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Abstract Impulse oscillometry (IOS) is a sensitive tool for assessing small airway function in patients with chronic obstructive pulmonary disease (COPD). This study aimed to differentiate between COPD, small airway disease (SAD), and normal groups using IOS, and to evaluate the clinical applicability of IOS. This retrospective cohort study was conducted from January 2020 to February 2022. The eligible population comprised adult patients who simultaneously underwent IOS and pulmonary function tests. The diagnostic value of IOS in differentiating SAD and/or COPD from control was analyzed, and the correlations among IOS parameters, lung function, and radiological assessment results were determined. Among the enrolled 306 patients, 38 (12.4%) had SAD and 134 (43.8%) had COPD. The remainder comprised the control group without COPD and/or SAD. Abnormal airway resistance according to IOS parameters was detected in 17.2% of the patients in the control group, 47.2% of those in the SAD group, and 55.2% of those in the COPD group. Airway resistance estimated by IOS were significantly higher in the SAD and COPD groups than in the control group and correlated with lung function and radiological airway wall thickness. We developed a composite index called the IOS severity index (IOSsi) using IOS parameters that can predict SAD and COPD, and IOSsi showed significantly differentiation of SAD and/or COPD from control. Especially, IOSsi value ≥ 4 was associated with an increased risk of SAD and/or COPD and also with risk for moderate-to-severe exacerbation in patients with COPD. IOS may be a useful tool to differentiate disease status and evaluate disease severity and prognosis in patients with SAD and/or COPD, and a prognostic factor of COPD.

Abstract Inhaler therapy and physical activity (PA) are important methods of chronic obstructive pulmonary disease (COPD) management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in patients with COPD using a long-acting beta-agonists (LABA)/long-acting muscarinic antagonist (LAMA) combination. We emulated a target trial to estimate the benefit of MVPA in patients with COPD using a dual ultra-long-acting bronchodilators. We enrolled patients aged ≥ 40 who were diagnosed with COPD between 2014 and 2018, initiated a LABA/LAMA combination, and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days/week or moderate aerobic exercise > 30 min per day on ≥ 5 days/week. The main outcomes were the future usage of inhaled corticosteroids (ICS) and severe exacerbation. We identified 1,526 patients who initiated MVPA and 4,516 who did not. The median follow-up period was 3.0 years. The hazard ratio (HR) for future ICS usage in the MVPA initiation group was 0.83 (95% confidence intervals (CI): 0.72, 0.97) compared to the control group. The HR for severe exacerbation in the MVPA initiation group was 0.81 (95% CI: 0.68, 0.96) compared to the control group. Subgroup analyses by age, sex, body mass index, residence area, smoking and drinking status showed consistent benefits in these outcomes. Initiation of MVPA may offer an additional benefit for even COPD patients who use a dual ultra-long-acting bronchodilators.

Objectives This study was conducted to develop a mobile application for digital health coaching to support self-management in older adults with multiple chronic conditions. Additionally, the usability of this application was evaluated. Methods The HAHA2022 mobile application was developed through a multidisciplinary team approach, incorporating digital health coaching strategies targeting community-dwelling older adults with multiple chronic conditions. Usability was assessed with the Korean version of the Mobile Application Rating Scale. The usability tests involved eight expert panel members and 10 older adults (mean age, 74 ± 3 years; 90% women) from one senior welfare center. Results HAHA2022 is an Android-based mobile application that is also integrated into wearable devices to track physical activity. It features an age-friendly design and includes five main menus: Home, Action Plan, Education, Health Log, and Community. The average overall usability test scores—covering engagement, functionality, aesthetics, and information—were 4.27 of 5 for the expert panel and 4.53 of 5 for the older adults. Conclusions The HAHA2022 application was developed to improve self-management among community-dwelling older adults with multiple chronic conditions. Usability tests indicate that the application is highly acceptable and feasible for use by this population. Consequently, HAHA2022 is anticipated to be widely implemented. Nonetheless, further research is required to confirm its effectiveness through digital health intervention.

