Using Pre-Clinical Studies to Explore the Potential Clinical Uses of Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem cells.

Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine.

Predictors for infection severity for open tibial fractures: major trauma centre perspective.

INTRODUCTION: Open diaphyseal tibial fractures are the most common long-bone fractures and require a rapid approach to prevent devastating complications. Current literature reports the outcomes of open tibial fractures. However, there is no robust, up-to-date research on the predictive indicators of infection severity in a large open tibial fracture patient cohort. This study investigated the predictive factors of superficial infections and osteomyelitis in open tibial fractures. MATERIALS AND METHODS: A retrospective analysis of the tibial fracture database was carried out from 2014 to 2020. Criteria for inclusion was any tibial fracture including tibial plateau, shaft, pilon or ankle, with an open wound at the fracture site. Exclusion criteria included patients with a follow-up period of less than 12 months and who are deceased. A total of 235 patients were included in our study, of which 154 (65.6%), 42 (17.9%), and 39 (16.6%) developed no infection, superficial infection, or osteomyelitis, respectively. Patient demographics, injury characteristics, fracture characteristics, infection status and management details were collected for all patients. RESULTS: On multivariate modelling, patients with BMI > 30 (OR = 2.078, 95%CI [1.145-6.317], p = 0.025), Gustilo-Anderson (GA) type III (OR = 6.120, 95%CI [1.995-18.767], p = 0.001), longer time to soft tissue cover (p = 0.006) were more likely to develop a superficial infection, and patients with wound contamination (OR = 3.152, 95%CI [1.079-9.207], p = 0.036), GA-3 (OR = 3.387,95%CI [1.103-10.405], p = 0.026), longer to soft tissue cover (p = 0.007) were more likely to develop osteomyelitis. Univariate analysis also determined that risk factors for superficial infection were: BMI > 35 (OR = 6.107, 95%CI [2.283-16.332], p = 0.003) and wound contamination (OR = 2.249, 95%CI [1.015-5.135], p = 0.047); whilst currently smoking (OR = 2.298, 95%CI [1.087-4.856], p = 0.025), polytrauma (OR = 3.212, 95%CI [1.556-6.629], p = 0.001), longer time to definitive fixation (p = 0.023) were for osteomyelitis. However, none of these reached significance in multivariate analysis. CONCLUSION: Higher GA classification is a significant risk factor for developing superficial infection and osteomyelitis, with a stronger association with osteomyelitis, especially GA 3C fractures. Predictors for superficial infection included BMI and time to soft tissue closure. Time to definitive fixation, time to soft tissue closure, and wound contamination were associated with osteomyelitis.

A retrospective analysis of the definitive management of open talus fractures at a major trauma centre, comparing ORIF to FUSION: cohort study and audit of BOAST 4 guidelines.

PURPOSE: Open talus fractures are notoriously difficult to manage, and they are commonly associated with a high level of complications including non-union, avascular necrosis and infection. Currently, the management of such injuries is based upon BOAST 4 guidelines although there is no suggested definitive management, and thus, definitive management is based upon surgeon preference. The key principles of open talus fracture management which do not vary between surgeons are early debridement, orthoplastic wound care, anatomic reduction and definitive fixation whenever possible. However, there is much debate over whether the talus should be preserved or removed after open talus fracture/dislocation and proceeded to tibiocalcaneal fusion. METHODS: A review of electronic hospital records for open talus fractures from 2014 to 2021 returned fourteen patients with fifteen open talus fractures. Seven cases were initially managed with ORIF, and five cases were definitively managed with FUSION, while the others were managed with alternative methods. We collected patient's age, gender, surgical complications, surgical risk factors and post-treatment functional ability and pain and compliance with BOAST guidelines. The average follow-up of the cohort was 4 years and one month. EQ-5D-5L and FAAM-ADL/Sports score was used as a patient reported outcome measure. Data were analysed using the software PRISM. RESULTS: Comparison between FUSION and ORIF groups showed no statistically significant difference in EQ-5D-5L score (P = 0.13), FAAM-ADL (P = 0.20), FAAM-Sport (P = 0.34), infection rate (P = 0.55), surgical times (P = 0.91) and time to weight bearing (P = 0.39), despite a higher proportion of polytrauma and Hawkins III and IV fractures in the FUSION group. CONCLUSION: FUSION is typically used as second line to ORIF or failed ORIF. However, there is a lack of studies that directly compared outcome in open talus fracture patients definitively managed with FUSION or ORIF. Our results demonstrate for the first time that FUSION may not be inferior to ORIF in terms of patient functional outcome, infection rate and quality of life, in the management of patients with open talus fracture patients. Of note, as open talus fractures have increased risks of complications such as osteonecrosis and non-union, FUSION should be considered as a viable option to mitigate these potential complications in these patients.

