Aims. The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225

Background. Procedural sedation (PS) requires two suitably qualified clinicians and a dedicated monitored bed space. We present the results of intra-articular haematoma blocks (IAHB), using local anaesthetic, for the manipulation of closed ankle fracture dislocations and compared resource use with PS. Methods. Patients received intra-articular ankle haematoma blocks for displaced ankle fractures requiring manipulation between October 2020 to April 2021. The technique used 10ml of 1% lignocaine injected anteromedially into the tibiotalar joint. Pain scores (VAS), time from first x-ray to reduction, and acceptability of reduction were recorded. A comparison was made by retrospective analysis of patients who had undergone PS for manipulation of an ankle fracture over the six month period March – August 2020. Results. During the periods assessed, 25 patients received an IAHB and 28 received PS for ankle fractures requiring manipulation (mean age 57.8yr vs 55.1yr). Time from first x-ray to manipulation was 65.9 min (IAHB) vs 82.9 min (PS) (p = 0.087). In the IAHB group mean pain scores pre, during and post manipulation were 6.1, 4.7 and 2.0 respectively (‘pre’ to ‘during’ p < 0.05; ‘pre’ to ‘post’ p < 0.01). In the IAHB group, 23 (92%) had a satisfactory reduction without need of PS or general anaesthetic. In the PS group 23 (82%) had a satisfactory reduction. There was no significant difference in the number of unsatisfactory first attempt reductions between the groups. There were no cases of deep infection post operatively in either group. Conclusion. Intra-articular haematoma block of the ankle appears to be an efficacious, safe and inexpensive means of providing analgesia for manipulation of displaced ankle fractures. Advantages of this method include avoiding the risks of procedural sedation, removing the requirement of designated clinical space and need for qualified clinicians to give sedation, and the ability to re-manipulate under the same block

Regional anaesthesia is integral to best practice analgesia for patients with neck of femur fractures (NOFFs). These patients are generally frail and are vulnerable to side effects of opioid analgesia. Femoral nerve block (FNB) or fascia-iliaca block (FIB) can reduce opioid requirement. Literature supports good efficacy for extra-capsular NOFFs however it is acknowledged to be suboptimal for intracapsular fractures. We present a novel technique, using point of care ultrasound guidance to perform hip ultrasound guided haematoma (HUSH) aspiration, and injection of local anaesthetic (block) for intracapsular NOFFs. This a case control series. A consecutive series of cognitively intact patients, with an isolated intra-capsular NOFF, received a HUSH block using 10mls of 0.75% Ropivicaine. Haematoma was aspirated and volume recorded. This was performed in addition to standard NOFF pathway analgesia that includes a FIB and multimodal analgesia including opioids. Visual Analogue Scale (VAS)pain scores at rest and on movement were recorded pre and post procedure as well as combined morphine equivalent units administered post HUSH block. The control arm was a retrospective group of similar patients who followed the routine care pathway including a FIB. VAS pain scores from observation charts and usage of morphine equivalent units were calculated. Ten patients consented to receive HUSH blocks and we included thirty-eight patients in our control series. The HUSH block group showed mean VAS pain score of 4.2/10 at rest and 8.6 on movement prior to block. In the time after the block, VAS pain scores reduced to 1.5 at rest (p=0.007) and 3.1 on movement (p=0.0001) with a mean total morphine equivalent use of 8.75mg. This is significantly different from the control group's mean VAS pain at rest score 6.9 (p=0.0001) and 24.1mg total morphine equivalent (p=0.07). HUSH Block in addition to fascia iliaca block appears to significantly better pain relief in intracapsular neck of femur fracture patients when compared to fascia iliaca block alone. We believe it is relatively easy to perform with readily available ultrasound scanners in emergency departments

Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures

Introduction and Objective. Joint malleolar fractures have been estimated around 9% of all fractures. They are characterized by different both early and late complications. Among the latter, arthrofibrosis and early secondary arthrosis represent the two most common ones. Moreover, these two complications could be considered related to each other. Their real cause is still under investigation, even if residual post-operative hematoma and acute post-traumatic synovitis appear to be the most accredited. Supporting this hypothesis, joint debridement and the evacuation of the post-operative hematoma could represent a possible solution. The aim of this prospective study is to evaluate the role of arthroscopic lavage and debridement during internal fixation in order to prevent late joint complications. Materials and Methods. Sixty consecutive patients who reported dislocated articular ankle fractures with surgical indication of open reduction and internal fixation (ORIF) have been included in this study. 27 patients underwent ORIF surgery associated with arthroscopic washout and debridement, while 33 patients, representing the control group, underwent just internal reduction and osteosynthesis. Patients with pure dislocations, non-articular fractures, polytrauma, previous local trauma, metabolic and connective pathologies were excluded. Follow-up was performed at 40 days (T1), 3 (T2) and 6 months (T3) after trauma for all patients. If necessary, some have been re-evaluated 12 months after the trauma. Efficacy of the treatment was evaluated through the VAS scale, Maryland scale, search for local complications such as dehiscence or infections, and finally radiographic evaluation. T-Student was estimated in order to individuate statistical significance. Results. VAS scale showed higher values for the case group than the control group with mean values of 2.7 and 4.2 at T1 and 2.1 and 3.8 at T2, respectively. At 6 months follow-up, the VAS values resulted similar with 2.6 for the case group and 2.8 for the control group. The same projections were found for the Maryland scale, with values of 61.5 and 40.7 at T1, 80.8 and 68.0 at T2 and 87.8 and 85.0 with no significant differences at T3 respectively. No significant differences were detected for complications or radiographic evaluation. Conclusions. Our study has shown significance differences in terms of pain and time for recovery only in the very short term follow up. Although our study, due to the specific limits, cannot be considered diriment, on the basis of the data, we could hypothesize that the aforementioned hypothesis may remain valid for the non-acute hematoma or that the cause of the arthrofibrosis should be sought somewhere else. However, evidence is low, and further research is needed

Introduction: Patients with multiple skeletal injuries are susceptible to Systemic Inflammatory Response Syndrome (SIRS) and consequently Acute Respiratory Distress Syndrome (ARDS). Fracture haematoma contains pro-inflammatory mediators. The aim of our study was to show in vitro that fracture haematoma is implicated in neutrophil mediated injury, SIRS, ARDS and MOF. Methods: Fracture haematoma was isolated from 10 patients at the time of surgery. Neutrophils (PMN) were isolated from 10 healthy volunteers. PMN were exposed to the fracture haematoma supernatant and PMN activation in both primed and unprimed neutrophils were examined (CD11b and CD18 adhesion receptor expression and respiratory burst). PMN phagocytosis and apoptosis were also assessed using flow cytometry. Transmigration across an endothelial barrier was also measured following exposure to fracture haematoma. Results: Fracture haematoma had a marked effect on respiratory burst in primed PMNs (control = 100% vs 20% fracture haematoma = 1044% ± 405, p=0.04). CD11b and CD18 adhesion receptor expression were not upregulated in the fracture haematoma group. PMN phagocytosis of E coli was increased following treatment with fracture haematoma (control = 100% vs fracture haematoma = 171% ± 6SE, p=0.0001). Transendothelial migration of treated neutrophils was unaffected. Treatment of endothelial monolayers with fracture haematoma did not result in upregulated ICAM1 expression but was observed to induce significant endothelial cell death. PMN apoptosis was significantly delayed following exposure to fracture haematoma (control = 46% ± 5 vs fracture haematoma = 8% ±2, p=0.0005). Discussion: We have shown that fracture haematoma activates neutrophils, increases phagocytosis and respiratory burst whilst delaying apoptosis. These effects, whilst beneficial at the site of injury, may cause neutrophil mediated tissue injury systemically

