The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes.

AIMS: To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events. MATERIALS AND METHODS: In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the 51 Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included. RESULTS: From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by -7.9 mL/min (95% confidence interval [CI] -11.1 to -4.7; P < 0.001), estimated ECV by -192.5 mL (95% CI -318.0 to -66.9; P = 0.003) and estimated PV by -128.9 mL (95% CI -218.0 to 39.8; P = 0.005) at Week 13. CONCLUSIONS: Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.

Effect of near infrared autofluorescence guided total thyroidectomy on postoperative hypoparathyroidism: a randomized clinical trial.

PURPOSE: The purpose of this single-blinded, 2-centre, randomized controlled trial was to test if near-infrared (NIR) autofluorescence image guidance for parathyroid gland (PG) detection during total thyroidectomy can reduce the incidence of hypoparathyroidism in both malignant and benign cases. METHOD: Patients admitted for primary or completion total thyroidectomy were randomized to either the NIR intervention group or the standard care NONIR (no near infrared) group. The primary endpoint was the rate of hypoparathyroidism at the 3-month follow-up, defined as hypocalcemia and inappropriately low parathyroid hormone levels and/or continuous treatment with active vitamin D. The secondary endpoint was the PG identification rate. RESULTS: A total of 147 patients were included of whom 73 were allocated to NIR. Primary or completion thyroidectomy was conducted in 84 and 63 cases, respectively. A total of 130 completed 3 months follow-up. Postoperative hypoparathyroidism in the NIR group at 12 h, 1 month and 3 months was, respectively, 31.8, 14.1, 6.5% compared with 35.9, 18.9, 11.8% in the NONIR group (all p > 0.46). In the NIR group, the identification rate of PGs was 69.5% (146 of 210 PGs), and 9% (19 of 210 PGs) were identified only due to additional use of NIR. For 15 out of 69 patients (21.7%) additionally PGs was found. CONCLUSION: Hypoparathyroidism was nominally less frequent in the NIR group, although not statistically significant. Further studies are needed to confirm if NIR may be a supportive PG identification tool to minimize the number of PG which would have been otherwise missed, especially during more complicated thyroid procedures. TRIAL REGISTRY: ClinicalTrials.gov: NCT04193332. Registration date: 16.08.2019.

A Model for Estimating Biological Age From Physiological Biomarkers of Healthy Aging: Cross-sectional Study.

BACKGROUND: Individual differences in the rate of aging and susceptibility to disease are not accounted for by chronological age alone. These individual differences are better explained by biological age, which may be estimated by biomarker prediction models. In the light of the aging demographics of the global population and the increase in lifestyle-related morbidities, it is interesting to invent a new biological age model to be used for health promotion. OBJECTIVE: This study aims to develop a model that estimates biological age based on physiological biomarkers of healthy aging. METHODS: Carefully selected physiological variables from a healthy study population of 100 women and men were used as biomarkers to establish an estimate of biological age. Principal component analysis was applied to the biomarkers and the first principal component was used to define the algorithm estimating biological age. RESULTS: The first principal component accounted for 31% in women and 25% in men of the total variance in the biological age model combining mean arterial pressure, glycated hemoglobin, waist circumference, forced expiratory volume in 1 second, maximal oxygen consumption, adiponectin, high-density lipoprotein, total cholesterol, and soluble urokinase-type plasminogen activator receptor. The correlation between the corrected biological age and chronological age was r=0.86 (P<.001) and r=0.81 (P<.001) for women and men, respectively, and the agreement was high and unbiased. No difference was found between mean chronological age and mean biological age, and the slope of the regression line was near 1 for both sexes. CONCLUSIONS: Estimating biological age from these 9 biomarkers of aging can be used to assess general health compared with the healthy aging trajectory. This may be useful to evaluate health interventions and as an aid to enhance awareness of individual health risks and behavior when deviating from this trajectory. TRIAL REGISTRATION: ClinicalTrials.gov NCT03680768; https://clinicaltrials.gov/ct2/show/NCT03680768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19209.

A Biological Age Model Designed for Health Promotion Interventions: Protocol for an Interdisciplinary Study for Model Development.

BACKGROUND: Actions to improve healthy aging and delay morbidity are crucial, given the global aging population. We believe that biological age estimation can help promote the health of the general population. Biological age reflects the heterogeneity in functional status and vulnerability to disease that chronological age cannot. Thus, biological age assessment is a tool that provides an intuitively meaningful outcome for the general population, and as such, facilitates our understanding of the extent to which lifestyle can increase health span. OBJECTIVE: This interdisciplinary study intends to develop a biological age model and explore its usefulness. METHODS: The model development comprised three consecutive phases: (1) conducting a cross-sectional study to gather candidate biomarkers from 100 individuals representing normal healthy aging people (the derivation cohort); (2) estimating the biological age using principal component analysis; and (3) testing the clinical use of the model in a validation cohort of overweight adults attending a lifestyle intervention course. RESULTS: We completed the data collection and analysis of the cross-sectional study, and the initial results of the principal component analysis are ready. Interpretation and refinement of the model is ongoing. Recruitment to the validation cohort is forthcoming. We expect the results to be published by December 2021. CONCLUSIONS: We expect the biological age model to be a useful indicator of disease risk and metabolic risk, and further research should focus on validating the model on a larger scale. TRIAL REGISTRATION: ClinicalTrials.gov NCT03680768, https://clinicaltrials.gov/ct2/show/NCT03680768 (Phase 1 study); NCT04279366 https://clinicaltrials.gov/ct2/show/NCT04279366 (Phase 3 study). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19209.

Autonomic dysfunction in HIV patients on antiretroviral therapy: studies of heart rate variability.

BACKGROUND: The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction. AIM: To evaluate whether autonomic dysfunction is present in an ART-treated HIV population. METHODS: HIV patients receiving ART for at least 3 years (n = 16) and an age-matched control group of healthy volunteers (n = 12) were included. All were non-smokers, non-diabetic and had never received medication for dyslipidaemia or hypertension. Following a 10 min resting period a 5 min ECG recording was performed. Heart rate variability (HRV) analysis was performed in accordance with current guidelines and data reported as median (interquartile range). RESULTS: The resting heart rate was higher in HIV patients compared with controls [69 (62-74) versus 57 (52-60); P<0.001]. Total HRV measured as standard deviation of normal-to-normal (SONN) was lower in the HIV group compared with the controls [36 (25-55) versus 74 (57-84) ms; P<0.01] as was parasympathetic activity measured as square root of the mean squared difference of successive normal-to-normal intervals (RMSSD) [22 (9-30) versus 35 (24-62) ms; P<0.05]. Low frequency power was lower in the HIV group compared with the control group [294 (161-602) versus 946 (711-1668) ms(2); P<0.01]. High frequency power as well as systolic and diastolic blood pressure did not differ between the groups. CONCLUSIONS: The HIV patients in ART have increased resting heart rate and decreased short-term heart rate variability indicating parasympathetic dysfunction.

[Radionuclide therapy for neuroendocrine tumours]. / Radionuklidbehandling af neuroendokrine tumorer.

Peptide receptor radionuclide therapy using somatostatin analogues labelled with beta-emitting isotopes can be given to patients with metastasized or inoperable neuroendocrine tumours provided these have increased uptake on octreotide scintigraphy. This is a brief review of the treatment principle, indications and contraindications and practices with (177)Lu-DOTATATE treatment used at Rigshospitalet. Side effects are generally mild and reversible. Severe long-term side effects are rare. The majority of patients will experience increased quality of life and partial tumour reduction or stabilization for a period of time. However, up to 20% will experience no treatment effect.