Comparison of Simplified Creatinine Index and Systemic Inflammatory Markers for Nutritional Evaluation of Hemodialysis Patients.

Protein-energy wasting (PEW) is associated with adverse outcomes in hemodialysis patients. This study compares the simplified creatinine index (SCI) and circulating inflammatory markers as nutritional screening tools for hemodialysis patients. Maintenance hemodialysis patients (230 total patients, 34.8% women, 64.0 ± 14.3 years old) from a tertiary medical center were assessed for demographic data, body composition analysis, biochemistry tests, and circulating inflammatory biomarkers. The SCI was calculated using Canaud's formula. Reduced fat-free mass index (FFMI), a surrogate of lean body mass, was identified according to the European Society for Clinical Nutrition and Metabolism guidelines. Nutritional status was assessed by the geriatric nutritional risk index (GNRI) and International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Multivariate logistic regression revealed independent risk factors for low FFMI and malnutrition. Of the patients, 47.4% had low FFMI. Patients with a reduction in FFMI tended to be older females with lower body mass index, SCI, and GNRI scores but significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-8. SCI was found to be an independent predictor for reduced FFMI (OR 0.57, 95% CI 0.40-0.81) and presence of PEW according to ISRNM criteria (OR 0.38, 95% CI 0.21-0.68). Although a positive association between systemic inflammatory markers and low FFMI was observed, this association disappeared in multivariate analysis. Moreover, the inflammatory markers examined in this study were not associated with malnutrition after adjusting for potential confounders. Compared with markers of systemic inflammation, SCI achieved better performance in assessing the nutritional status of hemodialysis patients.

Easy clinical predictor for low BCAA to tyrosine ratio in chronic liver disease patients with hepatocellular carcinoma: Usefulness of ALBI score as nutritional prognostic marker.

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

Vitamin D in dysphagic patients who have undergone endoscopic gastrostomy for long-term enteral feeding.

OBJECTIVE: Vitamin D plays a major role in biological processes. Its deficiency is associated with increased morbidity and mortality. Patients who have undergone endoscopic gastrostomy (PEG) present with protein-energy malnutrition, and may be at risk for Vitamin D deficiency, due to their age, less sunlight exposure and lower dietary intake. We aimed to determine the prevalence of hypovitaminosis D in PEG-patients, its change under PEG-feeding, and its relationship with serum proteins and risk factors for Vitamin D deficiency. METHODS: This was a prospective observational study, over 4 weeks, after gastrostomy. Data were collected at the initial PEG procedure (T0), and after 4 weeks (T1). Initial evaluation included age, gender, underlying disorder, NRS-2002, BMI, serum albumin, transferrin and Vitamin D. At T1 we assessed Vit. D, albumin, and transferrin. Vitamin D was performed with Electrochemiluminescence through Elecsys 2010 assay. Patients were fed with blended homemade meals. RESULTS: 200 patients (118 males), 22-92 years of age, were studied. There were initial low values for Vit. D (181), albumin (96), transferrin (121), and BMI (124). A correlation was found between Vit. D and serum albumin (r=0.49, p=0.005) but not with transferrin (r=0.26, p=0.195). At T1 the subgroup who had Vit. D levels assessed (n=48) was part of the initial study group maintained low levels of Vitamin D despite nutritional intervention. CONCLUSION: We recommend systematic Vitamin D supplementation of PEG fed patients using homemade meals or at least screening for hypovitaminosis D as a routine part of their care.

Relationship between protein-energy wasting in adults with chronic hemodialysis and the response to treatment with erythropoietin.

BACKGROUND: It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO). METHODS: Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the "Malnutrition Inflammation Score" (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant. RESULTS: Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329-0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05). CONCLUSIONS: PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.

Association of serum IL-18 with protein-energy wasting in end-stage renal disease patients on haemodialysis.

