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Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with inferior outcomes in the chemotherapy setting. We hypothesized that allogeneic hematopoietic cell transplantation (allo-HCT)-based post-remission therapy would improve outcomes of this entity. We examined the frequency and long-term outcomes of adults with Ph-like ALL, particularly focusing on allo-HCT outcomes for Ph-like ALL versus non-Ph-like ALL. Ph-like ALL was determined by anchored multiplex PCR-based targeted next-generation sequencing. Of the 344 patients, 57 (16.6%) had Ph-like ALL, 197 (57.3%) had Ph-positive ALL, and 90 (26.1%) had B-other ALL. To further evaluate the prognosis of Ph-like ALL, outcome analyses were restricted to 147 patients, excluding Ph-positive ALL. The actual allo-HCT rates in complete remission were 87.7% for Ph-like ALL, 71.4% for B-other standard-risk ALL, and 70.4% for B-other poor-risk ALL. Patients with Ph-like ALL had a higher 5-year overall survival (60.6% vs 27.1%; P = 0.008) than B-other poor-risk ALL subgroup, while no difference was observed compared with B-other standard-risk ALL subgroup. Similar results were noted in a separate analysis for patients receiving allo-HCT in complete remission. In multivariate analyses, B-other poor-risk ALL was associated with poorer outcomes. Our data showed that allo-HCT-based post-remission therapy may have contributed to non-inferior outcomes of adult Ph-like ALL.

Background Plasma cell myeloma (PCM) is a genetically heterogeneous disease. The genetic spectrum of PCM has been expanded to mutations such as KRAS, NRAS, and BRAF genes in the RAS-RAF-MAPK pathway. In this study, we have evaluated the frequency of these mutations and their significance, including baseline characteristics and clinical outcomes. Methods We explored 50 patients who were newly diagnosed with PCM between 2009 and 2012 at a single Korean institute. Clinical and laboratory parameters were gathered through careful review of medical records. Mutation analysis was carried out using DNA from the bone marrow at the time of diagnosis. Pyrosequencing was performed to detect KRAS G12V, KRAS G13D, and NRAS G61R. BRAF V600E was analyzed by allele-specific real- time PCR. Comparison of clinical and laboratory parameters was carried out according to those mutations. Results We identified 14 patients (28%) with activating mutations in the RAS-RAF-MAPK pathway (RAS/RAF mutations): KRAS (N=3), NRAS (N=4), BRAF (N=7), and both KRAS and BRAF (N=1). RAS/RAF mutations were more frequently observed in patients with complex karyotypes and showed poorer progression free survival (PFS). Specifically, the BRAF V600E mutation had a significantly negative impact on median PFS. Conclusion We first showed the frequency of RAS/RAF mutations in Korean patients with PCM. Screening of these mutations could be considered as a routine clinical test at the time of diagnosis and follow-up due to their influence on clinical outcome, as well as its potential as a therapeutic target.

Background: Computer-aided methods for analyzing white blood cells (WBC) are popular due to the complexity of the manual alternatives. Recent works have shown highly accurate segmentation and detection of white blood cells from microscopic blood images. However, the classification of the observed cells is still a challenge, in part due to the distribution of the five types that affect the condition of the immune system.Methods: (i) This work proposes W-Net, a CNN-based method for WBC classification. We evaluate W-Net on a real-world large-scale dataset that includes 6,562 real images of the five WBC types. (ii) For further benefits, we generate synthetic WBC images using Generative Adversarial Network to be used for education and research purposes through sharing.Results: (i) W-Net achieves an average accuracy of 97%. In comparison to state-of-the-art methods in the field of WBC classification, we show that W-Net outperforms other CNN- and RNN-based model architectures. Moreover, we show the benefits of using pre-trained W-Net in a transfer learning context when fine-tuned to specific task or accommodating another dataset. (ii) The synthetic WBC images are confirmed by experiments and a domain expert to have a high degree of similarity to the original images. The pre-trained W-Net and the generated WBC dataset are available for the community to facilitate reproducibility and follow up research work.Conclusion: This work proposed W-Net, a CNN-based architecture with a small number of layers, to accurately classify the five WBC types. We evaluated W-Net on a real-world large-scale dataset and addressed several challenges such as the transfer learning property and the class imbalance. W-Net achieved an average classification accuracy of 97%. We synthesized a dataset of new WBC image samples using DCGAN, which we released to the public for education and research purposes.

Background Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired pluripotent hematopoietic stem cell disorder associated with an increase in the number of glycosyl-phosphatidyl inositol (GPI)-deficient blood cells. We investigated PNH clonal proliferation in the three cell lineages-granulocytes, T lymphocytes, and red blood cells (RBCs)-by analyzing PIGA gene mutations and T-cell receptor (TCR) clonality. Methods Flow cytometry was used on peripheral blood samples from 24 PNH patients to measure the GPI-anchored protein (GPI-AP) deficient fraction in each blood cell lineage. PIGA gene mutations were analyzed in granulocytes and T lymphocytes by Sanger sequencing. A TCR clonality assay was performed in isolated GPI-AP deficient T lymphocytes. Results The GPI-AP deficient fraction among the three lineages was the highest in granulocytes, followed by RBCs and T lymphocytes. PIGA mutations were detected in both granulocytes and T lymphocytes of 19 patients (79.2%), with a higher mutation burden in granulocytes. The GPI-AP deficient fractions of granulocytes and T lymphocytes correlated moderately (rs=0.519, P=0.049) and strongly (rs=0.696, P=0.006) with PIGA mutation burden, respectively. PIGA mutations were more frequently observed in patients with clonal rearrangements in TCR genes (P=0.015). The PIGA mutation burden of T lymphocytes was higher in patients with clonal TCRB rearrangement. Conclusions PIGA mutations were present in approximately 80% of PNH patients. PNH clone size varies according to blood cell lineage, and clonal cells may obtain proliferation potential or gain a survival advantage over normal cells.

Objective Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population. Methods Systemic lupus erythematosus patients ( n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio ( n = 105,080). Results During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327–1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk. Conclusions Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.

Background Minimal residual disease (MRD) monitoring is a powerful tool to predict the risk of relapse. Herein, we present an MRD monitoring strategy for B-cell lymphoblastic leukemia (B-ALL) using high-throughput sequencing (HTS) of immunoglobulin (Ig) clonality before implementation into routine practice. Methods We selected 74 bone marrow (BM) specimens from 47 patients who were diagnosed with B-ALL. Ig clonality was analyzed using both fragment analysis and HTS. The performance of Ig clonality was evaluated through comparison of the results from real-time quantitative polymerase chain reaction (qPCR) of leukemia-specific fusion transcripts and flow cytometry. Results IGH clonality was observed in all patients, and the sum of clonal burden varied (9.47%–96.77%). IGK clonality was identified in 70% of patients and availed in cases with low IGH clonal burden. The total IGH clonal burden was significantly correlated with the proportion of leukemic blasts, leukemia-specific fusion transcripts, and flow cytometry. We recognized the different responses of each clone and emerging clones originating from the trace of Ig rearrangement presented in the initial specimen. IGH clonal burden after chemotherapy represented patient outcomes well. IGH assay also provided information of repertoire diversity of IGH rearrangement. Conclusion The Ig clonality assay via HTS will be a promising tool for MRD monitoring of B-ALL through an adequate strategy to identify and monitor individual clones and determine repertoire diversity.

