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.

Background: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. Methods: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. Results: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. Conclusion In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

Background/Aims: Intensive care unit (ICU) quality is largely determined by the mortality rate. Therefore, we aimed to develop and validate a novel prognostic model for predicting mortality in Korean ICUs, using national insurance claims data. Methods: Data were obtained from the health insurance claims database maintained by the Health Insurance Review and Assessment Service of South Korea. From patients who underwent the third ICU adequacy evaluation, 42,489 cases were enrolled and randomly divided into the derivation and validation cohorts. Using the models derived from the derivation cohort, we analyzed whether they accurately predicted death in the validation cohort. The models were verified using data from one general and two tertiary hospitals. Results: Two severity correction models were created from the derivation cohort data, by applying variables selected through statistical analysis, through clinical consensus, and from performing multiple logistic regression analysis. Model 1 included six categorical variables (age, sex, Charlson comorbidity index, ventilator use, hemodialysis or continuous renal replacement therapy, and vasopressor use). Model 2 additionally included presence/absence of ICU specialists and nursing grades. In external validation, the performance of models 1 and 2 for predicting in-hospital and ICU mortality was not inferior to that of pre-existing scoring systems. Conclusions The novel and simple models could predict in-hospital and ICU mortality and were not inferior compared to the pre-existing scoring systems.

Purpose: Acute kidney injury (AKI) following sepsis is associated with higher mortality; however, reliable biomarkers for AKI development and recovery remain to be elucidated. Materials and Methods: Patients with sepsis admitted to the medical intensive care unit (ICU) of Severance Hospital between June 2018 and May 2019 were prospectively analyzed. Patients were divided into those with and without AKI within 48 hours. Patients with septic AKI were subdivided into AKI-recovery and non-recovery groups based on whether their kidney injury recovered within 7 days. Results: A total of 84 patients were enrolled. The baseline creatinine (2.9 mg/dL vs. 0.8 mg/dL vs. 1.2 mg/dL, p<0.001), Charlson Comorbidity Index (4.5 vs. 2.0 vs. 3.0, p=0.002), Sequential Organ Failure Assessment (10.0 vs. 6.5 vs. 8.0, p<0.001), and Acute Physiology and Chronic Health Evaluation II scores (32.0 vs. 21.5 vs. 30.5, p=0.004) were higher in the non-recovery AKI group compared to the non-AKI and AKI-recovery groups. The Kaplan-Meier curves revealed that non-recovery from AKI was associated with lower survival (p<0.001). High-lactate (p≤0.05) and kynurenine levels (p≤0.05) were associated with non-recovery of renal function following AKI. The areas under the curve for predicting non-recovery from AKI were 0.693 and 0.721 for lactate and kynurenine, respectively. The survival rate was lower in the high-kynurenine (p=0.040) and high-lactate (p=0.010) groups. Conclusion The mortality of patients who recovered from AKI was comparable to that of patients without AKI. Lactate and kynurenine could be useful biomarkers for the diagnosis and recovery of AKI following sepsis.

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death.While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation.Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.

Purpose: We aimed to determine the relationship between environmental exposure and nontuberculous mycobacterial pulmonary disease (NTM-PD) in Korea. Materials and Methods: A group of 150 patients with NTM-PD and a control group of 217 patients with other respiratory diseases were prospectively enrolled between June 2018 and December 2020 in Seoul, Korea. They were surveyed with a standardized questionnaire, and their medical records were reviewed. Odds ratio (OR) and 95% confidence intervals (CI) were calculated with multivariate logistic regression analysis. Results: The mean ages of the NTM-PD and control groups were similar (63.8±9.2 years vs. 63.5±10.0 years; p=0.737), and most patients were female (76.0% vs. 68.7%; p=0.157) and nonsmokers (82.0% vs. 72.8%; p=0.021). Mycobacterium avium (49.3%) was the most commonly identified strain among NTM-PD patients, followed by M. intracellulare (32.0%) and M. abscessus subspecies massiliense (12.7%). There were no differences in housing type or frequency of soil- or pet-related exposure between the case and the control groups. However, in subgroup analysis excluding patients with M. intracellulare infection, more case patients frequently visited public baths ≥1 time/week (35.3% vs. 19.4%, p=0.003); this remained significant after multivariate analysis (OR, 2.84; 95% CI, 1.58–5.17). Conclusion Frequent exposure to water at public baths might affect the odds of contracting NTM-PD, excluding individuals infected with M. intracellulare strains.

Purpose: We aimed to determine the relationship between environmental exposure and nontuberculous mycobacterial pulmonary disease (NTM-PD) in Korea. Materials and Methods: A group of 150 patients with NTM-PD and a control group of 217 patients with other respiratory diseases were prospectively enrolled between June 2018 and December 2020 in Seoul, Korea. They were surveyed with a standardized questionnaire, and their medical records were reviewed. Odds ratio (OR) and 95% confidence intervals (CI) were calculated with multivariate logistic regression analysis. Results: The mean ages of the NTM-PD and control groups were similar (63.8±9.2 years vs. 63.5±10.0 years; p=0.737), and most patients were female (76.0% vs. 68.7%; p=0.157) and nonsmokers (82.0% vs. 72.8%; p=0.021). Mycobacterium avium (49.3%) was the most commonly identified strain among NTM-PD patients, followed by M. intracellulare (32.0%) and M. abscessus subspecies massiliense (12.7%). There were no differences in housing type or frequency of soil- or pet-related exposure between the case and the control groups. However, in subgroup analysis excluding patients with M. intracellulare infection, more case patients frequently visited public baths ≥1 time/week (35.3% vs. 19.4%, p=0.003); this remained significant after multivariate analysis (OR, 2.84; 95% CI, 1.58–5.17). Conclusion Frequent exposure to water at public baths might affect the odds of contracting NTM-PD, excluding individuals infected with M. intracellulare strains.

Background/Aims: Delayed diagnosis and treatment of smear-negative pulmonary tuberculosis (TB) are major concerns for TB control. We evaluated characteristics of patients with smear-negative pulmonary TB who received a delayed diagnosis and identified risk factors that may have contributed to this delay. Methods: We reviewed medical records of patients with smear-negative culture-positive pulmonary TB treated at a tertiary care hospital in South Korea between January 2017 and December 2018. Patients who initiated anti-TB treatment after positive cultures were included in the missed TB group, and those who initiated empirical treatment before positive cultures were included in the control group. Results: Of 220 patients included, 117 (53.2%) and 103 (46.8%) were in the missed TB and control groups, respectively. Patients in the missed TB group were older (p = 0.001) and had a higher mean body mass index (BMI) (p = 0.019). Comorbidities (66.9% vs. 46.6%, p = 0.003) and immunocompromised patients (33.1% vs. 20.4%, p = 0.035) were more common in the missed TB group than in the control group. Old age (odds ratio [OR], 1.030; 95% confidence interval [CI], 1.012 to 1.048; p = 0.001), high BMI (OR, 1.114; 95% CI, 1.004 to 1.237; p = 0.042), and negative polymerase chain reaction (PCR) results (OR, 9.551; 95% CI, 4.925 to 18.521; p < 0.001) were associated with delayed diagnosis. Conclusions In more than half of patients with smear-negative pulmonary TB, the diagnosis was delayed. Patients with delayed TB diagnosis were older, had higher BMI, and negative PCR results.