Metformin use and cardiovascular outcomes in patients with diabetes and chronic kidney disease: a nationwide cohort study

Background Metformin has recently been shown not to increase the risk of lactic acidosis in patients with chronic kidney disease (CKD). Thus, the criteria for metformin use in this population has expanded. However, the relationship between metformin use and clinical outcomes in CKD remains controversial. Methods This study considered data from 97,713 diabetes patients with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcomes were all-cause mortality and incident end-stage renal disease (ESRD). Results Metformin users had a significantly higher risk of MACCE than non-users (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.14–1.26; p < 0.001). However, metformin users had a lower risk of all-cause mortality (HR, 0.78; 95% CI, 0.74–0.81; p < 0.001) and ESRD (HR, 0.44; 95% CI, 0.42–0.47; p < 0.001) during follow-up than non-users did. The relationships between metformin use and clinical outcomes remained consistent in propensity score matching analyses and subgroup analyses of patients with adequate adherence to anti-diabetes medication. Conclusion Treatment with metformin was associated with an increased risk of MACCE in patients with diabetes and CKD. However, metformin users had a lower risk of all-cause mortality and ESRD during follow-up than non-users did. Therefore, metformin needs to be carefully used in patients with CKD

Impact of low-density lipoprotein cholesterol on progression of aortic valve sclerosis and stenosis

BackgroundLittle research has been assessed atherosclerotic risk factors at various stages of calcific aortic valve disease. This study sought to determine risk factors of patients with aortic valve sclerosis (AVS) and mild to moderate aortic stenosis (AS).MethodsThe study included 1,007 patients diagnosed with AVS or mild to moderate AS according to echocardiographic criteria. Patients were identified as a rapid progression group if the annualized difference in peak aortic jet velocity (Vmax) between two echocardiographic examinations was &gt;0.08 m/s/yr in AVS and &gt;0.3 m/s/yr in AS, respectively. We used multivariable logistic regression analyses to assess the factors associated with rapid disease progression or progression to severe AS.ResultsAmong 526 AVS patients, higher LDL-C level (odds ratio [OR] 1.22/per 25 mg/dl higher LDL-C, 95% confidence interval [CI] 1.05–1.43) was significantly associated with rapid disease progression. Compared to patients with LDL-C level &lt;70 mg/dl, the adjusted OR for rapid progression were 1.32, 2.15, and 2.98 for those with LDL-C level of 70–95 mg/dl, 95–120 mg/dl, and ≥120 mg/dl, respectively. Among 481 mild to moderate AS patients, the baseline Vmax (OR 1.79/per 0.5 m/s higher Vmax, 95% CI 1.18–2.70) was associated with rapid progression. Compared to patients with Vmax 2.0–2.5 m/s, the adjusted OR for rapid progression were 2.47, 2.78, and 3.49 for those with Vmax of 2.5–3.0 m/s, 3.0–3.5 m/s, and 3.5–4.0 m/s, respectively. LDL-C and baseline Vmax values were independently associated with progression to severe AS.ConclusionAtherosclerotic risk factors such as LDL-C were significantly associated with the rapid progression in AVS and baseline Vmax was important in the stage of mild to moderate AS

Hepatocyte growth factor and soluble cMet levels in plasma are prognostic biomarkers of mortality in patients with severe acute kidney injury

Background Hepatocyte growth factor (HGF)/cMet pathway is necessary for repair and regeneration following acute kidney injury (AKI). We evaluated the clinical potential of plasma HGF and soluble cMet as prognostic biomarkers for severe AKI requiring continuous renal replacement therapy (CRRT). Methods One hundred thirty-six patients with severe AKI who participated in the VENUS (volume management under body composition monitoring in critically ill patients on CRRT) trial between 2017 and 2019 were enrolled in this study. We investigated associations between plasma HGF and cMet concentrations and all-cause mortality. Results Plasma HGF and soluble cMet levels were positively correlated. Patients were divided into three groups based on their HGF and soluble cMet concentrations. The day D 0, D2, and D7 highest concentration HGF groups had significantly higher in-hospital mortality after adjusting for sex, body mass index, Acute Physiology and Chronic Health Evaluation II, and age-adjusted Charlson comorbidity index score, especially on D7 (hazard ratio, 4.26; 95% confidence interval, 1.71–10.62; p = 0.002). D7 soluble cMet level was also associated with mortality. Receiver operating characteristic curve analysis indicated that D7 HGF and soluble cMet levels were best at predicting mortality. Addition of plasma HGF and soluble cMet to conventional prognostic indices significantly improved the predictive value for mortality on D7. However, plasma HGF and soluble cMet were not associated with fluid status. Conclusion Plasma HGF and soluble cMet levels were significant predictors of the outcomes of severe AKI patients undergoing CRRT. There was no correlation between plasma HGF and soluble cMet levels and fluid balance

