Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Background: Renal replacement therapy (RRT) is an important treatment option for sepsisassociated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies. Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsisassociated AKI, respectively. Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsisassociated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3–25) and vasopressor administration (median, 21; IQR, 5–26) than the late CKRT group did (median, 10.5; IQR, 0–23; P = 0.037 and median, 13.5;IQR, 0–25; P = 0.028, respectively). The Kaplan–Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040).In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237). Conclusion Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours.

Background: While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea. Materials and Methods: We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023. Results: A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively. Conclusion This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.

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.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. Methods: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. Results: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. Conclusion This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Background: Renal replacement therapy (RRT) is an important treatment option for sepsisassociated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies. Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsisassociated AKI, respectively. Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsisassociated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3–25) and vasopressor administration (median, 21; IQR, 5–26) than the late CKRT group did (median, 10.5; IQR, 0–23; P = 0.037 and median, 13.5;IQR, 0–25; P = 0.028, respectively). The Kaplan–Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040).In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237). Conclusion Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours.

Background: While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea. Materials and Methods: We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023. Results: A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively. Conclusion This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.

Background: Renal replacement therapy (RRT) is an important treatment option for sepsisassociated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies. Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsisassociated AKI, respectively. Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsisassociated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3–25) and vasopressor administration (median, 21; IQR, 5–26) than the late CKRT group did (median, 10.5; IQR, 0–23; P = 0.037 and median, 13.5;IQR, 0–25; P = 0.028, respectively). The Kaplan–Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040).In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237). Conclusion Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours.