Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib.

OBJECTIVES: This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors. METHODS: This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens. Results A total of 443 patients underwent rebiopsy, with 186 (42.0%) testing positive for the T790M mutation by the sixth rebiopsy. The final analysis included 143 eligible patients. Progression-free survival was not significantly different in terms of the methods (tissue: 13.3 months, 95% confidence interval [CI]: [9.4, 23.5] vs plasma: 11.1 months, 95% CI: [8.1, 19.4], p = 0.33) and numbers (one: 13.4 months, 95% CI: [9.4, 23.5] vs two or more: 11.0 months, 95% CI: [8.1, 14.8], p = 0.51) of repeated rebiopsies. Longer overall survival (OS) was found in patients in whom T790M was detected by tissue specimens rather than by plasma ctDNA (2-year OS rate: 81.7% for tissue vs 63.9% for plasma, p = 0.0038). Factors related to the lower numbers of rebiopsies included age and bone metastasis. Factor associated with T790M detection in tissue rather than in plasma was pleural metastasis, while advanced tumor stage was related to T790M confirmation in plasma rather than in tissue. CONCLUSIONS: Repeated rebiopsy for T790M detection in patients with NSCLC can increase the detection rate of the mutation. Detection of T790M by plasma ctDNA might be related to poor survival outcomes.

Nanoscale dosimetry for a radioisotope-labeled metal nanoparticle using MCNP6.2 and Geant4.

BACKGROUND: Metal nanoparticles (MNPs) labeled with radioisotopes (RIs) are utilized as radio-enhancers due to their ability to amplify the radiation dose in their immediate vicinity. A thorough understanding of nanoscale dosimetry around MNPs enables their effective application in radiotherapy. However, nanoscale dosimetry around MNPs still requires further investigation. PURPOSE: This study aims to provide insight into the radio-enhancement effects of MNPs by elucidating nanoscale dosimetry surrounding MNPs labeled with Auger-emitting RIs. We particularly focus on distinguishing the respective dose contributions of photons and electrons emitted by Auger-emitting RIs in the context of dose enhancement. METHODS: A 50 nm diameter NP of silver (Ag) core and gold (Au) shell (Ag@Au NP) was assumed to emit mono-energetic electrons and photons (3, 5, 10, 20, and 30 keV), or the energy spectrum corresponding to one of three Auger-emitting RIs (103Pd, 125I, and 131Cs) from the Ag core. Nanoscale radial dose distributions around a single radioactive Ag@Au NP were evaluated in spherical shells of water. Monte Carlo simulations were conducted using single-event and track structure transport methods implemented in MCNP6.2 and Geant4-DNA-Au physics, respectively. To evaluate the extent of radio-enhancement by the Ag@Au NP, two scenarios were considered: Ag@Au NPs (Au shell included) and Ag@water NPs (Au shell replaced by water). RESULTS: The radial doses of 10, 20, and 30 keV electrons estimated by both codes were comparable. However, the radial doses of 3 and 5 keV electrons by MCNP6.2 were much larger near the NP surface than those by Geant4. There was a dose enhancement of a few % to tens % by the Au shell in the region of the NP surface to 10 µm, depending on the electron energy. The radial doses of photons with the Au shell were higher up to their secondary electron ranges than those without the Au shell. The maximum dose enhancement factor of photons occurred at 20 keV and was 63.4 by MCNP6.2 and 50.5 by Geant4. The overall radial doses of electrons were 1-2 orders of magnitude larger than those of photons. As a result, in cases of RIs emitting both electrons and photons, the radial doses up to electron ranges were dominantly governed by electrons. The dose enhancement estimated by both codes for the RIs ranged from a few % except in the immediate vicinity of the NP surface. CONCLUSION: Given the dominant contribution of electrons to radial doses of MNP labeled with Auger-emitting RIs, physical dose enhancement expected by interactions with photons was hindered. Since there are no available RIs emitting exclusively photons, achieving enhanced physical doses within a cell through a combination of MNPs and RIs appears currently unattainable. The radial doses of photons near the NP surface exhibited considerable discrepancies between the codes, primarily attributed to low-energy electrons. The difference may arise from higher cross-sections of Au inelastic scattering in Geant4-DNA-Au compared to MCNP6.2.

Clinical characteristics of chronic obstructive pulmonary disease patients with superoptimal peak inspiratory flow rate.

