Evaluating the HYDRASHIFT 2/4 Daratumumab assay: a powerful approach to assess treatment response in multiple myeloma.

OBJECTIVES: This study evaluates the HYDRASHIFT assay's effectiveness in mitigating daratumumab interference on serum protein tests during multiple myeloma (MM) treatment, aiming to ensure an accurate assessment of treatment response. METHODS: We analyzed 113 serum samples from 68 MM patients undergoing daratumumab treatment, employing both standard IF and the HYDRASHIFT assay. The assay's precision was determined through intra-day and inter-day variability assessments, while its specificity was verified using serum samples devoid of daratumumab. Comparative analysis of IF results, before and after the application of the HYDRASHIFT assay, facilitated the categorization of treatment responses in alignment with the International Myeloma Working Group's response criteria. RESULTS: The precision underscored the assay's consistent repeatability and reproducibility, successfully eliminating interference of daratumumab-induced Gκ bands. Specificity assessments demonstrated the assay's capability to distinguish daratumumab from both isatuximab and naturally occurring M-proteins. Of the analyzed cases, 91 exhibited successful migration of daratumumab-induced Gκ bands, thereby enhancing the accuracy of treatment response classification. The remaining 22 cases did not show a visible migration complex, likely due to the low concentration of daratumumab in the serum. These findings underscore the assay's critical role in distinguishing daratumumab from endogenous M-protein, particularly in samples with a single Gκ band on standard IF, where daratumumab and endogenous M-protein had co-migrated. CONCLUSIONS: The HYDRASHIFT assay demonstrates high precision, specificity, and utility in the accurate monitoring of treatment responses in MM patients receiving daratumumab. This assay represents a significant advancement in overcoming the diagnostic challenges posed by daratumumab interference.

Differential decline of lung function in COPD patients according to structural abnormality in chest CT.

Background: Different progressions or prognoses of chronic obstructive pulmonary disease (COPD) have been reported according to structural abnormalities based on chest computed tomography (CT). This study aimed to investigate whether different structural abnormalities independently affect annual lung function changes and clinical prognosis in patients with COPD. Methods: This longitudinal multicenter observational study was conducted using the KOCOSS cohort (NCT02800499) database in Korea from January 2012 to December 2019. For COPD patients with chest CT findings at baseline enrolment and longitudinal spirometric data, annual forced expiratory volume in 1 s (FEV1) decline rate (mL/year) and clinical outcomes were compared according to structural abnormalities, including emphysema, bronchiectasis (BE), and tuberculosis-destroyed lung (TDL). We estimated the adjusted annual FEV1 changes using a mixed-effect linear regression model. Results: Among the enrolled 237 patients, 152 showed structural abnormalities. Emphysema, BE, and TDL were observed in 119 (78.3%), 28 (18.4%), and 27 (17.8%) patients, respectively. The annual decline in FEV1 was faster in COPD patients with structural abnormalities than those without (ß = -70.6 mL/year, P-value = 0.039). BE/TDL-dominant or emphysema-dominant structural abnormality contributed to an accelerated annual FEV1 decline compared to no structural abnormality (BE/TDL-dominant, ß = -103.7 mL/year, P-value = 0.043; emphysema-dominant, ß = -84.1 mL/year, P-value = 0.018). Structural abnormalities made no significant differences in acute exacerbation rate and mortality. Conclusion: The lung function decline rate in COPD differed according to structural abnormalities on CT. These findings may suggest that more focus should be placed on earlier intervention or regular follow-up with spirometry in COPD patients with BE or TDL on chest CT.

Machine learning-driven prediction of brain metastasis in lung adenocarcinoma using miRNA profile and target gene pathway analysis of an mRNA dataset.

BACKGROUND: Brain metastasis (BM) is common in lung adenocarcinoma (LUAD) and has a poor prognosis, necessitating predictive biomarkers. MicroRNAs (MiRNAs) promote cancer cell growth, infiltration, and metastasis. However, the relationship between the miRNA expression profiles and BM occurrence in patients with LUAD remains unclear. METHODS: We conducted an analysis to identify miRNAs in tissue samples that exhibited different expression levels between patients with and without BM. Using a machine learning approach, we confirmed whether the miRNA profile could be a predictive tool for BM. We performed pathway analysis of miRNA target genes using a matched mRNA dataset. RESULTS: We selected 25 miRNAs that consistently exhibited differential expression between the two groups of 32 samples. The 25-miRNA profile demonstrated a strong predictive potential for BM in both Group 1 and Group 2 and the entire dataset (area under the curve [AUC] = 0.918, accuracy = 0.875 in Group 1; AUC = 0.867, accuracy = 0.781 in Group 2; and AUC = 0.908, accuracy = 0.875 in the entire group). Patients predicted to have BM, based on the 25-miRNA profile, had lower survival rates. Target gene analysis of miRNAs suggested that BM could be induced through the ErbB signaling pathway, proteoglycans in cancer, and the focal adhesion pathway. Furthermore, patients predicted to have BM based on the 25-miRNA profile exhibited higher expression of the epithelial-mesenchymal transition signature, TWIST, and vimentin than those not predicted to have BM. Specifically, there was a correlation between EGFR mRNA levels and BM. CONCLUSIONS: This 25-miRNA profile may serve as a biomarker for predicting BM in patients with LUAD.

