Cardioprotective role of statins in chronic kidney disease: do we have the answer?

The observational study by Szummer et al. shows that patients with advanced chronic kidney disease (CKD) are treated less with statins after myocardial infarction, even though statins benefit survival in CKD classes 1–4. The study's limitations are obvious, but such a population may be more representative. The results indicate that statins should be used more frequently after myocardial infarction in CKD classes lower than 5, a conclusion supported by the recently presented Study of Heart and Renal Protection (SHARP)

Experimental inoculation of Treponema pedis T A4 failed to induce ear necrosis in pigs

Ear necrosis is a syndrome affecting pigs shortly after weaning and is regarded as an animal welfare issue. The etiology is unknown but Treponema spp., predominantly Treponema pedis, are commonly detected in the lesions. Oral treponemes have been suggested as source of infection, transferred by biting and licking behavior. In this study, five pigs were intradermally inoculated with Treponema pedis strain T A4 with the aim of investigating if this strain would induce ear lesions. Three pigs served as controls. The inoculation was repeated after 29 days, and the study continued for 56 days. Serum samples were collected throughout the study and analyzed by ELISA for IgG antibodies towards T. pedis T A4 lysate. Skin biopsies were taken from the inoculation area at the end of the study. Gingival samples were collected and cultivated for treponemes, for comparison to the inoculation strain and to follow colonisation. The challenged pigs did not develop any clinical signs of infection and no spirochetes were detected in sections from skin biopsies. The number of Treponema-positive gingival samples increased during the study. In the challenge group, IgG towards the bacterial lysate peaked 7 days after each inoculation and decreased rapidly hereafter. In the control group a weak IgG response was observed after the second inoculation, possibly caused by the oral treponemes

Renal transplant dysfunction—importance quantified in comparison with traditional risk factors for cardiovascular disease and mortality

Background. Renal transplant recipients (RTR) mainly die of premature cardiovascular disease. Traditional cardiovascular disease risk factors are prevalent in RTR. Additionally, non-traditional risk factors seem to contribute to the high risk. The impact of renal dysfunction was compared with traditional risk factors for cardiovascular morbidity and mortality in 1052 placebo-treated patients of the ALERT trial. Methods. All patients were on cyclosporine-based immunosuppressive therapy, follow-up was 5-6 years and captured endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke. Results. A calculated 84 µmol/l increase in serum creatinine was needed to double the risk for cardiac death, an increase of 104 µmol/l to double the risk for non-cardiovascular death and an increase of 92 µmol/l to double the risk for all-cause mortality. MACE risk was doubled if serum creatinine was elevated by 141 µmol/l, age was increased by 23 years, or LDL-cholesterol by 2 mmol/l. Diabetes increased the incidences of cardiac death, all-cause mortality, MACE, stroke and non-fatal MI. A serum creatinine increase of ∼130 µmol/l, or ∼20 years increase in age was calculated as similar in risk for cardiac death, all-cause mortality and MACE, and comparable to risk of diabetes in RTR. Conclusion. An increase in serum creatinine of 80-100 µmol/l doubles the risk for cardiac death, non-cardiovascular death and all-cause mortality in RTR. An increase of 130 µmol/l in serum creatinine or ∼20 years increase in age is comparable to risk of diabete

Survey on the occurrence of Brachyspira species and Lawsonia intracellularis in children living on pig farms

The occurrence of Brachyspira species and Lawsonia intracellularis was investigated by PCR analyses of faeces from 60 children living on European pig farms. In addition, 60 other children were included as controls. Two samples were positive for B. aalborgi but B. pilosicoli and L. intracellularis were not demonstrate

Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA Study

Background: Patients on haemodialysis (HD) are at high risk for cardiovascular events, but heart failure and sudden death are more common than atherosclerotic events. The A Study to Evaluate the Use of Rosuvastatinin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) trial was designed to assess the effect of rosuvastatin on myocardial infarction and death from any cardiac cause in 2773 HD patients. We studied predictors of the atherosclerotic cardiovascular events in AURORA. Methods: We readjudicated all deaths and presumed myocardial infarctions according to the criteria used in the Study of Heart and Renal Protection (SHARP); these were specifically developed to separate atherosclerotic from non-atherosclerotic cardiovascular events. The readjudicated atherosclerotic end point included the first event of the following: non-fatal myocardial infarction, fatal coronary heart disease, non-fatal and fatal non-haemorrhagic stroke, coronary revascularization procedures and death from ischaemic limb disease. Stepwise Cox regression analysis was used to identify the predictors of such events. Results: During a mean follow-up of 3.2 years, 506 patients experienced the new composite atherosclerotic outcome. Age, male sex, prevalent diabetes, prior cardiovascular disease, weekly dialysis duration, baseline albumin [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.94–0.99 per g/L increase], high-sensitivity C-reactive protein (HR 1.13; 95% CI 1.04–1.22 per mg/L increase) and oxidized low-density lipoprotein (LDL) cholesterol (HR 1.09; 95% CI 1.03–1.17 per 10 U/L increase) were selected as significant predictors in the model. Neither LDL cholesterol nor allocation to placebo/rosuvastatin therapy predicted the outcome. Conclusions: Even with the use of strict criteria for end point definition, non-traditional risk factors, but not lipid disturbances, predicted atherosclerotic events in HD patients

Randomised clinical trial and meta-analysis: mesalazine treatment in irritable bowel syndrome—effects on gastrointestinal symptoms and rectal biomarkers of immune activity

Background Low-grade immune activation in the gut is a potential treatment target in irritable bowel syndrome (IBS). Aims To determine improvement in IBS symptoms after mesalazine treatment, and the utility of measures of immune activity in the rectal mucosa Methods This was a randomised, double-blind, placebo-controlled, parallel-arm, multicentre trial in subjects with IBS (Rome III criteria), with an eight-week treatment period of mesalazine 2400 mg or plcebo once-daily. The primary endpoint was the global assessment of satisfactory relief of IBS symptoms in ≥50% of weeks during intervention. IBS symptoms were also measured with the IBS severity scoring system; immune activity was measured by mucosal patch technology. A post hoc meta-analysis of randomised placebo-controlled trials of mesalazine in IBS was added. Results Of 181 included patients, 91 received mesalazine and 90 received placebo. The primary endpoint was met by 32 (36%) patients after mesalazine and 27 (30%) after placebo (p = 0.40). There were no differences in response rates related to IBS subtype or post-infection symptom onset. More reduction of abdominal bloating was noted in the mesalazine group (p = 0.02). The meta-analysis showed no effect of mesalazine on IBS symptoms. No mucosal patch technology measure could predict response to mesalazine, and found no differences in the effects of intervention on levels of immune markers. Conclusions Mesalazine is ineffective in reducing IBS symptoms. Rectal measures of immune activity by the mucosal patch technology cannot predict a higher chance of response to mesalazine.publishedVersio

Transesophageal echocardiography in children: New peephole to the heart

Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration

Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation

Background. Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy. Methods. 2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years). Results. In patients starting treatment with fluvastatin 6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (120 months) (P = 0.033). Conclusions. Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart diseas

First isolation of 'Brachyspira hampsonii' from pigs in Europe

Swine dysentery in Europe is classically attributed to Brachyspira hyodysenteriae. However, other Brachyspira species have been increasingly associated with intestinal disorders in pigs. This case report describes the first diagnosis of a “Brachyspira hampsonii” infection in European pigs. In a routine quarantine monitoring protocol, two gilts were presented for necropsy, in which soft watery non-haemorrhagic colonic content was found. Microbial culture from the colonic content and from faecal samples revealed the presence of strongly haemolytic, ring-phenomenon positive spirochetes indicative for Brachyspira hyodysenteriae. A diagnostic commercial PCR could not confirm the presence of B. hyodysenteriae. Phenotypic characterisation and PCRs targeting the 16S rRNA, 23S rRNA, nox, hlyA and tlyA genes of different swine-related Brachyspira spp. were performed. Phylogenetic analysis of sequences of the partial nox and 16S rRNA genes and multi locus sequence typing demonstrated that the isolates in this case were “B. hampsonii” isolates. This case report shows that the diagnosis of infections caused by new, emerging Brachyspira species is not self-evident and that the combination of microbial culture and PCR is recommended, completed with more extensive genotyping if necessary