Introduction. The hematoma occurring at a fracture site is known to play an important role in fracture healing. Previously, we demonstrated that fracture hematoma contained multilineage mesenchymal progenitor cells. On the other hand, the process of fracture healing is associated by two different mechanisms, intramembranous and endochondral. However, there are no reports proving the details about cellular analysis in the process of endochondoral ossification. Hypothesis. We hypothesized that one of the cell origins for endochondral ossification after fracture was hematoma. Materials & Methods. Fracture hematoma was obtained during osteosynthesis. Hematoma-derived cells were isolated and cultured for 5-weeks of chondrogenic induction followed by 2-weeks hypertrophic induction using pellet culture system. The pellets were analyzed histologically and immunohistochemically. The gene expression levels of chondrogenic, hypertrophic, osteogenic and angiogenic markers were measured by real-time PCR. Results. The histological and immunohistochemical analysis revealed that the Hematoma-derived cells differentiated into hypertrophic chondrocytes through chondrocytes, and finally differentiate into calcifying chondrocytes. The same trend was seen in the gene expression using real-time PCR analysis. Discussion & Conclusions. Our results suggest that fracture hematoma may be an origin of cells which play key roles in the process of endochondoral ossification during fracture healing

Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats. Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT. Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling. The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects

Sciatic Nerve Palsy (SNP) is a recognised complication in Primary Total Hip Replacement after a transtrochanteric or a posterior approach (5). It is considered to be caused by direct trauma to the nerve during surgery. In our unit this complication was rare with an incidence of < 0.2% over the past ten years. However we know describe six cases of sciatic nerve palsy occurring in 355 consecutive primary THRs (incidence 1.60%) performed in our unit from June 2000 to June 2001. Each of these sciatic nerve palsies we believe was due to postoperative haematoma in the region of the sciatic nerve. To our knowledge there are only five reported cases in the literature of sciatic nerve palsy secondary to postoperative haematoma (1). (Each of the six patients who developed SNP was receiving prophylactic anticoagulation). Cases recognized early and drained promptly showed earlier and more complete recovery. Those in whom diagnosis was delayed and were therefore managed expectantly showed no or poor recovery. More than usual pain the buttock, significant swelling in the buttock region and sciatic nerve tenderness associated with signs of sciatic nerve irritation may suggest the presence of haematoma in the region of the sciatic nerve. It is therefore of prime importance to be vigilant for the signs and symptoms of sciatic nerve palsy in the early post operative period because if recognized and treated early the potential injury to the sciatic nerve may be reversible

Aim of the study: Mason type I radial head fractures are non-displaced fractures and are treated conservatively with early mobilization and excellent results. The aspiration of the accompanying haematoma is advocated by several authors in order to achieve an analgesic effect. The aim of this study was to investigate the effect of haematoma aspiration on intraarticular pressure and on pain relief after Mason I radial head fractures. Materials and Methods: 10 patients (6 men and 4 women, age 23–47 y), who presented in the emergency department after an elbow trauma. Following plain radiographs that showed a Mason I radial head fracture, the patients were subjected to haematoma paracentesis. Initially, the intraarticular pressure was measured by using the Stryker Intra-Compartmental Pressure Monitor System. Afterwards, aspiration of the haematoma was performed, followed by a new pressure measurement without moving the needle. Finally, a brachial-elbow-wrist back slab was placed and a questionnaire was completed, including among others pain evaluation before and after haematoma aspiration by using an analogue ten point pain scale. Results: The intraarticular elbow pressure prior to haematoma aspiration varied from 49 mmHg to 120 mmHg (mean 76.9 mmHg), while following aspiration it ranged from 9 mmHg to 25 mmHg (mean 16.7 mmHg). The mean quantity of the aspired blood was 3.45 ml (0.5 ml to 8.5 ml). Finally, the patients reported a pain decrease from 5.5 (4 to 8) before aspiration to 2.8 (1 to 4) after haematoma aspiration. Decrease for both pressure and pain was statistically significant (p< 0.001). Conclusion: The built of an intraarticular haematoma in the elbow joint following an undisplaced Mason I radial head fracture leads to a pronounced increase of the intraarticular pressure accompanied by intense pain for the patient. The aspiration of the haematoma results in an acute pressure decrease and an immediate patient relief

Aim: To assess the adequacy of reduction of Colles fracture by haematoma block and intravenous sedation and its outcome. Methodology: Retrospectively reviewed 70 Colles fracture reductions done in the A & E. 30 haematoma blocks and 40 intravenouss sedation. The prereduction radiographs were reviewed for the radial height & inclination and dorsal tilt. The outcome of the reduction was also reviewed. Results: The mean age was 59 years for haematoma block and 56 years for intravenous sedation. Fracture classifications were similar in both groups using the Frykman and Universal classification. The mean prereduction radial length, radial inclination and dorsal tilt were equal in both groups. There was significant difference in post reduction measurements between the two groups. 30% of the haematoma block group had further manipulation and K wiring done whereas only 15% of the intravenous sedation group had further procedures done. Conclusions: Our study showed that there was less remanipulation and better reduction in the intravenous group than the haematoma group. We recommend intravenous sedation as a preferred procedure for initial manipulation of Colles fratures for a better outcome

