A Gender-Bias-Mitigated, Data-Driven Precision Medicine System to Assist in the Selection of Biological Treatments of Grade 3 and 4 Knee Osteoarthritis: Development and Preliminary Validation of precisionKNEE.

Objective To identify key variables predictive of patient responses to microfragmented adipose tissue (MFAT) treatment in knee osteoarthritis (KOA) and evaluate its potential to delay or mitigate the need for total knee replacement (TKR). Methods We utilised a dataset comprising 329 patients treated with MFAT for KOA, incorporating variables such as gender, age, BMI, arthritic aetiology, radiological grade, and Oxford Knee Scores (OKS) pre- and post-treatment. We employed random forest regressors for model training and testing, with gender bias mitigation and outlier detection to enhance prediction accuracy. Model performance was assessed through root mean squared error (RMSE) and mean absolute error (MAE), with further validation in a TKR-suitable patient subset. Results The model achieved a test RMSE of 6.72 and an MAE of 5.38, reflecting moderate predictive accuracy across the patient cohort. Stratification by gender revealed no statistically significant differences between actual and predicted OKS improvements (p-values: males = 0.93, females = 0.92). For the subset of patients suitable for TKR, the model presented an increased RMSE of 9.77 and MAE of 7.81, indicating reduced accuracy in this group. The decision tree analysis identified pre-operative OKS, radiological grade, and gender as significant predictors of post-treatment outcomes, with pre-operative OKS being the most critical determinant. Patients with lower pre-operative OKS showed varying responses based on radiological severity and gender, suggesting a nuanced interaction between these factors in determining treatment efficacy. Conclusion This study highlights the potential of MFAT as a non-surgical alternative for KOA treatment, emphasising the importance of personalised patient assessments. While promising, the predictive model warrants further refinement and validation with a larger, more diverse dataset to improve its utility in clinical decision-making for KOA management.

A Quantum-Enhanced Precision Medicine Application to Support Data-Driven Clinical Decisions for the Personalized Treatment of Advanced Knee Osteoarthritis: The Development and Preliminary Validation of precisionKNEE_QNN.

Background Quantum computing and quantum machine learning (QML) are promising experimental technologies that can improve precision medicine applications by reducing the computational complexity of algorithms driven by big, unstructured, real-world data. The clinical problem of knee osteoarthritis is that, although some novel therapies are safe and effective, the response is variable, and defining the characteristics of an individual who will respond remains a challenge. In this study, we tested a quantum neural network (QNN) application to support precision data-driven clinical decisions to select personalized treatments for advanced knee osteoarthritis. Methodology After obtaining patients' consent and Research Ethics Committee approval, we collected the clinicodemographic data before and after the treatment from 170 patients eligible for knee arthroplasty (Kellgren-Lawrence grade ≥3, Oxford Knee Score (OKS) ≤27, age ≥64 years, and idiopathic aetiology of arthritis) treated over a two-year period with a single injection of microfragmented fat. Gender classes were balanced (76 males and 94 females) to mitigate gender bias. A patient with an improvement ≥7 OKS was considered a responder. We trained our QNN classifier on a randomly selected training subset of 113 patients to classify responders from non-responders (73 responders and 40 non-responders) in pain and function at one year. Outliers were hidden from the training dataset but not from the validation set. Results We tested our QNN classifier on a randomly selected test subset of 57 patients (34 responders, 23 non-responders) including outliers. The no information rate was 0.59. Our application correctly classified 28 responders out of 34 and 6 non-responders out of 23 (sensitivity = 0.82, specificity = 0.26, F1 Statistic = 0.71). The positive and negative likelihood ratios were 1.11 and 0.68, respectively. The diagnostic odds ratio was 2. Conclusions Preliminary results on a small validation dataset showed that QML applied to data-driven clinical decisions for the personalized treatment of advanced knee osteoarthritis is a promising technology to reduce computational complexity and improve prognostic performance. Our results need further research validation with larger, real-world unstructured datasets, as well as clinical validation with an artificial intelligence clinical trial to test model efficacy, safety, clinical significance, and relevance at a public health level.

Microbiological Profile of Fracture Related Infection at a UK Major Trauma Centre.