We reviewed our leukemia database to reclassify 610 patients previously diagnosed as having acute myeloid leukemia (AML) according to the updated 2016 WHO classification. Nine patients were categorized as having myelodysplastic syndrome and myeloid neoplasms with germline predisposition. AML with recurrent genetic abnormalities accounted for 57.4% (345/601) of the patients under the 2016 WHO classification. AML with mutated NPM1 was the most common form (16.5%), with the majority associated with monocytic differentiation (63.6%). AML with double CEBPA mutations accounted for 8.3% of these cases, and the majority were previously diagnosed as AML with/without maturation (78.0%). These newly classified mutations were mutually exclusive without overlapping with other forms of AML with recurrent genetic abnormalities. AML with mutated NPM1 and AML with myelodysplasia-related changes comprised the oldest patients, whereas AML with RUNX1-RUNX1T1 included the youngest patients. The leukocyte count was highest in AML with mutated NPM1, and the percentage of peripheral blood blasts was the highest in AML with double CEBPA mutations. Our results indicate that implementation of the 2016 WHO classification of AML would not pose major difficulties in clinical practice. Hematopathologists should review and prepare genetic tests for the new classification, according to their clinical laboratory conditions.

Background: Hemophagocytic lymphohistiocytosis (HLH) can be life-threatening if not detected and treated appropriately. The diagnosis of HLH can be confusing due to other similar febrile diseases that present with cytopenia. Natural-killer cell (NK)-cytotoxicity is an important diagnostic parameter for primary HLH; however, its role in secondary HLH in adults has not been well-elucidated. Methods: We prospectively enrolled 123 adult patients with febrile conditions accompanied by cytopenia or marrow hemophagocytosis. A diagnosis of HLH was based on HLH-2004 criteria and treated based on HLH-94 protocol. NK-cytotoxicity was calculated at the time of diagnosis by K562-cell direct lysis using flow-cytometry. Results: HLH ( n = 60) was determined to be caused by Epstein–Barr virus (EBV) ( n = 11), infection other than EBV ( n = 16), malignancies ( n = 19), and unknown ( n = 14). Febrile diseases other than HLH ( n = 63) were diagnosed as autoimmune disease ( n = 22), malignancies ( n = 21), infection ( n = 12), non-malignant hematological diseases ( n = 6), and unknown ( n = 2). A lower NK-cytotoxicity level was observed at diagnosis in patients with HLH, compared with other causes of febrile disease (12.1% versus 26.2%, p Conclusions: Febrile disease with cytopenia was associated with decreased NK-cytotoxicity, especially in adults with HLH; however, its diagnostic role for adult HLH is still arguable. The diagnostic criteria for adult HLH should be further discussed. Trial registration: Clinical Research Information Service [Internet]; Osong (Chungcheongbuk-do), Korea, Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); https://cris.nih.go.kr/cris/index.jsp ; Feb, 16th 2016; KCT0001886 (KC15TISE0936)

Introduction Patients with malignancies are known to have an increased risk of atrial fibrillation (AF). However, there is a paucity of information regarding the cancer type and the risk of AF. We aimed to evaluate the risk of AF according to the type of cancer. Methods We enrolled 816,811 patients who were diagnosed with cancer from the Korean National Health Insurance Service database between 2009 and 2014. Age and sex-matched non-cancer control subjects (1:2, n=1,633,663) were selected and compared with patients with malignancy. Newly diagnosed nonvalvular AF was identified using the claims data. Besides, we performed a sensitivity analysis using lag periods from cancer diagnosis to AF for more than 1 year and more than 5 year. Results During a mean follow up of 4.7 years, AF was newly diagnosed in 25,356 patients with cancer (6.6 per 1000 person-years) whereas 31,801 patients in the control group (3.6 per 1000 person-years). In multivariate Cox regression analysis, cancer was an independent risk factor for incident AF (HR 1.97; 95% CI 1.94–2.00). Hematologic malignancies show higher correlation with incident AF (multiple myeloma, the hazard ratio (HR) 4.57; 95% confidence interval (CI) 4.08–5.12; leukemia, HR 4.15; 95% CI 3.75–4.59). Malignancies of the nervous system, esophagus, lung, and pancreatic cancer show higher risks of AF more than 3 times than control, whereas prostate cancer shows the lowest association with AF risk (HR 1.36; 95% CI 1.29–1.44). In subgroup analysis, the effect of cancer on AF development was more prominent in patients with younger age ( In sensitivity analysis using lag periods, the strength of risks of AF decline with time from cancer diagnosis but remain significant (“>1yr” HR 1.77; 95% CI 1.74–1.81; “>5yrs” HR 1.12; 95% CI 1.07–1.16). However, AF risk was more diverse according to the types of cancers in patients surviving above five years. Multiple myeloma, leukemia, lymphoma, ovarian, liver, and lung cancer show higher risks of AF than control while other types of cancer show no significant association with AF incidence after five years from a cancer diagnosis. Conclusion Although patients with cancer showed a higher risk of AF, but the impact on AF development was diverse among cancer types. Hematologic malignancies showed the highest risk of AF, and the risk was maintained up to 5 year after diagnosis of cancer. Therefore it would be reasonable to screen AF especially in those malignancies with high-risk for AF. Different AF risk in cancer patients Funding Acknowledgement Type of funding source: None

Introduction Regular exercise is known to decrease the risk of dementia. There is a paucity of information about the impact of the change of exercise habit on cardiovascular outcomes after a new diagnosis of atrial fibrillation (AF). We aimed to investigate whether regular exercise is associated with the risk of developing dementia in patients with AF. Methods Using the Korean National Health Insurance Service database, we enrolled patients with newly diagnosed AF who had undergone health screening between 2010 and 2016. The study population was divided into four groups based on the consistency of regular exercise before and after AF diagnosis: (1) persistent non-exerciser, (2) exercise starter, (3) exercise quitter, and (4) exercise maintainer. We investigated the association between exercise and the risk of dementia. Results A total of 126,555 patients were included (mean age 62.7 years, male 62.0%, and mean CHA2DS2-VASc Score 2.7). During a median follow-up duration of 3.0 years, 5,943 patients were newly diagnosed as dementia (1.57 per 100 person-years). Among patients with incident dementia, 4,410 patients had Alzheimer's dementia and 951 patients had vascular dementia (1.16 and 0.25 per 100 person-years, respectively). Persistent non-exerciser, exercise starter, quitter, and maintainer groups were 65.1%, 12.8%, 12.7%, and 9.4%, respectively. After multivariable adjustment, we found that exercise was associated with a lower risk of developing overall dementia. When compared to persistent non-exerciser, exercise starter and maintainer showed reduced risk of developing dementia (hazard ratio [HR] 0.80, 95% confidence interval [95% CI] 0.73–0.88 and HR 0.63, 95% CI 0.54–0.73, respectively, all p-value 0.05, Figure). Conclusions Regular exercise showed a lower risk of dementia in patients with new-onset AF. Starting exercise even after the diagnosis of AF was beneficial to patients who had little physical activity previously. These findings may support physicians to recommend that AF patients should start exercise or keep their physical activity to reduce the risk of dementia. Funding Acknowledgement Type of funding source: None

