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.

Pre-Sepsis Length of Hospital Stay and Mortality: A Nationwide Multicenter Cohort Study.

BACKGROUND: Prolonged length of hospital stay (LOS) is associated with an increased risk of hospital-acquired conditions and worse outcomes. We conducted a nationwide, multicenter, retrospective cohort study to determine whether prolonged hospitalization before developing sepsis has a negative impact on its prognosis. METHODS: We analyzed data from 19 tertiary referral or university-affiliated hospitals between September 2019 and December 2020. Adult patients with confirmed sepsis during hospitalization were included. In-hospital mortality was the primary outcome. The patients were divided into two groups according to their LOS before the diagnosis of sepsis: early- (< 5 days) and late-onset groups (≥ 5 days). Conditional multivariable logistic regression for propensity score matched-pair analysis was employed to assess the association between late-onset sepsis and the primary outcome. RESULTS: A total of 1,395 patients were included (median age, 68.0 years; women, 36.3%). The early- and late-onset sepsis groups comprised 668 (47.9%) and 727 (52.1%) patients. Propensity score-matched analysis showed an increased risk of in-hospital mortality in the late-onset group (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.69-5.34). The same trend was observed in the entire study population (aOR, 1.85; 95% CI, 1.37-2.50). When patients were divided into LOS quartile groups, an increasing trend of mortality risk was observed in the higher quartiles (P for trend < 0.001). CONCLUSION: Extended LOS before developing sepsis is associated with higher in-hospital mortality. More careful management is required when sepsis occurs in patients hospitalized for ≥ 5 days.

Clinical course of nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis.

OBJECTIVES: The impact of rheumatoid arthritis (RA) on nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been well established. In this study, we investigated the clinical course of NTM-PD in patients with RA and the impact of RA on the prognosis of NTM-PD. METHODS: We analyzed patients who developed NTM-PD after being diagnosed with RA from January 2004 to August 2023 at a tertiary referral hospital in South Korea. The patient's baseline characteristics, clinical course, and prognosis were evaluated. An optimal matching analysis was performed to measure the impact of RA on the risk of mortality. RESULTS: During the study period, 18 patients with RA [median age, 68 years; interquartile range (IQR) 59-73; female, 88.9%] developed NTM-PD. The median interval between RA diagnosis and subsequent NTM-PD development was 14.8 years (IQR, 8.6-19.5). At a median of 30 months (IQR, 27-105) after NTM-PD diagnosis, 10 of 18 (55.6%) patients received anti-mycobacterial treatment for NTM-PD and 5 (50.0%) patients achieved microbiological cure. When matched to patients with NTM-PD but without RA, patients with both RA and NTM-PD had a higher risk of mortality (adjusted hazard ratio, 8.14; 95% confidence interval, 2.43-27.2). CONCLUSION: NTM-PD occurring after RA is associated with a higher risk of mortality than NTM-PD in the absence of RA.

Rates and Risk Factors of Progression in Patients With Nontuberculous Mycobacterial Pulmonary Disease: Secondary Analysis of a Prospective Cohort Study.

BACKGROUND: The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy. RESEARCH QUESTION: What is the rate of NTM-PD progression, and what are the predictors of progression? STUDY DESIGN AND METHODS: Patients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022, were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician's intention to treat. The rate of progression was calculated and the predictors for progression were analyzed. RESULTS: Of the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% CI, 9.5-12.7 cases per 100 person-years). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.19-2.39), elevated erythrocyte sedimentation rate (aHR, 1.79; 95% CI, 1.31-2.43), FEV1 % predicted (aHR, 0.89; 95% CI, 0.82-0.96), and the presence of a cavity (aHR, 2.78; 95% CI, 2.03-3.80) as predictors of progression. INTERPRETATION: About half of patients with NTM-PD experienced progression during an observation period of > 5 years. Patients with risk factors for progression should be observed closely. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01616745; URL: www. CLINICALTRIALS: gov.

Treatment Outcomes of Clofazimine-Containing Regimens in Severe Mycobacterium avium Complex Pulmonary Disease.

