Impact of diabetes and glycaemic control on peripheral artery disease in Japanese patients with end-stage renal disease: long-term follow-up study from the beginning of haemodialysis

Aims/hypothesis

End-stage renal disease (ESRD) patients with diabetes have been regarded as being at the highest risk of cardiovascular disease. We therefore investigated the relationship between diabetes and the incidence of peripheral artery disease (PAD) in new haemodialysis patients.

Methods

We enrolled 1,513 ESRD patients who had just begun haemodialysis therapy. They were divided into two groups: those with (n?=?739) and those without diabetes (n?=?774). The endpoint was the development of PAD, defined as ankle brachial pressure index ≤0.9 or toe brachial pressure index <0.7 in patients with an ankle brachial pressure index >0.9.

Results

According to the Kaplan–Meier method, the 10?year event-free rate for development of PAD and lower limb amputation was significantly lower in the diabetes group than in the non-diabetes group (60.3% vs 82.8%, HR 2.99, 95% CI 2.27, 3.92, p?p?=?0.0005 for PAD and lower limb amputation, respectively). In patients with diabetes, quartile analysis of HbA_1c levels showed that the highest quartile group (≥6.8% [51?mmol/mol]) had significant development of PAD and lower limb amputation compared with lower quartile groups (PAD HR 1.63, 95% CI 1.17, 2.28, p?=?0.0038; lower limb amputation HR 2.99, 95% CI 1.17, 7.70, p?=?0.023).

Conclusions/interpretation

Diabetes was a strong predictor of PAD after initiation of haemodialysis therapy in patients with ESRD. In addition, higher HbA_1c levels were associated with increased risk of developing PAD and requiring limb amputation in such diabetic populations.     

The role of bilirubin and its protective function against coronary heart disease

Background

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality both in industrialized and developing countries. Atherosclerosis is a chronic inflammatory disease of the arterial wall, which also involves deposition and peroxidation of lipids. Bilirubin, an important endogenous antioxidant, may limit lipid peroxidation and retard the progression of atherosclerosis. Previous studies have reported an inverse relationship between serum bilirubin levels and the risk of coronary artery disease (CAD). Taking into account that atherosclerosis is a complex process that is initiated and accelerated by diverse risk factors, we aimed to test the antiatherosclerotic effects of bilirubin in a population with multiple risk factors for CAD.

Methods

The study included 221 patients who underwent coronary angiography owing to symptoms suggestive of ischemia and/or positive noninvasive stress test results. Of the patients, 76 had normal coronary angiograms and served as the control group. The remaining 145 patients with documented CAD and two or more cardiovascular risk factors constituted the study group. The study group (n=145) was further classified according to the Gensini score as follows: group 1 if Gensini score was 1–19 (minimal CAD, n=82), and group 2 if Gensini score was 20 or higher (significant CAD, n=63). Biochemical assessments including total and direct serum bilirubin levels were carried out using standard methods in automated systems.

Results

All of the cardiovascular risk factors were found significantly more frequently in the study group (groups 1 and 2) than in the control group. Total and direct serum bilirubin levels did not differ significantly between the control group, group 1, and group 2. There was a moderate and significant positive correlation between direct bilirubin levels and the Gensini score (r?=?0.158, p?=?0.019). There was no significant correlation between total bilirubin levels and the Gensini score.

Conclusion

In conclusion, our findings suggest that in the presence of multiple risk factors, similar concentrations of serum bilirubin may not confer the same level of protection against CAD as in an individual with a more favorable risk profile. The relationship between direct bilirubin levels and the Gensini score is unlikely to be causative, given the established antiatherosclerotic effects of bilirubin.     

Determinants of the clinical outcome of patients with severe acute exacerbation of chronic hepatitis B virus infection

Background

Severe acute exacerbation of chronic hepatitis B can sometimes occur and lead to hepatic failure and death. The objective of this study was to elucidate the predictors of progression to hepatic decompensation during severe acute exacerbation.

Methods

We prospectively analyzed 37 consecutive patients with acute exacerbation of chronic hepatitis B (accompanied by jaundice and coagulopathy) for clinical outcome and factors that influenced the development of severe acute exacerbation, including viral kinetics.

