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Competing Interests: The authors have no potential conflicts of interest to disclose.

Understanding marine bacterioplankton composition and distribution is necessary for improving predictions of ecosystem responses to environmental change. Here, we used 16S rRNA metabarcoding to investigate marine bacterioplankton diversity and identify potential pathogenic bacteria in seawater samples collected in March, May, September, and December 2013 from two sites near Jeju Island, South Korea. We identified 1343 operational taxonomic units (OTUs) and observed that community diversity varied between months. Alpha- and Gamma-proteobacteria were the most abundant classes, and in all months, the predominant genera were Candidatus Pelagibacter , Leisingera , and Citromicrobium . The highest number of OTUs was observed in September, and Vibrio (7.80%), Pseudoalteromonas (6.53%), and Citromicrobium (6.16%) showed higher relative abundances or were detected only in this month. Water temperature and salinity significantly affected bacterial distribution, and these conditions, characteristic of September, were adverse for Aestuariibacter but favored Citromicrobium . Potentially pathogenic bacteria, among which Vibrio (28 OTUs) and Pseudoalteromonas (six OTUs) were the most abundant in September, were detected in 49 OTUs, and their abundances were significantly correlated with water temperature, increasing rapidly in September, the warmest month. These findings suggest that monthly temperature and salinity variations affect marine bacterioplankton diversity and potential pathogen abundance.

Objective: Population-based studies of the familial aggregation of gout are scarce, and gene/environment interactions are not well studied. This study was undertaken to evaluate the familial aggregation of gout as well as assess interactions between family history and obesity or alcohol consumption on the development of gout., Methods: Using the Korean National Health Insurance database, which includes information regarding familial relationships and risk factor data, we identified 5,524,403 individuals from 2002 to 2018. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare the risk in individuals with and those without affected first-degree relatives. Interactions between family history and obesity/alcohol consumption were assessed on an additive scale using the relative excess risk due to interaction (RERI)., Results: Individuals with a gout-affected first-degree relative had a 2.42-fold (95% CI 2.39, 2.46) increased risk of disease compared to those with unaffected first-degree relatives. Having both a family history of gout and being either overweight or having moderate alcohol consumption was associated with a markedly increased risk of disease, with HRs of 4.39 (95% CI 4.29, 4.49) and 2.28 (95% CI 2.22, 2.35), respectively, which exceeded the sum of their individual risks but was only statistically significant in overweight individuals (RERI 0.96 [95% CI 0.85, 1.06]). Obese individuals (RERI 1.88 [95% CI 1.61, 2.16]) and heavy drinkers (RERI 0.36 [95% CI 0.20, 0.52]) had a more prominent interaction compared to overweight individuals and moderate drinkers, suggesting a dose-response interaction pattern., Conclusion: Our findings indicate the possibility of an interaction between gout-associated genetic factors and obesity/alcohol consumption., (© 2023 American College of Rheumatology.)

Background: Although several studies have examined the epidemiological features of vertebral compression fractures (VCF) among elderly patients, few studies have reported the epidemiology of VCF among younger individuals., Objective: To examine trends in the incidence and mortality of VCF in both the old (>= 65 years) and young (< 65 years) age groups. This study aimed to investigate the incidence and mortality of VCF among all age groups in Korea., Study Design: Population-based cohort study., Setting: A nationwide, population-based setting., Methods: Using the Korean National Health Insurance database, which has complete population coverage, we identified patients diagnosed with VCF between 2005 to 2018. Differences in incidence, survival and mortality were compared across groups using Kaplan-Meier analysis and Cox regression for all age groups and both genders., Results: We identified a total of 742,993 VCF patients and the annual incidence was 140.09/100,000 individuals. Although the incidence of VCF was significantly higher in the older age compared to younger age group (556.38/100,000 vs. 44.09/100,000 individuals), the mortality rate ratio for VCF patients was higher among younger compared to older individuals (old: 1.59 vs. young: 2.87). In our multivariable-adjusted analysis, the hazard ratio for multiple fractures, traumatic injury and osteoporosis were higher in patients aged < 65 years compared to patients aged >= 65 years, suggesting that the impact of these clinical variables on mortality is more significant in the younger age group., Limitation: A limitation of this study was its lack of information on clinical features, such as disease severity and laboratory data. The precise cause of death of VCF patients could not be confirmed from the study database., Conclusions: The mortality rate ratio and hazard ratio were significantly higher among younger patients with VCF, indicating the need for further research on VCF in younger age groups.

Long-term exposure to volatile organic compounds (VOCs) and carbonyl compounds in beauty products may adversely impact the health of beauty salon technicians. Previous studies have focused on assessing indoor air concentrations of chemicals, such as benzene and toluene, and not on personal exposure concentrations. This study measured the indoor and personal exposure concentrations of VOCs and carbonyl compounds in fifty-three beauty salons in Korea. Non-carcinogenic and carcinogenic risks and sensitivity were analyzed using the Monte Carlo simulation technique. The indoor and personal exposure concentrations of acetone were 82.24 µg/m 3 and 104.97 µg/m 3 , respectively, the highest among all measured chemicals. Beauty salon technicians who experienced adverse health effects had significantly higher concentrations of acetone, benzaldehyde, and toluene than those who did not experience adverse health effects (p-value < 0.05). The average hazard quotients of formaldehyde and acetaldehyde were higher than the acceptable risk level (1), and the average cancer risks of formaldehyde exceeded the acceptable risk level (10 -6 ). Wearing personal protective equipment was the most efficient risk reduction strategy for reducing the non-cancer risks of acetaldehyde and formaldehyde and the carcinogenic risks of formaldehyde. The results of this study can be used as a basis for reducing exposure to VOCs and carbonyl compounds among salon technicians., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

