Osteogenic gene expression correlates with development of heterotopic ossification in war wounds.

BACKGROUND: Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. QUESTION/PURPOSES: The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. METHODS: Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. RESULTS: The transcripts of 13 genes (ALPL [p = 0.006], BMP-2 [p < 0.001], BMP-3 [p = 0.06], COL2A1 [p < 0.001], COLL10A1 [p < 0.001], COL11A1 [p = 0.006], COMP [p = 0.02], CSF2 [p = 0.003], CSF3 [p = 0.012], MMP8 [p < 0.001], MMP9 [p = 0.014], SMAD1 [p = 0.024], and VEGFA [p = 0.017]) were upregulated greater than twofold in wounds in which HO developed compared with wounds in which it did not develop. Gene transcript expression of BMP-2 also correlated directly with functional protein expression in the wounds that formed HO (p = 0.029). CONCLUSIONS: Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds. CLINICAL RELEVANCE: Understanding the osteogenic environment associated with war wounds may allow for the development of novel therapeutic strategies for HO.

Outcomes of manipulation under anesthesia versus surgical management of combat-related arthrofibrosis of the knee.

The purpose of this study was to compare the outcomes of manipulation under anesthesia (MUA) to arthrolysis for combat-related arthrofibrosis. Sixty-one knees in 56 patients who underwent treatment for arthrofibrosis secondary to lower extremity trauma were reviewed. Knee range of motion preoperatively, postoperatively, and at follow-up was analyzed. The primary outcome measure was the difference in knee arc of motion between the two cohorts. Forty-one knees (67.2%) underwent MUA and 20 knees (32.8%) were managed operatively. There was no difference in the preoperative arc of motion. Knees that underwent MUA had significant improvements in arc of motion compared to knees that underwent arthrolysis (106.3° vs. 82.3°) at a follow-up of 2 years (p = .008). The complication rate was greater in knees that underwent arthrolysis (40%) compared to knees that underwent MUA (12.2%; p = .04). In conclusion, knees that underwent MUA demonstrated significant improvements in arc of motion at 2-year follow-up with fewer complications.

Predisposing risk factors for non-contact ACL injuries in military subjects.

PURPOSE: The goal of this study was to document the incidence of anterior cruciate ligament (ACL) tears and possible risk factors for these injuries in a large population of young, athletic subjects. METHODS: The authors retrospectively reviewed the US Naval Academy's database of midshipmen admitted in 1999 and 2000 (n = 2,345) and prospectively followed until graduation 4 years later or disenrollment. Excluded were 658 who had a history of preadmission ACL injury or surgery, those without initial radiographs or documented baseline height and weight, or those who had documented contact ACL injuries. Therefore, 1,687 subjects comprised the study group. Standard radiographic measurements, including condylar width, notch width, and femoral notch width index (notch width divided by condyle width), were obtained for all subjects. Statistical analyses were used to determine differences between injured and uninjured subjects. RESULTS: The overall incidence of non-contact ACL injury was 2.9% (37 men, 12 women). The average BMI was 25.6 and 24.4 kg/m(2) for the injured and uninjured groups, respectively (P < 0.05). Although femoral notch width alone was not associated with non-contact ACL injuries, subjects with higher than average BMI in combination with narrow notch width were at significant risk for ACL injury (P = 0.021). CONCLUSIONS: Elevated BMI combined with narrow notch width may predispose young athletes to non-contact ACL injury. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Occult femoral neck fracture associated with vitamin D deficiency diagnosed by MRI: case report.

Hip fractures in the young are exceedingly rare and are usually seen in instances of high energy trauma or metabolically altered bone states. In this case report, we present an occult femoral neck fracture, diagnosed by magnetic resonance imaging, in an otherwise healthy, young, active duty male patient with an isolated vitamin D deficiency treated using cannulated percutaneous screws.

Incidence of pulmonary embolus in combat casualties with extremity amputations and fractures.