Characteristics of chronic obstructive pulmonary disease (COPD) patients with superoptimal peak inspiratory flow rates (PIFR) has not been thoroughly investigated. This study aimed to compare the characteristics between COPD patients with superoptimal PIFR and those with optimal and sub-optimal PIFR. PIFR was measured using In-Check DIAL G16 and categorized into sub-optimal (PIFR lower than that required by the patient's device), optimal, and superoptimal (peak PIFR ≥ 90 L/min). Considering COPD patients with sub-optimal PIFR as the reference group, analyses were performed to identify PIFR-related factors. Subgroup analysis was performed according to the forced expiratory volume in 1 s (FEV1) % of the predicted value (%pred). Among 444 post-bronchodilator-confirmed COPD patients from seven tertiary hospitals in South Korea, 98, 223, and 123 were classified into the sub-optimal, optimal, and superoptimal PIFR groups, respectively. The superoptimal PIFR group were younger, had an increased proportion of males, a higher body mass index, lowest number of comorbidities and less frequent exacerbation in the previous year, as well as the highest forced vital capacity %pred. The adjusted odds ratio for frequent exacerbation in the previous year was lower in the superoptimal PIFR group than in the sub-optimal PIFR group and was more pronounced in patients with an FEV1%pred of < 70%. COPD patients with superoptimal PIFR have clinical characteristics different from those patients with the sub-optimal and optimal PIFR. Having a high inspiratory flow may be a favorable trait in COPD.

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.

Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study.

BACKGROUND: The association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated. METHODS: This retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed. RESULTS: BMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively. CONCLUSIONS: A decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Association of resistance training and moderate-to-vigorous physical activity with clinical outcomes in men with airflow limitation: a nationwide population-based study.

Aerobic moderate-to-vigorous physical activity (MVPA) is recommended for individuals with chronic diseases. However, the association between resistance training (RT) in addition to moderate to vigorous physical activity (MVPA) and sleep duration, as well as respiratory symptoms, in patients with chronic obstructive pulmonary disease has not been thoroughly investigated. This population-based cross-sectional study used data from the Korea National Health and Nutrition Examination Survey between 2014 and 2019. A total of 61,754 individuals were identified and men with airflow limitation (FEV1/FVC < 0.7) who engaged in aerobic MVPA were selected (n = 794). Weighted percentages and odds ratio (OR) of sleep problems (≤ 5 or ≥ 9 h), chronic cough, and chronic sputum were estimated. A multivariate-adjusted complex sample logistic regression model was used to calculate ORs and 95% confidence intervals (CI). Subgroup analyses were conducted using the forced expiratory volume (FEV1) % of the predicted value (%pred) ≥ 80 vs. < 80. The percentages of sleep problems, chronic cough, and chronic sputum production were lower in men who underwent aerobic MVPA + RT than in those who underwent aerobic MVPA alone. The multivariable-adjusted OR of sleep problems was 0.44 (95% CI 0.25-0.77) in individuals undergoing aerobic MVPA + RT compared to aerobic MVPA alone. The ORs of chronic cough and sputum were 0.35 (95% CI 0.13-0.94) and 0.51 (95% CI 0.30-0.87), respectively. These associations were only significant in individuals with FEV1 < 80% pred. Compared with aerobic MVPA alone, aerobic MVPA + RT was associated with appropriate sleep duration and a decrease in chronic cough and sputum in male with airflow limitation. This was more pronounced in individuals with a FEV1 < 80% pred.

Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study.

BACKGROUND: The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years. METHODS: This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable. RESULTS: During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56-0.98) and quitters (adjusted HR 0.78, 95% CI:0.64-0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01). CONCLUSIONS: In patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Time-Sequential Monitoring of the Early Mesothelial Reaction in the Pleura after Cryoinjury.