Abstract It remains unclear whether pulmonary fibrosis-like changes differ in patients with different SARS-CoV-2 variants. This study aimed to compare pulmonary fibrotic changes between two SARS-CoV-2 variant periods (delta vs. pre-delta) in critically ill patients with SARS-CoV-2 pneumonia. Clinical data and chest CT images of patients with SARS-CoV-2 pneumonia receiving mechanical ventilation were collected from 10 hospitals in South Korea over two periods: delta (July-December, 2021; n = 64) and pre-delta (February, 2020-June, 2021; n = 120). Fibrotic changes on chest CT were evaluated through visual assessment. Of 184 patients, the mean age was 64.6 years, and 60.5% were ale. Fibrosis-like changes on chest CT (median 51 days from enrollment to follow up CT scan, interquartile range 27–76 days) were identified in 75.3%. Delta group showed more fibrosis-like changes (≥ 2) (69.8% vs. 43.1%, P = 0.001) and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Even after propensity score matching with clinical variables, delta group had more severe (≥ 2) fibrosis-like changes (71.4% vs. 38.8%, P = 0.001), and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Our data suggest that critically ill patients with SARS-CoV-2 in delta period had more severe pulmonary fibrosis-like changes than those in pre-delta period.

Abstract The somatic BRCA1 or BRCA2 Pathogenic Variant (PV)/Likely PV (LPV) from Next Generation Sequencing (NGS) is the most important biomarker for PARP inhibitor use and maintenance-targeted therapies. A discrepancy in the detection rates of BRCA1 and BRCA2 PV/LPV was identified among the NGS platforms. The objective of this study was to compare the somatic BRCA results from two distinct platforms using the same cohort and to identify the causes of these differences. Patients with epithelial ovarian cancer who concurrently underwent tumor NGS using two different platforms between January 2022 and June 2023 were included in this study. The two platforms used were in-house tumor NGS (Illumina NextSeq 550Dx, SureSelectXT library kit, and datasets from 1000 Genomes, ESP6500, ExAC, and ClinVar) and GreenPlan homologous recombination deficiency (HRD) test (Illumina NextSeq 550Dx, customized Twist Bioscience library kit, and datasets from COSMIC and OncoKB). The results of somatic mutations in BRCA1 and BRCA2 were compared between the two platforms. Of the 118 patients, 11.9% (n = 14) exhibited a discordant interpretation of BRCA1 or BRCA2 between the two platforms. Eleven patients (9.3%) exhibited negative results in the in-house platform but positive results (eight seven as PV of BRCA1, one as PV of BRCA2, one as LPV of BRCA1, and two as LPV of BRCA2) in the GreenPlan HRD test, while three patients (2.6%) had positive BRCA pathogenic variants (two as PV of BRCA1 [c.3340G > T, c.5152 + 3 A > C], one as LPV of BRCA2 [c.8174G > T], and one as LPV of BRCA1 [c.5017_5019delCAC]) in the in-house platform but a negative result in the GreenPlan HRD test. The discordance rate of somatic BRCA1 or BRCA2 mutations from different platforms was approximately 12%. In the case of the strong implication of BRCA PV/LPV with a negative result with one genetic test, different platforms could be considered in limited cases. Careful interpretation and further studies for the cross-validation of gene analysis platforms are needed.

Abstract Epidermally mounted sensors using triaxial accelerometers have been previously used to monitor physiological processes with the implementation of machine learning (ML) algorithm interfaces. The findings from these previous studies have established a strong foundation for the analysis of high-resolution, intricate signals, typically through frequency domain conversion. In this study we integrate a wireless mechano-acoustic sensor with a multi-modal deep learning system for the real-time analysis of signals emitted by the laryngeal prominence area of the thyroid cartilage at frequency ranges up to 1 kHz. This interface provides real-time data visualization and communication with the ML server, creating a system that assesses severity of chronic obstructive pulmonary disease and analyzes the user’s speech patterns.

Abstract There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph

This study was conducted to investigate the effects of feeding Artemia nauplii enriched with poly-β-hydroxybutyrate (PHB) on Pacific white shrimp (Penaeus vannamei) post-larvae. A total 900 shrimp (initial average body weight: 2.50 ± 0.01 mg) were randomly distributed into 9 acrylic tanks (96 L) in triplicate groups. The Artemia reared in 0%, 0.25% and 0.50% PHB dissolved water (designated as Con, PHB25 and PHB50, respectively) were fed to the shrimp post-larvae for 14 days. The growth performance of shrimp was significantly higher in PHB25 and PHB50 groups than those in Con group. Survival was not significantly different among all the groups. Relative gene expressions of trypsin and amylase were significantly upregulated in PHB25 group than those of Con group. Relative gene expression of chymotrypsin was significantly upregulated in PHB25 and PHB50 groups compared to Con group. Relative gene expression of insulin-like growth factor-I was significantly upregulated in PHB25 group than in Con group. Relative gene expression of insulin-like growth factor-binding protein was significantly upregulated in both PHB25 and PHB50 groups than that of Con group. Relative expression of prophenoloxidase gene was significantly upregulated in PHB25 and PHB50 groups as compared to Con group. Relative expression of penaeidin-3a gene was significantly upregulated in PHB50 group as compared to Con group. This study demonstrated that PHB, as a functional nutritional enrichment for Artemia, improves the growth, digestibility and immunity of shrimp post-larvae.

