Long-term outcomes of index cryoballoon ablation or point-by-point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure.

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long-term follow-up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first-line AF ablation approach in the setting of heart failure.

Doege-Potter Syndrome.

Doege-Potter syndrome is a rare paraneoplastic syndrome presenting as a hypoinsulinaemic hypoglycaemia from the ectopic secretion of a prohormone of insulin-like growth factor II (IGF-II) from a solitary fibrous tumour. Surgical resection is curative in the majority of cases. If, however, the diagnosis is not suspected and treatment is delayed, it can lead to hypoxic cerebral injury or death. The underlying tumour can be a benign or malignant pleural tumour but may be present in extrapleural sites. For a diagnosis of Doege-Potter syndrome, symptoms attributable to hypoglycaemia and low blood glucose levels should be present along with the secretion of prohormone IGF-II. We report a case of severe hypoglycaemia in a 76-year-old inpatient admitted for resection of a recurrent left-sided pleural tumour. Investigation revealed true hypoglycaemia and Doege-Potter syndrome was diagnosed. The tumour was completely resected and the patient made a full recovery with no further hypoglycaemic episodes.

Relationships between adipokines, biomarkers of endothelial function and inflammation and risk of type 2 diabetes.

AIMS: Identification of novel biomarkers of diabetes risk help to understand mechanisms of pathogenesis and improve risk prediction. Our objectives were to examine the relationships between adipokines, biomarkers of inflammation and endothelial function and development of type 2 diabetes; and to assess the relevance of including these biomarkers in type 2 diabetes prediction risk models. METHODS: 1345 subjects from the SU.VI.MAX study, who were free of diabetes at baseline and who completed 13 years of follow-up were included in the present analyses. Odds ratios (OR) with 95% confidence intervals (95% CI) of incident type 2 diabetes associated with a 1-SD increase in adiponectin, leptin, C-reactive protein (CRP), soluble intracellular adhesion modecule-1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), E-selectin and monocyte chemoattractant protein-1 (MCP-1) were estimated. Predicitive performances of models including biomarkers were assessed with area under the receiver operating curves (AUC) and integrated discrimination improvement (IDI) statistics. RESULTS: 82 subjects developed type 2 diabetes during follow-up. The risk of developing type 2 diabetes increased with increasing concentrations of leptin (2.04 (1.28;3.26)), sICAM-1 (1.39 (1.08;1.78)) and sVCAM-1 (1.29 (1.01;1.64)). Type 2 diabetes associations with leptin remained significant after adjusting for a combination of biomarkers. Models adjusted for novel biomarkers had improved performance compared to models adjusted for classical risk factors as assessed by IDI, but not by AUC. CONCLUSIONS: Adipokines, biomarkers of inflammation and endothelial function were significantly associated to onset of type 2 diabetes. However their inclusion in predictive scores is not supported by the present study.

A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

Dietary patterns, inflammation and the metabolic syndrome.

AIM: The study of dietary patterns offers a comprehensive, real-life approach towards examining the complex diet and disease relationship. The simultaneous association of dietary patterns with inflammation and the metabolic syndrome (MetS) has not been extensively reviewed. This report reviews the association of dietary patterns with inflammation in the context of the MetS. METHODS: Original English-language research studies with humans were identified via MEDLINE, using inflammation, MetS, whole diets and dietary patterns as keywords. The findings were carefully examined and synthesized along consistent axes. RESULTS: Many observational and a few prospective studies, as well as some randomized controlled trials (RCTs), support an inverse association between a Mediterranean dietary pattern and markers of inflammation. The link is generally independent of traditional cardiovascular disease (CVD) risk factors and weight loss. The few studies that have examined the association between following a healthy dietary pattern, evaluated using various diet quality scores, and inflammation report an inverse association; however, this association was attenuated upon adjusting for CVD risk factors. A Mediterranean dietary pattern has also been associated with a reduced risk of the MetS in several cross-sectional studies and a few prospective studies conducted with healthy people. Few RCTs (lasting 1-2years) have confirmed the benefits of following a Mediterranean diet on MetS risk in obese individuals, in those with the MetS or in those at CVD risk. The evidence, albeit limited, for a link between healthy diets based on other diet quality scores and the MetS supports a similar inverse association for the primary and secondary prevention of the MetS. CONCLUSION: Adhering to healthy diets such as the Mediterranean diet and/or national dietary guidelines can reduce inflammation and the MetS.