Results

Fourteen (37.8%) patients progressed to severe acute exacerbation (accompanied by encephalopathy). Multivariate analysis identified serum bilirubin (>5?mg/dl, P?=?0.002) as a significant determinant of progression to hepatic failure and prothrombin activity (<45%, P?=?0.028) and as a determinant of liver-related death. The hepatitis B virus (HBV) DNA level before therapy was measured in 25 patients. HBV DNA levels increased or did not change from before commencement of treatment in all 11 patients who progressed to severe acute exacerbation. On the other hand, HBV DNA levels did not change or increased in 8 of 14 patients (57%) with acute exacerbation (P?=?0.02).

Conclusions

Serum bilirubin and prothrombin activities were significant predictors of clinical outcome in patients with severe acute exacerbation of chronic hepatitis B. Viral kinetics until commencement of therapy can predict the severity of acute exacerbation of chronic hepatitis B.     

Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals

Aims/hypothesis

The newly identified liver- and fat-derived hormone, betatrophin, has recently been linked to insulin resistance and pancreatic beta cell growth in mice. These preclinical findings have suggested betatrophin as a potential candidate for novel glucose-lowering treatment concepts involving beta cell regeneration. However, the role of betatrophin in human insulin resistance and type 2 diabetes is currently unknown. Hence, the aim of this study was to investigate circulating betatrophin concentrations in two distinct cohorts with insulin resistance.

Methods

Betatrophin concentrations were analysed in (1) age- and sex-matched lean (n?=?20) and morbidly obese individuals (n?=?19), and (2) age-, sex- and BMI-matched non-diabetic (n?=?19) and type 2 diabetic individuals (n?=?18).

Results

Betatrophin concentrations did not differ between lean and morbidly obese or between non-diabetic and type 2 diabetic participants. No association was found with variables of beta cell function and glucose homeostasis. However, betatrophin did correlate significantly with plasma atherogenic lipids including total cholesterol, LDL-cholesterol and apolipoprotein B in morbidly obese and type 2 diabetic patients but not in controls. Insulin-resistant individuals with hypercholesterolaemia (≥5.2 mmol/l) had significantly higher betatrophin concentrations than those with normal cholesterol (<5.2 mmol/l).

Conclusions/interpretation

Betatrophin is a recently identified hormone, the circulating concentrations of which are unaltered in human insulin resistance but correlate significantly with atherogenic lipid profiles in high-risk cohorts with morbid obesity or type 2 diabetes. Betatrophin could therefore be a novel pathomechanistic player in dysfunctional lipid metabolism associated with high cardiovascular risk.     

Effects of obstructive sleep apnea severity on serum lipid levels in Greek children with snoring

Background

Although obstructive sleep apnea (OSA) is related to dyslipidemia in adults, limited data are available regarding its effects on serum lipids during childhood. Aim of this study was to assess the potential relationships between severity of OSA and cholesterol or triglyceride levels in a cohort of Greek children.

Methods

Data from children with snoring who underwent polysomnography and complete serum lipids measurements during a specified study period were analyzed retrospectively.

Results

Overall, obese children (n?=?261) had lower HDL cholesterol levels than non-obese subjects (n?=?113) (49.6?±?10.5 vs. 53.9?±?11.4 mg/dL; p?=?0.001) and higher triglyceride concentrations (69.8?±?32.2 vs. 63.2?±?27 mg/dL; p?=?0.041). Non-obese subjects with moderate-to-severe OSA did not differ in triglycerides, total, and LDL cholesterol concentrations but had lower HDL cholesterol, when compared to non-obese children with primary snoring/mild OSA (50.4?±?13.1 vs. 54.9?±?10.7 mg/dL; p?=?0.008). The risk for having low HDL cholesterol (??40 mg/dL) was threefold higher in non-obese subjects with moderate-to-severe OSA than in those with primary snoring/mild OSA, even after adjustment for age and gender [OR?=?3.44 (95% CI 1.44 to 8.24; p?=?0.006)]. Concentrations of serum lipids in obese children were not associated with severity of OSA. HDL cholesterol was 48.5?±?8.7 mg/dL in subjects with moderate-to-severe OSA and 50.0?±?11.1 mg/dL in children with primary snoring/mild OSA (p?=?0.519).

Conclusions

HDL cholesterol levels are inversely related to severity of OSA in non-obese children with snoring.     

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

Aims/hypothesis

Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate??s renal effects overall and in a FIELD washout sub-study.

Methods

Type 2 diabetic patients (n?=?9,795) aged 50 to 75?years were randomly assigned to fenofibrate (n?=?4,895) or placebo (n?=?4,900) for 5?years, after 6?weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year?2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8?weeks after treatment cessation at close-out (washout sub-study, n?=?661). Analysis was by intention-to-treat.

Results

During fenofibrate run-in, plasma creatinine increased by 10.0???mol/l (p?p?=?0.01), with less estimated GFR loss (1.19 vs 2.03?ml min^?1 1.73?m^?2 annually, p??1 1.73?m^?2, p?=?0.065) than on placebo (6.9?ml min^?1 1.73?m^?2, p??1 1.73?m^?2 (95% CI 2.3?C7.7, p?n?=?169 vs 491 without) alone, or combined with low HDL-cholesterol (n?=?140 vs 520 without) and reductions of ??0.48?mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n?=?356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p?p?p?n?=?21 vs 26, p?=?0.48).

Conclusions/interpretation

Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5?years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited.

Trial registration

ISRCTN64783481

Funding

The study was funded by grants from Laboratoires Fournier SA (Dijon, France; now part of Abbott Pharmaceuticals) and the National Health and Medical Research Council, Australia     

The Effects of Intraperitoneal Sildenafil Administration on Healing of Left Colonic Anastomoses and Intra-Abdominal Adhesion Formation in the Presence of Intra-Abdominal Infection

Purpose

The objective of this pilot study was to establish an animal model for intra-abdominal infection and to examine the effect of sildenafil on anastomotic healing of the left colon and intra-abdominal adhesion formation.

Methods

Fourteen Winstar rats underwent colonic transsection and primary anastomosis after performing intra-abdominal infection. Rats were divided into two groups: Group 1 (n?=?7): intra-abdominal infection, resection, and anastomoses; Group 2 (n?=?7): intra-abdominal infection, resection, anastomoses, and sildenafil. Anastomotic bursting pressures, hydroxyproline levels, histopathologic grading, and abdominal adhesions were accessed on the postoperative Day 7.

Results

Anastomotic healing was found to be improved in terms of a bursting pressure (P?=?0.02). Histopathological examination revealed an increase in angiogenesis (P?=?0.007). Moreover, intra-abdominal adhesions were significantly less in rats given sildenafil (P?=?0.03).

Conclusion

Sildenafil may improve anastomotic healing of the left colon and diminishes peritoneal adhesion formation in the presense of abdominal infection.     

Serum L-ficolin levels in patients with systemic lupus erythematosus

Objective

L-ficolin plays an important role in innate immunity and is involved in apoptosis. The objective of this study was to investigate the relationship between serum L-ficolin levels and clinical manifestations in patients with systemic lupus erythematosus (SLE).

Methods

Serum L-ficolin levels were determined by enzyme-linked immunosorbent assay in 66 SLE patients and 50 healthy controls.

Results

Median serum L-ficolin levels were 5.0 and 8.7?μg/ml in SLE patients and controls, respectively (p?=?0.0001). There were no significant differences in serum L-ficolin levels between the active disease group [SLE Disease Activity Index (SLEDAI) >6] and the inactive disease group (SLEDAI <5). Decreased serum L-ficolin levels were associated with thrombocytopenia (median of with vs. without thrombocytopenia 3.4 vs. 5.3?μg/ml, p?=?0.008). There were no correlations between serum L-ficolin levels and SLEDAI, serum C3, or serum C4 levels.

Conclusion

The association between L-ficolin and thrombocytopenia suggests a pathogenic role for L-ficolin in thrombocytopenia in SLE.     

Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Aims/hypothesis

In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n?=?9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses.

Methods

Women (n?=?3,657) and men (n?=?6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex.

Results

Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p?p?p?=?0.008) and 13% in men (95% CI ?1%, 24%; p?=?0.07) with no treatment-by-sex interaction (p?>?0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI ?7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p?>?0.1).

Conclusions/interpretation

Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.     

Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Background

Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to cause systemic insulin resistance in the absence of adipose tissue metabolic dysfunction. To determine if this holds true for humans, we studied the relationship between insulin resistance and markers of adipose tissue dysfunction in non-obese individuals.

Method

32 non-obese first-degree relatives of Type 2 diabetic patients were recruited. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was measured with the hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene/protein expression and adipocyte cell size measurements.