Background: Paralysis of the crural nerve secondary to a compressive haematoma of the psoas in the pelvis is a well-known complication of anticoagulant therapy. This complication has also been described after hip or pelvic surgery. Its occurrence in a context of trauma is exceptional. Case report: A 16-year-old female adolescent sought emergency care for total deficit of knee extension. The patient had an enlarged painful knee subsequent to a skateboard fall. She reported knee trauma involving the patella and a direct shock to the homolateral hip, on the trochanter. Physical examination confirmed the knee and hip pain. Rest was advised. One and a half month after the accident, the patient again consulted for total deficit of active knee extension. The initial diagnosis suggested was posttraumatic rupture of the patellar tendon. An emergency MRI was normal, ruling out this diagnosis. More attentive physical examination revealed the presence of a complete paralysis of the quadriceps muscle by crural nerve palsy. MRI of the pelvic region revealed the presence of a voluminous haematoma of the psoas compressing the crural nerve. Emergency evacuation of the haematoma was performed. The patient underwent rehabilitation for one year and achieved progressive and complete recovery of the quadriceps function. An electromyogram obtained at one year was normal. Conclusion: This was an exceptional case of crural nerve palsy secondary to a posttraumatic haematoma of the psoas, with no notion of anticoagulation therapy. The initial knee injury was misinterpreted as involving a local patellar problem but in reality had caused a paralysis of the quadriceps muscle. MRI provided the diagnosis of psoas haematoma

A previously fit and well 58 year old male suffered from a bilateral psoas haematoma (PH) following 52 days of veno-venous extracorporeal membranous oxygenation (VV-ECMO) for severe Coronavirus disease (COVID-19), refractory to all non-invasive and medical therapies. He developed multiple complications, including inability to walk or weight-bear, due to lumbar plexopathy triggered by bilateral PH compression, compounded by COVID-19-related mononeuritis multiplex. The patient was referred to our institution with a known diagnosis of bilateral PH and after spinal multidisciplinary team (MDT) input, was deemed not for surgical or interventional radiology treatments. The patient received extensive neurorehabilitation, coordinated by multiple MDTs. Although PH has been correlated to COVID-19, to the best of our knowledge this is the first reported case of such a complex presentation resulting in a dramatic bilateral PH. Health records from 3 large UK teaching hospitals were collected regarding treatment and follow up appointments, following patient's written informed consent. Patient's comorbidities, duration in hospital units, MDT inputs, health assessments, mobilisation progress and neurologic assessments, were all recorded. Data was collected retrospectively then prospectively due to lengthy in-patient stay. The literature review was conducted via PubMed and open access sources, selecting all the relevant studies and the ECMO guidelines. Patient received treatment from 3 different units in 3 hospitals over 212 days including 103 days in neurorehabilitation. Involvement of physiotherapy, dietitians, speech and language teams, neurologist, neurophysiotherapists, occupational therapists was required. The patient progressed from a bed-bound coma and inability to walk, to standing with lower limb backslab at discharge. Additionally, he was referred for elective exploratory surgery of the psoas region for scar debridement and potential nerve graft repair of the lumbosacral plexus. The surgery outcome is cautiously optimistic, with some improvement in nerve conduction studies, however is currently unknown regarding recovery progress and return to premorbid functional baseline. The novelty of this presentation yields significant learning points regarding early recognition of PH, requirements for vast MDT input and specialist use of VV-ECMO in severe COVID-19 patients. It also highlights the broad pathophysiology of SARS-CoV-2 causing neuropathy and coagulopathy; understanding this will optimise robust anticoagulation guidelines, required in VV-ECMO

