International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Evidence-based surgery

Every year an estimated 234 million major surgical procedures are undertaken worldwide. In 2009�10, 4.8 million hospital admissions involved surgical input in England alone, and around 4 in 5 adults are likely to have an operation in their lifetime. Despite these enormous numbers, lack of objective evidence for the indications and benefits (or otherwise) of surgical procedures is often lacking. Lack of robust research into surgical disease and treatments has been criticized. Less than 5% of national funding for health research involves surgery. This seems surprising as inappropriate surgical treatments can be hazardous for the patient and costly to the health care system. The demand for evidence-based clinical practice is increasing, driven by public and professional expectations. The scarcity of high-quality studies across many different fields of surgery has led to ambiguity in the management of many common surgical conditions with widely varying clinical outcomes in different geographical areas. Surgical treatments are costly and need to be justified not only on clinical benefit, but on their cost effectiveness compared to other treatments. Several approaches have been adopted to evaluate evidence of benefit for surgical treatments. This article outlines these and their application in a clinical setting. The components of evidence-based medicine and the GRADE method of evaluating quality of evidence are explored. The importance of taking into consideration cost effectiveness and patient attitudes to treatment are also discussed.</p

Managing hypercholesterolemia and its correlation with carotid plaque morphology in patients undergoing carotid endarterectomy

Purpose: hypercholesterolemia is a critical problem in patients with carotid atherosclerosis. The adequacy of attention to lipid risk factors in patients with carotid stenosis awaiting carotid endarterectomy (CEA) has rarely been studied. We also assessed patient awareness of hypercholesterolemia and carotid plaque morphology.Methods: a prospective study was conducted of 141 consecutive patients admitted electively for CEA. Each patient’s medical history was taken. Plasma cholesterol concentrations were determined. Plaque histology was scored according to American Heart Association criteria and their modification.Results: of patients who were aware of their hypercholesterolemia and who were receiving treatment, 28.6% had total cholesterol levels ?5 mmol/L. Among those patients who had been told that they had no problem with hypercholesterolemia, 32.5% had plasma cholesterol concentrations ?5 mmol/L. Among those patients who had never had their plasma cholesterol measured, 48.4% had total cholesterol levels ?5 mmol/L. Patients in this last group tended to have more severe types of plaque pathology than those in other groups (12.9% plaque rupture).Conclusions: hypercholesterolemia does not seem to be well managed in patients awaiting CEA

Sex difference in composition of plaques of patients undergoing carotid endarterectomy

Our study aimed to examine the hypothesis that women have more stable plaques (a lower proportion of lipid component and a higher proportion of fibrous tissue) compared to men. Plaque specimens of 141 consecutive carotid endarterectomy patients (60 females and 81 males) were studied. Medical histories were recorded and the plasma concentrations of cholesterol and inflammatory markers were measured. We found that plaques from females had significantly less lipid than those from males (p = .01): the mean percentage of plaque lipid for women and men was 47.8% and 58.2%, respectively. Plaques from females had more fibrous tissue than those from men (p = .02): the mean percentage of fibrous tissue for women and men was 38.8% and 29.8%, respectively. This study concluded that the histology of carotid artery plaques from women appears to be more stable than that of those from men. <br/

Managing hypercholesterolemia and its correlation with carotid plaque morphology in patients undergoing crotid endarterectomy

Purpose: hypercholesterolemia is a critical problem in patients with carotid atherosclerosis. The adequacy of attention to lipid risk factors in patients with carotid stenosis awaiting carotid endarterectomy (CEA) has rarely been studied. We also assessed patient awareness of hypercholesterolemia and carotid plaque morphology.Methods: a prospective study was conducted of 141 consecutive patients admitted electively for CEA. Each patient’s medical history was taken. Plasma cholesterol concentrations were determined. Plaque histology was scored according to American Heart Association criteria and their modification.Results: of patients who were aware of their hypercholesterolemia and who were receiving treatment, 28.6% had total cholesterol levels ?5 mmol/L. Among those patients who had been told that they had no problem with hypercholesterolemia, 32.5% had plasma cholesterol concentrations ?5 mmol/L. Among those patients who had never had their plasma cholesterol measured, 48.4% had total cholesterol levels ?5 mmol/L. Patients in this last group tended to have more severe types of plaque pathology than those in other groups (12.9% plaque rupture).Conclusions: hypercholesterolemia does not seem to be well managed in patients awaiting CEA

Management of median arcuate ligament syndrome in patients who require pancreaticoduodenectomy

Pancreaticoduodenectomy is the standard treatment for localised neoplasms of the pancreatic head. The operation can be performed safely in specialist units but good outcome is compromised if postoperative blood flow to the liver and biliary tree is inadequate. Coeliac artery occlusion with blood supply to the liver arising from the superior mesenteric artery via the gastroduodenal artery is difficult to recognise, especially intraoperatively. Recognition of absent hepatic artery pulsation after occlusion of the gastroduodenal artery opens a dilemma: should the resection be abandoned or should vascular reconstruction be undertaken, adding risk to an already complex procedure? We describe two cases with a resectable pancreatic endocrine tumour in which coeliac artery occlusion caused by median arcuate ligament compression was identified from cross-sectional imaging and reconstructions. We highlight two different strategies to correct the vascular insufficiency and allow safe pancreatic resection