To understand the co-variance between common free-living bacteria and Cochlodinium polykrikoides harmful algal blooms (HABs) and their metabolic functions, we investigated 110 sampling sites in the Southern Sea of South Korea. These sampling sites were divided into three groups based on environmental factors and phytoplankton data with a similarity of 85% using non-metric multidimensional scaling. One group represented high-severity C. polykrikoides blooms, while the other two represented low-severity or no blooms. In high-severity HABs, inorganic phosphorous and dissolved organic carbon concentrations were strongly correlated with C. polykrikoides density (p < 0.01). This may reflect the changes in biochemical cycling due to inorganic and organic substrates released by HAB cells (or by cell destruction). Furthermore, 88 common bacterial operational taxonomic units (OTUs, with mean relative abundance > 1%) were identified. These included Gammaproteobacteria (36 OTUs), Flavobacteriia (24), Alphaproteobacteria (18), and other taxa (11). When C. polykrikoides blooms intensified, the relative abundances of Gammaproteobacteria also increased. OTU #030 (Flavicella sp., Flavobacteria, 96%) was positively correlated with C. polykrikoides abundance (r = 0.77, p < 0.001). Functional analysis based on the dominant bacterial OTUs revealed that chemoheterotrophy-related functions were more common in high-severity sites of HABs than in other groups. Therefore, the occurrence of HABs highlighted their interactions with bacteria and affected the bacterial community structure and metabolic functions., Competing Interests: Declaration of Competing Interest There are no conflicts of interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: This study investigated the association between the use of statins, the incidence of gastric, colorectal, and esophageal cancers, and mortality between January 2005 and June 2013 in South Korea., Methods: We compared patients aged 45-70 years statin users for at least 6 months to non-statin users matched by age and sex, from 2004 to June 2013 using the National Health Insurance database. Main outcomes were gastric, colorectal, and esophageal cancer incidence and mortality. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) among overall cohort and matched cohort after propensity score matching with a 1:1 ratio., Results: Out of 1,008,101 people, 20,473 incident cancers, 3938 cancer deaths occurred and 7669 incident cancer, 1438 cancer death in matched cohort. The aHRs for the association between the risk of cancers and statin use were 0.7 (95% CI 0.65-0.74) for gastric cancer, 0.73 (95% CI 0.69-0.78) for colorectal cancer, and 0.55 (95% CI 0.43-0.71) for esophageal cancer. There were associations between statin use and decreased gastric cancer mortality (HR 0.46, 95% CI 0.52-0.57), colorectal cancer mortality (HR 0.43, 95% CI 0.36-0.51), and esophageal cancer mortality (HR 0.41, 95% CI 0.27-0.50) in the overall cohort and this pattern was similar in the matched cohort., Discussion: Statin use for at least 6 months was significantly associated with a lower risk of stomach, colorectal, and esophageal cancer incidence as well as cancer mortality after a diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The taxonomy of the extant dinoflagellate genus Gonyaulax is challenging since its thecate morphology is rather conservative. In contrast, cysts of Gonyaulax are varied in morphology and have been related with the fossil-based genera Spiniferites and Impagidinium. To better understand the systematics of Gonyaulax species, we performed germination experiments on cysts that can be identified as S. ristingensis, an unidentified Spiniferites with petaloid processes here described as Spiniferites pseudodelicatus sp. nov. and Impagidinium variaseptum from Chinese and Portuguese waters. Despite marked differences in cyst morphology, motile cells of S. pseudodelicatus and I. variaseptum are indistinguishable from Gonyaulax baltica. Motile cells hatched from S. ristingensis are morphologically similar to G. baltica as well but differ in the presence of one pronounced antapical spine. Three new species, Gonyaulax amoyensis (cyst equivalent S. pseudodelicatus), Gonyaulax bohaiensis (cyst equivalent I. variaseptum), and Gonyaulax portimonensis (cyst equivalent S. ristingensis), were erected. In addition, a new ribotype (B) of G. baltica was reported from South Korea and a bloom of G. baltica ribotype B is reported from New Zealand. Molecular phylogeny based on LSU and SSU rRNA gene sequences revealed that Gonyaulax species with minute or short antapical spines formed a well-resolved clade, whereas species with two pronounced antapical spines or lack of antapical spines formed the sister clade. Six strains of four above species were examined for yessotoxin production by liquid chromatography coupled with tandem mass spectrometry, and very low concentrations of yessotoxin were detected for one G. bohaiensis strain., (© 2022 Phycological Society of America.)

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

Background & Aims: Donor death is the most serious complication of living liver donation but is reported rarely. We investigated the actual mortality of living liver donors (LLDs) compared with matched control groups based on analysis of the Korean National Health Insurance Services (NHIS) database., Methods: This cohort study included 12,372 LLDs who donated a liver graft between 2002 and 2018, and were registered in the Korean Network for Organ Sharing. They were compared to 3 matched control groups selected from the Korean NHIS and comprising a total of 123,710 individuals: healthy population (Group I); general population without comorbidities (Group II); and general population with comorbidities (Group III)., Results: In this population, 78.5% of living liver donors were 20-39 years old, and 64.7% of all donors were male. Eighty-nine donors (0.7%) in the LLD group died (68 males and 21 females), a mortality rate (/1,000 person-years) of 0.91 (0.74-1.12). Mortality rate ratio and the adjusted hazard ratio of the LLD group was 2.03 (1.61-2.55) and 1.71 (1.31-2.25) compared to Control Group I, 0.75 (0.60-0.93) and 0.63 (0.49-0.82) compared to Control Group II, and 0.58 (0.46-0.71) and 0.49 (0.39-0.60) compared to Control Group III. LLD group, depression, and lower income were risk factors for adjusted mortality. The incidence of liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the LLD group was significantly higher than in Control Group I., Conclusions: Outcomes of the LLD group were worse than those of the matched healthy control group despite the small number of deaths and medical morbidities in this group. LLDs should receive careful medical attention for an extended period after donation., Lay Summary: The incidence of mortality, liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the living liver donor group was significantly higher than in the matched healthy group. Careful donor evaluation and selection processes can improve donor safety and enable safe living donor liver transplantation., Competing Interests: Conflict of interest The authors of this manuscript have no conflicts of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: Long-term population-based data on change in the incidence of Behçet's disease (BD) are scarce, although a possible decline has been reported. The present study was undertaken to investigate the incidence, survival, and mortality of BD patients from 2004 to 2017 in the Republic of Korea., Methods: We analyzed a registry of rare intractable diseases and a claims database from the Health Insurance and Review Agency with information on BD patients between 2004 and 2017 using uniform diagnostic criteria. The study period was divided into 3 time periods: 2004-2006, 2007-2010, and 2011-2017., Results: The annual incidence of BD decreased from 8.15 per 100,000 in 2004 to 1.51 in 2017, an 81.5% decrease. The annual percentage change was 6.32% for female patients and 6.15% for male patients. The decrease in BD incidence was greater for women and middle-aged people. The 3-year survival rate of BD patients during the 2011-2017 period was lower than that of BD patients in 2004-2006 and 2007-2010, although there was no statistical difference. The standardized mortality rates increased significantly in the 2011-2017 period compared to the first 2 periods., Conclusion: BD incidence decreased from 2004 to 2017 in the Republic of Korea. This decline in incidence might be attributable to changes in environmental factors, including a reduction in the burden of infectious diseases in the past decades and improvement in oral health during childhood. The unprecedented decline in the incidence of BD in the Republic of Korea without major changes in genetic background suggests that environmental factors are very important to the development of BD., (© 2020, American College of Rheumatology.)

