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This study investigated the case of a nineteen-year-old female patient with chronic nausea, vomiting, and abdominal distension, who was diagnosed with CNVS and Spleen-Qi deficiency. Subjective symptoms were recorded with the Numerical Rating Scale (NRS) every morning, and the Gastrointestinal Symptom Rating Scale (GSRS) was used on the days of admission and discharge. For eleven days following admission, she took Bojungikki-tang-gagam and received acupuncture and moxibustion therapy. After three days of treatment, her nausea and vomiting ceased, and abdominal distension improved from NRS 3 to 0 after seven days of treatment. The GSRS score for the specific symptoms improved from 3 to 2; however, the total score remained largely unchanged (from 20 to 21). This case suggests that Korean medical treatment may improve CNVS.

Critical limb ischemia is a condition in which tissue necrosis occurs due to arterial occlusion, resulting in limb amputation in severe cases. Both endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are needed for the regeneration of peripheral arteries in ischemic tissues. However, it is difficult to isolate and cultivate primary EC and SMC from patients for therapeutic angiogenesis. Induced pluripotent stem cells (iPSCs) are regarded as useful stem cells due to their pluripotent differentiation potential. In this study, we explored the therapeutic efficacy of human iPSC‐derived EC and iPSC‐derived SMC in peripheral artery disease model. After the induction of mesodermal differentiation of iPSC, CD34+ progenitor cells were isolated by magnetic‐activated cell sorting. Cultivation of the CD34+ progenitor cells in endothelial culture medium induced the expression of endothelial markers and phenotypes. Moreover, the CD34+ cells could be differentiated into SMC by cultivation in SMC culture medium. In a murine hindlimb ischemia model, cotransplantation of EC with SMC improved blood perfusion and increased the limb salvage rate in ischemic limbs compared to transplantation of either EC or SMC alone. Moreover, cotransplantation of EC and SMC stimulated angiogenesis and led to the formation of capillaries and arteries/arterioles in vivo. Conditioned medium derived from SMC stimulated the migration, proliferation, and tubulation of EC in vitro, and these effects were recapitulated by exosomes isolated from the SMC‐conditioned medium. Together, these results suggest that iPSC‐derived SMC enhance the therapeutic efficacy of iPSC‐derived EC in peripheral artery disease via an exosome‐mediated paracrine mechanism., Co‐transplantation of the induced pluripotent stem cell (iPSC)‐derived endothelial cells and smooth muscle cells enhanced the therapeutic efficacies of endothelial cells and smooth muscle cells in a murine hindlimb ischemia model. Smooth muscle cells promoted angiogenesis and therapy of peripheral artery disease through exosome‐mediated paracrin mechanism.

Metformin is the first option in managing type 2 diabetes mellitus (DM) and has pleotropic effects. We studied the incidence of lung cancer in patients who received metformin therapy.This study was retrospectively designed and based on the Korean National Health Insurance Service-National Health Screening Cohort to determine whether metformin reduces lung cancer risk in the diabetic population. At baseline, all participants were 40 to 69 years old and were categorized into 3 groups: metformin nonrecipients with DM, metformin recipients with DM, and the nondiabetic group.A total of 336,168 individuals were included in the final analysis (314,291 nondiabetic individuals, 8806 metformin recipients, and 13,071 metformin nonrecipients). The study median follow-up period was 12.86 years. The estimated cumulative lung cancer incidence of metformin nonrecipients, metformin recipients, and the nondiabetic group was 1.80%, 1.97%, and 1.24% in men and 1.87%, 0.61%, and 0.41% in women, respectively (P .05). Compared to metformin nonrecipients, the hazard ratios (95% confidence intervals) for lung cancer incidence of metformin recipients and the nondiabetic group were 1.287 (0.979-1.691) and 0.835 (0.684-1.019) in men and 0.664 (0.374-1.177) and 0.553 (0.359-0.890) in women, respectively. The hazard ratios (95% confidence intervals) were statistically significant in male ever smokers (0.784 [0.627-0.979]) and female nonsmokers (0.498 [0.320-0.774]) after stratification according to smoking status.Metformin therapy did not reduce lung cancer incidence in the diabetic population. However, individuals without DM were at a lower risk of lung cancer, especially in male ever smokers and female nonsmokers.

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].

Cancer is the number one cause of death in Korea. This study aimed to investigate if statin use in cancer survivors was inversely associated with all-cause mortality.Data from the 2002 to 2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) were used. The Kaplan-Meier estimator was used to estimate the survival function according to statin usage. Cox proportional hazards regression models were adopted after stepwise adjustment for potential confounders to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The median follow-up duration was 10.0 years. Statin users had a higher percentage of diabetes and hypertension in both sexes. Survival rates of statin users were higher than non-users (p-values0.001 in men and 0.021 in women). Compared to non-users, the HRs (95% CIs) of statin users for all-cause mortality were 0.327 (0.194-0.553) in men and 0.287 (0.148-0.560) in women after adjustment for potential confounding factors.Statin users in cancer survivors had higher survival rate than non-users in both sexes.

