The effect of quercetin on bone healing in an experimental rat model.

OBJECTIVES: This study aims to evaluate the effect of quercetin on fracture healing in an open fracture model in rats. MATERIALS AND METHODS: A total of 80 Wistar-Albino male rats were used in this study. The rats were divided into 10 groups. Daily oral treatment of 100 mg/kg of quercetin dissolved in corn oil were given to four groups, whereas the other four group of control rats were treated with corn oil only. Histopathological and radiological examinations of fracture healing were performed at the end of Weeks 2 and 4 in these rats, while biomechanical and biochemical examinations were performed at the end of Weeks 4 and 6, since harder callus was required. Among the rats in the last two group that were not subjected to the open fracture model, one group was given only quercetin for three weeks and the other for six weeks, and the biochemical markers in the blood were compared between these two groups. Computed tomography images were taken for radiological evaluation. The modified Lane and Sandhu scoring system was used for histological evaluation. The 3-point bending test was performed for biomechanical evaluation. For biochemical evaluation, plasma alkaline phosphatase (ALP), acid phosphatase (AP), total antioxidant status (TAS) and total oxidant status (TOS) levels were measured. RESULTS: Radiologically, there was no significant difference between the early-stage results of quercetin and control groups (p=0.247), while quercetin caused a significant increase in callus tissue in terms of latestage results (p=0.012). Histopathologically, there was no significant difference in the early stage (p=0.584); however, in the late stage, a borderline significant increase was observed in the quercetin group compared to the control group (p=0.091). Biomechanical analysis showed that quercetin significantly increased the fracture strength in the healing bone both in the early period (p=0.036) and in the late period (p=0.027). Among biochemical markers, TOS and AP were found to be significantly decreased in the quercetin group. In the non-operated and quercetin given groups, TAS levels was significantly higher (p=0.001) and AP levels were borderline significantly lower at the end of Week 6 (p=0.063). CONCLUSION: Quercetin did not have a significant effect on bone healing in the early period, but significantly promoted bone healing in the late period in rats. We recommend the use of quercetin, a strong antioxidant, in cases with high oxidative stress and conditions such as diabetes, smoking, and malnutrition which may inhibit fracture union, although further clinical studies are needed to confirm these findings.

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

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

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Low Infection Rate for Hand Fractures Managed with Surgical Fixation under Wide-Awake Local Anesthesia with No Tourniquet in Minor Surgery.

BACKGROUND: The purpose of this study was to review the rate and type of infectious complications after surgical fixation of hand fractures managed under wide-awake local anesthesia with no tourniquet (WALANT) in minor procedure rooms outside the main operating room. METHODS: A two-surgeon retrospective chart review was performed of patients who received surgical fixation of hand fractures under WALANT in minor surgery from March of 2014 to March of 2019. RESULTS A TOTAL OF: patients, with distal phalanx ( n = 16), middle phalanx ( n = 7), proximal phalanx ( n = 11), or metacarpal ( n = 26) fractures, were included in the study. The average patient age was 37 years, with a higher proportion of male patients (51:7). Two patients had two fractures each. Thirty of the 58 cases were already open fractures. Fixation was performed using either plates and screws (25 of 58) or nonburied Kirschner wires (31 of 58). Thirty-six percent of patients (21 of 58) were treated with prophylactic antibiotics. One patient developed postoperative cellulitis. The only case of osteomyelitis occurred in a patient with risk factors known to increase rates of infectious complications (open fracture, smoking history, and >24 hours from injury to treatment). No infectious complications occurred in those who sustained closed fractures. CONCLUSIONS: Although the minor surgery environment varies significantly from that of the main operating room, infection rates after surgical fixation of hand fractures using WALANT in this setting remain low (3.4 percent), with no documented infections in fractures that were referred closed and opened surgically for operative fixation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Locally delivered adjuvant biofilm-penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection.

Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 µg) and high-dose (300 µg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (µCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1ß stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high-dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). µCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin-loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.

Lower limb paediatric trauma with bone and soft tissue loss: Ortho-plastic management and outcome in a major trauma centre.

