Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

BACKGROUND: Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. METHODS: A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. RESULTS: Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. CONCLUSION: Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

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.

Epidemiological Characteristics of Nontuberculous Mycobacterial Pulmonary Disease in South Korea: A Meta-Analysis of Individual Participant Data.

Rationale: Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), there are geographical variations in clinical characteristics. We investigated the clinical characteristics of patients with NTM-PD in South Korea. Methods: We systematically reviewed articles about patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. Results: The data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5 ± 11.7 years, and 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and Mycobacterium abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Reported cases of NTM-PD increased over the years, but the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 vs. 59.9 years, P<0.001) and had more cavitary lesions than women (38.8% vs. 21.0%, P<0.001). The older group (≥65 years) had a higher proportion of patients with body mass index <18.5 kg/m2 (27.4% vs. 18.6%, P<0.001) and cavitary lesions (29.9% vs. 27.6%, P=0.009) than the younger group. Conclusion: We performed a meta-analysis of the clinical characteristics of patients with NTM-PD in South Korea. We found age- and sex-related differences in disease-specific severity. Further investigation would enhance our comprehension of the disease's nature and inherited and acquired host factors.

Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.

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.

Factors affecting accuracy of clinical staging in resectable non-small cell lung cancer in a real-world study.

BACKGROUND: The clinical staging of non-small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real-world data. METHODS: Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. RESULTS: Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET-CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32-0.76, p = 0.001) and a higher clinical stage (p < 0.001) contributed to the clinical staging inaccuracy. Additionally, the presence of a bronchoscopy specialist was significantly associated with clinical staging accuracy (OR 1.53; 95% CI: 1.10-2.13, p = 0.011). CONCLUSION: Clinical staging accuracy in NSCLC improved compared to before the widespread use of PET-CT and EBUS in clinical staging work-up. Smoking history and absence of expert bronchoscopy specialists showed a meaningful correlation with the inaccuracy of clinical staging. Thus, training more bronchoscopy experts would improve the staging accuracy of NSCLC, which could positively affect the prognosis of NSCLC.

A Quasi-experimental Study on the Effect of Pre-entry Tuberculosis Screening for Immigrants on Treatment Outcomes in South Korea: A Difference-in-Differences Analysis.

OBJECTIVE: This study ascertains the effects of the pre-entry tuberculosis (TB) screening policy, which was implemented as a strategy for managing TB among immigrants, on the treatment outcomes of immigrants in South Korea. METHODS: This study linked three different datasets from 2013 to 2018, namely (1) Korean National Tuberculosis Surveillance System; (2) National Health Information Database for patients diagnosed with TB with ICD code A15-A19, B90, or U84.3; and (3) Statistics Korea database related to cause of deaths. To identify the effect of the policy, cohorts comprising Korean and immigrant TB patients notified before (January 1, 2013-December 31, 2015) and after (September 1, 2016-December 31, 2018), the implementations of the policy were established. A difference-in-differences (DID) analysis of the treatment success and mortality rates was performed. RESULTS: Data from 100,262 TB patients were included in the analysis (before policy implementation: 1240 immigrants and 65,723 Koreans; after policy implementation: 256 immigrants and 33,043 Koreans). The propensity score matching-DID analysis results showed that the difference in the treatment success rate between immigrants and Koreans decreased significantly, from 16% before to 6% after the policy implementation. The difference in the mortality rate between the two groups decreased from - 3% before to - 1% after the policy implementation; however, this difference was insignificant. CONCLUSION: The treatment outcomes of immigrant TB patients in South Korea improved after the implementation of the pre-entry active TB screening policy. Future immigrant TB policies should consider establishing active patient support strategies and a healthcare collaboration system between countries.

Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Diagnosis of Primary Ciliary Dyskinesia via Whole Exome Sequencing and Histologic Findings.

PURPOSE: To assess the diagnostic potential of whole-exome sequencing (WES) and elucidate the clinical and genetic characteristics of primary ciliary dyskinesia (PCD) in the Korean population. MATERIALS AND METHODS: Forty-seven patients clinically suspected of having PCD were enrolled at a tertiary medical center. WES was performed in all patients, and seven patients received biopsy of cilia and transmission electron microscopy (TEM). RESULTS: Overall, PCD was diagnosed in 10 (21.3%) patients: eight by WES (8/47, 17%), four by TEM. Among patients diagnosed as PCD based on TEM results, two patients showed consistent results with WES and TEM of PCD (2/4, 50%). In addition, five patients, who were not included in the final PCD diagnosis group, had variants of unknown significance in PCD-related genes (5/47, 10.6%). The most frequent pathogenic (P)/likely pathogenic (LP) variants were detected in DNAH11 (n=4, 21.1%), DRC1 (n=4, 21.1%), and DNAH5 (n=4, 21.1%). Among the detected 17 P/LP variants in PCD-related genes in this study, 8 (47.1%) were identified as novel variants. Regarding the genotype-phenotype correlation in this study, the authors experienced severe PCD cases caused by the LP/P variants in MCIDAS, DRC1, and CCDC39. CONCLUSION: Through this study, we were able to confirm the value of WES as one of the diagnostic tools for PCD, which increases with TEM, rather than single gene tests. These results will prove useful to hospitals with limited access to PCD diagnostic testing but with relatively efficient in-house or outsourced access to genetic testing at a pre-symptomatic or early disease stage.