Real-world treatment patterns and clinical outcomes in patients with stage III NSCLC in Korea: The KINDLE study.

OBJECTIVE: KINDLE-Korea is part of a real-world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The KINDLE was an international real-world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE-Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. RESULTS: A total of 461 patients were enrolled. The median age was 66 years (range: 24-87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)-based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. CONCLUSION: This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes.

Identification of the novel HLA-B*13:191 allele by next-generation sequencing.

The novel HLA-B*13:191 allele was detected during the HLA typing for kidney transplantation.

Highly Efficient Room-Temperature Spin-Orbit-Torque Switching in a Van der Waals Heterostructure of Topological Insulator and Ferromagnet.

All-Van der Waals (vdW)-material-based heterostructures with atomically sharp interfaces offer a versatile platform for high-performing spintronic functionalities at room temperature. One of the key components is vdW topological insulators (TIs), which can produce a strong spin-orbit-torque (SOT) through the spin-momentum locking of their topological surface state (TSS). However, the relatively low conductance of the TSS introduces a current leakage problem through the bulk states of the TI or the adjacent ferromagnetic metal layers, reducing the interfacial charge-to-spin conversion efficiency (qICS). Here, a vdW heterostructure is used consisting of atomically-thin layers of a bulk-insulating TI Sn-doped Bi1.1Sb0.9Te2S1 and a room-temperature ferromagnet Fe3GaTe2, to enhance the relative current ratio on the TSS up to ≈20%. The resulting qICS reaches ≈1.65 nm-1 and the critical current density Jc ≈0.9 × 106 Acm-2 at 300 K, surpassing the performance of TI-based and heavy-metal-based SOT devices. These findings demonstrate that an all-vdW heterostructure with thickness optimization offers a promising platform for efficient current-controlled magnetization switching at room temperature.

Differential response to roflumilast in patients with chronic obstructive pulmonary disease: real-world evidence.

Background: Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD. Methods: A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period. The primary outcome was to estimate the ratio of hazard ratio (RHR) of roflumilast for moderate-to-severe exacerbation in prespecified subgroups. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) for moderate-to-severe exacerbations. Results: Among 823,862 patients with COPD, 0.6% used roflumilast. The adjusted HR of roflumilast for moderate-to-severe exacerbations was reduced when treated for ≥3 months (RHR =0.558). Interaction effects of the variables on the HR of roflumilast for moderate-to-severe exacerbation were identified. The adjusted HR of roflumilast for moderate-to-severe exacerbation was significantly reduced in several subgroups: older age (65 years > age ≥50 years, RHR =0.838; age ≥65 years, RHR =0.818), a higher Charlson comorbidity index (1, RHR =0.832; 2, RHR =0.798; ≥3, RHR =0.790), history of exacerbation (RHR =0.886), bronchiectasis (RHR =0.774), chronic bronchitis (RHR =0.793), inhaled therapy [mono-bronchodilator, RHR =0.824; inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), RHR =0.591; LABA/long-acting muscarinic antagonist (LAMA), RHR =0.822; ICS/LABA/LAMA, RHR =0.570], methylxanthine (RHR =0.853), and statin (RHR =0.888). Conclusions: The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD. Personalised approaches to roflumilast based on clinical phenotypes would be effective for COPD.

Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study.

OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

Water-Based Generators with Cellulose Acetate: Uncovering the Mechanisms of Power Generation.

Power generation technologies based on water movement and evaporation use water, which covers more than 70% of the Earth's surface and can also generate power from moisture in the air. Studies are conducted to diversify materials to increase power generation performance and validate energy generation mechanisms. In this study, a water-based generator was fabricated by coating cellulose acetate with carbon black. To optimize the generator, Fourier-transform infrared spectroscopy, specific surface area, zeta potential, particle size, and electrical performance analyses were conducted. The developed generator is a cylindrical generator with a diameter of 7.5 mm and length of 20 mm, which can generate a voltage of 0.15 V and current of 82 µA. Additionally, we analyzed the power generation performance using three factors (physical properties, cation effect, and evaporation environment) and proposed an energy generation mechanism. Furthermore, we developed an eco-friendly and low-cost generator using natural fibers with a simple manufacturing process. The proposed generator can contribute to the identification of energy generation mechanisms and is expected to be used as an alternative energy source in the future.