Background: Clofazimine is suggested as a promising drug for the treatment of nontuberculous mycobacterial pulmonary disease. However, the role of clofazimine in severe Mycobacterium avium complex pulmonary disease (MAC-PD) remains unclear. In this study, we investigated the treatment outcomes of patients with severe MAC-PD treated with regimens containing clofazimine. Methods: This study included patients diagnosed with severe MAC-PD at Seoul National University Hospital who underwent anti-mycobacterial treatment between 1 January 2011 and 31 December 2022. We assessed the rate of culture conversion within 6 months and microbiological cure in patients receiving clofazimine-containing regimens, considering the dose and duration of clofazimine administration. Results: A total of 170 patients with severe MAC-PD, treated with regimens containing clofazimine, were included in the analysis. The median age of patients was 68 years (interquartile range, 59-75 years), with a female predominance (n = 114 [67.1%]). Cavities were identified in 121 patients (71.2%). Within 6 months, 77 patients (45.3%) achieved culture conversion, and 84 of 154 (54.6%) patients attained microbiological cure. The dose of clofazimine (100 mg vs 50 mg) was not associated with culture conversion (adjusted odds ratio [aOR], 0.64 [95% confidence interval {CI}, .29-1.42]) or microbiological cure (aOR, 1.21 [95% CI, .52-2.81]). The microbiological cure rate reached 71.0% when clofazimine was administered for 6-12 months, compared to 23.1% when administered for <6 months. Conclusions: Clofazimine demonstrated a relatively favorable efficacy in severe MAC-PD, regardless of the maintenance dose. This effect was more pronounced when administered for a duration exceeding 6 months.

Metabolomic Characteristics of Nontuberculous Mycobacterial Pulmonary Disease.

BACKGROUND: The therapeutic challenges posed by nontuberculous mycobacterial pulmonary disease (NTM-PD) contribute to an unmet medical need. In this study, we aimed to investigate NTM-PD-specific metabolic pathways using serum metabolomics to understand disease pathogenesis. METHODS: Mass spectrometry-based untargeted metabolomic profiling of serum from patients with NTM-PD (n = 50), patients with bronchiectasis (n = 50), and healthy controls (n = 60) was performed. Selected metabolites were validated by an independent cohort and subjected to pathway analysis and classification modeling. RESULTS: Leucine, tyrosine, inosine, proline, 5-oxoproline, and hypoxanthine levels increased in the NTM-PD group compared with the healthy control group. Furthermore, levels of antioxidant metabolites (ferulic acid, α-lipoic acid, biotin, and 2,8-phenazinediamine) decreased in patients with NTM-PD. These changes were associated with arginine- and proline-related metabolism, leading to generation of reactive oxygen species. Interestingly, the observed metabolic changes in the NTM-PD group overlapped with those in the bronchiectasis group. CONCLUSION: In NTM-PD, 11 metabolites linked to increased oxidative stress were significantly altered from those in healthy controls. Our findings enhance a comprehensive understanding of NTM-PD pathogenesis and provide insights for novel treatment approaches.

The Impact of Trehalose Dimycolate on the Clinical Course of Mycobacterium avium Complex Pulmonary Disease.

Rationale The clinical implications of trehalose 6,6'-dimycolate (TDM) in nontuberculous mycobacterial pulmonary disease have not been studied. Objective To examine the presence of TDM in clinical isolates obtained from patients with Mycobacterium avium complex (MAC) pulmonary disease (PD) and its impact on disease severity and treatment outcomes. Methods We analyzed clinical isolates from patients diagnosed with MAC-PD at Seoul National University Hospital between January 1, 2019, and December 31, 2021. The lipids were extracted from clinical isolates obtained at the time of diagnosis using mass spectrometry. Mass peaks between 300 and 3,500 m/z were obtained, and the peak patterns of the total lipids were analyzed. Results TDMs were identified in clinical isolates from 176 out of 343 patients. Cavities were more prevalent in patients with TDM-negative isolates (19.8%) than in patients with TDM-positive isolates (10.2%) (P=0.015). The time to antibiotic treatment was shorter in patients with TDM-negative isolates (4 months, interquartile range [IQR] 2-10) than in patients with TDM-positive isolates (7 months, IQR 3-16, P=0.032). Patients with TDM-negative isolates had a significantly lower proportion of culture conversions (P=0.012). TDM was associated with higher likelihood of culture conversion (adjusted hazard ratio, 2.29; P=0.035). Conclusions TDM-negative isolates were linked to a higher occurrence of cavities, earlier initiation of treatment, and worse treatment outcome in MAC-PD patients.

