Changes in oxidative nucleic acid modifications and inflammation following one-week treatment with the bile acid sequestrant sevelamer: Two randomised,placebo-controlled trials

AimsSevelamer has been reported to have anti-oxidative and anti-inflammatory effects as well as effects on glycaemic control and plasma lipids. The aim of this study was to determine the effects of one-week treatment with sevelamer on oxidative nucleic acid modifications and inflammation markers.MethodsTwo double-blinded studies including 30 patients with type 2 diabetes (T2D) and 20 healthy individuals were conducted. Participants were randomised to one week of treatment with sevelamer (1600 mg three times daily) or placebo. RNA and DNA oxidation, measured by urinary excretion of 8-oxo-7,8-dihydroguanosine(8-oxoGuo) and (8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxodG), and markers of inflammation were determined before and after the intervention.ResultsIn patients with T2D there was no significant placebo-corrected reduction in 8-oxoGuo or 8-oxodG. However, a reduction in 8-oxoGuo was observed within the group treated with sevelamer (∆8-oxoGuo/creatinine (median[IQR]): −0.04 [−0.24; 0.01] nmol/mmol, p = 0.02). A sevelamer-mediated reduction in interleukin-2 (p = 0.04) and a trend towards reduction in interleukin-6 (p = 0.053) were found in patients with T2D.ConclusionsThis study reveals a potential effect of sevelamer treatment on inflammation and possible oxidative RNA modifications. The potential protective effects of sevelamer in terms of cardiovascular disease in patients with T2D need further investigation.     

Natural history of descending thoracic and thoracoabdominal aortic aneurysms

ObjectivesElucidating critical aortic diameters at which natural complications (rupture, dissection, and death) occur is of paramount importance to guide timely surgical intervention. Natural history knowledge for descending thoracic and thoracoabdominal aortic aneurysms is sparse. Our small early studies recommended repairing descending thoracic and thoracoabdominal aortic aneurysms before a critical diameter of 7.0 cm. We focus exclusively on a large number of descending thoracic and thoracoabdominal aortic aneurysms followed over time, enabling a more detailed analysis with greater granularity across aortic sizes.MethodsAortic diameters and long-term complications of 907 patients with descending thoracic and thoracoabdominal aortic aneurysms were reviewed. Growth rates (instrumental variables approach), yearly complication rates, 5-year event-free survival (Kaplan–Meier), and risk of complications as a function of aortic height index (aortic diameter [centimeters]/height [meters]) (competing-risks regression) were calculated.ResultsEstimated mean growth rate of descending thoracic and thoracoabdominal aortic aneurysms was 0.19 cm/year, increasing with increasing aortic size. Median size at acute type B dissection was 4.1 cm. Some 80% of dissections occurred below 5 cm, whereas 93% of ruptures occurred above 5 cm. Descending thoracic and thoracoabdominal aortic aneurysm diameter 6 cm or greater was associated with a 19% yearly rate of rupture, dissection, or death. Five-year complication-free survival progressively decreased with increasing aortic height index. Hazard of complications showed a 6-fold increase at an aortic height index of 4.2 or greater compared with an aortic height index of 3.0 to 3.5 (P < .05). The probability of fatal complications (aortic rupture or death) increased sharply at 2 hinge points: 6.0 and 6.5 cm.ConclusionsAcute type B dissections occur frequently at small aortic sizes; thus, prophylactic size-based surgery may not afford a means for dissection protection. However, fatal complications increase dramatically at 6.0 cm, suggesting that preemptive intervention before that criterion can save lives.     

Mendelian randomization as a tool to gain insights into the mosaic causes of autoimmune diseases

Autoimmune diseases (ADs) are a broad range of disorders which are characterized by long-term inflammation and tissue damage arising from an immune response against one's own tissues. It is now widely accepted that the causes of ADs include environmental factors, genetic susceptibility and immune dysregulation. However, the exact etiology of ADs has not been fully elucidated to date. Because observational studies are plagued by confounding factors and reverse causality, no firm conclusions can be drawn about the etiology of ADs. Over the years, Mendelian randomization (MR) analysis has come into focus, offering unique perspectives and insights into the etiology of ADs and promising the discovery of potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly dispensed during meiosis, usually irrespective of environmental or lifestyle factors) is used instead of modifiable exposure to explore the link between exposure factors and disease or other outcomes. Therefore, MR analysis can provide a valuable method for exploring the causal relationship between different risk factors and ADs when its inherent assumptions and limitations are fully considered. This review summarized the recent findings of MR in major ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM), focused on the effects of different risk factors on ADs risks. In addition, we also discussed the opportunities and challenges of MR methods in ADs research.     

Simultaneous epicardial–endocardial mapping of the sinus node in humans with structural heart disease: Impact of overdrive suppression on sinoatrial exits

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The Effectiveness of Community Health Workers for CVD Prevention in LMIC

Community health workers (CHW) may be effective in tackling the burden of cardiovascular diseases in low- and middle-income countries (LMIC). This review examines whether CHWs can improve the identification and control of cardiovascular risk factors in LMIC. We searched for studies that used CHW as a basis for cardiovascular risk factor management. Our search yielded 11 articles that targeted cardiovascular risk factor assessment, hypertension, diabetes, smoking, diet and physical activity. There were 4 randomized controlled trials, 3 quasi-experimental studies, 3 cross-sectional studies, and 1 retrospective analysis. Eight studies reported positive results with CHW being able to effectively screen for cardiovascular risk factors, decrease systolic blood pressure, decrease fasting blood glucose, increase quit rates of smoking, decrease weight, and improve diet and physical activity. Our review demonstrates that CHW may be effective in helping tackle the burden of cardiovascular disease in LMIC.     

Succès du traitement par paclitaxel d’une rechute viscérale d’un sarcome de Kaposi après transplantation rénale

We report the observation of a patient who presented with post-transplant Kaposi's sarcoma after a delay of eight months with a dual cutaneous and palatal localisation. The reduction in immunosuppressive treatment and the introduction of Rapamune® allowed good clinical progress initially with regression of the skin lesions. He subsequently presented later a skin relapse with visceral localisation. Chemotherapy was conducted based on weekly paclitaxel infusions allowing partial remission and maintenance of renal graft function with good clinical tolerance.