Abstract Severe pneumonia results in high morbidity and mortality despite advanced treatments. This study investigates thoracic muscle mass from chest CT scans as a biomarker for predicting clinical outcomes in ICU patients with severe pneumonia. Analyzing electronic medical records and chest CT scans of 778 ICU patients with severe community-acquired pneumonia from January 2016 to December 2021, AI-enhanced 3D segmentation was used to assess thoracic muscle mass. Patients were categorized into clusters based on muscle mass profiles derived from CT scans, and their effects on clinical outcomes such as extubation success and in-hospital mortality were assessed. The study identified three clusters, showing that higher muscle mass (Cluster 1) correlated with lower in-hospital mortality (8% vs. 29% in Cluster 3) and improved clinical outcomes like extubation success. The model integrating muscle mass metrics outperformed conventional scores, with an AUC of 0.844 for predicting extubation success and 0.696 for predicting mortality. These findings highlight the strong predictive capacity of muscle mass evaluation over indices such as APACHE II and SOFA. Using AI to analyze thoracic muscle mass via chest CT provides a promising prognostic approach in severe pneumonia, advocating for its integration into clinical practice for better outcome predictions and personalized patient management.

Abstract 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

Background Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. Methods We retrospectively analyzed 107 COPD patients without a history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion (ppb) were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. Results The median FeNO value was 32 ppb (interquartile range, 19 to 45) and 34 (20.0%) patients were classified as high FeNO group (median 74 ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥300 cells/μL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01 to 6.91; p=0.049). Conclusion High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

Background/purpose: No consensus has been established regarding the exact amount of bone grafting in maxillary sinus augmentation. The aim of this study was to estimate the minimum bone volume for sinus augmentation and to investigate the factors that influence the augmentation volume (AV). Materials and methods: This study included patients with cone-beam computed tomography scanning. Dome-shaped sinus augmentation was performed virtually at vertical heights (VH) of 3, 5, 7, and 9 mm in Group A (without implantation) and Group B (with implantation). The augmentation angle (AA) and the sinus width (SW) were measured. The AV was measured using the three-dimensional image processing program 3D Slicer. Univariable and multivariable analyses were conducted. Results: This study included 30 patients (120 subjects). In Group A, the mean AVs were 0.062, 0.271, 0.642, and 1.287 cc at VHs of 3, 5, 7, and 9 mm, respectively, in Group B, the mean AVs were 0.037, 0.230, 0.594, and 1.230 cc. Univariable analysis indicated that factors significantly associated with the AV in both groups included SW, AA, and VH (P

SMARCA4 (BRG1) is a core unit of the SWI/SNF complex, regulating gene transcription through chromatin remodeling. Germline SMARCA4 variants have been reported to be associated with various malignancies. Here, we report the first case of extraskeletal Ewing sarcoma in a young female patient with a germline pathogenic variant of SMARCA4 (c.3546 + 1G>A), diagnosed with next generation sequencing (NGS). This alteration was also identified in her familial lineage, including her sister who was previously diagnosed with small cell carcinoma of the ovary, hypercalcemic type, a malignancy highly associated with SMARCA4 mutations. Despite undergoing radical surgery and receiving systemic treatments including VeIP (vinblastine, ifosfamide, cisplatin), and VDC (vincristine, doxorubicin, cyclophosphamide) regimens, the patient succumbed to death due to disease progression. With the implementation of NGS, we anticipate that more cases with SMARCA4 mutations will be diagnosed in the future. Further research is necessary to unveil therapeutic targets associated for this oncogenic alteration.

