R. Aller

Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography: advantages over contrast transthoracic echocardiography.

The aim of this study was to study theprevalence of hepatopulmonary syndrome (HPS) incirrhotic patients, comparing the results obtained usingcontrast transthoracic echocardiography (CTTE) andcontrast transesophageal echocardiography (CTEE) in thedemonstration and grading of pulmonary vasodilatation(PV). We also analyzed the correlation betweengas-exchange abnormalities and PV when it wasdemonstrated with both techniques. The prevalence of PV andHPS with CTEE in the 88 cirrhotic patients was 28% and22%, respectively, and with CTEE, 42% (P < 0.05)(middle PV: 35% and significant PV: 7%) and 30% (P < 0.05), respectively. Fifty-six percentof patients diagnosed with PV and with CTTE presentedwith hypoxemia as did 49% using CTEE (83% of patientswith significant PV had hypoxaemia). PaCO and diffusing capacity of CO were significantly moredecreased in 2 patients with PV than in patients withoutPV when CTEE was employed. We conclude that CTEE issuperior to CTTE in the diagnosis and grading of PV in the diagnosis of HPS in cirrhotic patients,being more sensitive and presenting a better correlationwith gas-exchange abnormalities. Given its highsensitivity, CTEE should be carried out in all patients with suspicion of HPS and normal or uncertainCTTE.

Association of Helicobacter pylori infection with cardiovascular and cerebrovascular disease in diabetic patients.

OBJECTIVE Infection by Helicobacter pylori has been epidemiologically linked to some extradigestive conditions, including ischemic heart disease. Diabetic patients are an at-risk population for cardiovascular and thrombo-occlusive cerebral disease. The aim of the study was to examine a possible relationship between H. pylori infection and cardiovascular or cerebrovascular disease in diabetic patients. RESEARCH DESIGN AND METHODS This was a cross-sectional case-control study with 127 diabetic patients (both IDDM and NIDDM). Special emphasis was placed on the detection of clinical macro- and microvascular complications, cardiovascular risk factors, acute phase reactants, and serological markers of increased cardiovascular disease risk. H. pylori infection was assessed through the determination of specific Ig-G titers, measured by a commercial enzyme-linked immunosorbent assay. RESULTS Coronary heart disease was more prevalent in diabetic patients with than without H. pylori (odds ratio [OR] 4.07; 95% Cl 1.21–13.6; P < 0.05). A history of thrombo-occlusive cerebral disease was also more frequent in H. pylori–positive diabetic patients (OR 4.8; 95% CI 1.24–18.51; P < 0.05). Other complications such as peripheral arteriopathy, advanced nephropathy, neuropathy, or retinopathy were no differently distributed according to serological status. Alterations in the levels of the following acute-phase reactants and blood chemistry determinations were significantly more profound in H. pylori–positive diabetic patients: high fibrinogen (P < 0.05), high erythrocyte sedimentation rate (P < 0.001), high triglycerides (P < 0.001), and low HDL cholesterol (P < 0.001). These values were also more deeply altered in H. pylori–positive diabetic patients with a history of coronary heart disease, thrombo-occlusive cerebral disease, or both, when compared with H. pylori–positive diabetic patients without those complications. CONCLUSIONS Our data indicate a possible association of H. pylori infection and the development of coronary heart disease, thrombo-occlusive cerebral disease, or both, in diabetic patients. The importance of this link is highlighted by the possibility of an effective intervention against H. pylori infection.

Postsurgery enteral nutrition in head and neck cancer patients

Objective: Patients with head and neck cancer undergoing surgery have a high incidence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients, using an arginine-enriched diet, could improve nutritional variables as well as clinical outcomes.Design: Randomized clinical trial.Setting: Tertiary care.Subjects: A population of 47 patients with oral and laryngeal cancer were enrolled.Interventions: At surgery patients were randomly allocated to two groups: (a) patients receiving an enteral diet supplemented with arginine and fiber (group I); (b) patients receiving an isocaloric, isonitrogenous enteral formula (group II).Results: No significant intergroup differences in the trend of the three plasma proteins and lymphocytes were detected. Gastrointestinal tolerance (diarrhea) of both formulas was good (17.4% group I and 8.3% group II; NS). During the 3 months after hospital discharge five patients died; no diferences were detected between groups (13% group I and 8.3% group II; NS). The incidences postoperative infection complications were similar (nine patients) in both groups (21.7% group I and 16.7% group II; NS). Fistula were less frequent in enriched nutrition group (0% group I and 20.8% group II; P<0.05); wound infection was more frequent in group II, but without statistical difference (4.3% group I and 12.5% group II; NS). The length of postoperative stay was 22.8±11.8 days in the enriched group and 31.2±19.1 days in the control group (P=0.07).Conclusions: In conclusion, enriched formula improves local wound complications in postoperative head and neck cancer patients. Our results suggest that these patients could benefit from an immunonutrient-enhanced enteral formula.

