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.

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.

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.

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.

The use of calcium sulfate impregnated with vancomycin in the treatment of open fractures of long bones: a preliminary study.

The purpose of this study was to investigate the effect of calcium sulfate impregnated with vancomycin combined with internal fixation in the treatment of open fractures of long bones. Between October 2007 and January 2008, twenty-eight patients (24 men, 4 women) who sustained open fractures of long bones were enrolled. Mean patient age was 34.5 years (range, 19-57 years). According to the classification system developed by Gustilo and Anderson, there were 15 type II open fractures, 11 type IIIa open fractures, and 2 type IIIc open fractures. All the patients were treated with vancomycin-loaded calcium sulphate and internal fixation. Clinical signs of wound infection were recorded. Postoperative radiographs were used to evaluate the bone healing and absorption process.Twenty-six of 28 patients were followed-up successfully, with an average follow-up of 10.5 months (range, 6-16 months). No infection was present in the 26 patients. Exudation from the incision or the drain incision was observed in 2 patients. Bacteria culture was negative and the wound healed with dressing change within 15 days. Bone union was observed in 23 patients, with a mean bone union time of 5.8 months (range, 4-9 months). All the calcium sulfate pellets had completely resorbed in an average of 1.4 months (range, 1-2 months). Our study showed that the combination of internal fixation and calcium sulfate impregnated with vancomycin could decrease the incidence of deep infection without impairment to the bone healing process in the treatment of open fractures of long bones.

Host classification predicts infection after open fracture.

UNLABELLED: We propose that the classification commonly used in patients with osteomyelitis, the Gustilo classification, also is applicable to patients with open fractures as a method of identifying increased risk of infection because of comorbid medical illness. The records of 174 adult patients sustaining open fractures of long bones were retrospectively reviewed. Each patient was sorted into Class A, B, or C based on 14 immune system compromising factors. Class A has no compromising factors, Class B has one or two compromising factors, and Class C has more than three compromising factors. The association between class and infection was examined. The incidence of infection was 4%, 15%, and 30% in patients in Classes A, B, and C, respectively. Patients in Class B were 2.86 times more likely to have an infection, and patients in Class C were 5.72 times more likely to have an infection when both groups of patients were compared with patients in Class A. The Gustilo classification, location of fracture, and tobacco use are all factors associated with infection. Patients in Class B or C are at markedly increased risk of infection and may benefit from additional or alternative therapies that decrease the risk of infection. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.

[Open pelvic fracture. Treatment strategy and results for 12 patients]. / Die offene Beckenfraktur. Behandlungsstrategie und Resultate anhand von 12 Patienten.

This article presents treatment priorities for open pelvic fracture and the results of 12 patients. In a retrospective study we analyzed 12 patients treated at a level 1 trauma center between 1994 and 1998 of whom eight were male and four female with an average age of 29.6 years. Six type C (6 x III degrees open) and six type B (4 x II degrees and 2 x III degrees open) were identified. On average, 15 EKs were necessary within the first 12 h of treatment (type C=17, type B=13). All type C fractures underwent emergency stabilization with the pelvic C-clamp. Early laparotomy was performed in 60%. Perineal laceration was identified in 58%, followed by nerve and plexus lesions in 42%, injuries of the genitourinary tract in 33%, and lesions of the fecal stream in 25%. Altogether, there were more peripelvic injuries associated with type C fracture than with type B (12 vs 8). On average, there were 27 second-look operations necessary with 3-.2 operations per patient. The average stay in the ICU was 82 days (80-360); 25% died. Control of hemorrhage is fundamental; therefore, emergency stabilization of the pelvis is essential followed by surgical procedures. Early surgical definitive stabilization of the fracture decreases septic complications. Such complex injuries should be treated at specialized trauma centers.