Fracture Related Infection (FRI) represents one of the biggest challenges for Trauma and Orthopaedic surgery. A better understanding of the microbiological profile should assist with decision-making and optimising outcomes. Our primary aim was to report on the microbiological profile of FRI cases treated over a six-year period at one of Europe's busiest trauma centres. Secondarily, we sought to correlate our findings with existing anti-microbiological protocols and report on diagnostic techniques employed in our practice. All adult cases of FRI treated in our institution between 2016 and 2021 were identified, retrospectively. We recorded patient demographics, diagnostic strategies, causative organisms and antibiotic susceptibilities. There were 330 infection episodes in 294 patients. A total of 463 potentially pathogenic organisms (78 different species) were identified from cultures, of which 57.2% were gram-positive and 39.7% gram-negative. Polymicrobial cultures were found in 33.6% of cases and no causative organism was found in 17.5%. The most prevalent organisms were Staphylococcus aureus (24.4%), coagulase-negative Staphylococci (14%), Pseudomonas aeruginosa (8.2%), Enterobacter species (7.8%) and Escherichia coli (6.9%). Resistant gram-positive organisms (methicillin resistant Staphylococcus aureus or vancomycin-resistant Enterococci) were implicated in 3.3% of infection episodes and resistant gram-negatives (extended-spectrum beta-lactamase, ampC or carbapenemase-producing bacteria) in 13.6%. The organisms cultured in 96.3% of infection episodes would have been covered by our empirical systemic antibiotic choice of teicoplanin and meropenem. To our knowledge, this is the largest reported single-centre cohort of FRIs from a major trauma centre. Our results demonstrate patterns in microbiological profiles that should serve to inform the decision-making process regarding antibiotic choices for both prophylaxis and treatment.

Complications after talus fractures: A trauma centre experience.

BACKGROUND: Talus fractures are anatomically complex, high-energy injuries that can be associated with poor outcomes and high complication rates. Complications include non-union, avascular necrosis (AVN) and post-traumatic osteoarthritis (OA). The aim of this study was to analyse the outcomes of these injuries in a large series. METHODS: We retrospectively collected data on 100 consecutive patients presenting to a single high volume major trauma centre with a talus fracture between March 2012 and March 2020. All patients were over the age of 18 with a minimum of 12 months follow up post injury. Retrospective review of case notes and imaging was conducted to collate demographic data and to classify fracture morphology. Whether patients were managed non-operatively or operatively was noted and where used, the type of operative fixation, outcomes and complications were recorded. RESULTS: The mean age was 35 years (range: 18-76 years). Open injuries accounted for 22% of patients. An isolated talar body fracture was the most frequent fracture (47%), followed by neck fractures (20%). The overall non-union rate was 2% with both cases occurring in patients with open fractures. The AVN rate was 6%, with the highest prevalence in talar neck fractures. Overall rates of post-traumatic OA of the tibio-talar, sub-talar and talo-navicular joints were 12%, 8%, and 6%, respectively. These were higher after a joint dislocation, and higher in neck or head fractures. The postoperative infection rate was 6%. The overall secondary surgery rate was 9%. There were 2% of patients who subsequently underwent a joint arthrodesis. CONCLUSION: Our study found that talar body fractures are more common than previously reported; however, talar neck fractures cause the highest rates of AVN and post-traumatic arthritis. Open fractures also carry a greater risk of complications. This information is useful during consenting and preoperatively when planning these cases to ensure adverse outcomes may be anticipated.

A major trauma centre experience with gentamicin-coated tibial intramedullary nails (ETN PROtect™) in acute primary open fracture fixation and complex revision surgery.