Backgrounds The management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in patients with severe COVID-19 pneumonia.Methods Clinical and radiological data were prospectively collected from 64 patients who required mechanical ventilation due to COVID-19 pneumonia and were enrolled from eight hospitals in South Korea. Fibrotic changes on chest CT were evaluated by visual assessment, and extent of fibrosis (mixed disease score) was measured using automatic quantification system.Results 64 patients were enrolled, and their mean age was 58.2 years (64.1% were males). On chest CT (median interval: 60 days [IQR; 41–78 days] from enrolment), 35 (54.7%) patients showed ≥3 fibrotic lesions. The most frequent fibrotic change was traction bronchiectasis (47 patients, 73.4 %). Median extent of fibrosis measured by automatic quantification was 10.6% (IQR, 3.8–40.7%). In a multivariable Cox proportional hazard model, which included nine variables with a p value of

Abstract This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020–December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2

BACKGROUND: Patients with glioblastoma (GBM) and high-grade glioma (HGG, World Health Organization [WHO] grade IV glioma) have a poor prognosis. Consequently, there is an unmet clinical need for accessible and noninvasively acquired predictive biomarkers of overall survival in patients. This study evaluated morphological changes in the brain separated from the tumor invasion site (ie, contralateral hemisphere). Specifically, we examined the prognostic value of widespread alterations of cortical thickness (CT) in GBM/HGG patients. METHODS: We used FreeSurfer, applied with high-resolution T1-weighted MRI, to examine CT, evaluated prior to standard treatment with surgery and chemoradiation in patients (GBM/HGG, N = 162, mean age 61.3 years) and 127 healthy controls (HC; 61.9 years mean age). We then compared CT in patients to HC and studied patients associated changes in CT as a potential biomarker of overall survival. RESULTS: Compared to HC cases, patients had thinner gray matter in the contralesional hemisphere at the time of tumor diagnosis. patients had significant cortical thinning in parietal, temporal, and occipital lobes. Fourteen cortical parcels showed reduced CT, whereas in 5, it was thicker in patients cases. Notably, CT in the contralesional hemisphere, various lobes, and parcels was predictive of overall survival. A machine learning classification algorithm showed that CT could differentiate short- and long-term survival patients with an accuracy of 83.3%. CONCLUSIONS: These findings identify previously unnoticed structural changes in the cortex located in the hemisphere contralateral to the primary tumor mass. Observed changes in CT may have prognostic value, which could influence care and treatment planning for individual patients.

Objective We aimed to elucidate the clinical factors associated with acute exacerbation and disease progression in young patients with chronic obstructive pulmonary disease (COPD).Methods This retrospective longitudinal observational study included patients with COPD aged between 20 and 50 years with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)300/µL (aHR=1.469, 95% CI=[1.038–2.081]) and low FEV1 (%) (aHR=0.979, 95% CI=[0.970–0.987]). A history of asthma, sputum, blood eosinophil count >300/µL, low FEV1 (%) and low diffusing capacity of the lung for carbon monoxide (DLCO) (%) were identified as clinical factors associated with the early initiation of regular inhalation therapy. The risk factors associated with worsened FEV1 decline were increasing age, female sex, history of pulmonary tuberculosis, sputum, low FEV1 (%) and low DLCO (%).Conclusions In young COPD patients, specific high-risk features of acute exacerbation and disease progression need to be identified, including a history of previous respiratory diseases, current respiratory symptoms, blood eosinophil counts, and structural or functional pulmonary impairment.

Abstract 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.

Abstract 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

Abstract 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

Abstract 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.

Abstract A weak correlation between diffusing capacity of the lung for carbon monoxide (DLCO) and emphysema has been reported. This study investigated whether impaired DLCO in chronic obstructive pulmonary disease (COPD) is associated with increased risk of acute exacerbation independent of the presence or extent of emphysema. This retrospective cohort study included patients with COPD between January 2004 and December 2019. The participants were divided into four groups based on visually detected emphysema and impaired DLCO. Among 597 patients with COPD, 8.5% had no emphysema and impaired DLCO whereas 36.3% had emphysema without impaired DLCO. Among the four groups, patients with impaired DLCO and emphysema showed a higher risk of moderate-to-severe or severe exacerbation than those with normal DLCO. Impaired DLCO was an independent risk factor for severe exacerbation (hazard ratio, 1.524 [95% confidence interval 1.121–2.072]), whereas the presence of emphysema was not. The risk of moderate-to-severe or severe exacerbation increases with the severity of impaired DLCO. After propensity-score matching for the extent of emphysema, impaired DLCO was significantly associated with a higher risk of moderate-to-severe (p = 0.041) or severe exacerbation (p = 0.020). In patients with COPD and heterogeneous parenchymal abnormalities, DLCO can be considered an independent biomarker of acute exacerbation.

