Artificial intelligence-based radiographic extent analysis to predict tuberculosis treatment outcomes: a multicenter cohort study.

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.

Timing and predictors of death during treatment in patients with multidrug/rifampin-resistant tuberculosis in South Korea.

Background/Aims: This study aimed to investigate the timing and predictors of death during treatment among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB) in South Korea. Methods: This was a retrospective cohort study that included MDR/RR-TB cases notified between 2011 and 2017 in South Korea. Results: Among 7,226 MDR/RR-TB cases, 699 (9.7%) died at a median of 167 days (IQR 51-358 d) from the initiation of MDR-TB treatment. The cumulative proportion of all-cause death was 35.5% at 90 days and 52.8% at 180 days from treatment initiation. TB-related deaths occurred at a median of 133 days (IQR 32-366 d), which was significantly earlier than the median of 184 days (IQR 68-356 d) for non-TB-related deaths (p = 0.002). In a multivariate analysis, older age was the factor most strongly associated with death, with those aged ≥ 75 years being 68 times more likely to die (aHR 68.11, 95% CI 21.75-213.26), compared those aged ≤ 24 years. In addition, male sex, comorbidities (cancer, human immunodeficiency virus, and end stage renal disease), the lowest household income class, and TB-specific factors (previous history of TB treatment, smear positivity, and fluoroquinolone resistance) were identified as independent predictors of all-cause death. Conclusions: This nationwide study highlights increased deaths during the intensive phase and identifies high-risk groups including older people and those with comorbidities or socioeconomic vulnerabilities. An integrated and comprehensive strategy is required to reduce mortality in patients with MDR/RR-TB, particularly focusing on the early stages of treatment and target populations.

QMAC-DST for Rapid Detection of Drug Resistance in Pulmonary Tuberculosis Patients: A Multicenter Pre-Post Comparative Study.

Background/Objectives: This study explores the impact of QMAC-DST, a rapid, fully automated phenotypic drug susceptibility test (pDST), on the treatment of tuberculosis (TB) patients. Methods: This pre-post comparative study, respectively, included pulmonary TB patients who began TB treatment between 1 December 2020 and 31 October 2021 (pre-period; pDST using the Löwenstein-Jensen (LJ) DST (M-kit DST)) and between 1 November 2021 and 30 September 2022 (post-period; pDST using the QMAC-DST) in five university-affiliated tertiary care hospitals in South Korea. We compared the turnaround times (TATs) of pDSTs and the time to appropriate treatment for patients whose anti-TB drugs were changed based on these tests between the groups. All patients were permitted to use molecular DSTs (mDSTs). Results: A total of 182 patients (135 in the M-kit DST group and 47 in the QMAC-DST group) were included. The median TAT was 36 days for M-kit DST (interquartile range (IQR), 30-39) and 12 days for QMAC-DST (IQR, 9-15), with the latter being significantly shorter (p < 0.001). Of the total patients, 10 (5.5%) changed their anti-TB drugs based on the mDST or pDST results after initiating TB treatment (8 in the M-kit DST group and 2 in the QMAC-DST group). In the M-kit DST group, three (37.5%) patients changed anti-TB drugs based on the pDST results. In the QMAC-DST group, all changes were due to mDST results; therefore, calculating the time to appropriate treatment for patients whose anti-TB drugs were changed based on pDST results was not feasible. In the QMAC-DST group, 46.8% of patients underwent the first-line line probe assay compared to 100.0% in the M-kit DST group (p < 0.001), indicating that rapid QMAC-DST results provide quicker assurance of the ongoing treatment by confirming susceptibility to the current anti-TB drugs. Conclusions: QMAC-DST delivers pDST results more rapidly than LJ-DST, ensuring faster confirmation for the current treatment regimen.

Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Relationship between metformin use and mortality in tuberculosis patients with diabetes: a nationwide cohort study.

BACKGROUND/AIMS: To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM. METHODS: This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI). RESULTS: The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67-0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01). CONCLUSION: Metformin use in patients with TB-DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.

Dual Antiplatelet Therapy De-Escalation in Stabilized Myocardial Infarction With High Ischemic Risk: Post Hoc Analysis of the TALOS-AMI Randomized Clinical Trial.

