Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.

BACKGROUND: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.

Objective: Methamphetamine (METH) is a neurotoxic substance that can induce neurodegeneration in the human brain. Consequently chronic METH use can affect the cognitive functions in METH-dependent patients. In this study, we aimed to identify the relationship between cognitive function and brain-derived neurotrophic factor (BDNF), which reflects the status of neuroadaptive changes, by characterizing the effects on the cognitive function of METH-dependent patients. Methods: A total of 38 METH-dependent patients participated in this study. BDNF levels were measured using the enzyme-linked immunosorbent assay. We also examined the clinical features based on the measurements of the Consortium to Establish a Registry for Alzheimer’s Disease-Korean version (CERAD-K). Finally, the relationships between various parts of CERAD-K and BDNF were compared with one another. Results: METH-dependent patients were able to conduct most parts of CERAD-K stably. Among the parts of CERAD-K, only trail-making test part B was correlated with BDNF. Conclusion The trail-making test is specific for evaluating executive function; therefore, BDNF may play an essential role in detecting neurocognitive functional decline in METH dependence.

Objective: To analyze costs and cost-effectiveness of transforaminal endoscopic thoracic discectomy (TETD) for the treatment of symptomatic thoracic disc herniation (TDH) and compare it with open microdiscectomy (MD). Methods: This retrospective cohort study included patients who underwent TETD or MD for symptomatic TDH and had a minimum follow-up of 1 year. Cost analysis included direct costs (primary and secondary hospital costs), indirect costs (lost wages due to work absence), total costs (direct + indirect), and cost-effectiveness (cost per quality-adjusted life year [QALY] and incremental cost-effectiveness ratio [ICER]). Clinical outcomes included patient-reported outcome measures (Oswestry Disability Index [ODI], 36-item Short Form health survey [SF-36]), QALY gained, and reoperation and readmission rates at 1 year. TETD and MD groups were compared for outcome measures. Results: A total of 111 patients (57 TETD, 54 MD) were included. The direct ($6,270 TETD vs. $7,410 MD, p < 0.01), indirect costs ($1,250 TETD vs. $1,450 MD, p < 0.01), total costs ($7,520 TETD vs. $8,860 MD, p < 0.01), and cost per QALY ($31,333 TETD vs. $44,300 MD, p < 0.01) were significantly lower for TETD compared to MD. ICER of TETD was found to be -$33,500. At 1 year, TETD group showed significantly greater improvement in ODI (46% vs. 36%, p < 0.01) and SF-36 (64% vs. 53%, p < 0.01) and significantly greater QALY gained (0.24 vs. 0.2, p < 0.01) compared to MD group. No significant difference was found in reoperation and readmission rates. Conclusion TETD demonstrated significantly better clinical outcomes, lower overall costs, and better cost-effectiveness than MD in appropriately selected patients of symptomatic TDH.

Objective: To analyze costs and cost-effectiveness of transforaminal endoscopic thoracic discectomy (TETD) for the treatment of symptomatic thoracic disc herniation (TDH) and compare it with open microdiscectomy (MD). Methods: This retrospective cohort study included patients who underwent TETD or MD for symptomatic TDH and had a minimum follow-up of 1 year. Cost analysis included direct costs (primary and secondary hospital costs), indirect costs (lost wages due to work absence), total costs (direct + indirect), and cost-effectiveness (cost per quality-adjusted life year [QALY] and incremental cost-effectiveness ratio [ICER]). Clinical outcomes included patient-reported outcome measures (Oswestry Disability Index [ODI], 36-item Short Form health survey [SF-36]), QALY gained, and reoperation and readmission rates at 1 year. TETD and MD groups were compared for outcome measures. Results: A total of 111 patients (57 TETD, 54 MD) were included. The direct ($6,270 TETD vs. $7,410 MD, p < 0.01), indirect costs ($1,250 TETD vs. $1,450 MD, p < 0.01), total costs ($7,520 TETD vs. $8,860 MD, p < 0.01), and cost per QALY ($31,333 TETD vs. $44,300 MD, p < 0.01) were significantly lower for TETD compared to MD. ICER of TETD was found to be -$33,500. At 1 year, TETD group showed significantly greater improvement in ODI (46% vs. 36%, p < 0.01) and SF-36 (64% vs. 53%, p < 0.01) and significantly greater QALY gained (0.24 vs. 0.2, p < 0.01) compared to MD group. No significant difference was found in reoperation and readmission rates. Conclusion TETD demonstrated significantly better clinical outcomes, lower overall costs, and better cost-effectiveness than MD in appropriately selected patients of symptomatic TDH.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.

BACKGROUND: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: Diabetes in older adults is becoming a significant public burden to South Korea. However, a comprehensive understanding of epidemiologic trends and the detailed clinical characteristics of older adults with diabetes is lacking. Therefore, we evaluated epidemiologic trends and the metabolic and lifestyle characteristics of diabetes in Korean older adults. Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey to assess diabetes prevalence according to diabetes duration and lifestyle behaviors. In addition, we drew upon the National Health Information Database of the National Health Insurance System to assess physical activity levels, antidiabetic medication use, polypharmacy, medication adherence, and major comorbidities. Results: The absolute number of newly diagnosed cases of diabetes among older adults doubled over the past decade. Management rates of metabolic indicators were higher in older adults with diabetes compared to those without diabetes. The proportion of older adults with diabetes meeting the minimum recommended physical activity increased over the years. Compared to 10 years before, the use of dipeptidyl peptidase-4 inhibitor or sodium-glucose cotransporter-2 inhibitor had increased, as had comorbidities such as dyslipidemia, dementia, cancer, heart failure, atrial fibrillation, and chronic kidney disease. Initial medication adherence was significantly lower in those with end-stage kidney disease or dementia, insulin use, high-risk alcohol use, and living alone. Continuing insulin use 1 year after diagnosis of diabetes was significantly higher in those who initiated insulin therapy at diagnosis, had retinopathy, were on triple antidiabetic medications, and had a history of cancer. Conclusion Comprehensive management of metabolic indicators and physical activity is essential for older adults with diabetes. Improvements in prescribing guidelines, personalized management of age-related comorbidities, and individualized approaches that consider the heterogeneous nature of older adults with diabetes are desirable. Further research, such as high-quality cohort and intervention studies specific to older adults, is needed to establish evidence-based management for older adults with diabetes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.