Seoul Medical Center

The National Health Insurance Service–National Sample Cohort (NHIS-NSC) is a population-based cohort established by the National Health Insurance Service (NHIS) in South Korea. The sole purpose of constructing the cohort was to provide public health researchers and policy makers with representative, useful information regarding citizens’ utilization of health insurance and health examinations. Korea’s universal coverage health insurance system for all citizens was initiated in 1963, based on the National Medical Insurance Act, and was introduced for companies with over 500 employees in 1977. Universal healthcare coverage was achieved in 1989, only 12 years after its introduction, which is the fastest this has been achieved globally.1 In 2000 a single-insurer system, the NHIS, was launched by integrating more than 366 medical insurance organizations, for efficient system operation in Korea.1 The NHIS provides benefits for prevention, diagnosis, disease and injury treatment, as well as rehabilitation, births, deaths and health promotion. Currently the NHIS maintains and stores national records for healthcare utilization and prescriptions. The NHIS records have garnered academic interest due to the effectiveness of the system and relevance to public health and medical research. To meet this interest, a population database has been developed, the ‘National Health Information Database’ (NHID)2 containing personal information, demographics and medical treatment data for Korean citizens, who were categorized as insured employees, insured self-employed individuals or medical aid beneficiaries. The NHID was generated using participants’ medical bill expenses claimed by medical service providers. Data were rearranged according to date of medical treatment rather than date of claim. However, due to limited useability of the NHID’s unavoidably large volume and the lack of confidentiality regarding personal information, the NHIS decided to construct a representative sample database, the NHIS-NSC, with a substantial volume of representative information that does not require privacy regulation for research and policy development. To construct the NHIS-NSC, we first built a target population of 46 605 433 individuals using 47 851 928 individuals in the 2002 NHID by excluding non-citizens and special-purpose employees with an unidentifiable income level. From the target population a representative sample cohort of 1 025 340 participants was randomly selected, comprising 2.2% of the total eligible Korean population in 2002, and followed for 11 years until 2013 unless participants’ eligibility was disqualified due to death or emigration. Systematic stratified random sampling with proportional allocation within each stratum was conducted using the individual’s total annual medical expenses as a target variable for sampling.3 First, 1476 strata were constructed by age group, sex, participant’s eligibility status and income level. Specifically, strata were defined by 18 age groups (infants under 1 year, ages 1–4, 5-year age groups between 5 and 79, and 80 years and above), two groups according to sex (male, female) and 41 groups based on participant’s income level (upper 20 percentiles for insured employees, lower 20 percentiles for insured self-employed individuals, and the lowest level of income for medical aid beneficiaries). Next, within each stratum, systematic sampling was conducted after sorting population data by the value of total annual medical expenses and maintaining a sampling rate of 2.2%. Stratum samples were iteratively drawn until a maximum absolute percentage error—defined as a relative percentage difference between population and sample averages of total annual medical expenses to the population average—reached a predefined value of less than 5%. This technique was used to compensate for the severely positively skewed total annual medical expenses of the entire cohort and each stratum. During the follow-up period, the cohort was refreshed annually by adding a representative sample of newborns, sampled across 82 strata (two for sex, combined with 41 for parents’ income levels) using the 2.2% sampling rate (Figure 1). Participant’s residential information was not used as a stratum variable because the NHIS maintained records of workplace addresses until 2005 and residential addresses after 2006. A schematic representation of the cohort data construction. DB, database. Although the representativeness for follow-up years is not guaranteed, using an appropriate sampling design and sufficient sample size for the initial cohort can help ensure representativeness. The sample’s representativeness was, therefore, evaluated by examining whether a 95% confidence interval for the sample’s average total annual medical expenses contained the population average; it was satisfied in every stratum. Further, the sample cohort was compared with the population according to residence distribution across 16 regions in Korea. Moreover, the mean and standard deviation of health insurance premiums for the sample and population for each cohort year were compared; these were not used as a stratification or target variable for sampling. The difference in the proportion of residence is negligible for 2002, and changed slightly during the follow-up years 2003–13 by 0–0.3%. The