BACKGROUND: The objective of this retrospective study was to determine the incidence of pulmonary embolism (PE) in casualties of wartime extremity wounds and specifically in casualties with a trauma-associated amputation. METHODS: Records of all combat-wounded evacuated and admitted between March 1, 2003, and December 31, 2007, were retrospectively reviewed. Continuous and categorical variables were studied with the Student's t test, Fisher's exact test or χ² test; multivariate analysis was performed using a stepwise regression logistic model. RESULTS: A total of 1,213 records were reviewed; 263 casualties met the inclusion criteria. One hundred three (41.5%) had amputations and 145 (58.5%) had long-bone fractures not requiring amputation. The observed rate of PE in these 263 casualties was 5.7%. More casualties with amputations, 10 (3.7%), developed PE than those with long-bone fractures in the absence of amputation, 5 (1.9%) (p = 0.045). Casualties with bilateral lower extremity trauma-associated amputations had a significantly higher incidence of PE compared with those sustaining a single amputation (p = 0.023), and the presence of bilateral lower extremity amputations was an independent risk factor for development of a PE (p = 0.007, odds ratio 5.9) (univariate and multivariate analysis, respectively). CONCLUSION: The cumulative incidence of PE was 5.7%. The incidence of PE is significantly higher with trauma-associated amputation than with extremity long-bone fracture without amputation. Bilateral amputations, multiple long-bone fractures, and pelvic fractures are independent risk factors for the development of PE. The use of aggressive prophylaxis, deep venous thrombosis screening with ultrasound, and use of prophylactic inferior vena cava filters should be considered in this patient population.

Monitoring the healing of combat wounds using Raman spectroscopic mapping.

Soldiers wounded in modern warfare present with extensive and complicated acute wounds, confounded by an overwhelming inflammatory response. The pathophysiology of acute wounds is unknown and timing of wound closure remains subjective. Collagen gene expression profiles are presented for 24 patients. Impaired healing wounds showed a twofold decrease in the up-regulation of COL1A1 and COL3A1 genes in the beginning of the wound healing process, compared with normal healing wounds. By the final debridement, however, collagen gene expression profiles for normal and impaired healing wounds were similar for COL1A1 and COL3A1. In addition, Raman spectroscopic maps were collected of biopsy tissue sections, from the first and last debridements of 10 wounds collected from nine patients. Tissue components obtained for the debridement biopsies were compared to elucidate whether or not a wound healed normally. Raman spectroscopy showed a loss of collagen in five patients, indicated by a negative percent difference in the 1,665/1,445 cm(-1) band area ratios. Four healed patients showed an increased or unchanged collagen content. Here, we demonstrate the potential of Raman spectroscopic analysis of wound biopsies for classification of wounds as normal or impaired healing. Raman spectroscopy has the potential to noninvasively monitor collagen deposition in the wound bed, during surgical wound debridements, to help determine the optimal time for wound closure.

Case report: Fresh-stored osteochondral allograft for treatment of osteochondritis dissecans the femoral head.

Osteochondral defects of the femoral head are exceedingly rare, with limited treatment options. Restoration procedures for similar defects involving the knee and ankle have been well described. In this report, we present a young patient who had a symptomatic osteochondral defect of the femoral head develop secondary to trauma and underwent subsequent treatment using a fresh-stored osteochondral allograft via a trochanteric osteotomy. At the 1-year followup, the patient was symptom free with near-complete incorporation of the graft radiographically. Our observations in this case suggest osteoarticular implantation may be an appropriate alternative to consider when treating osteochondral defects of the femoral head.

Bioartificial dermal substitute: a preliminary report on its use for the management of complex combat-related soft tissue wounds.

OBJECTIVE: To report our institutional experience with the use of a bioartificial dermal substitute (Integra) combined with subatmospheric pressure [vacuum-assisted closure (VAC)] dressings followed by delayed split-thickness skin grafting for management of complex combat-related soft tissue wounds secondary to blast injuries. DESIGN: Retrospective review of patients treated December 2004 through November 2005. SETTING: Military treatment facility. PATIENTS/PARTICIPANTS: Integra grafting was performed 18 times in 16 wounds at our institution. Indications for Integra placement were wounds not amenable to simple split-thickness skin grafting, specifically those with substantial exposed bone and/or tendon. INTERVENTION: Patients underwent an average of 8.5 irrigation and debridement procedures and concurrent VAC dressings prior to placement of the Integra. Following Integra grafting, all patients were managed with VAC dressings, changed every 3 to 4 days at the bedside or in clinic, with subsequent split-thickness skin grafting an average of 19 days later. MAIN OUTCOME MEASUREMENTS: The mechanism and date of injury, size of residual soft tissue deficit, indication for Integra placement, number of irrigation and debridement procedures prior to Integra placement, days from injury to Integra placement, days from Integra placement to split-thickness skin grafting, and clinical outcome were recorded. RESULTS: Integra placement and subsequent skin grafting was successful in achieving durable and cosmetic definitive coverage in 15 of 16 wounds with two of these patients requiring repeat Integra application. Two patients with difficult VAC dressing placement had early Integra graft failure but successfully healed following repeated Integra application and skin grafting. CONCLUSIONS: Bioartificial dermal substitute grafting, when coupled with subatmospheric dressing management and delayed split-thickness skin grafting, is an effective technique for managing complex combat-related soft tissue wounds with exposed tendon. This can potentially lessen the need for local rotational or free flap coverage.

Injury severity score underpredicts injury severity and resource utilization in combat-related amputations.

OBJECTIVE: Assess effectiveness of Injury Severity Score (ISS) in predicting injury severity in combat-related amputations. DESIGN: Retrospective evaluation of prospectively collected data. SETTING: Military medical center. PATIENTS: One hundred and nine patients with major extremity amputations sustained in overseas combat. INTERVENTION: Standard combat casualty care. MAIN OUTCOME MEASUREMENTS: Difference in injury severity as measured by ISS, numbers of extremity(s) amputated, number of associated injuries, blood products used, intensive care unit length of stay, hospital length of stay in those with an upper extremity amputation (UEA) compared with those with an isolated lower extremity amputation. RESULTS: Thirteen patients (11.9%) sustained at least one UEA. Patients with an UEA had a greater number of amputations per casualty compared with patients with a lower extremity alone (2.5 vs. 1.5; P < 0.001). The mean hospital length of stay (P = 0.02) and intensive care unit length of stay (P = 0.02) were significantly greater in those with an UEA. Mean blood product utilization was also significantly greater in those with an upper extremity amputation (P < 0.05). There was no difference in ISS between the two groups (P > 0.05). CONCLUSIONS: The presence of an UEA is associated with increased injury severity as evident by increased intensive care unit requirements, blood product utilization, and hospital length of stay. ISS underestimates the severity of injury and therefore resource utilization in patients with multiple combat-related amputations. Recognition of this limitation in addition to the development of a military-specific ISS is required for more effective resource utilization to continue to improve combat casualty care. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Inflammatory cytokine and chemokine expression is associated with heterotopic ossification in high-energy penetrating war injuries.

OBJECTIVE: Heterotopic ossification (HO) develops frequently after modern high-energy penetrating war injuries. The purpose of this prospective study was to identify and characterize the unique cytokine and chemokine profile associated with the development of HO as it pertained to the systemic inflammatory response after penetrating combat-related trauma. METHODS: Patients with high-energy penetrating extremity wounds were prospectively enrolled. Surgical debridement along with the use of a pulse lavage and vacuum-assisted-closure device was performed every 48-72 hours until definitive wound closure. Wound bed tissue biopsy, wound effluent, and serum were collected before each debridement. Effluent and serum were analyzed for 22 relevant cytokines and chemokines. Tissue was analyzed quantitatively for bacterial colonization. Correlations between specific wound and patient characteristics were also analyzed. The primary clinical outcome measure was the formation of HO as confirmed by radiographs at a minimum of 2 months of follow-up. RESULTS: Thirty-six penetrating extremity war wounds in 24 patients were investigated. The observed rate of HO in the study population was 38%. Of the 36 wounds, 13 (36%) demonstrated HO at a minimum follow-up of 2 months. An elevated injury severity score was associated with the development of HO (P = 0.006). Wound characteristics that correlated with the development of HO included impaired healing (P = 0.005) and bacterial colonization (P < 0.001). Both serum (interleukin-6, interleukin-10, and MCP-1) and wound effluent (IP-10 and MIP-1α) cytokine and chemokine bioprofiles were individually associated and suggestive of the development of HO (P < 0.05). CONCLUSIONS: A severe systemic and wound-specific inflammatory state as evident by elevated levels of inflammatory cytokines, elevated injury severity score, and bacterial wound colonization is associated with the development of HO. These findings suggest that the development of HO in traumatic combat-related wounds is associated with a hyper-inflammatory systemic response to injury. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.