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Despite widespread concern about energy imbalance due to tumor and chemotherapy-related side effects, little is known about detailed variations in energy input, metabolic rate, and physical activity. This study explored changes in energy balance components and serum biomarkers of patients with hematologic malignancies undergoing chemotherapy. Our prospective study included 40 patients with hematologic malignancies hospitalized for chemotherapy. We measured energy balance components, physical function, and serum biomarkers at baseline and weekly after chemotherapy for 3 weeks. Significant weight loss, representing negative energy balance, occurred at 2 (p = 0.002) and 3 weeks (p 0.001) post-chemotherapy. Statistically reduced oral intake was observed at 3 weeks post-chemotherapy (p = 0.040), and resting energy expenditure statistically decreased according to Harris-Benedict equation, but not to Penn State University equation. Physical function according to DEMMI score decreased significantly at 3 weeks post-chemotherapy (p = 0.002). Serum biomarker analysis demonstrated significant changes in albumin, total protein, CXCL13, and GDF15, with exception of leptin. Although conventional serum biomarkers (total protein and albumin) did not reach pathological states despite their statistical differences, subgroup analysis showed CXCL13 in weight loss group and GDF15 in reduced oral intake group were significantly changed. Over half of patients (65.0%, n = 26) suffered from energy imbalance associated with weight loss and reduced oral intake during chemotherapy. Serial laboratory results suggested that novel biomarkers (CXCL13, GDF15) could be correlated with cachexic state and reduced food intake. Monitoring clinical and serum biomarkers associated with energy balance together can help identify needs for nutritional support in patients with hematologic malignancies undergoing chemotherapy.

Although the loss of skeletal limb muscle mass and muscle strength in the elderly have been demonstrated, the aging process of the back muscles to maintain core stability is not well known. This 1-year prospective observational study aimed to investigate the natural aging course of the lumbar extensor muscles (LEMs) compared with the extremity muscles and determine whether muscle strength or mass decreases more in community-dwelling older women.Twenty-four older urban-dwelling women aged 70 years or older were initially enrolled. Their demographic variables, conventional and spinal sarcopenia indices, and functional outcome parameters were evaluated. We also measured back extensor strength, radiological parameters for spinal sagittal balance on whole-spine radiography, and volumetric parameters of the LEM on computed tomography.After the exclusion of 6 subjects, 18 older women were finally analyzed. All variables related to extremity muscle mass, muscle strength, physical performance, and LEM volume declined over the study period, but the changes were insignificant. However, back extensor strength decreased significantly (median, first, and third quartile: 35.20 [30.80, 44.00] N to 31.40 [29.25, 37.90] N, P = 0.026). Among spinal sagittal balance-related parameters, lumbar lordosis (44.25 [39.30, 47.35]° to 43.15 [31.43, 45.75]°, P = 0.043) and sagittal vertical axis (33.85 [3.57, 58.75] mm to 45.15 [25.35, 58.68] mm, P = 0.004) showed significant changes during the study.When the natural aging course of LEM in women aged 70 years or older was observed for 1 year, muscle mass decreased less than back extensor strength and spinal sagittal balance. Measurements of back extensor strength and spinal sagittal balance are necessary for the clinical evaluation of spinal aging.

To compare the neurodevelopmental outcomes at 18-24 months of corrected age between preterm (32 weeks of gestational age) infants with very low birth weight (VLBW) conceived with and without the assistance of in vitro fertilization (IVF).Prospective cohort study.Not applicable.In total, 4,940 infants with VLBW were born before 32 weeks of gestational age from January 2013 to December 2015.In vitro fertilization.Neuromotor or sensory disability (primary outcome) and developmental delay assessed using the Bayley Scales of Infant and Toddler Development (secondary outcome) at 18-24 months of corrected age.Of the 4,940 infants with VLBW enrolled, 2,818 surviving infants who were followed up for neurodevelopmental assessment at 18-24 months of corrected age were included in the study. Of these 2,818 infants, 630 (22.4%) were conceived with the assistance of IVF, and 2,188 (77.6%) were not. After adjustment for potential confounders, no statistically significant differences were found in the rate of neuromotor or sensory disability at 18-24 months of corrected age between infants conceived with and without the assistance of IVF. After excluding infants with neuromotor or sensory disability, the rate of developmental delay was also comparable between those conceived with and without the assistance of IVF.This study showed comparable neurodevelopmental outcomes at 18-24 months of corrected age between preterm infants with VLBW conceived with and without the assistance of IVF.

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

The assessment of liver surface nodularity (LSN) for staging hepatic fibrosis is restricted in clinical practice because it requires customized software and time-consuming procedures. A simplified method to estimate LSN score may be useful in the clinic.To evaluate the regional analysis of LSN and processing time in a single axial liver MR image for staging liver fibrosis.Retrospective.A total of 210 subjects, a multicenter study.A 3 T/noncontrast gradient echo T1WI.Subjects were divided into five fibrosis groups (FRegional variations in LSN scores were compared using ANOVA with Tukey test. Agreement between the mean and regional LSN measurements was evaluated using Pearson correlation coefficients (r) and Bland-Altman plots. The diagnostic performance of mean and regional LSN scores according to fibrosis stage was evaluated with the AUROC. A P value 0.05 was considered statistically significant.Total processing time for a regional LSN measurement (3.6 min) was 75.5% less than that for mean LSN measurement (14.7 min). Mean LSN scores and all five regional LSN scores showed significant differences between fibrosis groups. Among regional LSN scores, ROIQuantitative regional LSN measurement in a single axial MR image reduces processing time. Regional ROI3 TECHNICAL EFFICACY: Stage 2.

Activation of the IRE-1/XBP-1s pathway supports tumor progression. Here, we report a novel prodrug, TC-D-F07, in which a thiol-reactive dinitrobenzenesulfonyl (Dns) cage was installed onto the C8 hydroxyl of the covalent IRE-1 inhibitor D-F07. The electron-withdrawing Dns group in TC-D-F07 stabilizes the neighboring 1,3-dioxane acetal, allowing for stimulus-mediated control of its inhibitory activity. TC-D-F07 exhibits high sensitivity to intracellular thiols. Because tumor cells exhibit higher concentrations of glutathione and cysteine, treatment with TC-D-F07 results in more sustained levels of D-F07 in transformed versus normal cells. In addition, we show that a dinitrophenyl cysteine adduct resulting from cleavage of the Dns group induces endoplasmic reticulum (ER) stress, causing tumor cells to increase the expression of XBP-1s. The accumulated levels of D-F07 and its gradual decomposition into the active IRE-1 inhibitor eventually deprive tumor cells of XBP-1s, leading to more severe apoptosis than those treated with its uncaged analogue.

