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.

The prevalence of thyroid cancer in pregnant women is unknown; however, given that thyroid cancer commonly develops in women, especially young women of childbearing age, new cases are often diagnosed during pregnancy. This recommendation summarizes the follow-up and treatment when thyroid cancer is diagnosed during pregnancy and when a woman with thyroid cancer becomes pregnant. If diagnosed in the first trimester, surgery should be postponed until after delivery, and the patient should be monitored with ultrasound. If follow-up before 24–26 weeks of gestation shows that thyroid cancer has progressed, surgery should be considered. If it has not progressed at 24–26 weeks of gestation or if papillary thyroid cancer is diagnosed after 20 weeks of pregnancy, surgery should be considered after delivery.

Surgical resection is typically the primary treatment for differentiated thyroid cancer (DTC), followed by radioactive iodine (RAI) and thyroid-stimulating hormone suppression therapies based on the cancer stage and risk of recurrence. Nevertheless, further treatment may be necessary for patients exhibiting persistent disease following RAI therapy, residual disease refractory to RAI, or unresectable locoregional lesions. This guideline discusses the role of external beam radiotherapy and chemotherapy following surgical resection in patients with DTC. External beam radiotherapy is ineffective if DTC has been entirely excised (Grade 2). Adjuvant external beam radiotherapy may be optionally performed in patients with incomplete surgical resection or frequently recurrent disease (Grade 2). In patients at high risk of recurrence following surgery and RAI therapy, adjuvant external beam radiotherapy may be optionally considered (Grade 3). However, external beam radiotherapy may increase the risk of serious adverse events after tyrosine kinase inhibitor therapy. Therefore, careful consideration is needed when prescribing external beam radiotherapy for patients planning to undergo tyrosine kinase inhibitor therapy. There is no evidence supporting the benefits of the routine use of adjuvant chemotherapy for DTC treatment (Grade 2).

Only a small percentage of patients (2-5%) with differentiated thyroid cancer (DTC) exhibit distant metastasis at the initial diagnosis or during the disease course. The most common metastatic sites of DTC are the lungs, followed by the bones. Radioactive iodine (RAI) therapy is considered the primary treatment for RAI-avid distant metastatic DTC. Depending on the characteristics of metastatic lesions, local treatment such as surgical resection, radiofrequency ablation, and external beam radiation therapy may be considered for some patients with metastatic DTC. Slowly growing and asymptomatic metastases can be monitored with follow-up while receiving thyroid-stimulating hormone (TSH) suppression therapy. In patients with a limited number of lung metastases and good performance status, surgical removal of the metastatic lesions may be considered. Systemic therapy should be considered for patients with progressive RAI refractory DTC. In this clinical guideline, we aim to outline the treatment principles for patients with lung, bone, and brain metastases of DTC.