(1) Background: An early mesothelial reaction of the pleura, leading to fibrosis, has been reported in animals after chemical or heavy metal exposure. However, the visual monitoring of early time-sequential mesothelial reaction-associated cryoinjury has not been fully investigated. Therefore, this study aimed to evaluate and visualize the early mesothelial reactions seen following cryoinjury using rabbit pleura. (2) Methods: We monitored the early mesothelial reaction in rabbit pleurae after cryoinjury using optical coherence tomography (OCT), in real-time, which was then compared with pathological images. Due to the penetration limit of OCT, we made a thoracic window to image the parietal and visceral pleurae in vivo. We also used an innovative technique for capturing the microstructure in vivo, employing a computer-controlled intermittent iso-pressure breath hold to reduce respiratory motion, increasing the resolution of OCT. We organized three sample groups: the normal group, the sham group with just a thoracic window, and the experimental group with a thoracic window and cryotherapy. In the experimental group, localized cryoinjury was performed. The mesothelial cells at the level of pleura of the cryotherapy-injured site were visualized by OCT within the first 30 min and then again after 2 days at the same site. (3) Results: In the experimental group, focal thickening of the parietal pleura was observed at the site of cryoinjury using OCT after the first injury, and it was then confirmed pathologically as focal mesothelial cell proliferation. Two days after cryoinjury, diffuse mesothelial cell proliferation in the parietal pleura was noted on the reverse side around the cryoinjured site in the same rabbit. In the sham group, no pleural reaction was found. The OCT and pathological examinations revealed different patterns of mesothelial cell reactions between the parietal and visceral pleurae: the focal proliferation of mesothelial cells was found in the parietal pleura, while only a morphological change from flat cells to cuboidal cells and a thickened monolayer without proliferation of mesothelial cells were found in the visceral pleural. (4) Conclusions: An early mesothelial reaction occurs following cryoinjury to the parietal and visceral pleurae.

Association Between Regular Moderate to Vigorous Physical Activity Initiation Following COPD Diagnosis and Mortality: An Emulated Target Trial Using Nationwide Cohort Data.

BACKGROUND: Moderate to vigorous physical activity (MVPA) in patients with COPD affects their overall health outcomes, including symptom relief and improved quality of life. However, the magnitude of the effect of MVPA initiation on real-world clinical outcomes has not been well investigated. RESEARCH QUESTION: How does MVPA initiation affect mortality and severe exacerbation in patients who have not engaged in MVPA prior to COPD diagnosis? STUDY DESIGN AND METHODS: This study included patients with COPD aged ≥ 40 years who were not performing MVPA prior to COPD diagnosis and who had at least one health screening visit prior to and following their COPD diagnosis between January 1, 2010, and December 31, 2018. The main exposure was MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days per week or moderate aerobic exercise > 30 min per day on ≥ 5 days per week. The primary end point was all-cause mortality, and the secondary end point was initial severe exacerbation as the time to event following COPD diagnosis. RESULTS: In total, 110,097 person-trials were included (27,564 MVPA increases and 82,533 control groups). No differences were observed between the covariates following matching. The adjusted hazards ratio of all-cause mortality for the MVPA group compared with the control group was 0.84 (95% CI, 0.79-0.89). In the subgroup analysis, patients aged > 65 years, female patients, those who had never smoked, and patients with a higher Charlson Comorbidity Index score displayed a stronger effect of MVPA on reducing mortality than younger male patients, those who had ever smoked, and patients with a lower Charlson Comorbidity Index score (Pinteraction < .05). The fully adjusted hazards ratio for the risk of severe exacerbation (MVPA group vs control) was 0.90 (95% CI, 0.87-0.94). INTERPRETATION: Initiation of MVPA can potentially reduce mortality and severe exacerbations in patients with COPD, although personalized interventions and further clinical trials are necessary.

Risk factors for early-onset lung cancer in Korea: analysis of a nationally representative population-based cohort.

OBJECTIVES: We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. METHODS: The study included 6,794,287 individuals aged 20-39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. RESULTS: Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (<10 pack-years: mHR, 1.12; 95% CI, 1.01 to 1.24; ≥10 pack-years: mHR, 1.30; 95% CI, 1.18 to 1.45), but past smoking was not. Although mild alcohol consumption (<10 g/day) was associated with lower lung cancer risk (mHR, 0.92; 95% CI, 0.86 to 0.99), heavier alcohol consumption (≥10 g/day) was not. Higher income (highest vs. lowest quartile: mHR, 0.86; 95% CI, 0.78 to 0.94), physical activity for at least 1,500 metabolic equivalent of task-min/wk (vs. non-exercisers: mHR, 0.83; 95% CI, 0.69 to 0.99) and obesity (vs. normal weight: mHR, 0.89; 95% CI, 0.83 to 0.96) were associated with lower lung cancer risk, whereas metabolic syndrome was associated with increased risk (mHR, 1.13; 95% CI, 1.03 to 1.24). CONCLUSIONS: In young adults, age, female sex, smoking, and metabolic syndrome were risk factors for early-onset lung cancer, while high income, physical activity, and obesity displayed protective effects.

Muscle Mass Adjusted for Body Weight Is Associated with Significant Liver Fibrosis in Young Adults with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study from a Korean Military Hospital.