Purpose Digital Imaging and Communications in Medicine (DICOM), a standard file format for medical imaging data, contains metadata describing each file. However, metadata are often incomplete, and there is no standardized format for recording metadata, leading to inefficiency during the metadata-based data retrieval process. Here, we propose a novel standardization method for DICOM metadata termed the Radiology Common Data Model (R-CDM). Materials and Methods R-CDM was designed to be compatible with Health Level Seven International (HL7)/Fast Healthcare Interoperability Resources (FHIR) and linked with the Observational Medical Outcomes Partnership (OMOP)-CDM to achieve a seamless link between clinical data and medical imaging data. The terminology system was standardized using the RadLex playbook, a comprehensive lexicon of radiology. As a proof of concept, the R-CDM conversion process was conducted with 41.7 TB of data from the Ajou University Hospital. The R-CDM database visualizer was developed to visualize the main characteristics of the R-CDM database. Results Information from 2801360 cases and 87203226 DICOM files was organized into two tables constituting the R-CDM. Information on imaging device and image resolution was recorded with more than 99.9% accuracy. Furthermore, OMOP-CDM and R-CDM were linked to efficiently extract specific types of images from specific patient cohorts. Conclusion R-CDM standardizes the structure and terminology for recording medical imaging data to eliminate incomplete and unstandardized information. Successful standardization was achieved by the extract, transform, and load process and image classifier. We hope that the R-CDM will contribute to deep learning research in the medical imaging field by enabling the securement of large-scale medical imaging data from multinational institutions.

Background Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial. Methods This study will include 120 patients (60 per group, aged 20–80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols. Discussion It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery. Trial registration The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr) (KCT0006057; April 52,021).

Background Falls are one of the most serious health problems among older adults. Sarcopenia is characterized by a decrease in muscle mass, strength, and physical function. Due to potentially age-related conditions, both falls and sarcopenia have common risk factors. However, the association between sarcopenia and falls is controversial. Moreover, the sex differences in the impact of sarcopenia on falls is not yet clear. This study aimed to investigate the sex differences in the impact of sarcopenia, defined by the Asian Working Group for Sarcopenia (AWGS), on falls in Korean older adults. Methods In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 2323 community-dwelling older adults (1111 males and 1212 females) aged 70–84 years were recruited in this cross-sectional study. To evaluate sarcopenia, the AWGS diagnostic algorithm was used. We compared the faller and non-faller groups. We performed unadjusted and fully adjusted logistic regression analyses to evaluate the relationship between sarcopenia, falls, and fall-related fractures. Results A total of 239 (24.1%) females in the faller group had a history of falls in the past year, which was statistically higher than that in males (176, 15.8%). In the fully adjusted model, handgrip strength (odds ratio [OR] = 1.508, 95% confidence interval [CI] = 1.028–2.211), and short physical performance battery (OR = 2.068, 95% CI = 1.308–3.271) were significantly lower in the male faller group. However, in the fully adjusted model, the female faller group only showed a significantly low appendicular skeletal muscle mass index (OR = 1.419, 95% CI = 1.058–1.903). Conclusions This large cohort study aimed to identify the sex differences in the incidence of sarcopenia in the older Korean population, using the AWGS diagnostic algorithm, and its correlation with falls and fall-related fractures. The incidence of falls did not increase in the sarcopenia group. Among the sarcopenia components, sex differences affect the history of falls. Therefore, when studying the risk of falls in old age, sex differences should be considered.

Background Sarcopenia is defined as muscle wasting, characterized by a progressive loss of muscle mass and function due to ageing. Diagnosis of sarcopenia typically involves both muscle imaging and the physical performance of people exhibiting signs of muscle weakness. Despite its worldwide prevalence, a molecular method for accurately diagnosing sarcopenia has not been established. Methods We develop an artificial intelligence (AI) diagnosis model of sarcopenia using a published transcriptome dataset comprising patients from multiple ethnicities. For the AI model for sarcopenia diagnosis, we use a transcriptome database comprising 17 339 genes from 118 subjects. Among the 17 339 genes, we select 27 features as the model inputs. For feature selection, we use a random forest, extreme gradient boosting and adaptive boosting. Using the top 27 features, we propose a four‐layer deep neural network, named DSnet‐v1, for sarcopenia diagnosis. Results Among isolated testing datasets, DSnet‐v1 provides high sensitivity (100%), specificity (94.12%), accuracy (95.83%), balanced accuracy (97.06%) and area under receiver operating characteristics (0.99). To extend the number of patient data, we develop a web application (http://sarcopeniaAI.ml/), where the model can be accessed unrestrictedly to diagnose sarcopenia if the transcriptome is available. A focused analysis of the top 27 genes for their differential or co‐expression with other genes implied the potential existence of race‐specific factors for sarcopenia, suggesting the possibility of identifying causal factors of sarcopenia when a more extended dataset is provided. Conclusions Our new AI model, DSnet‐v1, accurately diagnoses sarcopenia and is currently available publicly to assist healthcare providers in diagnosing and treating sarcopenia.

Background Age-related obesity and body composition changes include loss of muscle mass and increased body fat. This study aimed to investigate sex differences in the impact of sarcopenia, defined by the Asian Working Group for Sarcopenia (AWGS), on obesity in Korean older adults. Methods In this 2-year longitudinal study, 3014 participants were excluded based on AWGS sarcopenia parameters (if any one of the sarcopenic parameter criteria was satisfied), including low handgrip strength (HGS), low appendicular skeletal muscle mass index (ASMI), and low short physical performance battery (SPPB). A total of 926 non-sarcopenic participants were recruited for the study. The obese and non-obese groups were compared according to the sarcopenia parameters. The following variables were selected for obesity analysis: body mass index (BMI), waist circumference (WC), and body fat percentage. Unadjusted and fully adjusted logistic regression analyses were performed for each variable to predict sarcopenia and sarcopenic obesity according to sex. Results Among the sarcopenia parameters, reduction in ASMI was significantly lower in the obese group with high WC and percentage of body fat (PBF) in both men and women (P Conclusions Our study identified that high BMI had a protective effect on the reduction of muscle mass in men and women. However, obesity parameters including BMI, WC, and PBF were positively correlated with a lower incidence of sarcopenia only in women. Obesity in older women may have a protective effect in reducing ASMI and the incidence of sarcopenia.

BACKGROUND AND PURPOSE There is a scarcity of information regarding the role of prothrombin kringle-2 (pKr-2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD). EXPERIMENTAL APPROACH To assess the role of pKr-2 in association with the neurotoxic symptoms of AD, we determined pKr-2 protein levels in post-mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age-matched controls and wild-type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr-2 up-regulation. KEY RESULTS Our results demonstrated that pKr-2 was up-regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid-β aggregation in 5XFAD mice. The up-regulation of pKr-2 expression was inhibited by preservation of the blood-brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up-regulation of pKr-2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice. CONCLUSION AND IMPLICATIONS We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr-2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr-2 represents a novel target for AD therapeutic strategies and those for related conditions.

