2024 |
King KL, Dewar DC, Briggs GD, Jones M, Balogh ZJ, 'Postinjury multiple organ failure in polytrauma: more frequent and potentially less deadly with less crystalloid.', Eur J Trauma Emerg Surg, 50 131-138 (2024) [C1]
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2023 |
Murphy NJ, Graan D, Briggs GD, Balogh ZJ, 'Acute minimally invasive bone grafting of long bone fractures to reduce the incidence of fracture non-union', Medical Hypotheses, 178 (2023) [C1]
Diaphyseal fractures of the femur and tibia are a frequent consequence of trauma and are most often managed with intramedullary nailing. Although outcomes from these fractures are... [more]
Diaphyseal fractures of the femur and tibia are a frequent consequence of trauma and are most often managed with intramedullary nailing. Although outcomes from these fractures are generally perceived as good, it is estimated that 7 to 14% of people with tibial and femoral shaft fractures progress to non-union and an even greater proportion suffer delayed union, which causes substantial health and economic burdens both for patients and health services. Compared to those whose fractures unite within the normal timeframe, patients suffering delayed union or non-union suffer more pain, worse functional outcomes, greater psychological disability and longer amounts of time off work. In response to non-union, invasive and costly secondary procedures such as exchange nailing, supplementary fixation and/or bone grafting are commonly required. We hypothesise that performing acute autologous bone grafting at the time of the primary intramedullary nailing procedure would reduce the incidence of fracture delayed union and non-union for tibial and femoral shaft fractures. The autologous cancellous bone retrieved during reaming with intramedullary nailing is usually discarded. We propose a minimally invasive surgical technique to transplant the retrieved intramedullary reamings to the fracture site during the primary fracture fixation. Autologous cancellous bone grafting is the gold standard for management of fracture non-union, and works by providing osteoprogenitor cells, an osteoconductive scaffold, and growth factors to the fracture site, where they are crucial for fracture healing. Proprietary biological products have also been developed that aim to replicate the results from bone grafting. Although autologous cancellous bone grafting is a proven and robust technique for the treatment of atrophic fracture non-union, it has not been widely studied in the acute management of femoral and tibial shaft fractures. The proposed hypothesis is amenable to testing in randomized clinical trials. If found to be effective in reducing rates of delayed union and non-union with minimal adverse events, this method could be adopted on a large scale, potentially transforming acute management of long bone fractures, and improving patient outcomes from these injuries.
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Nova |
2023 |
Rogers E, Pothugunta S, Kosmider V, Stokes N, Bonomini L, Briggs GD, et al., 'The Diagnostic, Therapeutic and Prognostic Relevance of Neutrophil Extracellular Traps in Polytrauma', Biomolecules, 13 1625-1625 [C1]
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Nova |
2023 |
Amico F, Efird JT, Briggs GD, Lott NJ, King KL, Hirani R, Balogh ZJ, 'Association between Blood Donor Demographics and Post-injury Multiple Organ Failure after Polytrauma', Annals of Surgery, 277 E170-E174 (2023) [C1]
Objective: To test the hypothesis that blood donor demographics are associated with transfused polytrauma patients' post-injury multiple organ failure (MOF) status. Summary o... [more]
Objective: To test the hypothesis that blood donor demographics are associated with transfused polytrauma patients' post-injury multiple organ failure (MOF) status. Summary of Background Data: Traumatic shock and MOF are preventable causes of death and post-traumatic hemorrhage is a frequent indication for transfusion. The role of blood donor demographics on transfusion recipients is not well known. Methods: A log-linear analysis accounting for the correlated structure of the data based on our prospective MOF database was utilized. Tests for trend and interaction were computed using a likelihood ratio procedure. Results: A total of 229 critically injured transfused trauma patients were included, with 68% of them being males and a mean age of 45 years. On average 10 units of blood components were transfused per patient. A total of 4379 units of blood components were donated by donors aged 46 years on average, 74% of whom were males. Blood components used were red blood cells (47%), cryoprecipitate (29%), fresh frozen plasma (24%), and platelets (less than 1%). Donor-recipient sex mismatched red blood cells transfusions were more likely to be associated with MOF (P = 0.0012); fresh frozen plasma and cryoprecipitate recipients were more likely to experience MOF when transfused with a male (vs female) component (P = 0.0014 and <0.0001, respectively). Donor age was not significantly associated with MOF for all blood components. Conclusions: Blood components donor sex, but not age, may be an important factor associated with post-injury MOF. Further validation of our findings will help guide future risk mitigation strategies specific to blood donor demographics.