Importance: In patients with acute myocardial infarction (AMI) who have high ischemic risk, data on the efficacy and safety of the de-escalation strategy of switching from ticagrelor to clopidogrel are lacking. Objective: To evaluate the outcomes of the de-escalation strategy compared with dual antiplatelet therapy (DAPT) with ticagrelor in stabilized patients with AMI and high ischemic risk following percutaneous coronary intervention (PCI). Design, Setting, and Participants: This was a post hoc analysis of the Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) trial, an open-label, assessor-blinded, multicenter, randomized clinical trial. Patients with AMI who had no event during 1 month of ticagrelor-based DAPT after PCI were included. High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, at least 3 lesions treated, total stent length greater than 60 mm, at least 3 stents implanted, left main PCI, or bifurcation PCI with at least 2 stents. Data were collected from February 14, 2014, to January 21, 2021, and analyzed from December 1, 2021, to June 30, 2022. Intervention: Patients were randomly assigned to either de-escalation from ticagrelor to clopidogrel or ticagrelor-based DAPT. Main Outcomes and Measures: Ischemic outcomes (composite of cardiovascular death, myocardial infarction, ischemic stroke, ischemia-driven revascularization, or stent thrombosis) and bleeding outcomes (Bleeding Academic Research Consortium type 2, 3, or 5 bleeding) were evaluated. Results: Of 2697 patients with AMI (mean [SD] age, 60.0 [11.4] years; 454 [16.8%] female), 1371 (50.8%; 684 assigned to de-escalation and 687 assigned to ticagrelor-based DAPT) had high ischemic risk features and a significantly higher risk of ischemic outcomes than those without high ischemic risk (1326 patients [49.2%], including 665 assigned to de-escalation and 661 assigned to ticagrelor-based DAPT) (hazard ratio [HR], 1.74; 95% CI, 1.15-2.63; P = .01). De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (HR, 0.88; 95% CI, 0.54-1.45; P = .62) and the non-high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; P = .21), without heterogeneity (P for interaction = .47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; P = .11) and the non-high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; P = .003), without heterogeneity (P for interaction = .32). Conclusions and Relevance: In stabilized patients with AMI, the ischemic and bleeding outcomes of an unguided de-escalation strategy with clopidogrel compared with a ticagrelor-based DAPT strategy were consistent without significant interaction, regardless of the presence of high ischemic risk.

Association between diabetes mellitus and cause of death in patients with tuberculosis: A Korean nationwide cohort study.

Despite its significant impact on mortality, tuberculosis (TB)-diabetes mellitus (DM) co-prevalence has not been well-elucidated for the cause of death. We investigated the impact of DM on TB-related and non-TB-related deaths in patients with TB. This retrospective nationwide cohort study included patients diagnosed with TB between 2011 and 2017 in South Korea. We performed Fine and Gray regression model analyses to assess the mortality risk of DM classified by cause of death. Of 239,848 patients, 62,435 (26.0%) had DM, and 20,203 died during anti-TB treatment. Of all deaths, 47.9% (9,668) were caused by TB, and the remaining 52.1% (10,535) was attributed to various non-TB-related causes. The mortality rate was higher in the DM than in the non-DM groups in both men and women. DM was associated with a higher risk of TB-related (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.01-1.13) and non-TB-related (aHR 1.21, 95% CI 1.15-1.27) deaths in men; however, only a higher risk of non-TB-related deaths (aHR 1.29, 95% CI 1.20-1.38) in women. Our findings indicate that DM is independently associated with a greater risk of death during anti-TB treatment among patients with TB for both TB-related and non-TB-related deaths.

De-escalation from ticagrelor to clopidogrel in patients with acute myocardial infarction: the TALOS-AMI HBR substudy.

BACKGROUND: The benefits of de-escalation of P2Y12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status. AIMS: We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status. METHODS: This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria. RESULTS: A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84). CONCLUSIONS: In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y12 inhibition on reducing haemorrhagic events was greater in patients with HBR.

Retreatment after loss to follow-up reduces mortality in patients with multidrug/rifampicin-resistant tuberculosis.

Background: This study evaluated the risk factors of long-term mortality in patients with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in South Korea who were lost to follow-up (LTFU). Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases, which included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Post-treatment outcomes of patients who were LTFU were compared with those of patients who achieved treatment success. Results: Of the 7226 MDR/RR-TB cases, 730 (10.1%) were LTFU. During a median follow-up period of 4.2 years, 101 (13.8%) of the LTFU patients died: 25 deaths (3.4%) were TB related and 76 (10.4%) were non-TB related. In the LTFU group, the adjusted hazard ratio (aHR) of all-cause mortality (aHR 2.50, 95% CI 1.99-3.15, p<0.001), TB-related mortality (aHR 5.38, 95% CI 3.19-9.09, p<0.001) and non-TB-related mortality (HR 2.21, 95% CI 1.70-2.87, p<0.001) was significantly higher than that in the treatment success group. Independent risk factors for all-cause mortality in the LTFU group were age >55 years, fluoroquinolone resistance, cancer and no retreatment. In the LTFU patients who did not receive retreatment, the risk of non-TB-related mortality (aHR 5.00, 95% CI 1.53-16.37, p=0.008) and consequent all-cause mortality (aHR 2.18, 95% CI 1.08-4.40, p=0.030) was significantly higher than that of patients who received retreatment. Conclusion: Non-TB-related mortality was the main cause of death and might be reduced by retreatment in LTFU patients with MDR/RR-TB.