Background Atrial fibrillation (AF) is a risk factor for dementia and oral anticoagulant (OAC) use is associated with a decreased risk of dementia in patients with AF. Objective We sought to find whether the risk of dementia would be different between patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) and those treated with warfarin. Methods Using the Korean National Health Insurance database from January 2014 to December 2017, we identified OAC naïve non-valvular AF patients aged 40 years or older. For the comparison, warfarin and NOAC groups were balanced using the inverse probability of treatment weighting method (IPTW). The primary outcome was incident dementia. Patients were censored at the occurrence of dementia, discontinuation of index treatment, or the end of the study period (December 31, 2018). Results Among 72,846 of total study patients, 25,948 were treated with warfarin and 46,898 were treated with NOAC (17,193 with rivaroxaban, 9,882 with dabigatran, 11,992 with apixaban, and 7,831 with edoxaban). Crude incidence of dementia was 4.65 per 100 person-years in warfarin group and 4.98 per 100 person years in NOAC group. Baseline characteristics were well-balanced after IPTW (mean age 72 years, 93% CHA2DS2-VASc ≥2, 58% men). Compared to warfarin, NOAC showed a comparable risk of dementia (hazard ratio [HR] 0.944, 95% confidence interval [CI] 0.934–1.059), vascular dementia (HR 0.921, 95% CI 0.814–1.043) and Alzheimer dementia (HR 1.101, 95% CI 1.019–1.191). When comparing individual NOACs with warfarin, edoxaban was associated with a lower risk of dementia (HR 0.830, 95% CI 0.740–0.931). Rivaroxaban (HR 0.767, 95% CI 0.648–0.907) and edoxaban (HR 0.786, 95% CI 0.620–0.996) were associated with a lower risk of vascular dementia than warfarin. In subgroup analyses, NOAC was associated with a lower incidence of dementia than warfarin particularly in patients with prior stroke (HR 0.891, 95% CI 0.820–0.968) and in patients aged 65–74 years (HR 0.815, 95% CI 0.709–0.936). Conclusion In this large Asian population with AF, NOAC showed a comparable result with warfarin on the risk of dementia. Edoxaban was associated with a lower risk of dementia. NOAC appeared more beneficial especially in those with AF who had a history of prior stroke and aged 65–74 years. Funding Acknowledgement Type of funding source: None

Background There are limited data about the impact of modifying behavior such as smoking cessation after atrial fibrillation (AF) diagnosis on the clinical outcome. Purpose To evaluate the association between smoking cessation after newly diagnosed AF and the risk of stroke. Methods Among subjects with new-onset AF between 2010 and 2016, those who received a national health checkup exam within 2 years before and after the AF diagnosis were included. Subjects were categorized into 4 groups according to the status of smoking before and after AF diagnosis: (i) never smoker; (ii) new smoker after AF diagnosis; (iii) quit-smoker after AF diagnosis; and (iv) persistent smoker. The primary outcome was incident stroke during follow-up. Results A total of 97,869 patients were included (mean age 61±12, men 62%, and mean CHA2DS2-VASc 2.3±1.5). During a median of 3 years of follow-up, stroke occurred in 3,121 patients (1.0 per 100 person-years). Never smoker, new smoker, quit-smoker, and persistent smoker was 79%, 2%, 7%, and 12% of the total study population, respectively. After multivariable adjustment, new smoker and persistent smoker were associated with an increased risk of stroke compared to never smoker (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.48–2.28 for new smoker; HR 1.66, 95% CI 1.48–1.86 for persistent smoker) (Figure). Quit-smoker who stopped smoking after AF diagnosis also showed a higher risk of stroke than never smoker (HR 1.19, 95% CI 1.03–1.38). The quit-smoker group showed a lower compared to those who continued smoking after AF diagnosis (HR 0.720, 95% CI 0.608–0.851). Conclusion Smoking cessation after AF diagnosis showed a lower risk of stroke compared to patients smoking persistently. Lifestyle change as smoking cessation after diagnosis of AF could modify the risk of stroke in patients with new-onset AF. Hazard ratio of smoking status for AF Funding Acknowledgement Type of funding source: None

Introduction There is a paucity of information about cardiovascular impacts related to the change of exercise habit after a new diagnosis of atrial fibrillation (AF). We aimed to investigate the influence of exercise on the risk of cardiovascular outcomes, such as ischemic stroke, heart failure (HF), and all-cause death, in patients with AF. Methods We included 66,692 patients with newly diagnosed AF (36.4% female, mean age 59.5 years, mean CHA2DS2-VASc 1.9) who underwent two serial health examinations before and after diagnosis of AF from 2010 to 2016, as provided by Korean National Health Insurance Corporation. The individuals self-reported a degree and frequency of exercise by questionnaires and doing vigorous physical activities ≥3 times/week or moderate physical activities ≥5 times/week was defined as a regular exercise group. The study population was divided into four categories according to the status of regular exercise before and after AF diagnosis: persistent non-exerciser (64.0%), new exerciser (13.4%), exercise drop-outs (12.5%), and exercise maintainer (10.1%). The primary outcomes were ischemic stroke, HF, and all-cause death during the follow-up. Results During a median 3.4 years follow-up, ischemic stroke, HF, and all-cause death occurred in 1905, 13112, and 2627 patients, respectively (incidence rates 8.5, 64.8, and 11.5 per 1,000 person-years, respectively). The change in exercise habits did not have a significant association with the risk of ischemic stroke (Figure 1). Regarding HF, those who newly initiated or maintained exercise after AF diagnosis showed a lower risk than those who do not exercise: hazard ratio, HR 0.93; 95% confidence interval, CI [0.88 to 0.98] and 0.90 [0.85 to 0.96] for each group, all p Conclusions Patients who started or continued exercising after a new diagnosis of AF showed a lower risk of HF and mortality, but did not show an association with ischemic stroke. Regular exercise might improve the cardiovascular outcomes in patients with newly diagnosed AF. Figure 1. CV impacts of exercise on AF patients Funding Acknowledgement Type of funding source: None

