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This study aimed to determine the association between TMB and treatment outcomes in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer that were treated with tyrosine kinase inhibitors (TKIs). The TMB was assessed using a 409-gene targeted next-generation sequencing panel. We compared the response rate (RR), progression-free survival (PFS), overall survival (OS), and frequency of secondary T790M mutations among the different TMB groups. The median TMB of the study population (n = 88) was 3.36/megabases. We divided 52 (59%) and 36 (41%) patients into the low and high TMB groups, respectively. A high TMB level was significantly associated with liver metastasis and more advanced stage (all p < 0.05). RR was significantly lower in the high TMB group than that of the low TMB group (50.0% vs. 80.7%, all p = 0.0384). In multivariate analysis, high TMB was independently associated with a shorter PFS (hazard ratio [HR] = 1.80, p = 0.0427) and shorter OS (HR = 2.05, p = 0.0397) than that of the low TMB group. Further, high TMB was independently associated with decreased T790M mutation development. These results suggest that high TMB may be a predictive biomarker for adverse treatment outcomes and represent a patients’ subgroup warranting tailored therapeutic approaches.

In this paper, we present a highly optimized implementation of elliptic curve cryptography (ECC) over NIST P-256 curve for an 8-bit AVR microcontroller. For improving the performance of ECC implementation, we focus on optimizing field arithmetics. In particular, we optimize the modular multiplication and squaring method exploiting the state-of-the-art optimization technique, namely range shifted representation (RSR). With optimized field arithmetics, we significantly improve the performance of scalar multiplication and set the speed record for execution time of variable base scalar multiplication over NIST P-256 curve. When compared with previous works, we achieve a performance gain of 17.3% over the best previous result on the same platform. Moreover, the execution time of our result is even faster than that over the NIST P-192 curve of the well-known TinyECC library. Our result shows that RSR can be applied to all field arithmetics and evaluate the impact of the adoption of RSR over the performance of scalar multiplication. Additionally, our implementation provides a high degree of regularity to withstand side-channel attacks.

Abstract The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil–lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI

BackgroundThe interaction between COVID-19 and tuberculosis (TB) is not yet fully understood, and large-scale research on the mortality outcome of such dual infection has been limited. This study aimed to investigate the impact of PTB on mortality among patients with COVID-19 within a Korean population by conducting an extensive analysis of a nationwide large dataset.MethodWe investigated the mortality and disease severity among COVID-19 patients who had PTB in South Korea. This study analyzed 462,444 out of 566,494 COVID-19 patients identified between January 2020 and December 2021.ResultA total of 203 COVID-19 with PTB patients and 812 matched COVID-19 without PTB were analyzed using 1:4 propensity score matching. COVID-19 patients with PTB exhibited higher in-hospital mortality (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.45–6.27, p-value = 0.003) and were at increased risk of requiring conventional oxygen therapy (OR 1.57, 95% CI 1.10–2.25, p-value = 0.013) as well as high flow nasal cannula (HFNC) or noninvasive ventilation (NIV) oxygen therapy (OR 1.91, 95 CI 1.10–3.32, p-value = 0.022) compared to those without PTB. Compared to matched COVID-19 without PTB, co-infected patients showed increased mortality rates across various timeframes, including during hospitalization, and at 30 day and 90 day intervals. In-hospital mortality rates were particularly elevated among women, individuals with malignancy, and those with lower incomes. Furthermore, the increased in-hospital mortality among PTB patients persisted irrespective of the timing of TB diagnosis or vaccination status against COVID-19.ConclusionWe suggest that physicians be aware of the risk of mortality and severity among COVID-19 patients with PTB; coinfection with COVID-19 is a critical situation that remains to be further explored and needs more attention in countries with an intermediate to high PTB burden.

Abstract Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5–13.2], P = 7.2 × 10−6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5–1423], P = 7.5 × 10−6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis.

Introduction Studies that comprehensively evaluate the association between physical activity (PA) levels, particularly by quantifying PA intensity, and healthcare use requiring emergency department (ED) visit or hospitalisation in patients with chronic obstructive pulmonary disease (COPD) are limited in Korea.Methods The risk of all-cause and respiratory ED visit or hospitalisation according to the presence or absence of COPD and the level of PA was evaluated in a retrospective nationwide cohort comprising 3308 subjects with COPD (COPD cohort) and 293 358 subjects without COPD (non-COPD cohort) from 2009 to 2017.Results The COPD group exhibited a higher relative risk of all-cause and respiratory ED visit or hospitalisation across all levels of PA compared with the highly active control group (≥1500 metabolic equivalents (METs)-min/week). Specifically, the highest risk was observed in the sedentary group (adjusted HR (aHR) (95% CI) = 1.70 (1.59 to 1.81) for all-cause ED visit or hospitalisation, 5.45 (4.86 to 6.12) for respiratory ED visit or hospitalisation). A 500 MET-min/week increase in PA was associated with reductions in all-cause and respiratory ED visit or hospitalisation in the COPD cohort (aHR (95% CI) = 0.92 (0.88 to 0.96) for all-cause, 0.87 (0.82 to 0.93) for respiratory cause).Conclusions Compared with the presumed healthiest cohort, the control group with PA>1500 METs-min/week, the COPD group with reduced PA has a higher risk of ED visit or hospitalisation.