Background & Aims: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship., Methods: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs., Results: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs., Conclusions: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Few small-scale studies have reported a genetic and familial predisposition in Hashimoto's thyroiditis (HT), however, quantified familial risk estimates from population-level data are unavailable. We aimed to estimate the incidence and familial risk of HT among first-degree relatives (FDR) according to age, sex, and family relationships. Methods: We conducted a population-based study in the general population of Korea from 2002 to 2017. Using the nationwide health insurance database, which has full population coverage and family relationship information, a cohort of 22 million individuals with blood-related FDR comprising 12 million families were followed up for a familial occurrence of HT. Age- and sex-adjusted incidence risk ratios (IRRs) were calculated in individuals with an affected FDR compared with those without an affected FDR. Results: Among 21,940,795 individuals, 234,912 had an HT-affected FDR, of whom 2425 familial cases developed HT with an incidence of 7.12/10,000 person-years. The familial risk for HT was 6.5-fold (95% confidence interval [CI]: 6.24-6.78) higher in individuals with versus without affected FDR. According to relationship, familial risks were IRR 102.71, IRR 7.80, IRR 5.54, and IRR 5.52 with an affected twin, sibling, mother, and father, respectively, and the corresponding incidence (/10,000 person-years) was 115.57, 10.66, 5.73, and 5.91. Same-sex twins had three times higher risk of developing HT than opposite-sex twins (IRR 121.01 vs. 21.46). The sex-specific familial risk was higher in males than females. The risks demonstrated age dependence, being higher in younger age groups. Conclusions: This study represents the largest population-based study of familial HT risk in Asia. We demonstrated elevated familial risk of incident HT among FDR, but with lower magnitude as those observed in previous studies. Familial risk increased with the degree of genetic relatedness among FDR indicating a prominent role of genetic factors in the familial aggregation of HT. Elevated risks in the younger age groups should motivate clinicians to screen people with a family history, especially those <30 years.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Objective: Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship., Methods: Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR., Results: Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females., Conclusion: This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling-sibling) vs between generations (parent-offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Type II (acute) intestinal failure (IF) is usually caused by complications of abdominal surgery resulting in enteric fistulas or proximal stomas and requires parenteral nutrition (PN) for several months. This study aimed to evaluate clinical management and outcome of type II IF patients in a single center., Methods: Medical records of patients referred to the Intestinal Rehabilitation Team (IRT) at Samsung Medical Center (Seoul, Korea) were retrospectively analyzed., Results: From 2014 to 2019, 34 patients with IF were referred. 28 patients were type II IF and were included in the analysis. There were 17 males and 11 females. Mean age of patients was 56.7 years. Pathophysiology of IF were high-output stoma in 16 cases, extensive bowel resection (with bowel in continuity) in 7 cases, and enterocutaneous fistula in 5 cases. The catastrophic events necessitating abdominal surgery in the patients were adhesive ileus in 9 cases, superior mesenteric artery thrombosis in 8 cases, internal herniation of bowel in 5 cases, traumatic bowel injury in 3 cases, and ischemic enteritis in 3 cases. Following medical and surgical rehabilitation, 10 patients (35.7%) were weaned off PN and overall mortality was 28.5%. Deaths were related to progression of underlying malignancies in 4 cases, liver failure in 3 cases, and sepsis in 1 case. Thirteen patients underwent surgery to restore bowel continuity. Six postoperative complications occurred in 4 patients (30.7%) and there were no postoperative mortalities., Conclusion: Standardized care including restorative surgery resulted in successful outcomes in type II IF patients in this cohort., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. The requirement of obtaining informed consent was waived by the Institutional Review Board of Samsung Medical Center., (Copyright © 2020. Published by Elsevier Taiwan LLC.)

Background/aims: We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population., Methods: This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex., Results: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years., Conclusion: The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

Characterizing ecological relationships between viruses, bacteria and phytoplankton in the ocean is critical to understanding the ecosystem; however, these relationships are infrequently investigated together. To understand the dynamics of microbial communities and environmental factors in harmful algal blooms (HABs), we examined the environmental factors and microbial communities during Akashiwo sanguinea HABs in the Jangmok coastal waters of South Korea by metagenomics. Specific bacterial species showed complex synergistic and antagonistic relationships with the A. sanguinea bloom. The endoparasitic dinoflagellate Amoebophrya sp. 1 controlled the bloom dynamics and correlated with HAB decline. Among nucleocytoplasmic large DNA viruses (NCLDVs), two Pandoraviruses and six Phycodnaviruses were strongly and positively correlated with the HABs. Operational taxonomic units of microbial communities and environmental factors associated with A. sanguinea were visualized by network analysis: A. sanguinea-Amoebophrya sp. 1 (r = .59, time lag: 2 days) and A. sanguinea-Ectocarpus siliculosus virus 1 in Phycodnaviridae (0.50, 4 days) relationships showed close associations. The relationship between A. sanguinea and dissolved inorganic phosphorus relationship also showed a very close correlation (0.74, 0 day). Microbial communities and the environment changed dynamically during the A. sanguinea bloom, and the rapid turnover of microorganisms responded to ecological interactions. A. sanguinea bloom dramatically changes the environments by exuding dissolved carbohydrates via autotrophic processes, followed by changes in microbial communities involving host-specific viruses, bacteria and parasitoids. Thus, the microbial communities in HAB are composed of various organisms that interact in a complex manner., (© 2020 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

The aim of the study was to estimate the dietary exposure to acrylamide (AA) from the consumption of various processed food and to assess the associated health risks in different age groups in Korea. Potato crisps and French fries presented the highest mean levels of AA (546 and 372 μg/kg, respectively) followed by coffee (353 μg/kg) and tea products (245 μg/kg). The mean AA dietary exposure values for toddlers (≤2 years), children (3-6 years), children (7-12 years), adolescents (13-19 years), adults (20-64 years), and seniors (≥65 years) were estimated to be 0.15, 0.13, 0.06, 0.06, 0.08, and 0.06 μg/kg body weight (BW)/day, respectively. Based on the benchmark dose lower confidence limit (BMDL 10 ) of 0.18 and 0.31 mg/kg BW/day, the calculated mean and 95th percentile values for the margin of exposure were below 10,000 for the all age groups suggesting possible health concern for Koreans. Biscuits, crisps, and coffee were the primary foods contributing to dietary AA exposure among these in the Korean populations. In children, considering the health risk of AA dietary exposure, especially from biscuits and crisps, there is a need to further control and modify dietary habits to ensure lower AA exposure.

