Metabolomic Characterization of Human Model of Liver Rejection Identifies Aberrancies Linked to Cyclooxygenase (COX) and Nitric Oxide Synthase (NOS)

BACKGROUND Acute liver rejection (ALR), a significant complication of liver transplantation, burdens patients, healthcare payers, and the healthcare providers due to an increase in morbidity, cost, and resources. Despite clinical resolution, ALR is associated with an increased risk of graft loss. A unique protocol of delayed immunosuppression used in our institute provided a model to characterize metabolomic profiles in human ALR. MATERIAL AND METHODS Twenty liver allograft biopsies obtained 48 hours after liver transplantation in the absence of immunosuppression were studied. Hepatic metabolites were quantitated in these biopsies by liquid chromatography and mass spectroscopy (LC/MS). Metabolite profiles were compared among: 1) biopsies with reperfusion injury but no histological evidence of rejection (n=7), 2) biopsies with histological evidence of moderate or severe rejection (n=5), and 3) biopsies with histological evidence of mild rejection (n=8). RESULTS There were 133 metabolites consistently detected by LC/MS and these were prioritized using variable importance to projection (VIP) analysis, comparing moderate or severe rejection vs. no rejection or mild rejection using partial least squares discriminant statistical analysis (PLS-DA). Twenty metabolites were identified as progressively different. Further PLS-DA using these metabolites identified 3 metabolites (linoleic acid, γ-linolenic acid, and citrulline) which are associated with either cyclooxygenase or nitric oxide synthase functionality. CONCLUSIONS Hepatic metabolic aberrancies associated with cyclooxygenase and nitric oxide synthase function occur contemporaneous with ALR. Additional studies are required to better characterize the role of these metabolic pathways to enhance utility of the metabolomics approach in diagnosis and outcomes of ALR

The consequences of early childhood growth failure over the life course:

This paper examines the impact over the life course of early childhood growth failure as measured by achieved height at 36 months. It uses data collected on individuals who participated in a nutritional supplementation trial between 1969 and 1977 in rural Guatemala and who were subsequently reinterviewed between 2002 and 2004. It finds that individuals who did not suffer growth failure in the first three years of life complete more schooling, score higher on tests of cognitive skill in adulthood, have better outcomes in the marriage market, earn higher wages and are more likely to be employed in higher-paying skilled labor and white-collar jobs, are less likely to live in poor households, and, for women, fewer pregnancies and smaller risk of miscarriages and stillbirths. Growth failure has adverse impacts on body size and several dimensions of physical fitness in adulthood but does not have marked effects on risk indicators of cardiovascular and related chronic diseases. These results provide a powerful rationale for investments that reduce early-life growth failure.Chronic disease, early life growth failure, fertility, Human capital, Poverty, Undernutrition, Wages,

Telemonitoring in chronic ventilatory failure: a new model of survellaince, a pilot study

Background and Aim. The efficiency of tele-monitoring or tele-assistance in patients with severe chronic ventilatory failure in home mechanical ventilation (HMV) is still being investigated. Our aim was to test the feasibility of a model which consisted in: 1) once a week nocturnal telemonitoring, supervised by a doctor in charge in a Respiratory Intensive Care Unit, who also provided a telephone-counselling (24/7) on demand; 2) a scheduled visit every two months. Methods. A 2-year observational study was carried out on 16 patients ventilated for at least 1 year and for ≥ 8 hours /day. Once a week patients underwent a nocturnal monitoring during HMV. The compliance was evaluated by regular transmission of data and regular follow-up, the level of satisfaction by a telephonequestionnaire. Results. The adherence to the protocol study was good in 9/16 (56%) and poor in 7/16 (44%) patients. For each patient, the mean number of connections was 46,12 ± 36.39 (70.7% of that expected), in those with good compliance it increased to 63.8 ± 32.7 (114% of that expected). The median hours of connection was 343 (138- 1019) and 89 (0-521) for patients with good and poor compliance respectively, p=0.038. The mean scheduled visits for patient with good compliance was 6.9 ± 4.14 (100% of that expected). Emergency visits were avoided in 62.5% of cases. The satisfaction score was higher in compliant versus non compliant patients (p=0.019). Conclusion. This pilot study showed that the telemonitoring system employed was feasible and effective in more compliant patients who claimed a high rate of satisfaction

