Hemoglobin A1c and abdominal obesity as predictors of diabetes and ASCVD in individuals with prediabetes in UK Biobank: a prospective observational study.

Objectives: Whether "prediabetes" merits particular clinical attention beyond the management of associated risk factors is controversial, particularly given the expansion of the definition of prediabetes from HbA1c 6.0-6.4% to 5.

Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial.

Background: Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury.

Methods: In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.

Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

Background And Aims: Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care.

Methods: A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included.

A reliable, reproducible flow cytometry protocol for immune cell quantification in human adipose tissue.

The ability to accurately identify and quantify immune cell populations within adipose tissue is important in understanding the role of immune cells in metabolic disease risk. Flow cytometry is the gold standard method for immune cell quantification. However, quantification of immune cells from adipose tissue presents a number of challenges because of the complexities of working with an oily substance and the rapid deterioration of immune cell viability before analysis can be performed.

Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study.

Background: Pneumocystis jirovecii pneumonia (PJP) can be challenging to diagnose, often requiring bronchoscopy. Since most patients suspected of PJP undergo imaging, we hypothesized that the findings of these studies could help estimate the probability of disease prior to invasive testing.

Methods: We created a cohort of patients who underwent bronchoscopy specifically to diagnose PJP and conducted a nested case-control study to compare the radiographic features between patients with (n = 72) and without (n = 288) pathologically proven PJP.

An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring.

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS.

An evidence-based analysis of the National Lipid Association recommendations concerning non-HDL-C and apoB.

Background: The National Lipid Association (NLA) selected non-HDL-C as its prime index of the cardiovascular risk associated with the apoB lipoproteins. ApoB was recommended only as an optional secondary target after low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) targets were achieved.

Objective: The aims of this analysis were to determine whether (1) all relevant uses of apoB were considered by the NLA; (2) all the relevant evidence was considered by the NLA panel; and (3) all the evidence that was considered was interpreted correctly.

The proportion of all previous patients was a potential instrument for patients' actual prescriptions of nonsteroidal anti-inflammatory drugs.

Objectives: To investigate whether physician's prescribing preference is a valid instrumental variable (IV) for patients' actual prescription of selective cyclooxygenase-2 (COX-2) inhibitors in the German Pharmacoepidemiological Research Database (GePaRD).

Study Design And Setting: We compared the effect of COX-2 inhibitors vs. traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) on the risk of gastrointestinal complications using physician's preference as IV.

Effect of obesity and type 2 diabetes on protein anabolic response to insulin in elderly women.

Obesity and type 2 diabetes have been shown to alter the insulin sensitivity of glucose and protein metabolism in middle-aged women. We aimed to determine whether these findings translate to the elderly who are at increased risk of muscle loss. We assessed whole-body protein (1-(13)C-leucine) and glucose (3-(3)H-glucose) kinetics in 10 healthy (age: 71.

Long-term effects of 4 popular diets on weight loss and cardiovascular risk factors: a systematic review of randomized controlled trials.

Background: We conducted a systematic review to examine the efficacy of the Atkins, South Beach, Weight Watchers (WW), and Zone diets, with a particular focus on sustained weight loss at ≥12 months.

Methods And Results: We systematically searched MEDLINE, EMBASE, and the Cochrane Library of Clinical Trials to identify randomized controlled trials (RCTs) published in English with follow-up ≥4 weeks that examined the effects of these 4 popular diets on weight loss and cardiovascular risk factors. We identified 12 RCTs (n=2559) with follow-up ≥12 months: 10 versus usual care (5 Atkins, 4 WW, and 1 South Beach) and 2 head-to-head (1 of Atkins, WW, and Zone, and 1 of Atkins, Zone, and control).

Apolipoprotein E derived HDL mimetic peptide ATI-5261 promotes nascent HDL formation and reverse cholesterol transport in vitro.

Modulation of the reverse cholesterol transport (RCT) pathway may provide a therapeutic target for the prevention and treatment of atherosclerotic cardiovascular disease (CVD). In the present study, we evaluated a novel 26-amino acid apolipoprotein mimetic peptide (ATI-5261) designed from the carboxyl terminal of apoE, in its ability to mimic apoA-I functionality in RCT in vitro. Our data shows that nascent HDL-like (nHDL) particles generated by incubating cells over-expressing ABCA1 with ATI-5261 increase the rate of specific ABCA1 dependent lipid efflux, with high affinity interactions with ABCA1.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

Background: Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation.