Background/aims: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.
., Methods: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.
., Results: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P<0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, P=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20-17.02;P=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04-9.30; P=0.042) in COVID-19 patients.
., Conclusion: This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

Background and Purpose: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea., Methods: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships., Results: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/10 4 person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/10 4 person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs., Conclusions: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.

Purpose: To evaluate the incidence, visual prognosis, and mortality in retinopathy of prematurity (ROP) in Korea., Methods: We used the National Health Insurance and the Korean Disability Registry database, which covers the entire newborn population in 2006 to 2014 and includes information on all newborns diagnosed with ROP until 2016. Using these databases, we evaluated the incidence, rate of visual impairment (VI), and mortality in patients with ROP according to the birth weight categories and treatment modalities., Results: The ROP incidence per 1000 newborns was 1.99, which broke down into 317.14 in the very low birth weight (VLBW) less than 1500 g population, 25.45 in the 1500 to 2499 g population, and 0.29 in the 2500 g or greater population. When assessed at age 10, the VI rate was 2.2 per 100 person-years, which was highest at 4.5 per 100 person-years in the VLBW population compared with the population in other birth weight categories. Among treated cases, the proportion of VI in patients undergoing laser photocoagulation or cryotherapy was 1.6% (42/2595), which was lower than the 2.9% (2/68) of patients treated with anti-vascular endothelial growth factor injection, and 32.2% (82/255) of patients undergoing vitrectomy or scleral buckling. The mortality rate was 4.8 per 1000 person-years, which was highest in the VLBW population, but similar across treatment modalities., Conclusions: The ROP incidence in Korea was approximately 1 in 500 among all newborns, and 1 in 3 in the VLBW population. As the first nationwide population-based study of long-term visual prognosis in ROP, we report the higher VI rate in ROP than previously determined in other studies. Differences in visual outcomes and comparable mortality risks between treatment modalities require further verification.

Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodium-glucose cotransporter-2 (SGLT2) inhibitor showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2 inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend the long-term use SGLT2 inhibitor in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendation due to lack of long-term clinical trials testing reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after publication of several large-scale renal outcome trials., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Diabetes Association.)

Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging zoonotic virus in East Asia. However, SFTS virus (SFTSV) has not been reported to cause clinical infection in companion dogs to date. We report the case of a 4-year-old companion dog that presented with fever, vomiting, leukocytopenia and thrombocytopenia at a veterinary hospital in the Republic of Korea. It was diagnosed with SFTS, which was confirmed using real-time reverse transcription PCR, sequencing and an indirect immunofluorescence assay, and recovered after supportive care. Further studies are required to investigate SFTSV infection in companion animals, living in close contact with humans, as well as animal-to-human transmission., (© 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

There is still a paucity of studies on real-world outcome of screening clinic for hospital protection from coronavirus disease 2019 (COVID-19). As the number of COVID-19 cases was growing rapidly in Daegu, Korea, we started operating an active screening clinic outside the hospital premises. Over two weeks, 2,087 patients were screened using real-time reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2, with 42 confirmed cases. Before the screening clinic period, an average of 36 beds (maximum 67 beds) per day were closed due to unrecognized COVID-19 patients entering the hospital. In contrast, after the screening clinic operated well, only one event of closing emergency room (25 beds) occurred due to a confirmed COVID-19 case of asymptomatic patient. We report the operational process of screening clinic for COVID-19 and its effectiveness in maintaining the function of tertiary hospitals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: Hyperthyroidism is associated with various cardiovascular risk factors. However, the relationship between hyperthyroidism and myocardial infarction (MI) or stroke has not been fully elucidated; only a few studies have investigated the association of hyperthyroidism with survival after MI or stroke. Methods: We included 59,021 hyperthyroid patients and a control cohort with 1,180,420 age- and sex-matched subjects from the Korean National Health Insurance database. Blood pressure, body mass index (BMI), glucose and cholesterol levels, and smoking history were obtained during National Health screening examination. We compared the incidence of MI, stroke, and survival after cardiovascular events between subjects with hyperthyroidism and the control cohort. Results: Subjects with hyperthyroidism had higher blood pressure, fasting glucose, and smoking rate, but lower cholesterol levels and a lower obesity rate compared with the control cohort. After adjusting these differences, as well as atrial fibrillation, hyperthyroidism was associated with increased risk of MI and ischemic stroke. Adjusted hazard ratios (HRs) for MI and ischemic stroke with hyperthyroidism was 1.16 [95% confidence interval, CI 1.03-1.30] and 1.12 [CI 1.04-1.20], respectively. In age-, sex-, and BMI-stratified analyses, an increased risk of MI and ischemic stroke remained significant in females, the older age group (≥50 years), and nonobese subjects (BMI <25 kg/m 2 ), but not in males, the younger age group (<50 years), and obese subjects (BMI ≥25 kg/m 2 ). The risk of hemorrhagic stroke was not different between subjects with hyperthyroidism and controls. Adjusted HRs for mortality in subjects with hyperthyroidism who developed MI, ischemic stroke, and hemorrhagic stroke were 1.11 ([CI 0.86-1.43], p  = 0.44), 0.89 ([CI 0.75-1.05], p  = 0.16), and 1.13 ([CI 0.88-1.47], p  = 0.34), respectively. Conclusions: Hyperthyroidism is associated with increased risk of MI and ischemic stroke, independent of cardiovascular risk factors. This association is prominent in subjects with age ≥50 years, in females, and in the nonobese group. Hyperthyroidism did not significantly affect the mortality secondary to cardiovascular events.