The primary treatment for differentiated thyroid cancer (DTC) with distant metastasis is high-dose radioactive iodine (RAI) therapy, which can have various effects depending on the iodine uptake of thyroid cancer cells. The iodine uptake of metastatic lesions decreases over time, and approximately 40-70% of patients eventually develop RAI refractory disease. Although the prognosis of patients with RAI refractory DTC is very poor, clinical outcomes vary depending on the location and progression of metastatic lesions. Therefore, it is crucial to determine which patients should receive active systemic therapy with tyrosine kinase inhibitor (TKI) and how to apply local treatment before or during systemic therapy. This guideline covers the definition, treatment principles, systemic anticancer agents, and complications of progressive RAI-refractory DTC. RAI refractory DTC is defined as (1) the absence of RAI uptake on whole body scan, (2) presence of RAI uptake in some lesions but not in others, or (3) disease progression despite RAI uptake. Treatment options for RAI refractory DTC include surgery, external beam radiation therapy, locoregional therapies such as high-intensity focused ultrasound ablation, and systemic anticancer therapy.In patients with minimal symptoms and progression, active surveillance without specific treatment may be considered. Systemic treatment should be considered for patients with multiple progressive lesions by RECIST criteria. Furthermore, testing for cancer gene mutations, including BRAF, NTRK, and RET genes, is recommended for personalized therapy. Systemic therapy should be decided based on shared decision-making between the patient and specialist, considering anticipated benefits and risks. Regular assessment of treatment responses and evaluation of adverse events is essential, with dose adjustment based on these assessments. The optimal time of use, clinical approaches for the prevention and control of adverse events, and individualized treatment approaches based on patient characteristics will be of great help in the treatment of patients with RAI-refractory DTC.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Objective: Emergency department (ED) overcrowding is a global issue that negatively impacts the clinical outcome. Through the coronavirus disease 2019 (COVID-19) pandemic era, overcrowding of ED isolated territory (isolation bed) was aggravated. This study analyzed overcrowding indices of ED isolation beds during the COVID-19 pandemic. Methods: This study was a single-center, retrospective, observational study. The study analyzed 34,925 patients who visited the ED during the COVID-19 pandemic from April 2021 to August 2022. Patients who were treated in isolation beds and regular beds were compared. Among the patients using isolation beds, patients who stayed longer than 720 minutes were also classified and analyzed. Results: During the analysis period, 4,479 and 34,943 patients were treated in the ED isolation bed and ED regular bed, respectively. The overcrowding indices (general ward admission rate, intensive care unit admission rate, ED-length of stay, transfer rate, mortality rate, prolonged ED stay patient ratio) of the isolation beds were significantly higher than those of the ED regular bed (P<0.05). The prolonged ED stay-patient ratio of isolation beds and regular beds was affected by the number of COVID-19 patients (regular bed, r=0.617 and P=0.01; isolation bed, r=0.525 and P=0.03). The average ED-length of stay of isolation beds was longer than that of the ED regular beds. One hundred and forty-five patients were classified as prolonged ED stay patients. Their time from the decision point to the discharge point comprised a higher rate with an average of 76.52%. Conclusion ED isolation beds are more vulnerable to infectious disease outbreaks. A proper medical policy and arrangement management system that can flexibly deal with disaster emergencies are required

Background: Heterotopic ossification (HO) is difficult to characterize and classify on simple radiographs. Therefore, we attempted to evaluate intraobserver and interobserver reliability of simple radiography and computed tomography (CT) for detecting and classifying HO after reverse shoulder arthroplasty (RSA). It was hypothesized that CT would provide more reliable results than simple radiography. Methods: This retrospective study reviewed 30 patients who underwent RSA performed by a single surgeon. Patients were included if they had both postoperative simple radiographs and CT images taken immediately after surgery and at 1 year after surgery and if they had completed clinical assessment at least 1 year after surgery. We first evaluated the intraobserver and interobserver reliability for the detection of the presence of HO and Modified Brooker’s classification both on simple radiographs and CT scans with the use of Kappa statistics. Then, we analyzed the correlation of HO observed in simple radiographs and CT scans with clinical outcomes. All radiographic evaluations were performed by 2 independent reviewers in random orders with 3 weeks of intervals. Results: The intraobserver reliability outcomes of both reviewers in simple radiography and CT were almost perfect or perfect for the detection of HO and classification. However, CT images improved the interobserver reliability for the detection of HO (kappa value for simple radiographs [KXR ] = 0.6018 and kappa value for CT [KCT ] = 0.8316) and classification (KXR = 0.5300 and KCT = 0.6964).At a mean follow-up of 25 months (range, 12–54 months), clinical scores were not significantly different according to the presence of HO based on simple radiographs. However, when CT images were used, the University of California, Los Angeles score and physical component score of short-form 36-item health survey were significantly lower in patients with HO than in patients without HO (27.0 vs. 30.4, p = 0.045 and 57.6 vs. 70.7, p = 0.034, respectively). Conclusions Both simple radiography and CT provided excellent intraobserver reliability for detecting and classifying HO after RSA. Compared to simple radiography, CT tended to improve interobserver reliability and defined the presence and severity of HO more clearly.