Nutritional Assessment: Predictive Variables at Hospital Admission Related with Length of Stay

Background: Studies indicate that 40–50% of hospitalized patients show malnutrition, a variable that is associated with length of stay and morbidity. The aim of our study was to detect nutritional parameters, which could have an influence on length of stay in hospitalized patients. Material and Methods: All patients with a nutritional evaluation at hospital admission were elegible for inclusion. A total of 1,088 patients were studied from January 1999 to December 2003. Length of stay (LOS) data was obtained from the patient hospital record after the patient was discharged. All patients received instruction in 24-hour written food record keeping. Albumin, prealbumin, transferrin, glucose levels and total lymphocytes, were measured in all patients. Weight, body mass index, tricipital skinfold, midarm muscle circumference and midarm muscle area were assessed in a standard way. Weight loss in the previous 3 months was recorded. Results: A total of 1,088 patients were enrolled, mean age 61.8 ± 17 years, weight 64.2 ± 15 kg and BMI 23.9 ± 4.6, with a weight loss 4.15 ± 9.6 kg. The sex distribution of patients was 65.2% male and 34.8% females. Distribution of diagnosis showed leukemia and lymphoma (11.5%), solid cancer (37.4%), infections (3.5%), neurological disease (13.6%), respiratory tract disease (8.8%), and miscellaneous group (25.3%). Length of stay was 29.45 ± 25.13 days. In whole group, the correlation analysis among length of stay (days) and predictive parameters showed a positive association between albumin and length of stay (r = –0.2; p < 0.05). In the multivariant analysis with a dependent variable (length of stay (days)) and independent variables with an association in univariant analysis adjusted by age and sex, only albumin remained as an independent predictor in the model (F = 8.8; p < 0.05), with an increase of 6.2 days (95% CI: 3.5–8.9) with each decrease of 1 g/dl of albumin. Conclusion: The serum albumin levels are a good marker of LOS, a decrease in admission levels produces an increase in LOS.

Clinical and biochemical outcomes after a randomized trial with a high dose of enteral arginine formula in postsurgical head and neck cancer patients.

Objective:Patients with head and neck cancer undergoing surgery have a high incidence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients, using a higher dose of arginine-enhanced diet (17 g/day) than previous studies, could improve nutritional variables as well as clinical outcomes, when compared with a control enteral diet.Design:Randomized clinical trial.Setting:Tertiary care.Subjects:A population of 72 patients with oral and laryngeal cancer was enrolled.Interventions:At surgery, patients were randomly allocated to two groups: (a) 35 patients receiving an arginine-enhanced formula with arginine (group I) and (b) 37 patients receiving an isocaloric, isonitrogenous enteral formula (group II).Results:No significant intergroup differences in the trend of the three plasma proteins (albumin, transferrin, prealbumin) and lymphocytes were detected. Episodes of diarrhea rate were equal in both groups (22.8% group I and 21.6% group II: NS). The postoperative infections complications were equal in both groups (5.7% group I and 5.4% group II: NS). Fistula (wound complication) was less frequent in enriched nutrition group (2.8% group I and 18.9% group II: P<0.05), whereas wound infection was similar in both groups. The length of postoperative stay was similar in both (27.9±21 vs 28.2±12 days; NS).Conclusions:At this dose, arginine-enhanced formula improves fistula rates in postoperative head and neck cancer patients without a high rate of diarrhea.

Effects of a low-fat versus a low-carbohydrate diet on adipocytokines in obese adults.

Background and Aims: There are few studies addressing the effect of weight loss on circulating levels of adipocytokines. The aim of our study was to determine whether different diets would have different weight loss effects and to examine the changes in adipocytokine levels. Methods: A population of 90 obesity non-diabetic outpatients was analyzed in a prospective way. The patients were randomly allocated to two groups: (a) diet I (low-fat diet), and (b) diet II (low-carbohydrate diet). At baseline and after 3 months on the diet, adipocytokines were evaluated. Results: 43 patients were randomized to group I and 47 patients to diet group II. No differences were detected between weight loss in either group (3.3 ± 0.51 vs. 4.4 ± 0.6 kg; n.s.). In group I, a significant decrease in leptin levels was found. In group II, leptin and C-reactive protein (CRP) levels also decreased. The decrease in leptin levels was lower with diet I than II (16.4 vs. 22.8%; p < 0.05). Conclusion: The serum leptin concentration decreased due to the 3-month intervention with low-fat and low-carbohydrate diets, without changes in other adipocytokines. The decrease in leptin and CRP levels were higher with a low-carbohydrate diet than a low-fat diet.

