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

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

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

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

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

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods: Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

OBJECTIVE: Posttraumatic embitterment disorder (PTED), a subgroup of an adjustment disorder, is a feeling with anger and helplessness. Hemodialysis may be a trigger event leading to PTED. We investigated the prevalence of PTED in patients with each categorized stages of chronic kidney disease (CKD) and the association between PTED and depression and functional impairment. METHODS: Patients were categorized into three groups according to the stages of CKD (stage I–II, III–IV, and V). CKD (I–II) group was defined as estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m², CKD (III–IV) group as eGFR <60 ml/min/1.73 m², and CKD (V) group as CKD stage V including patients ongoing hemodialysis. Patients were assessed for the prevalence of PTED, depression, and decreased quality of life by using the scale of PTED, Patient Health Questionnaire-9 (PHQ-9), and EuroQol Five Dimensional Questionnaires, Visual Analogue Scale (EQ-5D-VAS), respectively. RESULTS: A total of 445 patients were analyzed. The number of patients in CKD (I–II) was 166, CKD (III–IV) was 172, and CKD (V) was 107. Multivariate analysis by binomial logistic regression demonstrated that CKD (V) was significantly associated with the prevalence of PTED (odds ratio, 4.13; 95% confidence interval, 1.56–15.6; p=0.006) after adjustment for age, gender, and diabetes mellitus. Also, a significant correlation existed between PTED and EQ-5D-VAS in all stages, but the correlation was nonsignificant between PTED and PHQ-9 score in group CKD (V). CONCLUSION: The findings suggest that PTED is underdiagnosed in CKD patients. Acknowledgment and diagnosis of PTED in CKD patients may lead to a better quality of life.
Adjustment Disorders ; Anger ; Depression ; Diabetes Mellitus ; Diagnosis ; Dialysis ; Glomerular Filtration Rate ; Humans ; Logistic Models ; Multivariate Analysis ; Prevalence ; Quality of Life ; Renal Dialysis ; Renal Insufficiency, Chronic

PURPOSE: The purpose of this study was to evaluate the effects of reminiscence therapy on depressive symptoms in older adults with dementia using a systematic review and meta-analysis. METHODS: Randomized controlled trials (RCTs) published from January 2000 to January 2018 were searched through Research Information Sharing Service (RISS), Korean Studies Information Service System (KISS), Korean Medical Database (KMbase), KoreaMed, PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Ovid MEDLINE. Two researchers independently performed the search, selection, and coding. Comprehensive Meta-Analysis 3.0 was used for meta-analysis, and Review Manager program 5.3 was used for quality assessment. RESULTS: Out of the 1,250 retrieved articles, 22 RCTs were selected for analysis. The overall effect size of reminiscence therapy for mitigating depressive symptoms in older adults with dementia was −0.62 (95% Cl: −0.92 to −0.31). The effect size was greater in older adults under 80, those with less disease severity, and those for whom the therapy session lasted less than 40 minutes. CONCLUSION: Reminiscence therapy is an effective non-pharmacological therapy to improve depressive symptoms in older adults with dementia. Because its effectiveness is also influenced by age, disease severity, and application method, it is necessary to consider treatment designs based on individual characteristics as well as methodological approaches.
Adult ; Clinical Coding ; Dementia ; Depression ; Humans ; Information Dissemination ; Information Services ; Mental Recall ; Methods ; Nursing

PURPOSE: The purpose of this study was to evaluate the effects of reminiscence therapy on depressive symptoms in older adults with dementia using a systematic review and meta-analysis. METHODS: Randomized controlled trials (RCTs) published from January 2000 to January 2018 were searched through Research Information Sharing Service (RISS), Korean Studies Information Service System (KISS), Korean Medical Database (KMbase), KoreaMed, PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Ovid MEDLINE. Two researchers independently performed the search, selection, and coding. Comprehensive Meta-Analysis 3.0 was used for meta-analysis, and Review Manager program 5.3 was used for quality assessment. RESULTS: Out of the 1,250 retrieved articles, 22 RCTs were selected for analysis. The overall effect size of reminiscence therapy for mitigating depressive symptoms in older adults with dementia was −0.62 (95% Cl: −0.92 to −0.31). The effect size was greater in older adults under 80, those with less disease severity, and those for whom the therapy session lasted less than 40 minutes. CONCLUSION Reminiscence therapy is an effective non-pharmacological therapy to improve depressive symptoms in older adults with dementia. Because its effectiveness is also influenced by age, disease severity, and application method, it is necessary to consider treatment designs based on individual characteristics as well as methodological approaches.

PURPOSE: The aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM. METHODS: A retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day. RESULTS: Seventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults. CONCLUSION: LEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.
Adult ; Drug Monitoring ; Half-Life ; Humans ; Infant, Newborn* ; Pharmacokinetics* ; Retrospective Studies ; Seizures*