Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).

Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling.

Lung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2-/- mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2-/- mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.

Associations of plasma sphingolipids with measures of insulin sensitivity, ß-cell function, and incident diabetes in Japanese Americans.

BACKGROUND AND AIMS: To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, ß-cell function, and incident diabetes in the Japanese American Community Diabetes Study. METHODS AND RESULTS: Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), ß-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %). CONCLUSION: Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes.

Pulmonary function and sarcopenia as predictors of dysphagia in cervical spinal cord injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the risk factors associated with dysphagia in individuals with cervical spinal cord injury (CSCI) and analyze the differences between individuals with improved penetration-aspiration (PA) and persistent PA on follow-up. SETTING: Tertiary inpatient rehabilitation facilities. METHODS: Medical records of individuals with CSCI admitted between December 2009 and February 2023 who underwent a videofluoroscopic swallowing study (VFSS) were retrospectively reviewed. Multivariate logistic regression analysis was performed to assess risk factors for dysphagia. Differences between individuals with improved PA and persistent PA were analyzed using an independent t-test. RESULTS: In total, 149 participants were enrolled. Age (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.04-1.12), percentage of forced vital capacity to predicted normal (FVC (% predicted)) (OR 0.90, 95% CI 0.85-0.94), and skeletal muscle index (OR 0.89, 95% CI, 0.79-0.99) were significant factors associated with the risk of PA. Based on the receiver operating characteristic curve analysis, the cut-off values for age, FVC (% predicted), and skeletal muscle index were determined as 56.0, 45.7, and 41.0, respectively. A secondary analysis of the follow-up VFSS was conducted on 38 participants. The follow-up FVC (% predicted) and degree of weight loss differed significantly between the improved PA and persistent PA groups. CONCLUSIONS: Older age, low FVC (% predicted), and low skeletal muscle index can be predictors of dysphagia in patients with CSCI. On follow-up VFSS, individuals with improved PA demonstrated greater improvement in FVC (% predicted).

Maximal detrusor pressure can be predicted using technetium-99m-mertcaptoacetyltriglycine renal scintigraphy in the early stages of spinal cord injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the potential of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3) renal scintigraphy for predicting maximal detrusor pressure in the early stages of spinal cord injury (SCI). SETTING: Tertiary rehabilitation facility. METHODS: Medical records of individuals with SCI admitted between January 2020 and April 2023 who underwent both 99mTc-MAG-3 renal scintigraphy and urodynamic study within 90 days of SCI onset were retrospectively reviewed. Pearson's coefficient analysis was performed to determine the relationship between 99mTc-MAG-3 renal scintigraphy findings and urodynamic study findings. A multivariate linear regression analysis was performed to determine the best predictors of maximal detrusor pressure. A multivariate logistic regression analysis was performed to determine risk factors for high detrusor pressure. RESULTS: Ninety-four participants were enrolled in this study. Pearson's correlation analysis showed that effective renal plasma flow (ERPF) and ERPF (% predicted) were significantly correlated with maximal detrusor pressure. The multivariate linear regression analysis demonstrated that ERPF (% predicted) was a significant predictor of maximal detrusor pressure. The multivariate logistic regression analysis showed that ERPF (% predicted) was significantly associated with high detrusor pressure. The receiver operating characteristic curve demonstrated that the predictive model had an area under the curve of 0.725, with an ERPF (% predicted) cut-off of 64.05%, sensitivity 1.000, and specificity 0.429. CONCLUSIONS: These results suggest that 99mTc-MAG-3 renal scintigraphy may be useful for predicting high detrusor pressure in early SCI and may guide the timing of urodynamic studies in individuals with early SCI for appropriate management of neurogenic lower urinary tract dysfunction.

Feasibility of 24-h urine creatinine clearance as a renal function monitoring tool in spinal cord injury patients.

