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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. [ABSTRACT FROM AUTHOR]

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 DNTM disease. [ABSTRACT FROM AUTHOR]

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 TBrelated 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Isoniazid (INH) mono-resistant tuberculosis (Hr-TB) is a highly prevalent type of drug-resistant TB, possibly associated with unfavorable treatment outcomes. However, definitive guidelines on an optimal treatment regimen and duration for Hr-TB are currently under discussion. We evaluated the characteristics and treatment outcomes of Hr-TB patients. Materials and Methods: We retrospectively reviewed the medical records of Hr-TB patients treated at a South Korean tertiary referral hospital from January 2005 to December 2018. Results: We included 195 Hr-TB patients. 113 (57.9%) were male, and the median age was 56.6 [interquartile range, 40.2-68.6] years. Mutations in katG were the most frequent [54 (56.3%)], followed by those in the inhA [34 (35.4%)]. Favorable and unfavorable outcomes were noted in 164 (84.1%) and 31 (15.9%) patients, respectively. Smoking history [odds ratio (OR)=5.606, 95% confidence interval (CI): 1.695-18.543, p=0.005], low albumin level (OR=0.246, 95% CI: 0.104-0.578, p=0.001), and positive acid-fast bacilli culture at 2 months (OR=7.853, 95% CI: 1.246-49.506, p=0.028) were associated with unfavorable outcomes. Conclusion: A tailored strategy targeting high-risk patients is imperative for improved treatment outcomes. Further research on the rapid and accurate detection of resistance to INH and other companion drugs is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Acute kidney injury (AKI) is common in critically ill patients. Serum cystatin C has emerged as a reliable marker of AKI. We sought to assess the value of serum cystatin C for early detection and prediction of renal function recovery in patients with sepsis. Materials and Methods: Sepsis patients (113 AKI patients and 49 non-AKI patients) admitted to the intensive care unit (ICU) were included. Serum creatinine and cystatin C levels and glomerular filtration rate were measured on days 0, 1, 3, and 7. Results: Serum cystatin C levels were significantly higher in AKI patients than in non-AKI patients at all time points. Multivariate analysis showed that only serum cystatin C levels on day 0 were associated with AKI development [odds ratio (OR)=19.30; 95% confidence interval (CI)= 2.58-144.50, p<0.001]. Linear mixed model analysis showed significant variation in cystatin C levels between the recovery and non-recovery groups over time (p=0.001). High levels of serum cystatin C at day 0 (OR=1.64; 95% CI=1.00-2.68, p=0.048) were associated with recovery of AKI. Conclusion: Serum cystatin C level was found to be associated with the development and worsening of AKI in ICU patients with sepsis. [ABSTRACT FROM AUTHOR]

Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of not only healthcare-associated pneumonia (HCAP) but also community-acquired pneumonia (CAP). We determined the impact of MRSA on differences in clinical characteristics, courses, and outcomes between CAP and HCAP. Materials and Methods: We conducted a retrospective observational study on 78 adult patients admitted with MRSA pneumonia at a university-affiliated tertiary hospital between January 2008 and December 2011. We compared baseline characteristics, chest radiographs, treatment outcomes, and drug resistance patterns between the CAP and HCAP groups. Results: Of the 78 patients with MRSA pneumonia, 57 (73.1%) were HCAP and 21 (26.9%) were CAP. MRSA infection history in the previous year (29.8% vs. 14.3%, p=0.244) tended to be more common in HCAP than in CAP. Despite similar Pneumonia Severity Index scores (151 in CAP vs. 142 in HCAP), intubation rates (38.1% vs. 17.5%; p=0.072) and intensive care unit admission (42.9% vs. 22.8%; p=0.095) tended to be higher in the CAP group, while 28-day mortality was higher in the HCAP group (14.3% vs. 26.3%; p=0.368), although without statistical significance. All patients showed sensitivity to vancomycin and linezolid; meanwhile, HCAP patients showed greater resistance to gentamicin than CAP patients (58.3% vs. 16.6%; p=0.037). The median total hospital charges were 6899 American dollars for CAP and 5715 American dollars for HCAP (p=0.161). Conclusion: MRSA pneumonia showed significantly differences in baseline characteristics, chest radiographs, treatment outcomes, and medical expenses between HCAP and CAP groups. [ABSTRACT FROM AUTHOR]

Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

Purpose: Endobronchial metastasis is defined as documented extrathoracic malignancies metastatic to the endobronchus within a bronchoscopically visible range. Although the clinical and radiologic findings of endobronchial metastasis are similar to primary lung cancer, treatment and prognosis may be different. We hereby investigated the clinical, radiologic and bronchoscopic aspects of endobronchial metastases (EBM) in Korean patients. Materials and Methods: A total of 43 patients with EBM who underwent bronchoscopic biopsies from June 1991 to December 2009 at Severance Hospital, Yonsei University College of Medicine in Seoul, Korea, were analyzed retrospectively. We evaluated clinical, radiologic and bronchoscopic characteristics of EBM. Results: The patients consisted of 27 males and 16 females and their ages ranged from 18 to 77 years. The common primary cancers related to EBM were rectal (16.3%), colon (11.6%), breast (9.3%) and uterine (9.3%) cancers. The mean interval from diagnosis of primary cancer to EBM was 36 months, and the mean survival duration from diagnosis of EBM was 16.1 months in 33 deceased patients. Conclusion: EBM develop in various types of malignancies at various times with unremarkable manifestations. Therefore, physicians should consider the possibility of EBM, especially if a patient has a history of any malignancy, regardless of respiratory symptoms. Respiratory symptoms related with EBM can be treated by various safe procedures. [ABSTRACT FROM AUTHOR]

Purpose: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Materials and Methods: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. Results: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. Conclusion: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI. [ABSTRACT FROM AUTHOR]

Purpose: Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). Materials and Methods: The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. Results: The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRP group was significantly longer than with the high CRP group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRP level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). Conclusion: High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC. [ABSTRACT FROM AUTHOR]