Lumbar spinal fusion surgery outcomes in a cohort of injured workers in the Victorian workers' compensation system.

BACKGROUND: Lumbar spinal fusion (LSF) outcomes for workers' compensation patients are worse than for the general population. The objectives were to examine the long-term work capacity, opioid prescription and mental health outcomes of injured workers who have undergone LSF surgery in Victoria, Australia, and to identify demographic and pre- and post-operative characteristics associated with these outcomes. METHODS: Retrospective study of 874 injured workers receiving elective LSF from 2008 to 2016 in the Victorian workers' compensation system. WorkSafe Victoria's claims data were used to infer outcomes for recovery. Association of demographics, pre-surgery and surgery variables with outcomes were modelled using multivariate multinomial logistic regression analyses. RESULTS: Twenty-four months after LSF surgery, 282 (32.3%) of the 874 injured workers had substantial work capacity, 388 (44.4%) were prescribed opioids, and 330 (37.8%) were receiving mental health treatment. Opioid prescription and limited work capacity before surgery were independent strong predictors of opioid prescription, reduced work capacity and mental health treatment 24 months after LSF. Pre-operative mental health treatment was associated with the use of mental health treatment at 24 months. Other predictors for poor outcomes included a greater than 12-month duration from injury to surgery, LSF re-operation and common law or impairment benefit lodgement before surgery. CONCLUSION: An association between pre-operative factors and post-operative outcomes after LSF in a Victorian workers' compensation population was identified, suggesting that pre-operative status may influence outcomes and should be considered in LSF decisions. The high opioid use indicates that opioid management before and after surgery needs urgent review.

Chemerin is a novel adipokine associated with obesity and metabolic syndrome.

Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.

Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balance.

To identify genes involved in the central regulation of energy balance, we compared hypothalamic mRNA from lean and obese Psammomys obesus, a polygenic model of obesity, using differential display PCR. One mRNA transcript was observed to be elevated in obese, and obese diabetic, P. obesus compared with lean animals and was subsequently found to be increased 4-fold in the hypothalamus of lethal yellow agouti (A(y)/a) mice, a murine model of obesity and diabetes. Intracerebroventricular infusion of antisense oligonucleotide targeted to this transcript selectively suppressed its hypothalamic mRNA levels and resulted in loss of body weight in both P. obesus and Sprague Dawley rats. Reductions in body weight were mediated by profoundly reduced food intake without a concomitant reduction in metabolic rate. Yeast two-hybrid screening, and confirmation in mammalian cells by bioluminescence resonance energy transfer analysis, demonstrated that the protein it encodes interacts with endophilins, mediators of synaptic vesicle recycling and receptor endocytosis in the brain. We therefore named this transcript Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 encodes a large proline-rich protein that is expressed predominantly in the brain and is highly conserved between species. Together these data suggest that SGIP1 is an important and novel member of the group of neuronal molecules required for the regulation of energy homeostasis.

Identification of hypothalamic genes implicated in the development of obesity in Psammomys obesus using differential display PCR.

The hypothalamus is a key central controller of energy homeostasis and is the source and/or site of action of many neuropeptides involved in this process. The aim of this study was to isolate hypothalamic genes differentially expressed between lean and obese Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes. Differential display PCR was used to compare hypothalamic gene expression profiles of lean and healthy, obese and hyperinsulinemic, and obese, diabetic P. obesus in both the fed and fasted states. We conducted differential display with 180 separate primer combinations to amplify approximately 9,000 expressed transcripts. Sixty differentially expressed bands were excised. Taqman PCR was performed on 36 of these transcripts to confirm differential gene expression in a larger sample population. Of these 36 transcripts, 9 showed homology to known genes, and 27 were considered to be novel sequences. Gene expression profiles for two of these genes are presented here. In conclusion, differential display PCR was successfully used to isolate several transcripts that may be involved in the central regulation of energy balance. We are currently conducting numerous studies to further investigate the role of these genes in the development of obesity in P. obesus.

The hepatitis B virus and common mutants.

Most biological systems have developed complex mechanisms to maintain the stability of their genetic information. Exceptions to this include viruses that can undergo rapid and substantial genetic sequence changes and alterations. The hepatitis B virus (HBV) has evolved a unique life cycle resulting in the production of enormous viral loads during active replication without actually directly killing the infected cell. Because the virus uses reverse transcription to copy its DNA genome, mutant viral genomes are frequently found. Particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antivirals), readily select out these escape mutants. It is still not known which particular viral mutations or combination of mutations directly affects the clinical presentation of the liver disease, the nature of the viral persistence, or the course and outcome of chronic infection. Further studies are needed to identify the pathogenic basis for the selection of these mutants. Such research should help improve the basic understanding of this unique virus-host relationship and provide new strategies for complete control of HBV infections.

Tanis: a link between type 2 diabetes and inflammation?

Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P = 0.010) and insulin levels (P = 0.004) and in direct proportion with plasma triglyceride concentrations (P = 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P = 0.006) as well as in several other cell types (P = 0.001-0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.