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Yeon-Mok Oh,1,* Keu Sung Lee,2,* Yoonki Hong,3,* Sung Chul Hwang,2 Jae Yeol Kim,4 Deog Keom Kim,5 Kwang Ha Yoo,6 Ji-Hyun Lee,7 Tae-Hyung Kim,8 Seong Yong Lim,9 Chin Kook Rhee,10 Hyoung Kyu Yoon,11 Sang Yeub Lee,12 Yong Bum Park,13 Jin Hee Jung,14 Woo Jin Kim,3 Sang-Do Lee,1 Joo Hun Park2 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea; 3Department of Internal Medicine and Environmental Health Center, Kangwon National University, Kangwon National University Hospital, Chuncheon, Korea; 4Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 7Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 8Division of Pulmonology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea, Seoul, Korea; 11Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 12Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 13Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 14Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea *These authors contributed equally to this work Background: High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids. However, the prognostic role of blood eosinophil count remains underexplored. Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.Methods: Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital. The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%–5%), and low (

Sang-In Park,1,* Howard Lee,1,2,* Jaeseong Oh,1 Kyoung Soo Lim,3 In-Jin Jang,1 Jeong-Ae Kim,4 Jong Hyuk Jung,4 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, 4LG Life Sciences, Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Background: In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets.Methods: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.Results: The plasma DPP-4 activity–time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97–1.04) and 0.92 (0.82–1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration–time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80–1.25. Both the FDC and separate tablets were well tolerated.Conclusion: The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach. Keywords: dipeptidyl peptidase 4, DPP-4 inhibitor, type 2 diabetes mellitus, T2DM

Purpose: To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome.Methods: Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR.Results: Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis.Conclusion: Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma. [ABSTRACT FROM AUTHOR]

Background: Most ductal carcinoma in situ (DCIS) of the breast is asymptomatic and usually manifests as calcifications in screening mammography. On the other hand, little is known about ultrasonographic (US) features of asymptomatic DCIS, for US is rarely used for the diagnosis and evaluation of DCIS because of low sensitivity in detecting microcalcifications. Purpose: To evaluate US detection and characterization of DCIS in asymptomatic women and correlate these imaging findings with the histopathologic features. Material and Methods: This retrospective study evaluated mammographic and US images of 60 DCIS cases from 59 asymptomatic women. US was performed in knowledge of mammographic findings. The following histopathologic parameters were analyzed: Van Nuys classification, architectural pattern, and presence of microinvasion. Image detectability and US features were correlated with these histopathologic parameters. Results: Of the 54 cases (90.0%) detected on mammography, 48 cases (88.9%) had microcalcifications only, 5 (9.3%) had microcalcifications with associated density, and 1 (1.9%) had soft tissue density alone. Of the 38 cases (63.3%) identified by US, 29 cases (76.3%) had a mass with or without microcalcifications, six (15.8%) had microcalcifications only, and three (7.9%) had other findings. US identified lesions were associated with higher Van Nuys groups, microinvasion and comedocarcinoma (P = 0.044, P = 0.024, and P = 0.032, respectively). The most common US finding was a not-circumscribed, oval mass with parallel orientation and normal acoustic transmission. Microcalcifications were seen on US in 31 (81.6%) of the 38 US visible cases; this finding showed a trend of association with Van Nuys group 2 and 3 but was not statistically significant (P = 0.063). Conclusion: When DCIS was identified on US, it was associated with more aggressive histopathologic type. However, mammographic correlation is essential to differentiate benign from malignant lesion in cases seen by US; US findings of asymptomatic DCIS had a low suspicion of malignancy. [ABSTRACT FROM AUTHOR]

Background: A high-flexion posterior-stabilized rotating-platform mobile-bearing prosthesis was designed in an attempt to improve the range of motion after total knee arthroplasty without compromising the theoretical advantages of the posterior-stabilized rotating-platform mobile-bearing system. The aim of this study was to compare the outcomes of standard and high-flexion posterior-stabilized rotating-platform mobile-bearing total knee arthroplasties.Methods: One hundred and seventy knees were randomly allocated to receive either a standard (n = 85) or a high-flexion (n = 85) posterior-stabilized rotating-platform mobile-bearing prosthesis and were followed prospectively for a minimum of two years. Ranges of motion, functional outcomes determined with use of standard scoring systems, and radiographic measurements were assessed. In addition, patients' abilities to perform activities requiring deep knee flexion and patient satisfaction were evaluated with use of questionnaires.Results: The average postoperative maximal flexion was 130° for the knees with the standard design and 128° for those with the high-flexion design, and the difference was not significant. The two prosthetic designs also did not differ significantly with regard to the Knee Society scores; Hospital for Special Surgery (HSS) scores; or the scores on the pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). In addition, the numbers of knees able to perform deep-flexion-related activities and the rates of patient satisfaction were similar in the two study groups.Conclusions: This prospective randomized study revealed no significant differences between standard and high-flexion posterior-stabilized rotating-platform mobile-bearing total knee prostheses in terms of clinical or radiographic outcomes or range of motion at a minimum of two years postoperatively. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer's disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults., Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker., Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008)., Conclusion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.

