Background: Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated. Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood. Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively). Conclusion These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Background: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Ectopic kidney is a rare congenital anomaly which occurs in approximately 1 in 1,000 live births. Intrathoracic kidney is the rarest type of the ectopic kidney, which constitutes < 5% of all ectopic kidney cases. It is often associated with congenital diaphragmatic hernia, which can cause severe respiratory distress. However, most patients with intrathoracic kidney are asymptomatic, and incidentally diagnosed with prenatal ultrasonography or chest radiography after birth as intrathoracic mass-like lesion. In this study, we report a case of an asymptomatic neonate with intrathoracic kidney. An intrathoracic mass was detected in plain chest radiography of a 17-day-old boy, and it was identified as the right kidney in the thoracic cavity by computed tomography and ultrasonography.Correction of the ectopic kidney and repair of diaphragmatic hernia were successful at the age of 52 days. After the operation, the right kidney was normally detected in the right renal fossa, and there was no recurrence of diaphragmatic hernia. To the best of our knowledge, the present case is the only reported case of intrathoracic kidney at the neonatal period, in South Korea. Careful review of chest radiography at the neonatal period and clinical suspicion of rare diseases like herniation of intraabdominal organ are needed.

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.

Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment. Conclusion HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

Background: In vitro and animal studies have demonstrated that bone morphogenetic protein-7 (BMP-7), renowned for its osteogenic properties, also exerts beneficial effects on muscle metabolism by enhancing myogenesis and reversing muscle atrophy. Despite being proposed as a common regulatory factor for both muscle and bone, the impact of BMP-7 on human muscle health has not been thoroughly investigated. Methods: This cross-sectional study involved 182 community-dwelling older adults who underwent a comprehensive geriatric assessment in South Korea. Sarcopenia was diagnosed using Asian-specific cutoffs, and serum BMP-7 levels were quantified via enzyme immunoassay. Results: The mean age of the participants was 72.2±7.3 years, with 62.6% being female. After adjustments for confounders, serum BMP-7 levels were not significantly different between individuals with and without sarcopenia, nor were there differences based on skeletal muscle mass, strength, or physical performance levels (p=0.423 to 0.681). Likewise, no correlations were detected between circulating BMP-7 levels and any sarcopenia assessment metrics such as skeletal muscle index, grip strength, gait speed, or chair stand completion times (p=0.127 to 0.577). No significant associations were observed between increases in serum BMP-7 concentrations and the risk of sarcopenia or poor muscle phenotypes (p=0.431 to 0.712). Stratifying participants into quartiles based on serum BMP-7 levels also indicated no differences in sarcopenia-related parameters (p=0.663 to 0.996). Conclusion Despite experimental evidence supporting BMP-7’s role in muscle metabolism, this study found no significant association between serum BMP-7 levels and clinical indicators of muscle health in older adults. These findings challenge the utility of serum BMP-7 as a biomarker for sarcopenia in this demographic.

Purpose: There are limited data regarding changes in glucose control in pediatric patients with type 1 diabetes (T1D) affected by coronavirus disease 2019 (COVID-19). This study aimed to evaluate changes in the metrics of a continuous glucose monitoring (CGM) system during COVID-19 infection in children and adolescents with T1D. Methods: Eighteen patients with T1D (<18 years of age) were included in this retrospective study. The effects of COVID-19 on CGM metrics were assessed at 5 time points (2 weeks before COVID-19 [time 1], 1 week before COVID-19 [time 2], during COVID-19 [time 3], 1 week after COVID-19 [time 4], and 2 weeks after COVID-19 [time 5]). Results: All participants had at least 1 symptom of COVID-19 and did not need to be hospitalized. The glucose management indicator (GMI) was higher at time 3 (7.7%±1.4%) compared to time 1 (7.1%±1.1%; P=0.016) and time 5 (7.0%±1.2%; P=0.008). According to the insulin delivery method, the GMI at time 3 was significantly higher than that at time 5 in patients treated with multiple daily injections (MDI) (median and interquartile range, 8.0% [6.1%–8.5%] vs. 7.1% [5.8%–7.9%]; P=0.020) but not in those treated with continuous subcutaneous insulin infusion (CSII). Conclusion Pediatric patients with T1D and mild COVID-19 showed worsening glycemic control during COVID-19 infection, but it returned to preinfection levels within 2 weeks of infection. CSII is more effective in maintaining stable glycemic control during COVID-19 infection than is MDI therapy.