Serum Oxidized Albumin and Cardiovascular Mortality in Normoalbuminemic Hemodialysis Patients: A Cohort Study

Background

Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients.

Methods

We conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients’ survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA.

Results

After adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD.

Conclusions

Serum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.     

Magnesium Modifies the Cardiovascular Mortality Risk Associated with Hyperphosphatemia in Patients Undergoing Hemodialysis: A Cohort Study

Background

In vitro studies have shown inhibitory effects of magnesium (Mg) on phosphate-induced calcification of vascular smooth muscle cells, raising the possibility that maintaining a high Mg level may be useful for reducing cardiovascular risks of patients with hyperphosphatemia. We examined how serum Mg levels affect the association between serum phosphate levels and the risk of cardiovascular mortality in patients undergoing hemodialysis.

Methods

A nationwide register-based cohort study was conducted using database of the Renal Data Registry of the Japanese Society for Dialysis Therapy in 2009. We identified 142,069 patients receiving in-center hemodialysis whose baseline serum Mg and phosphate levels were available. Study outcomes were one-year cardiovascular and all-cause mortality. Serum Mg levels were categorized into three groups (lower, <2.7 mg/dL; intermediate, ≥2.7, <3.1 mg/dL; and higher, ≥3.1 mg/dL).

Results

During follow-up, 11,401 deaths occurred, out of which 4,751 (41.7%) were ascribed to cardiovascular disease. In multivariable analyses, an increase in serum phosphate levels elevated the risk of cardiovascular mortality in the lower- and intermediate-Mg groups, whereas no significant risk increment was observed in the higher-Mg group. Moreover, among patients with serum phosphate levels of ≥6.0 mg/dL, the cardiovascular mortality risk significantly decreased with increasing serum Mg levels (adjusted odds ratios [95% confidence intervals] of the lower-, intermediate-, and higher-Mg groups were 1.00 (reference), 0.81 [0.66–0.99], and 0.74 [0.56–0.97], respectively.). An interaction between Mg and phosphate on the risk of cardiovascular mortality was statistically significant (P = 0.03).

Conclusion

Serum Mg levels significantly modified the mortality risk associated with hyperphosphatemia in patients undergoing hemodialysis.     

Dietary Patterns and Clinical Outcomes in Hemodialysis Patients in Japan: A Cohort Study

Background & Objectives

Little is known about actual dietary patterns and their associations with clinical outcomes in hemodialysis patients. We identified dietary patterns in hemodialysis patients in Japan and examined associations between dietary patterns and clinical outcomes.

Design, setting, participants, measurements

We used data from 3,080 general-population participants in the Hisayama study (year 2007), and data from 1,355 hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study (JDOPPS: years 2005–2007). Food intake was measured using a brief self-administered diet-history questionnaire (BDHQ). To identify food groups with the Hisayama population data, we used principal components analysis with Promax rotation. We adjusted the resulting food groups for total daily energy intake, and then we used those adjusted food-group scores to identify dietary patterns in the JDOPPS patients by cluster analysis (Ward’s method). We then used Cox regression to examine the association between dietary patterns and a composite of adverse clinical outcomes: hospitalization due to cardiovascular disease or death due to any cause.

Results

We identified three food groups: meat, fish, and vegetables. Using those groups we then identified three dietary patterns: well-balanced, unbalanced, and other. After adjusting for potential confounders, we found an association between an unbalanced diet and important clinical events (hazard ratio 1.90, 95% C.I. 1.19–3.04).

Conclusions

Hemodialysis patients whose diet was unbalanced were more likely to have adverse clinical outcomes. Thus hemodialysis patients might benefit not only from portion control, but also from a diet that is well-balanced diet with regard to the food groups identified here as meat, fish, and vegetables.     

Aldosterone and Mortality in Hemodialysis Patients: Role of Volume Overload

Background

Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality.

Methods

We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL).

Results

Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25–0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33−0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69–3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28−4.15) in the absence of volume overload.

Conclusions

The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.     

Serum Zn Levels and Cu/Zn Ratios Worsen in Hemodialysis Patients,Implying Increased Cardiovascular Risk: A 2-Year Longitudinal Study

The objective of this study was to analyze serum Zn and Cu concentrations and Cu/Zn ratios in 116 hemodialysis patients (HPs) over a 2-year longitudinal study at four time points (6-month intervals). The relation exerted on these values by 26 biochemical and nutritional indexes, the age and drug consumption of the patients, and the etiology of their disease were also evaluated. A healthy control group (n?=?50) was also studied. Mean serum Zn concentrations were lower (p?=?0.009) and the Cu/Zn ratios higher (p?=?0.009) in HPs than in controls. Serum Cu levels in HP did not differ to those of controls. At all four sampling times, the mean serum Zn levels and Cu/Zn ratios were lower and higher, respectively, in HPs than in the controls. There was a significant reduction in serum Zn levels and an increase in Cu concentrations and Cu/Zn ratios in HPs from the second to the fourth sampling. Serum Zn levels of the HPs diminish with age older than 50 years. Serum Cu levels were significantly higher in patients consuming antihypercalcemic or anti-infarction drugs, whereas serum Cu levels and Cu/Zn ratios were significantly lower in those treated with diuretics. Diminished Zn levels were negatively correlated with low-density lipoprotein (LDL) cholesterol in HPs; however, enhanced Cu/Zn ratios were positively correlated with total cholesterol and LDL cholesterol. Both findings indicate an increased cardiovascular risk. We conclude that this study contributes the first evidence of a correlation between marked dyslipidemia and worsened Cu/Zn ratios in HPs, implying an increased risk of diseases associated with elevated oxidative stress, inflammation, and depressed immune function, such as cardiovascular diseases.     

Resistance to Erythropoiesis Stimulating Agents in Patients Treated with Online Hemodiafiltration and Ultrapure Low-Flux Hemodialysis: Results from a Randomized Controlled Trial (CONTRAST)

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; {"type":"clinical-trial","attrs":{"text":"NCT00205556","term_id":"NCT00205556"}}NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months'' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [−0.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (−2.52% [−4.72 to −0.31]; P = 0.02 and −49 ng/mL [−103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [−0.4 to 14.5]; P = 0.06).In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00205556","term_id":"NCT00205556"}}NCT00205556     

Healthy Dietary Interventions and Lipoprotein (a) Plasma Levels: Results from the Omni Heart Trial

Background

Increased lipoprotein(a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Studies of dietary interventions on changes in Lp(a) are sparse. We aimed to compare the effects of three healthy dietary interventions differing in macronutrient content on Lp(a) concentration.

Methods

Secondary analysis of a randomized, 3-period crossover feeding study including 155 (89 blacks; 66 whites) individuals. Participants were given DASH-type healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each diet.

Results

Compared to baseline, all interventional diets increased mean Lp(a) by 2 to 5 mg/dl. Unsat Fat increased Lp(a) less than Prot with a difference of 1.0 mg/dl (95% CI, −0.5, 2.5; p = 0.196) in whites and 3.7 mg/dl (95% CI, 2.4, 5.0; p<0.001) in blacks (p-value between races = 0.008); Unsat Fat increased Lp(a) less than Carb with a difference of −0.6 mg/dl, 95% CI, −2.1, 0.9; p = 0.441) in whites and −1.5 mg/dl (95% CI, −0.2, −2.8; p = 0.021) in blacks (p-value between races = 0.354). Prot increased Lp(a) more than Carb with a difference of 0.4 mg/dl (95% CI, −1.1, 1.9; p = 0.597) in whites and 2.2 mg/dl (95%CI, 0.9, 3.5; p = 0.001) in blacks (p-value between races = 0.082).

Conclusion

Diets high in unsaturated fat increased Lp(a) levels less than diets rich in carbohydrate or protein with greater changes in blacks than whites. Our results suggest that substitutions with dietary mono- and polyunsaturated fatty acids in healthy diets may be preferable over protein or carbohydrates with regards to Lp(a).

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00051350","term_id":"NCT00051350"}}NCT00051350     

Effects of Clopidogrel on Mortality,Cardiovascular and Bleeding Outcomes in Patients with Chronic Kidney Disease - Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.

Methods

In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m². The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.

Results

Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.

Conclusion

Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD.     

The Prognostic Value of Family History for the Estimation of Cardiovascular Mortality Risk in Men: Results from a Long-Term Cohort Study in Lithuania

Aim

To evaluate the additional prognostic value of family history for the estimation of cardiovascular (CVD) mortality risk in middle-aged urban Lithuanian men.

Methods

The association between family history of CVD and the risk of CVD mortality was examined in a population-based cohort of 6,098 men enrolled during 1972–1974 and 1976–1980 in Kaunas, Lithuania. After up to 40 years of follow-up, 2,272 deaths from CVD and 1,482 deaths from coronary heart disease (CHD) were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for CVD and CHD mortality.