Results

Our findings show that also in non-obese individuals low insulin sensitivity is associated with signs of adipose tissue metabolic dysfunction characterized by low expression of GLUT4, altered adipokine profile and enlarged adipocyte cell size. In this group, insulin sensitivity is positively correlated to GLUT4 mRNA (R?=?0.49, p?=?0.011) and protein (R?=?0.51, p?=?0.004) expression, as well as with circulating adiponectin levels (R?=?0.46, 0?=?0.009). In addition, insulin sensitivity is inversely correlated to circulating RBP4 (R?=??0.61, 0?=?0.003) and adipocyte cell size (R?=??0.40, p?=?0.022). Furthermore, these features are inter-correlated and also associated with other clinical features of the metabolic syndrome in the absence of obesity. No association could be found between the hypertrophy-associated adipocyte dysregulation and HIF-1alpha in this group of non-obese individuals.

Conclusions

In conclusion, these findings support the concept that it is not obesity per se, but rather metabolic dysfunction of adipose tissue that is associated with systemic insulin resistance and the metabolic syndrome.     

Oxidative stress and antioxidant capacity in patients with chronic pancreatitis with and without diabetes mellitus

Aim

To determine oxidant stress and antioxidant capacity in chronic pancreatitis (CP) patients with and without diabetes mellitus.

Methods

This study is a secondary data analysis of our earlier study on 127 (male?=?86) patients with CP, grouped as those with diabetes (case; n?=?23) and those without diabetes (control). Markers of antioxidant status included vitamins A and E, total antioxidant capacity (TAC; measured as ferric-reducing ability of plasma [FRAP]), and total glutathione (T-GSH). Markers for oxidative stress included lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS) and serum superoxide dismutase (s-SOD).

Results

Patients with diabetes were older (mean [SD] age 36.4 [9.7] vs. 29.3 [10.0] years; p?=?0.032), had longer duration of CP [4 (0.3?C21) vs. 3 (0.3?C24) years; p?=?0.07), and had a lower TAC (269.8 [92.4] vs. 355.5 [128.6] ??moles Fe⁺² liberated; p?=?0.003) compared to those without diabetes. In multiple logistic regression analysis taking all exploratory variables, FRAP (<270 ??moles Fe⁺² liberated) was associated with diabetes independent of duration of CP, age of patients, and TBARS levels. However, oxidative stress levels were not different between diabetic and nondiabetic patients.

Conclusions

Diabetes was found to be associated with longer duration of CP and with low antioxidant capacity. Further studies will be needed to evaluate a causal association.     

Direct bilirubin is associated with low-density lipoprotein subfractions and particle size in overweight and centrally obese women

Background and aims

Bilirubin has antioxidant and anti-inflammatory properties; serum bilirubin levels have been known to be inversely associated with cardiovascular disease. However, the effects of different bilirubin subtypes on cardiometabolic traits are unknown. In this study, we aimed to determine whether direct bilirubin is more strongly correlated with small, dense low-density lipoprotein (sdLDL) compared to other bilirubin subtypes. We also investigated which LDL subfractions exhibited the highest correlation with direct bilirubin.

Diabetes Control Among Hispanics in the Action to Control Cardiovascular Risk in Diabetes Trial

BACKGROUND

Hispanics in the United States represent diverse racial, ethnic, and socioeconomic groups, and manifest heterogeneous cardiovascular risks including diabetes. It is not known if there are residual differences in the control of diabetes among Hispanic groups given uniform access to diabetes care.

OBJECTIVE

To evaluate glucose control differences among Mexicans, Puerto Ricans, and Dominicans receiving substantial diabetes care and support in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

DESIGN

Secondary analysis of data from a randomized trial comparing two treatment strategies: intensive, targeting glycated hemoglobin below 6.0?%, and standard, targeting glycated hemoglobin between 7.0?% and 7.9?%.

PARTICIPANTS

Seven hundred and sixteen Hispanic and 6066 non-Hispanic white participants were recruited from 77 clinical sites across the United States and Canada. There were 243 Mexicans, 199 Puerto Ricans, and 150 Dominicans; and 135 of these Hispanic groups were born in the United States.