Background Accurate, rapid, and cost-effective screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be useful in laboratories that cannot afford automated chemiluminescent immunoassays (CLIAs). We evaluated the diagnostic performance of a novel rapid automated fluorescent lateral flow immunoassay (LFIA). Methods A fluorescent LFIA using a small bench-top fluorescence reader, Automated Fluorescent Immunoassay System (AFIAS; Boditech Med Inc., Chuncheon, Korea), was developed for qualitative detection of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HCV (anti-HCV) within 20 minutes. We compared the diagnostic performance of AFIAS with that of automated CLIAs—Elecsys (Roche Diagnostics GmbH, Penzberg, Germany) and ARCHITECT (Abbott Laboratories, Abbott Park, IL, USA)—using 20 seroconversion panels and 3,500 clinical serum samples. Results Evaluation with the seroconversion panels demonstrated that AFIAS had adequate sensitivity for HBsAg and anti-HCV detection. From the clinical samples, AFIAS sensitivity and specificity were 99.8% and 99.3% for the HBsAg test, 100.0% and 100.0% for the anti-HBs test, and 98.8% and 99.1% for the anti-HCV test, respectively. Its agreement rates with the Elecsys HBsAg, anti-HBs, and anti-HCV detection assays were 99.4%, 100.0%, and 99.0%, respectively. AFIAS detected all samples with HBsAg genotypes A-F and H and anti-HCV genotypes 1, 1a, 1b, 2a, 2b, 4, and 6. Cross-reactivity with other infections was not observed. Conclusions The AFIAS HBsAg, anti-HBs, and anti-HCV tests demonstrated diagnostic performance equivalent to current automated CLIAs. AFIAS could be used for a large-scale HBV or HCV screening in low-resource laboratories or low-to middle-income areas.

Objective To investigate the incidence and clinical significance of cardiovascular disease in systemic lupus erythematosus patients. Methods We included systemic lupus erythematosus patients ( n = 18,575) without previous cardiovascular disease and age- and sex-matched individuals without systemic lupus erythematosus (controls; n = 92,875) from the Korean National Health Insurance Service database (2008–2014). Both cohorts were followed up for incident cardiovascular disease and death until 2015. Results During follow up, myocardial infarction occurred in 203 systemic lupus erythematosus patients and 325 controls (incidence rate: 1.76 and 0.56 per 1000 person-years, respectively), stroke occurred in 289 patients and 403 controls (incidence rate: 2.51 and 0.70 per 1000 person-years, respectively), heart failure occurred in 358 patients and 354 controls (incidence rate 3.11 and 0.61 per 1000 person-years, respectively), and death occurred in 744 patients and 948 controls (incidence rate 6.54 and 1.64 per 1000 person-years, respectively). Patients with systemic lupus erythematosus had higher risks for myocardial infarction (hazard ratio: 2.74, 95% confidence interval: 2.28–3.37), stroke (hazard ratio: 3.31, 95% confidence interval: 2.84–3.86), heart failure (hazard ratio: 4.60, 95% confidence interval: 3.96–5.35), and cardiac death (hazard ratio: 3.98, 95% confidence interval: 3.61–4.39). Conclusions Here, systemic lupus erythematosus was an independent risk factor for cardiovascular disease, thus cardiac assessment and management are critical in systemic lupus erythematosus patients.

Background Carcinoembryonic antigen (CEA) is one of the tumor markers available for evaluating disease progression status after initial therapy and monitoring subsequent treatment modalities in colorectal, gastrointestinal, lung, and breast carcinoma. We evaluated the correlations and differences between widely used, automated CEA immunoassays at four different medical laboratories. Methods In total, 393 serum samples with CEA ranging from 3.0 to 1,000 ng/mL were analyzed on ADVIA Centaur XP (Siemens Diagnostics, Tarrytown, NY, USA), ARCHITECT i2000sr (Abbott Diagnostics, Abbott Park, IL, USA), Elecsys E170 (Roche Diagnostics, Indianapolis, IN, USA), and Unicel DxI800 (Beckman Coulter, Fullerton, CA, USA), and the results were compared. Deming regression, Passing-Bablok regression, and Bland-Altman analyses were performed to evaluate the data correlation and % differences among these assays. Results Deming regression analysis of data from Elecsys E170 and UniCel DxI800 showed good correlation (y=3.1615+0.8970x). According to Bland-Altman plot, no statistically significant bias (-1.78 ng/mL [95% confidence interval: -4.02 to 0.46]) was observed between Elecsys E170 and UniCel DxI800. However, the relative differences of CEA concentrations between assays exceeded the acceptable limit of 30%. Regarding the agreement of positivity with cut-off value 5.0 ng/mL, ARCHITECT i2000sr and Elecsys E170 showed the highest agreement (95.2%), whereas ADVIA Centaur XP and ARCHITECT i2000sr showed the lowest agreement (70.7%). Conclusions Agreements between automated CEA immunoassays are variable, and individual CEA concentrations may differ significantly between assays. Standardization of serum CEA concentrations and further harmonization are needed.

Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare disease and has a very fulminant clinical course with high mortality. A 21-month-old female patient was referred to our hospital with a 1 week history of fever and was subsequently diagnosed with systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood. After starting treatment with dexamethasone, she showed early defervescence and improvement of laboratory parameters, and has remained disease-free after stopping steroid treatment, although longer follow-up is necessary. Our report underscores the possibility that this disease entity may be heterogenous in terms of prognosis.

Electrostatic effects on the redox photochemistry of synthetic probes (1, 2, and 1–Zn) are examined by adjusting the thermodynamic driving force of their oxidation reactions. The redox photochemistry was simply controlled by introducing a zinc binding site (2,2′-dipicolylamine (DPA)) on the coumarin moiety of probe 2. Zinc complexation produced a positively charged environment on the coumarin (1–Zn), which lowered the electron density of a nearby 9 H-xanthene ring, attenuating the auto-oxidation of 1–Zn by 45 % compared with that of probe 1 at 298 K. The positive net charge of 1–Zn also provided an attractive Coulombic force toward the phosphate of flavin mononucleotide and flavin adenine dinucleotide, which lowered the reduction potential of the electron acceptor (isoalloxazine) and improved intermolecular electron transfer from the 9 H-xanthene ring to isoalloxazine. The flavin-mediated oxidation rate of 1–Zn was increased to 1.5 times that of probe 2. Probe 1–Zn showed highly selective sensing behaviour toward flavins, producing an intense brightness (ϵΦF=2.80×103 m−1 cm−1) in the long-wavelength regions (λmax=588 nm) upon flavin-mediated oxidation. Furthermore, probes 1–Zn and 2 were successfully applied to eosinophil imaging and the differential diagnosis of eosinophilia; this demonstrates their use as diagnostic tools.

Background The epidemiology of Adamantiades-Behcet's disease varies among ethnic populations worldwide. Trends in the incidence of Adamantiades-Behcet's disease have not been investigated based on the Korean National Health Insurance database. Objectives This study investigated the incidence and mortality of Adamantiades-Behcet's disease by age using nationwide population data in Korea. Methods A nationwide population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2006 to 2015. The incidence of Adamantiades-Behcet's disease was calculated by age, sex, calendar year and habitat. And comorbid metabolic diseases were also analysed in patients with Adamantiades-Behcet's disease. Results The annual incidence of Adamantiades-Behcet's disease per 100 000 person-years was 3.976 (2.587 for males and 5.373 for females) from 2006 to 2015. The incidence of Adamantiades-Behcet's disease peaked among people in their 40s (6.561 per 100 000 person-years). Incidence was significantly higher in subjects with comorbid metabolic conditions, such as diabetes mellitus, hypertension and dyslipidemia. The mortality rate per 1000 person-years increased with age in patients with Adamantiades-Behcet's disease. Conclusions This study showed the incidence, prevalence and mortality of Adamantiades-Behcet's disease. Metabolic conditions increased the risk of Adamantiades-Behcet's disease among Koreans.