Pulse versus non-pulse corticosteroid therapy in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Corticosteroids are commonly used for the treatment of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF); however, the optimal initial dose of corticosteroids remains uncertain due to a lack of sufficient evidence. We evaluated whether the administration of a pulse dose of corticosteroids resulted in improved survival outcomes compared with conventional non-pulse dose of corticosteroids. METHODS: We retrospectively analysed 238 patients with AE-IPF treated with corticosteroids at a tertiary referral hospital between January 2013 and December 2021. Based on whether a pulse dose of corticosteroids (methylprednisolone of ≥250 mg/day or equivalent) was administered within 7 days of hospitalization for AE-IPF, the patients were divided into the pulse and non-pulse regimen groups. The survival outcomes were compared between the two groups using multivariable regression and propensity score-matched analyses. RESULTS: Among the 238 patients, 59 patients received pulse dose of corticosteroids, whereas 179 patients received conventional non-pulse dose of corticosteroids. After adjusting for the confounding factors related to the baseline clinical and radiographic severity, compared with the conventional non-pulse regimen, the pulse regimen of corticosteroids did not reduce the risk of mortality at the 3-month (aHR 0.84, 95% CI 0.45-1.38) or 12-month (aHR 0.96, 95% CI 0.60-1.25) follow-ups. Propensity score-matched analysis revealed similar results. CONCLUSION: The survival outcomes of patients with AE-IPF who received a pulse dose of corticosteroids did not differ from those of patients who received conventional non-pulse dose of corticosteroids. Further prospective studies are required to establish the optimal initial dose of corticosteroids for the treatment of AE-IPF.

Post-treatment Radiographic Severity and Mortality in Mycobacterium avium Complex Pulmonary Disease.

Rationale: Imaging studies are widely performed when treating Mycobacterium avium complex pulmonary disease (MAC-PD); however, the clinical significance of post-treatment radiographic change is unknown. Objectives: To determine whether a deep neural network trained with pulmonary tuberculosis could adequately score the radiographic severity of MAC-PD and then to examine relationships between post-treatment radiographic severity and its change from baseline and long-term prognosis. Methods: We retrospectively collected chest radiographs of adult patients with MAC-PD treated for ⩾6 months at baseline and at 3, 6, 9, and 12 months of treatment. We correlated the radiographic severity score generated by a deep neural network with visual and clinical severity as determined by radiologists and mycobacterial culture status, respectively. The associations between the score, improvement from baseline, and mortality were analyzed using Cox proportional hazards regression. Results: In total, 342 and 120 patients were included in the derivation and validation cohorts, respectively. The network's severity score correlated with radiologists' grading (Spearman coefficient, 0.40) and mycobacterial culture results (odds ratio, 1.02; 95% confidence interval [CI], 1.0-1.05). A significant decreasing trend in the severity score was observed over time (P < 0.001). A higher score at 12 months of treatment was independently associated with higher mortality (adjusted hazard ratio, 1.07; 95% CI, 1.03-1.10). Improvements in radiographic scores from baseline were associated with reduced mortality, regardless of culture conversion (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.80). These findings were replicated in the validation cohort. Conclusions: Post-treatment radiographic severity and improvement from baseline in patients with MAC-PD were associated with long-term survival.

Genetic stability of Mycobacterium abscessus during antibiotic treatment.

