Malnutrition prevalence according to GLIM and its feasibility in geriatric patients: a prospective cross-sectional study.

PURPOSE: In 2019, the Global Leadership Initiative on Malnutrition (GLIM) suggested a 2-step diagnostic format for malnutrition including screening and diagnosis. Prospective validation and feasibility studies, using the complete set of the five GLIM criteria, are needed. The aims of this study were to determine the prevalence of malnutrition, and investigate how the prevalence varied with mode of screening. Furthermore, we assessed the feasibility of GLIM in geriatric patients. METHODS: Consecutive patients from two acute geriatric wards were included. For screening risk of malnutrition, the Mini Nutritional Assessment-Short Form (MNA-SF) or Malnutrition Screening Tool (MST) were used. In accordance with GLIM, a combination of phenotypic and etiologic criteria were required for the diagnosis of malnutrition. Feasibility was determined based on % data completeness, and above 80% completeness was considered feasible. RESULTS: One hundred patients (mean age 82 years, 58% women) were included. After screening with MNA-SF malnutrition was confirmed by GLIM in 51%, as compared with 35% after screening with MST (p = 0.039). Corresponding prevalence was 58% with no prior screening. Using hand grip strength as a supportive measure for reduced muscle mass, 69% of the patients were malnourished. Feasibility varied between 70 and 100% for the different GLIM criteria, with calf circumference as a proxy for reduced muscle mass having the lowest feasibility. CONCLUSION: In acute geriatric patients, the prevalence of malnutrition according to GLIM varied depending on the screening tool used. In this setting, GLIM appears feasible, besides for the criterion of reduced muscle mass.

Mature-onset obesity in interleukin-1 receptor I knockout mice.

Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(-/-) mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.

Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis.

BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.

Neuron-specific ablation of PDGF-B is compatible with normal central nervous system development and astroglial response to injury.

Members of the PDGF family have multiple roles during embryogenesis and in a variety of pathological situations in the adult. One of the major sites of PDGF-B expression in adult mammals are postmitotic CNS neurons. Combined with reported neurotrophic and neuroprotective effects of exogenously administered PDGFs, this has led to the speculation that PDGF-B may have a role in CNS development, in maintenance, or in response to CNS injury. To test these hypotheses, we developed mice in which PDGF-B was ablated genetically in postmitotic neurons at sites where PDGF-B is normally expressed. We found that these mice develop to adulthood without apparent defects. We demonstrate PDGF-B expression in the postnatal mouse hippocampus and forebrain cortex. We show that neuron-specific knockout of PDGF-B does not influence the astroglial and angiogenic responses to injury in the hippocampus or forebrain cortex. We conclude that the role of neuron-derived PDGF-B remains obscure. A role for neuron-derived PDGF-B, if existing, might be redundant with other CNS growth factors. Alternatively, other and more specific analyses of CNS functions in the normal and injured states will be required to demonstrate such a role.

Role of platelet-derived growth factor in mesangium development and vasculopathies: lessons from platelet-derived growth factor and platelet-derived growth factor receptor mutations in mice.

PURPOSE OF REVIEW: The phenotypic consequences of null mutations in the platelet-derived growth factor-B and the platelet-derived growth factor beta-receptor genes in mice have demonstrated that these proteins play pivotal roles in the development of the vascular smooth muscle cell lineage, including pericytes and mesangial cells. RECENT FINDINGS: The lethality of these mutants has precluded analysis of the physiological and pathophysiological consequences of platelet-derived growth factor-B and platelet-derived growth factor beta-receptor deficiency in adults. This review summarizes and discusses recent data from certain tissue-specific and subtle mutations in the platelet-derived growth factor-B and platelet-derived growth factor beta-receptor genes that are compatible with postnatal viability in spite of severe developmental deficits in pericyte and mesangial cell recruitment. In the postnatal period, the animals studied developed a characteristic set of pathological changes to small blood vessels of the retina and the kidney glomerulus, which sheds light on the importance of pericytes and mesangial cells for vascular integrity and function after birth. SUMMARY: These microvascular abnormalities and their consequences bear a resemblance to diabetic microangiopathy and nephropathy. The platelet-derived growth factor-B and platelet-derived growth factor beta-receptor mutant mouse models, therefore, might serve as valuable tools in the dissection of some of the pathogenic events in diabetic microangiopathy.

Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities.

Platelet-derived growth factor-B (PDGFB) is necessary for normal cardiovascular development, but the relative importance of different cellular sources of PDGFB has not been established. Using Cre-lox techniques, we show here that genetic ablation of Pdgfb in endothelial cells leads to impaired recruitment of pericytes to blood vessels. The endothelium-restricted Pdgfb knockout mutants also developed organ defects including cardiac, placental and renal abnormalities. These defects were similar to those observed in Pdgfb null mice. However, in marked contrast to the embryonic lethality of Pdgfb null mutants, the endothelium-specific mutants survived into adulthood with persistent pathological changes, including brain microhemorrhages, focal astrogliosis, and kidney glomerulus abnormalities. This spectrum of pathological changes is reminiscent of diabetic microangiopathy, suggesting that the endothelium-restricted Pdgfb knockouts may serve as models for some of the pathogenic events of vascular complications to diabetes.

Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy.

Loss of pericytes from the capillary wall is a hallmark of diabetic retinopathy, however, the pathogenic significance of this phenomenon is unclear. In previous mouse gene knockout models leading to pericyte deficiency, prenatal lethality has so far precluded analysis of postnatal consequences in the retina. We now report that endothelium-restricted ablation of platelet-derived growth factor-B generates viable mice with extensive inter- and intra-individual variation in the density of pericytes throughout the CNS. We found a strong inverse correlation between pericyte density and the formation of a range of retinal microvascular abnormalities strongly reminiscent of those seen in diabetic humans. Proliferative retinopathy invariably developed when pericyte density was <50% of normal. Our data suggest that a reduction of the pericyte density is sufficient to cause retinopathy in mice, implying that pericyte loss may also be a causal pathogenic event in human diabetic retinopathy.

Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall.

Several platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) family members display C-terminal protein motifs that confer retention of the secreted factors within the pericellular space. To address the role of PDGF-B retention in vivo, we deleted the retention motif by gene targeting in mice. This resulted in defective investment of pericytes in the microvessel wall and delayed formation of the renal glomerulus mesangium. Long-term effects of lack of PDGF-B retention included severe retinal deterioration, glomerulosclerosis, and proteinuria. We conclude that retention of PDGF-B in microvessels is essential for proper recruitment and organization of pericytes and for renal and retinal function in adult mice.