Importance: Alopecia areata (AA) is a common autoimmune disease presenting as nonscarring hair loss. Although AA can be associated with other autoimmune comorbidities or atopic diseases, little is known about the risk of cardiovascular diseases in patients with AA., Objective: To investigate the risk of acute myocardial infarction (AMI) and cardiovascular risk profiles (CVRPs) in patients with AA via a large-scale epidemiologic study., Design, Setting, and Participants: This was a retrospective cohort study using data from the Korean National Health Insurance claims database, including data from the National Health Screening Program. Patients aged 30 to 89 years who were newly diagnosed with AA between January 1, 2006, and December 31, 2017, and controls without AA matched by age and sex were enrolled. Data were analyzed between July 2018 and August 2019., Exposures: Presence of AA., Main Outcomes and Measures: The CVRPs and incidence rates of AMI were assessed in participants with and without AA. The stratified Cox regression hazard model was used to estimate the relative hazards over time., Results: A total of 228 886 patients with AA, ranging in age from 30 to 89 years (mean [SE] age, 44.37 [0.005] years; 127 564 [55.7%] men) and 4 577 720 matched controls without AA were identified. Patients with AA tended to have slightly better CVRPs than controls in all items except smoking status before and after the diagnosis (participants with normal systolic blood pressure who were nonsmokers: 44.6% vs 42.7% and 57.8% vs 61.6% in patients with AA vs controls before and after the diagnosis, respectively). In the early phase of observation, the cumulative incidence of AMI in patients with AA was lower than that in controls (incidence rate ratio of AMI in patients with AA compared with that in controls, 0.52 [95% CI, 0.42-0.65] between 2-4 years); however, during the later phase of the 12-year follow-up period, it increased exponentially and was greater than in the control group (incidence rate ratio, 2.06 [95% CI, 1.71-2.45] between 8-10 years). Similarly, after adjusting for CVRPs, the risk of developing AMI was lower in patients with AA than in controls at the beginning of the observation period (adjusted hazard ratio (HR), 0.17 [95% CI, 0.12-0.25] between 0-2 years); however, by 8 years postdiagnosis, the risk was higher in those with AA (adjusted HR, 1.37 [95% CI, 1.11-1.70] between 8-10 years), and it increased thereafter (adjusted HR, 4.51 [95% CI, 3.65-5.58] between 10-12 years)., Conclusions and Relevance: In patients with AA, there was a significantly increased risk of AMI over time during the 12-year follow-up period independent of CVRPs. Close long-term monitoring of cardiovascular health in patients with AA might be appropriate.

Background: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes., Subjects, Materials, and Methods: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses., Results: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity., Conclusion: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period., Implications for Practice: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer., (© AlphaMed Press 2019.)

Background: Phase lag entropy (PLE) is a novel anesthetic depth indicator that uses four-channel electroencephalography (EEG) to measure the temporal pattern diversity in the phase relationship of frequency signals in the brain. The purpose of the study was to evaluate the anesthetic depth monitoring using PLE and to evaluate the correlation between PLE and bispectral index (BIS) values during propofol anesthesia., Methods: In thirty-five adult patients undergoing elective surgery, anesthesia was induced with propofol using target-controlled infusion (the Schneider model). We recorded the PLE value, raw EEG, BIS value, and hemodynamic data when the target effect-site concentration (Ce) of propofol reached 2, 3, 4, 5, and 6 μg/ml before intubation and 6, 5, 4, 3, 2 μg/ml after intubation and injection of muscle relaxant. We analyzed whether PLE and raw EEG data from the PLE monitor reflected the anesthetic depth as the Ce of propofol changed, and whether PLE values were comparable to BIS values., Results: PLE values were inversely correlated to changes in propofol Ce (propofol Ce from 0 to 6.0 μg/ml, r 2  = - 0.83; propofol Ce from 6.0 to 2.0 μg/ml, r 2  = - 0.46). In the spectral analysis of EEG acquired from the PLE monitor, the persistence spectrogram revealed a wide distribution of power at loss of consciousness (LOC) and recovery of consciousness (ROC), with a narrow distribution during unconsciousness. The power spectrogram showed the typical pattern seen in propofol anesthesia with slow alpha frequency band oscillation. The PLE value demonstrated a strong correlation with the BIS value during the change in propofol Ce from 0 to 6.0 μg/ml (r 2  = 0.84). PLE and BIS values were similar at LOC (62.3 vs. 61.8) (P > 0.05), but PLE values were smaller than BIS values at ROC (64.4 vs 75.7) (P < 0.05)., Conclusions: The PLE value is a useful anesthetic depth indicator, similar to the BIS value, during propofol anesthesia. Spectral analysis of EEG acquired from the PLE monitor demonstrated the typical patterns seen in propofol anesthesia., Trial Registration: This clinical trial was retrospectively registered at ClinicalTrials.gov at October 2017 (NCT03299621).

Background: Few national level, population-based studies are present on the epidemiology of sarcoidosis and it is unclear whether these patients have higher mortality than the general population. The objective of this study was to investigate the nationwide epidemiology, comorbidity and mortality in sarcoidosis in Korea., Material and Methods: For the period between 2008 to 2015, we used the national population-based database operated by Rare Intractable Disease registration program in which patients' diagnosis are based on uniform criteria. All sarcoidosis patients were identified and followed-up using the National Health Insurance database to determine their incidence, comorbidity, mortality, causes of death and standardised mortality ratio (SMR)., Results: During the study period, we identified 3,259 new sarcoidosis patients. The average annual incidence was 0.81 per 100,000. The annual mortality rate was 9.26 per 1,000 person-years. The mortality rate were significantly higher than those of the general population (SMR 1.91, 95% confidence interval 1.62-2.25). The major comorbidities of sarcoidosis patients were the diseases of the respiratory system (17.64%), heart (5.43%), eyes (4.27%) and cancer (2.3%). Mortality was higher in patients with lung involvement. Of the 84 deaths identified in this study from 2008-2013, the most common cause of death was cancer (41.7%), followed by respiratory disease (13.1%), sarcoidosis (13.1%) and heart disease (8.3%)., Conclusions: We reported a nationwide incidence of sarcoidosis as 0.81 per 100,000 in Korea. The mortality of sarcoidosis patients was higher compared to the general population and the major causes of death were cancer, respiratory disease and sarcoidosis. Sarcoidosis patients with comorbid diseases showed increased mortality. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 24-36) ., (Copyright: © 2020 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Objective: The purpose of this study was to investigate whether asymmetric hearing loss affects vestibular function., Study Design: Retrospective cross-sectional study., Patients: Data from the 2010 Korean National Health and Nutrition Survey for adults aged 40 years or more were used., Interventions: The modified Romberg test and pure-tone audiometry were performed. Data were analyzed using a complex sample χ test of independence and complex sample logistic regression analysis., Main Outcome Measures: Vestibular dysfunction and hearing thresholds., Results: The overall prevalence of vestibular dysfunction was 3.3% (95% confidence interval [CI], 2.5-4.3%). In adults more than 40 years of age, multivariate linear regression analyses showed that the odds ratio (OR) of vestibular dysfunction was 3.067 times higher than the reference for a 30-dB difference in hearing thresholds between both ears (CI, 1.481-6.351; p = 0.007) after adjusting for factors associated with vestibular dysfunction. Among these individuals, the risk of equilibrium disturbance was higher in the presence of low-frequency asymmetric hearing loss (OR, 2.148; CI, 1.216-3.793; p = 0.009); on the other hand, high-frequency asymmetry did not lead to a higher risk., Conclusions: As low-frequency asymmetric hearing thresholds tend to coexist with vestibular dysfunction in adults, those with asymmetric hearing loss should be closely monitored.