PURPOSE: Fracture-related infections (FRI) following intramedullary nailing for tibial shaft fractures remain challenging to treat with associated high patient morbidity and health care costs. Recently, antibiotic-coated nails have been introduced as a strategy to reduce implant related infection rates in high-risk patients. We present the largest single-centre case series on ETN PROtect® outcomes reporting on fracture union, infection rates and treatment complications. METHODS: Fifty-six adult patients underwent surgery with ETN PROtect® between 01/09/17 and 31/12/20. Indications consisted of acute open fractures and complex revision cases (previous FRI, non-union surgery and re-fracture) with a mean of three prior surgical interventions. We report on patient demographics, union rates and deep infection. Minimum follow-up was one year. RESULTS: One (1.8%) patient developed a deep surgical infection and associated non-union requiring further surgery. In addition, we identified three cases (5.4%) of aseptic non-union following facture treatment with ETN PROtect®. Of the five patients who underwent staged complex revision surgery for established FRI with ETN PROtect®, all had treatment failure with ongoing symptoms of deep infection requiring implant removal and further treatment. CONCLUSION: Use of the ETN PROtect® nail in high-risk patients (open fractures and those initially treated with external fixation) and in those patients with aseptic non-unions, demonstrates promising outcomes in the prevention of implant-related infection. In our limited series we have failed to observe any benefit over uncoated nails, when used in treating cases of previously established FRI/osteomyelitis and would therefore advise caution in their use, especially in view of the high cost.

Functional Outcomes of Dorsal Bridge Plating for Lisfranc Injuries With Routine Implant Retention: A Major Trauma Center Experience.

OBJECTIVES: To assess medium-term functional outcomes and the complication profile for unstable Lisfranc injuries treated with dorsal bridge plate (DBP) fixation when implants are not routinely removed. DESIGN: Large single-center retrospective case series. SETTING: Level-1 Trauma Center, London, United Kingdom. PATIENTS: Consecutive cases of skeletally mature individuals with unstable Lisfranc injuries treated operatively between 2014 and 2019. INTERVENTION: Open reduction and DBP fixation with implants not routinely removed. MAIN OUTCOME MEASUREMENTS: Patient-reported outcome measures at final follow-up. The Manchester-Oxford Foot Questionnaire summary index was the primary outcome measure. The American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scale, complications, and all-cause reoperation rates were secondary outcome measures. Logistic regression models were used to identify risk factors that influenced outcomes. RESULTS: Eighty-five patients were included. Mean follow-up was 40.8 months (24-72). The mean Manchester-Oxford Foot Questionnaire Summary Index was 27.0 (SD 7.1) and mean AOFAS score 72.6 (SD 11.6). The presence of an intra-articular fracture was associated with poorer outcomes, with worse MOXFQ and AOFAS scores (both P < 0.001). Eighteen patients (21%) required implants removal, with this more likely in female patients (OR 3.89, 95% confidence interval, 1.27 to 12.0, P = 0.02). Eight patients (9%) required secondary arthrodesis. CONCLUSIONS: This is the largest series of Lisfranc injuries treated with DBP fixation reported to-date and the only to routinely retain implants. Medium-term outcomes are comparable to existing literature in which implants are routinely removed. The presence of an intra-articular fracture is a poor prognostic indicator. Implant removal is more likely to be needed in female patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for authors for a complete description of levels of evidence.

Intramedullary application of local antibiotic bullets for the treatment of long bone fracture related infection.

PURPOSE: The optimal means of local antibiotic delivery for fracture related infection is unknown. Until now, intramedullary application of calcium sulphate based local antibiotics has been challenging. We report on the use of a newly available mode of preparation and delivery: the Stimulan Bullet Mat and Introducer (Biocomposites Ltd, Staffordshire, England). METHODS: A retrospective analysis of prospectively collected data for infection cases at two separate tertiary referral institutions was performed. We included cases of long bone FRI with a retained intramedullary nail, treated with a single stage protocol of metalwork removal, debridement, local antibiotic application using the novel mould and applicator, with additional bony stabilisation and soft tissue reconstruction where required. RESULTS: All 13 patients achieved infection remission rate with an average follow-up of 19.7 months (range 12-28). All 6 patients with infection around an unhealed fracture achieved union at an average 8 months (range 4-12) from debridement. No patients developed aseptic wound leak. CONCLUSIONS: Antibiotic impregnated calcium sulphate can be used safely as part of a single stage treatment protocol for the treatment of long bone fracture related infection following intramedullary nailing. We have demonstrated high rates of infection remission and union, using a newly available intramedullary applicator.

Pin-site Infection: A Systematic Review of Prevention Strategies.