AIM: We examined the management and outcome of patients suffering complex paediatric lower limb injuries with bone and soft tissue loss. METHOD: Patients were identified from our prospective trauma database (2013-2018). Inclusion criteria were age (<18 years) and open lower-limb trauma. We assessed severity of soft tissue and/or bone loss, fracture complexity, surgical techniques and time to surgery. Paediatric quality of life and psychological trauma impact scores (HRQOL and CRIES), Ganga Hospital Injury Severity score (GHISS), union and complication rates were measured. RESULTS: We identified 32 patients aged between 4 and 17 years. Twenty-nine patients had open tibia fractures including 14 patients with bone loss, one patient had an open femur fracture, one patient an open talus fracture and one an open ankle fracture with dorsal degloving. Thirty injuries were classified intra-operatively as Gustilo IIIB (or equivalent) and two injuries as Gustilo IIIC. In 10 patients primary skin closure was achieved by acute shortening following segmental bone loss. Twenty-two patients required soft tissue coverage: 17 free vascularised flaps, two fascio-cutaneous flaps and three split skin grafts were used. Two patients required vascular repair. Soft tissue coverage was achieved within 72 hours in 26 patients (81%) and within a week in 30 patients (94%). The surgical techniques applied were: circular fine wire frame (19), monolateral external fixator (4) and open reduction internal fixation (8). Median follow up time was 18 (7-65) months. Paediatric quality of life scores were available in 30 patients (91%) with a median total score of 77.2 out of 100. The psychological trauma impact scores showed one in three patients was at risk of developing post-traumatic stress symptoms (PTSD). The GHISS scores ranged from 6-13. All fractures went on to unite over a median time of 3.8 (2-10) months. Three patients (9%) had major complications; two flap failures requiring revision, one femur non-union requiring revision fixation. CONCLUSION: Limb salvage and timely fracture union is possible in children with complex lower limb trauma. Early intervention providing adequate debridement, skeletal stabilisation and early soft-tissue cover including the option of free microvascular reconstruction in small children when required, delivers acceptable outcomes. A multidisciplinary team approach including clinical psychologists to address the psychological impact of trauma provides optimal holistic care for these children and adolescents. Therefore, treatment for these patients should only be performed in paediatric major trauma centres.

Longitudinal in vivo monitoring of callus remodeling in BMP-7- and Zoledronate-treated fractures.

Pharmacological interventions that combine pro-anabolic and anti-catabolic drugs to treat recalcitrant fractures have shown remarkable efficacy in augmenting the regenerative response. Specifically, in rodent models of fracture repair, treatment with BMP-7 and Zoledronate (ZA) has almost uniformally resulted in complete union. However, delayed remodeling may be problematic for ZA-treated fractures. The increase in newly formed bone is substantial but if translated in humans, delayed remodeling may delay functional recovery. Our objective was to determine if, and to what extent, bone morphogenetic protein (BMP) (in synergistically administered BMP-7 + ZA) can modulate the delayed hard callus remodeling caused by ZA. Callus remodeling in BMP-7-only and BMP-7 + ZA-treated osteotomies were monitored using in vivo µCT to follow the progression of healing at 6-week intervals over 24 weeks in an open femoral fracture rat model. None of the groups recovered baseline cortical bone volumes within 24 weeks post-osteotomy. Treatment prolonged the remodeling phase but the kinetics of remodeling appeared to differ between BMP and BMP + ZA groups. However, the mechanical characteristics were largely restored. Callus/bone volumes in BMP-only treated fractures peaked as early as week 3 suggesting that remodeling is stimulated prematurely. However, this rate of remodeling was not maintained as BMP-7 was found to exhibit negligible changes in callus/bone volumes between weeks 6 and 18, whereas declines in callus/bone volumes were present at these time points in the BMP-7 + ZA group. Our findings suggest that inclusion of ZA as an anti-catabolic agent may not be detrimental to the regenerative process despite a prolonged remodeling phase.

New Alternative Therapeutic Strategy for Gustilo Type IIIB Open Fractures, Using an Intra-Wound Continuous Negative Pressure Irrigation Treatment System.

The treatment of Gustilo type IIIB and IIIC open fractures remains a challenging problem, because the infection rate is 15-45%. Infection can lead to serious complications such as osteomyelitis or amputation. The intra-wound continuous negative pressure and irrigation treatment (IW-CONPIT) was developed for infected wounds and intractable ulcers, and is very effective in suppressing infection and accelerating wound healing. Here the IW-CONPIT was applied to severe open fractures for the purpose of preventing infection. After thorough debridement and lavage of the wound, bony stabilization is performed by external fixation. Dermal matrix is grafted onto any areas where the bone or tendon is exposed. A sponge containing two tubes is placed over the entire surface of the wound including the dermal matrix. Then it is covered with a film dressing to make the wound completely airtight. A bottle of physiologic saline solution is attached to one tube, and a continuous aspirator is attached to the other. This system maintains negative pressure on the wound surface, which is continuously irrigated. Thirty-five patients were treated with this method. A superficial infection developed in two cases but was resolved by additional debridement and continued application of IW-CONPIT. Complete wound healing was obtained with split thickness skin graft in all cases. There were no complications such as osteomyelitis, delayed bone union or amputation. IW-CONPIT was able to definitively prevent wound infection in Gustilo type ⅢB open fractures. We believe this method will become a standard treatment option for this condition.

