José Francisco Martínez-Valls

Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy

To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.

Outcome of Esophageal Function and 24-hour Esophageal pH Monitoring after Vertical Banded Gastroplasty and Roux-en-Y Gastric Bypass

Background: One of the co-morbidities frequently associated with morbid obesity is gastro-esophageal reflux disease (GERD), present in >50 % of morbidly obese individuals. We compared the anti-reflux effect of vertical banded gastroplasty (VBG) and Roux-en-Y gastric bypass (RYGBP), and their effect on esophageal function. Methods: 10 patients underwent VBG and 40 patients underwent RYGBP. Anthropometric parameters, symptomatology of GERD, esophageal manometry (EM), isotopic esophageal emptying (IEE) and 24hr esophageal pH monitoring were recorded in all patients preoperatively, and at 3 months and 1 year postoperatively. Results: Preoperatively, there was a high prevalence of GERD, symptomatic and pH-metric in both groups (57% and 80% respectively). The preoperative values of EM and IEE parameters were within the normal range in most patients. After surgery, there was an improvement at 3 months postoperatively in both groups. 1 year after surgery, the VBG group presented symptomatic GERD in 30% and pH-metric reflux in 60% of patients while the RYGBP group presented symptomatic GERD and pH-metric reflux in 12.5% and 15% of patients, respectively. There was an increase in postoperative sensation of dysphagia in both groups (70% VBG, 30% RYGBP) one year after operation. After surgery, differences in all EM parameters were minimal, and never reached statistical significance for any group (VBG and RYGBP). The IEE showed a significantly higher percentage of esophageal retention after surgery, but this retention was always within the normal range. Both groups had an improvement in anthropometric parameters, but 1 year after surgery the results were significantly better in RYGBP patients (70% excess weight loss) than in VBG patients (46% excess weight loss). Conclusion: >50% of morbidly obese individuals suffer from GERD. We did not find changes in esophageal function of morbidly obese patients to explain their gastroesophageal reflux preoperatively and postoperatively. EM and IEE studies are not indicated as standard preoperative tests, except in patients with significant symptoms of gastroesophageal reflux. RYGBP is significantly better than VBG as an anti-reflux procedure, and had better weight loss.

A study of insulin resistance using the minimal model in nondiabetic familial combined hyperlipidemic patients

The presence of insulin resistance in 20 male nondiabetic patients with familial combined hyperlipidemia (FCH) and 20 controls of similar age and body mass index (BMI) was investigated using the minimal model method modified by the administration of insulin and an oral glucose tolerance test. The peripheral sensitivity of insulin, expressed as the insulin sensitivity index (Si), was 1.91+/-1.05 and 2.86+/-1.19 x 10(-4) x min(-1) x mU/L in FCH patients and controls, respectively (P < .01), and the corresponding value for the peripheral utilization of glucose independently of insulin (Sg) was 1.70+/-1.13 in FCH patients and 2.35+/-0.60 x 10(-2) x min(-1) in controls (P < .02). In the FCH group, the Si value correlated significantly (P < .05) with the waist to hip ratio (WHR), plasma triglycerides (TG), free fatty acids (FFA), and the area under the curve of glucose (AUCg) and insulin (AUCi). In the control group, the correlation also reached statistical significance (P < .05) with age, BMI, WHR, blood pressure, TG, AUCg, and AUCi. Subgrouping the subjects with respect to central obesity defined as a WHR of 0.95 or greater, we observed lower Si values in obese and non-obese FCH subjects relative to controls (P < .02). The mean Si value in obese subjects was significantly lower than in non-obese FCH subgroups (1.40+/-0.79 v 2.68+/-0.95 x 10(-4) x min(-1) x mU/L, respectively, P < .01). In conclusion, a higher degree of insulin resistance relative to control values appears to be an integral part of the metabolic derangements observed in FCH, and central-trunk obesity exacerbates the insulin resistance syndrome.

Vertical Banded Gastroplasty Converted to Roux-en-Y Gastric Bypass: Little Impact on Nutritional Status after 5-Year Follow-up

Background: Conversion to a Roux-en-Y gastric bypass (RYGBP) has been advocated after the failure of vertical banded gastroplasty (VBG). The aim of this study was to analyze the differences in anthropometric and nutritional parameters between patients with VBG and those converted to RYGBP. Methods: 45 patients initially underwent VBG. 22 of these patients have maintained this operation for more than 5 years (Group A) and 23 have been converted to RYGBP (Group B), after 2 years of follow-up. We analyzed anthropometric and nutritional parameters (macronutrients,micronutrients and lipid profile), and postoperative morbidity after both procedures. Data were recorded before the first operation and at 6 months, 1, 2 and 5 years follow-up. Results: VBG failure rate was 51%. The 23 patients converted to RYGBP have maintained an excess weight loss (EWL) of 70% 3 years after the revision, and all the complications related to VBG disappeared. Anthropometric parameters were significantly better after RYGBP. We found no significant differences in nutritional status between both groups except for levels of iron, vitamin B12 and transferrin saturation index, which significantly decreased in converted patients. The redo procedure had a low morbidity rate, with no mortality. Conclusion: More than 50% of VBGs failed after 2-year follow-up. Patients converted to RYGBP maintained mean EWL 73% at 5 years. The only significant nutritional deficiencies were iron and vitamin B12, in patients converted to RYGBP.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity

In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase‐generated cytokeratin‐18 (CK‐18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase‐generated CK‐18 fragments in patients with severe obesity.

Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery.

Obesity‐associated nonalcoholic fatty liver disease (NAFLD), covering from simple steatosis to nonalcoholic steatohepatitis (NASH), is a common cause of chronic liver disease. Aberrant production of adipocytokines seems to play a main role in most obesity‐associated disorders. Changes in adipocytokines in obesity could be mediated by alterations in cyclic GMP (cGMP) homeostasis. The aims of this work were: (1) to study the role of altered cGMP homeostasis in altered adipocytokines in morbid obesity, (2) to assess whether these alterations are different in simple steatosis or NASH, and (3) to assess whether these changes reverse in obese patients after bariatric surgery.

Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia

Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR).

Validez de la valoración subjetiva global como método de despistaje de desnutrición hospitalaria. Prevalencia de desnutrición en un hospital terciario

INTRODUCTION Hospital malnutrition is a highly prevalent problem that affects patient morbidity and mortality resulting in longer hospital stays and increased healthcare costs. Although there is no single nutritional screening method, subjective global assessment (SGA) may be a useful, inexpensive, and easily reproducible tool. METHODS A cross-sectional, observational, randomized study was conducted in 197 patients in a tertiary hospital. SGA, anthropometric data, and biochemical parameters were used to assess the nutritional status of study patients. RESULTS Fifty percent of subjects were malnourished according to SGA. A higher prevalence of malnutrition was found in medical (53%) as compared to surgical departments (47%). Half the subjects (50%) had malnutrition by SGA, but only 37.8% received nutritional treatment during their hospital stay. Mean hospital stay was longer for patients malnourished (13.5 days) or at risk of malnutrition (12.1 days) as compared to well nourished subjects (6.97 days). SGA significantly correlated (P<.012) with anthropometric and biochemical malnutrition parameters. CONCLUSIONS Prevalence of hospital malnutrition is very high in both medical and surgical departments and is inadequately treated. SGA is a useful tool for screening hospital malnutrition because of its high degree of correlation with anthropometric and biochemical parameters.

Hipoglucemia tras derivación gástrica en Y de Roux

La obesidad mórbida es una enfermedad grave asociada a múltiples comorbilidades, y a un incremento de la mortalidad1. Por su escasa respuesta al tratamiento conservador (dietético, conductual y farmacológico), y por el incremento de su prevalencia, se ha desarrollado una alternativa terapéutica, la cirugía bariátrica, que ha mostrado su eficacia para la reducción del peso a largo plazo y la mejora o resolución de comorbilidades asociadas como la diabetes, hipertensión arterial y dislipemia. Las complicaciones a medio y largo plazo de la cirugía gástrica han sido bien definidas, incluyendo déficits nutricionales, complicaciones gastrointestinales y neuropatía. Una complicación poco frecuente pero grave, descrita recientemente, es la hipoglucemia postprandial2, debida a hiperinsulinemia endógena. Aunque algunos autores lo consideran una manifestación tardía del síndrome de dumping3, sus características clínicas con síntomas neuroglucopénicos graves, su aparición tardía, tras meses o años de un by-pass gástrico, y la falta de respuesta a tratamiento dietético, la convierten en una entidad bien diferenciada cuyos mecanismos fisiopatológicos aún no han sido bien aclarados. Presentamos el caso de una mujer de 41 años con obesidad mórbida, sin historia previa de diabetes ni clínica previa similar, que mostró episodios repetidos de hipoglucemia grave, un año después de una re-intervención de by-pass gástrico (conversión a Y de Roux). La paciente acudió a nuestro servicio a los 34 años de edad. Refería incremento de peso progresivo desde la adolescencia, hábito dietético compulsivo con frecuentes atracones, picoteo habitual y seguimiento de múltiples regímenes dietéticos con ganancias ponderales posteriores, a pesar de recibir ayuda farmacológica ocasional. A la exploración física destacaba: peso de 142 kg, talla de 164 cm, con IMC (índice de masa corporal) de 52,8 kg/m2. Previamente a la cirugía, se realizó una sobrecarga oral de glucosa (SOG), destacando únicamente unos valores anormalmente elevados de insulina a las 2 horas (96,1 microU/ml) con glucemia dentro de los límites de la normalidad (132 mg/dl). Se programó para d c s c

Metabolism of cyclic GMP in non-alcoholic fatty liver disease in morbid obesity

Methods Patients: MO group: 48 patients (40 women and 8 men) diagnosed of MO with an age of 46.9± 7.9. Control group: 19 subjects without overweight and with normal analytical data and normal ultrasound scan of the liver. The following parameters were measured: A.Clinical data: Age, sex, weight, height, abdominal and hip perimeters, Body Mass Index (BMI), clinical history and pharmacological treatment, Metabolic Syndrome, morfometry and haematic chemistry, Insulin Resistance (HOMA) and viral markers. B Immunomodulators: (Leptin, Adiponectin, CK18Asp396 (CK18), Interleukin-6 (IL-6), aldosterone and rennin). C Histological analysis was performed after obtaining hepatic tissue during surgery for MO. The NAFLD Score was calculated: Steatosis Degree, Fibrosis, Inflammation, hepatocyte lesions and other injuries).