BACKGROUND Few studies have reported on the trends in influenza vaccination rates among cancer survivors in Korea. We investigated these trends over a recent 11-year period (2005-2015). METHODS Data were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) III- VI (2005-2015). After excluding individuals younger than 40 years of age, the participants included 2,210 cancer survivors (861 men and 1,349 women). We categorized these study participants into four groups according to age and sex. RESULTS The influenza vaccination rate decreased significantly among male cancer survivors, with rates of 74.8, 64.7, 56.2, and 55.2% (β coefficient=-0.257, P for trend

Background Insulin resistance is associated with the incidence of diabetes and cardiovascular diseases such as myocardial infarction. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is positively correlated with insulin resistance. This study aimed to investigate the relationship between the TG/HDL-C ratio and the incidence of diabetes in Korean adults. Methods This retrospective study used data from the National Health Insurance Service-National Health Screening Cohort. The TG/HDL-C ratio was divided into three tertiles, the T1, T2, and T3 groups, based on sex. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes using multivariate Cox proportional hazards regression analyses. Results A total of 80,693 subjects aged between 40 and 79 years were enrolled. The median follow-up period was 5.9 years. The estimated cumulative incidence of diabetes in the T1, T2, and T3 groups was 5.94%, 8.23%, and 13.50%, respectively, in men and 4.12%, 4.72%, and 6.85%, respectively, in women. Compared to T1, the fully adjusted HRs (95% CIs) of the T2 and T3 groups for new-onset diabetes were 1.17 (1.06–1.30) and 1.47 (1.34–1.62), respectively, in men and 1.20 (1.02–1.42) and 1.52 (1.30–1.78), respectively, in women. Conclusions Increased TG/HDL-C ratio was significantly associated with a higher risk of new-onset diabetes in both sexes.

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and “healthy aging” become more and more important, these guidelines are also expected to increase in clinical usefulness.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride–glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p &lt, 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

Single-incision cholecystectomy is a surgical method that offers comparable results to conventional laparoscopic cholecystectomy. However, a high risk of postoperative incisional hernia is an issue in single-incision cholecystectomy. This study evaluated the risk factors and incidences of incisional hernia after single-incision cholecystectomy and the advantage issue of using barbed suture material during wound closures.A total of 1,111 patients underwent laparoscopic or robotic single-incision cholecystectomy between March 2014 and February 2020 at our institution at CHA Bundang Medical Center. During this period, there were 693 patients who underwent wound closure with monofilament suture material (Monosyn 2-0; B. Braun) and the other 418 patients used barbed suture material (Stratafix 2-0; Ethicon).The two patient groups were comparable in age, body mass index, and diagnosis. The total incidence of incisional hernia after single-incision cholecystectomy was 0.5% (five cases). All patients who developed incisional hernia were in the monofilament suture material group (0.7% vs. 0%,Our study showed a low incidence of incisional hernia, all of which occurred in the monofilament suture material group. If technically appropriate, single-incision cholecystectomy does not appear to present a high incidence of hernia. Barbed suture material can be safely applied in wound closure showing comparable incisional hernia incidence to monofilament suture material.

We evaluated the potential serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) roles in diagnosing and monitoring brain metastases (BMs). We included 70 patients with newly diagnosed BMs, 71 age- and cancer type-matched patients without BMs, and 67 healthy controls (HCs). We compared sNfL and sGFAP levels among the groups using a single-molecule array immunoassay. We prospectively followed 26 patients with BMs every 2–3 months by measuring sNfL and sGFAP levels and performing magnetic resonance imaging (MRI) scans. The sNfL and the sGFAP levels were higher in patients with BMs (medians: sNfL, 63.7 µL, sGFAP, 819.5 pg/µL) than in those without BMs (sNfL, 13.3 µL, sGFAP, 154 pg/µL, p &lt, 0.001) and HCs (sNfL, 12.5 µL, sGFAP, 135 pg/µL, 0.001). The sNfL and the sGFAP cutoff levels had a sensitivity and a specificity of 91%. The sGFAP cutoff level had a sensitivity of 91% and a specificity of 97%. The sNfL and the sGFAP levels were related to the BM size but not to the primary cancer type. After BM treatment, sNfL and sGFAP levels decreased with reduced BM lesions on MRI, however, they increased when BMs progressed. sNfL and sGFAP are potential biomarkers for BM screening in cancer patients.

Background and aims We investigated the association between statin use and site-specific risk of colorectal cancer in individuals with hypercholesterolemia. Methods and results This study is based on the National Health Insurance Service-National Health Screening Cohort, conducted during 2002–2015. Statin users were classified as high and low users according to medication possession ratio (MPR). Statin nonusers comprised participants who did not use statins during the entire follow-up period. In total, 17,737 statin users and 13,412 statin nonusers were included in the analysis, with a median follow-up period of 12.7 years. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate prospective association between statin usage and colorectal cancer risk. In total, 378 (2.3%) of 16,588 male participants and 239 (1.6%) of 14,561 female participants had colorectal cancer during the follow-up period. Compared to nonusers, fully adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for colorectal cancer risk in high statin users were 0.56 (0.42–0.75) in men and 0.64 (0.46–0.90) in women. In men, the fully adjusted HRs for proximal and rectal cancer for high users were 0.29 (0.15–0.56) and 0.52 (0.35–0.78), respectively, compared to those for nonusers. In women, statistical significance was seen only in rectal cancer (HR 0.43 [0.25–0.72]) but not in proximal or distal colon cancer. Conclusions High statin users with hypercholesterolemia were associated with lower risk of overall colorectal cancer, especially proximal colon cancer in men and rectal cancer in both sexes.

Objectives: Serum neurofilament light chain (sNfL) has been proposed a potential biomarker in multiple sclerosis (MS) based on mainly cross-sectional observations in Western population. To clarify clinical implication of sNfL, we longitudinally analysed sNfL levels at multiple time points in Korean MS patients undergoing alemtuzumab therapy. Methods: Between 2016 and 2018, 144 sera from 17 MS patients treated with alemtuzumab at National Cancer Centre and 35 sera from 35 age- and gender-matched healthy controls (HCs) were collected for a longitudinal study with a mean 21-month follow-up. The sera were measured for sNfL levels using single molecule array. Patients were classified into two groups: evidence of disease activity (EDA) or no evidence of disease activity (NEDA). Results: During alemtuzumab therapy, sNfL levels in EDA patients were significantly higher than those in NEDA patients and HCs ( p Conclusion: These results suggest that sNfL is a promising monitoring biomarker for personalized therapeutics in MS patients.