Prevention of bone infection after open fracture using a chitosan with ciprofloxacin implant in animal model

Abstract Purpose To evaluate different concentrations of ciprofloxacin to prevent infection after open fracture contaminated with S. aureus in rats using absorbable local delivery system. Methods Fifty-two Wistar rats were assigned to six groups. After 4 weeks, all animals underwent 99mTc-ceftizoxima scintigraphy evaluation, callus formation measurement and histological analysis. ANOVA, t-Student and Kruskal Wallis were used for quantitative variables statistical analysis, whereas qui square and exact Fisher were used for qualitative variables. Results Treatment using 25% and 50% of ciprofloxacin incorporated at the fracture fixation device were effective in preventing bone infection compared to control group (p<0.05). Chitosan were not effective in preventing bone infection when used alone compared to control group (p>0.05). Histological findings demonstrated bone-healing delay with 50% of ciprofloxacin. No difference in callus formation were observed (p>0.05). Conclusion Local delivery treatment for contaminated open fracture using chitosan with ciprofloxacin is effective above 25%.

Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model.

BACKGROUND: Nonunion in cases of open fracture is common. Both bone morphogenetic protein 2 (BMP-2) and parathyroid hormone (PTH) have been used to enhance bone healing. We investigated the combination of BMP-2 and PTH and examined the effects on a rat model of open femoral fractures. METHODS: Group I (n = 11) was implanted with control carrier. Group II (n = 12) was implanted with carrier containing 1 µg of recombinant human BMP-2 (rhBMP-2). Group III (n = 12) was implanted with carrier alone, followed by injections of PTH 1-34. Group IV (n = 11) was implanted with carrier containing 1 µg of rhBMP-2, followed by injections of PTH 1-34. Group V (n = 11) was implanted with carrier containing 10 µg of rhBMP-2. Group VI (n = 11) was implanted with carrier containing 10 µg of rhBMP-2, followed by injections of PTH 1-34. Rats were euthanized after 8 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, micro-computerized tomography, and histological analysis. RESULTS: Manual palpation tests showed that the fusion rates of groups III (66.7%), IV (63.6%), V (81.8%), and VI (81.8%) were considerably higher than those of group I. Groups V and VI had higher radiographic scores compared to group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in groups V (61.88 ± 3.16%) and VI (71.14 ± 3.89%) versus group I (58.26 ± 1.86%). A histological analysis indicated that group VI had enhanced remodeling. CONCLUSION: The combination of abundant rhBMP-2 and PTH enhanced bone healing and remodeling of newly formed bone in a rat femoral open fracture model.

Patient experience of long-term recovery after open fracture of the lower limb: a qualitative study using interviews in a community setting.

OBJECTIVES: Treatment of open fractures is complex and patients may require muscle and skin grafts. The aim of this study was to gain a greater understanding of patient experience of recovery from open fracture of the lower limb 2-4 years postinjury. DESIGN: A phenomenological approach was used to guide the design of the study. Interviews took place between October 2016 and April 2017 in the participants' own homes or via telephone. SETTING: England, UK. PARTICIPANTS: A purposive sample of 25 patients were interviewed with an age range of 26-80 years (median 51), 19 were male and six female, and time since injury was 24-49 months (median 35 months). RESULTS: The findings identified a focus on struggling to recover as participants created a new way of living, balancing moving forward with accepting how they are, while being uncertain of the future and experiencing cycles of progress and setbacks. This was expressed through three themes: (i) 'being disempowered' with the emotional impact of dependency and uncertainty, (ii) 'being changed' and living with being fragile and being unable to move freely and (iii) 'being myself' with a loss of self, feeling and looking different, alongside recreation of self in which they integrated the past, present and future to find meaningful ways of being themselves. CONCLUSION: This study identified the long-term disruption caused by serious injury, the hidden work of integration that is required in order to move forward and maximise potential for recovery. Supportive strategies that help people to self-manage their everyday emotional and physical experience of recovery from injury are required. Research should focus on developing and testing effective interventions that provide support and self-management within a holistic rehabilitation plan. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN33756652; Post-results.