Immunoenhanced enteral nutrition, effect on inflammatory markers in head and neck cancer patients

The aim of our study was to evaluate the effect of enteral nutrition supplemented with arginine in inflammatory markers in surgical head and neck cancer patients. A population of 29 patients with oral and laryngeal cancer were enrolled in a randomized trial. At surgery patients were randomly allocated to two groups: (a) patients receiving an enteral diet supplements with arginine (group I, n=14); (b) patients receiving an isocaloric, isonitrogenous enteral formula (group II, n=15). The mean age was 61.1±10.8 y (five females/24 males). Characteristics of the patients on enrollment were similar for the two groups. Prealbumin and transferrin improved in both groups. c-reactive protein (CRP) levels decreased in both groups, (group I: 134.5±62.5 vs 75.3±51 mg/dl:P<0.05) and (group II: 103.6±62 vs 43.8±34.4 mg/dl:P<0.05). Interleukin-6 (IL-6) improved in both groups (group I: 20.35±11.2 vs 6.7±3.1 pg/ml:P<0.05) and (group II:22.8±40 vs 9.9±17.7 pg/ml:ns). Tumoral necrosis factor alpha and lymphocytes did not change. In conclusion, both formulas improved IL-6 and CRP levels. Further studies are needed to determine whether type of formula is the key in these patients or genetic background play a main role in inflammatory response.

Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients

Objective: Patients with head and neck cancer undergoing surgery have a high incidence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients using an arginine-enhanced formula could improve nutritional variables as well as clinical outcomes.Design: Randomized clinical trial.Setting: Tertiary care.Subjects: A population of 90 patients with oral and laryngeal cancer was enrolled.Interventions: At surgery, patients were randomly allocated to two groups: (a) patients receiving an arginine-enhanced formula with arginine and fiber (group I) and (b) patients receiving an isocaloric, isonitrogenous formula with fiber enteral formula (group II).Results: No significant intergroup differences in the trend of the three plasma proteins (albumin, transferrin, prealbumin) and lymphocytes were detected. Gastrointestinal tolerance (diarrhea) was better in group II than I (40% group I and 13% group II: P<0.05). The postoperative complications due to infections were similar in both groups (4% group I and 9% group II: ns). Fistula (wound complication) was less frequent in the enriched nutrition group (5% group I and 11% group II: P<0.05); wound infection was similar in both groups. The length of postoperative stay was better in group I than II (25.8±15 days vs 35±24.6 days; P<0.05).Conclusions: In conclusion, arginine-enhanced formula improves fistula rates in postoperative head and neck cancer patients and decreases length of stay.

Influence of ALA54THR Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects

Background/Aim: It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. Methods: A population of 69 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group. Results: The mean age was 45.5 ± 16.7 years, the mean body mass index was 34.1 ± 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 ± 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO2 increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups. Conclusions: Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients.

Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin

Hepatitis C virus causes significant morbidity and mortality worldwide. The infection induces up-regulation of cytokine and chemokines commonly linked to the development of cellular and pro-inflammatory antiviral responses. The current standard in hepatitis C treatment consists of combination regimens of pegylated interferon-alpha plus ribavirin. The impact of combined treatment in the host immune response is still poorly understood. In the present study, we profiled 27 cytokines, chemokines and growth factors involved in the innate and adaptive responses to the virus in the serum of 27 hepatitis C virus-infected patients, before and after 12 weeks of combined treatment, and compared them to 10 healthy controls. Hepatitis C virus infection induced not only the secretion of chemokines and cytokines participating in Th1 responses (MIP-1 alpha, IP-10, TNF-alpha, IL-12p70, IL-2), but also cytokines involved in the development of Th17 responses (IL-6, IL-8, IL-9 and IL-17) and two pro-fibrotic factors (FGF-b, VEGF). The most important increases included MIP-1 alpha (4.7-fold increase compared to the control group), TNF-alpha (3.0-fold), FGF-b (3.4-fold), VEGF (3.5-fold), IP-10 (3.6-fold), IL-17 (107.0-fold), IL-9 (7.5-fold), IL-12p70 (7.0-fold), IL-2 (5.6-fold) and IL-7 (5.6-fold). Combined treatment with pegylated interferon-alpha plus ribavirin down-modulated the secretion of key Th1 and Th17 pro-inflammatory mediators, and pro-fibrotic growth factors as early as 12 weeks after treatment initiation. MIP-1 alpha, FGF-b, IL-17 decreased in a more dramatic manner in the group of responder patients than in the group of non-responders (fold-change in cEVR; fold-change in NcEVR): MIP-1 alpha (4.72;1.71), FGF-b (4.54;1.21), IL-17 (107.1;1.8). Correlation studies demonstrated that the decreases in the levels of these mediators were significantly associated with each other, pointing to a coordinated effect of the treatment on their secretion (r coefficient; p value): [ FGF-b versus IL-17 (0.90; 0.00), IL-17 versus VEGF (0.88; 0.00), MIP-1 alpha versus IL-17 (0.84;0.00), FGF-b versus MIP-1 alpha (0.96;0.00), FGF-b versus IL-12p70 (0.90; 0.00), VEGF versus IL-12p70 (0.89; 0.00)]. Th17 immunity has been previously associated with autoimmune diseases and asthma, but this is the first work reporting a role for this profile in viral hepatitis. These results provide an opportunity to evaluate the impact of the treatment with Peg-INF-alpha and RBV on the prevention of immune-driven tissue damage in infected patients.