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Nova |
2022 |
Giles T, Weaver N, Varghese A, Way TL, Abel C, Choi P, Briggs GD, 'Acute kidney injury development in polytrauma and the safety of early repeated contrast studies: A retrospective cohort study', JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, 93 872-881 (2022) [C1]
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Nova |
2022 |
Briggs GD, Gelzinnis S, Meakes S, King KL, Balogh ZJ, 'NOT ALL CELL-FREE MITOCHONDRIAL DNA IS EQUAL IN TRAUMA PATIENTS', SHOCK, 58 231-235 (2022) [C1]
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Nova |
2021 |
Thurairajah K, Briggs GD, Balogh ZJ, 'Stem cell therapy for fracture non-union: The current evidence from human studies', JOURNAL OF ORTHOPAEDIC SURGERY, 29 (2021) [C1]
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Nova |
2021 |
Briggs GD, Lemmert K, Lott NJ, de Malmanche T, Balogh ZJ, 'Biomarkers to Guide the Timing of Surgery: Neutrophil and Monocyte L-Selectin Predict Postoperative Sepsis in Orthopaedic Trauma Patients', Journal of Clinical Medicine, 10 2207-2207 [C1]
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Nova |
2021 |
Ong LK, Briggs GD, Guan L, Dunkley PR, Dickson PW, 'Peripheral inflammation induces long-term changes in tyrosine hydroxylase activation in the substantia nigra', NEUROCHEMISTRY INTERNATIONAL, 146 (2021) [C1]
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Nova |
2020 |
Briggs GD, Balogh ZJ, 'Tranexamic acid and inflammation in trauma', ANZ JOURNAL OF SURGERY, 90 426-428 (2020)
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2019 |
Amico F, Briggs G, Balogh ZJ, 'Transfused trauma patients have better outcomes when transfused with blood components from young donors', Medical Hypotheses, 122 141-146 (2019) [C1]
The physiology of tissue healing and aging share common pathways. Both patient age and tissue healing are crucial factors predicting outcomes in trauma patients. The presented hyp... [more]
The physiology of tissue healing and aging share common pathways. Both patient age and tissue healing are crucial factors predicting outcomes in trauma patients. The presented hypothesis focuses on the concept that transfused trauma patients have better outcomes when transfused with blood components from young donors. The age of the donor of a blood transfusion could affect recovery following a major traumatic insult and help avoid postinjury immune paralysis and its associated complications. The frequent transfusion of blood components to the severely injured trauma patient provides an opportunity for the recipient to benefit from the potentially favourable effect of blood originating from young donors. Different types of evidence support the presented hypothesis including work on soluble circulating factors, research on animal parabiontic models and epidemiological studies. Theories on the role of transfusion of cells, on bone marrow and on senolytics also represent grounds to elaborate pathways to test this hypothesis. The precise molecular mechanism underlying this hypothesis is uncertain. A beneficial effect on trauma patients following transfusion of blood could be due to a positive effect of blood donated from younger donors or instead to the lack of a negative effect possibly occurring when transfusing blood from older donors. Either way, identifying this mechanism would provide a powerful tool enhance long and short term recovery after trauma.
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Nova |
2018 |
Thurairajah K, Briggs GD, Balogh ZJ, 'The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies', European Journal of Trauma and Emergency Surgery, 44 325-334 (2018) [C1]
Mitochondria play a key role in the pathophysiology of post-injury inflammation. Cell-free mitochondrial DNA (cf-mtDNA) is now understood to catalyse sterile inflammation after tr... [more]
Mitochondria play a key role in the pathophysiology of post-injury inflammation. Cell-free mitochondrial DNA (cf-mtDNA) is now understood to catalyse sterile inflammation after trauma. Observations in trauma cohorts have identified high cf-mtDNA in patients with systemic inflammatory response syndrome and multiple organ failure as well as following major surgery. The source of cf-mtDNA can be various cells affected by mechanical and hypoxic injury (passive mechanism) or induced by inflammatory mechanisms (active mechanism). Multiple forms of cf-mtDNA exist; mtDNA fragments, mtDNA in microparticles/vesicles and cell-free mitochondria. Trauma to cells that are rich in mitochondria are believed to release more cf-mtDNA. This review describes the current understanding of the mechanisms of cf-mtDNA release, its systemic effects and the potential therapeutic implications related to its modification. Although current understanding is insufficient to change trauma management, focussed research goals have been identified to pave the way for monitoring and manipulation of cf-mtDNA release and effects in trauma.