difference in average health insurance premium is also negligible during cohort years. The cohort sampled in the 2002 NHID database was followed until 2013, provided that participants were still eligible for health insurance. The total numbers of participants in each of cohort years are presented in Table 1. The number of infants (age 0) in the initial cohort and those added annually are also given in the table. Currently the NHIS plans to maintain regular annual cohort updates for the NHIS-NSC. Number of participants in each cohort year and number of infants added annually (unit: person) Number of participants in each cohort year and number of infants added annually (unit: person) The cohort comprises four databases on participants’ insurance eligibility, medical treatments, medical care institutions and general health examinations. The insurance eligibility database contains 14 variables including information on participant’s identity and socioeconomic variables such as gender, residential area, type of health insurance, level of income, type and grade of disability registered, birth and death. Variables for cause of death and residential area details are provided upon request (see the ‘Can I get hold of the data?’). The medical treatment database consists of 57 variables containing information about participants’ medical bills claimed by medical service providers. It comprises four databases: participant’s electronic medical treatment bills, bill details, details of diseases and details of prescriptions. All four databases are further classified according to type of medicine: ‘medical’ and ‘dental & Chinese medicine’ tables. A pharmacy table is also included in the first two databases. In the medical care institution database, information regarding the type of institution, establishment, location, number of beds, facilities and physicians are recorded under 10 variables. The general health examination database comprises information regarding nationwide health examinations conducted by the NHIS in 2002–13, including major health examination results and information about lifestyles and behaviours obtained from questionnaires. In Korea, nationwide health examinations are conducted for citizens aged 40 years and above.4 Two types of examinations are performed, a general and a life-transition health examination. The former, initiated in 1995, is administered biennially to citizens aged 40 years or older who are dependants of the insured employee or householder/family members of insured self-employed individuals. An insured employee and a householder of the insured self-employed can receive the general health examination regardless of his/her age. For blue-collar employees, this examination is conducted annually. According to the 2013 NHIS statistics, 72.1% of eligible beneficiaries had received general health examinations.5 The more comprehensive life-transition health examination, initiated in 2008, is given to individuals on reaching age 40 and age 66, twice in a lifetime, who are eligible for general health examinations. Both nationwide health examinations involve a screening and a confirmatory test. Examination details are summarized in Table 2. The NHIS-NSC database contains only the first-stage (screening) examination data for those who took the examination during cohort years, with two separate datasets for 2002–08 and 2009–13 because major changes were made to the content of health examinations and questionnaires in 2009 in accordance with a system reformation. Thus, the general health examination database contains 37 variables in the 2002–08 datasets and 41 in the 2009–13 datasets. The numbers of participants who received health examinations during the cohort years are presented in the fourth column in Table 1; 11% received an examination in the initial cohort year (2002), whereas this is more than doubled in 2013, reaching 23%. A detailed list of NHIS-NSC database variables is included in Appendix Table 1 (available as Supplementary data at IJE online). Types and content of general health examinations provided by the NHIS aEligibility: An insured employee and a householder of the insured self-employed regardless of his/her age, a dependant of the insured self-employed individual over 40 years old, or a dependant of the insured employee, over 40 years old. bEligibility: individuals aged 40 and 66. This examination was started in 2008. cThe second-stage examination is performed if an examinee is categorized with suspected hypertension or diabetes or if a 70- or 74-year-old examinee is classified into a high-risk cognitive impairment category from his/her first-stage examination. dThe second-stage examination is performed on all examinees who received the first-stage examination regardless of its result. Types and content of general health examinations provided by the NHIS aEligibility: An insured employee and a householder of the insured self-employed regardless of his/her age, a dependant of the insured self-employed individual over 40 years old, or a dependant of the insured employee, over 40 years old. bEligibility: individuals aged 40 and 66. This examination was started in 2008. cThe second-stage examination is performed if an examinee is categorized with suspected hypertension or diabetes or if a 70- or 74-year-old examinee is classified into a high-risk cognitive