A Role of the Bile Salt Receptor FXR in Atherosclerosis

This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly via the bile salt receptors FXR and TGR5. Activation of FXR has been shown to improve plasma lipid profiles, whereas Fxr(-/-) mice have increased plasma triglyceride and very-low-density lipoprotein levels. Nevertheless, high-density lipoprotein cholesterol levels are increased in these mice, suggesting that FXR has both anti-and proatherosclerotic properties. Interestingly, there is increasing evidence for a role of FXR in "nonclassical" bile salt target tissues, eg, vasculature and macrophages. In these tissues, FXR has been shown to influence vascular tension and regulate the unloading of cholesterol from foam cells, respectively. Recent publications have provided insight into the antiinflammatory properties of FXR in atherosclerosis. Bile salt signaling via TGR5 might regulate energy homeostasis, which could serve as an attractive target to increase energy expenditure and weight loss. Interventions aiming to increase cholesterol turnover (eg, by bile salt sequestration) significantly improve plasma lipid profiles and diminish atherosclerosis in animal models. Bile salt metabolism and bile salt signaling pathways represent attractive therapeutic targets for the treatment of atherosclerosi

Prolonged antibiotic prophylaxis after pancreatoduodenectomy:systematic review and meta-analysis

Background: Previous studies have reported conflicting results of prolonged antibiotic prophylaxis on infectious complications after pancreatoduodenectomy. This study evaluated the effect of prolonged antibiotics on surgical-site infections (SSIs) after pancreatoduodenectomy. Methods: A systematic review and meta-analysis was undertaken of SSIs in patients with perioperative (within 24 h) versus prolonged antibiotic (over 24 h) prophylaxis after pancreatoduodenectomy. SSIs were classified as organ/space infections or superficial SSI within 30 days after surgery. ORs were calculated using a Mantel–Haenszel fixed-effect model.Results:Ten studies were included in the qualitative analysis, of which 8 reporting on 1170 patients were included in the quantitative analysis. The duration of prolonged antibiotic prophylaxis varied between 2 and 10 days after surgery. Four studies reporting on 782 patients showed comparable organ/space infection rates in patients receiving perioperative and prolonged antibiotics (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, among patients with preoperative biliary drainage (5 studies reporting on 577 patients), organ/space infection rates were lower with prolonged compared with perioperative antibiotics (OR 2.09, 1.43 to 3.07). Three studies (633 patients) demonstrated comparable superficial SSI rates between patients receiving perioperative versus prolonged prophylaxis (OR 1.54, 0.97 to 2.44), as well as in patients with preoperative biliary drainage in 4 studies reporting on 431 patients (OR 1.60, 0.89 to 2.88). Conclusion: Prolonged antibiotic prophylaxis is associated with fewer organ/space infection in patients who undergo preoperative biliary drainage. However, the optimal duration of antibiotic prophylaxis after pancreatoduodenectomy remains to be determined and warrants confirmation in an RCT.</p

Evaluation of systematic assessment of asthma-like symptoms and tobacco smoke exposure in early childhood by well-child professionals: A randomised trial

Objectives: This study aimed to evaluate the effectiveness of systematic assessment of asthma-like symptoms and environmental tobacco smoke (ETS) exposure during regular preventive well-child visits between age 1 and 4 years by wellchild professionals. Methods: Sixteen well-child centres in Rotterdam, the Netherlands, were randomised into 8 centres where the brief assessment form regarding asthma-like symptoms and ETS exposure was used and 8 centres that applied usual care. 3596 and 4179 children (born between April 2002 and January 2006) and their parents visited the intervention and control centres, respectively. At child's age 6 years, physician-diagnosed asthma ever, wheezing, fractional exhaled nitric oxide (FeNO), airway resistance (Rint), health-related quality of life (HRQOL) and ETS exposure at home ever were measured. Linear mixed models were applied. Results: No differences in asthma, wheezing, FeNO, Rint or HRQOL measurements between intervention and control group were found using multilevel regression in an intention-to-treat analysis (p>0.05). Children of whom the parents were interviewed by using the brief assessment form at the intervention well-child centres had a decreased risk on ETS exposure at home ever, compared to children who

Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis:A national survey and case-vignette study

BACKGROUND: Splanchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT. AIM: To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. METHODS: A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey. The threshold to assume group agreement was set at 75%. RESULTS: The response rate was 67% (n = 93). Seventy-one pancreatologists (77%) regularly prescribed therapeutic anticoagulation in case of SVT, and 12 pancreatologists (13%) for narrowing of splanchnic vein lumen. The most common reason to treat SVT was to avoid complications (87%). Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation (90%). Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation (76%) and splenic vein thrombosis as the least preferred location (86%). The preferred initial agent was low molecular weight heparin (LMWH; 87%). In the case vignettes, therapeutic anticoagulation was prescribed for acute portal vein thrombosis, with or without suspected infected necrosis (82% and 90%), and thrombus progression (88%). Agreement was lacking regarding the selection and duration of long-term anticoagulation, the indication for thrombophilia testing and upper endoscopy, and about whether risk of bleeding is a major barrier for therapeutic anticoagulation. CONCLUSION: In this national survey, the pancreatologists seemed to agree on the use of therapeutic anticoagulation, using LMWH in the acute phase, for acute portal thrombosis and in the case of thrombus progression, irrespective of the presence of infected necrosis.</p

Molecular data show conserved DNA locations distinguishing lung cancer subtypes and regulation of immune genes

Introduction: Non-small-cell lung cancer exhibits a range of transcriptional and epigenetic patterns that not only define distinct phenotypes, but may also govern immune related genes, which have a major impact on survival. Methods: We used open-source RNA expression and DNA methylation data of the Cancer Genome Atlas with matched non-cancerous tissue to evaluate whether these pretreatment molecular patterns also influenced genes related to the immune system and overall survival. Results: The distinction between lung adenocarcinoma and squamous c

Overlapping Dialogue : On the Sound Editing in Nashville

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Splanchnic vein thrombosis in necrotizing pancreatitis:a post-hoc analysis of a nationwide prospective cohort

Background: Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. Methods: We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. Results: SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11–40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89–8.51), and younger age (OR 0.94; 95% CI 0.90–0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27–8.23 and OR 7.29; 95% CI 1.31–40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37–4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. Discussion: SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes.</p

Splanchnic vein thrombosis in necrotizing pancreatitis:a post-hoc analysis of a nationwide prospective cohort

Background: Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. Methods: We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. Results: SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11–40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89–8.51), and younger age (OR 0.94; 95% CI 0.90–0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27–8.23 and OR 7.29; 95% CI 1.31–40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37–4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. Discussion: SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes.</p