CD47 is expressed on cell surfaces and acts as a “don’t eat me” signal by interacting with signal-regulatory protein-α on the macrophage surface. Some cancer cells express CD47 protein and can evade macrophage phagocytosis. Herein, we evaluated the feasibility of targeting CD47 for osteosarcoma by analyzing its expression patterns, clinicopathological correlations, and immunotherapeutic potential. We performed a retrospective analysis on 24 biopsy samples from patients with osteosarcoma to investigate correlations between CD47 protein positivity and clinicopathological characteristics. CD47 protein expression was detected in 20.8% of the biopsy samples. CD47 positivity correlated with metastasis at diagnosis. Patients with CD47-positive tumors were older than those with CD47-negative tumors. However, CD47 protein expression was not associated with sex, tumor size, or histologic response to preoperative chemotherapy. In vitro, CD47 antibody (B6H12) did not affect osteosarcoma cell viability or apoptosis. In a wound-healing assay, CD47 inhibited the migration of osteosarcoma cells. Differentiated macrophages exhibited higher phagocytic activity against osteosarcoma cells when pretreated with B6H12 compared with the isotype control. Our preliminary data suggest a possible interaction between CD47 protein and macrophage phagocytosis in osteosarcoma metastasis. A better understanding of the role of CD47 is necessary to develop an innovative immunotherapeutic approach against osteosarcoma.

Introduction Amblyopia is a neurodevelopmental vision disorder typically affecting one eye, resulting in compromised binocular function. While evidence-based treatments exist for children, there are no widely accepted treatments for adults. This trial aims to assess the efficacy of appropriate optical treatment in improving vision and visual functions in adults with amblyopia. This is hypothesised to significantly improve visual acuity of the amblyopic eye and other visual functions.Methods and analysis SPEctacle Correction for the TReatment of Amblyopia is a prospective non-randomised interventional trial. The following criteria for amblyopia will be used: best corrected visual acuity (BCVA) in the amblyopic eye of 0.3 to 1.0 (inclusive) logMAR VA and in the fellow eye, 0.1 logMAR or better, with an interocular VA difference of ≥2 logMAR lines. Eligible participants aged 18–39 will receive full/near-full optical treatment requiring wear for at least half their waking hours for the trial duration. A difference of ≥1.00D spherical equivalent between a participant’s current refractive correction and the study prescription is required for eligibility. Primary outcome is the change in amblyopic eye BCVA from baseline to 24-week postenrolment. Secondary outcomes include distance and near VA of both eyes, stereoacuity, contrast sensitivity, interocular suppression, angle of strabismus and fixation stability measured at monthly intervals. Visual evoked potentials will also be measured at baseline, week 12 and week 24. Treatment compliance and quality of life for all participants will be monitored.Analyses comparing baseline and week 24 will utilise pairwise comparisons. Linear mixed models will be fitted to the data for measures taken monthly. This allows estimates and inferences to be drawn from the coefficients of the model, while handling missing data.Ethics and dissemination Human ethics approval was obtained from the respective ethics board of the Hong Kong Polytechnic University (HSEARS20210915002) and the University of Waterloo (#44235). The study protocol will conform to the principles of the Declaration of Helsinki. Results will be disseminated through peer-reviewed journals and conferences.Trial registration number NCT05394987; clinicaltrials.org.

Hypophosphatasia (HPP) is a rare condition characterized by abnormal bone mineralization. The manifestations of HPP vary from no symptoms to intrauterine fetal death; short stature is another indication of HPP. A 3 ½-year-old boy presented with short stature, transient hypercalcemia, and mild gait disturbance without definite bony deformity. Laboratory examination revealed transient hypercalcemia, normal phosphorous and 25-hydroxy vitamin D levels, and mildly low alkaline phosphatase levels. A targeted next-generation sequencing panel associated with inborn errors of metabolism revealed a pathogenic heterozygous mutation in the ALPL gene, c.979T>C (p.Phe327Leu). When a child visits a hospital with short stature, decreased height velocity, and low alkaline phosphatase level, clinicians should consider the possibility of HPP even if definite skeletal dysplasia is not evident.