OBJECTIVES: Genetic changes in Mycobacterium abscessus during antibiotic treatment are not fully understood. This study aimed to investigate the genetic changes in M. abscessus in patients receiving antibiotic treatment, and their clinical implications. METHODS: Pretreatment and 12-month post-treatment M. abscessus isolates were obtained from patients with M. abscessus pulmonary disease. Isolates from each time point were separated into six groups based on their distinctive morphological characteristics. Twenty-four isolates, comprising 12 from patient A exhibiting progressive disease and 12 from patient B demonstrating stable disease, underwent sequencing. Subsequently, minimal inhibitory concentrations (MICs) for the administered antibiotics were measured. RESULTS: Persistent infection with a single strain was observed in patients A and B. During 12 months of treatment, MICs for administered drugs did not generally change over time in either patient and single nucleotide variations (SNV) associated with antimicrobial resistance (rrl, rrs, erm(41), gyrA, gyrB, whiB7 and hflX) were not mutated. Although not significant, 47 and 52 non-synonymous SNVs occurred in M. abscessus from patients A and B, respectively, and the accumulation of these SNVs differed in patients A and B, except for five SNVs. The most variable positions were within a probable NADH-dependent glutamate synthase gene and a putative YrbE family protein gene in patients A and B, respectively. CONCLUSIONS: Persistent infections by a single strain of M. abscessus were observed in two patients with different clinical courses. Genetic changes in M. abscessus during antibiotic treatment were relatively stable in these patients. CLINICAL TRIALS IDENTIFIER: NCT01616745 (ClinicalTrials.gov ID).

Microbiological Cure at Treatment Completion Is Associated With Longer Survival in Patients With Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: Morbidity and mortality from nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing. Mycobacterium avium complex (MAC) is the most common cause of NTM-PD. Microbiological outcomes are widely used as the primary end point of antimicrobial treatment, but their long-term impact on prognosis is uncertain. RESEARCH QUESTION: Do patients who achieve microbiological cure at the end of treatment have longer survival than those who do not? STUDY DESIGN AND METHODS: We retrospectively analyzed adult patients who met the diagnostic criteria for NTM-PD, were infected with MAC species, and were treated with a macrolide-based regimen for ≥ 12 months per guidelines between January 2008 and May 2021 at a tertiary referral center. Mycobacterial culture was performed during antimicrobial treatment to assess the microbiological outcome. Patients with three or more consecutive negative cultures collected ≥ 4 weeks apart and no positive cultures until treatment completion were considered to have achieved microbiological cure. To assess the impact of microbiological cure on all-cause mortality, we performed multivariable Cox proportional hazards regression analysis adjusted for age, sex, BMI, presence of cavitary lesions, erythrocyte sedimentation rate, and underlying comorbid conditions. RESULTS: Among 382 patients enrolled, 236 (61.8%) achieved microbiological cure at completion of treatment. These patients were younger, had lower erythrocyte sedimentation rates, were less likely to use four or more drugs, and had shorter treatment duration than those who failed to achieve microbiological cure. During a median follow-up of 3.2 (first quartile to third quartile, 1.4-5.4) years after treatment completion, 53 patients died. Microbiological cure was significantly associated with reduced mortality after adjustment for major clinical factors (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.94). The association between microbiological cure and mortality was maintained in a sensitivity analysis that included all patients treated < 12 months. INTERPRETATION: Microbiological cure at completion of treatment is associated with longer survival in patients with MAC-PD.

Prognostic serum biomarkers in non-tuberculous mycobacterial pulmonary disease.

Increased serum C-reactive protein (CRP) levels at the time of diagnosis predicted worse prognosis in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). Approximately one-quarter of the patients with NTM-PD had higher than normal CRP levels, and this elevation led to a higher risk of death.