Digital breast tomosynthesis (DBT) system is a novel imaging modality that strongly depends on the detector performance. The effective detective quantum efficiency (eDQE) is a newly accepted system of performance analysis metric that solves the disadvantages of conventional DQE evaluations, which do not consider clinical operating conditions. To evaluate the eDQE, we used the direct-conversion based Anrad detector and the indirect-conversion based Dexela detector. Our aim is to study the performance of such detectors when they are mounted on a prototype DBT system. The prototype DBT system consists of a CsI(Tl) scintillator/CMOS-based flat panel digital detector and an a-Se based direct conversion detector developed by the Korea Electrotechnology Research Institute (KERI). The performance of the two detectors was compared on the basis of scatter fraction, transmission factor, effective modulation transfer function (eMTF), and effective normalized noise power spectrum (eNNPS). As a result, the Dexela detector is characterized by a decreasing eNNPS trend as the spatial frequency increases, whereas the Anrad eNNPS looks almost independent of the spatial frequency. The eMTF was found to be higher in the Anrad detector compared to that in the Dexela one for all frequencies. The eDQE values at 1 cycle/mm (low frequency) were 0.11 and 0.17 for the Anrad and Dexela detectors, respectively, and the values of the spatial frequency f e D Q E ( 0.1 ) , corresponding to eDQE = 0.1, were 1.25 and 2.81 cycles/mm for the Anrad and Dexela detectors, respectively. The Dexela detector also presented a higher contrast-to-noise ratios (CNRs) for all different sizes of μCa groups, thus demonstrating overall better eDQE results in imaging performance compared to the Anrad detector.

Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell–mediated disease within 1 year of the first cycle of alemtuzumab. We raise awareness that severe B cell–mediated disease activation could develop, even after two cycles of alemtuzumab, in some vulnerable MS patients; therefore, individualized therapeutic strategies should be considered in clinical practice. We also propose that a novel regulatory B-cell subset may be a candidate for a predictive biomarker of disease activation in MS patients treated with alemtuzumab.

(1) Background: Subclinical inflammation as a risk factor of cardiovascular diseases was clinically measured using C-reactive protein (CRP) level. (2) Methods: This study was cross-sectionally designed based the 2015&ndash, 2018 Korean National Health and Nutrition Examination Survey (KNHANES). The ratio of daily omega-3 fatty acids to energy intake (&omega, 3FA ratio) was classified into four quartile groups (Q1, &lt, 0.3%, Q2, 0.3%&ndash, &lt, 0.6%, Q3, 0.6%&ndash, 1.0%, and Q4, &ge, 1.0% in both sexes). Logistic regression analysis was conducted to investigate the association between the &omega, 3FA ratio and subclinical inflammation defined as CRP levels &ge, 3 mg/dL. (3) Results: The &omega, 3FA ratio in subjects without and with subclinical inflammation was 0.8% and 0.7% in men (p-value = 0.001), and 0.8% and 0.8% in women (p-value = 0.491), respectively. The prevalence of subclinical inflammation in males decreased with increasing quartile of &omega, 3FA ratio (12.9%, 9.6%, 7.4%, and 7.7%, p-value = 0.033), while female prevalence was not significant among quartile groups. Compared to Q1, odds ratios (95% confidence intervals) for subclinical inflammation of Q2, Q3, and Q4 were 0.740 (0.465&ndash, 1.177), 0.564 (0.341&ndash, 0.930), and 0.549 (0.317&ndash, 0.953) in males, and 1.066 (0.653&ndash, 1.741), 1.105 (0.600&ndash, 1.718), and 0.934 (0.556&ndash, 1.571) in females after full adjustment. (4) Conclusion: The &omega, 3FA ratio is associated with subclinical inflammation in men.

Blocking the immune evasion mechanism of tumor cells has become an attractive means for treating cancers. However, the usage of a drug such as nivolumab (αPD-1), which blocks programmed cell death protein 1 (PD-1), turned out to be only effective against certain types of cancer. Especially, vascular abnormal structures of which deter delivery route by leakage and cause the poor perfusion were considered to be environment unfavorable to T cells and immune checkpoint blockade (ICB) delivery within the tumor microenvironment (TME). Herein, we report stabilization of tumor blood vessels by endothelial dysfunctional blocker CU06-1004, which modified the TME and showed synergistic effects with immunotherapy anti-PD-1 antibody. CU06-1004 combination therapy consistently prolonged the survival of tumor-bearing mice by decreasing tumor growth. T-cell infiltration increased in the tumors of the combination group, with cytotoxic CD8+ T cell activity within the tumor parenchyma upregulated compared with anti-PD-1 monotherapy. Tumor inhibition was associated with reduced hypoxia and reduced vessel density in the central region of the tumor. These effects correlated significantly with enhanced expression of IFN gamma and PD-L1 in tumors. Taken together, our findings suggest that CU06-1004 is a potential candidate drug capable of improving therapeutic efficacy of anti-PD-1 through beneficial changes in the TME.

Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan–Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models. The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683–0.850) and 1.055 (0.966–1.152) in men and 0.805 (0.649–0.999), and 1.049 (0.873–1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839–1.071) and 0.530 (0.452–0.621) in men and 1.163 (0.921–1.469) and 0.439 (0.323–0.596) in women, respectively. Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality. Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates.