Aim: Rotaviruses have been associated with biliary atresia. This study investigated whether the rotavirus vaccine, which was introduced to Korea in 2008, had an impact on the incidence of biliary atresia., Methods: We identified all rotavirus infections (n = 436 826) and biliary atresia cases (n = 528) diagnosed from 2006 to 2015 from insurance and health databases. The annual and seasonal incidence of biliary atresia and rotavirus infection rates in neonates and children were calculated. The difference in the risk of biliary atresia between rotavirus-infected and non-infected neonates was analysed., Results: The incidence of rotavirus infections was 20.6 versus 13.4 per 1000 cases before (2006-2008) and after (2009-2015) vaccine implementation. However, neonatal rotavirus infection rates did not decrease, with an incidence of 14.5 versus 14.8 per 1000 cases before and after vaccination. The biliary atresia incidence remained constant at 12.0 per 100 000 cases. Rotavirus infections in neonates were a risk factor for biliary atresia (odds ratio 3.14, 95% confidence interval 1.87-5.26)., Conclusion: Rotavirus vaccination had no impact on the incidence of biliary atresia, possibly because the vaccination did not change the neonatal rotavirus infection rate through herd immunity. However, rotavirus infections in neonates were significantly associated with biliary atresia., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aberrant expression of CD5 has been reported in 5-10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an extremely unfavorable prognosis with frequent treatment failure. We retrospectively investigated 405 DLBCLs recruited from three university hospitals in Korea from 1997 to 2013. The clinical profile, immunophenotype, and chromosomal structural alterations of the BCL2 and MYC genes were compared according to CD5 expression. A total of 29 cases of de novo CD5+ DLBCL were identified out of 405 in our series (7.4%). Clinicopathologic correlation was performed in all 29 CD5+ DLBCLs and 166 CD5- DLBCLs which were eligible for full clinical review and further pathologic examination. Compared with CD5- counterparts, CD5+ DLBCLs showed female preponderance, frequent bone marrow involvement, higher lactate dehydrogenase level, advanced Ann Arbor stages and poorer prognosis (all p<0.05). Pathologically, the expression of CD5 positively correlated with that of BCL2, MYC and Ki-67 (all p<0.05). Coexpression of BCL2 and MYC, which is referred to as a double-expressor, was relatively more common in CD5+ DLBCL, whereas translocation or amplification of these genes was very rare. in conclusion, the expression of CD5 is an independent poor prognostic factor of DLBCLs, and this subgroup displays unique clinicopathologic features. Although the exact mechanism remains uncertain, consistent activation of BCL2 and MYC by alternative pathways other than chromosomal translocation may contribute to the pathogenesis., Competing Interests: The authors have declared that no competing interests exist.

Background: Nasal polyps are a common condition with a significant effect on quality of life. The association between nasal polyps and future risk of head and neck cancer is unknown., Objective: We sought to investigate the relative risk of nasal cavity and paranasal sinus (NCPS) and nasopharyngeal cancers in a nationwide, population-based, longitudinal retrospective cohort of patients with nasal polyps and matched comparators., Methods: The 2005-2017 National Health Insurance claims and National Health Screening program databases were used to construct a cohort of patients with nasal polyps and matched comparators in Korea. The relative risk of NCPS and nasopharyngeal cancer in patients with nasal polyps was examined., Results: The study consisted of 453,892 patients with nasal polyps and 4,583,938 matched comparators. The mean duration of follow-up was 6.2 years (range, 2-13 years). The incidence rate ratios of patients with nasal polyps compared with the comparators was 7.00 (95% CI, 5.28-9.25) for NCPS cancer and 1.78 (95% CI, 1.28-2.42) for nasopharyngeal cancer. Increased risks of these cancers were only evident in older subjects (age ≥50 years). There were trends toward weaker associations of nasal polyps with these cancers in younger subjects with comorbid asthma or allergic rhinitis (<50 years)., Conclusion: Although the absolute cancer incidence is very low, the relative risk of NCPS or nasopharyngeal cancers was significantly greater in older patients with nasal polyps. Given the regional and pathologic heterogeneity of nasal polyps, further studies are needed to explore the underlying mechanisms and validate the relationships., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A foot-and-mouth disease (FMD) outbreak during 2010 affected the entire country of South Korea and approximately 3.4 million swine and bovine mortalities were disposed of at approximately 4800 on-farm burial sites for a few months following the first outbreak. Furthermore, outbreaks of avian influenza (AI) have struck Korea consistently since 2014. Public concern regarding the deterioration of the surrounding environment has been raised aiming at the enormous infected animal carcass burials. On behalf of the Ministry of Environment (ME) of the Korean government, we conducted groundwater monitoring at approximately 3000 wells around the burial sites for 7 years from 2011 to 2017. The baseline groundwater already had enriched levels of nitrogen and chloride compounds masking the influence of leachate with the pre-existing anthropogenic contamination. Based on the trend analysis, most monitoring wells had no significant trends in NO 3 -N and Cl implying that an abrupt degradation in water quality was not expected across the country. Increasing proportions of total coliform detection in the groundwater of the majority of provinces will cause potential damage to human health around the carcass burial sites. Wells showing frequent upward and downward trends near the carcass burial pits were targeted for principal component analysis (PCA) and the results showed that NH 4 -N, TOC, Cl, and K could be indicators distinguishing the sole impacts of animal leachate on the groundwater. Analyses of the nationwide monitoring data indicated possibly delayed and prolonged impacts of the widespread burials of livestock mortalities on the groundwater environment. The finding provides realistic insight regarding how to manage the mass burial of livestock mortalities to protect groundwater resources., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Clinical manifestations of lipoid pneumonia (LP) vary depending on the causative agents or underlying causes. The aim of the present study was to investigate the clinical and radiological features of LP, classified according to etiologic agents., Methods: The clinico-radiological characteristics of LP patients were retrospectively compared among groups: exogenous versus idiopathic and squalene versus omega-3-acid ethyl esters (O-3-AEE) versus idiopathic. Idiopathic group was defined as LP with no proven or reported etiological evidence., Results: Twenty-two patients met the diagnostic criteria for LP: squalene (9 [41%]), O-3-AEE (6 [27%]), olive oil (1 [5%]), and idiopathic (7 [32%]). Compared with the exogenous group, the idiopathic group showed a higher recurrence rate; higher frequencies of bronchial anthracofibrosis (BAF) and bronchoalveolar lavage (BAL) lymphocytosis; and a higher rate of crazy-paving pattern and lower rate of consolidation on computed tomography scan. In three-group tests, compared with the O-3-AEE group, the squalene group exhibited a significantly higher percentage of neutrophils and a higher rate of right middle lobe (RML) involvement., Conclusions: In comparison with the exogenous group, the idiopathic group demonstrated BAL lymphocytosis, higher rates of recurrence and BAF, and a higher rate of crazy-paving pattern. Compared with the O-3-AEE group, the squlaene group showed a higher percentage of BAL neutrophils and predominant RML involvement., (© 2019 John Wiley & Sons Ltd.)