Introduction: Circular frame fixation remains a key tool in the armamentarium of the limb reconstruction surgeon. One of the key drawbacks is the onset of pin-site infection (PSI). As a result of limited evidence and consensus of PSI prevention, a wide variation in practice remains. Aim: The principal aim of this review is to synthesise primary research concerning all aspects of treatment regarded as relevant to PSI in frame constructs. Materials and methods: Comparative studies until week 26, 2021, were included in the trial. Studies were included that concerned patients undergoing management of a musculoskeletal condition in which pin-site care is necessary for over 4 weeks. Results: Eighteen studies over a 13-year period were captured using the search strategy. Sulphadiazine and hydrogen peroxide cleansing was found to reduce PSI, with the use of low-energy fine wires and hydroxyapatite (HA)-coated pins also associated with lower infection rate. The remainder of studies found no significant improvement across interventions. Conclusion: There is no superiority between weekly and daily care. Low-energy pin-insertion technique had lower rates of infection. Sulphadiazine has positive results as a pin-care solution, but more research is necessary to determine the most effective care regime. Current literature is limited by absence of established definitions and by a lack of studies addressing all aspects of care relevant to PSI. How to cite this article: Shields DW, Iliadis AD, Kelly E, et al. Pin-site Infection: A Systematic Review of Prevention Strategies. Strategies Trauma Limb Reconstr 2022;17(2):93-104.

Monomeric C-Reactive Protein: Current Perspectives for Utilization and Inclusion as a Prognostic Indicator and Therapeutic Target.

Monomeric C-reactive protein (mCRP), once thought to be a figment of the imagination and whose biological activity was ascribed to its sodium azide preservative, has now pronounced itself as a critical molecule playing a direct role in mediating many of the acute and chronic aberrant pathological responses to inflammation. In this focused mini review, we describe the currently attributed pathobiological interactions of mCRP in disease, where its tissue and cellular distribution and deposition have recently been clearly characterized and linked to inflammation and other pathway-associated progression of neurological and cardiovascular complications and deleterious outcomes. and focus upon current opinions as to the diagnostic and prognostic potential of mCRP-plasma circulating protein and define the possible future therapeutics including ongoing research attempting to block CRP dissociation with small molecule inhibitors or prevention of cell surface binding directly using antibodies or modified orphan drug targeting directed towards CRP, inhibiting its cellular interactions and signaling activation. There is no doubt that understanding the full influence of the biological power of mCRP in disease development and outcome will be considered a critical parameter in future stratified treatment.

Percutaneous subtalar joint screw fixation of comminuted calcaneal fractures: a salvage procedure.

INTRODUCTION: Malunited comminuted calcaneal fractures result in poor function due subtalar joint arthritis and altered biomechanics. We aimed to assess whether percutaneous subtalar joint screws after fracture reduction provide good outcomes for these difficult injuries. METHODS: We retrospectively analysed 15 comminuted calcaneal fractures (in 14 patients) treated with percutaneous subtalar screw fixation. All patients had a minimum of 12 months' follow-up. Six patients had open injuries. On the preoperative and the latest postoperative radiograph, Bohlers angle, Gissane angle, calcaneal inclination, width and length, absolute foot height, and posterior facet height were measured. Preoperative computed tomography scans were used to classify the fractures by Sanders classification. Clinical outcome scores were recorded postoperatively. RESULTS: Mean age was 34.2 ± 14.2 years. Minimum follow-up was 12 months (mean 17.2 ± 4.4 months). Nine patients had a Sanders 4, 3 had a Sanders 3AB, 2 had a Sanders 3BC, and 1 had a Sanders 3AC fracture. Eighty percent of patients had their angle of Gissane, absolute foot height, calcaneal length and inclination restored by this technique. Bohlers angle was restored back into the normal range in 54% of patients. Mean postoperative AOFAS score was 74 ± 11. AOFAS scores positively correlated with postoperative Bohlers angle (Pearson's correlation coefficient 0.85; p = 0.004). One patient (7%) had a wound breakdown postoperatively and three patients (20%) had heel pain from the screws, which improved after removal. CONCLUSION: Percutaneous subtalar screws offer a reliable option to restore calcaneal anatomy in comminuted calcaneal fractures, with low complication rates. Over 80% of patients had their angle of Gissane, calcaneal length and inclination restored, and over 50% of patients had all radiological parameters restored by this technique. It offers the benefits of percutaneous reduction and fixation and this procedure may be considered an effective first stage prior to definitive subtalar fusion. Further work is needed to review the longer-term outcomes and the conversion rate to arthrodesis. LEVEL OF EVIDENCE: IV (case series), Therapeutic.

