Proceso INFORNUT: validación de la fase de filtro-FILNUT--y comparación con otros métodos de detección precoz de desnutrición hospitalaria.

INTRODUCTION According to several series, hospital hyponutrition involves 30-50% of hospitalized patients. The high prevalence justifies the need for early detection from admission. There several classical screening tools that show important limitations in their systematic application in daily clinical practice. OBJECTIVES To analyze the relationship between hyponutrition, detected by our screening method, and mortality, hospital stay, or re-admissions. To analyze, as well, the relationship between hyponutrition and prescription of nutritional support. To compare different nutritional screening methods at admission on a random sample of hospitalized patients. Validation of the INFORNUT method for nutritional screening. MATERIAL AND METHODS In a previous phase from the study design, a retrospective analysis with data from the year 2003 was carried out in order to know the situation of hyponutrition in Virgen de la Victoria Hospital, at Malaga, gathering data from the MBDS (Minimal Basic Data Set), laboratory analysis of nutritional risk (FILNUT filter), and prescription of nutritional support. In the experimental phase, a cross-sectional cohort study was done with a random sample of 255 patients, on May of 2004. Anthropometrical study, Subjective Global Assessment (SGA), Mini-Nutritional Assessment (MNA), Nutritional Risk Screening (NRS), Gassull's method, CONUT and INFORNUT were done. The settings of the INFORNUT filter were: albumin < 3.5 g/dL, and/or total proteins <5 g/dL, and/or prealbumin <18 mg/dL, with or without total lymphocyte count < 1.600 cells/mm3 and/or total cholesterol <180 mg/dL. In order to compare the different methods, a gold standard is created based on the recommendations of the SENPE on anthropometrical and laboratory data. The statistical association analysis was done by the chi-squared test (a: 0.05) and agreement by the k index. RESULTS In the study performed in the previous phase, it is observed that the prevalence of hospital hyponutrition is 53.9%. One thousand six hundred and forty four patients received nutritional support, of which 66.9% suffered from hyponutrition. We also observed that hyponutrition is one of the factors favoring the increase in mortality (hyponourished patients 15.19% vs. non-hyponourished 2.58%), hospital stay (hyponourished patients 20.95 days vs. non-hyponourished 8.75 days), and re-admissions (hyponourished patients 14.30% vs. non-hyponourished 6%). The results from the experimental study are as follows: the prevalence of hyponutrition obtained by the gold standard was 61%, INFORNUT 60%. Agreement levels between INFORNUT, CONUT, and GASSULL are good or very good between them (k: 0.67 INFORNUT with CONUT, and k: 0.94 INFORNUT and GASSULL) and wit the gold standard (k: 0.83; k: 0.64 CONUT; k: 0.89 GASSULL). However, structured tests (SGA, MNA, NRS) show low agreement indexes with the gold standard and laboratory or mixed tests (Gassull), although they show a low to intermediate level of agreement when compared one to each other (k: 0.489 NRS with SGA). INFORNUT shows sensitivity of 92.3%, a positive predictive value of 94.1%, and specificity of 91.2%. After the filer phase, a preliminary report is sent, on which anthropometrical and intake data are added and a Nutritional Risk Report is done. CONCLUSIONS Hyponutrition prevalence in our study (60%) is similar to that found by other authors. Hyponutrition is associated to increased mortality, hospital stay, and re-admission rate. There are no tools that have proven to be effective to show early hyponutrition at the hospital setting without important applicability limitations. FILNUT, as the first phase of the filter process of INFORNUT represents a valid tool: it has sensitivity and specificity for nutritional screening at admission. The main advantages of the process would be early detection of patients with risk for hyponutrition, having a teaching and sensitization function to health care staff implicating them in nutritional assessment of their patients, and doing a hyponutrition diagnosis and nutritional support need in the discharge report that would be registered by the Clinical Documentation Department. Therefore, INFORNUT would be a universal screening method with a good cost-effectiveness ratio.

Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice.

BACKGROUND The lysophosphatidic acid LPA₁ receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA₁ receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory. METHODOLOGY/PRINCIPAL FINDINGS Male LPA₁-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice. CONCLUSIONS/SIGNIFICANCE These results reveal that the absence of the LPA₁ receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA₁ receptor pathway may be of interest with respect to the treatment of stress-induced hippocampal pathology.