Background: Sarcopenia has been associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the correlation between liver fibrosis and muscle mass in young adults with NAFLD. Methods: We conducted a retrospective review of 88 Korean soldiers <35 years of age who underwent bioelectrical impedance analysis and liver stiffness measurements. A FibroScan-aspartate aminotransferase score >0.35 was used to determine the presence of liver fibrosis. Results: Among the 88 patients, 38 were classified as having significant fibrosis. In the univariate analysis, muscle mass percentage (MMP), muscle-to-fat ratio (MFR), waist-to-hip ratio (WHR), body mass index, impaired fasting glucose or diabetes mellitus, and alanine transaminase (ALT) level were all significantly associated with fibrosis (P<0.001). After adjusting for ALT level, height, and age, MMP and WHR were associated with fibrosis. Conclusion: In young adults, MMP and MFR were significantly associated with hepatic fibrosis.

Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non-Small Cell Lung Cancer: Updated Analysis of the RESET Study.

PURPOSE: This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non-small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). MATERIALS AND METHODS: In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. RESULTS: The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). CONCLUSION: This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Prevalence, Trend, and Risk Factors for Early Chronic Obstructive Pulmonary Disease: An Analysis of the Nationwide Population-Based Survey from 2010 to 2019 in South Korea.

This study aimed to evaluate the prevalence, trends, and risk factors of early chronic obstructive pulmonary disease (COPD) by using a nationally representative sample. The datasets of the Korea National Health and Nutrition Examination Survey 2010-2019 were used, where 80,860 individuals were identified; of these, 9,045 participants aged 40-49 years who underwent spirometry with no missing data were analyzed. Early COPD was defined as forced expiratory volume in 1 s /forced vital capacity ratio < the lower limit of normal (2.5th percentile) in individuals aged <50 years without a history of asthma, inhaler therapy, or persistent respiratory symptoms. The prevalence and trend of early COPD were estimated according to features such as smoking status and pack-years. Joinpoint regression analysis was used to analyze the significant annual change in the trend according to sex, smoking status, and pack-years. A complex sample multivariable-adjusted regression model was used to identify factors affecting early COPD. The estimated population size during 2010-2019 was 82,326,178. Early COPD was present in 4.5% of patients (6.5% of men and 2.3% of women). It was present in 7.7% of current smokers, followed by former and never smokers. Among smokers with ≥ 10 pack-years, early COPD was present in 8.2%, whereas it was present in 2.6% of smokers with < 10 pack-years. Joinpoint regression analyses found a recent decrease in the trend of prevalence in males who were former and current smokers. The multivariable-adjusted logistic regression model showed that being male, lower educational level, smoking status, and pack-years were factors that affected the presence of early COPD. Continued surveillance of this pre-disease condition is required, and further research are warrant.

Transrenal DNA detection of Mycobacterium tuberculosis in patients with pulmonary tuberculosis.

Background: Multiple attempts have been made to use biological samples other than sputum to diagnose tuberculosis (TB). Sputum acid-fast bacillus (AFB) microscopy is the fastest, most straightforward, and most inexpensive method for diagnosing pulmonary TB. However, urine can be used in place of sputum owing to its various advantages, such as a noninvasive method of collection, convenient handling and storage, and minimal risk of infection in health-care workers involved in sample collection. In this study, we aimed to assess the suitability of urine as a sample to obtain transrenal DNA (trDNA) to diagnose TB. This study involved several patients with TB undergoing inpatient treatment, whose AFB microscopy showed negative inversion. Methods: Here, 51 urine samples were collected from 40 patients with TB and examined to confirm the presence of trDNA. First, we compared the efficiency of two trDNA extraction methods.An automated magnetic bead-based method and a more efficient anchoring extraction method. Statistical analyses were performed using Excel software (Microsoft Office Professional Plus 2019). Results: Although molecular diagnosis using GeneXpert yielded negative results, a peculiarity was observed. There was no significant difference between GeneXpert findings and our results nor was there any difference in the sequential trDNA samples obtained. However, even when GeneXpert results were negative, trDNA was detected in seven out of ten samples using the anchor extraction method. Conclusions: Further studies are needed to establish biomarkers for the progression of TB treatment.

Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

BACKGROUND: X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. PURPOSE: In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. METHODS: By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50 kV X-rays, respectively. An amount of 40 mg GNPs (1.9 nm in diameter) suspended in 0.20 ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60 min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. RESULTS: Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2 min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08 wt%. CONCLUSIONS: A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Relationship between obstructive sleep apnea, insulin resistance, and metabolic syndrome: a nationwide population-based survey.