Impact of Treatment on Long-Term Survival of Patients With Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: Whether antimicrobial treatment improves long-term survival in patients with Mycobacterium avium complex pulmonary disease (MAC-PD) is unclear. METHODS: We analyzed survival in patients aged ≥18 years who were treated for MAC-PD at a tertiary referral center in South Korea between 1 January 2009 and 31 December 2020. Treatment exposure was divided into 4 time intervals: <6, ≥6 to <12, ≥12 to <18, and ≥18 months. Time-varying multivariable Cox proportional hazards models were used to calculate the all-cause mortality risk in each time interval. The model was adjusted for major clinical factors related to mortality including age, sex, body mass index, presence of cavities, erythrocyte sedimentation rate, positive acid-fast bacilli (AFB) smear, clarithromycin resistance, and comorbid conditions. RESULTS: A total of 486 patients treated for MAC-PD were included in the analysis. A significant inverse correlation was observed between mortality and duration of treatment (P for trend = .007). Long-term treatment (≥18 months) was significantly associated with reduced mortality (adjusted hazard ratio, 0.32 [95% confidence interval, .15-.71]). In subgroup analyses, patients with cavitary lesions (adjusted hazard ratio, 0.17 [95% confidence interval, .05-.57]) or positive AFB smears (0.13 [.02-.84]) at baseline maintained this significant inverse relationship between treatment duration and mortality. CONCLUSIONS: Long-term antimicrobial treatment should be actively considered in patients with progressive MAC-PD, especially in the presence of cavities or positive AFB smears indicative of high mycobacterial burden.

The Clinical Course and Prognosis of Patients With Nontuberculous Mycobacterial Pulmonary Disease After Solid Organ Transplantation.

BACKGROUND: Due to impaired cell-mediated immunity, solid organ transplantation (SOT) recipients are at increased risk of developing nontuberculous mycobacterial pulmonary disease (NTM-PD). However, the clinical course of NTM-PD in SOT patients and the impact of SOT on the prognosis of NTM-PD remain unclear. METHODS: We analyzed patients who developed NTM-PD after receiving SOT between January 2001 and December 2020, at a tertiary referral hospital in South Korea. Baseline characteristics, clinical course, and prognosis were evaluated. Propensity score-matched analysis was performed to assess the impact of SOT on long-term survival in patients with NTM-PD. RESULTS: Among 4,685 SOT recipients over 20 years, 12 patients (median age, 64 years; interquartile range [IQR], 59-67 years; men, 66.7%) developed NTM-PD. Seven (58.3%) and five (41.7%) patients underwent kidney and liver transplantation, respectively, before the diagnosis of NTM-PD. The incidence of NTM-PD was 35.6 cases per 100,000 person-years among kidney transplant recipients and 28.7 cases per 100,000 person-years among liver transplant recipients. The median time between transplantation and the diagnosis of NTM-PD was 3.3 (IQR, 1.5-10.8) years. The most common mycobacterial species was Mycobacterium avium (50.0%). Antibiotic treatment was initiated in five (41.7%) patients, and two patients (40.0%) achieved microbiological cure. Two patients died during a median follow-up of 4.2 (IQR, 2.3-8.8) years and NTM-PD was assumed to be the cause of death in one patient. When matched to patients without a history of SOT, patients with a history of SOT did not show worse survival (P value for log-rank test = 0.62). CONCLUSION: The clinical course of NTM-PD in SOT recipients was comparable to that of patients without SOT, and SOT did not increase the risk of all-cause mortality in patients with NTM-PD.

Outcomes of Adjunctive Surgery in Patients With Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. Amidst the poor treatment success of antibiotic therapy, adjunctive surgery is gaining attention; however, discrepancies in reported outcomes exist. RESEARCH QUESTION: What are the treatment outcomes and complications of patients with NTM-PD undergoing adjunctive surgery? STUDY DESIGN AND METHODS: The MEDLINE, Embase, and Cochrane databases were searched for eligible studies before January 2022. Studies reporting the outcomes of adjunctive surgery in adult patients who satisfied the diagnostic criteria for NTM-PD were included. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Data were extracted by two independent observers. Estimates of proportion were pooled using a random-effects model. Sputum mycobacterial culture negative conversion, recurrence, complications, and in-hospital mortality after surgery were primary outcomes that had been set before data collection began. Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using funnel plots and the Egger test. RESULTS: Fifteen of the 2,739 screened studies, with 1,071 patients, were assessed. The weighted proportion of postoperative sputum culture negative conversion was 93% (95% CI, 87%-97%), and recurrence was 9% (95% CI, 6%-14%) for a median follow-up of 34 months. The proportion of patients who experienced postoperative complications was 17% (95% CI, 13%-23%), and in-hospital mortality was 0% (95% CI, 0%-2%). Studies that performed multilobar lung resection in > 30% of the study population showed comparable rates of complications with studies that did not. INTERPRETATION: Adjunctive surgery is an effective therapeutic option with acceptable rates of complications for selected patients with NTM-PD. TRIAL REGISTRY: PROSPERO; No.: CRD42022310663; URL: https://www.crd.york.ac.uk/prospero/.

