) , deptMinistry of Education , Chengdu, China;
                [6 ]Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , deptDepartment of Health and Human Services , Bethesda, MD, USA
                Author notes

                Contributions: (I) Conception and design: YXJ Wáng; (II) Administrative support: QS Song, CJ Zheng; (III) Provision of study materials or patients: QS Song, KP Wang; (IV) Collection and assembly of data: QS Song; (V) Data analysis and interpretation: QS Song, CJ Zheng, YXJ Wáng; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Dr. Yì Xiáng J. Wáng. Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Email: yixiang_wang@ 123456cuhk.edu.hk .
                Article
                jtd-14-07-2522
                10.21037/jtd-22-145
                9344412
                35928612
                4a70092e-35ff-4e15-b8e7-b150d53d57a6
                2022 Journal of Thoracic Disease. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 04 February 2022
                : 29 April 2022
                Categories
                Original Article

                differential diagnosis,tuberculosis (tb),multidrug-resistant (mdr),computed tomography,pulmonary

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