Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background: Deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) are employed to address highly urgent patients, including those with acute liver failure (ALF), acute-on-chronic liver failure (ACLF), or critical cirrhosis. This study compares outcomes between LDLT and DDLT patients with ALF, ACLF, or critical cirrhosis in highly urgent LDLT (HU-LDLT) applications. Methods: This study conducted a retrospective analysis of the Korean Network for Organ Sharing (KONOS) data, which included 391 consecutive HU-LDLT applications from 2017 to 2021. Results: The proportion of DDLT was 15.1% (n=59) within the cohort of HU-LDLT applications. The prevalence of hepatorenal syndrome, duration of pre-transplant intensive care unit (ICU) care, incidence of pre-transplant continuous renal replacement therapy, and median model for end-stage liver disease scores were significantly greater and prolonged in DDLT patients compared to LDLT patients. Statistical analysis revealed no significant differences in postoperative complications or overall survival between the two groups. In the multivariate analysis, only pre-transplant ventilator care emerged as a significant predisposing factor for mortality. Conclusion The present study indicates that LDLT is a viable option, yielding comparable perioperative and long-term outcomes to DDLT for HU patients, which can encourage living liver donation to overcome organ shortages in HU patients.

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.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

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.

The global burden of mental illness has increased significantly since the COVID-19 pandemic. In South Korea, despite this rising burden, the utilization of mental health services remains critically low compared to other countries. This study evaluated successful integrated treatment centers from various countries, including the United States, the United Kingdom, and Australia, to identify the best practices that can be applied to South Korean society. These international examples informed the development of Mind the SHIM (SNUH Health in Mind) center, an integrated treatment model designed to address the gaps in non-pharmacological mental health services in South Korea. Mind the SHIM center focuses on developing and validating programs tailored to local needs, emphasizing professional education, systematic program delivery, and community collaboration. The biopsychosocial approach of the center is expected to enhance the overall quality of life of the patients and increase the utilization of mental health services, reducing the broader economic and social burden of mental illness in South Korea.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Allergen immunotherapy (AIT) has been used for over a century and has been demonstrated to be effective in treating patients with various allergic diseases. AIT allergens can be administered through various routes, including subcutaneous, sublingual, intralymphatic, oral, or epicutaneous routes. Sublingual immunotherapy (SLIT) has recently gained clinical interest, and it is considered an alternative treatment for allergic rhinitis (AR) and asthma. This review provides an overview of the current evidence-based studies that address the use of SLIT for treating AR, including (1) mechanisms of action, (2) appropriate patient selection for SLIT, (3) the current available SLIT products in Korea, and (4) updated information on its efficacy and safety. Finally, this guideline aims to provide the clinician with practical considerations for SLIT.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.