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BACKGROUND: The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques. METHODS: Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis). RESULTS: NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased. CONCLUSIONS: NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation.
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Infecciones por Mycobacterium no Tuberculosas , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/inmunología , Infecciones por Mycobacterium no Tuberculosas/genética , Femenino , Persona de Mediana Edad , Anciano , Transcriptoma , Macrófagos/inmunología , Macrófagos/metabolismo , Pulmón/microbiología , Pulmón/inmunología , Pulmón/patología , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/inmunología , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/inmunología , Linfocitos T/inmunología , Perfilación de la Expresión Génica , Adulto , Bronquiectasia/inmunología , Bronquiectasia/genética , Bronquiectasia/microbiologíaRESUMEN
BACKGROUND: Developmental trajectories of clinical skills in training physicians vary among tasks and show interindividual differences. This study examined the predictors of medical internship performance and residency entrance and found subtypes of performance trajectory in training physicians. METHODS: This retrospective cohort study involved 888 training physicians who completed a medical internship between 2015 and 2019. After the internship, 627 physicians applied for residency training between 2016 and 2020. Finally, 160 of them completed their first-year residency in internal medicine, surgery, pediatrics, and psychiatry departments between 2016 and 2020. Pearson's correlation coefficients of internship performance and first year-residency performance (n = 160) were calculated. Latent profile analysis identified performance trajectory subtypes according to medical school grade point average (GPA), internship performance, English proficiency, and residency selection procedures. Multivariate logistic regression models of residency acceptance (n = 627) and performance in the top 30%/lower 10% in the first year of residency were also constructed. RESULTS: Medical internship performance showed a significant positive correlation with the medical school GPA (r = 0.194) and the written score for the medical licensing examination (r = 0.125). Higher scores in the interview (adjusted odds ratio [aOR], 2.57) and written examination (aOR, 1.45) of residency selection procedures and higher medical internship performance (aOR, 1.19) were associated with a higher chance of residency acceptance. The latent profile analyses identified three training physician subgroups: average performance, consistently high performance (top 30%), and adaptation to changes (lowest 10%). Higher scores in the interview for residency selection (aOR, 1.35) and lower scores for medical internship performance (aOR, 0.79) were associated with a higher chance of performing in the top 30% or lowest 10% in the first year of residency, respectively. CONCLUSION: Performance in the interview and medical internship predicted being among the top 30% and lowest 10% of performers in the first year of residency training, respectively. Individualized educational programs to enhance the prospect of trainees becoming high-functioning physicians are needed.
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Competencia Clínica , Internado y Residencia , Facultades de Medicina , Humanos , Estudios Retrospectivos , Femenino , Masculino , Estudios Longitudinales , Adulto , Médicos , Modelos Logísticos , Evaluación Educacional , Oportunidad RelativaRESUMEN
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.
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Inteligencia Artificial , Esputo , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Esputo/microbiología , Adulto , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/uso terapéutico , República de Corea , Tomografía Computarizada por Rayos X/métodos , Antituberculosos/uso terapéutico , Radiografía Torácica/métodosRESUMEN
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.
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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.
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Antibacterianos , Infecciones por Mycobacterium no Tuberculosas , Calidad de Vida , Humanos , Masculino , Femenino , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , República de Corea , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Micobacterias no Tuberculosas/efectos de los fármacos , Resultado del TratamientoRESUMEN
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.
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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.
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Artritis Reumatoide , Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Humanos , Femenino , Anciano , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Pronóstico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/etiología , Progresión de la EnfermedadRESUMEN
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.
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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 (100â mg vs 50â 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.
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Rationale: The clinical implications of trehalose 6,6'-dimycolate (TDM) in nontuberculous mycobacterial pulmonary disease have not been studied. Objectives: 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 with diagnoses of 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: TDM was identified in clinical isolates from 176 of 343 patients. Cavities were more prevalent in patients with TDM-negative isolates (19.8%) than in those with TDM-positive isolates (10.2%) (P = 0.015). The time to antibiotic treatment was shorter in patients with TDM-negative isolates (4 mo [interquartile range, 2-10 mo]) than in those with TDM-positive isolates (7 mo [interquartile range, 3-16 mo]) (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 patients with MAC PD.
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Antibacterianos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare , Humanos , Masculino , Femenino , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/microbiología , Infección por Mycobacterium avium-intracellulare/diagnóstico , Complejo Mycobacterium avium/aislamiento & purificación , Anciano , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Estudios Retrospectivos , República de Corea , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/tratamiento farmacológicoRESUMEN
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.