Background: Heterotopic ossification (HO) is difficult to characterize and classify on simple radiographs. Therefore, we attempted to evaluate intraobserver and interobserver reliability of simple radiography and computed tomography (CT) for detecting and classifying HO after reverse shoulder arthroplasty (RSA). It was hypothesized that CT would provide more reliable results than simple radiography. Methods: This retrospective study reviewed 30 patients who underwent RSA performed by a single surgeon. Patients were included if they had both postoperative simple radiographs and CT images taken immediately after surgery and at 1 year after surgery and if they had completed clinical assessment at least 1 year after surgery. We first evaluated the intraobserver and interobserver reliability for the detection of the presence of HO and Modified Brooker’s classification both on simple radiographs and CT scans with the use of Kappa statistics. Then, we analyzed the correlation of HO observed in simple radiographs and CT scans with clinical outcomes. All radiographic evaluations were performed by 2 independent reviewers in random orders with 3 weeks of intervals. Results: The intraobserver reliability outcomes of both reviewers in simple radiography and CT were almost perfect or perfect for the detection of HO and classification. However, CT images improved the interobserver reliability for the detection of HO (kappa value for simple radiographs [KXR ] = 0.6018 and kappa value for CT [KCT ] = 0.8316) and classification (KXR = 0.5300 and KCT = 0.6964).At a mean follow-up of 25 months (range, 12–54 months), clinical scores were not significantly different according to the presence of HO based on simple radiographs. However, when CT images were used, the University of California, Los Angeles score and physical component score of short-form 36-item health survey were significantly lower in patients with HO than in patients without HO (27.0 vs. 30.4, p = 0.045 and 57.6 vs. 70.7, p = 0.034, respectively). Conclusions Both simple radiography and CT provided excellent intraobserver reliability for detecting and classifying HO after RSA. Compared to simple radiography, CT tended to improve interobserver reliability and defined the presence and severity of HO more clearly.

Background: Heterotopic ossification (HO) is difficult to characterize and classify on simple radiographs. Therefore, we attempted to evaluate intraobserver and interobserver reliability of simple radiography and computed tomography (CT) for detecting and classifying HO after reverse shoulder arthroplasty (RSA). It was hypothesized that CT would provide more reliable results than simple radiography. Methods: This retrospective study reviewed 30 patients who underwent RSA performed by a single surgeon. Patients were included if they had both postoperative simple radiographs and CT images taken immediately after surgery and at 1 year after surgery and if they had completed clinical assessment at least 1 year after surgery. We first evaluated the intraobserver and interobserver reliability for the detection of the presence of HO and Modified Brooker’s classification both on simple radiographs and CT scans with the use of Kappa statistics. Then, we analyzed the correlation of HO observed in simple radiographs and CT scans with clinical outcomes. All radiographic evaluations were performed by 2 independent reviewers in random orders with 3 weeks of intervals. Results: The intraobserver reliability outcomes of both reviewers in simple radiography and CT were almost perfect or perfect for the detection of HO and classification. However, CT images improved the interobserver reliability for the detection of HO (kappa value for simple radiographs [KXR ] = 0.6018 and kappa value for CT [KCT ] = 0.8316) and classification (KXR = 0.5300 and KCT = 0.6964).At a mean follow-up of 25 months (range, 12–54 months), clinical scores were not significantly different according to the presence of HO based on simple radiographs. However, when CT images were used, the University of California, Los Angeles score and physical component score of short-form 36-item health survey were significantly lower in patients with HO than in patients without HO (27.0 vs. 30.4, p = 0.045 and 57.6 vs. 70.7, p = 0.034, respectively). Conclusions Both simple radiography and CT provided excellent intraobserver reliability for detecting and classifying HO after RSA. Compared to simple radiography, CT tended to improve interobserver reliability and defined the presence and severity of HO more clearly.