A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

Background: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.

Methods: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037).

Modelling and Simulation of the Combined Use of IABP and Impella as a Rescue Procedure in Cardiogenic Shock: An Alternative for Non-Transplant Centres?

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and the Impella 2.

The Impact of Ferric Derisomaltose on Cardiovascular and Noncardiovascular Events in Patients With Anemia, Iron Deficiency, and Heart Failure With Reduced Ejection Fraction.

Background: In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial.

Method And Results: IRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men).

Investigation and management of Wilson's disease: a practical guide from the British Association for the Study of the Liver.

Wilson's disease is an autosomal-recessive disorder of copper metabolism with hepatic, neurological, psychiatric, ophthalmological, haematological, renal, and rheumatological manifestations. Making a diagnosis can be challenging given that no single test can confirm or exclude the disease, and diagnostic delays are common. Treatment protocols vary and adverse effects, including paradoxical neurological worsening, can occur.

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

Background & Aims: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.

Methods: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included.

Understanding the uptake of new hip replacement implants in the UK: a cohort study using data from the National Joint Registry for England and Wales.

Objectives: Primary: describe uptake of new implant components (femoral stem or acetabular cup/shell) for total hip replacements (THRs) in the National Joint Registry for England and Wales (NJR). Secondary: compare the characteristics of: (a) surgeons and (b) patients who used/received new rather than established components.

Design: Cohort of 618 393 primary THRs performed for osteoarthritis (±other indications) by 4979 surgeons between 2008 and 2017 in England and Wales from the NJR.

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.

A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association; however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD).

Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement.

Objectives: To assess the Gram-positive-specific antibiotic linezolid and the broad-spectrum antibiotic tigecycline for use in local antibiotic delivery via antibiotic-loaded bone cement.

Methods: Linezolid and tigecycline were added to Biomet bone cement at varying concentrations. Antibiotic elution over 1 week was quantified by HPLC-MS.

London Trauma Conference 2015 : London, UK, 8-11 December 2015.

I1: Trauma, Pre-hospital and Cardiac Arrest Care 2015 Pascale Avery, Leopold Salm, Flora Bird A1: Retrospective evaluation of HEMS ‘Direct to CT’ protocol Anja Hutchinson, Ashley Matthies, Anthony Hudson, Heather Jarman A2 Rush hour – Crush hour: temporal relationship of cyclist vs. HGV trauma admissions. A single site observational study Maria Bergman Nilsson, Tom Konig, Nigel Tai A3 Semiprone position endotracheal intubation during continuous cardiopulmonary resuscitation in drowned children with regurgitation: a case report and experimental manikin study Espen Fevang, Børge Hognestad, Håkon B.

Bone Disease after Kidney Transplantation.

Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high- or low-turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism.

Impact of month of birth on the development of autoimmune thyroid disease in the United Kingdom and Europe.

Context: Viral/bacterial infection is proposed as a trigger for the autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies in European Caucasian AITD subjects found higher birth rates in the autumn/winter, suggesting those born in the autumn/winter experience increased viral/bacterial exposure after birth, impacting upon immune system development and predisposing to AITD later in life.

Objective: Month of birth effects were investigated in three independent European Caucasian AITD datasets.

Hirudin anticoagulation allows more rapid determination of P2Y₁₂ inhibition by the VerifyNow P2Y12 assay.

VerifyNow (VN) P2Y12 is a point-of-care assay used to assess response to P2Y12 inhibitors. Sodium citrate (citrate) is the standard anticoagulant used for this assay but requires a pre-incubation period. Hirudin is an alternative anticoagulant for platelet function studies that maintains physiological divalent cation levels.

Acute hepatic injury following treatment of a long-acting insulin analogue overdose necessitating urgent insulin depot excision.

Background: A 26-year-old man with Type 1 diabetes presented with an overdose of 4800 units of the long-acting insulin analogue, glargine (Lantus). Glucose supplementation of approximately 800 g/day was associated with acute hepatic injury.

Methods: On day 4, a depot of insulin was excised from the patient's abdominal wall; this was followed by a reduction in his glucose requirements and improvement in liver function.

Potentials and limitations of low-concentration contrast medium (150 mg iodine/ml) in CT pulmonary angiography.