Introduction: Spontaneous spinal epidural haematoma is an uncommon clinical problem which may lead to severe and permanent neurological deficit. The treatment options for spinal cord compression by extradural haematoma in the anticoagulated patient are limited. The majority of cases reported have been treated surgically. 1. Operative intervention carries a potential risk of extending the haematoma with further deterioration of the neurological deficit. Methods: A case of paraplegia following spontaneous epidural haemorrhage is reported with a review of the prognostic factors that determine likely improvement in neurological function post-surgery. Case report: A 59-year old man was referred to the regional Spinal Trauma Centre with a 34-hour history of severe lower back pain of sudden onset and 14 hour history of neurological deficit in both legs and urinary overflow incontinence. He had undergone aortic valve replacement two years previously, with subsequent anticoagulation with Warfarin. Examination showed complete paraplegia below L3 with grade 1 power on hip flexion only. On catheterisation, the residual volume of urine was 1200mls. The INR was 3.5. An MRI of the spine showed epidural haematoma that extended from the level of T11 to L5. The patient was treated non-operatively. On discharge at 10 weeks he had normal sensation to L3 and grade 5-power on left knee extension and grade 4-power on the right. There was no motor recovery distal to this. He had a hypotonic neurological bladder with sufficient resting tone in the sphincter to prevent incontinence. Discussion: Although associated with a definite mortality, surgical decompression of the spinal cord and evacuation of the haematoma improves neurological outcome and is the treatment of choice. 1. The decision to treat non-operatively should be based on the duration and severity of the neurological deficit. A literature review identifies neurological deficit greater than 12 hours and severe neurological deficit on presentation are poor prognostic indicators. 2. The prognosis for neurological recovery in this case was poor. In a patient with severe coexisting medical problems these factors can assist when making the decision to operate on an individual patient with spinal epidural haematoma

Twelve patients undergoing total hip replacements were given 600mg linezolid as a 20min intravenous infusion along with conventional prophylaxis of 1gm cefamandole immediately before surgery. Routine total hip arthroplasty was performed and at timed intervals during surgery, samples of bone, fat, muscle and blood were collected for assay by HPLC analysis. Samples of haematoma fluid that formed around the operation site and further blood samples were also collected at timed intervals following the operation for assay. The penetration of linezolid into bone was rapid with mean levels of 9.1mg/L (95% CI: 7.7–10.6mg/L) achieved at 10min after the infusion, decreasing to 6.3mg/L (95% CI: 3.9–8.6mg/L) at 30min. Correcting for the simultaneous blood concentrations gave values for bone penetration of 51% at 10min, 60% at 20min and 47% at 30min. although the penetration of linezolid into fat was also rapid, mean levels and degree of penetration were approximately 60% of those seen in bone at 10min: 4.5mg/L (95%CI:3–6.1mg/L; penetration 27%) 20min: 5.2mg/L (95% CI:4–6.4mg/L; penetration 37%) and 30min:4.1mg/L (95% CI:3.3–4.8mg/L; penetration 31%). For muscle, the corresponding values were 10min: 10.4mg/L (95%CI:8.1–12.7mg/L; penetration 58%), 20min 13.4mg/L (95%:10.2–16.5mg/L; penetration 94%) and 30min 12mg/L (95% CI:9.2–14.8mg/L; penetration 93%). Mean concentration of linezolid in the haematoma around the operation site were 8.2mg/L at 6–8h and 5.6mg/L at 8–10h after the infusion and 7mg/L at 2–4h following a second 600mg infusion given 12h postoperatively. We conclude that linezolid exhibits rapid penetration in bone, fat and muscle of patients undergoing hip arthroplasty to achieve levels in excess of the MIC for sensitive organisms (MIC of < _ 4mg/L); with therapeutic levels maintained in the drainage which surrounds the operation site for more than 16h. This pharmaco-kinetic profile is similar to those of agents currently used for the treatment of bone and associated soft tissue infections and suggests a role for linezolid in the management of such patients

