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.

Purpose: Erectile dysfunction (ED) is considered a microvascular disorder and serves as an indicator for the potential development of cardiovascular disease (CVD). Although left ventricular diastolic dysfunction (LVDD) reflects early myocardial damage caused by microvascular disorders, the association between ED and LVDD remains poorly elucidated. Materials and Methods: A cross-sectional study was conducted on 123 patients with ED. They underwent RigiScan, and conventional echocardiography, and attempted International Index of Erectile Function (IIEF) questionnaire. ED severity was evaluated by measuring changes in the penile base circumference and duration of penile rigidity (≥70%) during erection. The early diastolic velocity of mitral inflow (E) and early diastolic velocity of the mitral annulus (e′) were measured using echocardiography. The patients were grouped based on the presence of CVD. Results: Among 123 patients, 29 had CVD and 94 did not. Patients with CVD exhibited more pronounced ED and more severe LVDD. Associations between increased penile circumference with echocardiographic parameters were more prominent in patients with CVD than in those without CVD (ΔTtop and e′ wave, r=0.508 and r=0.282, respectively, p for interaction=0.033; ΔTbase and E/e′ ratio, r=-0.338 and r=-0.293, respectively, p for interaction <0.001). In the multivariate linear regression, the increase of penile base circumference was an independent risk factor for LVDD (e′, B=0.503; E/e′ ratio, B=-1.416, respectively, p<0.001). Conclusions ED severity correlated well with LV diastolic dysfunction, particularly in the presence of CVD. This study highlighted the potential role of ED assessment as early indicator of CVD development.

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.

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.

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.