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.

Real-world impact of the fixed-dose combination on improving treatment outcomes of drug-susceptible tuberculosis: a comparative study using multiyear national tuberculosis patient data.

BACKGROUND: The fixed-dose combination (FDC) for first-line antituberculosis (TB) treatment has long been a standard practice worldwide; however, there is limited evidence on whether the use of FDC improves long-term treatment outcomes in the real-world setting. METHODS: We identified 32 239 newly diagnosed patients with drug-susceptible (DS) TB in 2015 and 2016 who had been prescribed FDC or non-FDC TB treatment from a multiyear (2013-2018) national TB cohort database that linked the Korean National Tuberculosis Surveillance System, the National Health Insurance Database and the Health Insurance Review and Assessment Service database. Inverse probability of treatment weighting (IPTW) with a propensity score was used to control for differences in patient characteristics between 5926 patients with TB treated with FDC and 26 313 patients with non-FDC. Multivariable logistic regression analyses were performed to assess for the factors influencing treatment outcomes between the two groups. RESULTS: After IPTW, new patients with DS-TB treated with FDC had higher treatment completion rate (83.9% vs 78.9%, p<0.01) and lower death rates (8.2% vs 9.8%, p<0.01) with similar TB recurrence rate (2.3% vs 2.4%) compared with those treated with non-FDC. In multivariable analyses, FDC use had higher odds treatment completion (adjusted OR 1.45; 95% CI 1.34 to 1.56). Patients with TB with younger age (relative to 70+ age) and higher income level had higher odds for treatment completion. Use of FDC did not influence TB recurrence after treatment completion (adjusted HR 0.94; 95% CI 0.77 to 1.16). The acquired drug resistance rate was similar between the two groups (drug-resistant TB in FDC 4.7% vs non-FDC 5.3%; p=0.80). CONCLUSION: In Korea, prescription of FDC to treat newly diagnosed patients with DS TB improved patient's treatment completion. Use of FDC did not increase the risks of TB recurrence or development of drug resistance.

Alterations in lung and gut microbiota reduce diversity in patients with nontuberculous mycobacterial pulmonary disease.

BACKGROUND/AIMS: Although the incidence of nontuberculous mycobacteria pulmonary disease (NTM-PD), a chronic infectious disease, is increasing, lung and gut microbiota dysbiosis in NTM patients has rarely been studied and was therefore the focus of this study. METHODS: We analyzed the microbiota diversity in sputum and stool samples from 10 healthy subjects and 10 patients with NTM-PD through sequencing of the V3 and V4 regions of the 16S rRNA gene. In NTM-PD patients, we comparatively evaluated the microbiota diversity according to the body mass index (BMI), with BMI ≤ 18.5 kg/m2 defined as "underweight" and BMI > 18.5 kg/m2 as "others." RESULTS: The sputum microbiota from NTM-PD patients tended to have lower index values of amplicon sequence variant richness, Shannon evenness, and beta diversity than those from the control group. Furthermore, NTM-PD patients with a low BMI had a lower microbiota diversity than patients with high BMI. Fecal samples from NTM-PD patients also significantly differed in alpha and beta diversity compared with the control group and exhibited a diversity pattern similar to that found in sputum samples. CONCLUSION: Our results reveal that the lung and gut microbiota of patients with NTM-PD exhibit an altered distribution and reduced richness and diversity.

Disseminated Nontuberculous Mycobacterial Infection in a Tertiary Referral Hospital in South Korea: A Retrospective Observational Study.

