•Evaluation of EDITM ELISAs for detection of SARS-CoV-2 IgM and IgG in human plasma.•Antibodies were measured in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients.•with serial blood samples collected ...at different time points from symptom onset.•In 200 healthy blood donors, and in 256 intensive care unit patients.•High “true” vs. low “false” positivity rates for the SARS-CoV-2 IgM and IgG ELISAs.
Besides SARS-CoV-2 RT-PCR testing, serological testing is emerging as additional option in COVID-19 diagnostics. Aim of this study was to evaluate novel immunoassays for detection of SARS-CoV-2 antibodies in human plasma.
Using EDITM Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n = 104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used.
The positivity rates in the COVID-19 patients were 5.9% for IgM and 2.9% for IgG ≤ 5 days after symptom onset; Between day 5 and day 10 the positivity rates were 37.1% for IgM and 37.1% for IgG and rose to 76.4% for IgM and 82.4% for IgG after > 10–15 days. After 15–22 days the “true” positivity rates were 94.4% for IgM and 100% for IgG. The “false” positivity rates were 0.5% for IgM and 1.0% for IgG in the healthy blood donors, 1.6% for IgM and 1.2% for IgG in ICU patients.
This study shows high “true” vs. low “false” positivity rates for the EDITM SARS-CoV-2 IgM and IgG ELISAs.
Background and aimSeveral basic science studies support the existence of non-genomic glucocorticoid signaling in pancreas, liver, and adipocytes, but its clinical relevance has not yet been ...elucidated. This study aimed at investigating the rapid effects of hydrocortisone on the human metabolic response to glucose.Subjects and methodsIn a randomized placebo-controlled crossover study, ten healthy men received an i.v. bolus of 0.6 mg/kg hydrocortisone once and placebo once 4 min before the administration of 330 mg/kg glucose. Cortisol, glucose, insulin, C-peptide, ghrelin, and peptide YY (PYY) levels were measured during the following 3 h. Minimal model analysis was performed for evaluating the metabolic response.ResultsHydrocortisone attenuated the rise in plasma glucose during the initial 15 min following glucose administration (P=0.039), and it led to lower glucose levels during the first 2 h (P=0.017). This was accompanied by enhanced circulating insulin (P=0.02) and C-peptide (P=0.03) levels during the initial 15 min, and a 35% increase in the first-phase β-cell function (P=0.003). Hydrocortisone decreased PYY concentrations during the initial 30 min (P=0.014), but it did not affect the ghrelin response to glucose.ConclusionOne i.v. bolus of hydrocortisone induces rapid effects on carbohydrate metabolism increasing the first-phase β-cell function. The modulation of PYY plasma levels suggests the possible non-genomic effects of glucocorticoids on appetite-regulatory hormones.
Lipoproteins, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9), have been shown to play a key role in the innate immune response. However, knowledge about the role and kinetics of ...PCSK9 in human inflammation is currently insufficient. This study aimed to investigate the interaction between inflammation and lipid metabolism, including the possible role of PCSK9. A single-blinded, placebo-controlled cross-over study using the human endotoxin model was performed. Ten healthy men received lipopolysaccharide (LPS) or placebo on two different study days after overnight fasting. Lipoproteins as well as PCSK9 were measured repetitively over 48 h. PCSK9 plasma concentrations were not induced by LPS infusion, and no correlation between PCSK9 plasma concentrations and the degree of inflammation could be identified. The observed low-density lipoprotein (LDL) response to inflammation was more complex than anticipated, especially in the very early phase after the inflammatory stimulus. Baseline concentrations of LDL, as well as high-density lipoprotein (HDL), correlated negatively with inflammatory response. Our data suggest that the lipoprotein response to inflammation is independent of PCSK9. The proposed elevations of PCSK9 and suspected correlations between PCSK9 levels and inflammatory response are not supported by our data. (This study has been registered at ClinicalTrials.gov under registration no. NCT03392701.).
Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on ...the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals.
An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours.
We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion.
Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1.
NCT04488848.