In 2016, 9-valent human papillomavirus (HPV) vaccine has been newly introduced in Korea, thus the need to develop recommendations for the vaccine has raised. Until we decide to develop a guideline, no further studies on the bi-valent or quadri-valent HPV vaccine have been announced. We searched and reviewed the literatures focused on the efficacy of 9-valent HPV vaccine, the ideal age of 3-dose schedule vaccination, the efficacy of 9-valent HPV vaccine in middle-aged women, the efficacy of the 2-dose schedule vaccination, the safety of 9-valent HPV vaccine, the possibility of additional 9-valent HPV vaccination, and cross-vaccination of 9-valent HPV vaccine. So, Korean Society of Gynecologic Oncology (KSGO) developed a guideline only for 9-valent HPV vaccine., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objectives: We analyzed the incidence and mortality rates of second pancreatic ductal adenocarcinoma (PDAC) among survivors of digestive cancers in South Korea., Methods: We evaluated data from the Korea National Health Insurance to identify individuals with digestive cancers in 2005 to 2015. The standardized incidence ratios (SIRs) of second PDACs and survival rates were evaluated., Results: Among 772,534 patients with first digestive cancers, 1696 (0.22%) developed second PDACs. The incidence of second PDACs increased until 10 years since the first cancer diagnosis. Patients with biliary tract cancers (BTCs) showed a higher incidence of second PDACs than did those with gastrointestinal cancers or hepatocellular carcinoma. In ages 20 to 49 years, SIRs (95% confidence interval) were higher in survivors of hepatocellular carcinoma (3.08; 1.04-3.08), gastric cancer (3.40; 1.90-3.40), colorectal cancer (5.00; 2.75-5.00), gallbladder cancer (58.52; 11.81-58.52), intrahepatic cholangiocarcinoma (86.99; 1.73-86.99), extrahepatic cholangiocarcinoma (89.41; 27.42-89.41), and ampulla of Vater cancer (156.78; 48.08-156.78). In ages 50 to 64 years, colorectal cancer (1.42; 1.04-1.42), gastric cancer (1.66; 1.29-1.66), and BTCs revealed higher SIRs. In ages more than 65 years, SIR was increased only in BTCs. Second PDACs revealed a more favorable prognosis than first PDACs., Conclusions: Careful surveillance for second PDACs after curative treatment of BTCs and colorectal cancers should be considered.

Dementia is a major public health problem affecting 5.5 million people in USA. This qualitative study explored the caregiving experience of Korean American (KA) families of persons with dementia (PWD). Adult KA caregivers of PWD (n = 18) were recruited for semi-structured interviews. Thematic analysis yielded four themes: challenges in finding resources, struggling with mental health issues, traveling the path of acceptance, and finding ways to survive. Due to the language barrier, most KA caregivers reported using Korean Internet for information on dementia and caregiving. Some traveled to South Korea seeking medical assistance for dementia (medical tourism). Importantly, some KA caregivers expressed suicidal thoughts and depression. Unexpectedly, familism prevented help seeking and possible relief from their difficulties. There is an urgent need to improve access to dementia care services and education for the KA community. Building a trusting relationship with healthcare providers is even more important for KA caregivers to address their mental health concerns.

Background and Aim: Cholangiocarcinoma (CCA) often develops after the hepatic resection for hepatolithiasis as well as indwelling it. We studied the incidence and prognosis of subsequent CCA in patients with hepatolithiasis in South Korea., Methods: We identified individuals with diagnosed CCA at the time of or after surgery, during 2002-2016, from the Korean National Health Insurance. The incidences and survival rates of subsequent CCA were analyzed and compared with concomitant CCA. The standardized incidence ratios (SIRs) of CCA in this cohort were evaluated in the standard Korean population. All data were stratified by the presence of intrahepatic or extrahepatic CCA, age and sex., Results: Of the 7852 patients with hepatectomy for BDS, 433 (5.84%) had concomitant CCA. Over the 12-year follow-up, 107 of 7419 (1.98%) patients were diagnosed with subsequent CCA. Patients with hepatic resection for BDS revealed higher SIRs for subsequent CCA (12.89, 95% CI 10.96-15.15) in cases of both intrahepatic CCA (13.40, 10.55-17.02) and extrahepatic CCA (12.42, 9.98-15.46). The median survival time for subsequent CCA was 0.87 years, while that for concomitant CCA was 2.79 years. Having subsequent CCA (HR 2.71, 95% CI 2.17-3.40) and being male (HR 1.28, 1.05-1.57) were related to a shorter survival time. The CCA site and age at CCA diagnosis were not related to prognoses., Conclusions: Subsequent CCA developed in 2% of the patients with hepatic resection for benign BDS until 10 years and was associated with poorer prognoses than concomitant CCA. Future studies focused on the long-term surveillance for CCA in such patients are needed.