MAIN MEASURE

Glycated hemoglobin

RESULTS

Compared to Puerto Ricans, Mexicans were more likely (HR?=?1.38, CI:0.90?C2.10) and Dominicans as likely (HR?=?1.01, CI:0.66?C1.54) to achieve glycated hemoglobin goal in the intensive arm. Participants born in the United States achieved glycated hemoglobin goal at a higher rate than those born elsewhere (HR?=?1.57, CI:0.99?C2.51 in the intensive arm, HR?=?1.51, CI:0.95?C2.43 in the standard arm). These differences were not statistically significant. In the intensive arm, Puerto Ricans (OR?=?0.47, CI:0.31?C0.71), and Dominicans (OR?=?0.41, CI:0.26?C0.66) were less likely than non-Hispanic whites to achieve glycated hemoglobin goal, whereas the difference between non-Hispanic whites and Mexicans was not statistically significant, (OR?=?0.66, CI:0.43?C1.02).

CONCLUSIONS

Hispanic groups, given access to comprehensive diabetes care, differed from each other non-significantly and had a variable divergence from non-Hispanic whites in achieving intensive glycated hemoglobin goal. These differences, if confirmed, could be due to such factors as variable acculturation and functional health literacy levels that were not measured in the ACCORD trial, but should be further explored in future studies.     

Association analysis of genetic variants in microRNA networks and gastric cancer risk in a Chinese Han population

Purpose

To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer.

Methods

We genotyped 19 SNPs of the microRNA-related genes in a case–control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population.

Results

We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p?=?0.033, aOR?=?0.742, 95%CI?=?0.564–0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p?=?0.037, aOR?=?0.771, 95%CI?=?0.604–0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p?=?0.021, aOR?=?0.529, 95%CI?=?0.307–0.910) and TMN stage (p?=?0.021, aOR?=?0.532, 95%CI?=?0.311–0.908), respectively.

Conclusions

Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population.     

Serum lactonase and arylesterase activities in alcoholic hepatitis and hepatitis B

Background

PON1 is an HDL-associated enzyme having antioxidant activity. PON1 is synthesized in the liver, and there is decreased synthesis of PON1 with increased lipid peroxidation. The study was carried with the aim of establishing whether chronic liver disease (CLD) produced any significant changes in serum arylesterase (AE) and lactonase activities of PON. The second objective was to determine whether there was any correlation between serum AE and lactonase activities and the various routine liver function tests. The usefulness of adding serum lactonase and AE activity to standard liver function tests was analyzed by multiple logistic regression analysis. Finally, the diagnostic efficacy or analytical performance of AE and lactonase in assessing patients with CLD was determined using ‘receiver operating characteristic’ (ROC) plot.

Methods

The study group consisted of 120 subjects; 60 were patients with liver disease out of which 40 were having chronic alcoholic liver disease and 20, acute viral hepatitis B, and 60 were healthy controls. Serum PON1 lactonase activity was measured manually using dihydrocoumarin, and AE activity was measured using phenylacetate as substrate. Liver function tests (bilirubin, albumin, AST, ALT, alkaline phosphatise) were done by standard technique.

Result

The serum lactonase and AE activities were decreased significantly in patients with chronic alcoholic liver disease (p?<?0.001, p?<?0.001) and acute viral hepatitis B (p?<?0.001, p?<?0.001). Both measurements showed higher efficiency in testing liver dysfunction in multivariate regression analysis. Model 1 consisted of bilirubin, albumin, AST, ALT, and alkaline phosphatase, R2?=?0.912. Model 2 consisted of model 1+arylesterase having higher R2?=?0.0.954, and model 3 consisted of model 1+lactonase having R2?=?0.962. ROC plots demonstrated a high diagnostic accuracy for serum PON1 lactonase (area under ROC curve?=?0.982) and serum PON1 arylesterase (area under ROC curve?=?0.986).

Conclusion

Low PON1 lactonase and AE activity were found in acute viral hepatitis B and in chronic alcoholic hepatitis.     

Clinically Significant Endoscopic Findings in a Multi-Ethnic Population With Uninvestigated Dyspepsia

Introduction

The proportion of clinically significant endoscopic findings (CSEF) in dyspepsia affects the initial management of this condition. With the changing epidemiology of organic upper gastrointestinal diseases in Asia, current data on CSEF remains uncertain.

Methods

A cross-sectional study of consecutive adult patients attending an open access endoscopy list for the primary indication of dyspepsia was conducted. Independent epidemiological and clinical factors for CSEF were determined prospectively.