Comparison of the Effect of MFAT and MFAT + PRP on Treatment of Hip Osteoarthritis: An Observational, Intention-to-Treat Study at One Year.

Hip osteoarthritis (OA) is a major contributor to reduced quality of life and concomitant disability associated with lost working life months. Intra-articular injection of various biological materials has shown promise in alleviating symptoms and potentially slowing down the degenerative process. Here, we compared the effects of treatment of a cohort of 147 patients suffering from grade 1-4 hip OA; with either micro-fragmented adipose tissue (MFAT), or a combination of MFAT with platelet-rich plasma (PRP). We found significant improvements in both the visual analogue score for pain (VAS) and Oxford hip score (OHS) that were similar for both treatments with over 60% having an improvement in the VAS score of 20 points or more. These results suggest a positive role for intra-articular injection of MFAT + PRP as a treatment for hip osteoarthritis which may be important particularly in low body mass index (BMI) patients where the difficulty in obtaining sufficient MFAT for treatment could be offset by using this combination of biologicals.

A novel technique to assess rotational deformities in lower extremities using CT-based motion analysis.

Rotational deformities following intramedullary (IM) nailing of tibia has a reported incidence of as high as 20%. Common techniques to measure deformities following IM nailing of tibia are either based on clinical assessment, plain X-rays or Computed Tomography (CT) comparing the treated leg with the uninjured contralateral side. All these techniques are based on examiners manual calculation inherently subject to bias. Following our previous rigorous motion analysis and symmetry studies on hemi pelvises, femurs and orthopaedic implants, we aimed to introduce a novel fully digital technique to measure rotational deformities in the lower legs. Following formal institutional approval from the Imperial College, CT images of 10 pairs of human lower legs were retrieved. Images were anonymized and uploaded to a research server. Three dimensional CT images of the lower legs were bilaterally reconstructed. CT-based motion analysis (CTMA) was used and the mirrored images of the left side were merged with the right side proximally as stationary and distally as moving objects. Discrepancies in translation and rotation were automatically calculated. Our study population had a mean age of 54 ± 20 years. There were six males and four females. We observed a greater variation in translation (mm) of Centre of Mass (COM) in sagittal plane (95% CI - 2.959-.292) which was also presented as rotational difference alongside the antero-posterior direction or Y axis (95% CI .370-1.035). In other word the right lower legs in our study were more likely to be in varus compared to the left side. However, there were no statistically significant differences in coronal or axial planes. Using our proposed fully digital technique we found that lower legs of the human adults were symmetrical in axial and coronal plane. We found sagittal plane differences which need further addressing in future using bigger sample size. Our novel recommended technique is fully digital and commercially available. This new technique can be useful in clinical practice addressing rotational deformities following orthopaedic surgical intervention. This new technique can substitute the previously introduced techniques.

Effect of Demineralized Bone Matrix, Bone Marrow Mesenchymal Stromal Cells, and Platelet-Rich Plasma on Bone Tunnel Healing After Anterior Cruciate Ligament Reconstruction: A Comparative Micro-Computed Tomography Study in a Tendon Allograft Sheep Model.