Objectives: This study investigated whether there was any secular change in cranial vault morphology among Koreans born between the 1930s and 1970s, a period of dramatic shift in Korea's socioeconomic conditions., Materials and Methods: Using three-dimensional MRI volumetry, we obtained the intracranial volume (ICV) and craniometric measurements of 115 healthy Koreans: 58 individuals (32 males and 26 females) born in the 1930s (1926-1936) and 57 (28 males and 29 females) born in the 1970s (1972-1979)., Results: The intracranial volume of males was 1502.3 ± 110.3 cm 3 for the 1930s group and 1594.1 ± 99.5 cm 3 for the 1970s group, and for females, it was 1336.0 ± 53.0 cm 3 for the 1930s group and 1425.9 ± 79.6 cm 3 for the 1970s group. On average, ICV increased by 94 cm 3 in males and by 90 cm 3 in females. Cranial measurements for the 1970s group were significantly larger than the 1930s group for both sexes except in female cranial length. Each measurement was significantly correlated with ICV [cranial height (R = 0.720), breadth (R = 0.706), and length (R = 0.531)]. The cephalic index decreased from 0.846 to 0.828 in males, indicating the cranium became narrower relative to the cranial length. In females, the cephalic index increased from 0.831 to 0.850. Sex and birthyear were marginally interrelated in cephalic indices., Discussion: From the 1930s to 1970s, the Korean Peninsula experienced important historical shifts, and we speculate that the consequent shift in socioeconomic status is the most likely factor responsible for Koreans' cranial vault remodeling., (© 2018 Wiley Periodicals, Inc.)

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation., Competing Interests: Dong Hoon Suh, Suk-Joon Chang, Taejong Song, Sung Jong Lee, and Jae-Weon Kim serve as editors of the Journal of Gynecologic Oncology (JGO), but have no role in the decision to publish this article. No other conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Background: Understanding the risk factors that are associated with the development of interstitial lung disease might have an important role in understanding the pathogenetic mechanism of interstitial lung disease as well as prevention. We aimed to determine independent risk factors of interstitial lung disease development., Methods: This was a retrospective cohort study with nationwide population-based 9-year longitudinal data. We selected subjects who were aged > 40 years at cohort entry and with a self-reported history of cigarette smoking. Cases were selected based on International Classification of Diseases codes. A cohort of 312,519 subjects were followed until December 2013. We used Cox regression analysis to calculate the hazard ratios (HRs) for interstitial lung disease development., Results: Interstitial lung disease developed in 1972 of the 312,519 subjects during the 9-year period. Smoking (HR: 1.2; 95% confidence interval [CI]: 1.1-1.4), hepatitis C (HR: 1.6; 95% CI: 1.1-2.3), history of tuberculosis (HR: 1.5; 95% CI: 1.1-1.9), history of pneumonia (HR: 1.6; 95% CI: 1.3-2.0), and chronic obstructive pulmonary disease (HR: 1.8; 95% CI: 1.6-2.1), men (HR: 1.9; 95% CI: 1.7-2.1) were significantly associated with the development of interstitial lung disease. The risk of interstitial lung disease development increases with age, and the risk was 6.9 times higher (95% CI: 5.9-8.0) in those aged over 70 than in their forties., Conclusions: Smoking, hepatitis C, history of tuberculosis, history of pneumonia, chronic obstructive pulmonary disease, male sex, and older age were significantly associated with interstitial lung disease development.

The total dinoflagellate cyst community and the cysts of Cochlodinium polykrikoides in the surface sediments of South Sea (Tongyeong coast), South Korea, were analysed using next-generation sequencing (NGS) and morphological approaches. Dinoflagellate cysts can be highly abundant (111-4,087 cysts g -1 dry weight) and have diverse species composition. A total of 35 taxa of dinoflagellate cysts representing 16 genera, 21 species (including four unconfirmed species), and 14 complex species were identified by NGS analysis. Cysts of Scrippsiella spp (mostly Scrippsiella trochoidea) were the most dominant and Polykrikos schwartzii, Pentapharsodinium dalei, Ensiculifera carinata, and Alexandrium catenella/tamarense were common. Thus, a combination of NGS and morphological analysis is effective for studying the cyst communities present in a given environment. Although C. polykrikoides developed massive blooms during 2013-2014, microscopy revealed low density of their cysts, whereas no cysts were detected by NGS. However, the vegetative C. polykrikoides not appeared during 2015-2017 in spite of the observation of C. polykrikoides cysts. This suggests that the C. polykrikoides blooms were not due to development of their cysts but to other factors such as currents transporting them to a marine environment suitable for their growth.

Purpose: Lower urinary tract symptoms (LUTS) can be distressing and socially isolating, and the economic impact can be substantial. Further data to characterize the epidemiology and effects of LUTS in South Korea would be beneficial., Materials and Methods: In an international, internet-based survey, the prevalence and impact of LUTS was evaluated in adults aged ≥40 years. Questions related to International Continence Society (ICS) symptom definitions and the bother associated with each symptom. The international prostate symptom score (IPSS) and the overactive bladder symptom score (OABSS) were assessed., Results: Of the 2,080 participants from South Korea, 1,090 (52.4%) were women and 740 (35.6%) were aged ≥60 years. The prevalence of LUTS according to ICS criteria was 68.2% (men, 70.6%; women, 66.0%). LUTS prevalence increased significantly with age (p=0.01 in men and women). Storage symptoms only were reported in 16.2% of men and 30.5% of women, making this the most common ICS symptom group overall. Individual symptoms with the highest prevalence in the overall population were nocturia, frequency, and weak stream (36%, 30%, and 29%, respectively). IPSS results showed that 40.1% of participants had at least moderate symptoms. The prevalence of OABSS-defined overactive bladder was 19.7% (men, 19.5%; women, 19.9%). Fourteen percent of individuals with any LUTS visited healthcare professionals regarding urinary symptoms., Conclusions: LUTS affect the majority of adults aged ≥40 years in South Korea. The low percentage of individuals with LUTS consulting healthcare professionals regarding urinary symptoms indicates a need to improve rates of diagnosis and treatment., Competing Interests: CONFLICTS OF INTEREST: TK Yoo and KS Lee acted as consultants for Astellas Pharma. B Sumarsono, ST Kim, HJ Kim, HC Lee, and SH Kim are employees for Astellas Pharma. The authors have nothing to disclose.