During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024.This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels—high, moderate, limited, or insufficient—while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as “convincingly supports” (“evidence established” in the 2024 NASEM report), “favors acceptance,” “favors rejection,” or “inadequate to accept or reject.” The CoVaSC has established an independent committee to conduct causality assessments using the weightof-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-ofevidence framework and to detail the considerations involved in its practical application in the CoVaSC.

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC’s initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC’s second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA’s COVID-19 vaccination data and the National Health Insurance Service’s claims data. The CoVaSC’s 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

BACKGROUND/AIMS: Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients. METHODS: In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication. RESULTS: Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died. CONCLUSIONS Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.
Cohort Studies ; Coronavirus ; Coronavirus Infections* ; Follow-Up Studies ; Humans ; Korea ; Middle East* ; Pneumonia* ; Prospective Studies ; Survivors

Extramedullary plasmacytoma (EMP) represent 3% of plasma cell neoplasms. Approximately 80-90% of EMPs involve the mucosa-associated lymphoid tissue of the upper airways and 75% of these involve the nasal and paranasal regions, while renal or retroperitoneal infiltration is very rare. EMPs are highly radiosensitive, with excellent results. The local control rate of radiotherapy can reach 90-97% and the 5-year overall survival rate can be 57-61%. EMP has an indolent course and the prognosis is generally favorable, with 70% of the patients remaining disease free for 10 years. However, about 30% may progress to plasma cell myeloma or relapse. Here, we report a case of a huge retroperitoneal solitary extramedullary plasmacytoma that grew rapidly.
Humans ; Lymphoid Tissue ; Multiple Myeloma ; Neoplasms, Plasma Cell ; Plasmacytoma* ; Prognosis ; Radiotherapy ; Recurrence ; Survival Rate

BACKGROUND: Hemodynamic and functional evaluation with Doppler and tissue Doppler study as a part of comprehensive echocardiography is essential but normal reference values have never been reported from Korean normal population especially according to age and sex. METHODS: Using Normal echOcaRdiographic Measurements in a KoreAn popuLation study subjects, we obtained normal reference values for Doppler and tissue Doppler echocardiography including tricuspid annular velocities according to current guidelines and compared values according to gender and age groups. RESULTS: Mitral early diastolic (E) and late diastolic (A) velocity as well as E/A ratio were significantly higher in women compared to those in men. Conversely, mitral peak systolic and late diastolic annular velocity in both septal and lateral mitral annulus were significantly lower in women compared to those in men. However, there were no significant differences in both septal and lateral mitral early diastolic annular (e') velocity between men and women. In both men and women, mitral E velocity and its deceleration time as well as both E/A and E/e' ratio considerably increased with age. There were no significant differences in tricuspid inflow velocities and tricuspid lateral annular velocities between men and women except e' velocity, which was significantly higher in women compared to that in men. However, changes in both tricuspid inflow and lateral annular velocities according to age were similar to those in mitral velocities. CONCLUSION: Since there were significant differences in Doppler and tissue Doppler echocardiographic variables between men and women and changes according to age were even more considerable in both gender groups, normal Doppler echocardiographic values should be differentially applied based on age and sex.
Deceleration ; Echocardiography* ; Echocardiography, Doppler ; Female ; Hemodynamics ; Humans ; Male ; Reference Values

BACKGROUND: It is important to understand the distribution of 2-dimensional strain values in normal population. We performed a multicenter trial to measure normal echocardiographic values in the Korean population. METHODS: This was a substudy of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL) study. Echocardiographic specialists measured frequently used echocardiographic indices in healthy people according to a standardized method at 23 different university hospitals. The strain values were analyzed from digitally stored images. RESULTS: Of a total of 1003 healthy participants in NORMAL study, 2-dimensional strain values were measured in 501 subjects (265 females, mean age 47 ± 15 years old) with echocardiographic images only by GE echocardiographic machines. Interventricular septal thickness, left ventricular (LV) posterior wall thickness, systolic and diastolic LV dimensions, and LV ejection fraction were 7.5 ± 1.0 mm, 7.4 ± 1.0 mm, 29.9 ± 2.8 mm, 48.9 ± 3.6 mm, and 62 ± 4%, respectively. LV longitudinal systolic strain (LS) values of apical 4-chamber (A4C) view, apical 3-chamber (A3C) view, apical 2-chamber (A2C) view, and LV global LS (LVGLS) were −20.1 ± 2.3, −19.9 ± 2.7, −21.2 ± 2.6, and −20.4 ± 2.2%, respectively. LV longitudinal systolic strain rate (LVLSR) values of the A4C view, A3C view, A2C view, and LV global LSR (LVGLSR) were −1.18 ± 0.18, −1.20 ± 0.21, −1.25 ± 0.21, and −1.21 ± 0.21(−s), respectively. Females had lower LVGLS (−21.2 ± 2.2% vs. −19.5 ± 1.9%, p < 0.001) and LVGLSR (−1.25 ± 0.18(−s) vs. −1.17 ± 0.15(−s), p < 0.001) values than males. CONCLUSION: We measured LV longitudinal strain and strain rate values in the normal Korean population. Since considerable gender differences were observed, normal echocardiographic cutoff values should be differentially applied based on sex.
Echocardiography* ; Female ; Healthy Volunteers ; Heart Ventricles* ; Hospitals, University ; Humans ; Male ; Methods ; Multicenter Studies as Topic ; Reference Values ; Specialization

BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.
Antiviral Agents ; Aspartate Aminotransferases ; Coronavirus Infections* ; Disease Outbreaks ; Dyspnea ; Extracorporeal Membrane Oxygenation ; Fever ; Humans ; Hypotension ; Leukocytosis ; Leukopenia ; Lung Diseases ; Middle East Respiratory Syndrome Coronavirus ; Middle East* ; Mortality ; Pneumonia ; Polymerase Chain Reaction ; Republic of Korea* ; Respiration, Artificial ; Thrombocytopenia