Cognitive impairment in the elderly causes a significant decline in the quality of life and a substantial economic burden on society. Yet, diagnosing cognitive impairment is apt to be missed or delayed due to its assessment being laborious. This study aimed to propose a new approach of classifying the risk of cognitive impairment in the elderly using sequential gait characteristics and machine learning techniques. A total of 108 community-dwelling elderly individuals participated in this study. The participants were categorized into three groups based on their scores of the mini-mental state examination. Each participant completed both the usual- and fast-paced walking on the straight path with two gyroscopes on each foot. By analyzing the foot sagittal angular velocity signals, the temporal gait parameters were extracted from each gait cycle. Five classical machine learning models and a long short-term memory network were respectively employed to produce the classifiers that used the time-consecutive temporal gait parameters as predictors of cognitive impairment. Five-fold cross-validation was applied to 70% of the data in each group, and the remaining 30% were used as test data. An F1-score of 0.974 was achieved in classifying the three groups by the long short-term memory network-based classifier that used the double-limb support, stance, step, and stride times at usual-paced walking and the double- and single-limb support, stance, and stride times at fast-paced walking as inputs. The proposed approach would pave the way for earlier diagnosis of cognitive impairment in non-clinical settings without professional help, which can facilitate more timely intervention.

Little is known about the association between body proportionality at birth and neonatal outcomes in preterm infants. Body mass index (BMI) is one of the weigh-for-length ratios that represent body proportionality. The objective of this study was to examine whether BMI at birth affects neonatal outcomes in preterm infants. We assessed 4,018 preterm (

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70–84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304–0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281–0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.

Background The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. Methods This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004–2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012–2016). Results The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p , p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96–15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42–11.1, p Conclusion Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.

This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia.This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (14 days) were also assessed.The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (7.5%) should be more carefully treated to reduce mortality.

Background our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. Methods Design systematic review and meta-analysis. Data sources Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. Eligibility criteria randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. Study records title/abstract and full-text screening by two reviewers. Risk of bias Cochrane Collaboration revised tool. Data synthesis results reported separately for different settings and sufficiently comparable studies meta-analysed. Results forty-nine heterogeneous studies were included. Community meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85–1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70–1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69–1.14, I2 = 0%, 2 s) for injurious falls. Hospital meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74–1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07–3.50, I2 = 72% %, 2 s) for number of fallers after and during admission, respectively. Long-term care meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72–1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64–1.35, I2 = 92%, 7 s) for number of falls. Conclusions the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls. PROSPERO registration number: CRD42020218231

An electrodiagnostic test is more useful than the lower extremity isometric strength test for objectively determining the degree of nerve damage and prognosis in cauda equina syndromes (CES). This study evaluated the correlation between nerve conduction study (NCS) parameters and the lower extremity isometric strength and manual muscle test (MMT) grades. The isometric strengths of knee extension (KE), ankle dorsiflexion (ADF), and ankle plantarflexion (APF) were measured. NCS parameters, MMT, and isometric strength of femoral, peroneal, and tibial nerves were evaluated, including their correlations with each other. A regression equation between the isometric strength and compound muscle action potential (CMAP) amplitudes was derived and cutoff values were used to confirm boundary values of strength and amplitude between the MMT grades. KE isometric strength and femoral nerve CMAP amplitude were significantly correlated (r = 0.738, P.001). ADF isometric strength and peroneal nerve CMAP amplitude were significantly correlated (tibialis anterior, r = 0.707, P.001). KE (r = 0.713, P.001), ADF (r = 0.744, P.001), and APF (r = 0.698, P.001) isometric strengths were correlated with the MMT grades. For the regression curve, the second-order curve was more reasonable than the first-order curve. Cutoff femoral nerve CMAP amplitude and isometric strength cutoff values were ≥2.05 mV and 17.3, respectively, for MMT grades 2 to 3 and 2.78 ± 1.08 and 20.8 ± 9.33, respectively, for grade 3. The isometric strengths of the KE, ADF, and APF and the CMAP amplitude of the electrophysiologic parameters were correlated in CES patients and a significant correlation with MMT grade was also identified. Accordingly, it is possible to identify the precise neurological condition, objectively evaluate the degree of paralysis and disability, and determine the quantitative muscle strength from MMT in order to establish an appropriate rehabilitation treatment plan.

Background This study investigated the impact of physical frailty on the development of disabilities in mobility, activities of daily living (ADL), and instrumental activities of daily living (IADL) according to sex among community-dwelling Korean older adults. Methods We used data of 2,905 older adults aged 70-84 years from the Korean Frailty and Aging Cohort Study (KFACS) at baseline (2016-2017) and Wave 2 (2018-2019). Fried’s physical frailty phenotype was used to identify frailty. Results After adjustment, frailty showed a higher impact for women than men on developing mobility disability (odds ratio [OR]=14.00, 95% confidence interval [CI]=4.8–40.78 vs. OR=9.89, 95% CI=4.28–22.86) and IADL disability after two years (OR=7.22, 95% CI=2.67–19.56 vs. OR=3.19, 95% CI=1.17–8.70). Pre-frailty led to mobility disability for women and men (OR=2.77, 95% CI=1.93–3.98 vs. OR=2.49, 95% CI=1.66–3.72, respectively), and IADL disability only for women (OR=3.01, 95% CI=1.28–7.09). Among the IADL components, both men and women who were prefrail or frail showed increased disability in ‘using transportation’. Among men, pre-frailty was significantly associated with disability in “going out” and “shopping”. In women, frailty was significantly associated with disability in “doing laundry,” “performing household chores,” “shopping,” and “managing money”. Conclusions Physical frailty increased disability over 2 years for women more than men. Physical frailty increased disability in outdoor activity-related IADL components in men and household work-related IADL components in women. This study highlights the need for gender-specific policies and preventative programs for frailty, particularly restorative interventions that focus on women who are physically frail.

We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms, and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients.This multicenter study analyzed epidemiological data and sensory symptoms of 649 patients with DPN. Cluster analysis was carried out to identify subgroups of patients with characteristic symptom profiles. Factor analysis was carried out to investigate the symptom patterns of the clustered groups of DPN patients.Three clusters of patients with DPN were identified: severe symptoms with decreased quality of life (cluster 1, n = 119, 18.3%), predominantly insensate symptoms with relatively good quality of life (cluster 2, n = 318, 49.0%), and moderate pain intensity and decreased quality of life (cluster 3, n = 204, 31.4%). The frequency of symptoms on each item of the Michigan Neuropathy Screening Instrument questionnaire showed a similar distribution according to pain intensities along with the three clusters.Our study supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach. Based on a multicenter study, we identified three clusters of patients with DPN. Our research supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach.

