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Background: Head trauma is a leading cause of death and disability worldwide. Young males, Indigenous people, and rural/remote residents have been identified as high-risk populations for head trauma, however, Australian research is limited. Our aim was to define and describe the incidence, demographics, causes, prehospital interventions, and outcomes of head trauma patients transported by aeromedical services within North Queensland, Australia. We hypothesized that young, Indigenous males living remotely would be disproportionately affected by head trauma., Methods: We conducted a retrospective study of all head trauma patients transferred by air to or between Townsville, Cairns, Mount Isa and Mackay Hospitals between January 1, 2016 and December 31, 2018. Patients were identified from the Trauma Care in the Tropics data registry and followed for a median 30-months post-injury. Primary endpoints were patient and injury characteristics. Secondary outcome measures were hospital stay and mortality., Results: A total of 981 patients were included and 31.1 % were Indigenous. Sixty-seven percent of injuries occurred remotely and the median time from injury to hospital was 5.8-hours (range 67-3780 min). Eighty percent of severe head injuries occurred in males (p = 0.007). Indigenous and remote patients were more likely to sustain mild injuries. The most common mechanism of injury overall was vehicle accident (37.5 %), compared to assault in the Indigenous subgroup (46.6 %, p<0.001). The overall mortality rate was 4.9 %, with older age and lower initial Glasgow Coma Score significant predictors of in-hospital mortality. Prehospital intubation was associated with a 7-fold increased risk of mortality (p = 0.056), while patients that received tranexamic acid (TXA) were almost 5-times more likely to die., Conclusions: In North Queensland, young Indigenous males are at highest risk of traumatic head injuries. Vehicle accidents are an important preventable cause of head injury in the region. TXA administration is an important consideration for remote head trauma retrievals, in which time to emergency care is prolonged. Appropriate treatment and risk stratification strategies considering time to definitive care, severity of injury, and other prehospital patient factors require further investigation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery., Methods: Male Sprague-Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery., Results: Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68 + cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28., Conclusion: Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty., (© 2021. The Author(s).)

Background: Tranexamic acid (TXA) is commonly used in orthopedic surgery to reduce excessive bleeding and transfusion requirements. Our aim was to examine if TXA was required in all osteoarthritis patients undergoing TKA surgery, and its possible effects on systemic inflammation and coagulation properties., Methods: Twenty-three patients (Oxford Score 22-29) were recruited consecutively; 12 patients received TXA before (IV, 1.2 g/90 kg) and immediately after surgery (intra-articular, 1.4 g/90 kg). Inflammatory mediators and ROTEM parameters were measured in blood at baseline, after the first bone-cut, immediately after surgery, and postoperative days 1 and 2., Results: After the bone cut and surgery, TXA significantly increased MCP-1, TNF-α, IL-1β and IL-6 levels compared to non-TXA patients, which was further amplified postoperatively. During surgery, TXA significantly prolonged EXTEM clot times, indicating a thrombin-slowing effect, despite little or no change in clot amplitude or fibrinogen. TXA was associated with three- to fivefold increases in FIBTEM maximum lysis (ML), a finding counter to TXA's antifibrinolytic effect. Maximum lysis for extrinsic and intrinsic pathways was < 8%, indicating little or no hyperfibrinolysis. No significant differences were found in postoperative hemoglobin between the two groups., Conclusions: TXA was associated with increased systemic inflammation during surgery compared to non-TXA patients, with further amplification on postoperative days 1 and 2. On the basis of little or no change in viscoelastic clot strength, fibrinogen or clot lysis, there appeared to be no clinical justification for TXA in our group of patients. Larger prospective, randomized trials are required to investigate a possible proinflammatory effect in TKA patients.