Objectives: This study compared serum lipid concentration according to drinking habits. Methods: We analyzed data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII). The study included 8,525 adults (3,651 males and 4,874 females), aged 30 – 59 years. Results: There were differences in age, gender, education level, smoking status, physical activity, and waist circumference between drinkers and abstainers. The serum low-density lipoprotein-cholesterol (LDL-C) level of the drinkers was lower than those of the abstainers (P < 0.05). The serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations were highest in the group that consumed alcohol ‘more than twice a week’ relative to the other groups (P < 0.001). The LDL-C and atherogenic index (AI) levels were lowest in the ‘more than twice a week’ drinking group compared to the other groups (P < 0.001). The serum TG and HDL-C concentrations were the highest in the ‘7 glasses/time’ group (P < 0.001). The serum LDL-C concentration was the lowest in the ‘7 glasses/time’ group (P < 0.001). Notably, the higher the frequency of binge drinking (7 glasses or more), the higher the concentration of TG (P < 0.001). The serum HDL-C concentration was significantly higher in the ‘no binge’ and ‘more than once a week’ groups compared to the other groups (P < 0.001). The serum LDL-C concentration and AI score were the lowest in the ‘more than once a week’ group (P < 0.001). Conclusions: As the quantity and frequency of drinking increased, the serum TC concentration increased. Moreover, an increase in the serum HDL-C concentration led to a decrease in AI. The factors exacerbating cardiovascular disease increased simultaneously due to drinking. Our results suggest that for individuals with hypertriglyceridemia and patients with low HDL-cholesterolemia, separate guidelines based on the quantity and frequency of alcohol consumption are warranted.

Abstract Residual antibiotics in agricultural soils can be of concern due to the development of antibiotic resistant microorganisms. Among various antibiotics, oxytetracycline (OTC), streptomycin (ST), and validamycin A (VA) have been used for agricultural purposes in South Korea; however, studies on the biodegradation of these antibiotics in soil are limited. Therefore, this study investigated the effects of pH (5.5, 6.8, and 7.4) and temperature (1.8, 23.0, and 31.2 °C) conditions on the biodegradation of these antibiotics in soil. The biodegradation tests were carried out in the field soil (FS) and rice paddy soil (RS) for 30 d with OTC and ST and 10 d with VA, and the residual antibiotics concentrations were monitored over the degradation period. Under various conditions, the degradation rates of ST was lower (11–69%) than that of OTC (60–90%) and VA (15–96%). The degradation half-lives of OTC and VA tend to decrease with increasing pH value, while the degradation half-life of ST tend to increase with increasing pH value. But, the effect of soil pH on the antibiotics degradation was not statistically significant, except for ST in the FS and RS and VA in the FS. The degradation of three antibiotics was greater at higher temperatures (23.0 °C and 31.2 °C) than at lower temperature (1.8 °C), and the degradation half-lives decreased with increasing temperature. The different degradation characteristics of different antibiotics in soil can be explained by the different characteristics of the antibiotics (e.g., sorption affinity, chemical forms) and soil (e.g., organic matter content). The results suggest that the degradation characteristics of antibiotics need to be considered in order to properly manage the residual antibiotics in soil.

Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in the T2M mouse model of db/db mice. FMC showed a greater inhibition of lipid accumulation compared to unfermented ice plant extract. Two-week oral administration with FMC inhibited body weight gain, lowered fasting blood glucose, and improved glucose tolerance. Serum parameters related to T2D including insulin, glycosylated hemoglobin, adiponectin, and cholesterols were improved as well. Histological analysis confirmed the protective effect of FMC on pancreas and liver destruction. FMC treatment significantly increased the expression and phosphorylation of IRS-1, PI3K, and AKT. Additionally, AMP-activated protein kinase phosphorylation and nuclear factor erythroid 2–related factor 2 were also increased in the liver tissues of db/db mice treated with FMC. Overall, our results indicate the anti-diabetic effect of FMC; therefore, we suggest that FMC may be useful as a therapeutic agent for T2D.

Abstract Conventional severity-of-illness scoring systems have shown suboptimal performance for predicting in-intensive care unit (ICU) mortality in patients with severe pneumonia. This study aimed to develop and validate machine learning (ML) models for mortality prediction in patients with severe pneumonia. This retrospective study evaluated patients admitted to the ICU for severe pneumonia between January 2016 and December 2021. The predictive performance was analyzed by comparing the area under the receiver operating characteristic curve (AU-ROC) of ML models to that of conventional severity-of-illness scoring systems. Three ML models were evaluated: (1) logistic regression with L2 regularization, (2) gradient-boosted decision tree (LightGBM), and (3) multilayer perceptron (MLP). Among the 816 pneumonia patients included, 223 (27.3%) patients died. All ML models significantly outperformed the Simplified Acute Physiology Score II (AU-ROC: 0.650 [0.584–0.716] vs 0.820 [0.771–0.869] for logistic regression vs 0.827 [0.777–0.876] for LightGBM 0.838 [0.791–0.884] for MLP; P

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. Methods A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. Results More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. Conclusion Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

Abstract Objectives Persistent postural‐perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. Methods Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. Results Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space‐motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. Conclusion This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

PurposeTo report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection.MethodsData from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity.ResultsThe median follow-up was 28.9 months (range, 1.1–62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months’ post-PBT (p=0.047) and was maintained until 13 months (p=0.028).ConclusionHypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.