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Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Tuberculosis Pulmonar , Adulto , Humanos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Estudios Retrospectivos , Enfermedades Pulmonares/microbiología , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/complicacionesRESUMEN
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).
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Enfermedades Pulmonares , Mycobacterium abscessus , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad Microbiana , Mycobacterium abscessus/genéticaRESUMEN
OBJECTIVE: Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment. STUDY DESIGN AND SETTING: We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used. RESULTS: Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase. CONCLUSION: We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.
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Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Duración de la Terapia , Fluoroquinolonas/farmacología , Rifampin/farmacología , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
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.
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Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Adulto , Humanos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/microbiología , Estudios Retrospectivos , Enfermedades Pulmonares/diagnóstico , Antibacterianos/uso terapéuticoRESUMEN
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.
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Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Humanos , Micobacterias no Tuberculosas , Pronóstico , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Estudios Retrospectivos , Enfermedades Pulmonares/microbiología , BiomarcadoresRESUMEN
BACKGROUND: Clinical ethics support is a form of preventive ethics aimed at mediating ethics-related conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. METHODS: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultation-related documents. RESULTS: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. CONCLUSION: The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.
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Consultoría Ética , Ética Clínica , Masculino , Humanos , Femenino , Toma de Decisiones , Estudios Retrospectivos , Hospitales Universitarios , Muerte , República de CoreaRESUMEN
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.
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Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Adolescente , Adulto , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/microbiología , Estudios Retrospectivos , Enfermedades Pulmonares/microbiología , PulmónRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.
Asunto(s)
Fibrosis Pulmonar Idiopática , Células Madre Mesenquimatosas , Humanos , Animales , Ratones , Administración Intravenosa , Macrófagos , Monocitos , Bleomicina , Modelos Animales de EnfermedadRESUMEN
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.
Asunto(s)
Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Trasplante de Órganos , Masculino , Humanos , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/etiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Trasplante de Órganos/efectos adversos , Pronóstico , Enfermedades Pulmonares/microbiología , Progresión de la Enfermedad , Estudios RetrospectivosRESUMEN
Background: This study aimed (I) to investigate the clinical implication of computed tomography (CT) cavity volume in tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD), and (II) to develop a three-dimensional (3D) nnU-Net model to automatically detect and quantify cavity volume on CT images. Methods: We retrospectively included conveniently sampled 206 TB and 186 NTM-PD patients in a tertiary referral hospital, who underwent thin-section chest CT scans from 2012 through 2019. TB was microbiologically confirmed, and NTM-PD was diagnosed by 2007 Infectious Diseases Society of America/American Thoracic Society guideline. The reference cavities were semi-automatically segmented on CT images and a 3D nnU-Net model was built with 298 cases (240 cases for training, 20 for tuning, and 38 for internal validation). Receiver operating characteristic curves were used to evaluate the accuracy of the CT cavity volume for two clinically relevant parameters: sputum smear positivity in TB and treatment in NTM-PD. The sensitivity and false-positive rate were calculated to assess the cavity detection of nnU-Net using radiologist-detected cavities as references, and the intraclass correlation coefficient (ICC) between the reference and the U-Net-derived cavity volumes was analyzed. Results: The mean CT cavity volumes in TB and NTM-PD patients were 11.3 and 16.4 cm3, respectively, and were significantly greater in smear-positive TB (P<0.001) and NTM-PD necessitating treatment (P=0.020). The CT cavity volume provided areas under the curve of 0.701 [95% confidence interval (CI): 0.620-0.782] for TB sputum positivity and 0.834 (95% CI: 0.773-0.894) for necessity of NTM-PD treatment. The nnU-Net provided per-patient sensitivity of 100% (19/19) and per-lesion sensitivity of 83.7% (41/49) in the validation dataset, with an average of 0.47 false-positive small cavities per patient (median volume, 0.26 cm3). The mean Dice similarity coefficient between the manually segmented cavities and the U-Net-derived cavities was 78.9. The ICCs between the reference and U-Net-derived volumes were 0.991 (95% CI: 0.983-0.995) and 0.933 (95% CI: 0.897-0.957) on a per-patient and per-lesion basis, respectively. Conclusions: CT cavity volume was associated with sputum positivity in TB and necessity of treatment in NTM-PD. The 3D nnU-Net model could automatically detect and quantify mycobacterial cavities on chest CT, helping assess TB infectivity and initiate NTM-TB treatment.