Background The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers. Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents. Methods This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels. Results The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58–4.53), 31.02 (9.46–101.74), and 1.89 (1.12–3.17) in boys; and 6.50 (3.22–13.11), 20.09 (7.08–57.04), and 3.94 (1.98–7.77) in girls, respectively. Conclusion SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure. These findings remind us of the need to protect adolescents from SHS., Graphical Abstract

This study aimed to investigate the association between metformin usage and the risk of colorectal cancer (CRC) using data from the Korean National Health Insurance Service–National Health Screening Cohort database. Data from the NHIS-HEALS cohort between 2002 and 2015 were longitudinally analyzed. Subjects were divided into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and no DM group. CRC was defined using the ICD-10 code (C18.0-C20.0) at the time of admission. Cox proportional hazard regression models were adopted after stepwise adjustment for confounders to investigate the association between metformin usage and colorectal cancer risk. During the follow-up period, of the total 323,430 participants, 2341 (1.33%) of the 175,495 males and 1204 (0.81%) of the 147,935 females were newly diagnosed with CRC. The estimated cumulative incidence of CRC was significantly different among the three groups based on Kaplan-Meier’s survival curve (p values < 0.05 in both sexes). Compared with metformin non-users, hazard ratios (95% CIs) of metformin users and the no DM group were 0.66 (0.51–0.85) and 0.72 (0.61–0.85) in males and 0.59 (0.37–0.92) and 0.93 (0.66–1.29) in females, respectively, after being fully adjusted. Metformin users with diabetes appear to have a significantly lower risk of CRC compared with metformin non-users.

Inflammatory bowel disease is an autoimmune disease that causes chronic inflammation of the gastrointestinal tract. Endothelial dysfunction, defined by a reduced endothelial barrier and an increase in the expression of adhesion molecules, is part of the pathology of inflammatory bowel disease. In this study, we assessed the therapeutic effect of CU06-1004, an endothelial dysfunction blocker that reduces vascular hyperpermeability and inflammation in a mouse model of colitis. Acute colitis was induced in mice using 3% (w/v) dextran sodium sulfate added to their drinking water for 7 days. Twenty-four hours after the addition of dextran sodium sulfate, either mesalazine or CU06-1004 was administered orally each day. Administration of CU06-1004 significantly reduced the clinical manifestations (weight loss, diarrhea, and bloody stool) and histological changes (epithelium loss, inflammatory cell infiltration, and crypt destruction) induced by dextran sodium sulfate. Proinflammatory cytokines were also reduced, indicating that inflammation was ameliorated. From a vascular perspective, CU06-1004 reduced interrupted and tortuous vessels, enhanced junction protein expression, and reduced inflammatory adhesion molecules, indicating a broad improvement of endothelial dysfunction. Endothelial protection induced epithelial barrier restoration and decreased epithelial inflammation. Blocking endothelial dysfunction with CU06-1004 significantly ameliorated the progression of inflammatory bowel disease. Therefore, CU06-1004 may represent a potential therapeutic agent for the treatment of inflammatory bowel disease as well as other inflammatory diseases.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell–based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

ObjectivesInformation on subclinical astrocyte damage can provide further insight into neuromyelitis optica spectrum disorder (NMOSD) pathophysiology and disease-monitoring strategies. To investigate whether astrocyte and neuroaxonal damage occurs during interattack periods in individuals with NMOSD through longitudinal measurement of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) at multiple time points.MethodssGFAP and sNfL levels were measured in 187 serum samples from 20 participants with NMOSD treated with rituximab (median follow-up: 24 months) and 19 age-/sex-matched healthy controls using a highly sensitive single-molecule array assay. From the NMOSD cohort of National Cancer Center, Korea, 14 clinically stable participants were randomly selected for focused investigation of interattack periods, and 6 participants with clinical attacks despite treatment were enrolled for attack-related measurements.ResultsSignificant elevations of sGFAP levels were observed in all clinical attacks, and 95% (19/20) of patients showed reduction of sGFAP levels below the cutoff value (3 SDs above mean levels in age-/sex-matched healthy controls) within 3 months of their clinical attacks. The sGFAP levels were consistently low during interattack periods in 90% (17/19) of patients whose sGFAP levels returned to below the cutoff value. Changes in sNfL levels were similar to but slower than those in sGFAP levels.ConclusionsSubclinical astrocyte damage represented by increasing sGFAP levels rarely occurred during interattack periods in individuals with NMOSD; however, a certain degree of astrocyte damage did occur at the time of clinical attacks without exception, but it was not evident within 3 months of the attack.

Aims The aim of this study is to investigate the association between metformin usage and dementia in an elderly Korean population. Methods Participants were divided into five groups: metformin non-users with diabetes mellitus (DM), metformin users with DM (low-, mid-, and high-users), and non-diabetic Individuals. Dementia was defined with primary diagnostic dementia codes according to the 10th edition of the International Classification of Diseases. To compare the incidence rate of dementia among the five groups, Kaplan-Meier estimates and log-rank test were employed. Also, to control the confounding factors, Cox proportional hazards regression models were fitted in a sequential adjustment. Results The median follow-up was 12.4 years. The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73–1.28), 0.77 (0.58–1.01), 0.48 (0.35–0.67), and 0.98 (0.84–1.15), respectively, in men, respectively, and 0.90 (0.65–0.98), 0.61 (0.50–0.76), 0.46 (0.36–0.58), and 0.92 (0.81–1.04), respectively, in women, after full adjustment of confounding variables. Conclusions Metformin use in an elderly population with DM reduced dementia risk in a dose-response manner.

Background and purpose Data on the pregnancy outcome of neuromyelitis optica spectrum disorder (NMOSD) remain limited, especially for woman who had received immunosuppressive treatment before becoming pregnant. The aim was to evaluate the outcome of pregnancy amongst patients with NMOSD who attempted to become pregnant after NMOSD onset and to identify risk factors that predict pregnancy-related attack. Methods Medical records from 29 patients who attempted to become pregnant after NMOSD onset were retrospectively evaluated and the patients were interviewed for pregnancy outcomes. Pregnancy-related attack was defined as an attack that occurred during pregnancy or within 1 year of delivery. Results Amongst the 29 patients, 26 had 33 pregnancies after NMOSD symptom onset. The 33 pregnancies after NMOSD onset resulted in 24 live births (healthy neonates except one with low birth weight), six miscarriages and three elective abortions. Pregnancy-related attack occurred in nine (75%) of 12 pregnancies before initiation of immunosuppressive therapy, but in only five (24%) of 21 pregnancies after initiation of immunosuppressive therapy (P = 0.009). Multivariable analysis indicated that pregnancy-related attack was negatively associated with pregnancy after initiation of rituximab (odds ratio 0.048, 95% confidence interval 0.004-0.546). Conclusion Successful pregnancy without maternal and neonatal complications may be feasible in patients with NMOSD. Rituximab treatment before pregnancy might help to prevent pregnancy-related attack in patients with NMOSD.