// Jongmi Lee 1 , Ki Hyun Park 2 , Ji Hyeong Ryu 2 , Hyun Jin Bae 2 , Aeran Choi 1 , Hyeyoung Lee 1, 3 , Jihyang Lim 1 , Kyungja Han 1 , Cho Hyun Park 4 , Eun Sun Jung 5 and Eun-Jee Oh 1 1 Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea 2 Department of Biomedical Science, Graduate School, The Catholic University of Korea, Seoul, Korea 3 SamKwang Medical Laboratories, Seoul, Korea 4 Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea 5 Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Correspondence to: Eun-Jee Oh, email: ejoh@catholic.ac.kr Keywords: natural killer cell activity, interferon-gamma, diagnostic marker, gastric cancer Received: May 10, 2017 Accepted: June 28, 2017 Published: July 31, 2017 ABSTRACT Background/Aim: Decreased Natural killer cell activity (NKA) for interferon-gamma production (NKA-IFNγ) has been reported in cancer patients. The aim of this study was to determine the diagnostic performance of NKA-IFNγ for gastric cancer (GC). Results: NKA-IFNγ levels were decreased in 261 GC patients with all stages of tumor compared to those in 48 healthy donors ( P < 0.001), and lower levels of NKA-IFNγ were associated with higher GC stages. NKA-IFNγ levels were also associated with clinicopathological parameters including tumor size, depth of invasion, and lymph node metastasis. NKA-INFγ assay had better diagnostic value (AUC = 0.822) compared to serum CEA (0.624) or CA19-9 assay (0.566) ( P < 0.001). Using different cut-off levels, serum CEA and CA19-9 showed sensitivities of 6.1-14.2% and 4.2-28.0%, respectively, which were much lower than that of NKA-IFNγ (55.6-66.7%). Methods: This study included 261 patients with newly diagnosed GC and 48 healthy donors. NKA for IFNγ was determined by enzyme immunoassay after incubation of whole blood, and diagnostic performance was evaluated. Conclusions: NK cell activities for IFNγ production could be used as a supportive non-invasive tumor marker for GC diagnosis.

Objective Short tandem repeat (STR) loci are most frequently used for chimerism analysis after hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the practical informativeness of STR chimerism by integrating theoretical and analytical points. Methods Theoretical and practical informativess of 16 STR loci were evaluated from 1249 pairs of recipients and donors who were prepared for HSCT. Results Theoretical informativeness was influenced by genetic diversity including allele frequency and heterozygosity, and was higher in the unrelated HSCT group (90.5 ± 5.3%) compared to the related HSCT group (66.2 ± 4.4%). Practical informativeness was lower than theoretical (6.1 ± 1.7%) because several STR loci were excluded due to stutter peaks and less reliable results, especially in type II-2 donor-recipient match pattern with no recipient-specific allele. We simulated an efficient STR combination for reliable chimerism analysis. Eight informative STR loci were required to analyze chimerism with at least one practically informative locus in the related HSCT group (D18S51, FGA, D2S1338, D13S317, D8S1179, D21S11, D16S539 and D7S820) while only three loci were needed in the unrelated group (D2S1338, FGA and D18S51). A minimum set of 2, 4 or 7 STR loci were required to provide at least 1, 3 or 5 practically informative loci in 95% of the unrelated HSCT group while 3, 8 or 12 loci were required in the related HSCT group. Conclusion We deducted the practical informativeness of STR chimerism, identified the major influencing factors on the practical informativeness of each STR locus, and successfully simulated the efficient STR combination for reliable chimerism analysis.

PurposeTo investigate the association between urinary cotinine levels as an objective biological marker for exposure to nicotine and refractive status.Patients and methodsThis cross-sectional study analyzed data from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. A total of 1139 Korean adolescents aged 12-18 years were enrolled. Urinary cotinine concentrations and other potential risk factors for myopia were examined. Correlation analyses and multivariate regression analysis were performed to investigate the association between urinary cotinine level and refractive error.ResultsSpherical equivalent correlated significantly with urinary cotinine concentration (r=0.104, P=0.011). Lower urinary cotinine level was associated with a trend toward more myopic refractive errors (P for trend=0.003). After adjusting for age, sex, area of residence, physical activity, serum 25-hydroxyvitamin D level, parental income level, and receipt of basic livelihood security, subjects with a low urinary cotinine level had a significantly increased risk of myopia

There are several screening tools for colorectal cancer (CRC). Most are limited in their application. The fecal occult blood test (FOBT) is a first-step screen for CRC that is limited by low sensitivity. This study aimed to prove the efficacy of combined FOBT and fecal carcinoembryogenic antigen (fCEA) as a CRC screening test. Stool samples were collected preoperatively from 166 CRC patients expected to undergo elective surgery and from normal control patients. A fecal CEA/FOBT dual kit was created and the results from the use of this dual kit were compared against other clinicopathologic parameters. FOBT was positive in 103 of the 166 (62.0%) CRC patients and fCEA was positive in 114 (68.7%) patients, showing a statistically positive relationship. Among 63 FOBT negative patients, 29 (17%) cases were CEA positive. Thus, the CEA/FOBT dual test could detect CRC in 79.5% of the patients (132/166). The sensitivity and specificity of the dual FOBT/CEA test was 79.5% and 97.9%, respectively. The FOBT/CEA dual test has increased sensitivity compared to the FOBT test and may have merit as a screening device for colorectal cancer. Population-based studies are required to confirm this potential.

Background The association between atopic diseases and inflammatory bowel diseases (IBD) still remains unclear. We conducted a nationwide population-based study to investigate the effect of atopic diseases on the development of IBD. Methods A total of 9,950,548 subjects who received medical check-up between 2009 and 2012 were included and followed up until 2017. The presence of any atopic disease including atopic dermatitis (AD), allergic rhinitis (AR), and asthma were evaluated. Patients who developed IBD including Crohn’s disease (CD) and ulcerative colitis (UC) were identified using the claims data from National Health Insurance. Results During a mean follow up of 7.3 years, 1,426 (0.014%) subjects developed CD and 5,916 (0.059%) subjects developed UC. The incidences of CD (per 100,000 person-years) were 4.088, 2.255, and 2.344 in patients with AD, AR, and asthma,, respectively. The incidences of UC were 11.926, 9.857, and 9.377 in patients with AD, AR, and asthma, respectively. Multivariable analysis revealed that the adjusted hazard ratios (aHR) for incident CD in patients with AD, AR, and asthma were 2.21, 1.33, and 1.59 (95% confidence interval (CI) 1.251–3.896, 1.152–1.532, and 1.186–2.123, respectively) compared with controls. The risk for incident UC in patients in AD, AR, and asthma were 1.51, 1.32, and 1.28 (95% CI 1.081–2.101, 1.235–1.416, and 1.110–1.484, respectively) compared with controls. Moreover, increase in the number of atopic diseases gradually increased the risk for CD and UC; CD showed aHR of 1.36 and 1.65 (95% CI 1.180–1.571 and 1.143–2.370), and UC showed aHR of 1.30 and 1.49 (95% CI 1.216–1.398 and 1.247-1.170) in one, and two or more atopic diseases, respectively. Conclusion Patients with any atopic diseases showed an increased risk for IBD, while an increase in the number of atopic diseases gradually increased the risk for IBD.