BackgroundThe impact of long-term chronic periodontal conditions on the risk of lung cancer could not be accurately evaluated. Our aim was to provide more evidence on the connection between chronic periodontitis (CP) and lung cancer using a nationwide dataset.MethodsThis study used data from the Korean National Health Insurance Service National Sample Cohort. We enrolled 72,658 individuals with CP (CP cohort) between 2005 and 2019 and 1:1 age- and sex-matched controls without CP (non-CP cohort).ResultsDuring the median follow-up period of 5.1 (interquartile range, 2.8–8.0) years, 0.56% (n = 405/72,658) of the CP cohort and 0.29% (n = 212/72,658) of the matched non-CP cohort developed lung cancer, with incidence rates of 8.3 and 4.5 per 10,000 person-years. The risk of incident lung cancer was significantly higher in the CP cohort than in the matched non-CP cohort (adjusted hazard ratio = 2.27, 95% confidence interval = 1.94–2.65). The risk of incident lung cancer was 2.45-fold and 2.10-fold higher in mild and moderate-to-severe CP cohorts than in the matched non-CP control. The risk of incident lung cancer was especially higher in the 40–59 age group, females, and never-smokers than their counterparts.ConclusionWe demonstrate that the risk of incident lung cancer is higher in individuals with CP than in those without. The risk of lung cancer was especially high in individuals with more severe CP, females, never-smokers, and obese populations.

ObjectivesPrevious studies suggested that coronavirus disease 2019 (COVID-19) could lead to pulmonary fibrosis, but the incidence of newly diagnosed interstitial lung disease (ILD) after COVID-19 is unclear. We aimed to determine whether COVID-19 increases the risk of newly diagnosed ILD and whether vaccination against COVID-19 can reduce this risk.MethodsThis retrospective cohort study used data from the Korean National Health Insurance claim-based database. Two study groups and propensity score (PS)-matched control groups were constructed: Study 1: participants diagnosed with COVID-19 (COVID-19 cohort) and their PS-matched controls; Study 2: COVID-19 vaccinated participants (vaccination cohort) and their PS-matched controls.ResultsIn Study 1, during a median 6 months of follow-up, 0.50% of the COVID-19 cohort (300/60,518) and 0.04% of controls (27/60,518) developed newly diagnosed ILD, with an incidence of 9.76 and 0.88 per 1,000 person-years, respectively. The COVID-19 cohort had a higher risk of ILD [adjusted hazard ratio (aHR), 11.01; 95% confidence interval (CI), 7.42–16.32] than controls. In Study 2, the vaccination cohort had a lower risk of newly diagnosed ILD than controls (aHR, 0.44; 95% CI, 0.34–0.57).ConclusionUsing nationwide data, we demonstrated that COVID-19 was associated with a higher incidence rate of newly diagnosed ILD, but that this risk could be mitigated by COVID-19 vaccination.

Abstract Asthmatic patients are generally considered to have an increased risk of mortality compared with subjects without asthma. However, this issue has been less evaluated using nationally representative data. Moreover, it is unclear whether respiratory comorbidities other than chronic obstructive pulmonary disease (COPD) are associated with increased mortality in asthmatic patients compared with subjects without. Using a nationally representative sample database, we performed a retrospective cohort study of patients with asthma and age-sex-matched control cohort. We estimated the hazard ratio (HR) and stratified the asthma cohort based on respiratory comorbidities. During a median 8.9-year follow-up, the overall mortality rate was higher in the asthma cohort than in the control cohort (p