PURPOSE: Protein-energy wasting (PEW) is highly prevalent in end-stage renal disease (ESRD) patients with inflammation who are on haemodialysis treatment. Interleukin-18 (IL-18) is an important pro-inflammatory cytokine that is significantly elevated in ESRD patients. However, the relationship between PEW and IL-18 is unclear. We therefore performed a cross-sectional study on 100 ESRD patients undergoing haemodialysis to clarify this. METHODS: PEW was defined according to the diagnostic criteria of the International Society of Renal Nutrition and Metabolism. Inflammation was assessed based on the serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and IL-18. We analysed the association between PEW and IL-18 by using logistic analysis and linear regression after adjustment for basic characteristics, comorbidities and laboratory findings. RESULTS: Among the 100 haemodialysis patients who were recruited, 56 had PEW. Even though there was no difference between the PEW group and non-PEW group with regard to disease causes, age, gender, cholesterol, ferritin, and haemoglobin, the levels of inflammation indicators such as CRP, IL-6, TNF-α and IL-1ß were significantly higher in the PEW group. Moreover, IL-18 was found to contribute to PEW, but was negatively correlated with pre-albumin after adjustment for possible confounding factors. CONCLUSIONS: Thus, the findings indicate that IL-18 is associated with PEW in ESRD patients on haemodialysis, which suggests that IL-18 may be involved in the pathogenesis of PEW in this setting.

Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status.

In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2 O2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2 O2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2 O2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2 O2 (100 µM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.

O Cromo sérico baixo é raro em doentes submetidos a gastrostomia endoscópica para nutrição entérica de longa duração / Low serum chromium is rare in patients that underwent endoscopic gastrostomy for long term enteral feeding

ABSTRACT BACKGROUND Patients that underwent Percutaneous Endoscopic Gastrostomy (PEG) present with protein-energy malnutrition. Trace elements are required in small quantities and Chromium (Cr) displays a major role in the metabolism. OBJECTIVE This study aims to evaluate Cr levels and its relationship with serum proteins, BMI and underlying diseases during the first 3 months of PEG feeding. METHODS Prospective observational study during 3-months, when PEG was performed (T0), after 4 (T1), and 12 weeks (T3). Initial evaluation included: age, gender, underlying disease, NRS-2002, BMI, serum albumin, transferrin and Cr concentration. At T1 and T3 a blood sample was collected for Cr, albumin and transferrin. A Graphite Furnace Atomic Absorption Spectroscopy was used to assess Cr. According with the underlying disease, patients were divided into two groups: head and neck cancer (HNC) and neurological dysphagia (ND). All patients were fed with homemade meals. RESULTS A one hundred and twenty-nine patients (80 males), 26-95 years old were studied: HNC-52; ND-77. The observed data included low mean values of BMI from 71 patients; low Cr-8, low albumin-70, low transferrin-85 and 57 with both proteins low. Albumin was associated with survival time ( P =0.024) and there was a significant correlation between albumin and Cr (r=0.217, P =0.012). A good evolution of Cr and proteins values was observed, with no low Cr levels at T3. CONCLUSION Low serum Cr is rare in PEG-patients, with no relationship to other studied parameters. For the minority of patients displaying low Cr before gastrostomy, homemade PEG meals seem to be effective.

RESUMO CONTEXTO Doentes submetidos a gastrostomia endoscópica percutânea apresentam desnutrição energético-proteica. Os elementos traço são necessários em pequenas quantidades e o Cromo (Cr) tem um papel importante no metabolismo. OBJECTIVO Pretendeu-se avaliar os níveis séricos de Cr e sua relação com as proteínas séricas, índice de massa corporal (IMC) e as doenças subjacentes nos primeiros 3 meses de alimentação por gastrostomia endoscópica percutânea. MÉTODOS Estudo prospetivo observacional durando 3 meses: avaliações no momento do procedimento (T0), após 4 (T1) e 12 semanas (T3). A avaliação inicial incluiu: idade, gênero, doença subjacente, Nutricional Risk Screening 2002 , IMC, concentração sérica de Cr, albumina e transferrina. Em T1 e T3, colheu-se sangue para Cr, albumina e transferrina. Para avaliação do Cr, utilizou-se espectrometria de absorção atómica em forno de grafite. Classificaram-se os doentes em dois grupos: neoplasias cervicofaciais (NCF) e disfagia neurológica (DN). Todos foram alimentados com alimentos de preparação doméstica. RESULTADOS Avaliaram-se 129 doentes (80 homens), entre 26-95 anos: NCF-52; DN-77. Encontraram-se valores baixos do IMC-71; Cr-8, albumina-70, transferrina-85 e 57 com ambas as proteínas baixas. Identificou-se correlação com significado estatístico entre a albumina e Cr (r=0,217, P =0,012) e entre a albumina e tempo de sobrevivência ( P =0,024). Foi observada boa evolução do Cr e proteínas, não sendo encontrados valores baixos de Cr em T3. CONCLUSÃO O Cr baixo é raro em doentes com gastrostomia endoscópica percutânea, sem relação com outros parâmetros, incluindo o tipo de doença subjacente. Para a minoria dos doentes com Cr baixo antes da gastrostomia, refeições de preparação doméstica parecem ser adequadas.