Since the introduction of Enhanced Recovery After Surgery (ERAS), early diet after surgery has been emphasized and clinical outcomes have improved, though vomiting has been reported frequently. We defined diet failure based on clinical manifestation and images after colon cancer surgery and attempted to analyze underlying risk factors by comparing the early diet group with the conventional diet group. All consecutive patients underwent colectomy with curative intent at a single institution between August 2015 and July 2017. The early diet group was started on soft diet on the second day after surgery, while the conventional group started the same after flatulence. The primary outcome was the difference in the incidence of diet failure between the two groups. Secondary outcomes were analyzed to determine risk factors for diet failure and readmission due to ileus. Overall, 293 patients were included in the conventional diet group and 231 in the early diet group. There were no significant differences between the two groups, except for shorter hospital stays in the early diet group (median 8 days, p

This study validates behavior development screening for toddlers (BeDevel), which utilizes a combination of short caregiver interviews (BeDevel-I) and semistructured play observations (BeDevel-P). The data of 431 toddlers (male 66.2%; mean age (SD) = 29.11 (8.59) months; ASD, n = 201; developmental delay, n = 46; typically developing, n = 184), aged 18 ~ 42 months, were included in the validation of BeDevel. The best clinical estimate diagnosis, screening rate, validity, sensitivity, and reliability of BeDevel were determined based on data cross-sectionally collected using BeDevel and existing diagnostic/screening instruments: autism diagnostic observation schedule (ADOS), autism diagnostic interview (ADI-R), Vineland adaptive behavior scales-II (VABS-II), social response scales (SRS), sequenced language scale for infants (SELSI), Korean childhood autism rating scale (K-CARS), and Korean social communication questionnaire (K-SCQ). The k values of BeDevel-I and BeDevel-P were 0.055 ~ 0.732 and 0.291 ~ 0.752, respectively. Items related to social referencing in BeDevel-P had a particularly high diagnostic validity (k = 0.483 ~ 0.684). Reliabilities of BeDevel-I and BeDevel-P were sufficient (Cronbach's alpha = 0.86 ~ 0.88 and 0.92 ~ 0.95, respectively). BeDevel-I and BeDevel-P showed high sensitivity (BeDevel-I: 85.00 ~ 89.29%; BeDevel-P: 85.00 ~ 91.75%), specificity (BeDevel-I: 77.55 ~ 89.55%; BeDevel-P: 85.09 ~ 97.01%), PPV (BeDevel-I: 70.83 ~ 88.54%; BeDevel-P: 81.52 ~ 94.68%), and NPV (BeDevel-I: 76.00 ~ 95.24%; BeDevel-P: 84.62 ~ 95.45%). The agreement between the composite BeDevel score and ADOS, ADI-R, K-CARS, and K-SCQ was >67.6% (range = 67.6 ~ 90.8%). Combining a short caregiver interview and direct play observation is a valid and reliable screening process. More studies on social referencing as an important early marker are needed. BeDevel can be utilized as a secondary screening instrument before diagnostic confirmation in clinical and community settings. LAY SUMMARY: BeDevel, which consists of a short caregiver interview and direct play observation, is a valid and reliable screening instrument for autism spectrum disorder (ASD). We suggest that BeDevel can be utilized as a secondary instrument before administering diagnostic assessments in clinical and community settings. More studies examining social referencing as a potential behavioral marker of ASD are needed.

Purpose: Gastric cancer remains the leading cause of cancer-related deaths in Northeast Asia. Population-based endoscopic screenings in the region have yielded successful results in early detection of gastric tumors. Endoscopic screening rates are continuously increasing, and there is a need for an automatic computerized diagnostic system to reduce the diagnostic burden. In this study, we developed an algorithm to classify gastric epithelial tumors automatically and assessed its performance in a large series of gastric biopsies and its benefits as an assistance tool. Experimental Design: Using 2,434 whole-slide images, we developed an algorithm based on convolutional neural networks to classify a gastric biopsy image into one of three categories: negative for dysplasia (NFD), tubular adenoma, or carcinoma. The performance of the algorithm was evaluated by using 7,440 biopsy specimens collected prospectively. The impact of algorithm-assisted diagnosis was assessed by six pathologists using 150 gastric biopsy cases. Results: Diagnostic performance evaluated by the AUROC curve in the prospective study was 0.9790 for two-tier classification: negative (NFD) versus positive (all cases except NFD). When limited to epithelial tumors, the sensitivity and specificity were 1.000 and 0.9749. Algorithm-assisted digital image viewer (DV) resulted in 47% reduction in review time per image compared with DV only and 58% decrease to microscopy. Conclusions: Our algorithm has demonstrated high accuracy in classifying epithelial tumors and its benefits as an assistance tool, which can serve as a potential screening aid system in diagnosing gastric biopsy specimens.

Background While transarterial embolization (TAE) is an effective way to control arterial bleeding associated with pelvic fracture, the clinical outcomes according to door-to-embolization (DTE) time are unclear. This study investigated how DTE time affects outcomes in patients with severe pelvic fracture. Methods Using a trauma database between November 1, 2015 and December 31, 2019, trauma patients undergoing TAE were retrospectively reviewed. The final study population included 192 patients treated with TAE. The relationships between DTE time and patients’ outcomes were evaluated. Multiple binomial logistic regression analyses, multiple linear regression analyses, and Cox hazard proportional regression analyses were performed to estimate the impacts of DTE time on clinical outcomes. Results The median DTE time was 150 min (interquartile range, 121–184). The mortality rates in the first 24 h and overall were 3.7% and 14.6%, respectively. DTE time served as an independent risk factor for mortality in the first 24 h (adjusted odds ratio = 2.00, 95% confidence interval [CI] = 1.20–3.34, p = 0.008). In Cox proportional hazards regression analyses, the adjusted hazard ratio of DTE time for mortality at 28 days was 1.24 (95% CI = 1.04–1.47, p = 0.014). In addition, there was a positive relationship between DTE time and requirement for packed red blood cell transfusion during the initial 24 h and a negative relationship between DTE time and ICU-free days to day 28. Conclusion Shorter DTE time was associated with better survival in the first 24 h, as well as other clinical outcomes, in patients with complex pelvic fracture who underwent TAE. Efforts to minimize DTE time are recommended to improve the clinical outcomes in patients with pelvic fracture treated with TAE.

