Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants-a prospective cohort study (RESCUE-TX).

Background: The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation.

Methods: We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e.

Functional Natural Killer-cell Genetics and Microvascular Inflammation After Kidney Transplantation: An Observational Cohort Study.

Background: Recent evidence highlights the pivotal role of natural killer (NK) cells in allograft rejection.

Methods: We explored associations of missing self and gene polymorphisms determining the phenotype and/or functionality of NK cells with microvascular inflammation (MVI) in a single-center cohort of 507 consecutive kidney transplant recipients. Patients were genotyped for killer cell Ig-like receptors and polymorphisms in 4 selected genes (FCGR3AV/F158 [rs396991], KLRC2wt/del, KLRK1HNK/LNK [rs1049174], and rs9916629-C/T).

Morphologic and Molecular Features of Antibody-Mediated Transplant Rejection: Pivotal Role of Molecular Injury as an Independent Predictor of Renal Allograft Functional Decline.

Current knowledge about the factors correlating with functional decline and subsequent failure of kidney allografts in antibody-mediated rejection (ABMR) is limited. We conducted a cohort study involving 75 renal allograft recipients diagnosed with late ABMR occurring at least 6 months after transplantation. The study aimed to examine the correlation of molecular and histologic features with estimated glomerular filtration rate (eGFR) trajectories and death-censored graft survival.

Obesity is associated with a higher Torque Teno viral load compared to leanness.

Introduction: Obesity affects a rising proportion of the population and is an important risk factor for unfavorable outcomes in viral disease including severe acute respiratory syndrome coronavirus 2- associated diseases. Torque Teno virus (TTV) is a ubiquitous and apathogenic virus which reflects the immune function of its host. The aim of this study was to investigate the association between obesity and TTV load - an indirect marker of compromised viral immune response.

High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients with Peripheral Artery Disease Predict Long-Term Survival.

Low-density lipoprotein-cholesterol reduction showed a strong reduction of cardiovascular (CV) event rates in CV disease. However, the residual risk of future CV events remains high, which especially extends to peripheral arterial disease (PAD). Nuclear magnetic resonance (NMR) spectroscopy offers a novel method for analysis of the lipoprotein spectrum.

Brown Adipose Tissue Prevalence Is Lower in Obesity but Its Metabolic Activity Is Intact.

Due to its high metabolic activity, brown adipose tissue (BAT) has become a promising target for the development of novel treatment concepts for metabolic disease. Despite several reports of a negative association between the presence of active BAT and obesity, very little is known about the quantitative and qualitative differences of BAT in lean and obese individuals. Systematic studies directly comparing cold-induced BAT activity in leanness and obesity are currently lacking.

Deletion of the Natural Killer Cell Receptor NKG2C Encoding Gene and Kidney Transplant Outcome.

Natural killer (NK) cells may contribute to antibody-mediated rejection (ABMR) of renal allografts. The role of distinct NK cell subsets in this specific context, such as NK cells expressing the activating receptor NKG2C, is unknown. Our aim was to investigate whether gene deletion variants which determine NKG2C expression affect the pathogenicity of donor-specific antibodies (DSA) and, if so, influence long-term graft survival.

Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity.

Obesity is associated with increasing cardiometabolic morbidity and mortality worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested as a promoter of leanness and metabolic health.

The Association of Cortisol Excretion with Weight and Metabolic Parameters in Nondiabetic Patients with Morbid Obesity.

Introduction: Cortisol is involved in the regulation of gluconeogenesis and glucose utilization. In morbid obesity (MO), the association of cortisol excretion with metabolic parameters is not well-characterized. In our study, we evaluated cortisol excretion in nondiabetic subjects with MO and its effect on glucose metabolism.

Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.

Introduction: Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals.

Sex differences in brown adipose tissue activity and cold-induced thermogenesis.

Introduction: Brown adipose tissue (BAT) is suggested to exhibit a sexual dimorphism and thus contributes to the observed sex differences in cardiometabolic risk observed between women and men. Clinical data supporting this hypothesis are however scarce. The aim of this study was to investigate the relationship between BAT activity and sex using positron emission tomography (PET) - the current gold-standard for BAT quantification.

Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery.

Purpose: Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease.

Discovery of melanin-concentrating hormone receptor 1 in brown adipose tissue.

Although extensive research on brown adipose tissue (BAT) has stimulated optimism in the battle against obesity and diabetes, BAT physiology and organ crosstalk are not fully understood. Besides BAT, melanin-concentrating hormone (MCH) and its receptor (MCHR1) play an important role in energy homeostasis. Because of the link between hypothalamic MCH neurons and sympathetic BAT activation via β-adrenoceptors, we investigated the expression and physiological role of the MCHR1 in BAT.

Evaluation of sCD163 and sTWEAK in patients with stable peripheral arterial disease and association with disease severity as well as long-term mortality.