LOW SERUM CHROMIUM IS RARE IN PATIENTS THAT UNDERWENT ENDOSCOPIC GASTROSTOMY FOR LONG TERM ENTERAL FEEDING.

BACKGROUND: Patients that underwent Percutaneous Endoscopic Gastrostomy (PEG) present with protein-energy malnutrition. Trace elements are required in small quantities and Chromium (Cr) displays a major role in the metabolism. OBJECTIVE: This study aims to evaluate Cr levels and its relationship with serum proteins, BMI and underlying diseases during the first 3 months of PEG feeding. METHODS: Prospective observational study during 3-months, when PEG was performed (T0), after 4 (T1), and 12 weeks (T3). Initial evaluation included: age, gender, underlying disease, NRS-2002, BMI, serum albumin, transferrin and Cr concentration. At T1 and T3 a blood sample was collected for Cr, albumin and transferrin. A Graphite Furnace Atomic Absorption Spectroscopy was used to assess Cr. According with the underlying disease, patients were divided into two groups: head and neck cancer (HNC) and neurological dysphagia (ND). All patients were fed with homemade meals. RESULTS: A one hundred and twenty-nine patients (80 males), 26-95 years old were studied: HNC-52; ND-77. The observed data included low mean values of BMI from 71 patients; low Cr-8, low albumin-70, low transferrin-85 and 57 with both proteins low. Albumin was associated with survival time ( P =0.024) and there was a significant correlation between albumin and Cr (r=0.217, P =0.012). A good evolution of Cr and proteins values was observed, with no low Cr levels at T3. CONCLUSION: Low serum Cr is rare in PEG-patients, with no relationship to other studied parameters. For the minority of patients displaying low Cr before gastrostomy, homemade PEG meals seem to be effective.

Association of anemia with functional and nutritional status in the German multicenter study "GeriAnaemie2013".

OBJECTIVES: Anemia and malnutrition are risk factors for frailty in older people but data from multicenter studies among German geriatric inpatients are lacking. This analysis evaluated data from the multicenter study "GerAnaemie2013" commissioned by the German Geriatric Society. PATIENTS AND METHODS: The study involved an analysis of the 579 geriatric inpatients recruited in the context of the German multicenter study "GeriAnaemie2013". Study parameters: Barthel index (BI), handgrip strength, nutritional data (e.g. loss of appetite, loss of weight and decreased food intake). INCLUSION CRITERIA: in-patient age ≥70 years, exclusion criteria: current cancer disease or cancer-associated treatment. Anemia was defined according to the World Health Organization (WHO) criteria. RESULTS: The mean age of patients was 81.9 years, overall prevalence of anemia 55.1 %, mean hemoglobin (Hb) level 11.9 g/dl, average BI 50.8 points and 30.3 % of all patients were at risk of malnutrition. While univariate analysis revealed a significantly lower BI in anemic patients, this association was no longer seen in multivariate analysis. Regression analysis revealed that a drug intake of > 5 drugs/day doubles the chance of suffering from anemia with an adjusted odds ratio (OR) of 2.17 (confidence interval (CI) 1.28-3.68, p = 0.004) as well as a serum albumin level below 3.5 g/dl with an adjusted OR of 2.11 (range 1.40-3.19, p < 0.001). CONCLUSION: Polymedication and low serum albumin were independent risk factors for anemia in geriatric patients, probably reflecting disease severity.

Serum hyaluronic acid predicts protein-energy malnutrition in chronic hepatitis C.

Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient <0.85 using indirect calorimetry as having PEM. We investigated the effect of serum HA level on the presence of PEM. Receiver operating characteristic curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for serum HA level, platelet count, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, and Forns index for the presence of PEM. The median serum HA level in this study was 148.0 ng/mL (range: 9.0-6340.0 ng/mL). In terms of the degree of liver function (chronic hepatitis, Child-Pugh A, B, and C), the analyzed patients were well stratified according to serum HA level (overall significance, P < 0.0001). The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6-6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0-783.0 ng/mL) (P < 0.0001). Among 6 fibrosis markers, serum HA level yielded the highest AUROC with a level of 0.849 at an optimal cut-off value of 151.0 ng/mL (sensitivity 93.4%; specificity 62.0%; P < 0.0001). In the multivariate analysis, serum HA level was found to be a significant prognostic factor related to the presence of PEM (P = 0.0001).In conclusion, serum HA level can be a useful predictor of PEM in patients with CHC.

