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.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Objective: This study aimed to compare the efficacy and safety of romosozumab, a bone anabolic agent, versus vertebroplasty, a conventional surgical intervention, in treating osteoporotic vertebral compression fractures (OVCFs). Methods: A retrospective analysis included 86 thoracic/lumbar compression fracture patients from 2014 to 2022 at a medical center. Forty-two patients received romosozumab (monthly injections for 1 year) followed by 1 year of denosumab, while 44 underwent vertebroplasty followed by denosumab injections biannually for 2 years. Outcomes were assessed using the Numerical Rating Scale (NRS) for pain, bone mineral density (BMD), vertebral compression ratio, and Cobb angle over 12 months. Results: At 12 months, the romosozumab group showed a greater reduction in NRS scores (4.90 ± 1.01 vs. 4.27 ± 1.34, p = 0.015) and a higher increase in lumbar BMD (0.8 ± 0.5 vs. 0.5 ± 0.3, p = 0.000) compared to the vertebroplasty group. There were no significant differences in changes in hip total BMD and femur neck BMD (p = 0.190, p = 0.167, respectively). Radiographic assessments showed no significant differences in vertebral compression ratio (14.7% vs. 14.8%; p = 0.960) or Cobb angle (4.2° vs. 4.9°; p = 0.302). The incidence of major osteoporotic fractures was lower in the romosozumab group (7.1% vs. 25.0%, p = 0.051), with similar rates of cardiovascular events in both groups (4.8% vs. 9.1%, p = 0.716). Conclusion Romosozumab has demonstrated superior pain reduction and lumbar BMD improvement compared to vertebroplasty at 12 months, with no significant differences in radiographic outcomes or adverse events, suggesting it as an alternative to vertebroplasty for OVCF.

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.

Systemic corticosteroids play an essential role in the management of asthma. During acute exacerbation, the short-term use of systemic corticosteroids is recommended. For patients with uncontrolled asthma and severe asthma, long-term and low-dose oral corticosteroids (OCS) have frequently been advocated. However, both short-term and long-term use of systemic corticosteroids carry the risk of adverse events (AEs), including various morbidities and even mortality. Despite recent progress in adult severe asthma management and the availability of new treatment options, the current domestic guidelines for asthma do not provide specific recommendations for oral corticosteroid tapering in patients with severe asthma. Therefore, the task force team of the severe asthma working group in the Korean Academy of Allergy, Asthma, and Clinical Immunology has proposed a tapering protocol for systemic corticosteroid use in severe asthma. This includes practical recommendations for monitoring OCS-related AE, particularly for adrenal insufficiency and osteoporosis, which suggests corticosteroid-sparing strategies that include alternative therapies, modifying treatable traits, timely specialist assessment, and shared decision-making with patients. However, further real-world research and collaboration with doctors from primary and academic institutes, patients, and policymakers are necessary to establish an OCS stewardship approach. This should include realistic OCS-tapering strategies for patients with severe asthma using regular OCS, education, and campaigns for patients, the public, and healthcare providers about the burden of severe asthma, as well as improving timely access to specialized severe asthma services for optimal management.