Rosa Codoceo

Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end‐stage renal disease

Background and Objective  High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease.

Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function

objective  Adipose tissue is a hormonally active system that produces and releases different bioactive substances. Leptin, adiponectin and resistin are some of the recently discovered adipocytokines that participate in the regulation of intermediate metabolism. The aim of this study was to evaluate the circulating levels of leptin, adiponectin and resistin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy.

Eating behavior disorders in uremia: a question of balance in appetite regulation.

Eating and appetite disorders are frequent complications of the uremic syndrome which contribute to malnutrition in dialysis patients. The data suggest that uremic anorexia may occur with or without abdominal and visceral fat accumulation despite a lower food intake. This form of obesity (i.e., with low food intake and malnutrition) is more common in dialysis patients than obesity with high food intake. This article reviews the current knowledge regarding mechanisms responsible for appetite regulation in normal conditions and in uremic patients. Anorexia in dialysis patients has been historically considered as a sign of uremic toxicity due to ‘‘inadequate’’ dialysis as judged by uncertain means (‘‘middle molecule’’ accumulation, Kt/V, ‘‘peak‐concentration hypothesis,’’ and others). We propose the tryptophan‐serotonin hypothesis, based on a uremia‐induced disorder in patients’ amino acid profile—low concentrations of large neutral and branched‐chain amino acids with high tryptophan levels. A high rate of tryptophan transport across the blood‐brain barrier increases the synthesis of serotonin, a major appetite inhibitor. Inflammation may also play a role in the genesis of anorexia and malnutrition. For example, silent infection with Helicobacter pylori may be a source of cytokines with cachectic action; its eradication improves appetite and nutrition. The evaluation of appetite should take into account cultural and social aspects. Uremic patients showed a universal trend to carbohydrate preference and red meat refusal compared to healthy people. In contrast, white meat was less problematic. Uremic patients also have a remarkable attraction for citrics and strong flavors in general. Eating preferences or refusals have been related to the predominance of some appetite peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen) are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an orexigen) with repeated food intake. Obesity and elevated body mass index often falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia state), disorders in the regulation of fat distribution (insulin, leptin, insulin‐like growth factor [IGF]‐1, fatty acids, and disorders in receptors for insulin, lipoprotein lipase, mitochondrial uncoupling protein‐2, and β3‐adrenoreceptors) may cause abdominal fat accumulation without an increase in appetite. Finally, appetite regulation in uremia is highly complex. Disorders in adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced inflammatory end products, and central nervous system changes may all play a role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic state derived from a high concentration of tryptophan and low branched‐chain amino acids.

Gastrointestinal and pancreatic function in peritoneal dialysis patients: their relationship with malnutrition and peritoneal membrane abnormalities

BACKGROUND Malnutrition is frequent in peritoneal dialysis (PD) patients, but the contribution of gastrointestinal (GI) dysfunction has not been well established. METHODS We studied GI function in 49 stable PD patients to ascertain its relationship with malnutrition. After an overload fat diet, fecal fat, sugar, starch and nitrogen, intestinal protein permeability (alpha(1)-antitrypsin fecal clearance [C-alpha(1)-AT]), fecal chymotrypsin (CT), GI hormones and gastrin, pepsinogen I and II, cholecystokinin (CCK), gastrin releasing peptide (GRP), and neuropeptide Y (NPY) were measured. Vasoactive intestinal polypeptide (VIP), substance P (SP), and tumor necrosis factor (TNF-alpha) and biochemical nutritional markers were evaluated. RESULTS All patients showed high fecal sugar. Elevated fecal nitrogen was found in 21 patients, 6 with high C-alpha(1)-AT. High fecal starch levels appeared in 21, fat in 20, and low fecal CT in 39 patients. These determinations showed inverse relation with nutritional markers. Increased fecal C-alpha(1)-AT values were associated with lower serum albumin. Fecal CT values showed a negative linear correlation with serum albumin and were inversely associated with retinol-binding protein, normalized protein nitrogen appearance, and serum iron. High plasma levels of pancreatic stimulating hormones were found: gastrin, CCK, and VIP. These levels were higher in patients with a worse pancreatic exocrine function. Higher values of other GI hormones, gastrin, pepsinogen I and II, CCK, GRP, and TNF-alpha. Normal concentrations of NPY, VIP, and PS were observed. CONCLUSION GI abnormalities (malabsorption, maldigestion, pancreatic dysfunction, and protein losing enteropathy) are present in an important number of PD patients. These features are negatively associated to nutrition.

Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysis

Background   Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated.

Prognostic value of cell-free plasma DNA in patients with cardiac arrest outside the hospital: an observational cohort study.