Aims: Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. Neutrophils produce different subtypes of EVs during inflammatory responses. Neutrophil-derived trails (NDTRs) are generated by neutrophils migrating toward inflammatory foci, whereas neutrophil-derived microvesicles (NDMVs) are thought to be generated by neutrophils that have arrived at the inflammatory foci. However, the physical and functional characteristics of neutrophil-derived EVs are incompletely understood. In this study, we aimed to investigate the differences between NDTRs and NDMVs. Methods: The generation of neutrophil-derived EVs were visualized by live-cell fluorescence images and the physical characteristics were further analyzed using nanotracking analysis assay, scanning electron microscopic analysis, and marker expressions. Functional characteristics of neutrophil-derived EVs were analyzed using assays for bactericidal activity, monocyte chemotaxis, phenotype polarization of macrophages, and miRNA sequencing. Finally, the effects of neutrophil-derived EVs on the acute and chronic inflammation were examined in vivo. Results: Both EVs share similar characteristics including stimulators, surface marker expression, bactericidal activity, and chemoattractive effect on monocytes via MCP-1. However, the integrin-mediated physical interaction was required for generation of NDTRs whereas NDMV generation was dependent on PI3K pathway. Interestingly, NDTRs contained proinflammatory miRNAs such as miR-1260, miR-1285, miR-4454, and miR-7975, while NDMVs contained anti-inflammatory miRNAs such as miR-126, miR-150, and miR-451a. Although both EVs were easily uptaken by monocytes, NDTRs enhanced proinflammatory macrophage polarization whereas NDMVs induced anti-inflammatory macrophage polarization. Moreover, NDTRs showed protective effects against lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. Conclusion: These results suggest that NDTR is a proinflammatory subtype of neutrophil-derived EVs distinguished from NDMV.

In the present study, to verify the effect of polysaccharides derived from persimmon leaves (PLE) at epithelial-to-mesenchymal transition (EMT), A549 cells were treated with TGF-β1 alone or co-treated with TGF-β1 and PLE (50 and 75 μg/mL). PLE-treated cells showed higher expression of E-cadherin and lower expression of N-cadherin and vimentin compared to TGF-β1-treated cells by inhibiting the levels of transcription factors, including Snail, Slug, and ZEB1, all associated with EMT. PLE also significantly decreased migration, invasion, and anoikis resistance through TGF-β1 mediated EMT suppression, whereby PLE inhibited the levels of MMP-2 and MMP-9 while cleaving PARP. These inhibitory effects of PLE against EMT, migration, invasion, and anoikis resistance were determined by activating the canonical SMAD2/3 and non-canonical ERK/p38 signaling pathways. Therefore, these results suggest that PLE could be used as a potential chemical therapeutic agent for early metastasis of lung cancer in vitro.

The menopausal syndrome caused by rapid changes in hormone levels greatly influences the quality of life of women. Though hormone replacement therapy (HRT) is widely used to treat the menopausal syndrome, it exhibits many side effects, including the risk of thrombosis, cardiovascular diseases, and increased incidence of breast cancer; thus, diversifying the interest for phytotherapy-based materials as alternatives to HRT. Here, we isolated a crude polysaccharide fraction (CWPF) from Cynanchum wilfordii root that alleviated the ovariectomy-induced uterine atrophy and bone loss without changes in plasma estradiol concentration in mice. Increased plasma levels of follicle-stimulating hormone (FSH), alkaline phosphatase (ALP), osteocalcin (OC) in ovariectomized mice were also reduced to normal levels by CWPF administration. We found that the inhibitory effects of CWPF on menopausal symptoms were mediated by the estrogen receptor β (ER-β) specific activation, not ER-α. Moreover, CWPF treatment suppressed the phosphorylation of Akt, suggesting that CWPF alleviates post-menopausal symptoms by regulating ER-β related Akt signaling pathway. These results demonstrate that the polysaccharides corresponding to CWPF among the water-soluble extracts of CW could be used as a beneficial herbal alternative for the development of therapeutic agents to prevent menopausal syndrome in women.

Background Cardiac rehabilitation (CR) is a prognostic management strategy to help patients with CVD achieve a good quality of life and lower the rates of recurrence, readmission, and premature death from disease. Globally, cardiac rehabilitation is poorly established in hospitals and communities. Hence, this study aimed to investigate the discrepancies in the perceptions of the need for CR programs and relevant health policies between directors of hospitals and health policy personnel in South Korea to shed light on the status and to establish practically superior and effective strategies to promote CR in South Korea. Methods We sent a questionnaire to 592 public health policy managers and directors of selected hospitals, 132 of whom returned a completed questionnaire (response rate: 22.3%). The participants were categorized into five types of organizations depending on their practice of PCI (Percutaneous Coronary Intervention), establishment of cardiac rehabilitation, director of hospital, and government's policy makers. Differences in the opinions between directors of hospitals that perform/do not perform PCI, directors of hospitals with/without cardiac rehabilitation, and between hospital directors and health policy makers were analyzed. Results Responses about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, hospitals’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive among hospitals that perform PCI than those that do not. Responses to questions about the effectiveness of cardiac rehabilitation and hospitals’ roles in cardiac rehabilitation tended to be more positive in hospitals with cardiac rehabilitation than in those without. Hospital directors responded more positively to questions about targeting diseases for cardiac rehabilitation and governmental health policies’ roles in cardiac rehabilitation than policy makers, and both hospitals and public organizations provided negative responses to the question about patients’ roles in cardiac rehabilitation. Responses to questions about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive in hospitals that perform PCI than those that do not and public organizations. Conclusions Hospitals must ensure timely referral, provide education, and promote the need for cardiac rehabilitation. In addition, governmental socioeconomic support is needed in a varity of aspects.

Background Total knee arthroplasty (TKA) is an important management strategy for patients with knee osteoarthritis (OA) refractory to conservative management. Postoperative range of motion (ROM) exercise is important to recover patients’ activities of daily living. Continuous passive motion (CPM) is a machine that provides passive ROM exercises of the knee joint in a pre-defined arc of motion. The short- and long-term effects of CPM exercise are controversial. We hypothesized that the inconsistent results of the CPM exercise are due to poor fitting of CPM machines and measurement errors. This study aims to present a protocol for investigating a new type of CPM machine that could be applied in a sitting position in comparison with the conventional type of CPM machine for patients with unilateral TKAs. Methods This study presents the protocol of a prospective, multicenter, single-blinded, three-armed randomized controlled trial (RCT). One hundred and twenty-six patients receiving unilateral TKAs will be recruited at the physical medicine and rehabilitation clinics of two urban tertiary medical hospitals. The patients were randomly divided into three groups with a 1:1:1 allocation. The intervention group will receive two weeks of post-operative rehabilitation using a new type of CPM machine. The control group will receive 2 weeks of post-operative rehabilitation using conventional CPM machines. The third group will receive post-operative rehabilitation with both types of CPM machines. The primary outcome will be the change in the passive ROM of the affected knee joint from baseline to 2 weeks after baseline assessment. The secondary outcomes will be pain and functional measurements, and will include patient-reported outcomes and performance tests surveyed at multiple time points up to 3 months after TKA. Discussion This is the first RCT to investigate the effect of a new type of CPM machine. The results of this RCT will determine whether the position of the patients during CPM exercise is important in post-operative rehabilitation protocols after TKAs and will provide evidence for the development of proper rehabilitation guidelines after TKAs. Trial registration Clinical Research Information Service of Republic of Korea, KCT0005520, Registered on 21 October 2020, https://cris.nih.go.kr/cris/search/detailSearch.do/21750