Background and aim Several studies have reported the preventive effect of metformin on cancer development. This study aimed to investigate the relationship between use of metformin and risk of cancer in Koreans. Methods and Results This study was designed retrospectively using the National Health Insurance Service-National Health Screening Cohort conducted between 2002 and 2015. 40 to 69-year-old subjects who received a health screening examination from 2002 to 2003 were enrolled. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer were estimated in a multivariate Cox proportional regression analysis. A total of 323,430 subjects was enrolled (301,905 individuals without diabetes [No DM], 8643 diabetic patients with metformin treatment [metformin users], and 12,882 diabetic patients without metformin treatment [metformin non-users]). The median follow-up period was 12.7 years. Cumulative incidence of overall cancer was 7.9% (7.7, 10.3, and 11.1% in No DM, metformin users and non-users, respectively). Compared to metformin non-users, the fully adjusted HRs (95% CIs) of metformin users and No DM for overall cancer incidence were 0.73 (0.66–0.81) and 0.75 (0.64–0.88), respectively, in men and 0.83 (0.78–0.89) and 0.81 (0.72–0.92) in women. Conclusions Diabetic patients receiving metformin treatment, and individuals without diabetes were at lower risk for cancer incidence than diabetic patients without metformin treatment.

Background and purpose The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOG-antibody-positive demyelinating diseases in children. Methods This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. Results The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4-169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p=0.011). Conclusions MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.

Background We investigated the association between blood concentration of cadmium and smoking status including use of electronic cigarettes (E-cigars). Methods We used data from the Korea National Health and Nutritional Survey 2013 and 2016. A total of 4,744 participants (2,162 men and 2,582 women) were included and were categorized into five groups (Non-smokers, E-cigar non-users in past-smokers, E-cigar users in past-smokers, E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers). Cadmium blood concentration was categorized into tertiles. All sampling and weight variables were stratified, and analysis to account for the complex sampling design was conducted. Results In both genders, the geometric cadmium concentration was significantly different according to smoking status (both genders, analysis of variance P value < 0.001). In men, E-cigar users were significantly higher than the non-smokers (P value = past-smokers, 0.017; cigarette-smokers, < 0.001) when fully adjusted. Compared with non-smokers, fully-adjusted odds ratios (95% confidence intervals) for the highest cadmium tertiles of E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers were 6.56 (3.55–12.11) and 5.68 (1.96–16.50) in men and 2.74 (1.42–5.29) and 1.29 (0.10–17.44) in women. Conclusion Conventional cigarette smoking in men and women and E-cigar use in men are associated with higher risk of elevated blood cadmium level. Preventive management of cadmium exposure monitoring in conventional cigarette-smokers and E-cigar users may be needed., Graphical Abstract

Multiple autoimmune syndrome (MAS) is a rare condition, in which at least three well-defined autoimmune diseases co-occur in a single patient. Although the pathogenesis of MAS remains poorly understood, genetic, immunological, hormonal, and environmental factors may all play a role. Although three classic subtypes of MAS are well known, several cases that could not be placed into any of these three categories have recently been reported. To the best of our knowledge, the co-existence of psoriasis, vitiligo, and Crohn's disease has been reported in only one patient, who had a total of five autoimmune diseases (alopecia areata and oral lichen planus in addition to the three conditions mentioned). We herein describe a rare case of MAS presenting with psoriasis, vitiligo, and Crohn's disease, and suggest that tumor necrosis factor-α may be associated with the pathogenesis of all three conditions.

Aim We investigated the association between statin use and new-onset diabetes (NODM) in Korean adults with hypercholesterolemia. Methods This study performed based on data from the National Health Insurance Service-National Health Screening Cohort for the years from 2002 to 2015. Statin users classified as high- or low- users according to medication possession ratio. Statin non-users consisted of hypercholesterolemic participants who never used statin over the entire follow-up period. 21,469 participants (10,880 statin users, 10,589 statin non-users) with a median follow-up period of 12.5 years were included. We estimated the NODM risk based on the survival analyses. In particular, to adjust for confounding effects, we considered Cox proportional hazards regression models over three stages. Results Compared to non-users, statin users had a significantly higher risk for NODM. The fully adjusted hazard ratios (aHRs) (95% confidential intervals [95% CIs]) of statin users for NODM were 1.43 (1.31–1.57) in men, and 1.86 (1.66–2.10) in women, respectively after adjusted confounding factors including age and lifestyle factors. Compared to high-users, aHRs (95% CIs) of low-users for NODM were 1.16 (1.03–1.30) and 1.28 (1.16–1.43) in men and women, respectively. Conclusions In hypercholesterolemic patients, statin users have a higher risk of NODM than non-users.

