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: An ideal lung allocation system should reduce waiting list deaths, improve transplant survival, and ensure equitable organ allocation. This study aimed to develop a novel lung allocation score (LAS) system, the MaxBenefit LAS, to maximize transplant benefits. Methods: This study retrospectively analyzed data from the Korean Network for Organ Sharing database, including 1,599 lung transplant candidates between September 2009 and December 2020. We developed the MaxBenefit LAS, combining a waitlist mortality model and a post-transplant survival model using elastic-net Cox regression, was assessed using area under the curve (AUC) values and Uno’s C-index. Its performance was compared to the US LAS in an independent cohort. Results: The waitlist mortality model showed strong predictive performance with AUC values of 0.834 and 0.818 in the training and validation cohorts, respectively. The post-transplant survival model also demonstrated good predictive ability (AUC: 0.708 and 0.685). The MaxBenefit LAS effectively stratified patients by risk, with higher scores correlating with increased waitlist mortality and decreased post-transplant mortality. The MaxBenefit LAS outperformed the conventional LAS in predicting waitlist death and identifying candidates with higher transplant benefits. Conclusion The MaxBenefit LAS offers a promising approach to optimizing lung allocation by balancing the urgency of candidates with their likelihood of survival post-transplant. This novel system has the potential to improve outcomes for lung transplant recipients and reduce waitlist mortality, providing a more equitable allocation of donor lungs.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder affecting the sacroiliac joints and axial spine. Along with pharmacotherapy, non-pharmacological interventions for axSpA are crucial and constitute the cornerstone of treatment. Here, we review the evidence for non-pharmacological treatment of axSpA as a basis for the 2023 Korean treatment recommendations for patients with axSpA. The effectiveness of the core non-pharmacological approaches, such as education, smoking cessation, and exercise, has been reaffirmed. High-quality research on surgical treatment is limited. However, total hip replacement is advised in patients with ongoing pain or disability and visible structural damage to the hip on imaging. Urgent spinal intervention should be considered in cases of acute spinal pain with neurological deficiency or concurrent unstable fractures. Evidence for complementary therapies, including spas and acupuncture, remains insufficient.

Background: Malnutrition exacerbates the prognosis of numerous diseases; however, its specific impact on severe coronavirus disease 2019 (COVID-19) outcomes remains insufficiently explored. Methods: This multicenter study in Korea evaluated the nutritional status of 1,088 adults with severe COVID-19 using the Geriatric Nutritional Risk Index (GNRI) based on serum albumin levels and body weight. The patients were categorized into two groups: GNRI >98 (no-risk) and GNRI ≤98 (risk). Propensity score matching, adjusted for demographic and clinical variables, was conducted. Results: Of the 1,088 patients, 642 (59%) were classified as at risk of malnutrition. Propensity score matching revealed significant disparities in hospital (34.3% vs. 19.4%, p<0.001) and intensive care unit (ICU) mortality (31.5% vs. 18.9%, p<0.001) between the groups. The risk group was associated with a higher hospital mortality rate in the multivariate Cox regression analyses following propensity score adjustment (hazard ratio [HR], 1.64; p=0.001). Among the 670 elderly patients, 450 were at risk of malnutrition. Furthermore, the risk group demonstrated significantly higher hospital (52.1% vs. 29.5%, p<0.001) and ICU mortality rates (47.2% vs. 29.1%, p<0.001). The risk group was significantly associated with increased hospital mortality rates in the multivariate analyses following propensity score adjustment (HR, 1.66; p=0.001). Conclusion Malnutrition, as indicated by a low GNRI, was associated with increased mortality in patients with severe COVID-19. This effect was also observed in the elderly population. These findings underscore the critical importance of nutritional assessment and effective interventions for patients with severe COVID-19.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder affecting the sacroiliac joints and axial spine. Along with pharmacotherapy, non-pharmacological interventions for axSpA are crucial and constitute the cornerstone of treatment. Here, we review the evidence for non-pharmacological treatment of axSpA as a basis for the 2023 Korean treatment recommendations for patients with axSpA. The effectiveness of the core non-pharmacological approaches, such as education, smoking cessation, and exercise, has been reaffirmed. High-quality research on surgical treatment is limited. However, total hip replacement is advised in patients with ongoing pain or disability and visible structural damage to the hip on imaging. Urgent spinal intervention should be considered in cases of acute spinal pain with neurological deficiency or concurrent unstable fractures. Evidence for complementary therapies, including spas and acupuncture, remains insufficient.

Background: Malnutrition exacerbates the prognosis of numerous diseases; however, its specific impact on severe coronavirus disease 2019 (COVID-19) outcomes remains insufficiently explored. Methods: This multicenter study in Korea evaluated the nutritional status of 1,088 adults with severe COVID-19 using the Geriatric Nutritional Risk Index (GNRI) based on serum albumin levels and body weight. The patients were categorized into two groups: GNRI >98 (no-risk) and GNRI ≤98 (risk). Propensity score matching, adjusted for demographic and clinical variables, was conducted. Results: Of the 1,088 patients, 642 (59%) were classified as at risk of malnutrition. Propensity score matching revealed significant disparities in hospital (34.3% vs. 19.4%, p<0.001) and intensive care unit (ICU) mortality (31.5% vs. 18.9%, p<0.001) between the groups. The risk group was associated with a higher hospital mortality rate in the multivariate Cox regression analyses following propensity score adjustment (hazard ratio [HR], 1.64; p=0.001). Among the 670 elderly patients, 450 were at risk of malnutrition. Furthermore, the risk group demonstrated significantly higher hospital (52.1% vs. 29.5%, p<0.001) and ICU mortality rates (47.2% vs. 29.1%, p<0.001). The risk group was significantly associated with increased hospital mortality rates in the multivariate analyses following propensity score adjustment (HR, 1.66; p=0.001). Conclusion Malnutrition, as indicated by a low GNRI, was associated with increased mortality in patients with severe COVID-19. This effect was also observed in the elderly population. These findings underscore the critical importance of nutritional assessment and effective interventions for patients with severe COVID-19.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.