IntroductionMany approaches have been examined to try to predict patient outcome after cardiopulmonary resuscitation. It has been shown that plasma DNA could predict mortality in critically ill patients but no data are available regarding its clinical value in patients after out-of-hospital cardiac arrest. In this study we investigated whether plasma DNA on arrival at the emergency room may be useful in predicting the outcome of these patients.MethodsWe performed a prospective study of out-of-hospital patients with cardiac arrest who achieved return of spontaneous circulation after successful resuscitation. Cardiovascular co-morbidities and resuscitation history were recorded according to the Utstein Style. The outcome measures were 24 h and overall in-hospital mortality. Cell-free plasma DNA was measured by real-time quantitative PCR assay for the β-globin gene in blood samples drawn within two hours after the arrest. Descriptive statistics, multiple logistic regression analysis, and receiver operator characteristic (ROC) curves were calculated.ResultsEighty-five consecutive patients were analyzed with a median time to return of spontaneous circulation of 27 minutes (interquartile range (IQR) 18 to 35). Thirty patients died within 24 h and 58 died during the hospital course. Plasma DNA concentrations at admission were higher in non-survivors at 24 h than in survivors (median 5,520 genome equivalents (GE)/ml, vs 2810 GE/ml, P < 0.01), and were also higher in patients who died in the hospital than in survivors to discharge (median 4,150 GE/ml vs 2,460 GE/ml, P < 0.01). Lactate clearance at six hours was significantly higher in 24 h survivors (P < 0.05). The area under the ROC curves for plasma DNA to predict 24-hour mortality and in-hospital mortality were 0.796 (95% confidence interval (CI) 0.701 to 0.890) and 0.652 (95% CI 0.533 to 0.770). The best cut-off value of plasma DNA for 24-h mortality was 4,340 GE/ml (sensitivity 76%, specificity 83%), and for in-hospital mortality was 3,485 GE/ml (sensitivity 63%, specificity 69%). Multiple logistic regression analysis showed that the risk of 24-h and of in-hospital mortality increased 1.75-fold and 1.36-fold respectively, for every 500 GE/ml increase in plasma DNA.ConclusionsPlasma DNA levels may be a useful biomarker in predicting outcome after out-of hospital cardiac arrest.

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study

IntroductionCell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I)MethodsThis was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department.ResultsPlasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P < 0.001) and a plasma value of H-FBAP >6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality.Conclusionsmt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.

Association of cell-free plasma DNA with perioperative mortality in patients with suspected acute mesenteric ischemia

BACKGROUND Diagnosing patients with acute mesenteric ischemia (AMI) in the emergency ward is challenging. This study assesses the usefulness of plasma DNA in patients with clinically suspected AMI. METHODS 130 consecutive patients who underwent laparotomy were studied. Cell-free plasma DNA was measured by real-time quantitative PCR assay for the beta-globin gene. The primary endpoint was the accuracy of plasma DNA for predicting 30-day mortality. RESULTS Surgery revealed AMI in 99 patients and alternative diagnoses in 31 patients. Forty-six patients with AMI died (46.6%) as compared to 6 (19.4%) in the non-AMI group (p<0.05). The DNA concentration at admission was significantly higher in patients with AMI (median 7340 GE/ml, versus, 2735 GE/ml, p<0.01) and in AMI patients who died (8830 GE/ml, versus 4970 GE/ml, p<0.05). The area under the ROC curves for plasma DNA as a marker for mesenteric ischemia and independent predictor for 30-day mortality were 0.708 (95% CI 0.701-0.890) and 0.815 (95% CI 0.735-0.894). Multiple logistic regression analysis showed that the risk of hospital mortality increased 1.52-fold for every 1000 GE/ml increase in plasma DNA. CONCLUSIONS Plasma DNA levels may be a useful biomarker in predicting the outcome of patients with AMI.

Gastrointestinal peptide profile in children with celiac disease.

In order to investigate if a plasma profile of gastrointestinal peptides reflects changes in jejunal mucosa in celiac disease, we studied basal and postprandial plasma levels of gastrin, secretin, somatostatin, vasoactive intestinal polypeptide (VIP), and neurotensin in children with untreated and treated celiac disease and in a control group of children. Basal and 30-min postprandial secretin concentrations were statistically significantly lower in untreated celiac children compared to both treated celiac (p < 0.01 and p < 0.05, respectively) and control children (p < 0.001). Plasma secretin levels 30 min after a breakfast meal were also statistically significantly lower (p < 0.001) in treated celiac children with respect to the control group. In both untreated and treated celiac groups, basal and postprandial plasma levels of somatostatin and VIP were statistically significantly decreased (p < 0.001) compared to control children. Moreover, there was a significant rise in postprandial levels of neurotensin after a breakfast meal in untreated celiac children. On the contrary, there was no rise of neurotensin in healthy children. These findings seem to indicate that determination of plasma profile of gastrointestinal peptides in children with celiac disease may be useful in monitoring the development of this disease and, thus, the number of jejunal biopsies could be decreased.

Noninvasive diagnosis of hypolactasia with 4-Galactosylxylose (Gaxilose): a multicentre, open-label, phase IIB-III nonrandomized trial.

Goals and Background: Hypolactasia affects over half of the world population. Diagnosis remains problematic as currently available tests, such as the hydrogen breath test, have low reliability and lactose intolerance symptoms are unspecific. We evaluated the diagnostic performance and safety of a new noninvasive diagnostic test based on urine or serum measurement of D-xylose after lactase cleavage of orally administered 4-galactosylxylose (gaxilose). Study: In a multicentre, open-label, nonrandomized, phase IIb-III study, consecutive patients with symptoms suggestive of lactose intolerance sequentially underwent intestinal biopsy for direct measurement of lactase activity (reference standard), hydrogen breath test, and blood glucose test after lactose challenge, 4- and 5-hour urine-based gaxilose test, and blood-based gaxilose test. For the gaxilose tests, 0 to 4 and 4 to 5 hours urine samples were taken after a 0.45 g gaxilose dose, whereas serum samples were taken 90 minutes after a 2.7 g dose for D-xylose determination. Genetic testing of hypolactasia was also assessed. Results: Of the 222 patients enrolled, 203 completed all diagnostic tests; 108 were hypolactasic according to biopsy. The sensitivities and specificities and positive and negative predictive values of the gaxilose tests were all >90% versus 69% to 85% for the hydrogen breath test and the blood glucose test. The area under the ROC curve was significantly higher for the gaxilose tests (>0.9, P⩽0.007). These tests also had higher sensitivity than genetic testing for hypolactasia and were well tolerated. Conclusions: The diagnostic performance of the gaxilose tests is excellent and can substantially improve the diagnosis of hypolactasia.