Introduction. Low-intensity pulsed ultrasound (LIPUS) has been reported to enhance healing of fracture and nonunion. Bone morphogenetic protein-7 (BMP-7) has also been reported to promote bone formation. Recently, we demonstrated progenitor cells with osteogenic/chondrogenic differentiation potential existed in human fracture hematoma and nonunion tissue. Hypothesis. We hypothesised the combined application of LIPUS and BMP-7 would cause major effect on osteogenesis of hematoma-derived cells (HCs) and nonunion tissue-derived cells (NCs). Materials & Methods. HCs and NCs were isolated, and cultured. The cells were divided into two groups: (1) BMP-7 group: cells cultured in osteogenic medium (OM), and (2) BMP-7 + LIPUS group: cells cultured in OM with LIPUS treatment. LIPUS (30 mW/cm2, intensity at 1.5 MHz) was given for 20 minutes daily. Osteogenic differentiation potential and proliferation were analysed. Results. ALP activity, the gene expression of osteogenic genes, and mineralisation of HCs and NCs were shown to be higher in BMP-7 + LIPUS group than in BMP-7 group. There was no significant difference in cell proliferation between the two groups. Discussion. Our findings demonstrated the significant effect of LIPUS on the osteogenic differentiation of HCs and NCs induced by BMP-7. This study may provide significant evidence for the clinical combined application of BMP-7 and LIPUS for the treatment of severe bone fracture and nonunion

Early identification of patients at risk for impaired tendon healing and corresponding novel therapeutic approaches are urgent medical needs. This study aimed to clarify the role of CD3+ T-cells during acute Achilles tendon (AT) healing. Blood and hematoma aspirate were taken from 26 patients during AT reconstruction, and additional blood samples were obtained during clinical follow-up at 6, 26 and 52 weeks after surgery. T-cell subsets were analyzed by flow cytometry using CD3, CD4, CD8, CD11a, CD57 and CD28 antibodies. Clinical follow-up included functional tests, MRI assessments, and subjective questionnaires. In vitro, the functional behavior of patient-derived tenocytes was investigated in co-cultures with autologous unpolarized CD4+ or CD8+ T-cells, or IFNy-polarized CD8+ or IL17-polarized CD4+ Tcells (n=5-6). This included alterations in gene expression (qPCR), MMP secretion (ELISA), migration rate (scratch wound healing assay) or contractility (collagen gels). Analysis revealed that elevated CD4+ T-cell levels and reduced CD8+ T-cell levels (increased CD4/CD8 ratio) in hematoma aspirate and pre-operative blood were associated with inferior clinical outcomes regarding pain and function at 26 and 52 weeks. Increased levels of CD8+ -memory T-cell subpopulations in blood 6 weeks after surgery were associated with less tendon elongation. In vitro, tenocytes showed increased MMP1/2/3 levels and collagen III/I ratio in co-culture with unpolarized and/or IL17-polarized CD4+ T-cells compared to unpolarized CD8+ T-cells. This coincided with increased IL17 receptor expression in tenocytes co-cultured with CD4+ T-cells. Exposure of tenocytes to IL17-polarized CD4+ T-cells decreased their migration rate and increased their matrix contractility, especially compared to IFNy-polarized CD8+ T-cells. The CD4+ /CD8+ T-cell ratio could serve as prognostic marker for early identification of patients with impaired AT healing potential. Local reduction of CD4+ T-cell levels or their IL17 secretion represent a potential therapeutic approach to improve AT healing and to prevent weakening of the tendon ECM

Introduction and Objective. The early pro-inflammatory hematoma phase of bone healing is characterized by platelet activation followed by growth factor release. Bone marrow mesenchymal stromal cells (MSC) play a critical role in bone regeneration. However, the impact of the pro-inflammatory hematoma environment on the function of MSC is not fully understood. We here applied platelet-rich plasma (PRP) hydrogels to study how platelet-derived factors modulate functional properties of MSC in comparison to a non-inflammatory control environment simulated by fibrin (FBR) hydrogels. Materials and Methods. MSC were isolated from acetabular bone marrow of patients undergoing hip arthroplasty. PRP was collected from pooled apheresis thrombocyte concentrates. The phenotype of MSC was analyzed after encapsulation in hydrogels or exposure with platelet-derived factors with regards to gene expression changes, cell viability, extracellular vesicle (EV) release and immunomodulatory effects utilizing cellular and molecular, flow cytometry, RT-PCR, western blot and immunofluorescence stainings. Results. Our results showed that encapsulation of MSC in PRP induced changes in cell metabolism increasing lactate production and reducing mitochondria membrane potential. This was followed by significantly decreased mTOR phosphorylation and differential gene regulation. While PRP-released factors could support EV-biogenesis and immunoregulation-related gene expression, FBR hydrogel reduced CD63+ and CD81+ EV release by MSC. In co-cultures with mitogen stimulated PBMC, pre-exposure of MSC with PRP reduced the proliferation rate and frequency of peripheral blood CD4. +. and favored the persistence of FOXP3. +. regulatory T lymphocytes (32±4.7% compared to 9±2.3% in control co-cultures where MSC were exposed to FBR). Conclusions. Our data indicate that exposure of MSC with a hematoma environment causes metabolic adaptation of MSC followed by increased immune regulatory functions, which in turn might contribute to resolution of inflammation required for successful bone healing