impairment category from his/her first-stage examination. dThe second-stage examination is performed on all examinees who received the first-stage examination regardless of its result. To protect participants’ privacy, the Resident Registration Number (RRN, a unique identification number in Korea) which was initially used to construct the cohort, has been replaced with a newly-assigned eight-digit personal ID. Furthermore, to prevent the possibility of identifying a participant by merging information about rare disease status, age and residence, we replaced ICD-10 codes of 114 sensitive diseases with an asterisk except for the code’s initial. A comparison of socio-demographic variables in the NHIS-NSC database and population in 2002, as well as in 2013 (the most recent year of available data), are presented in Tables 3 and 4, respectively; and a comparison of health examination variables in 2002 and 2013 are presented in Appendix Table 1 (available as Supplementary data at IJE online) and Appendix Table 2 (available as Supplementary data at IJE online), respectively. A 95% confidence interval of each variable is also presented. For all demographic variables in 2002, the intervals contained the population average, indicating that the difference between the cohort and population was not significant (Table 3). Comparison of socio-demographic variables between the general population and sample cohort in 2002 [number of subjects (percentage)] CI, confidence interval. a95% confidence interval for the sample proportion. Comparison of socio-demographic variables between the general population and sample cohort in 2002 [number of subjects (percentage)] CI, confidence interval. a95% confidence interval for the sample proportion. Comparison of socio-demographic variables between the population and sample cohort in 2013, number of subjects (percentage) a95% confidence interval for the sample proportion. bThe population value has not been included in the 95% confidence i interval of the sample proportion. Comparison of socio-demographic variables between the population and sample cohort in 2013, number of subjects (percentage) a95% confidence interval for the sample proportion. bThe population value has not been included in the 95% confidence i interval of the sample proportion. In the year 2013, after 11 years of follow-up, the cohort proportion of insured employees underestimated that of the general population, whereas the cohort proportions of self-employed insured and medical-aid beneficiaries overestimated the population proportions for both males and females; however, the differences of less than 0.3% were trivial (Table 4). For smoking status—as a health examination variable—the cohort overestimated the proportion of male and female non-smokers compared with the general population at the time of data collection in the initiation year. The cohort included a significantly higher proportion of men who did not exercise and a lower proportion of men engaging in mild–moderate exercise, compared with the population. No statistical differences for other health variables between the cohort and population in 2002 were found (Appendix Table 2, available as Supplementary data at IJE online). In 2013, for males only the sample proportion of ex-smokers was 0.7% higher than that of the general population. There were differences between the cohort and the population in frequency of exercise (intensive physical activity more than 20 minute per week and moderate exercise more than 30 minute per week, variables that were surveyed since 2009; see Appendix Table 3, available as Supplementary data at IJE online). This finding implies that the cohort’s representativeness regarding some general health examination variables for health behaviour could be inadequate, requiring a periodic adjustment for future cohort years. We also would like to mention that the NHIS is currently preparing to build a special-purpose cohort, specific to general health examination data, using a population database of the NHID. Providing public access to the NHIS-NSC database can support research in auxiliary fields such as sociology, economics, environment policy and industry, besides evidence-based academic research in public health and medicine. As of March 2015, 8 months after becoming publicly available in July 2014, 109 studies (99 academic and 10 political researches) are being conducted using the NHIS-NSC database. Among these, Rim et al. found that the risk of stroke after retinal vein occlusion (RVO) was significantly higher especially for ischaemic stroke patients.6 They also showed that those with RVO had an approximately 2-fold higher hazard ratio among younger, compared with older, adults: suggesting that ophthalmologists need to specifically attend to this population.6 Kwon et al. examined the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis.7 They performed a nested case-control study using the NHIS-NSC database and found a positive relationship between the two, arguing that this relationship must be acknowledged for older adults requiring dental integration, to ensure that the benefits and risks are evaluated and that symptoms suggestive of ONJ are monitored.7 The NHIS-NSC database contains representative population-based cohort data, which is a major strength as it ensures its applicability in