Background Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC). Methods This retrospective cohort study included 11 420 participants aged ≥40 years with forced expiratory volume in 1 s (FEV1)/FVC ≥0.7 who underwent at least two health screening examinations with coronary computed tomography scan between 2003 and 2020, and were without a history of CVD or interstitial lung disease. Participants with PRISm, defined as FEV1/FVC ≥0.7 and FEV1

BackgroundSarcopenia is a risk factor for pneumonia in the elderly, and the timed up-and-go test (TUG) can be used as a screening tool for sarcopenia in this population. This study aimed to evaluate the association between TUG test results and future pneumonia or ventilator care.Materials and methodsFrom the National Health Insurance Service-Senior Cohort database, we identified 19,804 people without neurological diseases who underwent the TUG test in the National Screening Program for Transitional Ages at the age of 66 years during 2007-2008. Gait abnormality was defined as taking 10 s or longer to perform the TUG test. Pneumonia occurrence was defined using the International Classification of Diseases 10th Revision (ICD-10) code for pneumonia (J12-J18, J69), and ventilator care was defined by procedure codes (M5830, M5850, M5867, M5858, M5860, M5859) according to the Healthcare Common Procedure Coding system codes from 2007 to 2015.ResultsThe mean follow-up period was 7.4 years (standard error, SE 0.02). The incidence rates of pneumonia in the normal and slow TUG groups were 38 and 39.5/1000 person-years, respectively. The slow TUG group did not show a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.042; 95% confidence interval [95% CI], 0.988-1.107]). Regarding ventilator care, the incidence was 4.7 and 5.2 cases per 1,000 person-years in the normal and slow TUG groups, respectively. Slow TUG groups also did not show an increased risk of ventilator occurrence (aHR, 1.136, [95% CI = 0.947-1.363]).ConclusionThe TUG test result was not associated with future pneumonia or ventilator care and may not be useful for predicting pneumonia in community-dwelling elderly individuals. Further studies are needed to identify additional functional tools for sarcopenia associated with future pneumonia occurrences.

Abstract We developed a machine learning algorithm (MLA) that can classify human thyroid cell clusters by exploiting both Papanicolaou staining and intrinsic refractive index (RI) as correlative imaging contrasts and evaluated the effects of this combination on diagnostic performance. Thyroid fine-needle aspiration biopsy (FNAB) specimens were analyzed using correlative optical diffraction tomography, which can simultaneously measure both, the color brightfield of Papanicolaou staining and three-dimensional RI distribution. The MLA was designed to classify benign and malignant cell clusters using color images, RI images, or both. We included 1535 thyroid cell clusters (benign: malignancy = 1128:407) from 124 patients. Accuracies of MLA classifiers using color images, RI images, and both were 98.0%, 98.0%, and 100%, respectively. As information for classification, the nucleus size was mainly used in the color image; however, detailed morphological information of the nucleus was also used in the RI image. We demonstrate that the present MLA and correlative FNAB imaging approach has the potential for diagnosing thyroid cancer, and complementary information from color and RI images can improve the performance of the MLA.

Objectives Portal sites have become places to share queries about performing nursing and obtain expert know-how. This study aimed to analyze topics of interest in the field of infusion nursing among nurses working in clinical settings. Methods In total, 169 user query data were collected from October 5, 2018 to December 25, 2021. This exploratory study analyzed the semantic structure of posts on the nurse question-and-answer board of an infusion nursing-related internet portal by extracting major keywords through text data analysis and conducting term frequency (TF) and term frequency-inverse document frequency (TF-IDF) analysis, N-gram analysis, and CONvergence of iteration CORrelation (CONCOR) analysis. Word cloud visualization was conducted utilizing the “wordcloud” package of Python to provide a visually engaging and concise summary of information about the extracted terms. Results “Infusion” was the most frequent keyword and the highest-importance word. “Infusion→line” had the strongest association, followed by “vein→catheter,” “line→change,” and “peripheral→vein.” Three topics were identified: the replacement of catheters, maintenance of the patency of the catheters, and securement of peripheral intravenous catheters, and the subtopics were blood sampling through central venous catheter, peripherally inserted central catheter management, evidence-based infusion nursing, and pediatric infusion nursing. Conclusions These findings indicate that nurses have various inquiries in infusion nursing. It is necessary to re-establish the duties and roles of infusion nurses, and to develop effective infusion nursing training programs.

