Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy.

Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed multivariate genome-wide association studies (GWAS) for a correlation network of 11 circulating cytokines, then combined our results in meta-analysis. We identified a total of eight loci significantly associated with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously. In addition, conditional analyses revealed a further four secondary signals at three known cytokine loci. Integration, through the use of Bayesian colocalization analysis, of publicly available GWAS summary statistics with the cytokine network associations revealed shared causal variants between the eight cytokine loci and other traits; in particular, cytokine network variants at the ABO, SERPINE2, and ZFPM2 loci showed pleiotropic effects on the production of immune-related proteins, on metabolic traits such as lipoprotein and lipid levels, on blood-cell-related traits such as platelet count, and on disease traits such as coronary artery disease and type 2 diabetes.

Emergency department presentations with mammalian bite injuries: risk factors for admission and surgery.

OBJECTIVES: The incidence of animal bite injuries in Australia is high. There is currently no established method for reliably predicting whether a patient with a bite injury will require admission to hospital or surgery. DESIGN: A retrospective audit of mammalian bite injuries at seven major hospitals in Melbourne, Victoria, over a 2-year period. The associations between each predictor and outcome of interest were analysed with univariate and multiple regression analyses. SETTING: Seven major hospitals in Melbourne, Victoria: the Alfred Hospital, Austin Hospital, Frankston Hospital, Monash Medical Centre, Royal Melbourne Hospital, St Vincent's Hospital and Western Hospital. PARTICIPANTS: Patients presenting to emergency departments with mammalian bite injuries. MAIN OUTCOME MEASURES: Hospital admission, intravenous antibiotic therapy, surgery, reoperation, readmission. RESULTS: We identified 717 mammalian bite injuries. The mean age of the patients was 36.5 years (median, 34 years; range, 0-88 years), with an equal number of males and females. The overall rate of hospital admission was 50.8%, and the mean length of stay was 2.7 days. Intravenous antibiotics were administered in 46% of cases; surgery was undertaken in 43.1% of cases. The re-operation rate was 4.5%, the re-admission rate was 3%. CONCLUSIONS: Our study provides a detailed epidemiological analysis of animal bite injuries at seven major hospitals in Victoria. Risk factors for hospitalisation and surgery may assist in identifying patients who require admission and surgical intervention.

Axillary Artery Injury Associated with Proximal Humeral Fractures: Review of Long-Term Vascular, Orthopedic, and Neurologic Outcomes.

BACKGROUND: Fracture and dislocation of the proximal humerus is common. It is associated with a number of vascular, neurologic, and orthopedic complications; these include brachial plexopathy and avascular necrosis (AVN) of the humeral head. These complications are rare but can potentially cause severe disability to patients; however, they remain poorly described in the literature. To describe vascular, orthopedic, and neurologic outcomes after axillary artery repair, in patients with proximal humeral fractures or dislocations. METHODS: We conducted a retrospective review of patients admitted to 2 tertiary trauma centers in Victoria, Australia, with fracture or dislocation of the proximal humerus and associated axillary artery injury. Patients were selected according to guidelines for trauma call or alert and the presence of high-risk mechanism of injury. Data on vascular, orthopedic, and neurologic complications were collected. RESULTS: Twenty-one patients were identified. Injury to the first part of the axillary artery was noted in 11 patients (52%). Brachial plexus exploration was performed in 17 patients (81%). Four patients (19%) underwent nerve repair. Long-term neurologic recovery was universally poor. Major orthopedic complications included AVN of the humeral head, delayed union, and the need for prosthesis or arthrodesis. Eleven patients (52%) received upper limb fasciotomy. Five patients (24%) underwent delayed secondary upper limb amputation. CONCLUSIONS: There was an unusually high rate of injuries to the first part of the axillary artery. Close clinical observation is recommended for such patients. AVN of the humeral head and brachial plexopathy remain significant and debilitating complications.