In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Background: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. Methods: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. Results: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. Conclusion A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

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: The optimal duration and net clinical benefit of dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) have not been elucidated in realworld situations. Methods: Using nationwide claims data from 2013 to 2021, we selected patients who underwent TAVR and categorized them into two groups: short- and long-term (≤ 3 and > 3 months, respectively) DAPT group. Propensity score matching was used to balance baseline characteristics. The primary endpoint was the occurrence of net adverse clinical events (NACEs), including all-cause death, myocardial infarction, stroke, any coronary and peripheral revascularization, systemic thromboembolism, and bleeding events, at 1 year. Survival analyses were conducted using Kaplan-Meier estimation and Cox proportional hazards regression. Results: Patients who met the inclusion criteria (1,695) were selected. Propensity score matching yielded 1,215 pairs of patients: 416 and 799 in the short- and long-term DAPT groups, respectively. In the unmatched cohort, the mean ages were 79.8 ± 6.1 and 79.7 ± 5.8 years for the short- and long-term DAPT groups, respectively. In the matched cohort, the mean ages were 80.6 ± 5.9 and 79.9 ± 5.9 years for the short- and long-term DAPT groups, respectively. Over one year in the unmatched cohort, the NACE incidence was 11.9% and 11.5% in the short- and long-term DAPT groups, respectively (P = 0.893). The all-cause mortality rates were 7.4% and 4.7% (P = 0.042), composite ischemic event rates were 2.5% and 4.7% (P = 0.056), and bleeding event rates were 2.7% and 4.7% (P = 0.056) in the shortand long-term groups, respectively. In the matched cohort, the incidence of NACE was 9.6% in the short-term DAPT group and 11.6% in the long-term DAPT group, respectively (P = 0.329).The all-cause mortality rates were 6.5% and 4.9% (P = 0.298), composite ischemic event rates were 1.4% and 4.5% (P = 0.009), and bleeding event rates were 2.2% and 4.4% (P = 0.072) in the short- and long-term groups, respectively. Conclusion In patients who successfully underwent transfemoral TAVR, the short- and longterm DAPT groups exhibited similar one-year NACE rates. However, patients in the long-term DAPT group experienced more bleeding and ischemic events.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

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: The optimal duration and net clinical benefit of dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) have not been elucidated in realworld situations. Methods: Using nationwide claims data from 2013 to 2021, we selected patients who underwent TAVR and categorized them into two groups: short- and long-term (≤ 3 and > 3 months, respectively) DAPT group. Propensity score matching was used to balance baseline characteristics. The primary endpoint was the occurrence of net adverse clinical events (NACEs), including all-cause death, myocardial infarction, stroke, any coronary and peripheral revascularization, systemic thromboembolism, and bleeding events, at 1 year. Survival analyses were conducted using Kaplan-Meier estimation and Cox proportional hazards regression. Results: Patients who met the inclusion criteria (1,695) were selected. Propensity score matching yielded 1,215 pairs of patients: 416 and 799 in the short- and long-term DAPT groups, respectively. In the unmatched cohort, the mean ages were 79.8 ± 6.1 and 79.7 ± 5.8 years for the short- and long-term DAPT groups, respectively. In the matched cohort, the mean ages were 80.6 ± 5.9 and 79.9 ± 5.9 years for the short- and long-term DAPT groups, respectively. Over one year in the unmatched cohort, the NACE incidence was 11.9% and 11.5% in the short- and long-term DAPT groups, respectively (P = 0.893). The all-cause mortality rates were 7.4% and 4.7% (P = 0.042), composite ischemic event rates were 2.5% and 4.7% (P = 0.056), and bleeding event rates were 2.7% and 4.7% (P = 0.056) in the shortand long-term groups, respectively. In the matched cohort, the incidence of NACE was 9.6% in the short-term DAPT group and 11.6% in the long-term DAPT group, respectively (P = 0.329).The all-cause mortality rates were 6.5% and 4.9% (P = 0.298), composite ischemic event rates were 1.4% and 4.5% (P = 0.009), and bleeding event rates were 2.2% and 4.4% (P = 0.072) in the short- and long-term groups, respectively. Conclusion In patients who successfully underwent transfemoral TAVR, the short- and longterm DAPT groups exhibited similar one-year NACE rates. However, patients in the long-term DAPT group experienced more bleeding and ischemic events.