Results

After adjustment for traditional CVD risk factors, the HR for CVD mortality was 1.24 (95% CI 1.09–1.42) and for CHD mortality 1.20 (1.02–1.42) in men with first-degree relatives having a history of myocardial infarction (MI), compared to men without positive family history. A significant effect on the risk of CVD and CHD mortality was also observed for the family history of sudden cardiac death and any CVD. Addition of family history of MI, sudden death, and any CVD to traditional CVD risk factors demonstrated modest improvement in the performance of Cox models for CVD and CHD mortality.

Conclusions

Family history of CVD is associated with a risk of CVD and CHD mortality significantly and independently of other risk factors in a middle-aged male population. Addition of family history to traditional CVD risk factors improves the prediction of CVD mortality and could be used for identification of high-risk individuals.     

Gender Differences in 1-Year Clinical Characteristics and Outcomes after Stroke: Results from the China National Stroke Registry

Background

Previous reports have shown inconsistent results on clinical outcomes between women and men after stroke, and little is known about gender differences on outcomes in Chinese post-stroke patients. The aim of this study was to explore whether there were gender differences on clinical characteristics and outcomes in Chinese patients after ischemic stroke by using the data from the China National Stroke Registry (CNSR).

Methods and Findings

Out of 12,415 consecutively recruited patients with acute ischemic stroke in the CNSR from 2007 to 2008, 11,560 (93.1%) patients were followed up for 12 months. Their clinical characteristics and outcomes on death, recurrence, and dependency were recorded. The multivariate logistic regression was performed to determine whether there were gender differences in these outcomes. Women were older than men at baseline (67.9 vs. 64.0 years, P<0.001). Women had a higher mortality, recurrence rate, and dependency rate at 3, 6, and 12 months than men, but after adjusting for age, history of diabetes, pre-stroke dependency, stroke severity, in-hospital complications, and other confounders, there were no statistically significant differences in gender on mortality and recurrence rate at 3, 6, and 12 months; and dependency rate at 3, and 6 months. However, the dependency rate at 12 months remained significantly higher in women (odds ratio, 1.24; 95% confidence interval, 1.06 to 1.45).

Conclusions

There are many differences in clinical characteristics between women and men after ischemic stroke in China. Compared with men, women are more dependent at 12 months after stroke. This difference still exists after controlling the potential confounders.     

The Activities of Some Energy-Metabolising Enzymes in Nonsynaptic (Free) and Synaptic Mitochondria Derived from Selected Brain Regions

Abstract: The enzyme complement of two different mitochondrial preparations from adult rat brain has been studied. One population of mitochondria (synaptic) is prepared by the lysis of synaptosomes, the other (nonsynaptic or free) by separation from homogenates. These populations have been prepared from distinct regions of the brain: cortex, striatum, and pons and medulla oblongata. The following enzymes have been measured: pyruvate dehydrogenase (EC 1.2.4.1), citrate synthase (EC 4.1.3.7), NAD-linked isocitrate dehydrogenase (EC 1.1.1.41), NADP-linked isocitrate dehydrogenase (EC 1.1.1.42), fumarase (EC 4.2.1.2), NAD-linked malate dehydrogenase (EC 1.1.1.37), D-3-hydroxybutyrate dehydrogenase (EC 1.1.1.30), and mitochondrially bound hexokinase (EC 2.7.1.1) and creatine kinase (EC 2.7.3.2). The nonsynaptic (free) mitochondria show higher enzyme specific activities in the regions studied than the corresponding values recorded for the synaptic mitochondria. The significance of these observations is discussed in the light of the different metabolic activities of the two populations of mitochondria and the compartmentation of the metabolic activities of the brain.     

Change in Body Size and Mortality: Results from the Melbourne Collaborative Cohort Study

Background

The association between change in weight or body mass index, and mortality is widely reported, however, both measures fail to account for fat distribution. Change in waist circumference, a measure of central adiposity, in relation to mortality has not been studied extensively.

Methods

We investigated the association between mortality and changes in directly measured waist circumference, hips circumference and weight from baseline (1990–1994) to wave 2 (2003–2007) in a prospective cohort study of people aged 40–69 years at baseline. Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for confounding variables, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for change in body size in relation to mortality from all causes, cardiovascular disease and cancer.

Results

There were 1465 deaths (109 cancer, 242 cardiovascular disease) identified during an average 7.7 years of follow-up from 21 298 participants. Compared to minimal increase in body size, loss of waist circumference (HR: 1.26; 95% CI: 1.09–1.47), weight (1.80; 1.54–2.11), or hips circumference (1.35; 1.15–1.57) were associated with an increased risk of all-cause mortality, particularly for older adults. Weight loss was associated with cardiovascular disease mortality (2.40; 1.57–3.65) but change in body size was not associated with obesity-related cancer mortality.