Abstract Chronic kidney disease (CKD) affects approximately 13% of people globally, including 20%–48% with type 2 diabetes (T2D), resulting in significant morbidity, mortality, and healthcare costs. ...There is an urgent need to increase early screening and intervention for CKD. We are experts in diabetology and nephrology in Central Europe and Israel. Herein, we review evidence supporting the use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors for kidney protection and discuss barriers to early CKD diagnosis and treatment, including in our respective countries. SGLT2 inhibitors exert cardiorenal protective effects, demonstrated in the renal outcomes trials (EMPA‐KIDNEY, DAPA‐CKD, CREDENCE) of empagliflozin, dapagliflozin, and canagliflozin in patients with CKD. EMPA‐KIDNEY demonstrated cardiorenal efficacy across the broadest renal range, regardless of T2D status. Renoprotective evidence also comes from large real‐world studies. International guidelines recommend first‐line SGLT2 inhibitors for patients with T2D and estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m 2 , and that glucagon‐like peptide‐1 receptor agonists may also be administered if required for additional glucose control. Although these guidelines recommend at least annual eGFR and urine albumin‐to‐creatinine ratio screening for patients with T2D, observational studies suggest that only half are screened. Diagnosis is hampered by asymptomatic early CKD and under‐recognition among patients with T2D and clinicians, including limited knowledge/use of guidelines and resources. Based on our experience and on the literature, we recommend robust screening programmes, potentially with albuminuria self‐testing, and SGLT2 inhibitor reimbursement at general practitioner (GP) and specialist levels. High‐tech tools (artificial intelligence, smartphone apps, etc.) are providing exciting opportunities to identify high‐risk individuals, self‐screen, detect abnormalities in images, and assist with prescribing and treatment adherence. Better education is also needed, alongside provision of concise guidelines, enabling GPs to identify who would benefit from early initiation of renoprotective therapy; although, regardless of current renal function, cardiorenal protection is provided by SGLT2 inhibitor therapy.
Sunitinib and sorafenib are tyrosine kinase inhibitors that have important antitumor activity in metastatic renal cell carcinoma (mRCC). Hypothyroidism constitutes a commonly reported side effect of ...both drugs, and particularly of sunitinib. The objective of this analysis was to investigate whether the occurrence of hypothyroidism during treatment with sunitinib and sorafenib affects the outcome of patients with mRCC.
Eighty-seven consecutive patients with mRCC who were to receive treatment with sunitinib or sorafenib were included in a prospective analysis. Thyroid function was assessed in each patient every 4 weeks during the first 2 months of treatment and every 2 to 4 months thereafter. Assessment included serum levels of thyroid-stimulating hormone (TSH), tri-iodthyronine (T3), and thyroxine (T4). Subclinical hypothyroidism was defined as an increase in TSH above the upper limit of normal (>3.77 μM/mL) with normal T3 and T4 levels.
Subclinical hypothyroidism was evident in 5 patients at baseline and occurred in 30 patients (36.1%) within the first 2 months after treatment initiation. There was a statistically significant correlation between the occurrence of subclinical hypothyroidism during treatment and the rate of objective remission (hypothyroid patients vs euthyroid patients: 28.3% vs 3.3%, respectively; P < .001) and the median duration of survival (not reached vs 13.9 months, respectively; hazard ratio, 0.35; 95% confidence interval, 0.14-0.85; P = .016). In multivariate analysis, the development of subclinical hypothyroidism was identified as an independent predictor of survival (hazard ratio, 0.31; P = .014).
The current results indicated that hypothyroidism may serve as a predictive marker of treatment outcome in patients with mRCC. Thus, the interpretation of hypothyroidism during treatment with sunitinib and sorafenib as an unwanted side effect should be reconsidered.
Aim
To assess predictors of in‐hospital mortality in people with prediabetes and diabetes hospitalized for COVID‐19 infection and to develop a risk score for identifying those at the greatest risk of ...a fatal outcome.
Materials and Methods
A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID‐19. The primary outcome was in‐hospital mortality and the predictor variables upon admission included clinical data, co‐morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in‐hospital mortality.
Results
The mean age of people hospitalized (n = 238) for COVID‐19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P = .128). A score including age, arterial occlusive disease, C‐reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in‐hospital mortality with a C‐statistic of 0.889 (95% CI: 0.837‐0.941) and calibration of 1.000 (P = .909).
Conclusions
The in‐hospital mortality for COVID‐19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in‐hospital mortality.
Diabetes education and self-management play a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and subsequent treatment ...modification as well as the ability of patients to integrate diabetes into their daily life and to appropriately adapt diabetes to their life style situation. Diabetes education has to be made accessible for all persons with the disease. In order to be able to provide a structured and validated education program, adequate personnel as well as space, organizational and financial prerequisites are required. Besides an increase in knowledge about the disease it has been shown that a structured diabetes education is able to improve diabetes outcome as measured by parameters, such as blood glucose, HbA1c, lipids, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes into everyday life, stress physical activity besides healthy eating as important components of life style therapy and use interactive methods in order to increase the acceptance of personal responsibility. Specific situations (e.g. impaired hypoglycemia awareness, illness, travel), the occurrence of diabetic complications and the use of technical devices such as glucose sensor systems and insulin pumps require additional educational measures supported by adequate electronic tools (diabetes apps and diabetes web portals). New data demonstrate the effect of telemedicine and internet-based services for diabetes prevention and management.
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