research—for example, when evaluating the effects of medical practice on health outcomes. Moreover, the data are large-scale, extensive and stable because it is constructed based on nationwide health insurance data generated by the government or public institutions’ involvement. Therefore, the cohort can also be used by policy makers to create higher value-added policies. Similar databases such as the Healthcare Cost and Utilization Project-National Inpatient Sample (NIS)8 in the USA or the National Health Insurance Research Database (NHIRD)9 in Taiwan, are available. Because the primary sampling unit of the NIS database, however, is the hospital, overlapping participants may introduce a selection bias. The NHIRD database uses a simple random sampling strategy; hence, the representativeness of major health-related indicators including the population’s demographic characteristics may have been lost. Moreover, they may not free of inherent limitations of cross-sectional data in evaluating, for example, an effect of medical practice on a health outcome. However, since the NHIS-NSC is a cohort based on nationwide health insurance data, it is both representative of the population and overcomes the limitations of cross-sectional data. The NHIS-NSC database has several limitations. Although the cohort comprises over one million participants, information on rare diseases may not be sufficient. Therefore, it is necessary to conduct a pre-evaluation of study size when using the NHIS-NSC database. The NHIS is currently preparing special-purpose cohort databases such as a cohort of older adults and of female workers, as well as customized databases for policy development/evaluation and academic research. Disease codes listed in the cohort may not represent participant’s true disease status because the code was created to claim health insurance serviced to participants, an inherent limitation of insurance databases. Hence, it warrants careful use by researchers. In this cohort, non-insurance benefits data such as cosmetic surgeries and information for over-the-counter drugs have not been included. Moreover, evaluating details of a participant’s specific medical treatment is difficult if his/her insurance claims were made under the diagnosis-related-group (DRG) policy. In contrast to the traditional fee- for-service payment system, the DRG system reimburses a fixed amount of medical fees to all hospitalized patients, depending on the patient’s illness and regardless of the type or cost of medical services provided during hospitalization.10,11 In Korea, nearly all types of healthcare providers follow the fee-for-service payment system and the DRG is applied only to seven disease groups (for details, see Health Insurance Review & Assessment Service of Korea website) [http://kostat.go.kr/portal/english/index.action].12 Currently, the NHIS-NSC database consists of 156 SAS® data files, comprising 13 files—for participants’ insurance eligibility (1 file), medical treatments (10 files), medical care institutions (1 file) and health examination (1 file)—for each of the 12 years of the cohort between 2002 and 2013. The total cohort file size is approximately 211 gigabytes with 2619 million cases in 2002–13. Data can be accessed through the NHIS’ National Health Insurance Data Sharing Service website [http://nhiss.nhis.or.kr/bd/ab/bdaba021eng.do]. To gain access to NHIS-NSC data, a completed application form, a research proposal and the applicant’s institutional review board (IRB) approval document should be submitted to and reviewed by the Review Committee of Research Support in NHIS. After granting approval, data are provided to an applicant for a fee. The data application process is described in Figure 2. Upon request, causes of death prepared by Statistics Korea12 and information regarding participant’s district of residence can be provided by the NHIS after the committee’s review. The process for accessing the NHIS-NSC database. IRB, Institutional Review Board. The NHIS-NSC profile in a nutshell The NHIS-NSC database is a population-based sample cohort. Its purpose is to provide representative, useful health insurance and health examination data to public health researchers and policy makers. A total of 1 025 340 participants of the cohort, 2.2% of the total eligible population, were randomly sampled from the 2002 Korean (nationwide) health insurance database to obtain baseline data. Cohort participants were followed for 11 years, until 2013. During the follow-up period, a representative sample of newborns (age 0) was added annually and deceased or emigrated participants were excluded. In 2013, the database included 1 014 730 participants. Information about participants’ insurance eligibility, medical treatment history, healthcare provider’s institution and general health examination are included. The NHIS-NSC database access on [http://nhiss.nhis. or.kr/bd/ab/bdaba021eng.do] requires a completed application form, a research proposal and the institutional review board’s approval document. A list of variables and other NHIS-NSC data are included in the Appendix, available as Supplementary data at IJE online. This work was supported by the NHIS in South Korea. This study used NHIS-NSC data (NHIS-2014-2-001) from the National Health Insurance Service (NHIS). Conflict of interest: None declared.