Background The incidence of inflammatory bowel disease (IBD) is increasing in Asia. Numerous risk factors associated with IBD development have been investigated. This study aimed to demonstrate the risk factors of Crohn’s disease (CD) diagnosed in persons aged >40 years in South Korea and to specify any differences between age groups by using the National Health Insurance Service (NHIS) database. Methods Using the National Health Insurance Service (NHIS) database, a total of 14,060,821 persons aged >40 years who underwent national health screening in 2009 were followed up until December 2017. Patients with newly diagnosed CD were enrolled and compared with non-CD cohort. CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration programme codes from the NHIS database. The mean follow-up periods were 7.39 years. Age and sex were adjusted for in the multivariate analysis model. Results During the follow-up, 1337 (1.33/100,000) patients developed CD. Men in the middle-aged group (40–64 years) had a higher risk than women (adjusted HR [aHR] 1.46, 95% CI 1.29–1.66); however, this difference tended to disappear as the age of onset increases. In the middle-aged group, patients with a history of smoking (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 1.06–1.58) and anemia (aHR 1.99, 95% CI 1.67–2.36) had a significantly higher CD risk. In the elderly group (age, ³65 years), ex-smoking and anemia also increased the CD risk (aHR 1.58 [95% CI 1.16–2.18] and 1.91 [95% CI 1.53–2.38], respectively). Especially in the middle-aged group, those with chronic kidney disease (CKD) had a statistically elevated CD risk (aHR 1.38, 95% CI 1.06–1.79). Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups. (Middle-aged: aHR 0.76 [95%CI 0.65–0.87] and aHR 0.38 [95%CI 0.27–0.53], respectively) (elderly-group: aHR 0.57 [95%CI 0.42–0.77] and aHR 0.52 [95%CI 0.32-.83], respectively) For regular physical activity and dyslipidemia, negative correlation between CD incidences was proved only in the middle-aged group (aHR 0.85 [95%CI 0.74–0.96] and aHR 0. [95%CI 0.75 [95% CI 0.63–0.89], respectively). Conclusion This study demonstrated four risk factors (ex-smoking, anemia, CKD, and lower BMI) and three possible protective factors (alcohol consumption, physical activity, and dyslipidemia) for CD in Asians age >40 years. Individuals with potential risk factors need more cautious monitoring for CD.

Background Although rivaroxaban 15 mg was only given to patients with creatinine clearance (CrCl) Methods Using the Korean National Health Insurance Service database, patients with AF and normal or mildly impaired renal function (CrCl ≥50mL/min) and naïve to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: rivaroxaban 20 mg (R20) vs. warfarin (n=15,584), rivaroxaban 15 mg (R15) vs. warfarin (n=11,554), and R20 vs. R15 (n=10,392). Hazard ratios (HRs) for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed. Results Among the pooled total study population, mean age was 66.9±10.9 years, 62.2% were male, mean CHA2DS2-VASc score was 3.16±1.79, and mean CrCl was 83.6±42.0 mL/min (median 78.4 mL/min, IQR 67.7–91.0 mL/min). A substantial proportion (42.6%) of patients with CrCl ≥50 mL/min were prescribed off-label R15 for stroke prevention in the Korean AF population. Compared to warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of ICH), and all-cause death (Figure). Overall, both R20 and R15 had better results for the composite clinical outcome compared to warfarin (HR: 0.617, 95% CI: 0.550–0.691 for R20, and HR: 0.759, 95% CI: 0.675–0.853 for R15). Compared to off-label R15, on-label R20 showed a nonsignificant trend toward lower risks of ischemic stroke, hospitalization for GI bleeding, hospitalization for major bleeding, and all-cause death. Overall, on-label R20 had better results for the composite clinical outcome compared to off-label R15 in patients with CrCl ≥50 mL/min (HR: 0.852, 95% CI: 0.735–0.988). This benefit was consistently observed in patients aged ≥80 years and those Conclusions Among Asians with AF and CrCl ≥50mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, ICH, major bleeding, and all-cause death without significantly increased risk of GI bleeding compared with warfarin. In patients with CrCl ≥50mL/min, on-label R20 showed better results for the composite clinical outcome compared to off-label R15.

Background Visit-to-visit blood pressure (BP) variability is a known risk factor for stroke, but the association between BP variability and atrial fibrillation (AF) incidence is uncertain. We sought to evaluate the association between BP variability and incident AF. Methods We identified 8,063,922 subjects (mean age 48 years; 59% men) who had ≥3 health checkups provided by the Korean National Health Insurance Corporation between 2004 and 2010. Systolic and diastolic BP variability was defined as variability independence of the mean (VIM). VIM was divided into four groups and high variability of BP was defined as the highest quartile values. The primary end point was new-onset atrial fibrillation. Results During a mean 7 years of follow-up, 140,086 subjects were newly diagnosed with AF (2.53 per 1000 person-years). High variation in BP was associated with an increase in the risk of AF (SBP: hazard ratio [HR], 1.060; 95% confidence interval [CI], 1.044–1.075, DBP: HR, 1.066; 95% CI, 1.050–1.082) compared with subjects with lowest quartile of BP. Among subjects with high variation both in SBP and DBP, the risk of AF was 7.6% higher than subjects without high variation in SBP and DBP. The risk of high BP variation on new-onset AF was more obvious in high-risk patients. The association of high BP variability with AF was being stronger for high-risk subjects who were older (≥65 years), with diabetes, or with CKD compared with subjects who were younger, without diabetes, or without CKD. Conclusions Fluctuation in SBP and DBP was associated with higher incidence of AF, especially in high-risk subjects, independent of traditional AF risk factors.