The Rise in Prevalence and Related Costs of Nontuberculous Mycobacterial Diseases in South Korea, 2010-2021.

Between 2010 and 2021, the annual prevalence of nontuberculous mycobacterial (NTM) diseases in South Korea increased from 11.4 to 56.7 cases per 100 000 population. Prevalence in the population aged ≥65 years quadrupled from 41.9 to 163.1 cases per 100 000 population. Accordingly, the overall cost associated with NTM diseases increased.

Blood Krebs von den Lungen-6 levels predict treatment response to antifibrotic therapy in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Antifibrotic therapy can slow disease progression (DP) in patients with idiopathic pulmonary fibrosis (IPF). However, the prognostic biomarkers for DP in patients with IPF receiving antifibrotic therapy have not been identified. Therefore, we aimed to evaluate the prognostic efficacy of serum Krebs von den Lungen-6 (KL-6) for DP in patients with IPF receiving antifibrotic therapy. METHODS: The clinical data of 188 patients with IPF who initiated antifibrotic therapy at three tertiary hospitals was retrospectively analyzed. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, diffusing capacity for carbon monoxide ≥ 15%, acute exacerbation, or deaths during 6 months after antifibrotic therapy. RESULTS: The mean age of patients was 68.9 years, 77.7% were male, and DP occurred in 43 patients (22.9%) during follow-up (median, 7.6 months; interquartile range, 6.2-9.8 months). There was no difference in baseline KL-6 levels between the DP and no-DP groups; however, among patients with high baseline KL-6 levels (≥ 500 U/mL), changes in KL-6 levels over 1 month were higher in the DP group than those in the non-DP group, and higher relative changes in KL-6 over 1 month were independently associated with DP (odds ratio, 1.043; 95% confidence interval 1.005-1.084) in the multivariable logistic analysis adjusted for age and FVC. In the receiver operating characteristic curve analysis, the 1-month change in KL-6 was also useful for predicting DP (area under the curve = 0.707; P < 0.012). CONCLUSIONS: Our data suggest that the relative change in KL-6 over 1 month might be useful for predicting DP in patients with IPF receiving antifibrotic therapy when baseline KL6 is high.

The effects of hypomagnesemia on delirium in middle-aged and older adult patients admitted to medical intensive care units.

BACKGROUND: In critically ill patients, the most common manifestation of brain dysfunction is delirium, which is independently associated with higher morbidity and mortality. While electrolyte imbalance is one of the precipitating factors, the impact of hypomagnesemia on the incidence of delirium remains unknown. METHODS: We retrospectively analyzed patients admitted to the medical intensive care unit (ICU) of a tertiary referral center between January and June 2020. Patients with ICU stay ≥48 hours and aged 40-85 years were included. The primary outcome was cumulative incidence of delirium in the ICU. Patients were divided into two groups based on serum magnesium level at ICU admission. Multivariable Cox proportional hazards regression analysis was performed, and covariates were selected using the least absolute shrinkage and selection operator (LASSO) method. RESULTS: A total of 109 patients included 43 (39.4%) women and had a median age of 69.0 years (interquartile range [IQR], 60.0-76.0 years). The median magnesium level was 1.7 mg/dl (IQR, 1.5-1.9 mg/dl), and the cumulative incidence of delirium was 32.1% (35 patients). Hypomagnesemia was independently associated with delirium (adjusted hazard ratio [aHR], 2.12; 95% confidence interval [CI], 1.03-4.38), along with prior use of immunosuppressants (aHR, 3.08; 95% CI, 1.46-6.48) or benzodiazepines (aHR, 4.02; 95% CI, 1.54-10.50), body mass index (aHR, 0.93; 95% CI, 0.84-1.02), and alcohol history (aHR, 1.68; 95% CI, 0.74-3.80). CONCLUSIONS: In critically ill adults, hypomagnesemia increases the risk of delirium by more than two-fold compared to patients with normal magnesium level.