Predictors of protein-energy wasting in haemodialysis patients: a cross-sectional study.

BACKGROUND: Protein-energy wasting (PEW) is a highly prevalent condition in haemodialysis patients (HD). The potential usefulness of nutritional-inflammatory markers in the diagnosis of PEW in chronic kidney disease has not been established completely. We hypothesised that a combination of serum albumin, percentage of mid-arm muscle circumference and standard body weight comprises a better discriminator than either single marker of nutritional status in HD patients. METHODS: A cross-sectional study was performed in 80 HD patients. Patients were categorised in two groups: well-nourished and PEW. Logistic regression analysis was applied to corroborate the reliability of the three markers of PEW with all the nutritional-inflammatory markers analysed. RESULTS: PEW was identified in 52.5% of HD patients. Compared with the well-nourished patients, PEW patients had lower body mass index, serum pre-albumin and body cell mass (all P < 0.001) and higher C-reactive protein (s-CRP) (P < 0.01). Logistic regression analyses showed that the combination of the three criteria were significantly related with s-CRP >1 mg dL(-1) , phase angle <4°, and serum pre-albumin <30 mg dL(-1) (all P < 0.05). Other indicators, such as lymphocytes <20% and Charlson comorbidity index, were significantly involved (both P < 0.01). A receiver operating characteristic curve (area under the curve) of 0.86 (P < 0.001) was found. CONCLUSIONS: The combined utilisation of serum albumin, percentage of mid-arm muscle circumference and standard body weight as PEW markers appears to be useful for nutritional-inflammatory status assessment and adds predictive value to the traditional indicators. Larger studies are needed to achieve the reliability of these predictor combinations and their cut-off values in HD patients and other populations.

Gelsolin and adipokines are associated with protein-energy wasting in hemodialysis patients.

Protein-energy wasting (PEW) contributes to mortality in hemodialysis (HD) patients. Adipokines regulate energy homeostasis and body weight. Circulating gelsolin can modulate inflammation and is correlated with HD mortality. Whether adipokines and gelsolin play important roles in PEW remains unclear. Based on the criteria proposed by the International Society of Renal Nutrition and Metabolism, we examined the associations between PEW and biomarkers (gelsolin, leptin, adiponectin, interleukin-6, tumor necrosis factor alpha [TNF-α]) in 188 stable HD patients. Patients with PEW had significantly lower serum leptin levels, and tended to have higher adiponectin, TNF-α, and lower gelsolin levels. Logistic regression analysis revealed that gelsolin, leptin, adiponectin, and blood urea nitrogen were independently associated with PEW score. Serum creatinine, TNF-α, gender, renin-angiotensin system (RAS) blockade, and lipid-lowering agents were not associated with PEW score. Patients on lipid-lowering agents had lower PEW scores and those with RAS blockade had higher PEW scores. Our study confirms that gelsolin, adiponectin, and leptin are significant associates with PEW in HD patients. Further understanding of how these factors contribute to PEW may help design novel therapeutic strategies for PEW in chronic kidney disease.

Dietary supplementation with Lactobacilli improves emergency granulopoiesis in protein-malnourished mice and enhances respiratory innate immune response.

This work studied the effect of protein malnutrition on the hemato-immune response to the respiratory challenge with Streptococcus pneumoniae and evaluated whether the dietary recovery with a probiotic strain has a beneficial effect in that response. Three important conclusions can be inferred from the results presented in this work: a) protein-malnutrition significantly impairs the emergency myelopoiesis induced by the generation of the innate immune response against pneumococcal infection; b) repletion of malnourished mice with treatments including nasally or orally administered Lactobacillus rhamnosus CRL1505 are able to significantly accelerate the recovery of granulopoiesis and improve innate immunity and; c) the immunological mechanisms involved in the protective effect of immunobiotics vary according to the route of administration. The study demonstrated that dietary recovery of malnourished mice with oral or nasal administration of L. rhamnosus CRL1505 improves emergency granulopoiesis and that CXCR4/CXCR12 signaling would be involved in this effect. Then, the results summarized here are a starting point for future research and open up broad prospects for future applications of probiotics in the recovery of immunocompromised malnourished hosts.

Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition.

BACKGROUND AND AIMS: Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine-a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis-is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice. METHODS: Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 µg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated. RESULTS: Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway. CONCLUSIONS: These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.

[Protein malnutrition in patient in the early postoperative period after uncomplicated removal of the brain tumors].

Malnutrition leads to adverse effects and may worsen clinical outcome. Surgery as a stress factor activates pathological reactions changing metabolism structure. The aim of this study was to evaluate changes of protein metabolism in patients after elective neurosurgical operation. 24 patients were prepared for elective surgery and were enrolled in this study. Evaluation of each patient included: measurement of anthropometric indices--height, weight, arm circumference and the triceps skinfold thickness, the definition of protein loss by determining the loss of nitrogen in the urine, assessment of protein catabolism, determining the violations of nutritional status upon the base of laboratory parameters. During the course of the conducted investigation significant (p < 0.05) decrease in the indices of total protein, albumin, transferrin and the absolute numbers of lymphocytes in the postoperative period was revealed. All the patients developed severe protein catabolism. It became clear that uncomplicated elective surgical intervention, together with the adopted scheme of the nutritional therapy leads to severe protein catabolism in all patients.

Effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition.

Protein-calorie malnutrition (PCM) could occur frequently in cancer patients and alter the pharmacokinetics of drugs. Also cysteine shows anti-oxidative effect and changes the activities of drug metabolizing enzyme and/or transporters. Herein, we investigated the effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of tamoxifen were assessed using control, CC (control with cysteine), PCM, PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of tamoxifen were further investigated through in vitro transport studies using rat intestine. The AUCs of intravenous tamoxifen in PCM rats were significantly greater than control rats due to the decrease in the hepatic metabolism via CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels by oral cysteine supplement. The AUC of oral tamoxifen in PCM rats was significantly smaller than in control rats mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of tamoxifen probably via intestinal P-gp inhibition. The present study demonstrated that PCM state and/or oral cysteine supplement had a profound impact on the pharmacokinetics of tamoxifen in rats. If the present rat data are extrapolated to humans, the alterations in tamoxifen absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM and/or oral cysteine supplement.

Early administration of branched-chain amino acid granules.

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.41 and 10.05, and a Fischer's ratio of 1.8 corresponds to a BTR of 3.5) in patients with decompensated liver cirrhosis, and BCAA inhibits hepatic carcinogenesis in patients with compensated cirrhosis. This review discusses data regarding the effect of early administration of BCAA granules based on the ratio of BCAA to BTR on prognosis in patients with cirrhosis.

Eixo hormônio de crescimento/fator de crescimento semelhante à insulina-1: um possível fator não nutricional para o retardo de crescimento em crianças com paralisia cerebral / Growth hormone/insulin-like growth factor-1 axis: a possible non-nutritional factor for growth retardation in children with cerebral palsy

OBJETIVO: Avaliar o eixo hormônio de crescimento (GH)/fator de crescimento semelhante à insulina 1 (IGF-1) como possível fator não nutricional para o retardo de crescimento em crianças com paralisia cerebral (PC). MÉTODOS: Um estudo caso-controle foi realizado em um hospital universitário terciário. Trinta crianças com PC [sete crianças com crescimento normal (PC-N) e 23 com retardo de crescimento (PC-R)], 30 crianças com desnutrição proteico-energética (DPE), e 30 crianças sadias (grupo REF) tiveram avaliados seus parâmetros de crescimento, IGF-1 sérico, GH basal, e pico de GH após estímulo com insulina. RESULTADOS: Os pacientes com DPE apresentaram níveis basais mais elevados de GH do que os grupos PC-N, PC-R e REF (p = 0,026, p < 0,001 e p = 0,001, respectivamente). Após estímulo com insulina, os grupos PC-N, PC-R e DPE apresentaram níveis menores de GH se comparados ao grupo REF (p = 0,04, p = 0,007, p = 0,036, respectivamente). O nível de IGF-1 foi menor no grupo PC-R se comparado aos grupos PC-N e REF (p = 0,037 e p < 0,001, respectivamente), e no grupo DPE se comparado aos grupos PC-N e REF (p < 0,001 e p < 0,001, respectivamente). CONCLUSÕES: Os pacientes com PC-R não demonstraram a mesma resposta basal elevada do GH apresentada pelos pacientes com DPE, e responderam de forma inadequada ao estímulo com insulina, mas apresentaram níveis de IGF-1 comparáveis aos dos pacientes com DPE. Por outro lado, os pacientes com PC-N tiveram comportamento semelhante ao dos controles com relação aos níveis basais de GH e IGF-1, mas não responderam adequadamente ao estímulo com insulina. O grupo DPE apresentou GH basal elevado e IGF-1 baixo. Esses achados sugerem que fatores não nutricionais contribuem para o retardo de crescimento em crianças com PC.