BACKGROUND: The glomerular filtration rate (GFR) and albumin-to-creatinine ratio (ACR) have been widely used to identify and manage diabetic kidney disease (DKD). However, classifications based on these two indices do not always concur in terms of DKD diagnosis; for example, cases of high ACR with normal GFR or normal ACR with low GFR may occur. A recent study suggested that critical shear stress (CSS), a hemorheological parameter to represent aggregating force of red blood cells (RBCs), is a potential screening index for DKD. In the present study, we investigated the diagnostic potential of CSS for DKD according to the KDIGO 2012 Guideline. METHODS: A total of 378 patients with type 2 diabetes who visited Yeungnam University Hospital between 2014 and 2017 were included. CSS was measured using a transient microfluidic hemorheometer, Rheoscan-D300® (Rheomeditech, Seoul, Republic of Korea) with whole blood. Patients who were DKD negative (green zone) were compared with patients who were DKD positive (red zone) as Model 1 and patients at risk for (orange zone) and red zones as Model 2, respectively. RESULTS: After exclusion criteria such as eGFR

To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy.In this phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low-dose or standard-dose lobeglitazone. The primary endpoint was non-inferiority of low-dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard-dose lobeglitazone, using 0.5% non-inferiority margin.At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low-dose and standard-dose lobeglitazone groups, respectively (p = .031). The between-group difference was 0.18% (95% confidence interval 0.017-0.345), showing non-inferiority of the low-dose lobeglitazone. Mean body weight changes were significantly greater in the standard-dose group (1.36 ± 2.23 kg) than in the low-dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA-IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment-emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard-dose group.Adding low-dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non-inferior glucose-lowering outcome and fewer adverse events compared with standard-dose lobeglitazone. Therefore, low-dose lobeglitazone might be one option for individualized strategy in patients with T2DM.

Background: This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults.Methods: We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018.Results: Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c)

Anti-dementia medications are widely prescribed to patients with Alzheimer’s dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format—the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009–2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-d-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.

The 5-times chair stand test (5CST) is a proxy tool for measuring physical performance and muscle strength in diagnosing sarcopenia. The Asian Working Group for Sarcopenia 2019 guidelines recommends the 5CST for evaluating gait speed, whereas the European Working Group on Sarcopenia in Older People guidelines recommend the chair stand test as a proxy for muscle strength.This study sought to determine whether the chair stand test correlates with handgrip strength and gait speed, and investigate sex differences in these relationships.We used data collected from 1416 participants (678 men and 738 women) in the 2017 Korean Frailty and Aging Cohort Study (KFACS).The 5CST time had a higher correlation with gait speed (r = - 0.470) than handgrip strength (r = - 0.309). In addition, 5CST time predicted low gait speed (area under the curve [AUC] 0.727) better than low handgrip strength (AUC 0.641). The optimal cutoff values of the 5CST to estimate low gait speed were 10 s for men (sensitivity 62%, specificity 64%) and 11 s for women (sensitivity 68%, specificity 67%). The optimal cutoff values of the 5CST for low handgrip strength were the same as those for low gait speed (10 s for men and 11 s for women).The 5-times chair stand test fits with gait speed and handgrip strength but seems to be a better proxy of gait speed than handgrip strength. The optimal cutoff values of the 5CST to estimate low gait speed and low handgrip strength were lower in men than women. Although none of the AWGS 2019 or EWGSOP guidelines present sex-specific cutoffs for the 5CST, it needs to be considered in the next guidelines.

Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and survival in type 2 diabetes (T2D) due to the low expression level of endogenous antioxidants in the β-cells. Peroxiredoxin-3 (PRDX3) is a mitochondria specific H202 scavenger and protects the cell from mitochondrial damage. However, nothing is known about how glucotoxicity influences PRDX3 function in the pancreatic beta cells. Exposure of rat insulinoma INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30mM) stimulated acetylation of PRDX3 which facilitates its hyper-oxidation causing mitochondrial dysfunction by SIRT1 degradation. SIRT1 deficiency induces beta cell apoptosis via NOX-JNK-p66Shc signalosome activation. Herein we investigated the direct effect of Teneligliptin, a newer DPP-4 inhibitor on beta-cell function and survival in response to high glucose conditions. Teneligliptin treatment enhances SIRT1 protein levels and activity by USP22, an ubiquitin specific peptidase. Activated SIRT1 prevents high glucose-induced PRDX3 acetylation by SIRT3 resulted in inhibition of PRDX3 hyper-oxidation thereby strengthening the mitochondrial antioxidant defense. Notably, we identify PRDX3 as a novel SIRT3 target and show their physical interaction. Intriguingly, inhibition of SIRT1 activity by EX-527 or SIRT1 siRNA knockdown exacerbated the SIRT3 mediated PRDX3 deacetylation which leads to peroxiredoxin-3 hyper-oxidation and beta-cell apoptosis by the activation of NOX-JNK-p66Shc signalosome. Collectively, our results unveil a novel and first direct effect of high glucose on PRDX3 acetylation on beta-cell dysfunction by impaired antioxidant defense and SIRT1 mediated SIRT3-PRDX3 activation by Teneligliptin suppresses high glucose-mediated mitochondrial dysfunction.

Study design A retrospective observational study. Objective To identify the difference between patients with and without healthcare-associated infection (HAI) after spinal cord injury (SCI), changes in the quantity of rehabilitation after HAI, and resistance to and application of empirical antibiotics. Setting University hospital-affiliated rehabilitation center. Methods Altogether, 338 patients with SCI receiving inpatient rehabilitation from January 2015 to March 2018 were categorized into two groups based on the presence or absence of HAI. Demographic and clinical characteristics, amount of rehabilitation performance between before and after HAI, resistance to antibiotics, and empirical antibiotic change rates were investigated. Results In 79 patients, 117 HAI cases occurred, with an overall incidence of 34.6%. Male sex, complete SCI, and trauma history were more frequent in the HAI group than in the non-HAI group. Length of stay (LOS) was longer at 28.9 days in the HAI group. The incidence of lower respiratory tract infections (LRIs) and urinary tract infections (UTIs) was 5.0 and 16.9%, respectively. The rehabilitation loss rates due to LRIs and UTIs were 40.0 and 20.2%, respectively, which were not statistically significant. The rates of resistance to recommended empirical antibiotics for LRIs and UTIs were 26.9-57.7% and 54.2-67.8%, respectively. The rates of empirical antibiotic changes for LRIs and UTIs were 35.3 and 43.9%, respectively. Conclusions HAI after SCI was more common in men, complete SCI and trauma history. LOS was prolonged in the HAI group. A quantitative reduction of rehabilitation treatment after HAI was observed, but further research is needed for validation.