Early outcome of culture-negative infection in open fractures of the lower limb: A prospective study.

Background: Culture-negative infections in open long bone fractures are frequently encountered in clinical practice. We aimed to identify the rate and outcome of culture-negative infections in open long bone fractures of lower limb. Methodology: A prospective cohort study was conducted from November 2015 to May 2017 on Gustilo and Anderson Grade III open long bone fractures of the lower limb. Demographic data, injury details, time from injury to receiving antibiotics and index surgical procedure were noted. Length of hospital stay, number of additional surgeries and occurrence of complications were also noted. Patients with infected open fractures were grouped as culture positive or culture negative depending on the isolation of infecting microorganisms in deep intraoperative specimen. The clinical outcome of these two groups was statistically analysed. Results: A total of 231 patients with 275 open fractures involving the femur, tibia or fibula were studied. There was clinical signs of infection in 84 patients (36.4%) with 99 fractures (36%). Forty-three patients (51.2%) had positive cultures and remaining 41 patients had negative cultures (48.8%). The rate of culture-negative infection in open type III long bone fractures in our study was 17.7%. There was no statistical difference in the clinical outcome between culture-negative and culture-positive infections. Conclusion: Failure to identify an infective microorganism in the presence of clinical signs of infection is routinely seen in open fractures and needs to be treated aggressively.

Effects of BMP-2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss.

Traumatic composite bone-muscle injuries, such as open fractures, often require multiple surgical interventions and still typically result in long-term disability. Clinically, a critical indicator of composite injury severity is vascular integrity; vascular damage alone is sufficient to assign an open fracture to the most severe category. Challenging bone injuries are often treated with bone morphogenetic protein 2 (BMP-2), an osteoinductive growth factor, delivered on collagen sponge. Previous studies in a composite defect model found that a minimally bridging dose in the segmental defect model was unable to overcome concomitant muscle damage, but the effect of BMP dose on composite injuries has not yet been studied. Here, we test the hypotheses that BMP-2-mediated functional regeneration of composite extremity injuries is dose dependent and can be further enhanced via co-delivery of adipose-derived microvascular fragments (MVF), which have been previously shown to increase tissue vascular volume. Although MVF did not improve healing outcomes, we observed a significant BMP-2 dose-dependent increase in regenerated bone volume and biomechanical properties. This is the first known report of an increased BMP-2 dose improving bone healing with concomitant muscle damage. While high dose BMP-2 delivery can induce heterotopic ossification (HO) and increased inflammation, the maximum 10 µg dose used in this study did not result in HO and was associated with a lower circulating inflammatory cytokine profile than the low dose (2.5 µg) group. These data support the potential benefits of an increased, though still moderate, BMP-2 dose for treatment of bone defects with concomitant muscle damage. Published 2019. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res.

Effects of hyperbaric oxygen therapy on open tibial fractures in rabbits after transient seawater immersion.

OBJECTIVE: To explore the effect and mechanism of hyperbaric oxygen (HBO2) therapy of open tibial fractures in rabbits after transient seawater immersion. METHODS: Forty-eight (48) New Zealand rabbits were randomly and averagely divided into an HBO2 therapy group (Group A) and a control group (Group B). All rabbits were subjected to unilateral open tibial fractures, while immersed in artificial seawater (20-22 °C) for three hours prior to debridement and external fixation. Group A was treated with HBO2 at 2 atmospheres absolute (ATA) for 50 minutes once daily for two weeks; Group B received postoperative routine treatments only. The fracture zone in each group was compared by radiological, histological and immunohistochemical examinations. RESULTS: In Group A, bony callus and mature osteocytes without infiltration of inflammatory cells were observed in the fracture zone. Vascular endothelial growth factor (VEGF) was expressed mainly in the cytoplasm of osteoblasts, chondrocytes and osteocytes, and exhibited significant changes at different time points. The gray value of bony callus in Group A was 190.58 ± 7.52; that of Group B was 144 ± 8.11. Difference between the groups was statistically significant (P ⟨ 0.01). The content of malondialdehyde (MDA) in Group A was significantly lower than Group B (P ⟨ 0.01), and the activity of superoxide dismutase (SOD) in Group A was higher than Group B (P ⟨ 0.01) at four weeks. There were no significant differences in MDA content and SOD activity between groups at eight and 12 weeks. CONCLUSIONS: HBO2 treatment of open tibial fractures in seawater can reduce the inflammatory reaction and reperfusion injury, and promote osteocytic proliferation and fracture healing.

Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment.

The tenth European Consensus Conference on Hyperbaric Medicine took place in April 2016, attended by a large delegation of experts from Europe and elsewhere. The focus of the meeting was the revision of the European Committee on Hyperbaric Medicine (ECHM) list of accepted indications for hyperbaric oxygen treatment (HBOT), based on a thorough review of the best available research and evidence-based medicine (EBM). For this scope, the modified GRADE system for evidence analysis, together with the DELPHI system for consensus evaluation, were adopted. The indications for HBOT, including those promulgated by the ECHM previously, were analysed by selected experts, based on an extensive review of the literature and of the available EBM studies. The indications were divided as follows: Type 1, where HBOT is strongly indicated as a primary treatment method, as it is supported by sufficiently strong evidence; Type 2, where HBOT is suggested as it is supported by acceptable levels of evidence; Type 3, where HBOT can be considered as a possible/optional measure, but it is not yet supported by sufficiently strong evidence. For each type, three levels of evidence were considered: A, when the number of randomised controlled trials (RCTs) is considered sufficient; B, when there are some RCTs in favour of the indication and there is ample expert consensus; C, when the conditions do not allow for proper RCTs but there is ample and international expert consensus. For the first time, the conference also issued 'negative' recommendations for those conditions where there is Type 1 evidence that HBOT is not indicated. The conference also gave consensus-agreed recommendations for the standard of practice of HBOT.

Local transplantation of bone marrow concentrated granulocytes precursors can cure without antibiotics infected nonunion of polytraumatic patients in absence of bone defect.

PURPOSE: Infected, long bone non-unions present a significant clinical challenge. New and alternative therapies are needed to address this problem. The purposes of this study were to compare the number of circulating granulocyte-macrophage colony-forming units (CFU-GM) in the peripheral blood of polytraumatic patients with infected tibial non-unions and in the peripheral blood of control patients with the hypothesis that their number was decreased in polytraumatic patients; and to treat their infection without antibiotics and with local transplantation of bone marrow concentrated granulocytes precursors. METHODS: Thirty (18 atrophic and 12 hyperthrophic ) infected tibial non-unions (without bone defect) that occurred after open fractures in polytraumatic patients were treated without antibiotics and with percutaneous injection of autologous bone marrow concentrate (BMC) containing granulocytes precursors (CFU-GM). CFU-GM progenitors were assessed in the bone marrow aspirate, peripheral blood, and fracture site of these patients. The number of these progenitors was compared with the CFU-GM progenitors of control patient samples (healthy donors matched for age and gender). Outcome measures were: timing of union, callus formation (radiographs and CT scan), and recurrence of clinical infection. RESULTS: As compared to control patients, the number of CFU GM derived colonies was lower at peripheral blood in patients with infected nonunions. The bone marrow graft injected in nonunions contained after concentration 42 621 ± 20 350 CFU-GM-derived colonies/cc. Healing and cure of infection was observed at six months for 25 patients and at one year follow up for 30 patients. At the median ten year follow-up (range: 5 to 15), only one patient had clinical recurrent infection after healing (between 6 months and last follow-up). CONCLUSION: The peripheral blood of these polytraumatic patients with infected nonunions had a remarkable decrease in CFU-GM-derived colonies as compared with normal controls. Local transplantation of concentrated CFU-GM-derived colonies aspirated from bone marrow allowed cure of infection and healing without antibiotics.

The 6-Hour Rule for Surgical Debridement of Open Tibial Fractures: A Systematic Review and Meta-Analysis of Infection and Nonunion Rates.