Background: Tranexamic acid (TXA) is increasingly used during major surgery with the goal to reduce excessive bleeding, transfusion requirements, and reexploration. Our aim was to examine the effect of TXA on coagulation at different times during cardiac surgery using rotational thromboelastometry., Materials and Methods: Nineteen adult males (EuroSCORE 4-5) were recruited consecutively for first-time cardiopulmonary bypass (CPB) surgery. Ten patients received TXA at anesthesia and nine received no TXA. Rotational thromboelastometry analysis occurred before anesthesia (baseline), after sternotomy, after CPB-heparinization and surgery, and after protamine administration-sternal closure., Results: A median sternotomy had no effect on clot time (CT), formation, amplitude, or lysis in non-TXA patients. In contrast, TXA patients had twofold prolonged clotting time (all-tests) and ∼30% reduced FIBTEM (A5-30) and maximum clot firmness, indicating reduced thrombin generation and lower clot fibrinogen. After CPB, CTs in both groups were prolonged, possibly linked to overheparinization. In addition, TXA patients had significantly decreased EXTEM (A5-30), suggesting lower clot strength. After protamine-sternal closure, clotting time remained prolonged in both groups, and TXA patients had a persistently 25%-33% lower FIBTEM (A5-30) and maximum clot firmness. TXA patients also had significantly reduced platelet numbers (37% from baseline), which continued Days 1 and 2. Maximum clot lysis was <10% indicating little or no hyperfibrinolysis during cardiac surgery., Conclusions: In this nonrandomized, nonblinded, observational trial, patients in the TXA group displayed prolonged CTs and clot fibrinogen (FIBTEM A5-30) after sternotomy, decreased clot strength (EXTEM) after CPB/surgery, and acute thrombocytopenia after protamine-sternal closure. There was no significant decrease in clot lysis, questioning the need for TXA in this medium-risk group., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: ALM solution, a combination of adenosine, lidocaine and Mg2+, is an emerging small volume therapy that has been shown to prevent and correct coagulopathy and surgery-related inflammation in preclinical models, though its application in orthopaedic surgery is yet to be demonstrated. The effect of ALM solution on chondrocytes is unknown. The aim of this preliminary study was to investigate the effect of ALM solution on viability and inflammatory responses of chondrogenically-differentiated human bone marrow-derived mesenchymal stem cells (chondro-MSC), in vitro. Methods: Chondro-MSC were exposed to media only, saline (0.9% NaCl or 1.3% NaCl) only, or saline containing ALM (1 mM adenosine, 3 mM lidocaine, 2.5 mM Mg2+) or tranexamic acid (TXA, 100 mg/ml) for 1 or 4 h. Responses to ALM solutions containing higher lidocaine concentrations were also compared. Chondrocyte viability was determined using WST-8 colorimetric assays and inflammatory cytokine (TNF-α, IL-1β, IL-8) and matrix metalloproteinases (MMP-3, MMP-12, MMP-13) concentrations using multiplex bead arrays. Results: The viability of chondro-MSC was significantly greater after 1 h treatment with ALM compared to saline (96.2 ± 7.9 versus 75.6 ± 7.3%). Extension of exposure times to 4 h had no significant adverse effect on cell viability after treatment with ALM (1 h, 85.4 ± 5.6 v 4 h, 74.0 ± 15.2%). Cytotoxicity was evident following exposure to solutions containing lidocaine concentrations greater than 30 mM. There were no significant differences in viability (80 ± 5.4 v 57.3 ± 16.2%) or secretion of IL-8 (60 ± 20 v 160 ± 50 pg/ml), MMP-3 (0.95 ± 0.6 v 3.4 ± 1.6 ng/ml), and MMP-13 (4.2 ± 2.4 v 9.2 ± 4.3 ng/ml) in chondro-MSC exposed to saline, ALM or TXA. Conclusions: Short-term, in vitro exposure to clinically-relevant concentrations of ALM solution had no adverse inflammatory or chondrotoxic effects on human chondro-MSC, with responses comparable to saline and TXA. These findings provide support for continued evaluation of ALM solution as a possible therapeutic to improve outcomes following orthopaedic procedures. [ABSTRACT FROM AUTHOR]