Cancer cachexia and diabetes: similarities in metabolic alterations and possible treatment.

Cancer cachexia is a metabolic syndrome featuring many alterations typical of type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia, epidemiological evidence also supports an accelerated age-related muscle loss in T2D. Insulin resistance manifests in both conditions and impairs glucose disposal and protein anabolism by tissues.

The transcultural diabetes nutrition algorithm: a canadian perspective.

The Transcultural Diabetes Nutrition Algorithm (tDNA) is a clinical tool designed to facilitate implementation of therapeutic lifestyle recommendations for people with or at risk for type 2 diabetes. Cultural adaptation of evidence-based clinical practice guidelines (CPG) recommendations is essential to address varied patient populations within and among diverse regions worldwide. The Canadian version of tDNA supports and targets behavioural changes to improve nutritional quality and to promote regular daily physical activity consistent with Canadian Diabetes Association CPG, as well as channelling the concomitant management of obesity, hypertension, dyslipidemia, and dysglycaemia in primary care.

Inhibition of mammalian target of rapamycin augments lipopolysaccharide-induced lung injury and apoptosis.

Acute lung injury during bacterial infection is associated with neutrophilic inflammation, epithelial cell apoptosis, and disruption of the alveolar-capillary barrier. TLR4 is required for lung injury in animals exposed to bacterial LPS and initiates proinflammatory responses in part via the transcription factor NF-κB. Ligation of TLR4 also initiates a proapoptotic response by activating IFN-β and STAT1-dependent genes.

Postprandial hyperaminoacidaemia overcomes insulin resistance of protein anabolism in men with type 2 diabetes.

Aims/hypothesis: Although protein is usually ignored when considering insulin resistance, we have shown resistance of protein concurrent with glucose metabolism in men with type 2 diabetes during a hyperinsulinaemic clamp at euglycaemia and fasting aminoacidaemia. We hypothesised that this resistance is even worse during conditions that simulate the postprandial state, when anabolism should be maximal.

Methods: Eight overweight and obese men with type 2 diabetes underwent a hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with plasma amino acids at postabsorptive (Hyper-2) then at postprandial concentrations (Hyper-3).

Receptor activation and inhibition in cellular response to chemotherapeutic combinational mimicries: the concept of divergent targeting.

The antiproliferative effect of tandem somatostatin receptor (SSTR) activation, epidermal growth factor receptor (EGFR) inhibition, and induction of DNA damage was analyzed using octreotide (OCT), a SSTR agonist, the clinical DNA methylating agent temozolomide (TMZ), Iressa, an EGFR inhibitor, and dual EGFR-DNA targeting agents termed "combi-molecules". Using SSTR-expressing glioma cells harbouring low levels of EGFR (U87MG) or transfected to overexpress EGFR (U87/EGFR) or a variant (U87/EGFRvIII), we showed that Iressa, alone or in combination with the DNA damaging agent TMZ, and combi-molecules RA2 and RA5 inhibited EGF-induced phosphorylation of EGFR in U87MG and more moderately in U87/EGFR and U87/EGFRvIII transfected cells. This translated into equivalent levels of Erk 1/2 inhibition.

High-density lipoproteins and cardiovascular disease: 2010 update.

High-density lipoprotein-cholesterol (HDL-C) is a continuous inverse cardiovascular risk factor. The mechanisms by which HDLs protect against atherosclerosis are multiple. The major effect is thought to be reverse cholesterol transport, the mechanism by which excess cellular cholesterol is returned to the liver for excretion in the bile.

Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL).

Background: Bevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial.

Patients And Methods: Patients (n = 1043) received cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles plus bevacizumab 7.

Organ donation: a portrait of family refusal in Québec.

Many studies from around the world have reported different reasons why families refuse organ donation. In Quebec, however, there are no known data on the subject. To enable us to better communicate with families, a research project was conducted from January to December 2007 in hospital centers with personnel who specialize in supporting families.