Initial Tumor Necrosis Factor-Alpha and Endothelial Activation Are Associated with Hemorrhagic Complications during Extracorporeal Membrane Oxygenation.

Studies on inflammatory markers, endothelial activation, and bleeding during extracorporeal membrane oxygenation (ECMO) are lacking. Blood samples were prospectively collected after ECMO initiation from 150 adult patients who underwent ECMO for respiratory failure between 2018 and 2021. After excluding patients who died early (within 48 h), 132 patients were finally included. Their tumor necrosis factor-alpha (TNF-α), tissue factor (TF), soluble thrombomodulin (sTM), and E-selectin levels were measured. A Cox proportional hazards regression model was used to estimate the hazard ratio for hemorrhagic complications during ECMO. The 132 patients were divided into hemorrhagic (n = 23, H group) and non-complication (n = 109, N group) groups. The sequential organ failure assessment score, hemoglobin level, and ECMO type were included as covariates in all Cox models to exclude the effects of clinical factors. After adjusting for these factors, initial TNF-α, TF, sTM, E-selectin, and activated protein C levels were significantly associated with hemorrhagic complications (all p < 0.001). TNF-α, TF, and E-selectin better predicted hemorrhagic complications than the model that included only the aforementioned clinical factors (clinical factors only (area under the curve [AUC]: 0.804), reference; TNF-α (AUC: 0.914); TF (AUC: 0.915); E-selectin (AUC: 0.869)). Conclusions: TNF-α levels were significantly predictive of hemorrhagic complications during ECMO.

Impact of Anti-Tuberculosis Drug Use on Treatment Outcomes in Patients with Pulmonary Fluoroquinolone-Resistant Multidrug-Resistant Tuberculosis: A Nationwide Retrospective Cohort Study with Propensity Score Matching.

BACKGROUND: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. METHODS: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. RESULTS: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). CONCLUSION: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

Effect of Angiotensin Receptor Blocker Dose in Myocardial Infarction With Preserved Left Ventricular Systolic Function.

ABSTRACT: There have been few studies of angiotensin receptor blocker (ARB) dose in myocardial infarction (MI) with preserved left ventricular (LV) systolic function. We evaluated the association of ARB dose with clinical outcomes after MI with preserved LV systolic function. We used MI multicenter registry. Six months after discharge, the ARB dose was indexed to the target ARB doses used in randomized clinical trials and grouped as >0%-25% (n = 2333), >25% of the target dose (n = 1204), and no ARB (n = 1263). The primary outcome was the composite of cardiac death or MI. Univariate analysis showed that mortality of those with any ARB dose was lower than those without ARB therapy. After multivariable adjustment, patients receiving >25% of target dose had a similar risk of cardiac death or MI compared with those receiving ≤25% or no ARB [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.83-1.33; HR 0.94, 95% CI 0.82-1.08, respectively]. Propensity score analysis also demonstrated that patients with >25% dose had no difference in primary endpoint compared with those ≤25% dose or the no ARB group (HR 1.03, 95% CI 0.79-1.33; HR 0.86, 95% CI 0.64-1.14, respectively). The present study demonstrates that patients treated with >25% of target ARB dose do not have better clinical outcomes than those treated with ≤25% of target ARB dose or those with no ARB dose in MI patients with preserved LV systolic function.

Prevalence and associated factors of diabetes mellitus among patients with tuberculosis in South Korea from 2011 to 2018: a nationwide cohort study.