PURPOSE: Disseminated nontuberculous mycobacterial (D-NTM) disease occurs primarily in immunocompromised hosts. However, these cases have rarely been reported in South Korea. This study aimed to describe the clinical manifestations, disease course, and underlying immune deficiencies of patients with D-NTM disease. MATERIALS AND METHODS: We retrospectively reviewed the cases of D-NTM disease from January 2005 to December 2019 at a tertiary referral hospital in South Korea. D-NTM disease was defined as a bloodstream infection or infection of two or more non-contiguous body organs with species identification. RESULTS: Of the 53342 mycobacterial samples from 23338 patients, extrapulmonary NTM was detected in 104 patients, and 3 (2.9%) were diagnosed with D-NTM disease. Mycobacterium avium was isolated from two patients, while M. abscessus subspecies abscessus was identified in one. The patients were aged between 18 and 25 years, and two patients were male. All patients were immunocompromised - one received lung transplantation, one was diagnosed with anhidrotic ectodermal dysplasia with T-cell immune deficiency, and one had monocytopenia and mycobacterial infection syndrome associated with GATA2 mutations. All patients underwent a standard macrolide-based regimen for >5 months, and their sputum tested negative. However, one patient died of bacterial sepsis, while the other two survived. CONCLUSION: D-NTM disease is rare in a tertiary referral center in South Korea. They occur primarily in immunocompromised patients at a relatively young age. Careful investigation of the underlying immune status is required when treating patients with D-NTM disease.

Incidence and associated risk factors of nontuberculous mycobacterial infection in patients with depression.

BACKGROUND: It has been reported that the risk of mental health problems such as anxiety or depression increases in patients with nontuberculous mycobacterial (NTM) infection. However, no studies have investigated whether the incidence of NTM infection increases in patients with depression. This study aimed to investigate the incidence of NTM infection in patients with depression and evaluate the association between NTM infection and depression stratified by age and sex. METHODS: Data from 2002 to 2013 were collected from patients aged ≥ 20 years in the National Health Insurance Service-National Sample Cohort database. Patients with and without depression aged over 20 years were matched with 1 to 4 by sex, age, and year of diagnosis. The incidence rate was calculated in 100,000 person-years, and a multivariable subdistribution hazard model was used to evaluate the adjusted hazard ratio (aHR) for the development of NTM infection. RESULTS: We included 37,554 individuals (12,752 men and 24,802 women) and 149,213 controls in the depression and non-depression groups, respectively. The cumulative incidence of NTM infection did not differ significantly between the depression and non-depression groups during the follow-up period (22.2 vs. 24.5 per 100,000 person-years, p = 0.571). The age- and sex-stratified effects on the incidence of NTM infection were not significantly higher in patients with depression than in those without depression. After adjusting for covariates including age, sex, comorbidity, income, and region, the risk of NTM infection did not significantly differ between the depression and non-depression groups (aHR 0.83, 95% confidence interval 0.58-1.17). CONCLUSION: The incidence of NTM infections in patients with depression was not significantly higher than that in patients without depression. However, due to the small number of NTM infections, we might have underestimated the differences between the two groups. Further studies are needed to identify factors associated with NTM pulmonary disease in patients with depression.

Myosteatosis as a prognostic factor of Mycobacterium avium complex pulmonary disease.

Quantitative body composition affects the prognosis of patients with Mycobacterium avium complex pulmonary disease (MAC-PD). However, whether the qualitative body composition obtained indirectly through computed tomography (CT) affects their prognosis is debatable. We retrospectively analyzed patients with MAC-PD who underwent non-contrast CT at MAC-PD diagnosis. The cross-sectional area of the erector spinae muscle (ESM area), the Hounsfield unit of the erector spinae muscle (ESM HU), and the cross-sectional area of subcutaneous fat (SQF area) were measured at the level of the first lumbar vertebra. Myosteatosis were defined below the median value of ESM HU for each sex. Of 377 patients, 45 (11.9%) died during the follow-up. Patients who died were older and had a lower ratio of females (33.3%). In body compositions, SQF area and ESM HU were lower in the patients who died. In multivariable analysis, a low ESM HU was associated with increased mortality (ESM HU adjusted hazard ratio [aHR] 0.95, 95% confidence interval [CI] 0.93-0.97) through body composition. SQF area revealed protective effects in MAC-PD patients with body mass index ≥ 18.5 kg/m2 (aHR 0.98, 95% CI 0.95-1.00). In conclusion, the decrease in ESM HU, which indirectly reflects myosteatosis, is associated with mortality in patients with MAC-PD.

Utilization of artificial intelligence for tuberculosis screening in Nepal.