Adherence to Mediterranean diet reduces the risk of metabolic syndrome: a 6-year prospective study.

BACKGROUND AND AIMS: Benefits of Mediterranean diet on MetS risk have been suggested, but overall prospective evidence in the general population is limited. For the first time, the prospective association of adherence to Mediterranean diet with the 6-y risk of MetS and its components was evaluated in a large cohort in Europe. METHODS AND RESULTS: Subjects included were participants from the Supplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) study. Adherence to Mediterranean diet was assessed using traditional Mediterranean diet score (MDS), an updated Mediterranean score (MED) and Mediterranean style-dietary pattern score (MSDPS) calculated from at least three 24-h records. In 3232 subjects, the association between Mediterranean diet scores and 6-y risk of MetS was evaluated. The association between Mediterranean scores and MetS components was also estimated. A lower risk of MetS was observed with increasing MED score (P-trend = 0.001) and MDS (P-trend = 0.03) in multivariate models. The adjusted odds ratios (95% Confidence Interval) for MetS risk were 0.47 (0.32-0.69) and 0.50 (0.32-0.77) in subjects in the highest versus lowest tertile of MED score and MDS, respectively. The MED score was inversely associated with waist circumference, systolic blood pressure and triglycerides, and directly associated with HDL-cholesterol. The MDS was negatively associated with waist circumference and triglycerides, and MSDPS was positively associated with HDL-cholesterol. CONCLUSIONS: All Mediterranean diet scores were associated in a potentially beneficial direction with components of MetS or MetS incidence. Our findings support that individuals should be encouraged to follow a Mediterranean dietary pattern for reduction of MetS risk.

Prevention of overweight in preschool children: results of kindergarten-based interventions.

OBJECTIVE: Given the increasing prevalence of pediatric obesity, we evaluated two kindergarten-based strategies for reducing overweight in preschool children in the Haute-Garonne Department in France. METHODS: Kindergartens (n=79) were randomly assigned to one of the two strategies and followed for 2 years. In the first group (Epidémiologie et prévention de l'obésité infantile, EPIPOI-1), parents and teachers received basic information on overweight and health, and children underwent screening to identify those with overweight (body mass index (BMI) > or = 90th percentile) or at risk for overweight (BMI between 75 and 90th percentile), who were then followed up by their physicians. EPIPOI-2 children, in addition, received kindergarten-based education to promote healthy practices related to nutrition, physical activity and sedentary behaviors. Data on control children from non-intervention kindergartens (n=40) were retrieved from medical records at the Division of School Health. RESULTS: At baseline, groups differed significantly on age and school area (underprivileged/not). Owing to a significant interaction between school area and group, analyses were stratified by school area. At baseline, groups did not differ on overweight prevalence and BMI z-scores for any school area. After intervention, prevalence of overweight, BMI z-score and change in BMI z-score were significantly lower in intervention groups compared with controls in underprivileged areas. Using multilevel analysis adjusted for potential confounders, a significant effect on overweight prevalence at the end of the study was noted for EPIPOI-1 in underprivileged areas only (odds ratio and 95% confidence interval: 0.18 (0.07-0.51). In non-underprivileged areas, the gain in BMI z-score was lower in EPIPOI-2 group compared with control and EPIPOI-1. CONCLUSION: Our results suggest that simple measures involving increasing awareness on overweight and health, and periodic monitoring of weight and height with follow-up care when indicated, could be useful to reduce overweight in young children from underprivileged areas. A reinforced strategy with an education component, in addition, may be indicated in children in non-underprivileged areas.