OBJECTIVES: This study aimed to identify the prevalence of diabetes mellitus (DM) among patients with tuberculosis (TB) using a nationwide cohort in South Korea. DESIGN: A retrospective cohort study. SETTING: This study used the Korean Tuberculosis and Post-Tuberculosis cohort, which was constructed by linking the Korean National Tuberculosis Surveillance, National Health Information Database (NHID) and Statistics Korea data for the causes of death. PARTICIPANTS: During the study period, all notified patients with TB with at least one claim in the NHID were included. Exclusion criteria were age less than 20 years, drug resistance, initiation of TB treatment before the study period and missing values in covariates. OUTCOME MEASURES: DM was defined as having at least two claims of the International Classification of Diseases (ICD) code for DM or at least one claim of the ICD code for DM and prescription of any antidiabetic drugs. Newly diagnosed DM (nDM) and previously diagnosed DM (pDM) were defined as DM diagnosed after and before TB diagnosis, respectively. RESULTS: A total of 26.8% (70 119) of patients were diagnosed with DM. The age-standardised prevalence increased as age increased or income decreased. Patients with DM were more likely to be men, older, had the lowest income group, had more acid-fast bacilli smear and culture positivity, had a higher Charlson Comorbidity Index score and had more comorbidities compared with patients without DM. Approximately 12.5% (8823) patients had nDM and 87.4% (61 296) had pDM among those with TB-DM. CONCLUSIONS: The prevalence of DM among patients with TB was considerably high in Korea. To achieve the goal of TB control and improve the health outcomes of both TB and DM, integrated screening of TB and DM and care delivery in clinical practice are necessary.

Nationwide Treatment Outcomes of Patients With Multidrug/Rifampin-Resistant Tuberculosis in Korea, 2011-2017: A Retrospective Cohort Study (Korean TB-POST).

BACKGROUND: The treatment outcomes of patients with multidrug/rifampin-resistant (MDR/RR) tuberculosis (TB) are important indicators that reflect the current status of TB management and identify the key challenges encountered by TB control programs in a country. METHODS: We retrospectively evaluated the treatment outcomes as well as predictors of unfavorable outcomes in patients with MDR/RR-TB notified from 2011 to 2017, using an integrated TB database. RESULTS: A total of 7,226 patients with MDR/RR-TB were included. The treatment success rate had significantly increased from 63.9% in 2011 to 75.1% in 2017 (P < 0.001). Among unfavorable outcomes, the proportion of patients who failed, were lost to follow up, and were not evaluated had gradually decreased (P < 0.001). In contrast, TB-related death rate was not significantly changed (P = 0.513), while the non-TB related death rate had increased from 3.2% in 2011 to 11.1% in 2017 (P < 0.001). Older age, male sex, immigrants, low household income, previous history of TB treatment, and comorbidities were independent predictors of unfavorable outcomes. Of the 5,308 patients who were successfully treated, recurrence occurred in 241 patients (4.5%) at a median 18.4 months (interquartile range, 9.2-32.4) after completion treatment. CONCLUSION: The treatment outcomes of patients with MDR/RR-TB has gradually improved but increasing deaths during treatment is an emerging challenge for MDR-TB control in Korea. Targeted and comprehensive care is needed for vulnerable patients such as the elderly, patients with comorbidities, and those with low household incomes.

Sex differences in the impact of diabetes mellitus on tuberculosis recurrence: a retrospective national cohort study.

OBJECTIVES: Whether diabetes mellitus (DM) increases tuberculosis (TB) recurrence risk is debatable. We determined the effect of DM on TB recurrence. METHODS: This retrospective nationwide cohort study included patients with TB who successfully completed TB treatment during 2011-2017 and were followed up for TB recurrence until August 2020. We performed subdistribution hazard model analyses stratified by sex to assess DM risk related to TB recurrence after successful treatment. RESULTS: Of 199,571 participants who had received successful TB treatment, 47,952 (24%) had DM. There were more men (64.4%), positive acid-fast bacilli smears (35.9%), and positive cultures (49.5%) in the DM group. There were 6208 (3.1%) TB recurrences during 5.1 years of follow-up: 38.9% and 26.6% occurred 1 and 1-2 years after treatment completion, respectively. The recurrence rate was higher in the DM group (3.8%) than in the non-DM group (2.9%, P <0.0001). DM was associated with a higher TB recurrence risk, especially in men (adjusted hazard ratio 1.23, 95% confidence interval 1.15-1.32) but not in women (adjusted hazard ratio 0.96, 95% confidence interval 0.85-1.09). CONCLUSION: The TB recurrence rate after successful treatment was higher in patients with DM than in patients without DM. DM is associated with TB recurrence in men.

Isolation and Antimicrobial Susceptibility of Nontuberculous Mycobacteria in a Tertiary Hospital in Korea, 2016 to 2020.