BACKGROUNDS: Tuberculosis (TB) is an infectious disease that needs to be diagnosed and enrolled for treatment. Artificial intelligence for TB (AI4TB) software screens TB suspected cases at the point of care and helps in quick diagnosis. This study aims to explore the significance and usefulness of AI4TB by comparing its performance with different diagnostic test results. METHODS: A cross-sectional study was conducted among 197 participants who had symptoms suggestive to TB. The chest X-ray images were analyzed by AI4TB software and human expert readers. The bacteriological test results were obtained, and Kappa test was applied to calculate the inter-reader reliability. The sensitivity, specificity, positive predictive value and negative predictive value was calculated and ROC curve was generated. RESULTS: Among 85 sputum smear microscopy, about 21% of the had sputum positivity rate. At 0.4 threshold: 62.4%, at 0.5 threshold: 58.4% and at 0.6 threshold: 50.3% symptoms suggestive cases were identified having abnormal X-ray images. Reader-I identified 28.4% and Reader-II identified 37.1% of the symptoms suggestive cases of TB as positive cases. There was a significant substantial agreement between two human expert readers (k-0.783, p-value: <0.001). The ROC curve explored the fair sensitivity accuracy of the AI4TB test results at 0.5 threshold level (AUC = 0.72) and at 0.6 threshold level (AUC = 0.77). CONCLUSION: The sensitivity of the AI4TB was higher compared to different human readers. AI4TB can be the relevant screening tool for the TB symptoms suggestive cases prior to the laboratory test in the countries like Nepal with deficient health manpower.

Safety and Immunogenicity of the ID93 + GLA-SE Tuberculosis Vaccine in BCG-Vaccinated Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This randomized, double-blind, placebo-controlled, phase 2a trial was conducted to evaluate the safety and immunogenicity of the ID93 + glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) vaccine in human immunodeficiency virus (HIV)-negative, previously Bacillus Calmette-Guérin (BCG)-vaccinated, and QuantiFERON-TB-negative healthy adults in South Korea. METHODS: Adults (n = 107) with no signs or symptoms of tuberculosis were randomly assigned to receive three intramuscular injections of 2 µg ID93 + 5 µg GLA-SE, 10 µg ID93 + 5 µg GLA-SE, or 0.9% normal saline placebo on days 0, 28, and 56. For safety assessment, data on solicited adverse events (AEs), unsolicited AEs, serious AEs (SAEs), and special interest AEs were collected. Antigen-specific antibody responses were measured using serum enzyme-linked immunosorbent assay. T-cell immune responses were measured using enzyme-linked immunospot and intracellular cytokine staining. RESULTS: No SAEs, deaths, or AEs leading to treatment discontinuation were found. The solicited local and systemic AEs observed were consistent with those previously reported. Compared with adults administered with the placebo, those administered with three intramuscular vaccine injections exhibited significantly higher antigen-specific antibody levels and Type 1 T-helper cellular immune responses. CONCLUSION: The ID93 + GLA-SE vaccine induced antigen-specific cellular and humoral immune responses, with an acceptable safety profile in previously healthy, BCG-vaccinated, Mycobacterium tuberculosis-uninfected adult healthcare workers. TRIAL REGISTRATION: This clinical trial was retrospectively registered on 16 January 2019 at Clinicaltrials.gov (NCT03806686).

Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer.

Introduction: Regarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC). Methods: A review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0). Results: Among 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth's bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration. Conclusions: Given the incidence and favorable outcome of BM in patients with suspected early-stage NSCLC, selective screening with brain MRI may be considered, especially in patients with high-risk features.

Cost-Effectiveness of Age-Expanding Strategy of Latent Tuberculosis Infection Treatment in Household Contacts in South Korea.

PURPOSE: The strategy of latent tuberculosis infection (LTBI) treatment in household tuberculosis (TB) contacts has been expanding in South Korea. However, there is little evidence of the cost-effectiveness of LTBI treatment in patients over 35 years of age. This study aimed to evaluate the cost-effectiveness of LTBI treatment among household TB contacts in different age groups in South Korea. MATERIALS AND METHODS: An age-structured model of TB was developed based on the reports from the Korea Disease Control and Prevention Agency and the National Health Insurance Service. Quality-adjusted life-years (QALY) and the averted number of TB-related deaths were estimated along with discounted costs for a measure of incremental cost-effectiveness ratios. RESULTS: The number of cumulative active TB cases would decrease by 1564 and 7450 under the scenario of LTBI treatment for those aged <35 years and <70 years, respectively, relative to the no-treatment scenario. The treatment strategies for patients aged 0 to <35 years, <55 years, <65 years, and <70 years would add 397, 1482, 3782, and 8491 QALYs at a cost of $660, $5930, $4560, and $2530, respectively, per QALY. For the averted TB-related deaths, LTBI treatment targeting those aged 0 to <35 years, <55 years, <65 years, and <70 years would avert 7, 89, 155, and 186 deaths at a cost of $35900, $99200, $111100, and $115700 per deaths, respectively, in 20 years. CONCLUSION: The age-specific expansion policy of LTBI treatment not only for those under 35 years of age but also for those under 65 years of age among household contacts was cost-effective in terms of QALYs and averted TB deaths.

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.