Conclusion

This study confirms the association between weight loss and increased mortality from all-causes for older adults. Based on evidence from observational cohort studies, weight stability may be the recommended option for most adults, especially older adults.     

Elevated Levels of Circulating DNA in Cardiovascular Disease Patients: Metagenomic Profiling of Microbiome in the Circulation

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An expanding body of evidence supports the role of human microbiome in the establishment of CVDs and, this has gained much attention recently. This work was aimed to study the circulating human microbiome in CVD patients and healthy subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD patients (n = 80) than in healthy controls (n = 40). More specifically, the relative levels of circulating bacterial DNA and the ratio of 16S rRNA/β-globin gene copy numbers were higher in the circulation of CVD patients than healthy individuals. In addition, we found a higher circulating microbial diversity in CVD patients (n = 3) in comparison to healthy individuals (n = 3) by deep shotgun sequencing. At the phylum level, we observed a dominance of Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that in healthy controls, where Proteobacteria was predominantly enriched, followed by Actinobacteria. The circulating virome in CVD patients was enriched with bacteriophages with a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages in contrast to that in healthy individuals, where a relatively greater abundance of eukaryotic viruses dominated by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the release of bacterial and viral DNA elements in the circulation could play a major role leading to elevated circDNA levels in CVD patients. The increased circDNA levels could be either the cause or consequence of CVD incidence, which needs to be explored further.     

Genetics of Plasma Soluble Receptor for Advanced Glycation End-Products and Cardiovascular Outcomes in a Community-based Population: Results from the Atherosclerosis Risk in Communities Study

Plasma soluble Receptor for Advanced Glycation End-products (sRAGE) is a strong marker of vascular outcomes although evidence on the direction of association is mixed. Compared to whites, blacks have lower levels of sRAGE. We hypothesized that genetic determinants of sRAGE would help clarify the causal role of sRAGE and the black-white difference in sRAGE levels. We conducted a genome-wide analysis of sRAGE in whites and blacks from the Atherosclerosis Risk in Communities Study. Median plasma sRAGE levels were lower in blacks than whites (728 vs. 1067 pg/ml; P<0.0001). The T (vs. C) allele of rs2070600, a missense variant in AGER, the gene encoding RAGE, was associated with approximately 50% lower sRAGE levels in both whites (N = 1,737; P = 7.26x10^-16; minor allele frequency (MAF) = 0.04) and blacks (N = 581; P = 0.02; MAF = 0.01). In blacks, the T (vs. C) allele of rs2071288, intronic to AGER, was associated with 43% lower sRAGE levels (P = 2.22x10^-8; MAF = 0.10) and was nearly absent in whites. These AGER SNPs explained 21.5% and 26% of the variation in sRAGE in blacks and whites, respectively, but did not explain the black-white difference in sRAGE. These SNPs were not significantly associated with incident death, coronary heart disease, diabetes, heart failure, or chronic kidney disease in whites (N = 8,130–9,017) or blacks (N = 2,293–2,871) (median follow up ~20 years). We identified strong genetic determinants of sRAGE that did not explain the large black-white difference in sRAGE levels or clearly influence risk of clinical outcomes, suggesting that sRAGE may not be a causal factor in development of these outcomes.     

Xylem Transfer of Organic Solutes inSantalum albumL. (Indian Sandalwood) in Association with Legume and Non-legume Hosts

Indian sandalwood (Santalum album), a commercially importantroot hemi-parasitic angiosperm, was partnered singly in potculture with one of three nitrogen-fixing legumes or a eucalypthost. Xylem (tracheal) sap of stems of host and parasite andethanolic extracts of endophytic tissue of haustoria of theparasite were analysed for amino acids, organic acids and sugarsto determine which sets of solutes were available to and obtainedby the parasite from different hosts. There were high concentrationsof asparagine, followed by glutamate, aspartate and     

The Korean Clinical Research Center for End-Stage Renal Disease Study Validates the Association of Hemoglobin and Erythropoiesis-Stimulating Agent Dose with Mortality in Hemodialysis Patients

Background

Anemia is an important risk factor for mortality in hemodialysis (HD) patients. However, higher hemoglobin (Hb) is not necessarily better, as seen in several studies. This study aimed to validate the clinical use of an Hb target of 10–11 g/dL in Korean HD patients.