Socioeconomic position, macroeconomic environment and overweight among adolescents in 35 countries.

OBJECTIVE: It is important to understand levels and social inequalities in childhood overweight within and between countries. This study examined prevalence and social inequality in adolescent overweight in 35 countries, and associations with macroeconomic factors. DESIGN: International cross-sectional survey in national samples of schools. SUBJECTS: A total of 11-, 13- and 15-year-olds from 35 countries in Europe and North America in 2001-2002 (N=162 305). MEASUREMENTS: The main outcome measure was overweight based on self-reported height and weight (body mass index cut-points corresponding to body mass index of 25 kg/m(2) at the age of 18 years). Measures included family and school affluence (within countries), and average country income and economic inequality (between countries). RESULTS: There were large variations in adolescent overweight, from 3.5% in Lithuanian girls to 31.7% in boys from Malta. Prevalence of overweight was higher among children from less affluent families in 21 of 24 Western and 5 of 10 Central European countries. However, children from more affluent families were at higher risk of overweight in Croatia, Estonia and Latvia. In Poland, Lithuania, Macedonia and Finland, girls from less affluent families were more overweight whereas the opposite was found for boys. Average country income was associated with prevalence and inequality in overweight when considering all countries together. However, economic inequality as measured by the Gini coefficient was differentially associated with prevalence and socioeconomic inequality in overweight among the 23-high income and 10-middle income countries, with a positive relationship among the high income countries and a negative association among the middle income countries. CONCLUSION: The direction and magnitude of social inequality in adolescent overweight shows large international variation, with negative social gradients in most countries, but positive social gradients, especially for boys, in some Central European countries. Macroeconomic factors are associated with the heterogeneity in prevalence and social inequality of adolescent overweight.

Association of macronutrient intake patterns with being overweight in a population-based random sample of men in France.

AIM: Diet is considered an important modifiable factor in the overweight. The role of macronutrients in obesity has been examined in general in selected populations, but the results of these studies are mixed, depending on the potential confounders and adjustments for other macronutrients. For this reason, we examined the association between macronutrient intake patterns and being overweight in a population-based representative sample of middle-aged (55.1+/-6.1 years) men (n=966), using various adjustment modalities. METHODS: The study subjects kept 3-day food-intake records, and the standard cardiovascular risk factors were assessed. Weight, height and waist circumference (WC) were also measured. RESULTS: Carbohydrate intake was negatively associated and fat intake was positively associated with body mass index (BMI) and WC in regression models adjusted for energy intake and other factors, including age, smoking and physical activity. However, with mutual adjustments for other energy-yielding nutrients, the negative association of carbohydrate intake with WC remained significant, whereas the associations between fat intake and measures of obesity did not. Adjusted odds ratios (95% confidence interval) comparing the highest and lowest quartiles of carbohydrate intake were 0.50 (0.25-0.97) for obesity (BMI>29.9) and 0.41 (0.23-0.73) for abdominal obesity (WC>101.9 cm). CONCLUSION: Consistent negative associations between carbohydrate intake and BMI and WC were seen in this random representative sample of the general male population. The associations between fat intake and these measures of being overweight were attenuated on adjusting for carbohydrate intake. Thus, the balance of carbohydrate-to-fat intake is an important element in obesity in a general male population, and should be highlighted in dietary guidelines.

Metabolic syndrome is associated with markers of subclinical atherosclerosis in a French population-based sample.