BACKGROUND: The effect of demineralized bone matrix (DBM), bone marrow-derived mesenchymal stromal cells (BMSCs), and platelet-rich plasma (PRP) on bone tunnel healing in anterior cruciate ligament reconstruction (ACLR) has not been comparatively assessed. HYPOTHESIS: These orthobiologics would reduce tunnel widening, and the effects on tunnel diameter would be correlated with tunnel wall sclerosis. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 sheep underwent unilateral ACLR using tendon allograft and outside-in interference screw fixation. The animals were randomized into 4 groups (n = 5 per group): Group 1 received 4mL of DBM paste, group 2 received 10 million BMSCs in fibrin sealant, group 3 received 12 mL of activated leukocyte-poor platelet-rich plasma, and group 4 (control) received no treatment. The sheep were euthanized after 12 weeks, and micro-computed tomography scans were performed. The femoral and tibial tunnels were divided into thirds (aperture, midportion, and exit), and the trabecular bone structure, bone mineral density (BMD), and tunnel diameter were measured. Tunnel sclerosis was defined by a higher bone volume in a 250-µm volume of interest compared with a 4-mm volume of interest surrounding the tunnel. RESULTS: Compared with the controls, the DBM group had a significantly higher bone volume fraction (bone volume/total volume [BV/TV]) (52.7% vs 31.8%; P = .020) and BMD (0.55 vs 0.47 g/cm3; P = .008) at the femoral aperture and significantly higher BV/TV at femoral midportion (44.2% vs 32.9%; P = .038). There were no significant differences between the PRP and BMSC groups versus controls in terms of trabecular bone analysis or BMD. In the controls, widening at the femoral tunnel aperture was significantly greater than at the midportion (46.7 vs 41.7 mm2; P = .034). Sclerosis of the tunnel was common and most often seen at the femoral aperture. In the midportion of the femoral tunnel, BV/TV (r = 0.52; P = .019) and trabecular number (r S = 0.50; P = .024) were positively correlated with tunnel widening. CONCLUSION: Only DBM led to a significant increase in bone volume, which was seen in the femoral tunnel aperture and midportion. No treatment significantly reduced bone tunnel widening. Tunnel sclerosis in the femoral tunnel midportion was correlated significantly with tunnel widening. CLINICAL RELEVANCE: DBM might have potential clinical use to enhance healing in the femoral tunnel after ACLR.

Medial approach for subtalar distraction bone block arthrodesis.

Subtalar distraction bone block arthrodesis is a useful technique commonly employed in the management of calcaneal and talar fracture malunion. Traditionally it is performed via a posterolateral or extensile lateral approach, however such approaches have been associated with wound complications, particularly secondary to the added stress caused by the subtalar distraction crucial to this technique. Medial approaches to the subtalar joint have been used in other procedures but have not been reported in subtalar distraction bone block arthrodesis. A novel case and technique illustrating the medial approach for subtalar distraction bone block arthrodesis is discussed. LEVEL OF CLINICAL EVIDENCE: Level 4.

Microfragmented Adipose Tissue Injection (MFAT) May Be a Solution to the Rationing of Total Knee Replacement: A Prospective, Gender-Bias Mitigated, Reproducible Analysis at Two Years.

BACKGROUND: Knee osteoarthritis (KOA) is a significant cause of disability in a globally ageing population. Knee replacement surgery has been shown to improve function and quality of life. Access to this intervention can be limited for a number of reasons including rationing of care, lack of healthcare provision in austere environments, and more recently, due to the cessation of elective orthopaedic care as a result of the COVID pandemic. Referral for knee replacement surgery is often guided by the patient's Oxford Knee Score (OKS). Recent therapies including treatment with microfragmented adipose tissue (MFAT) have emerged as alternatives to relieve pain and improve function in such patients. METHOD: We identified all patients with KOA Kellgren-Lawrence grade 3 and 4 in our dataset of patients treated with a single injection of MFAT and applied published OKS thresholds for referral for TKR to separate them into 3 cohorts according to their functional impairment. 220 patients (95 females, 125 males) with KOA were given one MFAT injection. The function (OKS) and quality of life (EuroQol-5) prior to and 24 months after therapy were compared. RESULTS: MFAT injection provided a statistically significant improvement in the quality of life (EQ-5D) at 24 months in patients with a baseline OKS of 39 or less (p value: <0.001) as well as those with OKS of 27 or less who are deemed suitable for a knee replacement (p value: <0.001). CONCLUSION: MFAT injection improves quality of life in patients with KOA who are deemed suitable for the knee replacement. MFAT is a low-morbidity alternative biological treatment and can delay the need for total knee replacement in suitable patients.

The Effect of Delayed Surgical Debridement in the Management of Open Tibial Fractures: A Systematic Review and Meta-Analysis.