Various branch anomalies of the aortic arch have been reported, but cases with separate origins of the internal and external carotid arteries with combined direct aortic arch origin of the left vertebral artery are extremely rare. Herein, we present a rare case of aplasia of the left common carotid artery with separate origins of the ipsilateral internal and external carotid arteries and vertebral artery from the aortic arch in a 10-year-old girl. In addition, we review the embryological development and clinical implications of these anatomical variations.

Abstract Risk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02–1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05–1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89–1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.

Background Limited data are available in COVID-19 patients on the prediction of treatment response to systemic corticosteroid therapy based on systemic inflammatory markers. There is a concern whether the response to systemic corticosteroid is different according to white blood cell (WBC) counts in COVID-19 patients. We aimed to assess whether WBC count is related with the clinical outcomes after treatment with systemic corticosteroids in severe COVID-19.Methods We conducted a retrospective cohort study and analysed the patients hospitalised for severe COVID-19 and received systemic corticosteroids between July 2020 and June 2021. The primary endpoint was to compare the composite poor outcome of mechanical ventilation, extracorporeal membrane oxygenation, and mortality among the patients with different WBC counts.Results Of the 585 COVID-19 patients who required oxygen supplementation and systemic corticosteroids, 145 (24.8%) belonged to the leukopoenia group, 375 (64.1%) belonged to the normal WBC group, and 65 (11.1%) belonged to the leukocytosis group. In Kaplan-Meier curve, the composite poor outcome was significantly reduced in leukopoenia group compared to leukocytosis group (log-rank p-value < 0.001). In the multivariable Cox regression analysis, leukopoenia group was significantly associated with a lower risk of the composite poor outcome compared to normal WBC group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.14–0.76, p-value = 0.009) and leukocytosis group (aHR = 0.30, 95% CI = 0.12–0.78, p-value = 0.013). There was no significant difference in aHR for composite poor outcome between leukocytosis and normal WBC group.Conclusion Leukopoenia may be related with a better response to systemic corticosteroid therapy in COVID-19 patients requiring oxygen supplementation.KEY MESSAGESIn severe COVID-19 treated with systemic corticosteroids, patients with leukopoenia showed a lower hazard for composite poor outcome compared to patients with normal white blood cell counts or leukocytosis.Leukopoenia may be a potential biomarker for better response to systemic corticosteroid therapy in COVID-19 pneumonia.

The field study was undertaken to examine the potential for adverse effects of transgenic soybean expressing bioactive human epidermal growth factor (with tolerance to the herbicide glufosinate, PPT) on the abundance and diversity of plant‐dwelling arthropods by comparing with those of a non‐GM parental cultivar, Gwangan soybean. Field surveys of soybean fields were carried out over two consecutive years, 2016 and 2017 at Ochang and Jeonju, Korea. The number of captured individuals associated with either of EGF and Gwangan soybean plants increased in 2017 compared with 2016 in both Ochang and Jeonju. During the survey period, the diversity and richness of the occurred insects and arachnids increased, dominance decreased, and the evenness of the insects remained static. The insects of Hymenoptera Order occurred most often comprised 25.4% of total captured insect pests. On the contrary, natural enemy from Hymenoptera Order and other insects from Diptera Order occurred more frequently (29.9% and 19.0%, respectively) in both the survey regions during the study periods. The score from PROXSCAL multidimensional scaling using combined data showed that the occurrence of insects and arachnids were separated due to their cultivation regions and years, irrespective of soybean cultivars. Consequently, the results indicated that there happened no notable change in the composition of arthropod communities in soybean agroecosystem due to GM event in soybean expressing EGF.

ABSTRACTCoxsackievirus B3 (CVB3) is a single-stranded RNA virus that belongs to the Enterovirus genus. CVB3 is a human pathogen associated with serious conditions such as myocarditis, dilated cardiomyopathy, and pancreatitis. However, there are no therapeutic interventions to treat CVB3 infections. In this study, we found that CVB3 induced metabolic alteration in host cells through increasing glycolysis level, as indicated by an increase in the extracellular acidification rate (ECAR). CVB3-mediated metabolic alteration was confirmed by metabolite change analysis using gas chromatography-mass spectrometry (GC-MS). Based on findings, a strategy to inhibit glycolysis has been proposed to treat CVB3 infection. Indeed, glycolysis inhibitors (2-Deoxy-D-glucose, sodium oxide) significantly reduced CVB3 titers after CVB3 infection, indicating that glycolysis inhibitors can be used as effective antiviral agents. Taken together, our results reveal a novel mechanism by which CVB3 infection is controlled by regulation of host cell metabolism.