In recent decades, the quantitative and technological development of laparoscopic liver resection has resulted in an extension into the transplantation area.1,2 However, laparoscopic living donor hepatectomy is still in its infancy due to technical difficulties and extreme caution regarding donor safety.3 Several experienced major centers have demonstrated the feasibility and safety of laparoscopic living donor hepatectomy, and recent advances in laparoscopic imaging technology support this move.4 In particular, indocyanine green near-infrared fluorescence imaging helps determine the correct liver parenchyma anatomical resection and the exact point of bile duct division.4–6 This video demonstrates the technique of pure laparoscopic living donor right hepatectomy and the usefulness of indocyanine green fluorescence imaging. The donor was a 32-year-old gentleman who decided to donate part of his liver to his wife who was suffering from viral liver cirrhosis and hepatocellular carcinoma. His BMI was 20.3 kg/m2 and the preoperatively estimated donor’s right liver volume was 836 ml, representing 63.6% of his entire liver. With the recipient’s weight of 57 kg, the graft-to-recipient weight ratio (GRWR) was 1.6%. The liver had classic hilar anatomy except that the right posterior intrahepatic duct was joined separately to the left main hepatic duct. The patient setting and the placement of the trocars were the same as for our conventional laparoscopic right hepatectomy technique.7 After right hepatic artery and portal vein isolation and clamping, 2.5 mg of indocyanine green was injected intravenously. Total operation time was 370 min and estimated blood loss was 150 ml without transfusion. Indocyanine green fluorescence imaging clearly demonstrated the anatomical demarcation between the lobes and visualized the running of the biliary tree. His postoperative course was uneventful, and he was discharged on postoperative day 7. Real-time indocyanine green fluorescence imaging may be particularly helpful for delineating the anatomical surgical plane and determining the appropriate division point of the hepatic duct during laparoscopic living donor hepatectomy.

ObjectiveTo evaluate the outcomes of immunosuppressive therapy (IST) discontinuation in patients with neuromyelitis optica spectrum disorder (NMOSD) after a sustained remission period.MethodsWe retrospectively reviewed the medical records of 17 patients with antiaquaporin-4 antibody-positive NMOSD who discontinued IST after a relapse-free period of ≥3 years.ResultsIST was discontinued at a median age of 40 years (interquartile range [IQR], 32–51) after a median relapse-free period of 62 months (IQR, 52–73). Among the 17 enrolled patients, 14 (82%) relapsed at a median interval of 6 months (IQR, 4–34) after IST discontinuation, 3 (18%) of whom experienced severe attacks; notably, all 3 of these patients had a history of severe attack before IST. These 3 patients received steroids, followed by plasma exchange for acute treatment, but 2 exhibited poor recovery and significant disability worsening at 6 months after relapse.ConclusionsIST discontinuation may increase the risk of relapse in seropositive patients with NMOSD even after 5 years of remission. Given the potentially devastating consequence of a single attack of NMOSD, caution is advised with IST discontinuation, particularly in patients with severe attack before IST.

Background Given that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG associated diseases. Here, we aim to validate a new in-house live cell-based assay (CBA) for screening MOG-IgG in patients with central nervous system inflammatory diseases. Methods We generated a full length MOG transfected HEK293 stable cell line using pIRES2-eGFP vector. Sera from 355 patients with central nervous system inflammatory diseases and 25 healthy individuals were evaluated for MOG-IgG seropositivity using in-house cell-based immunofluorescence assay (CBA-IF). The specificity of IgG ( H + L) and IgG1-Fc secondary antibodies as well as IgM binding were determined by cell-based flow cytometry (CBA-FACS). The optimal cut-offs for determining seropositivity in CBA-FACS were calculated and the concordance of CBA-IF score and CBA-FACS was studied. The results of our CBA-IF were compared with the Oxford CBA-IF. Results 11.5% (41/355) of patients were seropositive for MOG-IgG and had clinical phenotypes that were within the known clinical spectrum of MOG-IgG associated diseases. No typical multiple sclerosis patients, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder or healthy individuals were MOG-IgG seropositive. Using CBA-FACS, the anti-human IgG ( H + L) was found to be comparable to IgG1-Fc antibody. No IgM binding was observed in all the samples tested. CBA-IF score and CBA-FACS yielded high correlation. The concordance of the NCC CBA-IF with the Oxford CBA-IF was 98%. Conclusion We have developed MOG-IgG CBAs that have different characteristics and benefits but with high specificity and concordance. The complementary use of two methods and follow-up study with larger cohort will increase the clinical usefulness of MOG-IgG CBAs.

BACKGROUND AND PURPOSE The anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS. METHODS The antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients. RESULTS The overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52-4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years). CONCLUSIONS The seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.

Background Regulatory B cells (Bregs), which protect from autoimmunity, are deficient in multiple sclerosis (MS). Novel regulatory B cell subsets CD19+CD24hiCD38hi cells and CD19+PD-L1hi cells, with disparate regulatory mechanisms have been defined. Alemtuzumab provides a long-lasting suppression of disease activity in MS. In contrast to its documented efficacy, alemtuzumab’s mechanism of action is not fully understood and information about the composition of repopulating B cell pool is scarce. Aim To characterize repopulated B cell subsets and elucidate alemtuzumab’s mechanism of action in B cell perspective. Methods The frequency and the absolute number of Bregs were studied in peripheral blood mononuclear cells (PBMC) of 37 MS patients and 11 healthy controls (HC). Longitudinal analysis of the frequency and the absolute number of Bregs in PBMC of 11 MS patients was evaluated, before and at 6, 9, and 12 months post alemtuzumab. Results We found deficiency of CD19+CD24hiCD38hi cells during relapse compared to remission and HC (relapse vs remission: p = 0.0006, relapse vs HC: p = 0.0004). CD19+PD-L1hi cells were deficient during relapse than remission and HC (relapse vs remission: p = 0.0113, relapse vs HC: p = 0.0007). Following alemtuzumab, the distribution of B cells shifts towards naïve phenotype and Breg deficiency is restored. The frequency of CD19+CD24hiCD38hi cells was significantly increased at 6 M and 9 M compared to 0 M (6 M vs 0 M: p = 0.0004, 9 M vs 0 M: p = 0.0079). At 9 M, the frequency of CD19+CD24hiCD38hi cells started to decrease and by 12 M the frequency was reduced compared to 6 M, although it was significantly higher than baseline level (12 M vs 0 M: p = 0.0257). The absolute number was significantly increased at 6 M and 9 M post-alemtuzumab (6 M vs 0 M: p = 0.0063, 9 M vs 0 M: p = 0.02). The frequency of CD19+PD-L1hi cells significantly increased until 12 M (6 M vs 0 M: p = 0.0004, 12 M vs 0 M: p = 0.0036). The frequency of CD19+PD-L1hi cells at 12 M was significantly higher than 9 M (p = 0.0311). We further pinpoint that CD19+CD24hiCD38hi cells were deficient at severe relapses following alemtuzumab infusion and restored during recovery. Conclusions Our results highlight the preferential reconstitution of Bregs as a possible mechanism of action of alemtuzumab and CD19+CD24hiCD38hi cells as a potential biomarker for disease activity.