Background High levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease. We investigated their roles in the development of atrial fibrillation (AF). This is the largest cohort study yet on the association between lipid levels and AF, and the first study on the association between lipid variability and AF. Methods A nationwide population-based cohort of 3,828,652 adults (mean age 43.9 years) from the Korean National Health Insurance Service database without prevalent AF, not on lipid-lowering medication, and with at least 3 measurements of each lipid parameter at 1–2 year intervals over a 4-year period were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured, and lipid variability was calculated using variability independent of mean. The cohort was divided into quartiles by baseline lipid levels and lipid variability, and followed up for incident AF. Results During median 3.4 years of follow-up, AF was newly diagnosed in 13,240 (0.35%). AF development was inversely associated with TC and LDL-C levels (for top vs. bottom quartile; TC, hazard ratio [HR] 0.76, 95% confidence interval [95% CI] 0.72–0.80); LDL-C, HR 0.78, 95% CI 0.74–0.82) in both sexes, and with TG levels in men (HR 0.85, 95% CI 0.80–0.90). Meanwhile, AF development was associated with higher LDL-C and HDL-C variability (for top vs. bottom quartile; LDL-C, HR 1.16, 95% CI 1.10–1.22; HDL-C, HR 1.08, 95% CI 1.03–1.14) in both sexes, and with TC variability in men (HR 1.16, 95% CI 1.10–1.22). Conclusions Lower cholesterol levels (TC, LDL-C) and higher cholesterol variability (LDL-C, HDL-C) were associated with higher risk for AF. Low TG levels and high TC variability were also associated with AF incidence in men. These findings support the “cholesterol paradox” in AF, and suggest that cholesterol variability is also a risk factor for AF development.

Background Bodyweight fluctuation is a risk factor for cardiovascular events and death. We investigated whether bodyweight variability is also a risk factor for atrial fibrillation (AF) development. Methods A nationwide population-based cohort of 8,091,401 adults from the Korean National Health Insurance Service database without previous history of AF and with at least 3 measurements of bodyweight over a 5-year period was followed up for incident AF. Intra-individual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quartile with highest bodyweight variability (Q4) with Q1–3 as reference. Results During median 8.1 years of follow-up, AF was newly diagnosed in 158,347 (2.0%). Increasing bodyweight variability was associated with AF development after adjustment for baseline bodyweight, height, age, sex, lifestyle factors and comorbidities: each increase of 1-SD in bodyweight variability was associated with 5% increased risk of AF development (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.04–1.05), and subjects with highest bodyweight variability (Q4) showed 14% increased risk of AF development compared to those in the quartile with lowest bodyweight variability (HR 1.14, 95% CI 1.12–1.15). When the cohort was grouped by body mass index (BMI) into underweight, normal weight, overweight, obese (Figure 1A), subjects with high bodyweight variability showed a shallow U-shaped relationship of BMI with AF incidence, with the highest incidence rate of AF in the underweight group. On the other hand, subjects with reference bodyweight variability showed a proportional increase of AF incidence with BMI, with the highest AF incidence in the obese group. High bodyweight variability was significantly associated with AF development in all BMI groups except in the very obese (BMI≥30) in multivariable analysis, and this association was stronger in subjects with lower bodyweight. In underweight subjects, high bodyweight variability was associated with 16% increased risk of AF development (HR 1.16, 95% CI 1.08–1.24). Obese subjects with high bodyweight variability compared to those with reference variability showed lower crude AF incidence rates, but after multivariable analysis, AF risk was increased (obese stage I) or comparable (obese stage II). When the cohort was grouped by total bodyweight change (Figure 1B), subjects with high bodyweight variability showed higher AF incidence and elevated AF risk on multivariable analysis in all weight change groups. Subjects with overall weight loss (≥-5%) and high bodyweight variability showed the highest AF incidence and AF risk (HR 1.12, 95% CI 1.09–1.15). Figure 1 Conclusions Fluctuation in bodyweight was independently associated with higher risk of AF development. The association of high bodyweight variability with AF development was especially stronger in subjects with lower bodyweight, and in subjects with overall weight loss (≥-5%)

Background Patients with atrial fibrillation (AF) often have concomitant valvular heart disease (VHD), especially in Asia. There are limited data on non-vitamin K antagonist oral anticoagulants (NOAC) impact on outcomes for stroke prevention and bleeding for these patients in real world clinical practice. Purpose To investigate the effectiveness and safety of NOACs compared with warfarin in patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHD. Methods We identified oral anticoagulants naive patients with AF and EHRA type 2 VHD from the Korean National Health Insurance Service database between 2014 and 2016 (n=2,671 taking warfarin; n=3,058 taking NOAC). Six clinical outcomes including ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GI), major bleeding, all-cause death, and their composite outcome and fatal clinical events (any events that led to death within 30-day of its occurrence) were evaluated. Inverse probability of treatment weighting (IPTW) method was used to balance covariates between the two groups. Results After weighted using 5% trimmed IPTW method (n=2371 taking warfarin; n=2792 taking NOAC), the mean age was 71.2 years, male was 57% and CHA2DS2-VASc score was 3.9. During a mean 1.4-year follow-up, weighted incidence rate of ischemic stroke, ICH, GI bleeding, and all-cause death were lower in the NOAC group than in the warfarin group. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53–0.96), GI bleeding (HR 0.50, 95% CI 0.35–0.72) and major bleeding (HR 0.61, 95% CI 0.45–0.80). Although NOAC and warfarin groups showed similar incidence rate of ICH, NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group (HR 0.28, 95% CI 0.07–0.83). Overall, NOACs were associated with a lower risk of the composite outcome (HR 0.68, 95% CI 0.58–0.80). For an exploratory analysis, patients with EHRA type 1 VHD (n=366 taking warfarin; n=345 taking NOAC) was evaluated. In multivariable Cox regression analysis, NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death and composite outcome. Clinical outcome in AF patients with VHD Conclusion In this nationwide Asian AF population with EHRA type 2 VHD, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin.

We investigated whether oral health, represented by missing teeth, was associated with an increased risk of cardiovascular disease, including myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality. Subjects who underwent routine dental examinations and health checkups provided by the Korean National Health Insurance from 2007 to 2008 ( n = 4,440,970) were followed up for incident MI, HF, stroke, and death until 2016. During follow-up of 7.56 y, 68,063 (1.5%) subjects died, and 31,868 (0.7%) were admitted for MI, 22,637 (0.5%) for HF, and 30,941 (0.7%) for stroke. Cardiovascular events and mortality increased in proportion to tooth loss. Tooth loss was an independent risk factor for cardiovascular events after multivariable analysis adjusted for cardiovascular risk, behavioral, and income factors. Each missing tooth was associated with an approximately 1% increase in MI (HR, 1.010; 95% CI, 1.007 to 1.014), 1.5% increase in HF (HR, 1.016; 95% CI, 1.013 to 1.019) and stroke (HR, 1.015; 95% CI, 1.012 to 1.018), and 2% increase in mortality (HR, 1.022; 95% CI, 1.020 to 1.023). Having ≥5 missing teeth substantially increased risk for cardiovascular outcomes, and even a small number of missing teeth (1 to 4) was associated with an increased risk for MI, stroke, and death. This association was consistent in subgroup analyses and especially strong among the younger subjects (age