Fracture Related Infections and Their Risk Factors for Treatment Failure-A Major Trauma Centre Perspective.

Fracture related infections (FRI) are debilitating and costly complications of musculoskeletal trauma surgery that can result in permanent functional loss or amputation. Surgical treatment can be unsuccessful, and it is necessary to determine the predictive variables associated with FRI treatment failure, allowing one to optimise them prior to treatment and identify patients at higher risk. The clinical database at a major trauma centre was retrospectively reviewed between January 2015 and January 2021. FRI treatment failure was defined by infection recurrence or amputation. A univariable logistic regression analysis was performed, followed by a multivariable regression analysis for significant outcomes between groups on univariable analysis, to determine risk factors for treatment failure. In total, 102 patients were identified with a FRI (35 open, 67 closed fractures). FRI treatment failure occurred in 24 patients (23.5%). Risk factors determined by our multivariate logistic regression model were obesity (OR 2.522; 95% CI, 0.259-4.816; p = 0.006), Gustilo Anderson type 3c (OR 4.683; 95% CI, 2.037-9.784; p = 0.004), and implant retention (OR 2.818; 95% CI, 1.588-7.928; p = 0.041). Given that FRI treatment in 24 patients (23.5%) ended up in failure, future management need to take into account the predictive variables analysed in this study, redirect efforts to improve management and incorporate adjuvant technologies for patients at higher risk of failure, and implement a multidisciplinary team approach to optimise risk factors such as diabetes and obesity.

Perioperative use of intra-articular steroids during the COVID-19 pandemic.

PURPOSE: There are growing concerns with the widely used glucocorticoids during the Coronavirus disease-19 (COVID-19) pandemic due to the associated immunosuppressive effects, which may increase the risk of COVID-19 infection and worsen COVID-19 patient outcome. Heavily affecting orthopaedics, the pandemic led to delay and cancellation of almost all surgical cases, and procedures including perioperative intra-articular corticosteroid injections (ICIs) saw similar decreases. However, the benefits of ICI treatments during the pandemic may outweigh these potential risks, and their continued use may be warranted. METHODS: A literature search was conducted, and all relevant articles including original articles and reviews were identified and considered in full for inclusion, and analysed with expert opinion. Epidemiological statistics and medical guidelines were consulted from relevant authorities. RESULTS: ICIs allow a targeted approach on the affected joint and are effective in reducing pain while improving functional outcome and patient quality-of-life. ICIs delay the requirement for surgery, accommodating for the increased healthcare burden during the pandemic, while reducing postoperative hospital stay, bringing significant financial benefits. However, ICIs can exert systemic effects and suppress the immune system. ICIs may increase the risk of COVID-19 infection and reduce the efficacy of COVID-19 vaccinations, leading to important public health implications. CONCLUSION: Perioperative ICI treatments may bring significant, multifaceted benefits during the pandemic. However, ICIs increase the risk of infection, and perioperative COVID-19 is associated with mortality. The use of ICIs during the COVID-19 pandemic should therefore be considered carefully on an individual patient basis, weighing the associated risks and benefits.

The role of hydrogen peroxide in hip arthroplasty: A narrative review.

