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Obstructive sleep apnea (OSA) patients are at high risk of postoperative complications following bariatric surgery. The aim of our study was to compare peri- and postoperative outcomes in OSA patients awaiting laparoscopic bariatric surgery who were prescribed CPAP treatment or not before surgery using nocturnal home oximetry and capillary blood gas measurements. Data on 1094 eligible patients were analyzed. In accordance with our algorithm, those with ODI

RATIONALE/OBJECTIVES: Due to a higher risk of postoperative complications in obstructive sleep apnea (OSA) patients, a systematic screening for OSA is recommended for patients undergoing bariatric ...

BackgroundBiological biomarkers to stratify cancer risk before kidney transplantation are lacking. Several data support that tumor development and growth is associated with a tolerant immune profile. T cells expressing low levels of CD45RC preferentially secrete regulatory cytokines and contain regulatory T cell subset. In contrast, T cells expressing high levels of CD45RC have been shown to secrete proinflammatory cytokines, to drive alloreactivity and to predict acute rejection (AR) in kidney transplant patients. In the present work, we evaluated whether pre-transplant CD45RClow T cell subset was predictive of post-transplant cancer occurrence.MethodsWe performed an observational cohort study of 89 consecutive first time kidney transplant patients whose CD45RC T cell expression was determined by flow cytometry before transplantation. Post-transplant events including cancer, AR, and death were assessed retrospectively.ResultsAfter a mean follow-up of 11.1±4.1 years, cancer occurred in 25 patients (28.1%) and was associated with a decreased pre-transplant proportion of CD4+CD45RChigh T cells, with a frequency below 51.9% conferring a 3.7-fold increased risk of post-transplant malignancy (HR 3.71 [1.24-11.1], p = 0.019). The sensibility, specificity, negative predictive and positive predictive values of CD4+CD45RChigh52.1% were 94.5, 68.0, 34.7 and 98.6% respectively. Frequency of CD4+CD45RChigh T cells was positively correlated with those of CD8+CD45RChigh (pConclusionHigh frequency of CD45RChigh T cells was associated with AR, while low frequency was associated with cancer. Thus, CD45RC expression on T cells appears as a double-edged sword biomarker of promising interest to assess both cancer and AR risk before kidney transplantation.

Abstract —Cardiac left ventricular hypertrophy (LVH) is commonly associated with hypertension, but its variance is determined for more than 50% by blood pressure–independent genetic factors. Because it constitutes one of the most important risk factors for cardiovascular mortality, we have performed a genome-wide scan of the F2 progeny of crosses between inbred WKY and WKHA rats to detect quantitative trait loci (QTL) linked to cardiac mass. In addition to left ventricular mass (LVM), we also measured left ventricle (LV) concentration of atrial natriuretic factor (ANF), because we have previously established that there was a genetic link between these 2 traits in the same animal cross. We found 2 contiguous QTL on chromosome 5 that were linked to either LVM (logarithm of odds [LOD]=3.5) or log n (LV ANF) (LOD=12). The 1-LOD support intervals of both QTL shared a region overlapping the locus of natriuretic peptide precursor A ( Nppa ) (ie, the ANF-coding gene). We found by sequencing 2 single nucleotide polymorphisms (SNPs) within the first 650 bp of the Nppa minimal promoters of the genes from both strains. One of these SNPs increased the transcriptional activity of the Nppa minimal promoter in transfected neonatal cardiomyocytes in keeping with the higher LV concentration of ANF observed in WKY versus WKHA rats. Taken together with the previous reports showing that ANF may protect cardiomyocytes against hypertrophy, our genetic data single out Nppa as a strong candidate gene for the determination of LVM.

Most cardiovascular traits of interest can be defined as “complex traits,” with the first step in the identification of genetic factors affecting such traits being the detection of quantitative trait loci (QTLs). Animal models have proven particularly useful in this regard. However, only very few of the QTLs identified to date have led to the identification of candidate genes. We describe an example of our own work where the combination of anatomical and a biochemical intermediate phenotypes have led to the identification of the natriuretic peptide precursor A ( Nppa ) gene as a candidate gene for left ventricular hypertrophy (LVH). Combined with the power of comparative genetics, these strategies will continue to improve the chances of finding candidate genes for cardiovascular traits such as susceptibility to heart diseases, hypertension, and hypertension-induced end-organ damage.

55 The cardiac ventricular mass of WKHA inbred rats is higher than that of WKY rats, yet both strains exhibit normal and identical values of blood pressure (as verified by telemetry). We have shown previously in the F2 male progeny of WKY/WKHA crosses that low ventricular concentration of atrial natriuretic factor (ANF) co-segregated significantly with high cardiac ventricular mass (Circ. Res. 84:1453-1458, 1999). To extend these findings, we have performed a scan of the whole genome of 158 rats originating from the male F2 progeny of the WKY/WKHA cross. By linkage analysis, we have identified on chromosome 5 one QTL that was linked to left ventricular ANF concentration (QTL ANF ) with a LOD score of 17, and one QTL that was was linked to left ventricular mass (QTL LVM ) with a LOD score of 3.5. The 2-LOD confidence interval for the location of QTL ANF ranged from positions 94 to 104 cM, which overlaps partly with the 2-LOD confidence interval for the location of QTL LVM between positions 80 to 103 cM. The locus of the natriuretic peptide precursor A ( Nppa ) gene (at about 100 cM) is located within an interval covered by both QTL’s. Sequencing of a 600 bp fragment of the promoter regions of the Nppa genes from WKY and WKHA revealed that there were single nucleotide polymorphisms within two different regions of the promoters. These mutations lie within regions known to contain response elements to transcription factors, but the results of ongoing experiments are needed to determine whether they can affect the ability of the respective promoters to drive the expression of reporter genes in transfected cardiomyocytes. Altogether, these data suggest that the Nppa gene may be considered as a candidate gene to explain, at least in part, the variance of left ventricular ANF concentration and/or left ventricular mass in WKY and WKHA rats. They also define the region that will be studied in congenic lines to obtain a better spatial resolution of the QTL’s, and in particular to determine whether QTL ANF and QTL LVM are identical or adjacent.

Wistar-Kyoto (WKY) and WKY-derived hyperactive (WKHA) rats are two genetically-related inbred strains of rats that are both normotensive yet exhibit differences in left ventricular mass (LVM). We had shown previously that cardiomyocytes from male WKHA are wider than that of male WKY, and that there was genetic linkage between LVM and a locus on chromosome 5 (RNO5) in the male progeny of a F2 WKHA/WKY cross. We show here that cardiomyocyte width is linked to the same RNO5 locus in male reciprocal congenic rats derived from WKHA and WKY. Contrary to males, we found no genetic linkage between LVM and the RNO5 locus in female rats. However, ventricular hypertrophy in females might be of a different nature, because cardiomyocytes from female WKHA were shorter than their WKY counterparts (with no difference in width). The RNO5 locus contains that of the natriuretic peptide precursor A (Nppa) gene. In male congenic rats, changes in cardiomyocyte width always correlated with reciprocal changes in the LV concentration of atrial natriuretic factor (ANF, i.e., the peptide product of Nppa). Taken together with other functional data, the small size of the RNO5 locus (∼63 cR) increased the likelihood that both cardiomyocyte width and LV ANF concentration could be linked to only one gene (possibly Nppa) in male rats. Moreover, our results support the notion that genes and sex interact to regulate cardiomyocyte width and length independently from one another.