INTRODUCTION: Open tibial fractures are complex injuries with variable outcomes that significantly impact patients' lives. Surgical debridement is paramount in preventing detrimental complications such as infection and non-union; however, the exact timing of debridement remains a topic of great controversy. The aim of this study is to evaluate the association between timing of surgical debridement and outcomes such as infection and non-union in open tibial fractures. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of the literature to capture studies evaluating the association between timing of initial surgical debridement and infection or non-union, or other reported outcomes. We searched the MEDLINE, PubMed Central, EMBASE, SCOPUS, Cochrane Central and Web of Science electronic databases. Our methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane handbook for systematic reviews of interventions. RESULTS: The systematic review included 20 studies with 10,032 open tibial fractures. The overall infection rate was 14.3% (314 out of 2193) and the overall non-union rate 14.2% (116 out of 817). We did not find any statistically significant association between delayed debridement and infection rate (OR = 0.87; 95% CI, 0.68 to 1.11; p = 0.23) or non-union rate (OR = 0.70; 95% CI, 0.42 to 1.15; p = 0.13). These findings did not change when we accounted for the effect of different time thresholds used for defining early and late debridement, nor with the Gustilo-Anderson classification or varying study characteristics. CONCLUSION: The findings of this meta-analysis support that delayed surgical debridement does not increase the infection or non-union rates in open tibial fracture injuries. Consequently, we propose that a reasonable delay in the initial debridement is acceptable to ensure that optimal management conditions are in place, such that the availability of surgical expertise, skilled staff and equipment are prioritised over getting to surgery rapidly. We recommend changing the standard guidance around timing for performing surgical debridement to 'as soon as reasonably possible, once appropriate personnel and equipment are available; ideally within 24-h'.

Monomeric C-Reactive Protein Localized in the Cerebral Tissue of Damaged Vascular Brain Regions Is Associated With Neuro-Inflammation and Neurodegeneration-An Immunohistochemical Study.

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and ß-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1ß) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury.

Characterisation of Novel Angiogenic and Potent Anti-Inflammatory Effects of Micro-Fragmented Adipose Tissue.

Adipose tissue and more specifically micro-fragmented adipose tissue (MFAT) obtained from liposuction has recently been shown to possess interesting medicinal properties whereby its application supports pain reduction and may enhance tissue regeneration particularly in osteoarthritis. Here we have characterised samples of MFAT produced using the Lipogems® International Spa system from eight volunteer individuals in order to understand the critical biological mechanisms through which they act. A variation was found in the MFAT cluster size between individual samples and this translated into a similar variation in the ability of purified mesenchymal stem cells (MSCs) to form colony-forming units. Almost all of the isolated cells were CD105/CD90/CD45+ indicating stemness. An analysis of the secretions of cytokines from MFAT samples in a culture using targeted arrays and an enzyme-linked immunosorbent assay (ELISA) showed a long-term specific and significant expression of proteins associated with anti-inflammation (e.g., interleukin-1 receptor alpha (Il-1Rα) antagonist), pro-regeneration (e.g., hepatocyte growth factor), anti-scarring and pro-angiogenesis (e.g., transforming growth factor beta 1 and 2 (TGFß1/2) and anti-bacterial (e.g., chemokine C-X-C motif ligand-9 (CXCL-9). Angiogenesis and angiogenic signalling were notably increased in primary bovine aortic endothelial cells (BAEC) to a different extent in each individual sample of the conditioned medium whilst a direct capacity of the conditioned medium to block inflammation induced by lipopolysaccharides was shown. This work characterises the biological mechanisms through which a strong, long-lasting, and potentially beneficial effect can be observed regarding pain reduction, protection and regeneration in osteoarthritic joints treated with MFAT.

Current concepts in the prevention, diagnosis and treatment of fracture-related infection (FRI).

Fracture-related infection (FRI) is one of the most challenging complications following operative management of fractures. It can have profound implications for the patient, can be associated with considerable morbidity and often lead to impaired outcomes. There are significant healthcare-related costs. In recent years, there has been significant progress towards developing preventative strategies. Furthermore, diagnostic algorithms and management protocols have recently been reported. Lack of a strong evidence base has previously hindered efforts to implement these and develop established standards of care. There are multiple aspects of care that need to be considered and a multi-disciplinary approach is recommended. In this narrative review, we present the most up-to-date recommendations in the prevention, diagnosis and management of FRI.