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1.  Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response 
EMBO Molecular Medicine  2015;7(5):547-561.
The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.
PMCID: PMC4492816  PMID: 25770819
bone; CCL2; fracture; inflammation; TNF
2.  Strategies to secure surgical research funding: fellowships and grants 
JRSM Open  2014;5(1):2042533313505512.
Innovation and advances in surgery are entirely dependent on research. Fellowships and grants are the principal means by which surgical research projects are funded. However, these are scarce and highly competitive. This article offers guidance through the application process for the aspiring academic surgeon. Approaching the application in a timely and structured manner, seeking advice from current and previous award-holders and members of review panels, and obtaining preliminary data are key ingredients to success.
PMCID: PMC4012679  PMID: 25057362
research; fellowship; funding; grant; surgery
3.  Optimal functional outcome measures for assessing treatment for Dupuytren’s disease: a systematic review and recommendations for future practice 
Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment.
A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures.
Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years.
There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes.
PMCID: PMC3637830  PMID: 23575442
Dupuytren’s disease; Hand function; Outcome measures; Systematic review
4.  Soft Tissue Reconstruction of Open Fractures of the Lower Limb: muscle versus fasciocutaneous flaps 
Plastic and reconstructive surgery  2012;130(2):284e-295e.
Early vascularized soft tissue closure has long been recognized to be essential in achieving eventual infection free union. The question of whether muscle or fasciocutaneous tissue is superior in terms of promoting fracture healing remains unresolved. Here we review the experimental and clinical evidence for the different tissue types and advocate that the biological role of flaps should be included as a key consideration during flap selection.
PMCID: PMC3408595  PMID: 22842425
5.  Alarmins: awaiting a clinical response 
The Journal of Clinical Investigation  2012;122(8):2711-2719.
Alarmins are endogenous molecules that are constitutively available and released upon tissue damage and activate the immune system. Current evidence indicates that uncontrolled and excessive release of alarmins contributes to the dysregulated processes seen in many inflammatory and autoimmune conditions, as well as tumorigenesis and cancer spread. Conversely, alarmins have also been found to play a major role in the orchestration of tissue homeostasis, including repair and remodeling in the heart, skin, and nervous system. Here, we provide an update and overview on alarmins, highlighting the areas that may benefit from this clinical translation.
PMCID: PMC3408740  PMID: 22850880
6.  Extracranial-intracranial bypass of the bilateral anterior cerebral circulation using a thoracodorsal axis artery-graft 
Asian Journal of Neurosurgery  2012;7(4):203-205.
Bilateral extracranial-intracranial (EC-IC) bypass-grafting of the cerebral circulation is uncommon. We report a case of anterior cerebral artery EC-IC bypass using the thoracodorsal axis artery-graft. The bifurcation of the thoracodorsal axis allows bypass of both anterior hemispheres, while matching appropriate small-vessel dimensions.
PMCID: PMC3613643  PMID: 23559988
Artery-graft; bilateral EC-IC bypass; thoracodorsal graft; unclippable intracranial aneurysm
7.  MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis 
Arthritis and rheumatism  2009;60(3):686.
A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness.
Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined.
MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix.
MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA.
PMCID: PMC2819053  PMID: 19248098
MT1-MMP; synovial pannus; rheumatoid arthritis

Results 1-9 (9)