Abstract The aim of this study is to examine the impact of tumor necrosis factor inhibitors (TNFI) on nontuberculous mycobacterium (NTM) infection in rheumatoid arthritis (RA) patients in a mycobacterium tuberculosis (MTB) endemic area. We selected 1089 TNFI-treated RA patients and 4356 untreated RA patients using propensity-matching analysis according to age, gender, and Charlson comorbidity index using the Korean National Health Insurance Service database from July 2009 to December 2010. Both groups were followed-up until the end of 2016 to measure the incidence of mycobacterial diseases. The incidence rate of NTM in TNFI-treated RA group was similar to those of MTB (328.1 and 340.9 per 100,000 person-years, respectively). The adjusted hazard ratio (aHR) of NTM for TNFI-treated RA compared to untreated RA was 1.751(95% CI 1.105–2.774). The risk of TNFI-associated NTM in RA was 2.108-fold higher among women than men. The age-stratified effects of TNFI on NTM development were significantly high in RA patients aged 50–65 years (aHR 2.018). RA patients without comorbidities had a higher incidence of NTM following TNFI treatment (aHR 1.742). This real-world, observational study highlights the need to increase awareness of NTM in TNFI-treated RA patients in an MTB endemic area.

Background/Aims Adjuvant chemotherapy is the standard of care for resected stage II–IIIA non-small cell lung cancer (NCSLC). The efficacy of adjuvant chemotherapy in stage IB (< 4 cm) NSCLC with high-risk factors is controversial. Methods This retrospective multicenter study included 285 stage IB NSCLC patients with high-risk factors according to the 8th edition tumor, node, metastasis (TNM) classification from four academic hospitals. High-risk factors included visceral pleural invasion, vascular invasion, lymphatic invasion, lung neuroendocrine tumors, and micropapillary histology patterns. Results Of the 285 patients, 127 (44.6%) were included in the adjuvant chemotherapy group and 158 (55.4%) were included in the non-adjuvant chemotherapy group. The median follow-up was 41.5 months. Patients in the adjuvant chemotherapy group had a significantly reduced recurrence rate and risk of mortality than those in the non-adjuvant chemotherapy group (hazards ratio, 0.408; 95% confidence interval, 0.221 to 0.754; p = 0.004 and hazards ratio, 0.176; 95% confidence interval, 0.057 to 0.546; p = 0.003, respectively). Adjuvant chemotherapy should be particularly considered for the high-risk factors such as visceral pleural involvement or vascular invasion. Based on the subgroup analysis, adjuvant chemotherapy should be considered when visceral pleural involvement is present, even if the tumor size is < 3 cm. Conclusions Adjuvant chemotherapy may be useful for patients with stage IB NSCLC with high-risk factors and is more relevant for patients with visceral pleural involvement or vascular invasion.

Background: Despite the importance of influenza vaccination, its rates in subjects with asthma are suboptimal, especially in the young population. Methods: Among 72,843 adults aged ⩾18 years from the Korea National Health and Nutrition Examination Survey conducted between 2010 and 2019, 1643 with asthma were included. The yearly trends and factors associated with influenza vaccination were analyzed in subjects with asthma. In addition, stratified analyses were performed by age group (

Abstract There are limited data regarding whether mortality is higher in patients with non cystic fibrosis bronchiectasis (bronchiectasis) than in those without bronchiectasis. Using 2005–2015 data from the Korean National Health Insurance Service, we evaluated hazard ratio (HR) for all-cause mortality in the bronchiectasis cohort relative to the matched cohort. The effect of comorbidities over the study period on the relative mortality was also assessed. All-cause mortality was significantly higher in the bronchiectasis cohort than in the matched cohort (2505/100,000 vs 2142/100,000 person-years, respectively; P

IntroductionAlthough respiratory infections are common causes of acute respiratory failure (ARF) in patients with myositis-interstitial lung disease (ILD), limited data are available regarding the treatment outcomes by the etiologies of acute exacerbation (AE) of myositis-related ILD (infectious vs. non-infectious). Our study aimed to investigate the treatment outcomes of AE in patients with myositis-related ILD focused on the infectious etiology.MethodsA single center-based retrospective cohort was performed at Hanyang University Hospital between January 2000 and December 2018. A total of 36 patients with AE of myositis-related ILD were consecutively included. The exposure was the etiologies of AE in myositis-related ILD, and the outcome was in-hospital mortality. The infectious etiology was defined as confirmation of bacteria, virus, or fungus in samples obtained from the respiratory tract.ResultsAmong the 36 patients, 17 were diagnosed with infectious AE. The overall in-hospital mortality rate of AE was 47.2%. Although the mortality rate in patients with infectious AE was lower (41.2%) than in those with non-infectious AE (52.6%), this difference was not statistically significant (p = 0.724). A survival analysis showed no significant difference in mortality between patients with infectious AE versus those with non-infectious AE [risk ratio = 0.78, 95% CI = 0.38–1.59].ConclusionOur study showed that infectious AE is an important cause of mortality in patients with myositis-related ILD, showing a similar risk of mortality as non-infectious AE.