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.

Abstract Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies in patients with advanced or metastatic solid tumors, including patients with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the recommended phase II dose. Entrectinib was well tolerated, with predominantly Grades 1/2 adverse events that were reversible with dose modification. Responses were observed in non–small cell lung cancer, colorectal cancer, mammary analogue secretory carcinoma, melanoma, and renal cell carcinoma, as early as 4 weeks after starting treatment and lasting as long as >2 years. Notably, a complete CNS response was achieved in a patient with SQSTM1–NTRK1-rearranged lung cancer. Significance: Gene fusions of NTRK1/2/3, ROS1, and ALK (encoding TRKA/B/C, ROS1, and ALK, respectively) lead to constitutive activation of oncogenic pathways. Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease. Cancer Discov; 7(4); 400–9. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 339

OBJECTIVE: This study presents a preliminary report on the chest radiographic and computed tomography (CT) findings of the 2019 novel coronavirus disease (COVID-19) pneumonia in Korea. MATERIALS AND METHODS: As part of a multi-institutional collaboration coordinated by the Korean Society of Thoracic Radiology, we collected nine patients with COVID-19 infections who had undergone chest radiography and CT scans. We analyzed the radiographic and CT findings of COVID-19 pneumonia at baseline. Fisher's exact test was used to compare CT findings depending on the shape of pulmonary lesions. RESULTS: = 0.006). CONCLUSION: COVID-19 pneumonia in Korea primarily manifested as pure to mixed ground-glass opacities with a patchy to confluent or nodular shape in the bilateral peripheral posterior lungs. A considerable proportion of patients with COVID-19 pneumonia had normal chest radiographs.

INTRODUCTION: The incidence and prevalence of various sexual dysfunctions in women and men are important to understand to designate priorities for epidemiologic and clinical research. AIM: This manuscript was designed to conduct a review of the literature to determine the incidence and prevalence of sexual dysfunction in women and men. METHODS: Members of Committee 1 of the Fourth International Consultation on Sexual Medicine (2015) searched and reviewed epidemiologic literature on the incidence and prevalence of sexual dysfunctions. Key older studies and most studies published after 2009 were included in the text of this article. MAIN OUTCOME MEASURES: The outcome measures were the reports in the various studies of the incidence and prevalence of sexual dysfunction among women and men. RESULTS: There are more studies on incidence and prevalence for men than for women and many more studies on prevalence than incidence for women and men. The data indicate that the most frequent sexual dysfunctions for women are desire and arousal dysfunctions. In addition, there is a large proportion of women who experience multiple sexual dysfunctions. For men, premature ejaculation and erectile dysfunction are the most common sexual dysfunctions, with less comorbidity across sexual dysfunctions for men compared with women. CONCLUSION: These data need to be treated with caution, because there is a high level of variability across studies caused by methodologic differences in the instruments used to assess presence of sexual dysfunction, ages of samples, nature of samples, methodology used to gather the data, and cultural differences. Future research needs to use well-validated tools to gather data and ensure that the data collection strategy is clearly described.

BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. METHODS: We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2-3 weeks. CONCLUSIONS: Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.

At magnetic resonance (MR) imaging and multidetector computed tomography (CT), artifacts arising from metallic orthopedic hardware are an obstacle to obtaining optimal images. Although various techniques for reducing such artifacts have been developed and corroborated by previous researchers, a new era of more powerful MR imaging and multidetector CT modalities has renewed the importance of a systematic consideration of methods for artifact reduction. Knowledge of the factors that contribute to artifacts, of related theories, and of artifact reduction techniques has become mandatory for radiologists. Factors that affect artifacts on MR images include the composition of the metallic hardware, the orientation of the hardware in relation to the direction of the main magnetic field, the strength of the magnetic field, the pulse sequence type, and other MR imaging parameters (mainly voxel size, which is determined by the field of view, image matrix, section thickness, and echo train length). At multidetector CT, the factors that affect artifacts include the composition of the hardware, orientation of the hardware, acquisition parameters (peak voltage, tube charge, collimation, and acquired section thickness), and reconstruction parameters (reconstructed section thickness, reconstruction algorithm used, and whether an extended CT scale was used). A comparison of images obtained with different hardware and different acquisition and reconstruction parameters facilitates an understanding of methods for reducing or overcoming artifacts related to metallic implants.