OBJECTIVE: Renal dysfunction is a major cause of morbidity in patients with spinal cord injury (SCI). A 24-h urine creatinine (Cr) clearance (24-h urine CCr) is cost-effective and easy to implement compared to renal scintigraphy in the evaluation of renal function. This study aimed to verify the feasibility of 24-h urine CCr in the SCI population by assessing the correlation with effective renal plasma flow (ERPF) on renal scintigraphy. METHODS: Data from 245 SCI patients (189 males, mean age: 50.2 years) were used in this retrospective review. Clinical characteristics, 24-h urine CCr, serum Cr, comorbidities, and body composition analyses were assessed for correlation with laboratory parameters including renal scintigraphy. Strong predictors of ERPF were determined by multivariate linear regression analysis. Areas under receiver-operating characteristic curves were calculated to evaluate the discriminating power of 24-h urine CCr to predict ERPF <250 ml/min. RESULTS: Spinal cord injury patients showed tubular dysfunction despite normal serum Cr and 24-h urine CCr. There was a significant correlation between 24-h urine CCr and ERPF, and 24-h urine CCr was one of the strongest predictors for ERPF (area under the curve 0.72, 95% CI 0.64-0.80, p < 0.000) among other parameters such as age, appendicular lean mass index, and body mass index. 24-h urine CCr was an independent predictor of ERPF in subacute (R2 = 0.497, p < 0.001) and chronic SCI patients (R2 = 0.664, p < 0.0001). The optimized 24-h urine CCr cut-off was 139.4 ml/min/1.72 m2 for predicting decreased ERPF <250 ml/min (sensitivity 67.6% and specificity 64.0%). CONCLUSION: 24-h urine CCr is a sensitive indicator for renal function deterioration of SCI patients. Further longitudinal studies with larger numbers of SCI patients are needed to confirm the feasibility of 24-h urine CCr for monitoring this population.

A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.

AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Activation of formyl peptide receptor 1 elicits therapeutic effects against collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder which shows production of autoantibodies, inflammation, bone erosion, swelling and pain in joints. In this study, we examined the effects of an immune-modulating peptide, WKYMVm, that is an agonist for formyl peptide receptors (FPRs). Administration of WKYMVm into collagen-induced arthritis (CIA) mice, an animal model for RA, attenuated paw thickness, clinical scores, production of type II collagen-specific antibodies and inflammatory cytokines. WKYMVm treatment also decreased the numbers of TH 1 and TH 17 cells in the spleens of CIA mice. WKYMVm attenuated TH 1 and TH 17 differentiation in a dendritic cell (DC)-dependent manner. WKYMVm-induced beneficial effects against CIA and WKYMVm-attenuated TH 1 and TH 17 differentiation were reversed by cyclosporin H but not by WRW4, indicating a crucial role of FPR1. We also found that WKYMVm augmented IL-10 production from lipopolysaccharide-stimulated DCs and WKYMVm failed to suppress TH 1 and TH 17 differentiation in the presence of anti-IL-10 antibody. The therapeutic administration of WKYMVm also elicited beneficial outcome against CIA. Collectively, we demonstrate that WKYMVm stimulation of FPR1 in DCs suppresses the generation of TH 1 and TH 17 cells via IL-10 production, providing novel insight into the function of FPR1 in regulating CIA pathogenesis.

A membrane-tethering pepducin derived from formyl peptide receptor 3 shows strong therapeutic effects against sepsis.

Formyl peptide receptors (FPRs) are G protein-coupled receptors mainly expressed in inflammatory myeloid cells. Previous reports demonstrated that human neutrophils express only FPR1 and FPR2 but not FPR3. Here, we found that FPR3 is expressed in sepsis patient derived neutrophils and Fpr3 is expressed in the mouse neutrophils. To test the role of Fpr3 in neutrophil activity, we synthesized Fpr3 pepducins and successfully developed an agonistic pepducin that stimulates Fpr3, eliciting calcium increase and chemotactic migration of neutrophils. We also found that administration of an Fpr3 pepducin in an experimental mouse sepsis model significantly increased the survival rate. The pepducin markedly inhibited lung injury, splenocyte apoptosis, and inflammatory cytokine production. Bacterial counts were significantly decreased by the pepducin in septic mice. Based on these results, we suggest that FPR3 can be regarded as a new target to control sepsis, and the newly generated Fpr3-based pepducin can be used for the development of anti-septic agents.

Comparison of the effects of gemigliptin and dapagliflozin on glycaemic variability in type 2 diabetes: A randomized, open-label, active-controlled, 12-week study (STABLE II study).

AIMS: The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients. MATERIALS AND METHODS: In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. RESULTS: Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups. CONCLUSIONS: Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve.

Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A 7-Year Longitudinal Study.

Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross-sectional studies. We explored the effects of relative skeletal muscle mass and changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population-based 7-year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check-up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7-year follow-up period. Using Cox proportional hazard analysis, compared with the lowest sex-specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio [AHR] = 0.44, 95% confidence interval [CI] = 0.38-0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02-4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59-0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90-6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.

