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Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management., (© 2024. The Author(s).)

Background: The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted., Methods: This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited., Discussion: This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB., Trial Registration: ClinicalTrials.gov NCT04485156 . Registered on July 24, 2020., (© 2022. The Author(s).)

Background Determining the activity of pulmonary tuberculosis on chest radiographs is difficult. Purpose To develop a deep learning model to identify active pulmonary tuberculosis on chest radiographs. Materials and Methods Chest radiographs were retrospectively gathered from a multicenter consecutive cohort with pulmonary tuberculosis who were successfully treated between 2011 and 2017, along with normal radiographs to enrich a negative class. The pretreatment and posttreatment radiographs were labeled as positive and negative classes, respectively. A neural network was trained with those radiographs to calculate the probability of active versus healed tuberculosis. A single-center consecutive cohort (test set 1; 89 patients, 148 radiographs) and data from one multicenter randomized controlled trial (test set 2; 366 patients, 3774 radiographs) were used to test the model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model and of the four expert readers. Results In total, 6654 pre- and posttreatment radiographs from 3327 patients (mean age ± standard deviation, 55 years ± 19; 1884 men) with pulmonary tuberculosis and 3182 normal radiographs from as many patients (mean age, 53 years ± 14; 1629 men) were gathered. For test set 1, the model showed a higher AUC (0.83; 95% CI: 0.73, 0.89) than one pulmonologist (0.69; 95% CI: 0.61, 0.76; P < .001) and performed similarly to the other readers (AUC, 0.79-0.80; P = .14-.23). For 200 randomly selected radiographs from test set 2, the model had a higher AUC (0.84) than the pulmonologists (0.71 and 0.74; P < .001 and .01, respectively) and performed similarly to the radiologists (0.79 and 0.80; P = .08 and .06, respectively). The model output increased by 0.30 on average with a higher degree of smear positivity (95% CI: 0.20, 0.39; P < .001) and decreased during treatment (baseline, 3 months, and 6 months: 0.85, 0.51, and 0.26, respectively). Conclusion A deep learning model performed similarly to radiologists for accurately determining the activity of pulmonary tuberculosis on chest radiographs; it also was able to follow posttreatment changes. © RSNA, 2021 Online supplemental material is available for this article.

Background: There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB., Methods: In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients., Results: Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients., Conclusion: DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.

Background: Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis., Methods: We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul-Seongnam, South Korea). Patients, aged 20-80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460., Findings: Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI -4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and -1·1% (-11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient., Interpretation: Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis., Funding: Ministry of Health and Welfare, South Korea., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background/aims: Patients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM., Methods: This retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012. The primary study outcome was sputum culture conversion after 2 months of treatment., Results: Of 499 patients diagnosed with culture-positive pulmonary TB, 105 (21%) had DM at diagnosis. Among them, 62 (59.5%) were treated with metformin. Baseline characteristics, except for the presence of chronic renal disease, were not significantly different between the metformin and non-metformin groups. Metformin treatment had no significant effect on sputum culture conversion (p = 0.60) and recurrence within 1 year after TB treatment completion (p = 0.39). However, metformin improved the sputum culture conversion rate in patients with cavitary pulmonary TB, who have higher bacterial loads (odds ratio, 10.8; 95% confidence interval, 1.22 to 95.63)., Conclusion: Among cavitary pulmonary TB patients with DM, metformin can be an effective adjunctive anti-TB agent to improve sputum culture conversion after 2 months of treatment.

Background and Objective: There are limited data on pulmonary arterial hypertension (PAH) in patients with tuberculosis-destroyed lung (TDL), a sequela of pulmonary tuberculosis. We identified the risk factors for PAH and their effects on acute exacerbation and mortality in patients with TDL, as well as the clinical differences in patients with chronic obstructive pulmonary disease (COPD) and PAH., Methods: A retrospective cohort study was conducted from 2010 through 2015 in a municipal referral hospital in South Korea. PAH was defined when echocardiographic pulmonary arterial pressure (PAP) was >40 mmHg. The clinical features and course of TDL patients with or without PAH were evaluated and differences between patients with COPD and PAH were analyzed., Results: Among the 195 patients with TDL, echocardiographic data were available in 53 patients, and their mean PAP was 50.72±23.99 mmHg. The PAH group (n=37) had a smaller lung volume (forced vital capacity % predicted, 51.55% vs 72.37%, P <0.001) and more extensively destroyed lungs (3.27 lobes vs 2 lobes, P <0.001) than those in the non-PAH group (n=16). A higher PAP was significantly correlated with a higher frequency of acute exacerbation ( r =0.32, P =0.02). Multivariate analyses did not reveal any significant risk factors contributing to PAH in patients with TDL. Compared to COPD patients with PAH, TDL patients with PAH have smaller lung volume but a less severe airflow limitation. Tricuspid regurgitation and a D-shaped left ventricle during diastole were more frequently observed in TDL patients. The risk of exacerbation was not different between patients with PAH in COPD and TDL., Conclusion: PAH in patients with TDL was associated with severity of lung destruction but risk of exacerbation and mortality did not significantly differ between patients with PAH and without PAH., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis., Methods/design: This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total)., Discussion: This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future., Trial Registration: ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors., Competing Interests: The authors have declared that no competing interests exist.

Background: Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis., Methods: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included., Results: Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20-1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59-0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46-2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate., Conclusions: Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis.

Background and Objective: There is limited data on size change during natural progression of pulmonary aspergilloma. We aimed at elucidating the clinical course and prognosis of aspergilloma according to its size change., Methods: A multicentre retrospective observational study was performed in 143 adult pulmonary aspergilloma patients with serial chest computed tomography images. The clinical course and risk of haemoptysis according to the size change of the cavity or mass of aspergillomas was evaluated., Results: Median follow-up duration was 5.1 years. The size of aspergillomas changed in 39.2% of study subjects. Decreased and increased volumes of aspergilloma were observed in 13.3% and 25.9%, respectively. Patients with decreased volume had significantly higher C-reactive protein, and more severe bronchiectasis and tuberculosis-destroyed lung. Clinically significant haemoptysis occurred in 50.3% of patients and was significantly associated with the cavity and mass volume of aspergilloma, but not the extent of volume change. A mean cavity diameter of more than 22 mm and a mass diameter of more than 18 mm increased the risk of clinically significant haemoptysis., Conclusions: A significant portion of pulmonary aspergilloma changed size in our population. The prevalence of clinically significant haemoptysis was associated with absolute size of cavity and mass of aspergilloma., (© 2014 Asian Pacific Society of Respirology.)