Cancer incidence in kidney transplant recipients: a study protocol

<p>Abstract</p> <p>Background</p> <p>Different publications show an increased incidence of neoplasms in renal transplant patients. The objective of this study is to determine the incidence of cancer in the recipients of renal transplants performed in the A Coruña Hospital (Spain) during the period 1981–2007.</p> <p>Methods/Design</p> <p>During the study period 1967 kidney transplants were performed, corresponding to 1710 patients. Patients with neoplasms prior to the transplant will be excluded (n = 38). A follow-up study was carried out in order to estimate cancer incidence after transplantation.</p> <p>For each patient, information included donor and recipient characteristics, patients and graft survival and cancer incidence after transplantation. Incident cancer is considered as new cases of cancer after the transplant with anatomopathological confirmation. Their location will be classified according to the ICD-9.</p> <p>The analysis will be calculated using the indirect standardisation method. Age-adjusted cancer incidence rates in the Spanish general population will be obtained from the Carlos III Health Institute, the National Epidemiology Centre of the Ministry of Science and Technology. Crude first, second and third-year post-transplantation cancer incidence rates will be calculated for male and female recipients. The number of cases of cancer at each site will be calculated from data in the clinical records. The expected number of cancers will be calculated from data supplied by the Carlos III Health Institute. For each tumour location we will estimate the standardized incidence ratios (SIRs), using sex-specific cancer incidence rates, by dividing the incidence rate for the transplant patients by the rate of the general population. The 95% confidence intervals of the SIRs and their associated p-values will be calculated by assuming that the observed cancers follow a Poisson distribution. Stratified analysis will be performed to examine the variation in the SIRs with sex and length of follow-up.</p> <p>Competing risk survival analysis methods will be applied to estimate the cumulative incidence of cancer and to identify variables associated to its occurrence.</p> <p>Discussion</p> <p>Information about cancer incidence in kidney transplant patients could be useful to adapt the guidelines on post-kidney transplant follow-up on tumour screening, and evaluate the impact of intervention measures for the prevention of cancer in these patients.</p

Measuring wealth in rural communities: Lessons from the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial.

BACKGROUND: Poverty and human capital development are inextricably linked and therefore research on human capital typically incorporates measures of economic well-being. In the context of randomized trials of health interventions, for example, such measures are used to: 1) assess baseline balance; 2) estimate covariate-adjusted analyses; and 3) conduct subgroup analyses. Many factors characterize economic well-being, however, and analysts often generate summary measures such as indices of household socio-economic status or wealth. In this paper, a household wealth index is developed and tested for participants in the cluster-randomized Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. METHODS: Building on the approach used in the Zimbabwe Demographic and Health Survey (ZDHS), we combined a set of housing characteristics, ownership of assets and agricultural resources into a wealth index using principal component analysis (PCA) on binary variables. The index was assessed for internal and external validity. Its sensitivity was examined considering an expanded set of variables and an alternative statistical approach of polychoric PCA. Correlation between indices was determined using the Spearman's rank correlation coefficient and agreement between quintiles using a linear weighted Kappa statistic. Using the 2015 ZDHS data, we constructed a separate index and applied the loadings resulting from that analysis to the SHINE study population, to compare the wealth distribution in the SHINE study with rural Zimbabwe. RESULTS: The derived indices using the different methods were highly correlated (r>0.9), and the wealth quintiles derived from the different indices had substantial to near perfect agreement (linear weighted Kappa>0.7). The indices were strongly associated with a range of assets and other wealth measures, indicating both internal and external validity. Households in SHINE were modestly wealthier than the overall population of households in rural Zimbabwe. CONCLUSION: The SHINE wealth index developed here is a valid and robust measure of wealth in the sample