Methods

A total of 1,276 HD patients from the Clinical Research Center (CRC) for End-Stage Renal Disease (ESRD) were investigated in a prospective observational study. Cox proportional hazard analysis was conducted for each category of time-dependent Hb level and erythropoiesis-stimulating agent (ESA) dose, with subgroup analysis stratified by age and diabetes status.

Results

Using a reference Hb level of 10–11 g/dL, the hazard ratios (HRs) of death were 5.12 (95% confidence interval [CI], 2.62–10.02, P <0.05) for Hb level <9.0 g/dL, and 2.03 (CI, 1.16–3.69, P <0.05) for Hb level 9.0–10.0 g/dL, after adjustment for multiple clinical variables. However, an Hb level ≥11 g/dL was not associated with decreased mortality risk. In an adjusted model categorized by Hb and ESA dose, the risk of death at an Hb level <10 g/dL and a higher dose of ESA (≥126 U/kg/week) had an HR of 2.25 (CI, 1.03–4.92, P <0.05), as compared to Hb level 10–11 g/dL and a lower dose of ESA. In subgroup analysis, those older than 65 years or who were diabetic had greater risk for mortality only in Hb category <9.0 g/dL. However, there was no significant interaction between age or diabetes status and Hb.

Conclusion

Using CRC-ESRD data, we validated the association between Hb and ESA dose and mortality in Korean HD patients. The clinical practice target of an Hb of 10–11 g/dL before the new KDIGO guideline era seems reasonable considering its survival benefit in HD patients.     

Serum Levels of Caspase-Cleaved Cytokeratin-18 and Mortality Are Associated in Severe Septic Patients: Pilot Study

Objective

Apoptosis is increased in sepsis. Cytokeratin 18 (CK-18), a protein of the intermediate filament group present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptosis. Circulating levels of CCCK-18 have scarcely been explored in septic patients. In one study with 101 severe septic patients, the authors reported higher serum CCCK-18 levels in non-survivors than in survivors; however, the sample size was too small to demonstrate an association between serum CCCK-18 levels and early mortality and whether they could be used as a biomarker to predict outcomes in septic patients. Thus, these were the objectives of this study with a large series of patients.

Methods

We performed a prospective, multicenter, observational study in six Spanish Intensive Care Units with 224 severe septic patients. Blood samples were collected at the time that severe sepsis was diagnosed to determine serum levels of CCCK-18, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10. The end point was 30-day mortality.

Results

Non-surviving patients (n = 80) showed higher serum CCCK-18 levels (P<0.001) than survivors (n = 144). Multiple logistic regression analysis showed that serum CCCK-18 levels>391 u/L were associated with 30-day survival (Odds ratio = 2.687; 95% confidence interval = 1.449–4.983; P = 0.002), controlling for SOFA score, serum lactic acid levels and age. Kaplan-Meier survival analysis showed that the risk of death in septic patients with serum CCCK-18 levels >391 u/L was higher than in patients with lower values (Hazard Ratio = 3.1; 95% CI = 1.96–4.84; P<0.001). Serum CCCK-18 levels were positively associated with serum levels of IL-6 and lactic acid, and with SOFA and APACHE scores.

Conclusions

The major novel finding of our study, the largest cohort of septic patients providing data on circulating CCCK-18 levels, was that serum CCCK-18 levels are associated with mortality in severe septic patients.     

The Immediate Results of Operations for Duodenal Ulcer: A Comparative Study of the Morbidity and Mortality of Vagotomy and Pyloroplasty versus Subtotal Gastrectomy

Immediate postoperative results of vagotomy and pyloroplasty were compared with those of subtotal gastrectomy. Ulcer recurrence rate and the long-term complications of the two procedures were not studied. Age and sex distribution, and preoperative indications in the two groups of patients were almost identical. Vagotomy and pyloroplasty has gradually superseded subtotal gastrectomy at St. Michael''s Hospital, Toronto. One hundred and seventy vagotomy and drainage procedures were compared with 173 subtotal gastric resections performed over a five-year period. There were 39 postoperative complications and five deaths in the subtotal gastrectomy group, an overall mortality of 2.8% and an elective mortality of 2.4%. In the vagotomy and pyloroplasty group there were 31 postoperative complications and two deaths, an overall mortality of 1.2% and an elective mortality of zero. Vagotomy and pyloroplasty is a relatively safe procedure, associated with fewer complications, shorter hospital stay and a lower mortality than subtotal gastrectomy.