Measurement of platelet thrombus formation in patients following severe thermal injury.

Severe thermal injury significantly impacts upon hemostasis and is associated with classical changes to the circulating platelet count with a nadir followed by a rebound thrombocytosis at days ~3 and ~15 post-injury, respectively. To date, few studies have assessed platelet function following thermal injury as platelet tests often require large quantities of blood, are not representative of normal platelet pathophysiology, and are usually dependent on a normal platelet count. The purpose of this study was to measure platelet thrombus formation using a whole blood flow chip-based system following thermal injury and to study how platelet counts may impact upon the measurement.

Accelerated aging of skeletal muscle and the immune system in patients with chronic liver disease.

Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls.

Establishing Predictors of Acute Sarcopenia: A Proof-Of-Concept Study Utilising Network Analysis.

Dynamic changes in sarcopenia status following stressor events are defined as acute sarcopenia; it is currently unknown how to stratify risk. Prospective observational study involving elective colorectal surgery, emergency abdominal surgery, and medical patients with infections aged ≥70 years-old. Handgrip strength, muscle quantity (ultrasound Bilateral Anterior Thigh Thickness, BATT, and Bioelectrical Impedance Analysis), and muscle quality (rectus femoris echogenicity) were measured preoperatively in the elective group, and within 48hours, 7days after, and 13weeks after admission/surgery.

Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.

Background: Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression.

Towards personalised anti-microbial and immune approaches to infections in acute care. Can real-time genomic-informed diagnosis of pathogens, and immune-focused therapies improve outcomes for patients? An observational, experimental study protocol.

Introduction: Infection causes a vast burden of disease, with significant mortality, morbidity and costs to health-care systems. However, identifying the pathogen causative infection can be challenging, resulting in high use of broad-spectrum antibiotics, much of which may be inappropriate. Novel metagenomic methods have potential to rapidly identify pathogens, however their clinical utility for many infections is currently unclear.

A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age.

An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to investigate whether a multi-component nutritional supplement could reduce systemic inflammation and epigenetic age in healthy older adults.

Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care.

Background: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs).

Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).

Introduction: Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed.

Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study.

Introduction: Burn-induced changes in the phenotype and function of neutrophils, cells which provide front-line protection against rapidly dividing bacterial infections, are emerging as potential biomarkers for the early prediction of sepsis. In a longitudinal study of adult burns patients, we recently demonstrated that a combined measurement of neutrophil phagocytic capacity, immature granulocyte (IG) count and plasma cell-free DNA (cfDNA) levels on the day of injury gave good discriminatory power for the prediction of later sepsis development. However, limited by a small sample size, single-centre design and focus on adult burns patients, these biomarkers require prospective validation in a larger patient cohort.

Coronary microvascular dysfunction is associated with degree of anaemia in end-stage renal disease.

Background: Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertension and left ventricular hypertrophy.

Cardiovascular Effects of Unilateral Nephrectomy in Living Kidney Donors at 5 Years.

[Figure: see text].

Coronary flow velocity reserve and inflammatory markers in living kidney donors.

Background: Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk.

Evidence for a shift to anaerobic metabolism in adipose tissue in efavirenz-containing regimens for HIV with different nucleoside backbones.

Background: Antiretroviral (ARV) treatment has been associated with abnormalities in lipid and mitochondrial metabolism. We compared patterns of gene expression in the subcutaneous adipose tissue (SAT) of HIV-positive subjects before and after 18-24 months of ARV therapy with HIV-negative controls.

Methods: HIV patients naive to ARV were randomized to receive zidovudine (AZT), lamivudine (3TC) with efavirenz (EFV) or tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) and EFV.

High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects.

Objective: To evaluate the changes in circulating endotoxin after a high-saturated fat meal to determine whether these effects depend on metabolic disease state.

Research Design And Methods: Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.

Visfatin is regulated by rosiglitazone in type 2 diabetes mellitus and influenced by NFκB and JNK in human abdominal subcutaneous adipocytes.

Visfatin has been proposed as an insulin-mimicking adipocytokine, predominantly secreted from adipose tissue and correlated with obesity. However, recent studies suggest visfatin may act as a proinflammatory cytokine. Our studies sought to determine the significance of this adipocytokine and its potential role in the pathogenesis of T2DM.

Acute and chronic saturated fatty acid treatment as a key instigator of the TLR-mediated inflammatory response in human adipose tissue, in vitro.

A post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activates an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels--a finding referred to as 'metabolic memory'. This study examined chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ads) and determined whether Ads are subject to "metabolic memory." Abdominal (Abd) subcutaneous (Sc) explants and Ads were treated with chronic low glucose (L-Glc): 5.

Lipopolysaccharide, high glucose and saturated fatty acids induce endoplasmic reticulum stress in cultured primary human adipocytes: Salicylate alleviates this stress.

Recent findings indicate that endoplasmic reticulum (ER) stress is significantly increased in adipose tissue of obese human subjects and is critical to the initiation and integration of pathways of inflammation and insulin action. But the factors inducing ER stress in human adipose tissue are unknown. The common factors increased in obesity and linked to insulin resistance are hyperglycaemia, hyperlipidemia and also endotoxemia.

Elevated endotoxin levels in non-alcoholic fatty liver disease.

Background: Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status.

Methods: Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters.

Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months.

Background: Abnormal lipid metabolism and cell oxidative mechanisms are reported in patients on antiretroviral treatment. We compared the expression of several key adipocyte genes in HIV-infected patients randomized to antiretroviral regimens containing zidovudine (AZT) or tenofovir disoproxil fumarate (TDF).

Methods: Subcutaneous fat was sampled from 32 HIV-positive treatment-naive patients before and 6 months after randomization to AZT/lamivudine/efavirenz (n=15) or TDF/emtricitabine/efavirenz (n=17) plus 15 HIV-negative matched controls.