Background And Aims: The TNF-superfamily member sTWEAK and its scavenger receptor sCD163 are potentially involved in pathophysiological processes of atherosclerosis. In patients with peripheral arterial disease, previous research has shown that sTWEAK and the sCD163/sTWEAK ratio were independently associated with long term all-cause and cardiovascular survival. Since previous investigations emphasized on symptomatic peripheral arterial disease including critical limb ischemia, this study evaluates sTWEAK and sCD163 in a cohort of stable peripheral arterial disease including asymptomatic (Fontaine stage I) and intermittent claudication (Fontaine stage II) patients.

GlycA for long-term outcome in T2DM secondary prevention.

Aims: Glycosylated acetyls (GlycA), a systemic marker of inflammation, were associated both with incident type 2 diabetes mellitus (T2DM) and incident cardiovascular (CV) disease. This study evaluates the predictive value of GlycA for long-term survival in patients with T2DM and peripheral artery disease (PAD).

Methods: GlycA (mmol/l) levels were measured by nuclear magnetic resonance spectroscopy in a cross-sectional cohort of patients with PAD (n = 319).

The Transcriptional Role of Vitamin A and the Retinoid Axis in Brown Fat Function.

In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called "browning.

Vascular peroxidase 1 is independently associated with worse kidney function in patients with peripheral artery disease.

Background: Oxidative stress is involved in cardiovascular disease such as peripheral artery disease (PAD). Vascular Peroxidase 1 (VPO1), a novel heme-containing peroxidase mainly expressed in the cardiovascular system, aggravates oxidative stress. Evidence in humans is limited.

Predictive power of novel and established obesity indices for outcome in PAD during a five-year follow-up.

Background And Aims: Previous data show contradicting results regarding relevance of obesity on outcome in peripheral arterial disease (PAD). Thus, this study aims to evaluate the predictive power of obesity as measured by established and novel obesity indices (waist circumference WC, waist-hip ratio WHR, body-mass index BMI, body adiposity index BAI, visceral adiposity index VAI, weight-adjusted waist index WWI) in a PAD cohort.

Methods And Results: In 367 patients with diagnosed PAD anthropometric parameters were assessed at study inclusion in an observational study.

The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans.

Background: Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg).

Peripheral arterial disease and type 2 diabetes: Older patients still exhibit a survival benefit from glucose control.

Objective: To investigate a possible beneficial effect of strict glycaemic control on all-cause mortality in patients with peripheral arterial disease and type 2 diabetes mellitus.

Methods: A total of 367 mainly older peripheral arterial disease patients [age: 69 (62-78) years, 34% women, Fontaine stage I-II] were categorized according to glycaemic control, that is, (a) no type 2 diabetes mellitus, (b) strict glucose control (HbA1c < 53 mmol/mol) and (c) lenient glucose control (HbA1c ⩾ 53 mmol/mol) at inclusion and by mean HbA1c over the first study year. Mortality was analysed using Kaplan-Meier and Cox-regression analyses after 7 years.

Albuminuria in Patients with Morbid Obesity and the Effect of Weight Loss Following Bariatric Surgery.

Background And Objectives: Patients with morbid obesity are at an increased risk for cardiovascular and renal complications, which are not only linked to traditional cardiovascular risk factors. Thus, we evaluated (a) the prevalence of albuminuria in non-diabetic and diabetic morbidly obese patients and (b) the effect of weight loss following bariatric surgery.

Material And Methods: We included 1307 patients (77% women, mean age 40 ± 12 years, BMI 45.

Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes.

Thrombospondin-4 (TSP-4) is an extracellular matrix protein of the vessel wall. Despite bench evidence, its significance in the clinical setting of atherosclerosis is missing. TSP-4 (ng/ml) was measured in 365 PAD patientsusing a commercially available ELISA.

Adipose tissue browning in mice and humans.

In the midst of an obesity epidemic, the promotion of brown adipose tissue (BAT) function and the browning of white adipose tissue (WAT) have emerged as promising therapeutic targets to increase energy expenditure and counteract weight gain. Despite the fact that the thermogenic potential of bone fide BAT in rodents is several orders of magnitudes higher than white fat containing brite/beige adipocytes, WAT browning represents a particularly intriguing concept in humans given the extreme amount of excess WAT in obese individuals. In addition, the clear distinction between classic brown and beige fat that has been proposed in mice does not exist in humans.

YKL-40 levels increase with declining ankle-brachial index and are associated with long-term cardiovascular mortality in peripheral arterial disease patients.

Background And Aims: YKL-40 is an inflammatory marker secreted by macrophages and is expressed in atherosclerotic plaques. YKL-40 increases in coronary artery disease (CAD) with poor coronary collateral vessel development. Higher levels are linked to reduced survival in CAD patients.