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). The relation of MetS with early stages of atherosclerosis, more important from a prevention perspective, has not been evaluated extensively. We examined the association of MetS, using WHO and NCEP definitions, with number of carotid and femoral plaques; carotid intima-media thickness (IMT); pulse wave velocity (PWV) in a random population-based sample of 1153 French adults (35-65 year). Impact of inflammatory factors (C-reactive protein and soluble intercellular adhesion molecule-1) on these parameters was also evaluated. Prevalence of MetS was 14.5 (CI: 12.3-16.0) and 17.5 (CI: 15.1-20.2)%, using NCEP and WHO definitions, respectively. MetS significantly predicted number of plaques, IMT, and PWV after adjustment for traditional risk factors (P<0.05). Inflammatory factors predicted peripheral plaques only. The risk of subclinical atherosclerosis was considerably increased with MetS (P<0.05); odds ratios ranged 1.80-2.15 with NCEP definition, and 1.48-1.97 with WHO definition. Individuals meeting both NCEP and WHO definitions had slightly greater risk of increased plaques, IMT, and PWV. MetS was strongly associated with subclinical atherosclerosis and aortic stiffness, and can be used as a surrogate marker for high CVD risk, deserving aggressive treatment.

Aging, nutrition and immune function.

Aging is usually associated with increase in chronic disease as well as infections and associated morbidity. This is often thought to be secondary to immunosenescence. Whether this decline in immune function with aging is due to the aging process per se or is secondary to poor health, inflammation, and other life style factors particularly suboptimal nutritional status is discussed. Aging is often associated with dysregulation of immune response even among healthy elderly; some of these changes may be secondary to deficiencies of macronutrients (energy and protein) and micronutrients (notably, vitamins B6, B12, and folic acid as well as iron and zinc). Older individuals often have multiple nutrient deficiencies because of physiological, social and economic factors. Nutrient supplementation is often accompanied by an improvement in immune function particularly in those who are nutrient-deficient. The long-term benefits of multinutrient supplements to healthy elderly not at risk for nutrient deficiencies, however, are currently not well-established. Priorities for future research and methodological considerations for future studies are discussed.

Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women.

Aging is often associated with a dysregulation of the immune system. We examined mitogen-stimulated production of interleukin (IL)-2 and proinflammatory cytokines, IL-1beta and IL-6, in apparently healthy and generally well-nourished old versus young women. Subjects were screened for health using the SENIEUR protocol and a panel of laboratory tests for inflammation, as well as for the adequacy of nutritional status using criteria related to undernutrition, and protein, iron, vitamin B(12), and folate status. Young (n=26, age: 20-40 years) and old (n=44, age: 62-88 years) cohorts did not differ on the number of circulating monocytes, granulocytes, B (CD19+) cells, and T (CD3+, CD4+, and CD8+) cells. No differences (P>0.10) were seen between the two age groups in IL-2, IL-1beta and IL-6 levels in whole blood cultures at 48 h after stimulation with PHA (5 mg/l). Furthermore, no age-related differences were noted in the absolute amounts (pg) of IL-1beta and IL-6 after normalizing for circulating monocytes, B cells, or T cells (P>0.10). Similarly, no age-related decline in absolute amount of IL-2 (pg) after normalizing for circulating T cells was noted (P>0.10). Thus, contrary to most previous reports, our results do not support an increase in the production of proinflammatory cytokines IL-1beta and IL-6, and a reduced production of IL-2 with aging when health and nutritional status are maintained. These findings support our previous results of no change in monocyte function and few alterations in acquired immune response in a carefully selected group of healthy and well-nourished elderly women.

CLO vs histology: optimal numbers and site of gastric biopsies to diagnose Helicobacter pylori.

OBJECTIVE: To determine the optimal numbers and sites of biopsies required for diagnosis of Helicobacter pylori by using the CLOtest and comparing the results with those of a routine histological assessment in a district general hospital (DGH) setting. METHODS: A prospective study comparing the sensitivity of the CLOtest containing one antral (CLO 1), two antral (CLO 2) and two antral and one body biopsy (CLO 3), and with histological examination for H. pylori. Consecutive patients undergoing upper gastrointestinal endoscopy (UGIE) at Stepping Hill Hospital, Stockport, UK, who had evidence of gastritis, gastric ulcer, duodenitis or duodenal ulcer were included in the study. RESULTS: Ninety-six patients were biopsied. Forty were positive on at least one of the CLOtests; of these, nine were negative on histological assessment. Of these nine, two were positive on all CLOtests and seven were positive only on CLO 3. One was positive on histology but negative on all CLOtests. This study showed that CLO 3 was more sensitive than CLO 1 (P = 0.004), CLO 2 (P = 0.016) and histology (P = 0.022). There was no significant difference between CLO 1 and CLO 2 (P = 0.500), CLO 1 and histology (P = 1.000), CLO 2 and histology (P = 1.00). CONCLUSION: We feel that in a busy clinical setting, taking two antral and one body biopsy in a single CLOtest is superior to routine histological assessment for the detection of H. pylori, with resulting cost saving.