Various perinatal morbidities may adversely affect postnatal nephrogenesis in preterm infants. Kidney ultrasonographic findings following acute kidney injury (AKI) have not been well described in preterm infants. Herein, we describe three cases of extremely preterm infants who showed abnormal kidney ultrasonographic findings resembling dysplasia of the kidneys following AKI. Their median gestational age and birth weight were 25+6 (range 23+3–26+6) weeks and 620 (480–840) g, respectively. All infants suffered severe AKI during their third to seventh week of life. Their kidney function recovered with conventional management. Kidney ultrasonographies performed after AKI revealed increased kidney echogenicity, loss of corticomedullary differentiation, and multiple cortical cysts, which were similar to cystic dysplasia of the kidneys and were absent in previous kidney imaging. Three infants eventually developed at least one of the long-term kidney sequelae following AKI, including proteinuria, hypertension, and elevated levels of serum creatinine or cystatin C as determined during the last follow-up at the corrected age of 9–18 months. Based on these cases, we can infer that AKI occurring during the early postnatal period may result in dysplasia of the kidneys with cortical cysts in extremely preterm infants, which may lead to chronic kidney disease in their later life. It is useful to follow up not only laboratory parameters but also kidney ultrasonographic findings in extremely preterm infants who suffered AKI during their early postnatal periods.

Background: In recent years, the use of the anterior half of the peroneus longus tendon (AHPLT) as an autograft source for ligament reconstruction has gained popularity. However, no reports are available regarding tendon regeneration after harvesting of the AHPLT. Hypothesis: When half of the tendon is preserved during tendon harvesting, the quality of the regenerated tendon is better than that of the regenerated tendon after full-thickness harvesting. Study Design: Case series; Level of evidence, 4; controlled laboratory study. Methods: A total of 21 patients who underwent AHPLT harvesting for lower extremity ligament reconstruction participated in the magnetic resonance imaging (MRI) study to evaluate tendon regeneration 1 year after the harvesting. An in vivo animal study was performed to compare the quality of the regenerated tendon after partial-thickness and full-thickness tendon harvesting. A total of 30 adult female Sprague-Dawley rats were allocated to 2 groups—15 rats underwent partial-thickness Achilles tendon harvesting (partial-thickness harvesting [PTH] group), and 15 rats underwent full-thickness Achilles tendon harvesting (full-thickness harvesting [FTH] group). The quality of the regenerated tendons was compared 180 days after tendon harvesting. Results: All 21 patients showed regeneration of the peroneus longus tendon (PLT) (homogeneously dark on both T1- and T2-weighted sequences). The cross-sectional area of the regenerated tendon divided by that of the preoperative tendon was 92.6% and 84.5% at 4 cm and 9 cm proximal to the tip of the distal fibula, respectively. In the animal study, the mean histologic score was better for the PTH group compared with the FTH group (9.17 ± 1.35 vs 14.72 ± 0.74; P < .001). The ultimate strength and the stiffness of the regenerated Achilles tendon were significantly higher for the PTH group compared with the FTH group (35.5 ± 8.3 vs 22.4 ± 8.3 N, P = .004; and 31.6 ± 7.7 vs 23.5 ± 4.8 N/mm, P = .016). Conclusion: The PLT was found to regenerate after partial-thickness harvesting on MRI. In the animal study, the quality of the regenerated tendon when half of the tendon was preserved during tendon harvesting was better than that after full-thickness tendon harvesting.

Background: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. Methods: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite out comes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clini cal features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. Results: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pres sure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P

Objective To describe the prevalence of sarcopenia in a large group of community-dwelling older adults using the Asian Working Group for Sarcopenia (AWGS) 2019 definition and algorithm. Design Cross-sectional data analysis of a cohort study. Setting The Nationwide Korean Frailty and Aging Cohort Study (KFACS). Participants A total of 2123 ambulatory community-dwelling older adults, aged 70 to 84 years (mean, 75.9 ± 3.9 years; 49.5% women) were enrolled in the KFACS. Methods Appendicular skeletal muscle mass was measured by dual-energy x-ray absorptiometry. Physical function was assessed by handgrip strength, usual gait speed, the 5-times-sit-to-stand test, the timed up-and-go test, and the Short Physical Performance Battery. In a case-finding assessment, screening for sarcopenia was performed using the calf circumference (CC), SARC-F questionnaire, and SARC-F combined with CC (SARC-CalF). Results According to the AWGS 2019 algorithm, 43.5%, 7.5%, and 26.0% of the subjects in the whole study sample were classified as those at risk for sarcopenia according to CC, SARC-F, and SARC-CalF, respectively. The prevalence rates of possible sarcopenia using 3 screening tools for case-finding and muscle strength or physical performance tests according to the AWGS 2019 diagnostic algorithm were 20.1% in men and 29.2% in women. The prevalence rates of sarcopenia, when defined as low muscle mass plus low handgrip strength and/or slow gait speed, were significantly higher according to the AWGS 2019 (21.3% in men and 13.8% in women) than the AWGS 2014 (10.3% in men and 8.1% in women) definitions. The prevalence of severe sarcopenia was 6.4% in men and 3.2% in women. Conclusions/Implications The results of our study suggest that the use of CC and SARC-CalF to screen for possible sarcopenia may be more suited than using the SARC-F questionnaire alone according to the AWGS 2019 diagnostic algorithm in community-dwelling adults aged 70 to 84 years. The prevalence of sarcopenia was significantly higher according to the AWGS 2019 than AWGS 2014 criteria.

Background/Aims Frailty is mainly due to an age-related decrease in the physiological reserves needed to maintain biological homeostasis, but it can also occur as a result of chronic diseases. The purpose of this study was to identify illnesses associated with frailty in Korean community-dwelling older adults. Methods This was a cross-sectional study that included 2,936 older adults aged between 70 and 84 years who had completed both interviews and physical function assessments for the Korean Frailty and Aging Cohort Study. Current illnesses diagnosed by physicians were included in the analysis. The definition of frailty was derived from the Fried frailty phenotype. Results The prevalence of hypertension, diabetes mellitus (DM), arthritis, osteoporosis, urinary incontinence, and lung disease (including asthma, chronic obstructive pulmonary disease, and chronic bronchitis) was higher in the frail group (p < 0.05). After adjusting for age, sex, physical activity, alcohol, smoking, education, and presence of a spouse, the odds ratios for DM and urinary incontinence in frailty were 1.51 (95% confidence interval [CI], 1.10 to 2.01; p = 0.01) and 1.88 (95% CI, 1.11 to 3.18; p = 0.02). Conclusions In Korean community-dwelling older adults, DM and urinary incontinence were associated with frailty after adjusting for various factors. In the future, the list of comorbid diseases that are appropriate for Korean population-specific frailty assessment should be inventoried.