Background:Many studies have shown a link between gout and metabolic syndrome (MetS). It is well known that lifestyle modifications such as weight reduction and abstinence from alcohol are effective in the treatment of gout, but data are lacking on how exactly the change of metabolic parameters affects gout.Objectives:The purpose of this study was to investigate the relationship between gout risk and metabolic parameters in a nationwide population based young adult cohort, and to determine whether changes in metabolic parameters affect gout risk changes.Methods:Among adults aged 20-39 years who participated in national health check-up programs from 2009 to 2012, a total of 6,290,914 subjects were included in the study, excluding subjects who were previously diagnosed with gout. To determine the effect of changes in metabolic parameters on gout incidence, 2,701,138 subjects who participated in the health examination once more 2 years later were used for the analysis. Outcome was defined as the occurrence of gout, when the ICD-10 code (M10) was registered twice in the claim database. The Cox proportional hazard model and Kaplan Meier curve were used for the analysis.Results:The incidence rate of gout was higher in those with MetS compared to those without (10.1 vs. 3.6 per 1,000 person-years). The risk of gout in people with MetS was 85% higher (adjusted HR 1.85, 95% CI 1.83-1.87) and was more significant in men than in women (adjusted HR 1.88 in male and 1.56 in female). Each component of MetS was also associated with increased gout risk, and hypertriglyceridemia showed the highest adjusted HR. The greater the number of MetS components, the higher the gout risk. The risk of gout was 70% higher in those who had MetS consistently (adjusted HR 1.71, 95% CI 1.67-1.75) and 44% higher in those with newly developed MetS (adjusted HR 1.47, 95% CI 1.40-1.48) than those who did not have MetS at the two health examinations. Similar risk patterns were observed according to the change of each metabolic parameter. Among the metabolic parameters, the change in hypertriglyceridemia was associated with the greatest difference in the change in gout risk.Conclusion:In young adults, MetS was associated with a higher risk of gout, especially with more components, the higher the risk. Since the occurrence of MetS is associated with an increased risk of gout, prevention of MetS would be important to reduce gout incidence.Disclosure of Interests:None declared

Background We evaluated the reliability and accuracy of the combined use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) bacterial identification and Vitek 2 antimicrobial susceptibility testing (AST) for bacteria from positive blood culture bottles. Methods Direct identification and AST were performed in parallel to the standard methods in monomicrobial positive blood culture bottles. In total, 254 isolates grown on aerobic and/or anaerobic bottles were identified with MALDI-TOF Vitek MS (bioMérieux, France), and 1,978 microorganism/antimicrobial agent combinations were assessed. For isolates from anaerobic bottles, an aliquot of the culture broth was centrifuged, washed, and filtered through a nylon mesh. For isolates from aerobic/pediatric bottles, a lysis step using 9.26% ammonium chloride solution and 2% saponin solution was included. Results The overall correct identification rate was 81.8% (208/254) and that for gram-positive/gram-negative isolates was 73.9%/92.6%, respectively, and it was 81.8%, 87.6%, and 57.9% for isolates from aerobic, anaerobic, and pediatric bottles, respectively. Identification was not possible in 45 cases, and most of these isolates were streptococci (N=14) and coagulase-negative staphylococci (N=11). Misidentification occurred only in one case. Compared with standard methods, direct AST showed 97.9% (1,936/1,978) agreement with very major error of 0.25%, major error of 0.05%, and minor error of 1.8%. Conclusions This simple and cost-effective sample preparation method gives reliable results for the direct identification and AST of bacteria. For the identification of streptococci and coagulase-negative staphylococci, the method should be further improved.

Whereas antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) have diagnostic significance, the dense fine speckled (DFS) pattern on HEp-2 cells may be an exclusionary marker for ANA-associated rheumatic disease (AARD). The aim of this study was to evaluate a new algorithm considering anti-DFS70 antibodies for routine ANA testing.From ANA requested sequential 10 528 sera, 181 sera samples showing the DFS pattern were additionally tested for anti-DFS70 antibodies by an enzyme-linked immunosorbent assay (ELISA-DFS70) and for specific-ANAs. Specific-ANAs(+)/IIF-DFS(-) control sera samples (n = 50) were also tested.Of the 181 IIF-DFS-positive sera samples, 82.9% (n = 150) were from non-AARD patients and 112 (61.9%) patients had non-rheumatic diseases (NRD), including the most common clinical feature of dermatitis (18.2%). The ELISA-DFS70 was positive in 109 (60.2%) sera and was negative in all control sera. Specific-ANAs were similarly detected as 25.7% (28/109) and 22.2% (16/72) of ELISA-DFS70(+) and ELISA-DFS70(+) patients, respectively (p 0.05). The prevalence of non-AARD was 95.1% and 25.1% in the ELISA-DFS70(+)/specific-ANAs(-) and ELISA-DFS70(-)/specific-ANAs (+) groups, respectively.In patients with a HEp-2 DFS pattern, the additional ELISA-DFS70 and specific-ANAs test could improve the efficiency of diagnosing AARD. The detection of anti-DFS70 antibodies should be included in test algorithms for ANA testing.

Background:Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect any organ of the body. Nervous system involvement of SLE lead to a variety of neurologic and psychiatric manifestations, which are called neuropsychiatric lupus. Cognitive dysfunction may appear as part of neuropsychiatric lupus. There are several papers on the increase in dementia risk in SLE patients, but data are not sufficient and there is little data on whether SLE affects dementia differently depending on the dementia subtype.Objectives:We evaluate dementia incidence and risk in SLE patients in a nationwide population-based cohort and determine whether the risk is different for each dementia subtype.Methods:We identified patients aged 40 years or more, with systemic lupus erythematosus between 2008 and 2014 using the database of the National Health Insurance Service (NHIS) of south Korea. Patients who had previously been diagnosed with dementia were excluded from the study. A total of 11,288 SLE patients and 56,440 control subjects with a 1:5 age- and sex-matching were included in the study. The primary outcome of the study was incident dementia, which was defined by an ICD-10 code and the use of dementia medications. Kaplan-Meier curves and Cox proportional hazards regression analysis were used for the analysis.Results:The incidence rate of dementia was higher in SLE cohort (3.90 per 1,000 person-years) than control cohort (2.73 per 1,000 person-years). Incidence rates of Alzheimer disease and vascular dementia were also higher in SLE cohort than control. SLE patients had a higher risk of dementia compared to control cohorts without SLE (crude hazard ratio 1.43, 95% CI 1.25-1.63). In patients with SLE, the risk of Alzheimer’s disease was 1.4 times higher and the risk of vascular dementia 1.6 times higher than non-SLE control.Conclusion:In this nationwide population-based cohort study, SLE patients had a 1.4-fold higher risk of incident dementia compared to patients without SLE. Further studies are warranted to identify mechanisms of increased risk of dementia in SLE patients. Monitoring of dementia incidence in SLE patients is needed in clinical practice.Disclosure of Interests:None declared

Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (n = 23), non-reactivation (n = 24) versus CMV disease (n = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcR&gamma, CD3&zeta, +NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFN&gamma, ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells&rsquo, maturation and cytotoxic/IFN&gamma, production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.