Evaluating the Allergic Risk of Genetically Modified Soybean

Genetically modified (GM) soybean (carrying the EPSPS transgene) is the most common GM food in Korea. In order to assess whether genetic modification increases the allergenic risk of soybeans, the allergenicity and IgE-reactive components of wild-type and GM soybean extracts were compared in allergic adults who had been sensitized to soybeans. We enrolled 1,716 adult allergy patients and 40 healthy, non-atopic controls. Skin prick tests and IgE enzyme linked immunosorbent assays (ELISAs) were performed using wild-type and GM soybean extracts, along with other common inhaled allergens. The specificities of serum IgE antibodies from allergic patients and the identities of the IgE-reactive components of the soybean extracts were compared using ELISA inhibition testing, 2-dimensional gel electrophoresis, and IgE immunoblotting. To evaluate the effects of digestive enzymes and heat treatment, the soybean extracts were heated or pre- incubated with or without simulated gastric and intestinal fluids. The IgE sensitization rates to wild-type and GM soybeans were identical (3.8% of allergic adults), and circulating IgE antibodies specific for the two extracts were comparable. The results of the ELISA inhibition test, SDS-PAGE, and IgE immunoblotting showed a similar composition of IgE-binding components within the wild-type and GM extracts, which was confirmed using two-dimensional gel electrophoresis, IgE immunoblotting, and amino acid sequencing. None of the subjects had a positive response to purified EPSPS protein in the skin prick test, ELISA, or IgE immunoblot analysis. These findings suggest that the IgE sensitization rate to GM soybean extracts is identical to that of wild-type soybean extracts in adult allergy patients. In addition, based on both in vivo and in vitro methods, the allergenicity of wild type and GM soybean extracts was identical

Early detection of cardiac involvement in Miyoshi myopathy: 2D strain echocardiography and late gadolinium enhancement cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Miyoshi myopathy (MM) is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR).</p> <p>Method</p> <p>Five consecutive MM patients (3 male) in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique.</p> <p>Results</p> <p>All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS) was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005). Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects (P < 0.0001, < 0.0001, 0.038 and 0.003, respectively). Four patients showed fibrosis by LGE. The reduced PSLS lesion detected by 2D strain tended to be in the same area as that which showed fibrosis by LGE.</p> <p>Conclusions</p> <p>Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up.</p

Evaluating a shared decision-making intervention regarding dialysis modality: development and validation of self-assessment items for patients with chronic kidney disease

Background Shared decision-making is a two-way symmetrical communication process in which clinicians and patients work together to achieve the best outcome. This study aimed to develop self-assessment items as a decision aid for choosing a dialysis modality in patients with chronic kidney disease (CKD) and to assess the construct validity of the newly developed items. Methods Five focus group interviews were performed to extract specific self-assessment items regarding patient values in choosing a dialysis modality. After survey items were refined, a survey of 330 patients, consisting of 152 hemodialysis (HD) and 178 peritoneal dialysis (PD) patients, was performed to validate the self-assessment items. Results The self-assessment for the decision aid was refined to 35 items. The structure of the final items appeared to have three dimensions of factors; health, lifestyle, and dialysis environment. The health factor consisted of 12 subscales (α = 0.724), the lifestyle factor contained 11 subscales (α = 0.624), and the dialysis environment factor was represented by 12 subscales (α = 0.694). A structural equation model analysis showed that the relationship between the decision aid factors (health, lifestyle, and dialysis environment), patients’ CKD perception, and cognition of shared decision-making differed between HD patients and PD patients. Conclusion We developed and validated self-assessment items as part of a decision aid to help patients with CKD. This attempt may assist CKD patients in making informed and shared decisions closely aligned with their values when considering dialysis modality

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

Purpose: Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). Materials and methods: Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. Results: AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p<0.001; 95% CI, 0.95-1.00). The summation of sensitivity and specificity was highest at the initial cTnT value of 0.35 ng/mL (sensitivity, 0.95; specificity, 0.97). Survival analysis showed a statistically significant difference in all-cause and cardiovascular mortalities for the group with an initial cTnT ≥0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. Conclusion: Because ESRD patients with an initial cTnT concentration ≥0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are ≥0.35 ng/mL.ope

Safety and efficacy of PG102P for the control of pruritus in patients undergoing hemodialysis (SNUG trial): study protocol for a randomized controlled trial

Background Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared from Actinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo. Methods This multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Becks Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated. Discussion The SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis. Trial registration Clinical Trials.gov, NCT03576235. Registered on 4 July 2018.This work was initiated and financially supported by Viromed Co. Ltd., Seoul, Republic of Korea, and Jinyangpharm. Co. Ltd., Seoul, Republic of Korea. The sponsors supported the expenses for the investigational products, laboratory tests, and clinical research coordinator. The funding body had no role in the writing of the manuscript based on the study protocol (Project No. VM_PG102P)