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

We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential

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

Sciatic nerve palsy is a recognised complication of primary total hip replacement. In our unit this complication was rare with an incidence of < 0.2% in the past ten years. We describe six cases of sciatic nerve palsy occurring in 355 consecutive primary total hip replacements (incidence 1.69%). Each of these palsies was caused by post-operative haematoma in the region of the sciatic nerve. Cases, which were recognised early and surgically-evacuated promptly, showed earlier and more complete recovery. Those patients for whom the diagnosis was delayed, and who were therefore managed expectantly, showed little or no recovery. Unexpected pain and significant swelling in the buttock, as well as signs of sciatic nerve irritation, suggest the presence of haematoma in the region of the sciatic nerve. It is, therefore, of prime importance to be vigilant for the features of a sciatic nerve palsy in the early post-operative period as, when recognised and treated early, the injury to the sciatic nerve may be reversed

In order to identify the risk factors and the incidence of post-operative spinal epidural haematoma, we analysed the records of 14 932 patients undergoing spinal surgery between 1984 and 2002. Of these, 32 (0.2%) required re-operation within one week of the initial procedure and had an International Classification of Diseases (ICD)-9 code for haematoma complicating a procedure (998.12). As controls, we selected those who had undergone a procedure of equal complexity by the same surgeon but who had not developed this complication. Risks identified before operation were older than 60 years of age, the use of pre-operative non-steroidal anti-inflammatories and Rh-positive blood type. Those during the procedure were involvement of more than five operative levels, a haemoglobin < 10 g/dL, and blood loss > 1 L, and after operation an international normalised ratio > 2.0 within the first 48 hours. All these were identified as significant (p < 0.03). Well-controlled anticoagulation and the use of drains were not associated with an increased risk of post-operative spinal epidural haematoma

1. Two cases of iliacus haematoma occurring after injury in otherwise healthy individuals are reported. 2. Both cases were complicated by infection of the haematoma, but both patients made a full recovery after operation

We prospectively randomised 78 patients into two groups, ‘drains’ or ‘no drains’ to assess the effectiveness of suction drains in reducing haematoma and effusion in the joint and its effect on wound healing after total knee replacement. Ultrasound was used to measure the formation of haematoma and effusion on the fourth post-operative day. This was a semi-quantitative assessment of volume estimation. There was no difference in the mean effusion between the groups (5.91 mm in the drain group versus 6.08 mm in the no-drain, p = 0.82). The mean amount of haematoma in the no-drain group was greater (11.07 mm versus 8.41 mm, p = 0.03). However, this was not clinically significant judged by the lack of difference in the mean reduction in the post-operative haemoglobin between the groups (drain group 3.4 g/dl; no-drain group 3.0 g/dl, p = 0.38). There were no cases of wound infection or problems with wound healing at six weeks in any patient. Our findings indicate that drains do not reduce joint effusion but do reduce haematoma formation. They have no effect on wound healing

1. Haemorrhage into the fascial compartment which contains the iliacus muscle and the femoral nerve is a common complication of haemophilia. 2. The iliacus haematoma syndrome is described and illustrated from the authors' study of thirty episodes occurring in twenty-four patients. 3. The anatomy of the iliopsoas fascia is described and the mechanism of femoral nerve compression explained. 4. Differential diagnosis, prognosis and treatment are discussed and the necropsy findings in one patient are presented. 5. An instance of iliacus haematoma occurring as a complication of anticoagulant therapy is recorded

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

The October 2023 Foot & Ankle Roundup. 360. looks at: Risk factors for failure of total ankle arthroplasties; Effects of synovial fluid fracture haematoma to tissue-engineered cartilage; Coronal plane deformity in CMT-cavovarus feet using automated 3D measurements; Immediate weightbearing after ankle fracture fixation – is it safe?; Unlocking the mystery of Mueller-Weiss disease; Diabetic foot management: predictors of failure

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

Iliacus haematoma is a relatively rare condition, which may cause a local compressive neuropathy. It is usually diagnosed in adults with haemophilia or those on anticoagulation treatment and may occur after trauma. We present the case of a healthy 15-year-old boy with a femoral neuropathy due to an iliacus haematoma which resolved following conservative treatment

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells. Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis

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

There have been no previous reports of a spinal subdural haematoma occurring as a complication of spinal surgery. We highlight the pitfalls in the diagnosis and management of a subacute subdural haematoma resulting from a dural tear which occurred as a surgical complication of microdiscectomy