Results

Data for 1167/1208 (96.6?%) adults (mean age 49.7?±?15.9?years, 42.4?% males, ethnic distribution: 30.5?% Malays, 36.9?% Chinese and 30.8?% Indians) were analysed between January 2007 and August 2008. Three-hundred and eight (26.4?%) patients were found to have CSEF, most often those with age ??45?years (30.3 vs 19?%, P?<?0.0001), male gender (34.1 vs 20.7?% female, P?<?0.0001), lower education levels (i.e. primary or no education), smoking (36.7 vs 24.9?%, P?=?0.003), H. pylori infection (40.6 vs 21.8?%, P?<?0.0001), and duration of dyspepsia ??5?months (32.8 vs 24.4?%, P?=?0.006). Age????45?years (OR 1.82, 95?% CI?=?1.38?C2.48), male gender (OR 1.84, 95?% CI?=?1.53?C2.59), H. pylori infection (OR 2.36, 95?% CI?=?1.83?C3.26), and duration of dyspepsia ??5?months (OR 1.44, 95?% CI?=?1.13?C2.03) were subsequently identified as independent risk factors for CSEF.

Conclusion

CSEF are found in 26.4?% of Asian adults with uninvestigated dyspepsia. Duration of symptoms <5?months, among other recognised factors, is predictive of CSEF.     

L-citrulline Prevents Alveolar and Vascular Derangement in a Rat Model of Moderate Hyperoxia-induced Lung Injury

Background

Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.

Methods

Newborn rats were exposed to FiO₂?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.

Results

Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).

Conclusions

We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.     

Quantitative profiling of CpG island methylation in human stool for colorectal cancer detection

Purpose

The aims of this study were to investigate the use of quantitative CGI methylation data from stool DNA to classify colon cancer patients and to relate stool CGI methylation levels to those found in corresponding tissue samples.

Methods

We applied a quantitative methylation-specific PCR assay to determine CGI methylation levels of six genes, previously shown to be aberrantly methylated during colorectal carcinogenesis. Assays were performed on DNA from biopsies of “normal” mucosa and stool samples from 57 patients classified as disease-free, adenoma, or cancer by endoscopy, and in tumour tissue from cancer patients. Additionally, CGI methylation was analysed in stool DNA from an asymptomatic population of individuals covering a broad age range (mean?=?47?±?24 years)

Results

CGI methylation levels in stool DNA were significantly higher than in DNA from macroscopically normal mucosa, and a significant correlation between stool and mucosa was observed for ESR1 only. Multivariate statistical analyses using the methylation levels of each CGI in stool DNA as a continuous variable revealed a highly significant (p?=?0.003) classification of cancer vs. non-cancer (adenoma + disease-free) patients (sensitivity?=?65 %, specificity?=?81 %).

Conclusion

CGI methylation profiling of stool DNA successfully identified patients with cancer despite the methylation status of CGIs in stool DNA not generally reflecting those in DNA from the colonic mucosa.     

Association of peripheral arterial disease with all-cause and cardiovascular mortality in hemodialysis patients: a meta-analysis

Background

Recent studies have shown an association between peripheral arterial disease (PAD) and increased risk of mortality in hemodialysis (HD) patients; however, the estimates vary widely and are inconsistent. It is necessary to elucidate the degree of mortality risk for PAD patients in HD population.

Methods

PubMed, EMBASE, Web of Science and Cochrane Library (from inception to September 4th, 2016) were systematically searched for cohort studies assessing the association between PAD and mortality in HD patients. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CI) of all-cause and cardiovascular (CV) mortality using random effects models. Subgroup analyses were conducted to explore the source of heterogeneity.

Results

The search identified 2,973 potentially eligible records and 10 studies (n?=?32,864) were included. Our meta-analysis revealed that PAD significantly increased the risk of all-cause mortality (RR 2.15, 95 % CI 1.67–2.77, n?=?32,864) and CV mortality (RR 2.99, 95 % CI 1.66-5.38, n?=?31,794) in HD patients after multivariate adjustment. Subgroup analyses showed the study design and follow-up time might be two sources of heterogeneity.

Conclusion

PAD may be a prognostic marker of all-cause and CV mortality in HD patients. More attention should be paid to diagnosis and management of PAD in HD patients.