Efficacy and safety of fixed-dose combination therapy with gemigliptin (50 mg) and rosuvastatin compared with monotherapy in patients with type 2 diabetes and dyslipidaemia (BALANCE): A multicentre, randomized, double-blind, controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of a fixed-dose combination (FDC) of gemigliptin and rosuvastatin in patients with type 2 diabetes and dyslipidaemia. RESEARCH DESIGN AND METHODS: A total of 33 hospitals in Korea participated in this randomized, double-blind trial of diabetic patients with dyslipidaemia. A total of 290 participants were randomly assigned at a 1:1:1 ratio to receive an FDC of gemigliptin (50 mg) and rosuvastatin (20 mg) (GEMI/ROSU FDC group), gemigliptin (50 mg) (GEMI group) or rosuvastatin (20 mg) (ROSU group). Rosuvastatin was up-titrated from 5 to 20 mg/d throughout the study period. Primary efficacy measures were changes in HbA1c and LDL-C from baseline to Week 24 between the GEMI/ROSU FDC and ROSU groups and between the GEMI/ROSU FDC and GEMI groups, respectively. Secondary efficacy measures were changes in HbA1c and LDL-C between the GEMI/ROSU FDC and GEMI groups and between the GEMI/ROSU FDC and ROSU groups, respectively. RESULTS: After 24 weeks of treatment, a significant reduction in HbA1c from baseline was noted in the GEMI/ROSU FDC group (-0.81% of LS mean; P < 0.0001 vs ROSU group), in addition to a significant reduction in LDL-C concentration (-51.9% of LS mean percentage changes, P < 0.0001 vs GEMI group). HbA1c was significantly reduced from baseline in both the GEMI/ROSU FDC and GEMI groups, but the reduction in HbA1c was significantly greater in the GEMI group than in the GEMI/ROSU FDC group, despite receiving the same dose of gemigliptin. The decrease in LDL-C over time was similar between the GEMI/ROSU FDC and ROSU groups. There were no significant differences in adverse events among the groups. CONCLUSION: The FDC of gemigliptin and rosuvastatin is safe and is effective in reducing both blood glucose and LDL-C levels; thus, it could be a good therapeutic choice for type 2 diabetic patients with dyslipidaemia.

Non-immune-related hypothyroidism and its relationship with excess iodine.

PURPOSE: In iodine-sufficient areas, autoimmune hypothyroidism has been regarded as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has received little attention because it is considered to be rare. The aim of this study was to evaluate the prevalence of non-immune-related hypothyroidism in Korea and to identify its associating factors. METHODS: A total of 6434 participants in the Korea National Health and Nutrition Examination Survey VI (2013-2015) without known thyroid disease who were examined for thyroid stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC) were enrolled. The weighted proportions, demographic variables, and severity of immune-related and non-immune-related hypothyroidism were compared. To assess the effect of iodine on hypothyroidism in TPO Ab positive or negative populations, the weighted prevalence of hypothyroidism was assessed in each population according to UIC or estimated iodine intake subgroups. RESULTS: The prevalence of undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171 (71.8%) were non-immune-related. In the TPO Ab negative population, the prevalence of hypothyroidism was increased significantly in the subgroup with UIC between 250 and 749 µg/L (HR 2.12 [1.17, 3.83]) and ≥ 750 µg/L (HR 3.42 [1.93, 6.04]) or the subgroups with estimated iodine intake ≥ 750 µg/day (HR 2.81 [1.64, 4.80]). CONCLUSIONS: This nationwide study demonstrated that most cases of hypothyroidism in iodine-sufficient areas are non-immune-related and are associated with excess iodine above a certain level. More attention to this unrecognized but widespread potential health risk is needed.

Parasympathetic Effect Induces Cell Cycle Activation in Upper Limbs of Paraplegic Patients with Spinal Cord Injury.

The present study aimed to investigate gene expression changes related to cell cycle activation in patients with spinal cord injury (SCI) and to further evaluate the difference between the upper and lower limbs of SCI patients. Fibroblasts were obtained from the upper and lower limbs of SCI patients and healthy subjects. To investigate gene expression profiling in the fibroblasts from SCI patients compared to the healthy subjects, RNA-Seq transcriptome analysis was performed. To validate the parasympathetic effects on cell cycle activation, fibroblasts from upper or lower limbs of SCI patients were treated with the anticholinergic agents tiotropium or acetylcholine, and quantitative RT-PCR and Western blot were conducted. Cell proliferation was significantly increased in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. The pathway and genes involved in cell cycle were identified by RNA-Seq transcriptome analysis. Expression of cell-cycle-related genes CCNB1, CCNB2, PLK1, BUB1, and CDC20 were significantly higher in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. When the fibroblasts were treated with tiotropium the upper limbs and acetylcholine in the lower limbs, the expression of cell-cycle-related genes and cell proliferation were significantly modulated. This study provided the insight that cell proliferation and cell cycle activation were observed to be significantly increased in the upper limbs of SCI patients via the parasympathetic effect.