Hydrogen peroxide has become more commonly used in hip arthroplasties due to high risk of periprosthetic infections. Its purported roles include irrigation, haemostasis, reduction of aseptic loosening and attachment of antibiotics. However, current literature does not provide conclusive evidence on the efficacy of hydrogen peroxide in preventing aseptic loosening, with some controversy around whether it in fact contributes to aseptic loosening. The complications of hydrogen peroxide across medicine are well distinguished; however, the risks within orthopaedic surgery and hip arthroplasties are not well known. Beyond cytotoxicity, the most dangerous reported risk associated with hydrogen peroxide in hip arthroplasties was an oxygen embolism in an unvented femoral canal and acrylic bone cement, consequentially leading to cardiac arrest. However, it may be inappropriate to solely attribute the oxygen embolism to the use of hydrogen peroxide and thus if used appropriately, hydrogen peroxide may have a justifiable role in hip arthroplasty surgery. In this narrative review, we present the current uses of hydrogen peroxide while evaluating its associated risks. We have summarised the key indications and aggregated recommendations to provide guidelines for the use of hydrogen peroxide in hip arthroplasty.

The role of acetic acid in orthopaedic surgery.

Acetic acid has become more commonly used in orthopaedic surgery. The purposed roles include biofilm eradication and surgical debridement, postoperative scar reduction and managing soft tissue injuries. Current research is scarce and does not provide conclusive evidence behind acetic acid's efficacy in orthopaedic procedures such as biofilm eradication or acetic acid iontophoresis in soft tissue injuries. Current literature on acetic acid's effects on biofilm eradication is composed of in-vitro studies, which do not demonstrate the potential clinical efficacy of acetic acid. Acetic acid iontophoresis is a novel technique which is now more commonly accepted for soft tissues injuries. Our literature search identified calcifying tendonitis of the shoulder, rotator cuff tendinopathy, heel pain syndrome, plantar fasciitis, achilles tendonitis, calcifying tendonitis of the ankle, myositis ossificans and cervical spondylosis as documented clinical uses. In this narrative review, we present the current uses of acetic acid and acetic acid iontophoresis, while evaluating the evidence revolving around its efficacy, benefits and risks.

Definitive management of open pilon fractures with fine wire fixation.

INTRODUCTION: The BOAST (British Orthopaedic Association Standards for Trauma) guidelines advise that open pilon fractures amongst other open lower limb fractures need to be treated at a specialist centre with Orthoplastic care. The purpose of this study was to determine clinical outcomes in patients with open pilon fractures treated as per BOAST guidelines alongside a treatment protocol which consisted of early wound debridement and spanning external fixation, delayed soft tissue coverage with a flap when necessary and delayed definitive fixation with the use of a Fine Wire Fixator. MATERIAL AND METHODS: We conducted a retrospective analysis of open pilon fractures treated between 2014 and 2019. All patients were included for the assessment of the rate of infection and fracture healing. Functional outcome assessment was performed in all patients according to the American Orthopaedic Foot and Ankle Score (AOFAS) at 12 months post injury. RESULTS: There were 20 patients including 16 males and 4 females. The mean age was 50.45 years. Initial wound with bone debridement and application of a spanning external fixator was performed within an average of 13.5 hours. The mean time from primary surgery to definitive fixation was 24.5 days. There were 3 patients with Gustilo Type I injuries, 6 with Type II, 4 Type with type IIIa and 7 with Type IIIb injuries. Average time to bone union was 10.4 (Range: 2-18) months. The mean AOFAS score was 74.2 (Range: 28-97). A Taylor Spatial Frame was used on 18 patients, while 2 patients had an Ilizarov frame. A corticotomy was performed on 4 patients with critical bone defect post debridement. There was 1 case of deep infection and 9 cases of superficial infection. There were also 4 cases of delayed union which required bone grafting from their femur using a RIA (Reamer Irrigation Aspirator). CONCLUSION: Our study suggests that the use of staged wound debridement including relatively aggressive bone debridement in conjunction with systemic and local antibiotics, external fixators and patient tailored conversion from spanning external fixator to fine wire frame achieves low rates of wound infection and complications for patients with open pilon fractures.