Influence of physical activity and dietary habits on lipid profile, blood pressure and BMI in subjects with metabolic syndrome

BACKGROUND The present study was determined the influence of physical activity and dietary habits on lipid profile, blood pressure (BP) and body mass index (BMI) in subjects with metabolic syndrome (MS). AIMS Identify the relationship between physical activity and proper nutrition and the probability of suffering from myocardial infarction (MI). METHODS Hundred chronically ill with MS who were active and followed a healthy diet were classified as compliant, while the remaining subjects were classified as non-compliant. RESULTS The compliant subjects show lower BMI values (30.8±4.9 vs 32.5±4.6), as well as lower levels of triacylglycerol (130.4±48.2 vs 242.1±90.1), total cholesterol (193.5±39 vs 220.2±52.3) and low-density lipoprotein cholesterol (105.2±38.3 vs 139.2±45). They show higher values in terms of high-density lipoprotein cholesterol levels (62.2±20.1 vs 36.6±15.3), with statistically significant differences. In terms of both systolic and diastolic pressure, no differences were revealed between the groups; however, those who maintain proper dietary habits show lower systolic blood pressure levels than the inactive subjects. The probability of suffering from MI greatly increases among the group of non-compliant subjects. CONCLUSIONS Our results demonstrate how performing aerobic physical activity and following an individualized, Mediterranean diet significantly reduces MS indicators and the chances of suffering from MI.

Cognitive impairment in patients with fibromyalgia syndrome as assessed by the mini-mental state examination.

This study evaluated the frequency of cognitive impairment in patients with Fibromyalgia syndrome (FMS) using the Mini Mental State Examination (MMSE). METHODS We analyzed baseline data from all 46 patients with FMS and 92 age- and sex-matched controls per diagnosis of neuropathic (NeP) or mixed pain (MP) selected from a larger prospective study. RESULTS FMS had a slight but statistically significant lower score in the adjusted MMSE score (26.9; 95% CI 26.7-27.1) than either NeP (27.3; 95% CI 27.2-27.4) or MP (27.3; 27.2-27.5). The percentage of patients with congnitive impairment (adjusted MMSE

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Decreased levels of uric acid after oral glucose challenge is associated with triacylglycerol levels and degree of insulin resistance

Hyperuricaemia is one of the components of metabolic syndrome. Both oxidative stress and hyperinsulinism are important variables in the genesis of this syndrome and have a close association with uric acid (UA). We evaluated the effect of an oral glucose challenge on UA concentrations. The study included 656 persons aged 18 to 65 years. Glycaemia, insulin, UA and plasma proteins were measured at baseline and 120 min after an oral glucose tolerance test (OGTT). The baseline sample also included measurements of total cholesterol, triacylglycerol (TAG) and HDL-cholesterol. Insulin resistance was calculated with the homeostasis model assessment. UA levels were significantly lower after the OGTT (281.93 (sd 92.19) v. 267.48 (sd 90.40) micromol/l; P < 0.0001). Subjects with a drop in UA concentrations >40.86 micromol/l (>75th percentile) had higher plasma TAG levels (P = 0.0001), baseline insulin (P = 0.02) and greater insulin resistance (P = 0.034). Women with a difference in plasma concentrations of UA above the 75th percentile had higher baseline insulin levels (P = 0.019), concentration of plasma TAG (P = 0.0001) and a greater insulin resistance index (P = 0.029), whereas the only significant difference in men was the level of TAG. Multiple regression analysis showed that the basal TAG levels, insulin at 120 min, glycaemia at 120 min and waist:hip ratio significantly predicted the variance in the UA difference (r2 0.077). Levels of UA were significantly lower after the OGTT and the individuals with the greatest decrease in UA levels are those who have greater insulin resistance and higher TAG levels.

Inverse relation between levels of anti-oxidized-LDL antibodies and eicosapentanoic acid (EPA).

