HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant Recipients

High-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B–depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan–Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.     

High friction moments in large hard‐on‐hard hip replacement bearings in conditions of poor lubrication

Disappointing clinical results for large diameter metal replacement bearings for the hip are related to compromised lubrication due to poor cup placement, which increases wear as well as friction moments. The latter can cause overload of the implant–bone interfaces and the taper junction between head and stem. We investigated the influence of lubrication conditions on friction moments in modern hip bearings. Friction moments for large diameter metal and ceramic bearings were measured in a hip simulator with cup angles varying from 0° to 60°. Two diameters were tested for each bearing material, and measurements were made in serum and in dry conditions, representing severely compromised lubrication. Moments were lower for the ceramic bearings than for the metal bearings in lubricated conditions, but approached those for metal bearings at high cup inclination. In dry conditions, friction moments increased twofold to 12 Nm for metal bearings. For ceramic bearings, the increase was more than fivefold to over 25 Nm. Although large diameter ceramic bearings demonstrate an improvement in friction characteristics in the lubricated condition, they could potentially replicate problems currently experienced due to high friction moments in metal bearings once lubrication is compromised. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 807–813, 2013     

Penetrance of the C28Y/C282Y genotype of the HFE gene

OBJECTIVE: Hereditary hemochromatosis is a common genetic disease caused by accumulation of iron in the body. Most cases are homozygous for the C282Y mutation in the HFE gene, but only a minority of homozygotes will ever suffer from clinical hemochromatosis. Estimates of the penetrance of the C282Y/C282Y genotype vary greatly. The purpose of this study was to estimate the penetrance using a stringent definition, i.e. liver cirrhosis. MATERIAL AND METHODS: The results from previous phenotypic population screening for hereditary hemochromatosis were combined with findings in hospital databases in order to estimate the number of C282Y homozygotes with and without liver cirrhosis in a Norwegian county. The penetrance of the C282Y/C282Y genotype was estimated as the fraction of C282Y homozygotes with liver cirrhosis. We also calculated the expected number of male C282Y homozygotes with liver cirrhosis using figures for age-specific accumulated risk. RESULTS: The prevalence of liver cirrhosis in male homozygotes is between 3.4% and 5.0%. This figure is compatible with an accumulated risk of liver cirrhosis that increases from 0.2% at 35 years to about 10% at 65 years of age. In female homozygotes, the prevalence of liver cirrhosis is 0.3%. CONCLUSIONS: A small but significant number of Norwegian male C282Y homozygotes will contract liver cirrhosis if their hemochromatosis is not diagnosed and treated in time. The penetrance is much lower in women than in men.     

Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis: a nationwide case-control study in Denmark

OBJECTIVE: To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs). METHODS: To address these issues, a nationwide case-control study was conducted in Denmark during 2002-2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex- and age-matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk. RESULTS: Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA (OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects were observed, with markedly increased risks of anti-CCP-positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154), heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE noncarriers who were not exposed to these environmental risk factors. CONCLUSION: Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.     

Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma

OBJECTIVE: Helicobacter pylori infection is an established risk factor for non-cardia gastric adenocarcinoma. Infection with H. pylori strains harbouring the cagA pathology island may augment this association. H. pylori infection may at the same time reduce the risk for oesophageal carcinoma. However, prospective data on the association between CagA seropositivity and gastric or oesophageal carcinomas are limited. The purpose of this study was to investigate whether CagA seropositivity among H. pylori seropositive subjects is associated with gastric or oesophageal carcinomas. MATERIAL AND METHODS: A nested case-control study was performed in the Malm? Preventive Medicine cohort consisting of 32,906 middle-aged subjects. Tumour cases were identified by the Swedish National Cancer Registry. The Western blot method Helicoblot 2.1 was used to detect H. pylori and CagA seropositivity. RESULTS: Non-cardia gastric adenocarcinoma was associated with H. pylori seropositivity, odds ratio 17.8 (95% CI: 4.2-74.8; 67 cases). The odds ratio for CagA seropositivity among H. pylori seropositive subjects was 9.7 (95% CI: 1.5-infinity). No significant associations were found between cardia gastric adenocarcinoma and H. pylori or CagA seropositivity among H. pylori seropositive subjects; odds ratios were 1.5 (95% CI: 0.51-4.8) and 2.7 (95% CI: 0.38-infinity), respectively (24 cases). Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma were not significantly associated with H. pylori seropositivity or with CagA seropositivity among H. pylori seropositive subjects; the odds ratios associated with oesophageal adenocarcinoma were 0.46 (95% CI: 0.07-2.6) and 0.38 (95% CI: 0.02-24), respectively. Corresponding odds ratios for oesophageal squamous cell carcinoma were 0.44 (95% CI: 0.15-1.2; 37 cases) and 2.0 (95% CI: 0.24-infinity), respectively. CONCLUSIONS: CagA seropositivity among H. pylori seropositive subjects is a risk factor for non-cardia gastric adenocarcinoma.