Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). Conclusion This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.