Four versus six cycles of platinum-based chemotherapy for advanced Urothelial carcinoma in the era of immune checkpoint inhibitors: A retrospective cohort study (FOCUS, KCSG-GU23-08).

INTRODUCTION: This study aimed to assess the survival outcomes of four versus six cycles of first-line platinum-based chemotherapy (PBCT) in the era of immune checkpoint inhibitor (ICI) for patients with advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Patients with histologically confirmed advanced UC were allocated to either the 4-cycle PBCT (C4) or 6-cycle PBCT (C6) groups and retrospectively analyzed. After the planned cycles, active surveillance was conducted every 6-8 weeks, followed by second-line treatments, including ICIs, upon progression. The primary endpoint was overall survival (OS). RESULTS: Of the 161 patients initiated with PBCT between September 2016 and February 2023, 27 were deemed ineligible, leaving 134 patients for analysis (C4, n = 58; C6, n = 77). Baseline characteristics, including cisplatin eligibility, were similar between the groups. With a median follow-up of 23.7 months (95 % confidence interval (CI), 20.3-27.1), no significant difference was observed in OS between the C6 and C4 groups (18.7 months vs. 17.0 months; hazard ratio (HR) 1.27, P = 0.343). In multivariate analysis adjusted for sex, initial presentation, metastatic lesion, and ECOG PS, no significant difference was observed between the C6 and C4 groups (HR 1.29, 95 % CI, 0.78-2.14, P = 0.315). CONCLUSIONS: This study showed that four cycles of PBCT do not differ from six cycles regarding OS.

Epigenetic alterations of TP53INP1 by EHMT2 regulate the cell cycle in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a type of cancer with high incidence and mortality rates. Although various chemical interventions are being developed to treat gastric cancer, there is a constant demand for research into new GC treatment targets and modes of action (MOAs) because of the low effectiveness and side effects of current treatments. METHODS: Using the TCGA data portal, we identified EHMT2 overexpression in GC samples. Using RNA-seq and EHMT2-specific siRNA, we investigated the role of EHMT2 in GC cell proliferation and validated its function with two EHMT2-specific inhibitors. Through the application of 3D spheroid culture, patient-derived gastric cancer organoids (PDOs), and an in vivo model, we confirmed the role of EHMT2 in GC cell proliferation. RESULTS: In this study, we found that EHMT2, a histone 3 lysine 9 (H3K9) methyltransferase, is significantly overexpressed in GC patients compared with healthy individuals. Knockdown of EHMT2 with siRNA induced G1 cell cycle arrest and attenuated GC cell proliferation. Furthermore, we confirmed that TP53INP1 induction by EHMT2 knockdown induced cell cycle arrest and inhibited GC cell proliferation. Moreover, specific EHMT2 inhibitors, BIX01294 and UNC0638, induced cell cycle arrest in GC cell lines through TP53INP1 upregulation. The efficacy of EHMT2 inhibition was further confirmed in a 3D spheroid culture system, PDOs, and a xenograft model. CONCLUSIONS: Our findings suggest that EHMT2 is an attractive therapeutic target for GC treatment.

Longitudinal Changes in Maximal Forced Inspiratory Flow and Clinical Outcomes in Patients With COPD.

BACKGROUND: COPD primarily impairs expiratory flow due to progressive airflow obstruction and reduced lung elasticity. Increasing evidence underlines the importance of inspiratory flow as a biomarker for selecting inhaler devices and providing ancillary aerodynamic information. RESEARCH QUESTION: Does the longitudinal changes in maximum forced inspiratory flow (FIFmax) influence acute exacerbations and lung function decline in patients with COPD? STUDY DESIGN AND METHODS: This longitudinal study evaluated FIFmax in patients with COPD over a 7-year period from 2004 to 2020. Eligible patients were categorized into 2 groups based on FIFmax trajectory: the increased FIFmax group and the decreased FIFmax group. The study assessed the annual rate of acute exacerbations and the annual decline rate of FEV1. Subgroup analyses were conducted based on treatment status, with a focus on inhaled therapy and inhaler device usage. RESULTS: Among the eligible 956 patients with COPD, 56.5% belonged to the increased FIFmax group. After propensity score matching, the increased FIFmax group experienced lower rates of severe exacerbations (0.16 per year vs 0.25 per year, P = .017) and a slower decline in FEV1 (0 [interquartile range, -51 to 71] mL/y vs -43 [interquartile range, -119 to 6] mL/y; P < .001) compared with the decreased FIFmax group. These associations were particularly prominent in patients using specific inhaler therapies such as dry powder inhalers. INTERPRETATION: This study showed that the longitudinal changes in FIFmax are associated with clinical outcomes in patients with COPD. Patients with increased FIFmax experienced a lower rate of severe exacerbations and a slower decline in lung function. These findings suggest the potential benefits of optimizing inspiratory flow in COPD management, although further studies are needed to confirm these observations due to potential confounding factors.

Preventive effect of Lacticaseibacillus paracasei LMT18-32 on Porphyromonas gingivalis induced periodontitis.

Periodontitis is a severe gum infection leading to chronic inflammation in the gums, damage of tissues around teeth, and destruction of alveolar bones. Porphyromonas gingivalis is the major causative pathogen that induces periodontitis. Numerous probiotic bacteria are reported to produce antibacterial substances against pathogens especially oral pathogens, and these are proposed as preventive measures for periodontitis. In this study, Lacticaseibacillus paracasei LMT18-32 was evaluated and its antibacterial activity against P. gingivalis, and antioxidant activity in vitro were established. In addition, when L. paracasei LMT18-32 was administered to periodontitis induced mice, it successfully alleviated the alveolar bone loss and suppressed induced expression of proinflammatory and tissue destruction related genes in the gingival tissue. In conclusion, L. paracasei LMT18-32 is proposed as a potential probiotics to prevent periodontitis.

The Destiny of the Subscapularis Tendon after Arthroscopic Supraspinatus Repair.

Background: The purpose of this study was to identify the changes in untreated subscapularis in patients who underwent supraspinatus repair and to evaluate the factors related to the changes in the subscapularis. Methods: A cohort of patients who underwent isolated supraspinatus repair with preservation of the subscapularis was reviewed. Changes in the subscapularis, including any newly formed lesion and aggravation of an existing lesion, were evaluated 12 months postoperatively on magnetic resonance imaging along with an examination to identify causative factors after supraspinatus repair. Clinical scores were compared between patients with and without subscapularis changes. Results: A total of 528 patients were reviewed. Changes in the subscapularis, including newly formed lesions and aggravation of an existing lesion, were shown in 90 patients (17.0%). Upon regression analysis, changes in the subscapularis were associated with the initial existence of a subscapularis lesion (grade I: p = 0.042, grade II: p = 0.025), an accompanying biceps lesion (p = 0.038), and a retear of the repaired supraspinatus (p = 0.024). No significant differences were shown in clinical scores between patients with and without subscapularis changes after supraspinatus repair. Conclusions: Untreated asymptomatic subscapularis may undergo morphological changes even after repair of the torn supraspinatus. Preoperative subscapularis lesions, biceps long head pathology, and retears of the repaired supraspinatus were associated with subscapularis pathology in patients who underwent supraspinatus repair.

Mucus Plugs as Precursors to Exacerbation and Lung Function Decline in COPD Patients.

BACKGROUND: Mucus plugs identified through chest computed tomography (CT) scans have emerged as potential prognostic factors in chronic obstructive pulmonary disease (COPD). This 5-year longitudinal study investigated their impact on exacerbations and FEV1 decline. METHODS: COPD patients with baseline chest CT and spirometric assessments were categorized based on mucus plug presence. Propensity-score matching yielded balanced groups. Exacerbation rates, time to exacerbation events, hazard ratio (HR) for exacerbations, and annual rates of FEV1 decline were evaluated. Sensitivity analysis was performed with stratification according to mucus plug scores of 0, 1-2, and ≥3. RESULTS: Among 623 eligible patients, the mucus plug group was 44.3%. Through 1:1 propensity-score matching, each group was comprised of 187 individuals with balanced covariates. The mucus plug group showed higher rates of moderate-to-severe (0.51/year vs. 0.58/year, P=0.035), severe exacerbations (0.21/year vs. 0.24/year, P=0.032), and non-eosinophilic exacerbations (0.45/year vs. 0.52/year, P=0.008). Mucus plugs were associated with increased hazard of moderate-to-severe (adjusted HR=1.502 [95% CI 1.116-2.020]), severe (adjusted HR=2.106 [95% CI, 1.429-3.103]), and non-eosinophilic exacerbations (adjusted HR=1.551 [95% CI, 1.132-2.125]). Annual FEV1 decline was accelerated in the mucus plug group (ß-coefficient=-62 [95% CI, -120 to -5], P=0.035). Sensitivity analysis showed higher risk of exacerbations and accelerated FEV1 decline in mucus plug score ≥3 compared to score 0. CONCLUSIONS: Mucus plugs are associated with increased risks of exacerbations, particularly non-eosinophilic, and accelerated FEV1 declines over 5 years. Our study identified the potential prognostic value of mucus plugs on future exacerbation risks and lung function decline trajectories.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Risk factors of acute exacerbation and disease progression in young patients with COPD.

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)<0.7. Eligible patients were followed up with ≥2 spirometry examinations at 1 year interval after COPD diagnosis. The primary outcome was moderate-to-severe acute exacerbation in young patients with COPD. Secondary outcomes were early initiation of regular inhalation therapy and accelerated annual post-bronchodilator FEV1 decline. RESULTS: A total of 342 patients were followed up during a median of 64 months. In multivariable analyses, risk factors for moderate-to-severe exacerbation were history of asthma (adjusted HR (aHR)=2.999, 95% CI=[2.074-4.335]), emphysema (aHR=1.951, 95% CI=[1.331-2.960]), blood eosinophil count >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.

Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition.

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.

Validity assessment of oral health promotion activities targeting the older population for community care in South Korea: A Delphi study.

OBJECTIVE: The purpose of this study was to establish an oral health activity assessment tool for older people and evaluate its validity. BACKGROUND: To provide reasonable and efficient oral health promotion services with limited medical resources, a tool including categories and items of oral health promotion activities for older people should be prepared. MATERIALS AND METHODS: The tool initially consisted of 76 items on oral health promotion activities for older people classified into assessment-performance-evaluation stages. Topics for each stage included general and oral health, daily health, oral health status, behaviour, and awareness. In addition, two Delphi surveys were conducted on 10 experts who met the selection criteria, and the final items were derived based on the review opinions. RESULTS: As a result of the first and second Delphi surveys, the content validity for all items was ≥0.60 and the content validity index was ≥0.80. In the first survey, the degree of convergence in some items was 0-0.88. After modifying the contents according to expert opinions, the degree of convergence was improved from 0 to 0.50 in the second survey. The degree of agreement ranged from 0.75 to 1.00, indicating that experts agreed. Finally, a total of 65 items were derived. CONCLUSION: A 65-item tool was derived through two Delphi surveys for the assessment of oral health activities for older people. The use of the tool developed in this study would likely contribute to better prevention of oral diseases and the promotion of oral health among older people.

Cluster analysis of thoracic muscle mass using artificial intelligence in severe pneumonia.

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.

Very early vs delayed invasive strategy in high-risk NSTEMI patients without hemodynamic instability: Insight from the KAMIR-NIH.

BACKGROUND: High-risk non-ST-elevation myocardial infarction (NSTEMI) patients' optimal timing for percutaneous coronary intervention (PCI) is debated despite the recommendation for early invasive revascularization. This study aimed to compare outcomes of NSTEMI patients without hemodynamic instability undergoing very early invasive strategy (VEIS, ≤ 12 hours) versus delayed invasive strategy (DIS, >12 hours). METHODS: Excluding urgent indications for PCI including initial systolic blood pressure under 90 mmHg, ventricular arrhythmia, or Killip class IV, 4,733 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Patients were divided into low and high- global registry of acute coronary events risk score risk score (GRS) groups based on 140. Both groups were then categorized into VEIS and DIS. Clinical outcomes, including all-cause death (ACD), cardiac death (CD), recurrent MI, and cerebrovascular accident at 12 months, were evaluated. RESULTS: Among 4,733 NSTEMI patients, 62% had low GRS, and 38% had high GRS. The proportions of VEIS and DIS were 43% vs. 57% in the low GRS group and 47% vs. 53% in the high GRS group. In the low GRS group, VEIS and DIS demonstrated similar outcomes; however, in the high GRS group, VEIS exhibited worse ACD outcomes compared to DIS (HR = 1.46, P = 0.003). The adverse effect of VEIS was consistent with propensity score matched analysis (HR = 1.34, P = 0.042). CONCLUSION: VEIS yielded worse outcomes than DIS in high-risk NSTEMI patients without hemodynamic instability in real-world practice.

Sleep Characteristics of an International Sample of Adult Gamers.

Introduction About 65% of adult Americans report playing video games. Despite potential impacts to functioning, there is limited research on the relationship between video game use and sleep, specifically among adults. The present study expands upon the literature by describing demographic, video game, and sleep characteristics of an international adult sample of gamers. Methods The participants were 3,481 adults aged 18 to 74 who responded to an online questionnaire about video game use (i.e., quantity of play, most common game type), general sleep characteristics (i.e., sleep onset latency [SOL]; duration, sleep timing, and sleep quality), and gaming-specific sleep disruptors (i.e., game-related night awakenings and sleep delays). Most identified as cisgender male (79.8%) and white (77%). Results Participants reported an average SOL of 24.63 minutes, and most (64.5%) had a sleep duration from 7 to 9 hours with an overall average of 8.42 hours. Most (58.7%) reported that their sleep quality was fair to very poor . Bed and wake times were generally delayed, with 51% reporting a late evening or early morning bedtime and an average wake time of 8:28 am. A majority (81.2%) indicated that their bedtime was delayed due to game-related activities, but game-related night awakenings were less common. Conclusion Although many report a sufficient amount of sleep, adult gamers tend to report sleep disruptions in other domains, particularly regarding a delayed sleep schedule and poor sleep quality. This may be attributable to game-related bedtime delays or other game-specific factors (e.g., game type) that should be evaluated in the future.

Falsiroseomonas oryziterrae sp. nov., and Falsiroseomonas oryzae sp. nov., isolated from rice paddy soil.

Three Gram-stain-negative, aerobic, non-motile and coccobacilli-shaped bacterial strains, designated as NPKOSM-4T, NPKOSM-8 and MO-31T, were isolated from rice paddy soil. They had 96.5-100 % 16S rRNA gene sequence similarity to each other, and strains NPKOSM-4T and NPKOSM-8 showed 100 % 16S rRNA gene sequence similarity, confirming that they were the same species. Comparative analysis of 16S rRNA genes with closely related type strains showed that three isolates were most closely related to Falsiroseomonas terricola EM0302T (96.1-97.8 %), Falsiroseomonas wooponensis WW53T (95.51-96.3 %) and Falsiroseomonas bella CQN31T (96.0-96.5 %), respectively. The genomes of strains NPKOSM-4T and MO-31T consisted of 4 632 875 and 6 455 771 bps, respectively, with 72.0 and 72.1 mol% G+C content. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strains NPKOSM-4T and MO-31T and type strains of Falsiroseomonas species were lower than the cut-offs (≥95 % for ANI, ≥95-96 % for AAI and ≥ 70 % for dDDH) required to define a bacterial species. The major fatty acids of strains NPKOSM-4T, NPKOSM-8 and MO-31T were C18 : 1 ω7c and C18 : 1 2-OH (<10 %) and the predominant quinone was Q-10. The polar lipids of strain NPKOSM-4T were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, one unidentified aminophospholipid and three unidentified aminolipids. The polar lipid profiles of strain MO-31T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, one unidentified aminolipid and three unidentified lipids. Based on their distinctive phenotypic, phylogenetic, and chemotaxonomic characteristics, strains NPKOSM-4T, NPKOSM-8 and MO-31T are considered to represent two novel species of the genus Falsiroseomonas, for which the names Falsiroseomonas oryziterrae sp. nov. [to accommodate strains NPKOSM-4T (= KACC 22135T=JCM 34745T), NPKOSM-8 (=KACC 22134=JCM 34746)] and Falsiroseomonas oryzae sp. nov. [to accommodate strain MO-31T (= KACC 22465T=JCM 35532T)] are proposed.

Phase II study of nivolumab in patients with genetic alterations in DNA damage repair and response who progressed after standard treatment for metastatic solid cancers (KM-06).

BACKGROUND: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies. METHODS: The KM-06 open-label, multicenter, single-arm, phase II trial evaluated the safety and efficacy of nivolumab in refractory solid cancers with DDR gene mutations assessed by clinically targeted sequencing. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or for 24 months. The primary endpoint was the objective response rate (ORR) as per RECIST V.1.1 criteria. RESULTS: A total of 48 patients were enrolled in the study (median age 61, 58.3% male). The most common cancer type was colorectal cancer (41.7%), followed by prostate and biliary tract cancer (8.3% each). Eight patients achieved a partial response as their best overall response, resulting in an ORR of 17.8%. The disease control rate was 60.0%. The median progression-free survival was 2.9 months. Treatment-related adverse events of any grade and grade ≥3 occurred in 44 (91.7%) and 4 (8.3%) patients, respectively. Clinically targeted sequencing data inferred both TMB and microsatellite instability (MSI). Using a TMB cut-off of 12 mut/Mb, there were significant differences in overall survival (p=0.00035), progression-free survival (p=0.0061), and the best overall response (p=0.05). In the RNA sequencing analysis, nivolumab responders showed activation of the interleukin signaling pathway. Patients who experienced early progression presented high epithelial-mesenchymal transition signaling pathway activation. The responders exhibited a marked increase in PD-1-/Ki67+CD8 T cells at the early stage of treatment (C3D1) compared with non-responders (p=0.03). CONCLUSIONS: In this phase II trial, nivolumab demonstrated moderate efficacy and manageable toxicity in patients with solid cancer harboring DDR gene mutations. A high TMB (>12 mut/Mb) and MSI score (>2.5) determined through clinically target sequencing presented significant discriminatory power for the nivolumab response. TRIAL REGISTRATION NUMBER: NCT04761744.

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.

Erythrobacter oryzae sp. nov., isolated from rice paddy soil.

Two novel bacterial strains, designated as COR-2T and CR-8, were isolated from paddy soil. These isolates were aerobic, Gram-stain-negative, non-spore-forming, non-motile, rod-shaped, and formed orange-coloured colonies. Phylogenetic analysis based on 16S rRNA gene sequences showed that two strains formed a clear phylogenetic lineage with the genus Erythrobacter. Strains COR-2T and CR-8 showed 99.9 % 16S rRNA gene sequence similarity. Both strains had the highest 16S rRNA gene similarity of 99.1-99.7 % to Erythrobacter colymbi TPW-24T, Erythrobacter donghaensis SW-132T and Erythrobacter tepidarius DSM 10594T, respectively. The genome of strain COR-2T comprised 3 559 918 bp and the genomic DNA G + C content was 67.7 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain COR-2T and its closely related species of the genus Erythrobacter were 79.3-85.5% and 24.1-29.1 %, respectively. The major respiratory quinone was Q-10, while the major fatty acids were C18 : 1 ω7c and C17 : 1 ω6c. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified phospholipids and eight unidentified lipids. Based on phylogenetic and phenotypic considerations, the two strains [COR-2T (type strain; = KACC 22941T=JCM 35529T) and CR-8 (= KACC 22945=JCM 35530)] are considered to represent novel species of the genus Erythrobacter, for which the name Erythrobacter oryzae sp. nov. is proposed.

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.

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.