The detection of thyroid nodules has become more common with the widespread use of ultrasonography (US). US is the mainstay for detecting and making the differential diagnosis of thyroid nodules as well as for providing guidance for a biopsy. The Task Force on Thyroid Nodules of the Korean Society of Thyroid Radiology has developed recommendations for the US diagnosis and US-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature, the results of multicenter studies and from the consensus of experts.

BACKGROUND: Although ultrasound (US) is routinely used for the preoperative evaluation of neck nodes in patients with papillary thyroid carcinoma (PTC), the diagnostic role of computed tomography (CT) has not been established. The purpose of our study is to determine the diagnostic accuracies of US, CT, and combined US and CT (US/CT) for detecting metastatic neck nodes in patients with PTC. METHODS: 165 consecutive patients (140 females and 25 males, mean age 47.9 years) with surgically proven PTC underwent US and CT for preoperative evaluation. CT was performed 2 or 3 months before radioiodine therapy. We assessed the diagnostic accuracies of US, CT, and US/CT using level-by-level analysis. RESULTS: In terms of predicting node metastases, overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of US were 51%, 92%, 77%, 81%, and 76%, respectively. Those of CT were 62%, 93%, 81%, 84%, and 80%, respectively, and those of US/CT were 66%, 88%, 79%, 77%, and 81%, respectively, at all neck levels. US/CT significantly increased sensitivity and demonstrated similar specificity compared with US alone in lateral neck levels (p = 0.02 and p = 1.0, respectively). US/CT increased sensitivity (p = 0.01), but decreased specificity compared with US alone in the central neck levels (p = 0.02). CT provided additional benefit for detecting metastatic nodes at more than one level in 8% of all patients, in 14% of patients with suspected nodal metastasis on US, and in 25% of patients with metastatic lymph nodes. CONCLUSIONS: The US/CT combination was found to be superior to US alone for the detection of metastatic lymph nodes in the lateral neck levels in PTC patients by level-by-level analysis.

The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with >9,000 confirmed cases as of March 25, 2020. COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world. Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea. These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

OBJECTIVE: We compared the diagnostic performance of gadoxetic acid-enhanced MRI with that of triple-phase 16-, 40-, and 64-MDCT in the preoperative detection of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Sixty-two consecutively registered patients (54 men, eight women; age range, 31-67 years) with 83 HCCs underwent triple-phase (arterial, portal venous, equilibrium) CT at 16-, 40-, or 64-MDCT and gadoxetic acid-enhanced 3-T MRI. The diagnosis of HCC was established after surgical resection. Three observers independently and randomly reviewed the MR and CT images on a tumor-by-tumor basis. The diagnostic accuracy of these techniques in the detection of HCC was assessed with alternative free response receiver operating characteristic (ROC) analysis. Sensitivity, positive and negative predictive values, and sensitivity according to tumor size were evaluated. RESULTS: For each observer, the areas under the ROC curve were 0.971, 0.959, and 0.967 for MRI and 0.947, 0.950, and 0.943 for CT. The differences were not statistically significant between the two techniques for each observer (p > 0.05). The differences in sensitivity and positive and negative predictive values between the two techniques for each observer were not statistically significant (p > 0.05). Among 10 HCCs 1 cm in diameter or smaller, each of the observers detected seven tumors with MRI. With CT, one observer detected five, one observer detected four, and one observer detected three HCCs with no statistically significant difference (p > 0.05). CONCLUSION: Gadoxetic acid-enhanced MRI and triple-phase MDCT have similar diagnostic performance in the preoperative detection of HCC, but MRI may be better than MDCT in the detection of HCC 1 cm in diameter or smaller.

Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development of vascular and lymphatic systems, tissue repair, and the maintenance of homeostasis. VEGF ligands and their receptors orchestrate endothelial cell proliferation, migration, and survival, playing a pivotal role in dynamic vascular remodeling. Dysregulated VEGF signaling drives diverse pathological conditions, including tumor angiogenesis, cardiovascular diseases, and ocular disorders. Excessive VEGF activity promotes tumor growth, invasion, and metastasis, while insufficient signaling contributes to impaired wound healing and ischemic diseases. VEGF-targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors, have revolutionized the treatment of diseases involving pathological angiogenesis, offering significant clinical benefits in oncology and ophthalmology. These therapies inhibit angiogenesis and slow disease progression, but they often face challenges such as therapeutic resistance, suboptimal efficacy, and adverse effects. To further explore these issues, this review provides a comprehensive overview of VEGF ligands and receptors, elucidating their molecular mechanisms and regulatory networks. It evaluates the latest progress in VEGF-targeted therapies and examines strategies to address current challenges, such as resistance mechanisms. Moreover, the discussion includes emerging therapeutic strategies such as innovative drug delivery systems and combination therapies, highlighting the continuous efforts to improve the effectiveness and safety of VEGF-targeted treatments. This review highlights the translational potential of recent discoveries in VEGF biology for improving patient outcomes.

The relationship between immunity and nutrition is well known and its role in coronavirus disease 2019 (COVID-19) is also being paid great attention. However, the nutritional status of COVID-19 patients is unknown. Vitamin B1, B6, B12, vitamin D (25-hydroxyvitamin D), folate, selenium, and zinc levels were measured in 50 hospitalized patients with COVID-19. Overall, 76% of the patients were vitamin D deficient and 42% were selenium deficient. No significant increase in the incidence of deficiency was found for vitamins B1, B6, and B12, folate, and zinc in patients with COVID-19. The COVID-19 group showed significantly lower vitamin D values than the healthy control group (150 people, matched by age/sex). Severe vitamin D deficiency (based on a cut-off of ≤10 ng/dl) was found in 24.0% of the patients in the COVID-19 group and 7.3% in the control group. Among 12 patients with respiratory distress, 11 (91.7%) were deficient in at least one nutrient. However, patients without respiratory distress showed a deficiency in 30/38 cases (78.9%; p = 0.425). These results suggest that a deficiency of vitamin D or selenium may decrease the immune defenses against COVID-19 and cause progression to severe disease. However, more precise and large-scale studies are needed.

BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined. METHODS: We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM). RESULTS: The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples. CONCLUSIONS: These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

Recent experimental evidences suggest protective and trophic effects of ginseng in the memory function of Alzheimer disease (AD). Thus, we investigated the clinical efficacy of Panax ginseng in the cognitive performance of AD patients in an open-label study. Consecutive AD patients were randomly assigned to the ginseng (n=58) or the control group (n=39), and the ginseng group was treated with Panax ginseng powder (4.5 g/d) for 12 weeks. Cognitive performances were monitored using the mini-mental state examination (MMSE) and Alzheimer disease assessment scale (ADAS) during 12 weeks of the ginseng treatment and at 12 weeks after the ginseng discontinuation. MMSE and ADAS scales showed no baseline difference between the groups. After ginseng treatment, the cognitive subscale of ADAS and the MMSE score began to show improvements and continued up to 12 weeks (P=0.029 and P=0.009 vs. baseline, respectively). After discontinuing ginseng, the improved ADAS and MMSE scores declined to the levels of the control group. These results suggest that Panax ginseng is clinically effective in the cognitive performance of AD patients.

Although ethanol ablation has been successfully used to treat cystic thyroid nodules, this procedure is less effective when the thyroid nodules are solid. Radiofrequency (RF) ablation, a newer procedure used to treat malignant liver tumors, has been valuable in the treatment of benign thyroid nodules regardless of the extent of the solid component. This article reviews the basic physics, techniques, applications, results, and complications of thyroid RF ablation, in comparison to laser ablation.