Background Trichomonas vaginalis (T. vaginalis) is the most common sexually transmitted parasite. It has been detected in prostatic tissue of patients with prostatitis and reported to be associated with chronic prostatitis and benign prostatic hyperplasia as well as prostate cancer. Recently, experimental rodent models of prostatitis induced by pathogen infection have been developed. However, there have so far been no reports of prostatitis caused by T. vaginalis infection in animals. Here, we investigated whether infection with T. vaginalis via the rat urethra could cause prostatitis. Methods T. vaginalis was injected into prostate through urethra of rat (Wistar rats), and the rats were killed 1, 2, or 4 weeks later. The presence of T. vaginalis trophozoites in the rat prostates was examined by immunohistochemistry, and pathological changes of the prostate were observed by hematoxylin-eosin staining and evaluated by grading from 0 to 5 for inflammatory cell infiltration, acinar changes, and interstitial fibrosis. Infiltrated mast cells were observed by toluidine blue staining of rat prostate tissue. Chemokine C-C motif ligand 2 (CCL2) levels of the rat prostates were measured by ELISA. Results T. vaginalis trophozoites were observed in acini in the prostates of the injected rats. The prostate tissues had higher pathological scores, and 83% (5/6) and 100% (6/6) of the ventral and dorsolateral lobes (n = 6), respectively, were inflamed. Infiltration and degranulation of mast cells were observed at higher rates in prostate sections of the T. vaginalis-infected rats. Also, prostate tissues of the injected rats had increased CCL2 levels. Conclusions Injection of T. vaginalis in rats caused prostatitis as revealed by pathologic changes, mast cell infiltration and increased CCL2 production. Therefore, this study provides the first evidence that T. vaginalis infection in rats causes prostatitis.

Folliculocystic and collagen hamartoma is a newly described complex hamartoma characterized by abundant collagen deposition, concentric perifollicular fibrosis, and keratin- filled infundibular cysts that are visible on histopathological examination. Here, we report the case of a 19-year-old Korean man who had large brownish infiltrated plaques with numerous follicular comedo-like openings and subcutaneous cystic masses on his right temporal scalp and ear since birth. Histopathological examination showed abundant collagen deposition in the dermis that extended up to the subcutaneous fat layer, multifocal infundibular cysts packed with keratin, and perifollicular inflammation and fibrosis. Hence, we describe a new type of hamartoma with folliculocystic and collagen components but without tuberous sclerosis.

Digital breast tomosynthesis (DBT) is a recently developed system for three-dimensional imaging that offers the potential to reduce the false positives of mammography by preventing tissue overlap. Many qualitative evaluations of digital breast tomosynthesis were previously performed by using a phantom with an unrealistic model and with heterogeneous background and noise, which is not representative of real breasts. The purpose of the present work was to compare reconstruction algorithms for DBT by using various breast phantoms; validation was also performed by using patient images. DBT was performed by using a prototype unit that was optimized for very low exposures and rapid readout. Three algorithms were compared: a back-projection (BP) algorithm, a filtered BP (FBP) algorithm, and an iterative expectation maximization (EM) algorithm. To compare the algorithms, three types of breast phantoms (homogeneous background phantom, heterogeneous background phantom, and anthropomorphic breast phantom) were evaluated, and clinical images were also reconstructed by using the different reconstruction algorithms. The in-plane image quality was evaluated based on the line profile and the contrast-to-noise ratio (CNR), and out-of-plane artifacts were evaluated by means of the artifact spread function (ASF). Parenchymal texture features of contrast and homogeneity were computed based on reconstructed images of an anthropomorphic breast phantom. The clinical images were studied to validate the effect of reconstruction algorithms. The results showed that the CNRs of masses reconstructed by using the EM algorithm were slightly higher than those obtained by using the BP algorithm, whereas the FBP algorithm yielded much lower CNR due to its high fluctuations of background noise. The FBP algorithm provides the best conspicuity for larger calcifications by enhancing their contrast and sharpness more than the other algorithms; however, in the case of small-size and low-contrast microcalcifications, the FBP reduced detectability due to its increased noise. The EM algorithm yielded high conspicuity for both microcalcifications and masses and yielded better ASFs in terms of the full width at half maximum. The higher contrast and lower homogeneity in terms of texture analysis were shown in FBP algorithm than in other algorithms. The patient images using the EM algorithm resulted in high visibility of low-contrast mass with clear border. In this study, we compared three reconstruction algorithms by using various kinds of breast phantoms and patient cases. Future work using these algorithms and considering the type of the breast and the acquisition techniques used (e.g., angular range, dose distribution) should include the use of actual patients or patient-like phantoms to increase the potential for practical applications.

The purpose of this study is to determine the optimal non-uniform angular dose distribution to improve the quality of the 3D reconstructed images and to acquire extra 2D projection images. In this analysis, 7 acquisition sets were generated by using four different values for the number of projections (11, 15, 21, and 29) and total angular range (±14°, ±17.5°, ±21°, and ±24.5° ). For all acquisition sets, the zero-degree projection was used as the 2D image that was close to that of standard conventional mammography (CM). Exposures used were 50, 100, 150, and 200 mR for the zero-degree projection, and the remaining dose was distributed over the remaining projection angles. To quantitatively evaluate image quality, we computed the CNR (contrast-to-noise ratio) and the ASF (artifact spread function) for the same radiation dose. The results indicate that, for microcalcifications, acquisition sets with approximately 4 times higher exposure on the zero-degree projection than the average exposure for the remaining projection angles yielded higher CNR values and were 3% higher than the uniform distribution. However, very high dose concentrations toward the zero-degree projection may reduce the quality of the reconstructed images due to increasing noise in the peripheral views. The zero-degree projection of the non-uniform dose distribution offers a 2D image similar to that of standard CM, but with a significantly lower radiation dose. Therefore, we need to evaluate the diagnostic potential of extra 2D projection image when diagnose breast cancer by using 3D images with non-uniform angular dose distributions.

Digital breast tomosynthesis (DBT) is a technique that was developed to overcome the limitations of conventional digital mammography by reconstructing slices through the breast from projections acquired at different angles. In developing and optimizing DBT, The x-ray scatter reduction technique remains a significant challenge due to projection geometry and radiation dose limitations. The most common approach to scatter reduction is a beam-stop-array (BSA) algorithm; however, this method raises concerns regarding the additional exposure involved in acquiring the scatter distribution. The compressed breast is roughly symmetric, and the scatter profiles from projections acquired at axially opposite angles are similar to mirror images. The purpose of this study was to apply the BSA algorithm with only two scans with a beam stop array, which estimates the scatter distribution with minimum additional exposure. The results of the scatter correction with angular interpolation were comparable to those of the scatter correction with all scatter distributions at each angle. The exposure increase was less than 13%. This study demonstrated the influence of the scatter correction obtained by using the BSA algorithm with minimum exposure, which indicates its potential for practical applications.

Background We evaluated the seroprevalence of myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG) and associated clinical features of patients from a large adult-dominant unselected cohort with mainly relapsing central nervous system (CNS) inflammatory diseases. We also investigate the clinical relevance of MOG-IgG through a longitudinal analysis of serological status over a 2-year follow-up period. Methods Serum samples from 505 patients with CNS inflammatory diseases at the National Cancer Center were analysed using cell-based assays for MOG-IgG and aquaporin-4 immunoglobulin G (AQP4-IgG). MOG-IgG serostatus was longitudinally assessed in seropositive patients with available serum samples and at least 2 years follow-up. Results Twenty-two of 505 (4.4%) patients with CNS inflammatory diseases were positive for MOGIgG. Patients with MOG-IgG had neuromyelitis optica spectrum disorder (NMOSD, n=10), idiopathic AQP4-IgGnegative myelitis (n=4), idiopathic AQP4-IgG-negative optic neuritis (n=4), other demyelinating syndromes (n=3) and multiple sclerosis (n=1). No relapses were seen in patients when they became MOG-IgG seronegative, whereas a persistent positive serological status was observed in patients with clinical relapses despite immunotherapy. Conclusions In a large adult-predominant unselected cohort of mainly relapsing CNS inflammatory diseases, we confirmed that NMOSD phenotype was most commonly observed in patients with MOG-IgG. A longitudinal analysis with 2-year follow-up suggested that persistence of MOG-IgG is associated with relapses.

Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system that preferentially affects the optic nerves, spinal cord, and area postrema. A series of evidence suggested that B cells play a fundamental role in the pathogenesis of NMOSD. However, there are still gaps left to be answered in NMOSD pathogenesis suggesting the roles of other immune cells. This study aimed to investigate the monocyte inflammatory characteristics, monocyte subset frequency and cytokine production, and cell-surface molecule expression in NMOSD, multiple sclerosis (MS), and healthy controls (HC). Methods Peripheral blood mononuclear cells of 20 aquaporin 4IgG-positive NMOSD patients, 20 MS patients, and 20 healthy controls were collected to analyze the monocyte subsets and to purify monocytes. To mimic the adaptive immunity, we have activated the monocytes using CD40L and IFN-γ to observe the production of cytokines and expression of cell-surface molecules. Results NMOSD monocytes showed a remarkable increase in the production of pro-inflammatory cytokines (IL-6, IL-1β) and increased expression of cell-surface molecules (CD80, HLA, ICAM-1, CD16), as well as a decrease in the levels of anti-inflammatory cytokine IL-10, compared to healthy control (HC) monocytes. As expected, MS monocytes also exhibit increased inflammatory cytokine production and increased cell-surface molecule expression compared to HC monocytes. Further analysis of monocyte subsets revealed that NMOSD monocytes have an increased frequency of the non-classical monocyte subset (CD14+CD16++) and a decreased frequency of the classical monocyte subset (CD14++CD16+) compared to HC monocytes. This finding was distinctly different from that of MS monocytes, which had an increased intermediate monocyte (CD14+CD16+) subset. In addition, these NMOSD non-classical monocyte subsets were highly dedicated, IL-6-producing monocytes. Conclusions Increased expression of cell-surface molecules and a reciprocal dysregulation of inflammatory and anti-inflammatory cytokines in NMOSD monocytes suggest an altered monocyte inflammatory response. CD14+CD16++ non-classical monocyte subset was more abundant in NMOSD monocytes than in HC or MS monocytes, and NMOSD non-classical monocyte subset had dysregulated IL-6 production, a phenotype which has been reported to be highly associated with NMOSD pathogenesis. Electronic supplementary material The online version of this article (10.1186/s12974-017-0961-z) contains supplementary material, which is available to authorized users.