The association between serum levels of vitamin D and frailty in older Korean adults was examined.Cross-sectional study. Older people living in the community across 10 study centers throughout South Korea. The baseline data (2016-2017) of 2872 participants aged 70-84 years in the Korean Frailty and Aging Cohort Study were evaluated.Serum vitamin D level was assessed with an electro-chemiluminescence immunoassay. Frailty was defined using Fried's frailty index. A multinomial logistic regression analysis was used to examine the association between serum levels of vitamin D and frailty.The percentages of those with serum vitamin D levels of25 nmol/L, 25-49 nmol/L, 50-74 nmol/L, and ≥75 nmol/L were 4.1 %, 37.0 %, 37.8 %, and 21.0 %, respectively. The prevalence of frailty was 9.7 %. Those with lower serum vitamin D levels, compared with ≥75 nmol/L, tended to have higher odds of being frail than being non-frail (OR: 1.58, 95 % CI: 1.05-2.39 for 50-74 nmol/L; OR: 1.49, 95 % CI: 0.98-2.26 for 25-49 nmol/L; OR: 1.37, 95 % CI: 0.65-2.88 for25 nmol/L). Among the components of frailty, low grip strength was significantly associated with lower serum levels of vitamin D.Low serum levels of vitamin D are associated with an increased likelihood of frailty in community-dwelling older adults, suggesting a potentially protective role of vitamin D against frailty.

Background Inflammation is a major risk factor for frailty, but n-3 polyunsaturated fatty acids (PUFA) has been suggested as an anti-inflammatory agent. The present study aimed to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion. Methods Cross-sectional analysis from the Korean Frailty and Aging Cohort Study, a total of 1,435 people aged 70–84 years were included. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and nonfrail according to the Cardiovascular Health Study index. Results The likelihood of frailty was inversely associated with the erythrocyte levels of eicosapentaenoic acid (EPA; odds ratio [OR] per unit 0.33; 95% confidence interval [CI] 0.14–0.77; p for trend = .002) and docosahexaenoic acid (DHA; OR per unit 0.42; 95% CI 0.20–0.87; p for trend = .018). Among each frailty criterion, the likelihood of slow walking speed was associated with erythrocyte levels of EPA and DHA, and the likelihood of exhaustion was inversely associated with the erythrocyte levels of DHA. Conclusions The present study showed that the frailty and frailty criterion were significantly associated with lower erythrocyte levels of long-chain n-3 PUFA, suggesting that lower n-3 PUFA could be a marker for the risk of frailty.

Sarcopenia is an age-related chronic condition that can lead to mobility disabilities. This study aimed to evaluate the risk factors for incident sarcopenia in older Korean adults.The Korean Frailty and Aging Cohort Study (KFACS) is a multicentre prospective study with a baseline examination in 2016-2017. A prospective follow-up study was conducted in 2018-2019. Changes in muscle-related variables were evaluated for subjects aged 70-84 years lacking sarcopenia at baseline. Sarcopenia was diagnosed according to the 2019 updated Asian Working Group for Sarcopenia consensus.Among the 1636 participants (54.4% women, age 75.9 ± 3.7) who did not have sarcopenia at baseline, 101 men (13.5%) and 104 women (11.7%) developed sarcopenia by the follow-up. Those who developed sarcopenia were older (men, 77.9 ± 3.9 vs. 75.7 ± 3.5, P 0.001; women, 77.5 ± 4.0 vs. 75.5 ± 3.6, P 0.001) with a lower body mass index at baseline (men, 23.9 ± 2.4 vs. 24.5 ± 2.9 kg/mIn this 2 year KFACS follow-up, modifiable risk factors for incident sarcopenia differed between genders. Resistance training (≥2 per week) helped to prevent sarcopenia in these community-dwelling older men. In older women, adequate nutritional support and being physically active might play a role in preventing progression to sarcopenia.

PURPOSE We examined whether superselective embolization of the renal artery could be effectively employed to preserve traumatic kidneys and assessed its clinical outcomes. METHODS Between December 2015 and November 2019, 26 patients who had American Association for the Surgery of Trauma grade V traumatic shattered kidneys were identified. Among them, a retrospective review was conducted of 16 patients who underwent superselective renal artery embolization for shattered kidney. The mean age was 41.2 ± 15.7 years, and the mean follow-up duration was 138.2 ± 140.1 days. Patient data including procedure details and clinical outcomes were reviewed, and the preserved volume of kidney parenchyma was calculated. RESULTS Bleeding control was achieved in 13 (81%) patients and kidney preservation was achieved in 11 (79%). There was no mortality, and the median intensive care unit stay was 1.5 days. The mean volume of remnant kidney was 122.3 ± 66.0 cm3 (70%) on the last follow-up computed tomography. The estimated glomerular filtration rate was not significantly changed after superselective renal artery embolization. CONCLUSION Superselective renal artery embolization using a microcatheter for the shattered kidney effectively controlled hemorrhage in acute stage trauma and enabled kidney preservation.

Background Obesity is a chronic disease that causes various medical health problems, increases morbidity, and reduces the quality of life. Obesity (especially central obesity) in older adults is expected to act with the development of sarcopenia. However, the relationship between obesity, central obesity, and sarcopenia remains controversial. This study aimed to investigate the impact of obesity on sarcopenia. Methods In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 1,827 community-dwelling older adults (883 men and 944 women) aged 70–84 years were recruited. The Asian Working Group for Sarcopenia (AWGS) criteria were used to evaluate sarcopenia. Subjects with a low appendicular skeletal muscle mass index (ASMI; men: 2, women: 2) and either low handgrip strength (HGS; men: 2, while central obesity was defined as WC measurements of ≥ 90 cm in men and ≥ 85 cm in women. Logistic regression analyses were performed to evaluate the impact of obesity and central obesity on sarcopenia and the parameters of sacropenia. Results In both sexes, the obese group, defined based on the BMI, had a significantly low prevalence of low ASMI (odds ratio [OR] = 0.14, 95% confidence interval CI = 0.10–0.20 in men, OR = 0.17, 95% CI = 0.12–0.25 in women) and sarcopenia (OR = 0.28, 95% CI = 0.16–0.50 in men, OR = 0.17, 95% CI = 0.08–0.35 in women) in the multivariable logistic regression analysis. In women, the central obese group had a low prevalence of sarcopenia (OR = 0.46, 95% CI = 0.27–0.77) in the multivariable logistic regression analysis. Meanwhile, the obese group had a significantly higher prevalence of low SPPB in women (OR = 1.75, 95% CI = 1.18–2.59). Conclusions Obesity may have a protective effect on low ASMI and sarcopenia, as defined by the AWGS criteria. Central obesity was associated with a low prevalence of sarcopenia in women only. However, obesity did not have a positive impact on functional parameters of sarcopenia including muscle strength and physical performance.