Old age is associated with worse treatment outcome and frequent adverse drug reaction in Mycobacterium avium complex pulmonary disease.

BACKGROUND: The number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly increasing globally, especially in the older population. However, there is a dearth of evidence regarding the impact of aging on the treatment outcomes of NTM-PD. METHODS: We analyzed consecutive patients who satisfied the diagnostic criteria for Mycobacterium avium complex (MAC)-PD and received antibiotic treatment between January 2009 and December 2020 at a tertiary referral hospital in Korea. The main outcomes were (1) long-term treatment success, defined by negative culture conversion for more than 12 months; and (2) adverse drug reactions (ADRs). Multivariable logistic regression model was used to evaluate the association between age and main outcomes. RESULTS: A total of 614 patients (median age, 65 years, interquartile range [IQR] 57-73 years; men, 35.3%) were included. Median treatment duration (530 days, IQR 290-678 days; P for trend < 0.001) and long-term treatment success (P for trend = 0.026) decreased, whereas ADRs (P for trend < 0.001) increased significantly with age. Multivariable analyses demonstrated that age ≥ 80 years was an independent factor associated with ADRs (adjusted odds ratio [aOR] 3.29; 95% confidence interval [CI] 1.05-10.28) and worse treatment outcome (aOR 0.42; 95% CI 0.19-0.91). CONCLUSIONS: Aging is associated with worse treatment outcome and frequent ADRs of patients with MAC-PD. Individualized treatment with reduced-intensity may be a reasonable alternative for older adults.

Outcomes of adjunctive surgery for nontuberculous mycobacterial pulmonary disease.

BACKGROUND: Owing to the unsatisfactory results of antibiotic treatment alone, surgical resection is currently considered as adjunctive therapy in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, reports regarding the outcomes of surgery vary considerably by institution. Here, we investigated the surgical outcomes and risk factors associated with unfavorable outcomes after surgery. METHODS: We analyzed patients with NTM-PD who underwent pulmonary resection at Seoul National University Hospital between January 1, 2006, and December 31, 2020, and assessed the types of surgical procedures, complications, and long-term outcomes. Multivariate logistic regression analysis was used to identify the risk factors associated with treatment refractoriness or recurrence after surgery. RESULTS: Among 67 patients who underwent surgery during the study period, the most common indication for surgery was persistent culture positivity despite rigorous medical treatment (80.6%), followed by longstanding cavitary lesions or radiographic aggravation (10.4%) and massive hemoptysis (4.5%). Among 53 patients with positive mycobacterial cultures at the time of surgery, 38 (71.7%) achieved initial negative culture conversion, 9 (17.0%) of whom experienced recurrence. Nine (13.4%) patients experienced postoperative complications, which were managed without lasting morbidity and mortality. Female sex (adjusted odds ratio [aOR] 6.63; 95% confidence interval [CI] 1.04-42.4; P = .046), preoperative positive mycobacterial culture (aOR 5.87; 95 %CI 1.04-33.08; P = .045), and residual lesions (aOR 6.86; 95 %CI 1.49-31.56; P = .013) were associated with refractoriness or recurrence. CONCLUSIONS: Pulmonary resection is a reasonable treatment modality for patients with refractory NTM-PD or major complications such as massive hemoptysis. The potential risk factors associated with unfavorable outcomes included female sex, preoperative positive mycobacterial culture, and residual lesions after surgery.