Acute Exacerbation and Longitudinal Lung Function Change of Preserved Ratio Impaired Spirometry.

Background: Preserved ratio impaired spirometry (PRISm) is a heterogeneous disease entity. Limited data are available regarding its prevalence, clinical course, or prognosis. We aimed to evaluate the longitudinal clinical course of patients with PRISm compared with chronic obstructive pulmonary disease (COPD). Methods: A retrospective study enrolled PRISm and COPD patients who underwent chest computed tomography and longitudinal pulmonary function tests between January 2013 and December 2020. We compared the incidence of acute exacerbations and lung function changes between PRISm and COPD patients. Results: Of the 623 patients, 40 and 583 had PRISm and COPD, respectively. Compared to COPD patients, PRISm patients were younger, more likely to be female and have a history of tuberculosis, and less likely to be smokers. They also had less severe comorbidities, lower forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). The clinical course was not significantly different between the PRISm and COPD patients in terms of the risk of moderate-to-severe acute exacerbations or proportion of frequent exacerbators. During follow-up, PRISm patients had a significantly slower annual decline of forced expiratory volume in 1 second, FVC, and DLCO than COPD patients. Conclusion: PRISm patients had no significant difference in the risk of acute exacerbations, but a significantly slower decline of lung function during longitudinal follow-up, compared with COPD patients.

Diffusing capacity as an independent predictor of acute exacerbations in chronic obstructive pulmonary disease.

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.

Systematic review and meta-analysis of cardiac neurosis for development of clinical practice guidelines of Korean medicine.

Background: The development of clinical practice guidelines in traditional medicine requires evidence that sufficiently reflects the medical field. Cardiac neurosis is a disease that occurs because of problems in the autonomic nervous system and is characterized by symptoms of the circulatory system that are representative of autonomic dysfunction. In traditional medicine, the heart is considered to be involved in mental health problems, and cardiac neurosis is accompanied by a variety of mental symptoms. Furthermore, there is a categorized diagnosis for cardiac neurosis, and active empirical research is being conducted in China. Objective: This study aimed to systematically review and quantitatively synthesize the effects of Korean medicine treatments in patients with cardiac neurosis to develop evidence-based clinical practice guidelines for the treatment of autonomic dysfunction. Methods: Nine databases were searched for articles published before September 13, 2022. The methodological quality of the studies was assessed using the RoB tool. The primary outcomes were somatization, depression, anxiety, and effectiveness rate. The secondary outcome was the rate of adverse effects. Results: Based on a systematic literature review, 151 randomized controlled trials were selected and analyzed. For patients with cardiac neurosis, herbal medicine, combined treatment of herbal medicine and Western medicine, combined treatment of herbal medicine and acupuncture, acupuncture, and combined treatment of acupuncture and Western medicine showed better overall effects than Western medicine alone. Furthermore, the combined treatment of herbal medicine and psychotherapy and that of herbal medicine, psychotherapy, and Western medicine showed an overall better effect than the combined treatment of Western medicine and psychotherapy. Conclusion: A meta-analysis of articles revealed the effectiveness of Korean medicine treatments and verified the effectiveness of a Korean medicine treatment alone, Korean medicine combined treatment, and combined treatment of Korean medicine and Western medicine on cardiac neurosis. Limitations included the inability to verify the cause of high heterogeneity between studies and the poor quality of the included studies. Nevertheless, this systematic review and meta-analysis of cardiac neurosis showed that the disease concept of traditional medicine can also be organized based on the latest research. Future research related to traditional diseases such as these should be conducted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022347992, identifier CRD42022347992.

Combined effect of changes in NO2, O3, PM2.5, SO2 and CO concentrations on small airway dysfunction.

BACKGROUND AND OBJECTIVE: When multiple complex air pollutants are combined in real-world settings, the reliability of estimating the effect of a single pollutant is questionable. This study aimed to investigate the combined effects of changes in air pollutants on small airway dysfunction (SAD). METHODS: We analysed Korea National Health and Nutrition Examination Survey (KNHANES) V-VIII database from 2010 to 2018 to elucidate the associations between annual changes in air pollutants over a previous 5-year period and small airway function. We estimated the annual concentrations of five air pollutants: NO2, O3, PM2.5, SO2 and CO. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%-75%) <65% was defined as SAD. Using the quantile generalized-Computation (g-Computation) model, the combined effect of the annual changes in different air pollutants was estimated. RESULTS: A total of 29,115 individuals were included. We found significant associations between SAD and the quartiles of annual changes in NO2 (OR = 1.10, 95% CI = 1.08-1.12), O3 (OR = 1.03, 95% CI = 1.00-1.05), PM2.5 (OR = 1.03, 95% CI = 1.00-1.05), SO2 (OR = 1.04, 95% CI = 1.02-1.08) and CO (OR = 1.16, 95% CI = 1.12-1.19). The combined effect of the air pollutant changes was significantly associated with SAD independent of smoking (OR = 1.31, 95% CI = 1.26-1.35, p-value <0.001), and this trend was consistently observed across the entire study population and various subgroup populations. As the estimated risk of SAD, determined by individual-specific combined effect models, increased and the log odds for SAD increased linearly. CONCLUSION: The combined effect of annual changes in multiple air pollutant concentrations were associated with an increased risk of SAD.

Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance.

Marginal zone (MZ) B cells, which are splenic innate-like B cells that rapidly secrete antibodies (Abs) against blood-borne pathogens, are composed of heterogeneous subpopulations. Here, we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels. CD80high MZ B cells exhibited greater Ab-producing, proliferative, and IL-10-secreting capacities than did CD80low MZ B cells. Notably, CD80high MZ B cells survived 2-Gy whole-body irradiation, whereas CD80low MZ B cells were depleted by irradiation and then repleted with one month after irradiation. Depletion of CD80low MZ B cells led to accelerated development of type II collagen (CII)-induced arthritis upon immunization with bovine CII. CD80high MZ B cells exhibited higher expression of genes involved in proliferation, plasma cell differentiation, and the antioxidant response. CD80high MZ B cells expressed more autoreactive B cell receptors (BCRs) that recognized double-stranded DNA or CII, expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences, and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80low MZ B cells. Adoptive transfer experiments showed that CD21+CD23+ transitional 2 MZ precursors preferentially generated CD80low MZ B cells and that a proportion of CD80low MZ B cells were converted into CD80high MZ B cells; in contrast, CD80high MZ B cells stably remained CD80high MZ B cells. In summary, MZ B cells can be divided into two subpopulations according to their CD80 expression levels, Ab-producing capacity, radioresistance, and autoreactivity, and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

Clinical outcomes of long-term inhaled combination therapies in patients with bronchiectasis and airflow obstruction.

BACKGROUND AND OBJECTIVES: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction. METHODS: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC). RESULTS: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted ß-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL. CONCLUSION: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction.

Medial entorhinal cortex plays a specialized role in learning of flexible, context-dependent interval timing behavior.

Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether MEC time cells display learning dynamics required for encoding different temporal contexts. To explore this, we developed a novel behavioral paradigm that requires distinguishing temporal contexts. Combined with methods for cellular resolution calcium imaging, we find that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we find that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we find evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience.

Spirometric Interpretation and Clinical Relevance According to Different Reference Equations.

BACKGROUND: Global Lung Function Initiative (GLI)-2012 reference equation is currently suggested for interpretation of spirometry results and a new local reference equation has been developed in South Korea. However, lung function profiles according to the different reference equations and their clinical relevance have not been identified in chronic obstructive pulmonary disease (COPD) patients. METHODS: Our cross-sectional study evaluated Choi's, Korean National Health and National Examination Survey (KNHANES)-VI, and GLI-2012 reference equations. We estimated the percentages of predictive forced expiratory volume in one second (FEV1) and airflow limitation severity according to reference equations and analyzed their associations with patient reported outcomes (PROs): COPD assessment test (CAT) score, St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) score, and six minute walk distance (6MWD). RESULTS: In the eligible 2,180 COPD patients, lower predicted values of FEV1 and forced vital capacity (FVC) were found in GLI-2012 compared to Choi's and KNHANES-VI equations. GLI-2012 equation resulted in a lower proportion of patients being classified as FEV1 < 80% or FVC < 80% compared to the other equations. However, the Z-scores of FEV1 and FVC were similar between the KNHANES-VI and GLI-2012 equations. Three reference equations exhibited significant associations between FEV1 (%) and patient-reported outcomes (CAT score, SGRQ-C score, and 6MWD). CONCLUSION: GLI-2012 reference equation may not accurately reflect FEV1 (%) in the Korean population, but the Z-score using GLI-2012 equation can be a viable option for assessing FEV1 and airflow limitation in COPD patients. Similar to the other two equations, the GLI-2012 equation demonstrated significant associations with PROs.

Association between timed up-and-go test and subsequent pneumonia: A cohort study.

BACKGROUND: Sarcopenia 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 METHODS: From 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. RESULTS: The 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]). CONCLUSION: The 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.

Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study.

BACKGROUND: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. METHODS: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.

Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study.

BACKGROUND: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC). METHODS: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m2 or dose level 2, 80 mg/m2) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis. RESULTS: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival. CONCLUSIONS: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy.