Impact of the coronavirus disease 2019 pandemic on the incidence of other infectious diseases in the hematology hospital in Korea.

BACKGROUND/AIMS: Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. METHODS: This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. RESULTS: The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). CONCLUSION: The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.

Associations of active and passive tobacco exposure with elevated blood pressure in Korean adolescents.

OBJECTIVES: To test the hypothesis that tobacco exposure is associated with elevated blood pressure (EBP) in Korean adolescents, and that the association is dose dependent. METHODS: This cross-sectional study used data from the 2011-2020 Korea National Health and Nutrition Survey (KNHANES). Subjects were eligible if they were 13-18 years at the time of participation in KNHANES. Tobacco exposure was defined by urine cotinine level. The main outcomes were EBP and hypertension. Statistical analyses were conducted using SAS version 9.4 with appropriate sampling weights to account for the complex survey design, stratification, and cluster variable. RESULTS: A total of 2,518 adolescents was included in the analysis, representing 2.5 million Korean adolescents. The mean± standard deviation participant age was 15.3±1.7 years, and 55.3% were male. The number of participants with active tobacco smoke exposure was 283 (11.2%), passive tobacco smoke exposure was 145 (5.8%), and no smoke exposure was 2,090 (83.0%). Analysis of the 2,518 urine-cotinine-verified participants showed that tobacco smoke exposure had a significant effect on EBP: with an odds of elevated blood pressure of 3.00 (95% confidence interval [CI], 1.14 to 7.89). The odds of hypertension were 3.61 (95% CI, 1.13 to 11.49) in the active smoking group compared with the no tobacco exposure group after adjustment for potential confounders. CONCLUSIONS: It is necessary to present a range of public health plans to reduce tobacco exposure that affects adolescents' blood pressure, and further research with a larger number of participants using urine cotinine as a biomarker is needed.

Gastric Cancer Incidence and Mortality After Endoscopic Resection of Gastric Adenoma: A Nationwide Cohort Study.

INTRODUCTION: Gastric adenoma is a precursor lesion of gastric cancer. We investigated whether the removal of gastric adenoma prevented gastric cancer incidence and its mortality. METHODS: Using the linkage of nationwide databases, we assessed gastric cancer incidence and mortality among patients who had gastric adenomas removed between 2011 and 2013 in Korea. These outcomes were compared primarily with those of the Korean general population by estimating the standardized incidence and mortality ratio and secondarily with internal control subjects who did not have gastric neoplasm after esophagogastroduodenoscopy and were matched for age, sex, and calendar year by calculating hazard ratios (HR) with the Cox proportional hazards model. RESULTS: We identified 44,405 adenoma removal patients. During a median follow-up of 8.4 years, 1,038 (2.34%) of them were given a diagnosis of gastric cancer and a total of 524 gastric cancers were expected for a standard incidence ratio of 1.98 (95% confidence interval [CI], 1.84-2.13). A total of 199 deaths from gastric cancer were expected and 99 were observed for a standard mortality ratio of 0.50 (95% CI, 0.40-0.60). Compared with the nonadenoma cohort (n = 39,826), the adenoma removal patients had a higher risk of gastric cancer (HR, 2.84; 95% CI, 2.51-3.21) and associated mortality (HR, 1.66; 95% CI, 1.19-2.31). DISCUSSION: Removal of gastric adenoma resulted in lower-than-expected mortality but higher-than-expected incidence due to gastric cancer than that in the general population. Our analyses indicated the importance of follow-up strategy after removal of gastric adenoma.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

The Eyelid Angiosarcoma: A Systematic Review of Characteristics and Clinical Course.

A systematic search for eyelid angiosarcoma was performed from inception to December 2020 in Medline, EMBASE, and the Cochrane databases. Forty two eyelid angiosarcoma cases in 32 articles were analyzed. Eyelid angiosarcomas showed an incidence peak in the eighth decade of life, and was reported more frequently in Caucasian males. Eyelid angiosarcomas were associated with a mortality rate of 26.2%, a recurrence rate of 14.3%, and a cure rate of 45.2%. Four years event-free survival (EFS) rate was 36.0%, with median EFS of 36 months. Eyelid angiosarcomas with bilateral involvement or metastasis showed higher mortality and recurrence rates than unilateral eyelid invasion cases. In the prognosis analysis according to treatment modalities, the mortality and recurrence rates were the lowest in patients who underwent surgical excision. The 4-year EFS probability in a group with surgical excision was 60.6%, but in a group without surgical excision it was 30.3%. A total of 45.2% of the cases was misdiagnosed and 21.4% of the cases could not be correctly diagnosed with the first biopsy trial. The prognosis for eyelid angiosarcomas was better than that of angiosarcomas invading the face and scalp. Surgical excision was the most important treatment modality; thus, should be considered as the first treatment of choice.

Characteristics and clinical outcome of high-risk multiple myeloma patients in Korea (KMM 1805).

Optimal treatments for multiple myeloma (MM) patients with high-risk cytogenetics must be determined, but subgroup features are not well-defined. We used real-world data from the Korean Myeloma Registry (KMR) to analyze the characteristics and clinical outcomes of newly diagnosed MM patients with ≥ 1 high-risk cytogenetic abnormality: Group 1: t(4;14) or t(14;16); Group 2: del(17p); Group 3: t(4;14)/del(17p) or t(14;16)/del(17p). Overall, 347 high-risk patients were identified (males, 48.7%; median age, 63 years). Median progression-free survival (PFS) and overall survival (OS) were 19.0 months (95% CI 17.0-20.0) and 50.0 months (95% CI 37.0-61.0), respectively. PFS (p = 0.047) and OS (p = 0.020) differed significantly between groups. After stratification by transplant eligibility, PFS and OS were significantly poorer in Group 3 among transplant-eligible patients, and even poorer in those with gain(1q). Patients stratified by cytogenetic abnormality and revised International Staging System (R-ISS) had significantly different PFS (p < 0.001) and OS (p = 0.003), with the worst survival in R-ISS III/Group 3 (median OS 21.0 months). Higher number of high-risk cytogenetic abnormalities was a negative prognostic marker for PFS and OS (p < 0.001). Real-world KMR data showed that risk factors for poor prognosis of MM patients included del(17p), R-ISS stage, and number of cytogenetic abnormalities.

Latent Tuberculosis Infection Screening and Treatment in Congregate Settings (TB FREE COREA): Demographic Profiles of Interferon-Gamma Release Assay Cohort.

In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferon-gamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, three-quarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort.

Therapeutic Efficacy of Autologous Platelet Concentrate Injection on Macular Holes with High Myopia, Large Macular Holes, or Recurrent Macular Holes: A Multicenter Randomized Controlled Trial.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon's skill.

Development of a Short Form Depression Screening Questionnaire for Korean Soldiers.

BACKGROUND: The frequencies of South Korean soldiers' depression and resulting suicide are increasing every year. Thus, this study aimed to develop and confirm the reliability and validity of a simple short form depression screening scale for soldiers. METHODS: This study was conducted as part of a 2013 research project named 'The Epidemiological Study on the Prevalence of Depression in Military Service and a Search for High Risk Group Management.' Clinical depression was diagnosed using the Korean version of the Mini International Neuropsychiatric Interview and suicide risk was assessed through the Korean version of the Composite International Diagnostic Interview. Furthermore, the Center for Epidemiological Studies for Depression Scale (CES-D), the Stress Response Inventory, and the Barret Impulsiveness Scale were employed. Of the 20 CES-D items, three of the most correlated items with clinical diagnosis were derived to form the short form scale. Analyses for internal consistency, concurrent validity, and factor analysis were implemented for its validation. We performed a receiver operating curve (ROC) analysis using a clinical diagnosis of depression as a gold standard to calculate the area under the curve (AUC) value, cut-off score, and corresponding sensitivity and specificity to that cut-off score. RESULTS: According to the results of the correlation analysis, 7, 18, and 4 were selected to be on our scale. The three-item scale was reliable with a Cronbach's alpha value of 0.720, and a factor was derived from the factor analysis. The ROC analysis showed a high discriminant validity, with an AUC value of 0.891. The sensitivity and specificity were 84.8% and 78.2%, and 71.7% and 91.6%, respectively, for each when the selected cut-off scores were 2 and 3, respectively. Depression screened through the scale when the cut-off score was 2 or 3 was significantly associated with suicidality, stress, and social support. CONCLUSION: The depression screening questionnaire for Korean soldiers developed through this study demonstrated high reliability and validity. Since it comprises only three items, it can be utilized easily and frequently. It is expected to be employed in a large-scale suicide prevention project targeting military soldiers in the future; it will be beneficial in selecting high-risk groups for depression.

Use of Proton Pump Inhibitors vs Histamine 2 Receptor Antagonists for the Risk of Gastric Cancer: Population-Based Cohort Study.

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed medications. Long-term use of PPIs has been suspected to have a provocative effect on gastric cancer. This study was to determine the association between PPI vs histamine 2 receptor antagonist (H2RA) use and the risk of gastric cancer in a region where the risk of this malignancy is high. METHODS: A population-based cohort study using the Korean National Health Insurance Services Database. The participants with first prescription of PPIs and H2RA with normal esophagogastroduodenoscopy finding from 2004 through 2015 were collected. Among them, 50% of participants were systematic stratified randomly sampled. There were 122,118 users of PPIs or H2RAs who use medication more than cumulative defined daily dose of 180 days. The users were followed up from long-term use threshold until gastric cancer, death from non-gastric cancer cause, gastric surgery, or study end (December 2017). RESULTS: After calculating propensity score weights, we included 39,799 PPI and 38,967 H2RA users. Among the new PPI and H2RA users, we identified 411 cases of incident gastric cancer from 182,643 person-years of follow-up observation and 397 cases from 178,846 person-years of follow-up observation, respectively. Compared with H2RA users, PPI users did not experience significantly different gastric cancer incidence (adjusted hazard ratio, 1.01; 95% confidence interval, 0.88-1.16; P = 0.89). Sensitivity analyses confirmed that gastric cancer incidence did not differ between PPI and H2RA users. DISCUSSION: In this large study, long-term treatment with PPIs vs H2RAs did not show higher risk of gastric cancer even in a high-risk region.

The development and validation of a predictive model for recurrence in rectal cancer based on radiological and clinicopathological data.

OBJECTIVE: To develop a prediction model for recurrence by incorporating radiological and clinicopathological prognostic factors in rectal cancer patients. METHODS: All radiologic and clinicopathologic data of 489 patients with rectal cancer, retrospectively collected from a single institution between 2009 and 2013, were used to develop a predictive model for recurrence using the Cox regression. The model performance was validated on an independent cohort between 2015 and 2017 (N = 168). RESULTS: Out of 489 derivative patients, 103 showed recurrence after surgery. The prediction model was constructed with the following four significant predictors: distance from anal verge, MR-based extramural venous invasion, pathologic nodal stage, and perineural invasion (HR: 1.69, 2.09, 2.59, 2.29, respectively). Each factor was assigned a risk score corresponding to HR. The derivation and validation cohort were classified by sum of risk scores into 3 groups: low, intermediate, and high risk. Each of these groups showed significantly different recurrence rates (derivation cohort: 13.4%, 35.3%, 61.5 %; validation cohort: 6.2%, 23.7%, 64.7%). Our new model showed better performance in risk stratification, compared to recurrence rates of tumor node metastasis (TNM) staging in the validation cohort (stage I: 3.6%, II: 12%, III: 30.2%). The area under the receiver operating characteristic curve of the new prediction model was higher than TNM staging at 3-year recurrence in the validation cohort (0.853 vs. 0.731; p = .009). CONCLUSIONS: The new risk prediction model was strongly correlated with a recurrence rate after rectal cancer surgery and excellent for selection of high-risk group, who needs more active surveillance. KEY POINTS: • Multivariate analysis revealed four significant risk factors to be MR-based extramural venous invasion, perineural invasion, nodal metastasis, and the short distance from anal verge among the radiologic and clinicopathologic data. • Our new recurrence prediction model including radiologic data as well as clinicopathologic data showed high predictive performance of disease recurrence. • This model can be used as a comprehensive approach to evaluate individual prognosis and helpful for the selection of highly recurrent group who needs more active surveillance.

Association between chronic fatigue syndrome and suicidality among survivors of Middle East respiratory syndrome over a 2-year follow-up period.

Suicide is an important public health issue during the current pandemic of emerging infectious diseases (EIDs). In EIDs, various symptoms persist even after recovery, and chronic fatigue is among those that are commonly reported. The aim of this study was to examine the effects of chronic fatigue syndrome on suicidality during the recovery phase among survivors of Middle East respiratory syndrome (MERS). MERS survivors were recruited from five centers and prospectively followed up for 2 years. In total, 63 participants were registered at 12 months (T1), of whom 53 and 50 completed the assessments at 18 months (T2) and 24 months (T3), respectively. Suicidality and chronic fatigue were evaluated using the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Fatigue Severity Scale (FSS), respectively. We analyzed the relationship between chronic fatigue and suicidality during the follow-up period using the generalized estimating equation (GEE). The suicidality rates were 22.2% (n = 14), 15.1% (n = 8), and 10.0% (n = 5) at T1-T3, respectively. Of the 63 participants, 29 had chronic fatigue syndrome at T1. The group that reported chronic fatigue syndrome at T1 was more likely to experience suicidality during the 2-year follow-up than the group that reported otherwise (RR: 7.5, 95% CI: 2.4-23.1). This association was present even after adjusting for potential confounders (RR: 7.6, 95% CI: 2.2-26.0). Chronic fatigue syndrome and suicide risk among emerging infectious disease (EID) survivors should be acknowledged, and effective interventions must be developed.

TGF-ß induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer.

Transforming growth factor-ß (TGF-ß) promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). EMT is often related with acquisition of stemness characteristics. The objective of this study was to determine whether EMT and stemness characteristics induced by TGF-ß might be associated with epigenetic regulation in lung cancer. A human normal lung epithelial cell line and four lung cancer cell lines were treated with TGF-ß. Transcriptome analysis of BEAS-2B and A549 cells incubated with TGF-ß were analyzed through next-generation sequencing (NGS). Western blotting was carried out to investigate expression levels of epithelial and mesenchymal markers. Wound healing and Matrigel invasion assay, sphere formation assay, and in vivo mice tumor model were performed to evaluate functional characteristics of EMT and stemness acquisition. To investigate whether activation of EMT and stem cell markers might be involved in epigenetic regulation of lung cancer, experiment using a DNA methyltransferase inhibitor (5-azacytidine, AZA), methylation-specific PCR (MSP) and bisulfite sequencing were performed. NGS revealed changes in expression levels of EMT markers (E-cadherin, N-cadherin, fibronectin, vimentin, slug and snail) and stem cell markers (CD44 and CD87) in both BEAS-2B and A549 cells. Functional analysis revealed increased migration, invasion, sphere formation, and tumor development in mice after TGF-ß treatment. Expression of slug and CD87 genes was activated following treatment with AZA and TGF-ß. MSP and bisulfite sequencing indicated DNA demethylation of slug and CD87 genes. These results suggest that TGF-ß induced EMT and cancer stemness acquisition could be associated with activation of slug and CD87 gene by their promoter demethylation.

Associations between social network properties and metabolic syndrome and the mediating effect of physical activity: findings from the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) Cohort.

INTRODUCTION: Social isolation and loneliness are positively associated with metabolic syndrome. However, the mechanisms by which social isolation affects metabolic syndrome are not well understood. RESEARCH DESIGN AND METHODS: This study was designed as a cross-sectional study of baseline results from the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) Cohort. We included 10 103 participants (8097 community-based low-risk participants, 2006 hospital-based high-risk participants) from the CMERC Cohort. Participants aged 65 years or older were excluded. Multiple imputation by chained equations was applied to impute missing variables. The quantitative properties of social networks were assessed by measuring the 'size of social networks'; qualitative properties were assessed by measuring the 'social network closeness'. Metabolic syndrome was defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariate logistic regression analyses were conducted to assess association between social network properties and metabolic syndrome. The mediating effects of physical inactiveness, alcohol consumption, cigarette smoking and depressive symptoms were estimated. Age-specific effect sizes were estimated for each subgroup. RESULTS: A smaller social network was positively associated with higher prevalences of metabolic syndrome in all subgroups, except the high-risk male subgroup. There was no clear association between social network closeness and metabolic syndrome. In community-based participants, an indirect effect through physical activity was detected in both sexes; however, in hospital-based participants, no indirect effects were detected. Cigarette smoking, alcohol consumption and depression did not mediate the association. Age-specific estimates showed that the indirect effect through physical activity had a greater impact in older participants. CONCLUSIONS: A smaller social network is positively associated with metabolic syndrome. This trend could be partially explained by physical inactivity, especially in older individuals.

Latent tuberculosis infection screening and treatment in congregate settings (TB FREE COREA): protocol for a prospective observational study in Korea.

INTRODUCTION: South Korea regards tuberculosis (TB) incidence in congregate settings as a serious problem. To this end, systematic latent TB infection (LTBI) diagnosis and treatment were provided to approximately 1.2 million individuals in high-risk congregate settings. METHODS AND ANALYSIS: We designed a prospective cohort study of individuals tested for LTBI, based on the data collected on all persons screened for LTBI as part of the 2017 congregate settings programme in South Korea. Four types of databases are kept: LTBI screening database (personal information and LTBI test results), national health information (NHI) database (socio-demographic data and comorbidities), public healthcare information system (PHIS) database, and the Korean national TB surveillance system database (TB outcomes). Information regarding LTBI treatment at private hospitals and public health centres is collected from NHI and PHIS databases, respectively. The screening data are cleaned, duplicates are removed, and, where appropriate, re-coded to analyse specific exposures and outcomes. The primary objective is to compare the number of active TB cases prevented within 2 years between participants undergoing treatment and not undergoing treatment in the LTBI screening programme in congregate settings. Cascade of care for LTBI diagnosis and treatment will be evaluated among those with a positive LTBI test result. A Cox proportional hazards model will be applied to determine the risk factors for developing active TB. ETHICS AND DISSEMINATION: The protocol is approved by the institutional review boards of Incheon St. Mary's Hospital, the Catholic University of Korea. Study results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: KCT0003905.

Effects of birth months on rheumatic diseases in South Korea: a nationwide case-control study.

OBJECTIVES: Birth month/season impacts the development of certain diseases. However, the effect of birth month/season on the development of rheumatic diseases has not been thoroughly investigated. Thus, the objective of this study was to determine whether birth month/season might affect the development of rheumatic diseases. METHODS: Birth month patterns of patients with various rheumatic diseases were compared with those of the general population. The dataset included 17,247,458 individuals from the health insurance review and assessment service database of Korea. RESULTS: Among 24 rheumatic diseases, the development of Crohn's disease, ulcerative colitis (UC), rheumatoid arthritis, Sjögren's syndrome, polymyalgia rheumatica, ankylosing spondylitis (AS), gout, and fibromyalgia (FM) was significantly associated with birth month/season. UC and AS were more prevalent in individuals born in February/winter. On the contrary, those who were born in June or July/summer were at a higher risk of gout and FM. CONCLUSIONS: Seasonal variations in infectious agents, sun exposure, and food ingestion during gestation or early infancy seem to explain the association between birth month/season and development of rheumatic diseases.

Comparison of PANAMutyper and PNAClamp for Detecting KRAS Mutations from Patients With Malignant Pleural Effusion.

BACKGROUND/AIM: KRAS is one of the frequently mutated genes in human cancers and often relates with drug resistance and poor prognosis. PANAMutyper™ is a novel technology that integrates PNAClamp™ and PANA S-Melting™. In the present study, PANAMutyper™ and PNAClamp™ were compared for the detection of KRAS mutations using different samples of patients with malignant pleural effusion. PATIENTS AND METHODS: A total of 103 patients (including 56 lung adenocarcinoma, 10 lung squamous carcinoma, 17 small cell lung cancer, 3 large cell lung cancer, 3 stomach cancer, 2 ovarian cancer, and others) with malignant pleural effusion were investigated using matched tumor tissue, cell block, and pleural effusion samples. The diagnostic performance of these two methods was compared. RESULTS: KRAS mutations were detected in 18 (17.5%) of 103 patients using tissue, cell block, and pleural effusion samples. All 18 patients with KRAS mutations were detected by PANAMutyper™ using any sample type, however, only 7 cases were detected by PNAClamp™. Among the subtypes of KRAS mutations, substitution in codon 12, 35G>T was the most frequent, followed by substitution in codon 12, 35G>A and codon 12, 34G>A. In pleural effusion specimens, PANAMutyper™ showed a better diagnostic performance compared to PNAClamp™. CONCLUSION: PANAMutyper™ had a diagnostic superiority for the detection of KRAS mutations in patients with malignant pleural effusion compared to PNAClamp™, although there was a concordance between PANAMutyper™ and PNAClamp™ results. Therefore, PANAMutyper™ can be used for a more sensitive and accurate detection of KRAS mutations.

Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation.

BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood. METHODS: Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed. For validation, the EMT and stem cell characteristics were analyzed. To determine whether an epigenetic mechanism was involved, the cell lines were treated with a DNA methyltransferase inhibitor (AZA), and methylation-specific PCR and bisulfite sequencing were performed. RESULTS: Next-generation sequencing revealed that the CXCR4 expression was significantly higher after the hypoxic condition, which functionally resulted in the EMT and cancer stemness acquisition. The acquisition of the EMT and stemness properties was inhibited by treatment with CXCR4 siRNA. The CXCR4 was activated by either the hypoxic condition or treatment with AZA. The methylation-specific PCR and bisulfite sequencing displayed a decreased CXCR4 promoter methylation in the hypoxic condition. CONCLUSIONS: These results suggest that hypoxia-induced acquisition of cancer stem cell characteristics was associated with CXCR4 activation by its aberrant promoter demethylation.

Comparison of PNA Clamping-assisted Fluorescence Melting Curve Analysis and PNA Clamping in Detecting EGFR Mutations in Matched Tumor Tissue, Cell Block, Pleural Effusion and Blood of Lung Cancer Patients With Malignant Pleural Effusion.

BACKGROUND/AIM: This study compared the efficacy of PANAMutyper™, a novel technology that integrates PNAClamp™ and PANA S-Melting™, and PNAClamp™ alone for the detection of EGFR mutations in lung cancer patients. MATERIALS AND METHODS: PANAMutyper™ and PNAClamp™ were used to assess the EGFR mutation status in tissue, cell block, pleural effusion, and blood samples of 90 lung cancer patients with malignant pleural effusion. RESULTS: PANAMutyper™ detected more EGFR mutations than PNAClamp™, especially in body fluids (pleural effusion and serum). Patients with additional EGFR mutations detected using PANAMutyper™ had a favorable response to EGFR-tyrosine kinase inhibitor (TKI) treatment. CONCLUSION: The diagnostic performance of PANAMutyper™ was superior to that of PNAClamp™ for the detection of EGFR mutations. It was also better at identifying lung cancer patients with malignant pleural effusion who were likely to benefit from EGFR-TKI treatment.

Rheumatoid arthritis is associated with early tooth loss: results from Korea National Health and Nutrition Examination Survey V to VI.

BACKGROUND/AIMS: To examine the association between rheumatoid arthritis (RA) and periodontitis or tooth loss. METHODS: The study used data from the fifth and sixth Korea National Health and Nutrition Examination Surveys conducted from 2010 to 2015. RA was defined as participant-reported physician-diagnosed RA that was being treated. Periodontitis and the number of natural teeth were determined by dental examination. Periodontitis was defined according to the community periodontal index (periodontal probing depth ≥ 4 mm). The association between RA and periodontitis or tooth loss was examined after controlling for confounding variables (e.g., age, smoking status, socioeconomic status, dental caries, frequency of toothbrushing, body mass index, alcohol consumption, and diabetes) in men and women. Subgroup analyses stratified by age were also performed. RESULTS: The study enrolled 20,297 participants aged ≥ 19 years (157 RA patients and 20,140 non-RA controls). There was no association between RA and periodontitis or tooth loss in men and women. Subgroup analyses in those aged < 60 years revealed a non-significant association between RA and periodontitis (adjusted odds ratio, 1.53; p = 0.162), but they revealed a significant association between RA and tooth loss (adjusted ß, 0.20; p = 0.042). CONCLUSION: RA was not associated with periodontitis, but was associated with tooth loss in younger adults. Younger RA patients are more likely to suffer tooth loss than general younger population; thus dental management is required.