Iron status and stores decline with age in Lewis rats.

In the context of a larger study examining the interaction of vitamin A (VA) status and age on immune function, we examined age-related changes in hematologic and iron status variables in male Lewis rats. Animals were fed a nutritionally adequate purified diet containing either 0.35 (marginal), 4.0 (control) or 50 (supplemented) mg retinol equivalents (as retinyl palmitate) per kg of diet from the time of weaning until killing at 8-10 (middle-aged) or 20-22 (old) mo of age. Neither VA nor VA and age interaction effects were significant for most iron variables examined. After controlling for body weight, old rats had significantly lower hemoglobin, hematocrit and plasma iron than middle-aged rats. This decrease in hematologic and transport iron variables was not accompanied by a shift of iron into other storage compartments. Old rats also had significantly lower total iron content and iron concentration in liver, spleen and bone marrow. Hemosiderin iron in marrow smears correlated significantly (r = 0.43-0.76, P: < 0.05) with chemical estimates of iron in storage, transport and functional pools. Old rats also tended to have less stained iron in femur marrow smears. Thus, body iron in functional, transport and storage compartments, namely the liver, spleen and bone marrow, were significantly lower in old than in middle-aged rats. Although iron stores and status are usually considered to increase with advancing age, our data show a consistent pattern of lower hematologic and storage iron variables in old than in middle-aged Lewis rats. Future research is indicated to understand the biology and functional consequences of the observed age-associated decline in body iron.

Effects of erythropoietin therapy on iron absorption in chronic renal failure.

The effect of erythropoietin administration on the absorption of dietary and therapeutic iron was examined in patients with anemia of chronic renal failure on maintenance hemodialysis. Absorption from test meals tagged extrinsically with iron 55, iron 59, or both was determined 2 weeks later by using incorporated red blood cell radioactivity and whole body counting. In an initial study of food iron absorption, the effect of initiating erythropoietin therapy was determined by measuring the absorption of heme and nonheme iron before and 2 weeks after the administration of 64 U/kg body weight erythropoietin (range, 46-85 U/kg body weight) three times weekly. Absorption of heme iron increased 1.6-fold from 18.6% to 30.1% (P < .05), and nonheme iron increased 3.7-fold from 1.3% to 4.9% (P < .01) after erythropoietin therapy. In a second study therapeutic iron absorption was evaluated at baseline and after erythropoietin administration (63 U/kg body weight (range, 48-74 U/kg body weight) three times weekly). The absorption of 50 mg of iron as ferrous sulfate increased 2.4-fold from 3.8% to 9.4% (P < .05) when given without food and 4.2-fold from 1.4% to 5.9% (P < .05) when given with food after erythropoietin administration. After adjusting for changes in iron stores with serum ferritin after erythropoietin therapy, the enhanced erythropoiesis associated with erythropoietin therapy increased absorption about 2-fold, which was similar to the response observed previously in normal subjects. In a final study we examined the absorption of therapeutic iron during the steadystate phase of erythropoietin therapy after an erythroid response to erythropoietin had occurred. The absorption of 50 mg of iron was lower than that occurring with the initiation of erythropoietin therapy at 2.2% when given alone and 1.3% when taken with food. We conclude that iron absorption with or without erythropoietin stimulation is unimpaired in patients with chronic renal failure.