Response to vaccines generally varies according to individual factors of the vaccinated subjects such as demographics and immune status. While there are various reports of factors associated with immunogenicity of mRNA COVID-19 vaccines, little is known about those of adenovirus vector vaccines. We conducted a prospective observational study to assess the relationships of antibody level with age, sex, body mass index (BMI), and adverse reactions (ARs) to an adenovirus vector vaccine, ChAdOx1 nCoV-19. Healthcare workers who planned to receive both the first and second injections of the ChAdOx1 nCoV-19 vaccine at Hanyang University Hospital, Seoul, Korea, were enrolled in the study. Seven days after each injection, participants were asked to complete an online adverse reaction survey. In addition, anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody concentration was measured 4 weeks after the second injection. All participants (n = 447, 100%) showed serologic positivity (≥ 0.8 U/mL) 4 weeks after the second injection of ChAdOx1 nCoV-19 vaccine. Furthermore, the anti-SARS-CoV-2 S protein RBD concentration was similar among groups when stratified by age, sex, BMI, or presence and severity of AR; multivariable linear regression found no associations between antibody response to the ChAdOx1 nCoV-19 vaccine and age, BMI, sex, and vaccine-induced ARs. In conclusion, age, sex, obesity, and ARs were not associated with antibody responses after two doses of ChAdOx1 nCoV-19 vaccination.

Background: Long-term corticosteroid (CS) use is associated with increased mortality in patients with asthma, and comorbid bronchiectasis is also associated with frequent asthma exacerbation and increased healthcare use. However, there is limited information on whether bronchiectasis further increases mortality in patients with CS-dependent asthma. This study examined the impact of bronchiectasis on mortality in patients with CS-dependent asthma. Methods: A retrospective cohort of patients with CS-dependent asthma ⩾18 years old was established using records from the Korean National Health Insurance Service database from 2005 to 2015. Patients with CS-dependent asthma with and without bronchiectasis were matched by age, sex, type of insurance, and Charlson comorbidity index. We evaluated the hazard ratio (HR) for all-cause mortality in patients with bronchiectasis compared with those without bronchiectasis. Results: The study cohort included 754 patients with CS-dependent asthma with bronchiectasis and 3016 patients with CS-dependent asthma without bronchiectasis. Patients with CS-dependent asthma with bronchiectasis had a higher all-cause mortality than those without bronchiectasis (8429/100,000 versus 6962/100,000 person-years, p

Background: Chronic lung diseases, such as chronic obstructive pulmonary disease or asthma, are associated with an increased risk of dementia. However, few data are available regarding the risk of dementia in individuals with bronchiectasis. Objectives: To explore the association between bronchiectasis and the risk of incident dementia using a longitudinal population-based cohort. Methods: A total of 4,068,560 adults older than 50 years without previous dementia were enrolled from the Korean National Health Insurance Service database in 2009. They were followed up until the date of the diagnosis of dementia or December 31, 2020. The study exposure was the diagnosis of bronchiectasis, and the primary outcome was incident dementia comprising Alzheimer's disease and vascular dementia. Results: During the median follow-up duration of 9.3 years, the incidence of all-cause dementia was 1.6-fold higher in individuals with bronchiectasis than in those without bronchiectasis (15.0 vs. 9.3/1000 person-years, p < .001). In the multivariable Cox regression analysis, the risk of all dementia was significantly higher in individuals with bronchiectasis than in those without bronchiectasis (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 1.04-1.14). In a subgroup analysis by dementia type, individuals with bronchiectasis had an increased risk of Alzheimer's disease compared to those without bronchiectasis (aHR 1.07, 95% CI 1.01-1.12); the risk of vascular dementia did not significantly differ between the two groups (aHR 1.05, 95% CI 0.90-1.21). Conclusion: Bronchiectasis was associated with an increased risk of dementia, especially Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Pnuemocystis jirovecii pneumonia (PJP) is one of leading causes of acute respiratory failure in patients infected with human immunodeficiency virus (HIV), and the mortality rate remains high in mechanically ventilated HIV patients with PJP. There are several reported cases who received extracorporeal membrane oxygenation (ECMO) treatment for respiratory failure associated with severe PJP in HIV-infected patients. We report a patient who was newly diagnosed with HIV and PJP whose condition worsened after highly active antiretroviral therapy (HAART) initiation and progressed to acute respiratory distress syndrome requiring veno-venous ECMO. The patient recovered from PJP and is undergoing treatment with HAART. ECMO support can be an effective life-saving salvage therapy for acute respiratory failure refractory to mechanical ventilation following HAART in HIV-infected patients with severe PJP.