OBJECTIVES: The aim of this study was a systematic review and meta-analysis of studies comparing early (<6 hours) versus late (>6 hours) surgical debridement of open tibial fractures, with regards to infection and nonunion rates. METHODS: A systematic literature search of MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature (1961 to present), Allied and Complementary Medicine, and COCHRANE databases was conducted using any combination of the key words: "open," "tibial," and "fractures." After appropriate screening, 7 studies were included for analysis. Inclusion criteria were studies assessing the relation between time to debridement from injury and infection and/or nonunion rates. RESULTS: Three studies (n = 365) evaluated overall infection rates that varied from 7.7% to 8.9% in the early group versus 1%-18.5% in the late group. Three studies (n = 197) evaluated deep infection rates that varied from 13% to 18.5% in the early group versus 7.1%-18.6% in the late group. Four studies (n = 245) evaluated nonunion rates that varied from 13.2% to 26.1% in the early group versus 0%-32.6% in the late group. Meta-analysis showed no statistical difference between groups with regards to overall infection rates (risk ratio = 1.32; 95% CI, 0.54-3.23; P = 0.55), deep infection rates (risk ratio = 0.99; 95% CI, 0.48-2.07; P = 0.98), and nonunion rates (risk ratio = 1.49; 95% CI, 0.64-3.49; P = 0.36). CONCLUSIONS: The available literature suggests that there is no obvious difference in the overall/deep infection and nonunion rates between open tibial fractures debrided within 6 hours and those debrided at more than 6 hours. The findings presented here would appear to indicate that judicious delays of greater than 6 hours may not result in a significantly increased risk of adverse events or peri-operative morbidity. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Improving the care of patients with severe open fractures of the tibia: the effect of the introduction of Major Trauma Networks and national guidelines.

AIMS: The management of open lower limb fractures in the United Kingdom has evolved over the last ten years with the introduction of major trauma networks (MTNs), the publication of standards of care and the wide acceptance of a combined orthopaedic and plastic surgical approach to management. The aims of this study were to report recent changes in outcome of open tibial fractures following the implementation of these changes. PATIENTS AND METHODS: Data on all patients with an open tibial fracture presenting to a major trauma centre between 2011 and 2012 were collected prospectively. The treatment and outcomes of the 65 Gustilo Anderson Grade III B tibial fractures were compared with historical data from the same unit. RESULTS: The volume of cases, the proportion of patients directly admitted and undergoing first debridement in a major trauma centre all increased. The rate of limb salvage was maintained at 94% and a successful limb reconstruction rate of 98.5% was achieved. The rate of deep bone infection improved to 1.6% (one patient) in the follow-up period. CONCLUSION: The reasons for these improvements are multifactorial, but the major trauma network facilitating early presentation to the major trauma centre, senior orthopaedic and plastic surgical involvement at every stage and proactive microbiological management, may be important factors. TAKE HOME MESSAGE: This study demonstrates that a systemised trauma network combined with evidence based practice can lead to improvements in patient care.

BMP-2 delivered via sucrose acetate isobutyrate (SAIB) improves bone repair in a rat open fracture model.

Human bone morphogenetic proteins (BMPs) are an alternative to bone graft for the treatment of high-energy open fractures. The standard delivery system for BMP-2 is a porous collagen sponge, but we have previously found that the biocompatible, high viscosity carrier, Sucrose acetate isobutyrate (SAIB) is an effective and potentially less invasive alternative. The efficacy of SAIB as a BMP-2 delivery system was examined in an open fracture model featuring a femoral osteotomy with periosteal stripping in 9-week-old male Sprague Dawley rats. SAIB containing BMP-2 (SAIB/BMP-2) was delivered into the fracture site during surgery and an additional group was further co-treated with zoledronic acid and hydroxyapatite nanoparticles (SAIB/BMP-2/HA/ZA). These were compared to untreated fractures and SAIB carrier alone (negative controls), and BMP-2 loaded collagen sponge (positive control). The rate of radiographic union and the biomechanical properties of the healed fractures were compared after 6-week. Untreated and SAIB-treated fractures showed poor repair, with 53% and 64%, respectively, not bridged at 6 week. In contrast, collagen/BMP-2, SAIB/BMP-2, and SAIB/BMP-2/HA/ZA showed significantly increased union (100%, 100%, and 94%, respectively, p < 0.05). Four-point bend testing revealed that collagen/BMP-2 and SAIB/BMP-2/HA/ZA restored the strength of fractured femora to that of intact femora by 6 week, whereas untreated and SAIB remained less than intact controls by 60% and 67%, respectively (p < 0.05). Overall, the SAIB/BMP-2/HA/ZA formulation was comparable to BMP-2 infused collagen sponge in terms of promoting open fractures repair, but with the additional potential for less invasive delivery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1168-1176, 2016.

Ustilago echinata: Infection in a Mixed Martial Artist Following an Open Fracture.

Ustilago, a common fungal parasite of grains, is infrequently isolated as a pathogen in humans. We describe a case of Ustilago echinata infection following an open distal tibia fracture, review the current literature of this genus as a cause of invasive fungal infection in humans, and discuss management issues.