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Nova |
2017 |
Ong LK, Page S, Briggs GD, Guan L, Dun MD, Verrills NM, et al., 'Peripheral Lipopolysaccharide Challenge Induces Long-Term Changes in Tyrosine Hydroxylase Regulation in the Adrenal Medulla', Journal of Cellular Biochemistry, 118 2096-2107 (2017) [C1]
Immune activation can alter the activity of adrenal chromaffin cells. The effect of immune activation by lipopolysaccharide (LPS) on the regulation of tyrosine hydroxylase (TH) in... [more]
Immune activation can alter the activity of adrenal chromaffin cells. The effect of immune activation by lipopolysaccharide (LPS) on the regulation of tyrosine hydroxylase (TH) in the adrenal medulla in vivo was determined between 1 day and 6 months after LPS injection. The plasma levels of eleven cytokines were reduced 1 day after LPS injection, whereas the level for interleukin-10 was increased. The levels of all cytokines remained at control levels until 6 months when the levels of interleukin-6 and -4 were increased. One day after LPS injection, there was a decrease in TH-specific activity that may be due to decreased phosphorylation of serine 31 and 40. This decreased phosphorylation of serine 31 and 40 may be due to an increased activation of the protein phosphatase PP2A. One week after LPS injection, there was increased TH protein and increased phosphorylation of serine 40 that this was not accompanied by an increase in TH-specific activity. All TH parameters measured returned to basal levels between 1 month and 3 months. Six months after injection there was an increase in TH protein. This was associated with increased levels of the extracellular regulated kinase isoforms 1 and 2. This work shows that a single inflammatory event has the capacity to generate both short-term and long-term changes in TH regulation in the adrenal medulla of the adult animal. J. Cell. Biochem. 118: 2096¿2107, 2017. © 2016 Wiley Periodicals, Inc.
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Nova |
2017 |
Tuboly E, McIlroy D, Briggs G, Lott N, Balogh ZJ, 'Clinical implications and pathological associations of circulating mitochondrial DNA', Frontiers in Bioscience - Landmark, 22 1011-1022 (2017) [C1]
Mitochondria are membrane-enclosed organelles, the energy-producing centers in almost all eukaryotic cells. The evolutionary emergence of mitochondria is a result of the endocytos... [more]
Mitochondria are membrane-enclosed organelles, the energy-producing centers in almost all eukaryotic cells. The evolutionary emergence of mitochondria is a result of the endocytosis of a-proteobacteria. There are several characteristic features which refer to its prokaryotic ancestors including its independent sets of double-stranded mitochondrial DNA, which is uniquely circular in form and contains a significant amount of unmethylated DNA as CpG islands. Resent research has proven that free mitochondrial DNA found in blood was associated with innate immunomodulation in a broad-range of clinical conditions. Upon release, mitochondrial DNA acts as a danger-associated molecular pattern in the circulation, it is recognized by pattern recognition receptors and it facilitates inflammatory responses. Besides its high receptor activation potential, mitochondrial DNA is likely to perform direct crosstalk with activated leukocytes and to be contributed to other anti-microbial activities. Here we highlight the pathological conditions where cell free mtDNA is involved, describe the potential sources and mechanisms of extracellular mtDNA release and explore evidence for its mechanism of action after being excreted and potential therapeutic strategies.
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Nova |
2014 |
Briggs GD, Bulley J, Dickson PW, 'Catalytic domain surface residues mediating catecholamine inhibition in tyrosine hydroxylase', Journal of Biochemistry, 155 183-193 (2014) [C1]
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Nova |
2013 |
Briggs G, Bulley J, Dunkley PR, Dickson PW, 'Structural Basis for Regulation of Tyrosine Hydroxlyase by the Catecholamines 8-9 (2013) [E3]
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2013 |
Briggs GD, Nagy GM, Dickson PW, 'Mechanism of action of salsolinol on tyrosine hydroxylase', Neurochemistry International, 63 726-731 (2013) [C1]
Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in dopamine synthesis. Dopamine regulates TH as an end-product inhibitor through its binding to a high and low affi... [more]
Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in dopamine synthesis. Dopamine regulates TH as an end-product inhibitor through its binding to a high and low affinity site, the former being abolished by Ser40 phosphorylation only, and the latter able to bind and dissociate according to intracellular dopamine levels. Here, we have investigated TH inhibition by a dopamine metabolite found in dopaminergic brain regions, salsolinol (SAL). SAL is known to decrease dopamine in the nigrostriatal pathway and mediobasal hypothalamus, and to also decrease plasma catecholamines in rat stress models, however a target and mechanism for the effects of SAL have not been found. We found that SAL inhibits TH activity in the nanomolar range in vitro, by binding to both the high and low affinity dopamine binding sites. SAL produces the same level of inhibition as dopamine when TH is non-phosphorylated. However, it produces 3.7-fold greater inhibition of Ser40-phosphorylated TH compared to dopamine by competing more strongly with tetrahydrobiopterin, the cofactor of this enzymatic reaction. SAL's potent inhibition of phosphorylated TH would prevent TH from being fully activated to synthesise dopamine. Crown Copyright © 2013 Published by Elsevier Ltd. All rights reserved.
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Nova |
2011 |
Briggs GD, Gordon SL, Dickson PW, 'Mutational analysis of catecholamine binding in tyrosine hydroxylase', Biochemistry, 50 1545-1555 (2011) [C1]
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Nova |