Increased Mortality Amongst Patients Sustaining Neck of Femur Fractures as In-Patients in a Trauma Centre.

PurposeNeck of Femur (NOF) fracture is a common injury with high mortality that all orthopaedic departments must contend with [1]. The aim of this study was to report incidence and mortality of NOF fractures occurring while patients were being admitted to hospital for other conditions.MethodsA retrospective review was performed of all NOF fracture admissions between 1(st) of Jan 2010 to 31(st) of Dec 2012 at a University Hospital trauma centre. Fractures were divided according to the location where the fracture occurred, either in the community (acute NOF) or in-hospital (in-hospital NOF).ResultsIn-hospital mortality, 30-day, 90-day and 1 year mortality were recorded. There were 1086 patients in the acute NOF fracture group (93.9%) and 70 patients in the in-hospital group (6.1%) over three years. The odds of inpatient death was 2.25 times higher for inpatient NOFs (p=0.012). 86% of all in-hospital NOF fractures occurred on medical and rehabilitation wards. NOF fractures result in increased mortality and morbidity.ConclusionAll patients in hospital should be assessed to identify those at high risk of falls and implemented measures should be taken to reduce this

Delayed Denosumab Injections and Bone Mineral Density Response: An Electronic Health Record-based Study.

CONTEXT: Discontinuation of denosumab leads to a rapid reversal of its therapeutic effect. However, there are no data regarding how unintended delays or missed injections of denosumab impact bone mineral density (BMD) response. OBJECTIVE: We examined the association of delays in injections of denosumab with BMD change. DESIGN:We used electronic medical records from two academic hospitals from 2010 to 2017. PARTICIPANTS: Patients over 45 years of age and used at least two doses of 60mg denosumab. Denosumab adherence was evaluated by the medication coverage ratio (MCR). Good adherence corresponds to a dosing interval ≤7 months (defined by MCR ≥93%), moderate adherence corresponds to an interval of 7-10 months (MCR 75-93%), and poor adherence corresponds to an interval ≥10 months (MCR ≤74%). OUTCOME MEASURES: Annualized percent BMD change from baseline at the lumbar spine, total hip, and femoral neck. RESULTS:We identified 938 denosumab injections among 151 patients; the mean (SD) age was 69 (10) years, and 95% were female. Patients with good adherence had an annualized BMD increase of 3.9% at the lumbar spine, compared with patients with moderate (3.0%) or poor adherence (1.4%, p for trend 0.002). Patients with good adherence had an annualized BMD increase of 2.1% at the total hip, compared with patients with moderate (1.3%) or poor adherence (0.6%, p for trend 0.002). CONCLUSIONS: A longer interval between denosumab injections is associated with suboptimal BMD response at both spine and total hip. Strategies to improve the timely administration of denosumab in real-world settings are needed

Autoantibodies to Osteoprotegerin are Associated with Low Hip Bone Mineral Density and History of Fractures in Axial Spondyloarthritis: A Cross-Sectional Observational Study

Osteoporosis is a recognised complication of axial spondyloarthritis (axSpA) and is thought to be due to functional impairment and the osteoclast-activating effects of proinflammatory cytokines. The development of autoantibodies to OPG (OPG-Ab) has been associated with severe osteoporosis and increased bone resorption in rheumatoid arthritis. In this study, we screened for the presence of OPG-Ab in axSpA and reviewed their clinical significance. We studied 134 patients, recruited from two centres in the United Kingdom. Their mean age was 47.5 years and 75% were male. Concentrations of OPG-Ab were related to bone mineral density (BMD) and fracture history using linear and logistic regression models adjusting for age, gender, disease duration and activity, body mass index and bisphosphonate use. We detected OPG-Ab in 11/134 patients (8.2%). Femoral neck and total hip BMD were significantly reduced in OPG-Ab positive patients (0.827 vs. 0.967 g/cm2, p = 0.008 and 0.868 vs. 1.028 g/cm2, p = 0.002, respectively). Regression analysis showed that the presence of OPG-Ab was independently associated with total hip osteopenia (ORadj 24.2; 95% CI 2.57, 228) and history of fractures (ORadj 10.5; 95% CI 2.07, 53.3). OPG-Ab concentration was associated with total hip BMD in g/cm2 (ß = −1.15; 95% CI −0.25, −0.04). There were no associations between OPG-Ab concentration and bone turnover markers, but free sRANKL concentrations were lower in OPG-Ab-positive patients (median 0.04 vs. 0.11 pmol/L, p = 0.050). We conclude that OPG-Ab are associated with hip BMD and fractures in axSpA suggesting that they may contribute to the pathogenesis of bone loss in some patients with this condition

Enhancing Production of Bio-Isoprene Using Hybrid MVA Pathway and Isoprene Synthase in E. coli

The depleting petroleum reserve, increasingly severe energy crisis, and global climate change are reigniting enthusiasm for seeking sustainable technologies to replace petroleum as a source of fuel and chemicals. In this paper, the efficiency of the MVA pathway on isoprene production has been improved as follows: firstly, in order to increase MVA production, the source of the “upper pathway” which contains HMG-CoA synthase, acetyl-CoA acetyltransferase and HMG-CoA reductase to covert acetyl-CoA into MVA has been changed from Saccharomyces cerevisiae to Enterococcus faecalis; secondly, to further enhance the production of MVA and isoprene, a alanine 110 of the mvaS gene has been mutated to a glycine. The final genetic strain YJM25 containing the optimized MVA pathway and isoprene synthase from Populus alba can accumulate isoprene up to 6.3 g/L after 40 h of fed-batch cultivation

Sodium-glucose cotransporter 1 inhibition and gout:Mendelian randomisation study

Abstract Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce serum urate, but their efficacy depends on renal function which is often impaired in people with gout. SGLT1 is primarily expressed in the small intestine and its inhibition may be a more suitable therapeutic target. We aimed to investigate the association of genetically proxied SGLT1i with gout risk, serum urate levels and cardiovascular safety using Mendelian randomisation (MR). Methods: Leveraging data from a genome-wide association study of 344,182 individuals in the UK Biobank, we identified a missense variant in the SLC5A1 gene that associated with glycated haemoglobin (HbA1c) to proxy SGLT1i. Outcome genetic data comprised 13,179 gout cases and 750,634 controls, 457,690 individuals for serum urate levels, and up to 977,323 individuals for cardiovascular safety outcomes. We applied the Wald ratio method and investigated potential genetic confounding using colocalization. Results: The rs17683430 missense variant was selected to instrument SGLT1i. Genetically proxied SGLT1i was associated with 75% reduction in gout risk (OR 0.25; 95%CI 0.06, 0.99; p = 0.048) and 32.0 μmol/L reduction in serum urate (95%CI −56.7, −7.3; p = 0.01), per 6.7 mmol/mol reduction in HbA1c. SGLT1i was associated with increased levels of low-density lipoprotein cholesterol (0.37 mmol/L; 95%CI 0.17, 0.56; p = 0.0002) but not risk of coronary heart disease, stroke, or chronic kidney disease. Colocalization did not suggest that results are attributable to genetic confounding. Conclusion: SGLT1 inhibition may represent a novel therapeutic option for preventing gout in people with or without comorbid diabetes. Randomised trials are needed to formally investigate efficacy and safety