Objective: We intended to investigate the relationships between visual sensory impairment (VSI) or auditory sensory impairment (ASI) and brain pathological changes associated with cognitive decline in older adults., Methods: We primarily tried to examine whether each sensory impairment is related to Alzheimer's disease (AD) pathology, specifically beta-amyloid (Aβ) deposition, through both cross-sectional and longitudinal approaches in cognitively unimpaired older adults. Self-report questionnaires on vision and hearing status were administered at the baseline. Neuroimaging scans including brain [ 11 C] Pittsburgh Compound B PET and MRI, as well as clinical assessments, were performed at baseline and 2-year follow-up., Results: Cross-sectional analyses showed that the VSI-positive group had significantly higher Aβ deposition than the VSI-negative group, whereas there was no significant association between ASI positivity and Aβ deposition. Longitudinal analyses revealed that VSI positivity at baseline was significantly associated with increased Aβ deposition over 2 years (β = 0.153, p = 0.025), although ASI positivity was not (β = 0.045, p = 0.518). VSI positivity at baseline was also significantly associated with greater atrophic changes in AD-related brain regions over the 2-year follow-up period (β = -0.207, p = 0.005), whereas ASI positivity was not (β = 0.024, p = 0.753). Neither VSI nor ASI positivity was related to cerebrovascular injury, as measured based on the white matter hyperintensity volume., Conclusion: The findings suggest that VSI is probably related to AD-specific pathological changes, which possibly mediate the reported relationship between VSI and cognitive decline. In contrast, ASI appears not associated with AD pathologies but may contribute to cognitive decline via other mechanisms.