Oxidative modification of LDL is thought to play an important role in the development of atherosclerosis. Susceptibility of LDL to peroxidation may partly depend on the compositional characteristics of the antioxidant and fatty acid content. The aim of this study was to examine the association between levels of antibodies to oxidized LDL and the various serum fatty acids in women. A total of 465 women aged 18-65 years were selected randomly from the adult population census of Pizarra, a town in southern Spain. Measurement of anti-oxidized-LDL was done by ELISA and the fatty acid composition of serum phospholipids was determined by GC. The levels of anti-oxidized-LDL antibodies were significantly related with age (r - 0.341, P < 0.001), BMI (r - 0.239, P < 0.001), waist:hip ratio (r - 0.285, P < 0.001), glucose (r - 0.208, P < 0.001), cholesterol (r - 0.243, P < 0.001), LDL-cholesterol (r - 0.185, P = 0.002), EPA (r - 0.159, P = 0.003), DHA (r - 0.121, P = 0.026), and the sum of the serum phospholipid n-3 PUFA (r - 0.141, P = 0.009). Multiple regression analysis showed that the variables that explained the behaviour of the levels of anti-oxidized-LDL antibodies were age (P < 0.001) and the serum phospholipid EPA (P < 0.001). This study showed that the fatty acid composition of serum phospholipids, and especially the percentage of EPA, was inversely related with the levels of anti-oxidized-LDL antibodies.

Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes.

The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.

Fungal whip beats the heart.

A 24-year-old man was admitted to the hospital because of fever, cough, and dyspnea of 4 weeks’ duration. The patient gave a history of parenteral drug abuse since he was 17 years old and had been diagnosed with HIV infection 4 years before admission. A chest radiograph showed multiple alveolar infiltrates. Four blood cultures were positive for Candida albicans.

Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire.

BACKGROUND Several questionnaires have been used to measure health related quality of life (HRQoL) in patients with psoriasis, few have been adapted for use in Spain; none of them was developed specifically for the Spanish population. The purpose of the study was to validate and assess the sensitivity to change of a new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE). METHODS Observational, prospective, multicenter study performed in centers around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE together with other Dermatology Quality of Life Index (DLQI) and Psoriasis Disability Index (PDI). A control group of patients with urticaria or atopic dermatitis was also included. Internal consistency and test-retest reliability of the PSO-LIFE were assessed by calculating Cronbach's alpha and Intraclass Correlation Coefficient (ICC). Validity was assessed by examining factorial structure, the capacity to discriminate between groups, and correlations with other measures. Sensitivity to change was measured using effect sizes. RESULTS The final sample included for analysis consisted of 304 patients and 56 controls. Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14) years for controls (p < 0.01). Cronbach's alpha for the PSO-LIFE was 0.95 and test-retest reliability using the ICC was 0.98. Factor analysis showed the questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05), between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p < 0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs. 74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was moderate (r = -0.43) while correlations with DLQI and PDI dimensions ranged from moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients reporting 'much improved' health status at study completion was 1.01 (large effect size). CONCLUSIONS The present results provide substantial support for the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in the population for which it was designed.

Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications.

BACKGROUND We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.

Adipose tissue gene expression of factors related to lipid processing in obesity.

BACKGROUND Adipose tissue lipid storage and processing capacity can be a key factor for obesity-related metabolic disorders such as insulin resistance and diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim of this study was to analyze the gene expression of factors involved in lipid uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue according to body mass index (BMI) and the degree of insulin resistance (IR). METHODS AND PRINCIPAL FINDINGS VLDL receptor (VLDLR), lipoprotein lipase (LPL), acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR, 10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean controls. In SAT, LPL and FABP4 expression were also higher in lean controls. BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple regression analysis showed that BMI was the main variable contributing to LPL and FABP4 gene expression in both VAT and SAT. CONCLUSIONS Morbidly obese patients have a lower gene expression of factors related with lipid uptake and processing in comparison with healthy lean persons.

De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery.

OBJECTIVE De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes. METHODS We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). RESULTS When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression ≥ P50 before bariatric surgery had a lower percentage hip circumference loss (

Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations

Summary Points Brucellosis remains the commonest anthropozoonosis worldwide, and its treatment remains complex, requiring protracted administration of more than one antibiotic. In November 2006, a consensus meeting aimed at reaching a common specialist statement on the treatment of brucellosis was held in Ioannina, Greece under the auspices of the International Society of Chemotherapy and the Institute of Continuing Medical Education of Ioannina. The author panel suggests that the optimal treatment of uncomplicated brucellosis should be based on a six-week regimen of doxycycline combined either with streptomycin for 2–3 weeks, or rifampicin for six weeks. Gentamicin may be considered an acceptable alternative to streptomycin, while all other regimens/combinations should be considered second-line. The development of a common global therapeutic language for human brucellosis, and future, properly conducted clinical trials would definitely solve controversies regarding the disease.

Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.

Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.