Aim: To assess the feasibility of producing diagnostic multidetector computed tomography (MDCT) pulmonary angiography with low iodine concentration contrast media (150 mg iodine/ml) in patients with suspected acute pulmonary embolism.

Materials And Methods: Ninety-five randomized patients underwent MDCT (64 row) pulmonary angiography with 100ml iopromide either at low concentration (LC) of 150 mg iodine/ml (n=45) or high concentration (HC) of 300 mg iodine/ml (n=50), delivered at the rate of 5 ml/s via a power injector. Two experienced radiologists, blinded to the concentration used, subjectively assessed the diagnostic quality and confidence using a four-point scale [1=poor (not diagnostic), 2=satisfactory, 3=good, 4=excellent].

Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study.

OBJECTIVE A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy. RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks).

Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial.

Objective: The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type 1 diabetes mellitus (T1DM).

Methods: This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged > or = 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA1c) value < or = 11.0% at screening.

Evaluation of ChloraPrep (2% chlorhexidine gluconate in 70% isopropyl alcohol) for skin antisepsis in preparation for blood culture collection.

Objectives: Blood culture contamination is a significant adverse event. This study evaluated whether using ChloraPrep (2% alcoholic chlorhexidine) instead of 70% isopropyl alcohol wipes reduced contamination rates on two Medical Assessment Units (MAU1 and MAU2).

Methods: ChloraPrep was introduced for 2 to 3-month intervention periods, initially on MAU1 and MAU2 and subsequently on MAU1 only.

FTY720 reduces extracellular matrix expansion associated with ischemia-reperfusion induced injury.

Background: Ischemia-reperfusion (IR) is one of the strongest nonimmune factors associated with the development of chronic allograft nephropathy (CAN). This effect is often exacerbated by immunosuppressive medications, most notably cyclosporine. Although traditionally the macrophage was thought to stimulate fibroblast activity in CAN, recent evidence supports a role for lymphocytes.

Reduction of ischemia-reperfusion injury in the rat kidney by FTY720, a synthetic derivative of sphingosine.

Background: The current shortage of organ donors has led many centers to use marginal and nonheart-beating donors (NHBDs). Recent research has implicated the infiltration of lymphocytes as an important mediator of ischemia-reperfusion injury (IRI). FTY720 is an immunosuppressant that promotes lymphocyte sequestration into lymph nodes.

Common sequence variations in the P2Y12 and CYP3A5 genes do not explain the variability in the inhibitory effects of clopidogrel therapy.

The efficacy of the platelet P2Y12 receptor antagonist clopidogrel, which undergoes cytochrome-mediated metabolism to its active form, shows marked inter-individual variability. We investigated whether polymorphic variations in the P2Y12 gene, which have been linked to platelet aggregation phenotypes, or the cytochrome P450 3A5 gene 6986G > A polymorphism, which largely determines CYP3A5 expression, influence the response to clopidogrel therapy. Fifty-four patients listed for elective percutaneous coronary intervention were studied using ADP-induced optical aggregometry, whole-blood single platelet counting (WBSPC) aggregometry, and flow-cytometric analysis of platelet P-selectin expression and platelet-monocyte conjugate formation.

Utility of a whole blood single platelet counting assay to monitor the effects of tirofiban in patients with acute coronary syndromes scheduled for coronary intervention.

This study aimed to establish the utility of a whole-blood single-platelet counting (WBSPC) assay, a measure of microaggregation, in monitoring the effects of tirofiban, comparing this with optical aggregometry (OA) and the Ultegra TRAP cartridge system (UTC), measures of macroaggregation. Fifty-nine patients with acute coronary syndrome scheduled for coronary angiography +/- angioplasty were studied. WBSPC assay (ADP 0.

Glycoprotein IIb/IIIa and P2Y12 receptor antagonists yield additive inhibition of platelet aggregation, granule secretion, soluble CD40L release and procoagulant responses.

Glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists, including abciximab and tirofiban, are administered concurrently with clopidogrel, a P2Y12 antagonist, and aspirin in some patients undergoing percutaneous coronary intervention. We studied the effects of, and interactions between, abciximab, tirofiban, aspirin and the P2Y12 antagonist cangrelor on platelet aggregation, alpha and dense granule secretion and procoagulant responses in vitro. Blood was obtained from healthy volunteers.