Increase in relative skeletal muscle mass over time and its inverse association with metabolic syndrome development: a 7-year retrospective cohort study.

BACKGROUND: Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. METHODS: A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. RESULTS: During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54-0.68). Furthermore, compared with SMI changes < 0% over a year, multivariate-AHRs for metabolic syndrome development were 0.87 (95% CI 0.78-0.97) for 0-1% changes and 0.67 (0.56-0.79) for > 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. CONCLUSIONS: An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.

An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial.

BACKGROUND: A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. METHODS: This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. DISCUSSION: This clinical trial will reveal whether insulin dose adjustment based on a smartphone PHR application can facilitate the optimization of insulin doses in patients with DM. In addition, the process evaluation will provide information about the validity and stability of the ICT-based centralized clinical trial monitoring system in this research field. TRIAL REGISTRATION: Clinicaltrials.gov NCT 03112343 . Registered on 12 April 2017.

Erratum to: An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial.

After publication of the original article [1] it was noted that both the figures and captions and relating to Figs. 1 and 2 had been interchanged.

Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury.

In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs) transplanted into the injured cord after traumatic cervical spinal cord injury (SCI). Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS) grade improved in 5 of 19 transplanted patients, 2 (A → C), 1 (A → B), and 2 (B → D), whereas only one patient in the control group showed improvement (A → B). Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS), Registration Number: KCT0000879.

Comparison of the osteogenic potential of titanium- and modified zirconia-based bioceramics.

Zirconia is now favored over titanium for use in dental implant materials because of its superior aesthetic qualities. However, zirconia is susceptible to degradation at lower temperatures. In order to address this issue, we have developed modified zirconia implants that contain tantalum oxide or niobium oxide. Cells attached as efficiently to the zirconia implants as to titanium-based materials, irrespective of surface roughness. Cell proliferation on the polished surface was higher than that on the rough surfaces, but the converse was true for the osteogenic response. Cells on yttrium (Y)/tantalum (Ta)- and yttrium (Y)/niobium (Nb)-stabilized tetragonal zirconia polycrystals (TZP) discs ((Y, Ta)-TZP and (Y, Nb)-TZP, respectively) had a similar proliferative potential as those grown on anodized titanium. The osteogenic potential of MC3T3-E1 pre-osteoblast cells on (Y, Ta)-TZP and (Y, Nb)-TZP was similar to that of cells grown on rough-surface titanium. These data demonstrate that improved zirconia implants, which are resistant to temperature-induced degradation, retain the desirable clinical properties of structural stability and support of an osteogenic response.

Concordance between needle electromyography and manual muscle test findings for muscles with motor grades 0 and 1.

INTRODUCTION: When it is difficult to determine whether a muscle is grade 0 or 1, manual muscle test (MMT) accuracy can be further improved by using needle electromyography (EMG) as a supplementary and confirmatory examination tool. OBJECTIVE: To evaluate concordance between needle EMG and MMT findings for key muscles with motor grades 0 and 1 on the International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI) examination, and to potentially improve the prognosis for grade 0 muscles with proven muscle activity based on needle EMG findings. DESIGN: A retrospective analysis. SETTING: Inpatient tertiary rehabilitation facility. INTERVENTIONS: Not applicable. PATIENTS: One hundred seven patients with spinal cord injury (SCI) admitted for rehabilitation (n = 1218 key muscles, grades 0 or 1). MAIN OUTCOME MEASURES: Inter-rater reliability between MMTs and needle EMG was analyzed using Cohen's kappa coefficient (κ). A Mantel Haenszel linear-by-linear association chi-square test was used to determine whether the presence of motor unit action potentials (MUAPs) in muscles graded 0 on the initial MMT at admission was associated with MMT grades at discharge and readmission. RESULTS: Moderate-to-substantial agreement between needle EMG and MMT findings was observed (κ = 0.671, p < .01). Concerning key upper and lower extremity muscles, moderate and substantial agreement was identified, respectively. The lowest agreement was noted for C6 muscles. During follow up, 68.8% of muscles with proven MUAPs showed improved motor grades. CONCLUSIONS: At initial assessment, distinguishing between motor grades 0 and 1 is imperative because motor grade 1 muscles are more likely to have a better prognosis for improvement. Moderate-to-substantial agreement was observed between MMT and needle EMG findings. The MMT is a reliable method of muscle grading, yet needle EMG may be of value in certain clinical situations to evaluate for the presence of MUAPs when evaluating motor function.