Parallel assessment of albuminuria and plasma sTNFR1 in people with type 2 diabetes and advanced chronic kidney disease provides accurate prognostication of the risks of renal decline and death.

Identification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA1c ≥ 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/BSA) (n = 118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by - 0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of ≥ 40% decline in CKD-EPI eGFR (HR 1.5, p = 0.001) and doubling of serum creatinine (HR 2.0, p < 0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p = 0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.

Intraoperative assessment of femoral head perfusion during surgical hip dislocation for slipped capital femoral epiphysis.

Avascular necrosis is the most devastating complication of slipped capital femoral epiphysis, leading to collapse of the femoral head, increased risk of osteoarthritis and the requirement of early total hip arthroplasty. It is believed that intraoperative femoral head perfusion assessment may be an accurate predictor of post-operative avascular necrosis (radiographic collapse). At our institution, femoral head perfusion is assessed intraoperatively during all sub-capital realignment procedures. We hypothesize that our method is accurate in predicting the risk of developing post-operative avascular necrosis. In this retrospective study, we collected data from all patients that had intraoperative blood flow measurements during sub-capital realignment procedures. We correlated this with long-term radiographs looking for radiographic collapse. The intraoperative femoral head perfusion assessments during sub-capital realignment procedures for slipped capital femoral epiphysis at our institution, between January 2015 and March 2020 inclusive were assessed for reliability. In total, 26 of 35 patients had intraoperative femoral head perfusion present. Only 2 (8%) of these patients developed radiographic collapse. In contrast, 7 (78%) of the 9 patients who did not have femoral head perfusion present intraoperatively developed radiographic collapse, indicating that our method may be reliable in predicting a patient's post-operative risk of developing avascular necrosis.

Continuous Glucose Monitoring: A Brief Review for Primary Care Practitioners.

Glycated hemoglobin A1c (HbA1c) is routinely used as a marker of average glycemic control, but it fails to provide data on hypoglycemia and glycemic variability, both of which are associated with adverse clinical outcomes. Self-monitoring of blood glucose (SMBG), particularly in insulin-treated patients, is a cornerstone in the management of patients with diabetes. SMBG helps with treatment decisions that aim to reduce high glucose levels while avoiding hypoglycemia and limiting glucose variability. However, repeated SMBG can be inconvenient to patients and difficult to maintain in the long term. By contrast, continuous glucose monitoring (CGM) provides a convenient, comprehensive assessment of blood glucose levels, allowing the identification of high and low glucose levels, in addition to evaluating glycemic variability. CGM using newer detection and visualization systems can overcome many of the limitations of an HbA1c-based approach while addressing the inconvenience and fragmented glucose data associated with SMBG. When used together with HbA1c monitoring, CGM provides complementary information on glucose levels, thus facilitating the optimization of diabetes therapy while reducing the fear and risk of hypoglycemia. Here we review the capabilities and benefits of CGM, including cost-effectiveness data, and discuss the potential limitations of this glucose-monitoring strategy for the management of patients with diabetes. FUNDING: Sanofi US, Inc.

New Functional Tools for Antithrombogenic Activity Assessment of Live Surface Glycocalyx.

OBJECTIVE: It is widely accepted that the presence of a glycosaminoglycan-rich glycocalyx is essential for endothelialized vasculature health; in fact, a damaged or impaired glycocalyx has been demonstrated in many vascular diseases. Currently, there are no methods that characterize glycocalyx functionality, thus limiting investigators' ability to assess the role of the glycocalyx in vascular health. APPROACH AND RESULTS: We have developed novel, easy-to-use, in vitro assays that directly quantify live endothelialized surface's functional heparin weights and their anticoagulant capacity to inactivate Factor Xa and thrombin. Using our assays, we characterized 2 commonly used vascular models: native rat aorta and cultured human umbilical vein endothelial cell monolayer. We determined heparin contents to be ≈10 000 ng/cm(2) on the native aorta and ≈10-fold lower on cultured human umbilical vein endothelial cells. Interestingly, human umbilical vein endothelial cells demonstrated a 5-fold lower anticoagulation capacity in inactivating both Factor Xa and thrombin relative to native aortas. We verified the validity and accuracy of the novel assays developed in this work using liquid chromatography-mass spectrometry analysis. CONCLUSIONS: Our assays are of high relevance in the vascular community because they can be used to establish the antithrombogenic capacity of many different types of surfaces such as vascular grafts and transplants. This work will also advance the capacity for glycocalyx-targeting therapeutics development to treat damaged vasculatures.