BACKGROUND: There is a global increase in isolation of nontuberculous mycobacteria (NTM). The aim of the study was to analyze longitudinal trends of NTM identification and pattern of antimicrobial susceptibility testing. METHODS: NTM recovery rates, distribution of NTM species identification, and antimicrobial susceptibility pattern of NTM at Pusan National University Yangsan Hospital between January 2016 and December 2020 were retrospectively analyzed. RESULTS: A total of 52,456 specimens from 21,264 patients were submitted for mycobacterial culture, of which 2,521 from 1,410 patients were NTM positive over five years (January 2016 to December 2020). NTM isolation showed an increasing trend from 2016 to 2020 (p<0.001, test for trend) mainly caused by Mycobacterium avium complex. The vast majority of M. avium complex were susceptible to key agents clarithromycin and amikacin. For Mycobacterium kansasii, resistance to rifampin and clarithromycin is rare. Amikacin was the most effective drug against Mycobacterium abscessus subspecies abscessus and Mycobacterium subspecies massiliense. Most of M. subspecies massiliense were susceptible to clarithromycin, while the majority of M. abscessus subspecies abscessus were resistant to clarithromycin (p<0.001). CONCLUSION: There was an increasing trend of NTM isolation in our hospital. Resistance to key drugs was uncommon for most NTM species except for M. abscessus subspecies abscessus against clarithromycin.

9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea.

BACKGROUND: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis. METHODS: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994. FINDINGS: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group. INTERPRETATION: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis. FUNDING: Korea Disease Control and Prevention Agency, South Korea.

Treatment shortening of drug-sensitive pulmonary tuberculosis using high-dose rifampicin for 3 months after culture conversion (Hi-DoRi-3): a study protocol for an open-label randomized clinical trial.

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.

The feasibility of granzyme B levels using an amperometric immunosensor for lung cancer detection.

Background: Low-dose computed tomography (LDCT) has improved the early detection of lung cancer. However, LDCT scans present several disadvantages, including the abundance of false-positive results, which lead to a high socioeconomic cost, psychological burden, and repeated exposure to radiation. Therefore, the identification of complementary biomarkers is needed to select high-risk individuals for LDCT. Here, we showed that granzyme B testing with the novel immunosensor has diagnostic value for identifying patients with lung cancer. Methods: We enrolled 44 patients with lung cancer and 51 health controls at Pusan National University Yangsan Hospital in Korea between March 2018 and September 2019. The immunosensor analyzed serum granzyme B levels, and their association with lung cancer detection was evaluated with machine learning models. Results: Serum granzyme B levels were assessed in samples from patients with lung cancer and healthy individuals. Granzyme B testing showed 100% sensitivity, 80% specificity, and an area under the curve of 0.938 for lung cancer detection. After combining granzyme B testing with clinical predictors such as age, smoking status, or pack-years, results from the five-fold cross-validation with random forest model improved diagnostic accuracy of 92.1%, with a sensitivity, specificity, and area under the curve of 92.0%, 92.1%, and 0.977, respectively. Conclusions: This feasibility study suggested that granzyme B may be utilized to detect lung cancer.

Prognostic impact of preoperative respiratory colonization on early-onset pneumonia after lung transplantation.

Background: The number of lung transplantation procedures is rapidly increasing worldwide. Little is known about the effect of perioperative respiratory microbial colonization on pneumonia during lung transplantation. We evaluated the microbiome composition and incidence of early pneumonia in patients undergoing lung transplantation. We investigated factors related to post-transplant pneumonia (PTP) after lung transplantation. Methods: A retrospective analysis of patients subjected to lung transplantation between May 2013 and December 2019 was performed. Perioperative microbial colonization, and its relationship with early pneumonia, were examined in specimens from bronchial washing, bronchoalveolar lavage, and sputum aspiration before and after surgery. One-year mortality, as the primary outcome, was analyzed using the Kaplan-Meier curve model. Results: Among 76 patients who underwent lung transplantation, 34 donors (44.7%) and 28 recipients (36.8%) showed positive respiratory cultures with respect to preoperative respiratory colonization. A separate analysis of donors and recipients showed that 42 donors and 48 recipients were in respiratory non-colonized state, and 28 (53.8%) donors and 36 (69.2%) recipients survived 1 year after lung transplantation. Acinectobacter baumannii was the most common respiratory multidrug-resistant (MDR) pathogen. PTP was significantly lower in the survivor group (38.5% vs. 70.8%, P=0.009). Out of the recipients with preoperative respiratory colonization, 57.1% survived 1 year after lung transplantation. Patients with PTP had significantly higher 1-year mortality than those without PTP (P=0.009). Preoperative respiratory colonization of the recipients (P=0.010) and PTP patients (P=0.005) was associated with high 1-year mortality rate. Perioperative respiratory colonization of donors was not associated with the incidence of PTP and 1-year survival. Conclusions: Perioperative colonization of recipients was a powerful predictive factor for PTP, which was associated with 1-year mortality in patients subjected to lung transplantation. Our results suggest that donor acceptance criteria may change to better address potential shortages in organ donation.