Aims. Despite multiple trials and case series on hip hemiarthroplasty designs, guidance is still lacking on which implant to use. One particularly deficient area is long-term outcomes. We present over 1,000 consecutive cemented Thompson’s hemiarthroplasties over a ten-year period, recording all accessible patient and implant outcomes. Methods. Patient identifiers for a consecutive cohort treated between 1 January 2003 and 31 December 2011 were linked to radiographs, surgical notes, clinic letters, and mortality data from a national dataset. This allowed charting of their postoperative course, complications, readmissions, returns to theatre, revisions, and deaths. We also identified all postoperative attendances at the Emergency and Outpatient Departments, and recorded any subsequent skeletal injuries. Results. In total, 1,312 Thompson’s hemiarthroplasties were analyzed (mean age at surgery 82.8 years); 125 complications were recorded, necessitating 82 returns to theatre. These included 14 patients undergoing aspiration or manipulation under anaesthesia, 68 reoperations (5.2%) for debridement and implant retention (n = 12), haematoma evacuation (n = 2), open reduction for dislocation (n = 1), fixation of periprosthetic fracture (n = 5), and 48 revised stems (3.7%), for infection (n = 13), dislocation (n = 12), aseptic loosening (n = 9), persistent pain (n = 6), periprosthetic fracture (n = 4), acetabular erosion (n = 3), and metastatic bone disease (n = 1). Their status at ten years is summarized as follows: 1,180 (89.9%) dead without revision, 34 (2.6%) dead having had revision, 84 (6.6%) alive with the stem unrevised, and 14 (1.1%) alive having had revision. Cumulative implant survivorship was 90.3% at ten years; patient survivorship was 7.4%. Conclusion. The Thompson’s stem demonstrates very low rates of complications requiring reoperation and revision, up to ten years after the index procedure. Fewer than one in ten patients live for ten years after fracture. This study supports the use of a cemented Thompson’s implant as a cost-effective option for frail hip fracture patients. Cite this article: Bone Jt Open 2022;3(9):710–715

In reverse shoulder arthroplasty (RSA), a high complication rate is noted in the international literature (24.7%), and limited local literature is available. The complications in our developing health system, with high HIV, tuberculosis and metabolic syndrome prevalence may be different from that in developed health systems where the literature largely emanates from. The aim of this study is to describe the complications and complication rate following RSA in a South African cohort. An analytical, cross-sectional study was done where all patients’ who received RSA over an 11 year period at a tertiary hospital were evaluated. One-hundred-and-twenty-six primary RSA patients met the inclusion criteria and a detailed retrospective evaluation of their demographics, clinical variables and complication associated with their shoulder arthroplasty were assessed. All fracture, revision and tumour resection arthroplasties were excluded, and a minimum of 6 months follow up was required. A primary RSA complication rate of 19.0% (24/126) was noted, with the most complications occurring after 90 days at 54.2% (13/24). Instability was the predominant delayed complication at 61.5% (8/13) and sepsis being the most common in the early days at 45.5% (5/11). Haematoma formation, hardware failure and axillary nerve injury were also noted at 4.2% each (1/24). Keeping in mind the immense difference in socioeconomical status and patient demographics in a third world country the RSA complication rate in this study correlates with the known international consensus. This also proves that RSA is still a suitable option for rotator cuff arthropathy and glenohumeral osteoarthritis even in an economically constrained environment like South Africa