Our study contributes to the scholarship by examining the concrete ways in which two distinct types of interpersonal connection-strong/close versus weak/distant-are independently related to self-rated health and life satisfaction cross-nationally. In addition, we explore whether and how the two types of interpersonal connection modify the magnitude of the associations between subjective social status (SSS) and health and well-being of older populations cross-nationally. According to results from our multilevel analysis, social capital available through strong ties (family and friends) is positively associated with both outcomes. On the other hand, social capital via weak ties (acquaintances) is positively related to health but negatively related to well-being. We also find that social capital mediated by strong ties significantly buffers the harmful implications of status disadvantage or low SSS on health and well-being of older adults. In comparison, weak tie-mediated social capital provides buffering against status disadvantage only for well-being., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the number of affected patients is increasing worldwide. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard therapy for neovascular AMD (nAMD), and optical coherence tomography (OCT) is a crucial tool for evaluating the anatomical condition of the macula. However, OCT has limitations in accurately predicting the degree of functional and morphological improvement following intravitreal injections. Artificial intelligence (AI) has been proposed as a tool for predicting the treatment response of nAMD based on OCT biomarkers. Our study focuses on the development and assessment of an AI model utilizing the DenseNet201 algorithm. The model aims to predict anatomical improvement based on OCT images before, and during anti-VEGF therapy. The training process involves two scenarios: (1) using only preinjection OCT images and (2) utilizing both OCT images before and during anti-VEGF therapy for model training. The outcomes of our investigation, involving 2068 images from a cohort of 517 Korean patients diagnosed with nAMD, indicate that the AI model we introduced surpassed the predictive performance of ophthalmologists. The model exhibited a sensitivity of 0.915, specificity of 0.426, and accuracy of 0.820. Notably, its predictive capabilities were further enhanced with the inclusion of additional OCT images taken after the first and second injections during the loading phase. The treatment prediction performance of the model was the highest when using all input modalities (before injection, and after the first and second injections) and concatenation-based fusion layers. This study highlights the potential of AI in assisting individualized and tailored nAMD treatment., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Robot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi)., Methods: This retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed., Results: After PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15 ml/min/1.73 m², OKT: 64.53 ml/min/1.73 m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81 min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22 min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180-4.096, p = 0.848)., Conclusions: RAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT's viability for high-risk kidney transplant recipients., Trial Registration: The clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008|| https://www., Clinicaltrials: gov/ )., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the ethical standards of the institution and with the 1964 Helsinki Declaration and its later amendments. The study was approved by the Ethics Committee of Asan Medical Center (reference number: 2023-0085). Given the retrospective nature of the study, the requirement for informed consent was waived by the Ethics Committee. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Within the tumor microenvironment, altered lipid metabolism promotes cancer cell malignancy by activating oncogenic cascades; however, impact of lipid metabolism in CD4 + tumor-infiltrating lymphocytes (TILs) remains poorly understood. Here, we elucidated that role of stearoyl-CoA desaturase (SCD) increased by treatment with cancer-associated fibroblast (CAF) supernatant in CD4 + T cells on their subset differentiation and activity of CD8 + T cells., Results: In our study, we observed that CD4 + TILs had higher lipid droplet content than CD4 + splenic T cells. In tumor tissue, CAF-derived supernatant provided fatty acids to CD4 + TILs, which increased the expression of SCD and oleic acid (OA) content. Increased SCD expression by OA treatment enhanced the levels of Th1 cell markers TBX21, interleukin-2, and interferon-γ. However, SCD inhibition upregulated the expression of regulatory T (Treg) cell markers, FOXP3 and transforming growth factor-β. Comparative fatty acid analysis of genetically engineered Jurkat cells revealed that OA level was significantly higher in SCD-overexpressing cells. Overexpression of SCD increased expression of Th1 cell markers, while treatment with OA enhanced the transcriptional level of TBX21 in Jurkat cells. In contrast, palmitic acid which is higher in SCD-KO cells than other subclones enhanced the expression of Treg cell markers through upregulation of mitochondrial superoxide. Furthermore, SCD increased the secretion of the C-X-C motif chemokine ligand 11 (CXCL11) from CD4 + T cells. The binding of CXCL11 to CXCR3 on CD8 + T cells augmented their cytotoxic activity. In a mouse tumor model, the suppressive effect of CD8 + T cells on tumor growth was dependent on CXCR3 expression., Conclusion: These findings illustrate that SCD not only orchestrates the differentiation of T helper cells, but also promotes the antitumor activity of CD8 + T cells, suggesting its function in adverse tumor microenvironments., Competing Interests: Declarations Ethics approval and consent to participate All animal experiments were approved by the Institutional Animal Care and Use Committee of the Seoul National University, South Korea (SNU-200309-9). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: COVID-19 is known to cause psychological problems. Psychological rehabilitation can be performed to reduce anxiety, depression, and insomnia. Facing patients with infectious diseases can be difficult for medical staff. Therefore, this study compared the effects of psychiatric tele-rehabilitation (TR) and conventional psychiatric rehabilitation (CR) in isolated patients with COVID-19., Methods: This randomized controlled study, conducted at a single community-based hospital, included 40 patients (24 in the psychiatric tele-rehabilitation group [TRG] and 16 in the conventional psychiatric rehabilitation group [CRG]) with COVID-19 were recruited from November 18, 2021, to April 7, 2022. Psychiatric rehabilitation is an occupation-based intervention in which patients perform meaningful activities and tasks. Patients in the TRG selected activities, received counseling, and underwent monitoring over the phone, while those in the CRG participated in face-to-face sessions. The interventions were conducted for 50 min each day during an isolation period of 7 days in both groups, and all participants received the interventions individually. The primary outcome was anxiety assessed using the Visual Analog Scale (VAS) and the Zung Self-Rating Anxiety Scale (SAS). Secondary outcomes include the Visual Analog Scale (VAS) and the Patient Health Questionnaire-9 (PHQ-9) to evaluate depression, the Multidimensional State Boredom Scale-8 (MSBS-8) to assess boredom. The Korean version of the Insomnia Severity Index (ISI-K) was used to assess the quality of sleep, and the World Health Organization Quality of Life Assessment Instrument-BRIEF (WHOQOL-BREF) was used to evaluate quality of life. Questionnaires were administered at admission, discharge, and at the 6-month follow-up., Results: In the time × group analysis, the SAS total score (p = .033) and the VAS score for depression (p = .012) in the CRG were significantly lower than those in the TRG at the time of discharge. The VAS score for anxiety (p = .007), total SAS score (p = .050), and VAS score for depression (p = .003) in the CRG were also significantly lower than those in the TRG at the 6-month follow-up. The PHQ-9, MSBS-8, ISI-K, and WHOQOL-BREF scores showed no significant interactions in the time × group analysis., Conclusions: TR was effective in reducing anxiety and improving quality of life during hospitalization, but had no remained effects after discharge. Otherwise, CR was more effective than TR for anxiety and depression during hospitalization and had remained effects at 6-month follow-up. However, considering the characteristics of infectious conditions that involve risk in contact, TR will still play an important role, and efforts will be needed to improve the effect that remained., Trial Registration: The trial was registered with the Korea Clinical Trials Registry (KCT0006714, Date of registration 08/11/2021)., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Seoul National University Bundang Hospital (B-2111-719-302). The requirement for obtaining written informed consent was waived by the Institutional Review Board of Seoul National University Bundang Hospital (B-2111-719-302). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)