OBJECTIVE: To assess growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis as a possible non-nutritional factor for growth retardation in children with cerebral palsy (CP). METHODS: A case-control study was conducted at a tertiary university hospital. Thirty children with CP (seven children with normal growth [CP-N] and 23 with retarded growth [CP-R]), 30 children with protein energy malnutrition (PEM), and 30 healthy children (REF group) underwent an assessment of growth parameters, serum IGF-1, basal GH, and peak GH after stimulation with insulin. RESULTS: PEM patients had higher basal GH levels than CP-N, CP-R and REF groups (p = 0.026, p < 0.001, and p < 0.001 respectively). After insulin stimulation, CP-N, CP-R, and PEM patients had lower GH levels compared to the REF group (p = 0.04, p = 0.007, and p = 0.036 respectively). IGF-1 levels were lower in CP-R group compared to CP-N and REF groups (p = 0.037 and p < 0.001 respectively), and in PEM group compared to CP-N and REF groups (p < 0.001 and p < 0.001 respectively). CONCLUSIONS: CP-R patients failed to demonstrate the same high basal GH response as PEM patients, and responded inadequately to the insulin stimulation test, but they had IGF-1 levels comparable to those of PEM patients. On the other hand, CP-N patients behaved as controls regarding their basal GH and IGF-1 levels, but failed to respond adequately to the insulin stimulation test. The PEM group presented high basal GH and low IGF-1 levels. These findings suggest that non-nutritional factors contribute to growth retardation in CP children.

The effect of serum magnesium levels and serum Endothelin-1 levels on bone mineral density in protein energy malnutrition / Efecto de los niveles séricos de magnesio y los niveles séricos de Endotelina-1 sobre la densidad mineral osea en la malnutrición calórico-proteica

An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

El consumo inadecuado y desbalanceado de proteínas y calorías energía conduce a la malnutrición calórico-proteica (MCP). Se sabe que la densidad mineral ósea y los niveles séricos de magnesio son bajos en los ninos malnutridos. Sin embargo, no está claro el papel que desempenan los niveles séricos de magnesio y los niveles séricos de endotelina-1 (ET-1) en la patofisiología de la mineralización del hueso. Por consiguiente, las relaciones entre los niveles séricos de magnesio y los niveles séricos de ET-1, y los cambios en la densidad mineral ósea, constituyen el objeto de investigación de este estudio. Hubo un total de 32 sujetos; 25 de ellos tenían DCP y 7 eran considerados. Si bien los niveles séricos promedios de ET-1 de los ninos con kwashiorkor y marasmo no mostraron diferencia estadística significativa, los niveles séricos promedio de ET-1 de ambos grupos fueron significativamente más altos que los del grupo de control. Los niveles séricos de magnesio estuvieron por debajo del valor normal en 9 (36%) de 25 ninos malnutridos. Los ninos malnutridos incluidos en este estudio fueron divididos en dos sub-grupos según sus niveles de magnesio en suero. Mientras que los niveles séricos promedio de ET-1 en el grupo con niveles bajos de magnesio fueron significativamente más altos que los del grupo con niveles normales de magnesio (p < 0.05), la densidad mineral ósea promedio y los niveles promedio del contenido mineral óseo fueron significativamente más bajos (p < 0.05). En conclusión, muchos factores juegan un papel en la patofisiología de los cambios en la densidad mineral ósea por la malnutrición. Nuestro estudio sugirió niveles más bajos de magnesio y niveles más altos de ET-1 podrían ser factores importantes en los cambios de densidad mineral ósea en la malnutrición. Se recomienda que los pacientes malnutridos, especialmente a causa de hipomagnesemia, sean tratados con magnesio lo más pronto posible.

Is a body mass index of 23 kg/m² a reliable marker of protein-energy wasting in hemodialysis patients?

OBJECTIVE: To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI). METHODS: Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up. RESULTS: Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality. CONCLUSION: Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.