We aimed to identify the association between obstructive sleep apnea (OSA), insulin resistance (IR), and metabolic syndrome (MetS) in a nationwide population-based sample. A total of 7,900 adults with information on the STOP-Bang score and MetS (3,341 men and 4,469 women) were identified from the dataset of the Korea National Health and Nutrition Examination Survey 2019-2020. The association between OSA, IR, MetS, and its components was estimated using complex sample logistic regression analysis with adjustments for age, body mass index, residence, smoking status, alcohol consumption, household income, education, and the presence of diabetes. Participants with a high OSA score were more likely to have IR (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.96-3.95 in men and OR 2.64, 95% CI 0.55-12.80 in women), MetS (OR 6.05, 95% CI 4.23-8.69 in men and OR 4.20, 95% CI 1.23-15.70 in women), and components of MetS, compared to individuals with a low OSA score. Compared to premenopausal women, postmenopausal women had a more intense association between OSA and IR (OR 1.78, 95% CI 0.13-24.43 for premenopausal women and OR 3.64, 95% CI 0.60-22.28 for postmenopausal women) and MetS (OR 2.58, 95% CI 0.23-29.55 for premenopausal women and OR 5.36, 95% CI 1.42-20.21 for postmenopausal women). OSA was associated with abdominal obesity and hypertension in premenopausal women, while all components of MetS were associated with OSA in postmenopausal women. Further studies are necessary to elucidate the underlying mechanisms of these findings.

Application of several machine learning algorithms for the prediction of afatinib treatment outcome in advanced-stage EGFR-mutated non-small-cell lung cancer.

BACKGROUND: The present study aimed to evaluate the performance of several machine learning (ML) algorithms in predicting 1-year afatinib continuation and 2-year survival after afatinib initiation and to identify the differences in survival outcomes between ML-classified strata. METHODS: Data that were also used in the RESET study were retrospectively collected from 16 hospitals in South Korea. A stratified random sampling method was applied to split the data into training and test sets (70:30 split ratio). Clinical information, such as age, sex, tumor stage, smoking, performance status, metastasis, type of metastasis, dose adjustment, and pathologic information on EGFR mutations were inputted. Training was performed using eight ML algorithms: logistic regression, decision tree, deep neural network, random forest, support vector machine, boosting, bagging, and the naïve Bayes classifier. The model performance was assessed based on sensitivity, specificity, and accuracy. Area under the receiver operator characteristic curve (AUC) was calculated and compared between the ML models using DeLong's test. A Kaplan-Meier (KM) curve was used to visualize the identified strata obtained from the ML models. RESULTS: No significant differences in the input variables were observed between the training and test datasets. The best-performing models were support vector machine in predicting 1-year afatinib continuation (AUC 0.626) and decision tree in 2-year survival after afatinib start (AUC 0.644), although the performances of the ML models were comparable and did not display any predictive roles. KM analysis and log-rank test revealed significant differences between the strata identified from the ML model (p < 0.001) in terms of both time-on-treatment (TOT) and overall survival (OS). CONCLUSION: The performances of ML models in our study found no discernible roles in predicting afatinib-related outcomes, although the identified strata revealed different TOT and OS in the KM analysis. This implies the strength of ML in predicting the survival outcome, as well as the limitation of electronic medical record-based variables in ML algorithms. Careful consideration of variable inclusion is likely to improve the general model performance.

Development of selective mercury recovery technology by using iron iodide from waste sludge of non-ferrous metal smelting process.

The waste sludge from non-ferrous metal smelter contains high concentrations of mercury (Hg), arsenic (As) and sulfur (S). The Article 11 of the Minamata Convention on Mercury mandates the recovery of Hg before the disposal stage of Hg waste. However, As compounds have similar boiling points with Hg compounds, and they are considered interfering substances in the recovery of Hg. Moreover, a high concentration of S requires significant energy to volatilize Hg. This study examined the optimal conditions for selective recovery of Hg and energy reduction by introducing FeI2 as an additive during thermal treatment. Thermogravimetric analysis was utilized to evaluate the conversion of HgS to HgI2 under the influence of FeI2. The optimal conditions for thermal treatment such as temperature, treatment time, and molar ratio of [Hg]:[As]:[FeI2] were explored. The simulated waste indicated that the maximum separation efficiency of Hg was ∼95%, thereby allowing a selective separation of 81.5% of Hg from waste sludge with an Hg content of 0.33%, As content of 23.8%, and S content of 30.7%. Sequential extraction procedure was applied to evaluate the stability of Hg and As for residues. As a result, most Hg was vaporized and As was stabilized in sulfide, crystalline, and amorphous forms.