The Prognostic Value of High-sensitivity C-reactive Protein and Prealbumin for Short-term Mortality in Acutely Hospitalized Multimorbid Elderly Patients: A Prospective Cohort Study.

OBJECTIVES: To establish the predictive value on mortality after 2 months from hospital admission of two laboratory markers of nutritional and inflammatory status, high-sensitivity C-reactive protein (hs-CRP) and prealbumin, in a cohort of frail multimorbid elderly without terminal illness. DESIGN: Prospective cohort study. SETTING: Internal medicine ward of a large teaching hospital in Italy. PARTICIPANTS: 544 Caucasian patients with acute disease consecutively admitted from January to June 2013. 102 were excluded for being younger than 65 years old, having life expectancy <30 days or not having frailty syndrome. Further 42 patients were excluded for missing data or withdrawn at follow-up. Final analysis was performed on 400 subjects (179 M, 221 F, mean age 79±10). MEASUREMENTS: Serum prealbumin and hs-CRP were measured at admission. Death within 2 months from hospital admission was assessed through a telephonic interview with the caregiver for each patient discharged alive. Inhospital mortality was also recorded. Survival was calculated from date of admission to our unit. RESULTS: Mean prealbumin at admission was 17.3±7.7 mg/dl, while hs-CRP median was 24.2 mg/L (IQR 8.7 to 51.8). 108 patients (27%) died within two months from admission. In an age- and sex-adjusted analysis, log(hs-CRP) levels at admission, but not prealbumin, were independently associated with an increased risk for mortality (HR 1.40, 95% CI 1.18 to 1.66, p<0.001). After multiple adjustments for covariates, including comorbidity burden measured through Charlson score, log(hs-CRP) remained significantly associated with mortality (HR 1.38, 95% CI 1.08 to 1.76, p=0.01). A Receiver Operating Characteristic (ROC) curve was performed to test the predictive value of hs-CRP at admission on two-month mortality (AUC 0.68, 95% CI 0.63 to 0.72, p<0.001). Cut-off value was set at 38.4 mg/L. After dichotomization of hs-CRP values according to this cut-off, hs-CRP≥38.4 mg/L at admission proved to be a significant risk factor for mortality (HR 2.10, 95% CI 1.23 to 3.58, p=0.006). CONCLUSION: Serum hs-CRP, but not prealbumin, values at admission are predictors of short-term mortality at hospital admission in elderly multimorbid patients. Inflammation seems to affect prognosis more than malnutrition in this setting and may therefore guide clinicians' attitude towards therapeutic choices.

Dietary style and acid load in an Italian population of calcium kidney stone formers.

BACKGROUND AND AIMS: Animal protein intake may cause an acid load that predisposes individuals to stones by influencing calcium and citrate excretion. These associations were not confirmed in recent studies. Therefore the present study was aimed to compare acid load of diet in stone formers and controls. METHODS AND RESULTS: Participants to the study were 157 consecutive calcium stone formers and 144 controls. Diet was analyzed in these subjects using a software that evaluated nutrient intake from a three-day food intake diary. This software also estimated the potential renal acid load (PRAL, mEq/day). Twenty-four-hour urine excretion of ions and citrate was measured in stone formers. Stone former diet had lower intake of glucose, fructose, potassium and fiber and higher PRAL in comparison with controls. The multinomial logistic regression analysis showed that stone risk decreased in association with the middle and the highest tertiles of fiber intake and increased in association with the highest tertile of PRAL. The linear multiple regression analysis showed that calcium excretion was associated with the sodium excretion and that citrate excretion was associated with the PRAL and animal protein intake in stone formers. CONCLUSION: Our findings suggest that stone formers may undergo a greater dietary acid load sustained by a low vegetable intake and base provision. Dietary acid load does not appear as the main determinant of calcium excretion, but may promote stone risk by decreasing citrate excretion. Sodium intake may predispose to stones by stimulating calcium excretion.

PKCε is a negative regulator of PVAT-derived vessel formation.

RATIONALE: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive. OBJECTIVE: Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis. METHODS AND RESULTS: Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1. CONCLUSION: PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.

The role of malnutrition in older persons with mobility limitations.

Movement disability has a high prevalence in elderly population, either healthy or with chronic disease. Impaired nutritional status is a very common condition in geriatric patients too, especially if we consider elderly subjects admitted to hospital. There are growing evidences that nutrition and disability are strictly interconnected. On the one side, nutritional status is one of the multiple elements that influence the onset and the course of a functional disability; on the other side, disability itself may contribute to malnutrition onset and worsening. Nutrition may not be the sole factor involved in movement impairment in the elderly, but consciousness of its importance in frail elderly population is growing among clinicians and scientific community. In this paper we review the existing knowledge of these complex relationships, discussing the main observational and interventional studies that explored the role of nutrition in movement disability onset and recovery. We also point out how specific kinds of diet, such as Mediterranean diet or high-protein diet, are involved in disability prevention. Finally, we take a look at the existing evidence of the role of single nutrient dietary intake, such as carotenoids, selenium or vitamin D, in mobility impairment in the elderly population.

The impact of omega-3 fatty acids on osteoporosis.

The essential polyunsaturated fatty acids (PUFAs) comprise 2 main classes: n-6 and n-3 fatty acids. The most common source of n-6 fatty acids is linoleic acid (LA) which is found in high concentrations in various vegetable oils. Arachidonic acid (AA), the 20-carbon n-6 fatty acid, is obtained largely by synthesis from LA in the body. The n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) are found in fish and fish oils. Long-Chain polyunsaturated fatty acids (LCPUFAs) and lipid mediators derived from LCPUFAs have critical roles in the regulation of a variety of biological processes including bone metabolism. There are different mechanisms by which dietary fatty acids affect bone: effect on calcium balance, effect on osteoblastogenesis and osteoblast activity, change of membrane function, decrease in inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), modulation of peroxisome proliferators-activated receptor gamma (PPARgamma). Animal studies have shown that a higher dietary omega-3/omega-6 fatty acids ratio is associated with beneficial effects on bone health. In spite of increasing evidence of the positive effects of dietary fats on bone metabolism from animal and in vitro studies, the few studies conducted in humans do not allow us to draw a definitive conclusion on their usefulness in clinical practice.

Association of keratin 8 gene mutation with chronic pancreatitis.

BACKGROUND: Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue. AIM: To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis. METHODS: Mutations in the keratin 8 gene were determined by polymerase chain reaction/restriction fragment length polymorphism in 67 chronic pancreatitis patients and 100 normal controls. Sequence analysis was performed when necessary. RESULTS: Glycine-to-cysteine mutations at position 61 (G61C) of the keratin 8 gene were found in six patients (8.9 vs. 0%, p(c) < 0.003, odds ratio = 21.24, confidence interval = 2.74-164.42); none of the controls presented the mutation. No tyrosine-to-histidine mutations at position 53 (Y53H) were detected in any subject. CONCLUSION: G61C mutation of the keratin 8 gene, together with other environmental factors and/or genetic factors, could predispose to chronic pancreatitis, by interfering with the normal organization of keratin filaments.