Intrawound Antibiotic Powder Decreases Frequency of Deep Infection and Severity of Heterotopic Ossification in Combat Lower Extremity Amputations.

BACKGROUND: Amputations sustained owing to combat-related blast injuries are at high risk for deep infection and development of heterotopic ossification, which can necessitate reoperation and place immense strain on the patient. Surgeons at our institution began use of intrawound antibiotic powder at the time of closure in an effort to decrease the rate of these surgical complications after initial and revision amputations, supported by compelling clinical evidence and animal models of blast injuries. Antibiotic powder may be useful in reducing the risk of these infections, but human studies on this topic thus far have been inconclusive. PURPOSE: We sought to determine whether administration of intrawound antibiotic powder at the time of closure would (1) decrease the risk of subsequent deep infections of major lower-extremity combat-related amputations, and (2) limit formation and decrease severity of heterotopic ossification common in the combat-related traumatic residual limb. METHODS: Between 2009 and 2015, 252 major lower extremity initial and revision amputations were performed by a single surgeon. Revision cases were excluded if performed specifically to address deep infection, leaving 223 amputations (88.5%) for this retrospective analysis. We reviewed medical records to collect patient information, returns to the operating room for subsequent infection, and microbiologic culture results. We also reviewed radiographs taken at least 3 months after surgery to determine the presence and severity of heterotopic ossification using the Walter Reed classification system. We grouped cases according to whether limbs underwent initial or revision amputations, and whether the limbs had a history of a prior infection. Apart from the use of antibiotic powder and duration of followup, the groups did not differ in terms of age, mechanism of injury, or sex. We then calculated the absolute risk reduction for infection and heterotopic ossification and the number needed to treat to prevent an infection. RESULTS: Overall, administration of antibiotic powder resulted in a 13% absolute risk reduction of deep infection (14 of 82 [17%] versus 42 of 141 [30%]; p = 0.03; 95% CI, 0.20%-24.72%). In revision amputation surgery, the absolute risk reduction of infection with antibiotic powder use was 16% overall (eight of 58 versus 17 of 57; 95% CI, 1.21%-30.86%), and 25% for previously infected limbs (eight of 46 versus 14 of 33; 95% CI, 4.93%-45.14%). The number needed to treat to prevent one additional deep infection in amputation surgery is eight in initial amputations, seven in revision amputations, and four for revision amputation surgery on previously infected limbs. With the numbers available, we observed no reduction in the risk of heterotopic ossification with antibiotic powder use, but severity was decreased in the treatment group in terms of the number of residual limbs with moderate or severe heterotopic ossification (three of 12 versus 19 of 34; p = 0.03). CONCLUSIONS: Our findings show that administration of intrawound antibiotic powder reduces deep infection in residual limbs of combat amputees, particularly in the setting of revision amputation surgery in apparently aseptic residual limbs at the time of the surgery. Furthermore, administration of antibiotic powder for amputations at time of initial closure decreases the severity of heterotopic ossification formation, providing a low-cost adjunct to decrease the risk of two complications common to amputation surgery.Level of Evidence Level III, therapeutic study.

Early Characterization of Blast-related Heterotopic Ossification in a Rat Model.

BACKGROUND: Heterotopic ossification (HO) affects the majority of combat-related lower extremity wounds involving severe fracture and amputation. Defining the timing of early osteogenic-related genes may help identify candidate prophylactic agents and guide the timing of prophylactic therapy after blast and other combat-related extremity injuries. QUESTIONS/PURPOSES: Using a recently developed animal model of combat-related HO, we sought to determine (1) the timing of early chondrogenesis, cartilage formation, and radiographic ectopic bone development; and (2) the early cartilage and bone-related gene and protein patterns in traumatized soft tissue. METHODS: We used an established rat HO model consisting of blast exposure, controlled femur fracture, crush injury, and transfemoral amputation through the zone of injury. Postoperatively, rats were euthanized on Days 3 to 28. We assessed evidence of early ectopic bone formation by micro-CT and histology and performed proteomic and gene expression analysis. RESULTS: All rats showed radiographic evidence of HO within 28 days. Key chondrogenic (collagen type I alpha 1 [COL1α1], p = 0.016) and osteogenic-related genes (Runt-related transcription factor 2 [RUNX-2], p = 0.029; osteoclacin [OCN], p = 0.032; phosphate-regulating neutral endopeptidase, X-linked [PHEX], p = 0.0290, and POU domain class 5 transcription factor [POU5F], p = 0.016) and proteins (Noggin [NOG], p = 0.04, OCN, p = 0.02, RUNX- 2, p = 0.04, and substance P-1 [SP-1], p = 0.01) in the injured soft tissue, normalized to the contralateral limb and/or sham-treated naïve rats, increased on Days 3 to 14 postinjury. By 14 days, foci of hypertrophic chondrocytes, hyaline cartilage, and woven bone were present in the soft tissue surrounding the amputation site. CONCLUSIONS: We found that genes that regulate early chondrogenic and osteogenic signaling and bone development (COL1α1, RUNX-2, OCN, PHEX, and POU5F1) are induced early during the tissue reparative/healing phase in a rat model simulating a combat-related extremity injury. CLINICAL RELEVANCE: The ability to correlate molecular events with histologic and morphologic changes will assist researchers and clinicians to understand HO and hence formulate therapeutic interventions.

What Risk Factors Predict Recurrence of Heterotopic Ossification After Excision in Combat-related Amputations?

BACKGROUND: Heterotopic ossification (HO) is common after combat-related amputations and surgical excision remains the only definitive treatment for persistently symptomatic HO. There is no consensus in the literature regarding the timing of surgery, and recurrence frequency, reexcision, and complications have not been reported in large numbers of patients. QUESTIONS/PURPOSES: (1) What are the rates of symptomatic recurrence resulting in reexcision and other complications resulting in reoperation in patients with HO? (2) Is either radiographic or symptomatic recurrence dependent on timing and type of initial surgery, the experience of the surgeon in performing the procedure, the severity of preexcision HO, the presence of concomitant neurologic injury, or the use of postoperative HO prophylaxis? METHODS: Between March 2005 and March 2013 our institution treated 994 patients with 1377 combat-related major extremity amputations; of those, 172 amputations underwent subsequent excision of symptomatic HO. The mechanism of injury resulting in nearly all amputations (n = 168) was blast-related trauma. We reviewed medical records and radiographs to collect initial grade of HO, radiographic recurrence, complete compared with partial excision, concomitant neurologic injury, timing to initial surgery, surgeon experience, and use of postexcision prophylaxis with our primary study outcome being a return to the operating room (OR) for repeat excision of symptomatic HO. All 172 combat-related amputations were considered for this study irrespective of followup, which was noted to be robust, with 157 (91%) amputations having at least 6 months clinical followup by an orthopaedic surgeon or physiatrist (median, 20 months; range, 0-88 months). RESULTS: Eleven of 172 patients (6.5%) underwent reexcision of HO, and 67 complications resulting in return to the OR occurred in 53 patients (31%) of patients. Multivariate analysis of our primary outcome measure showed more frequent symptomatic recurrences requiring reexcision when initial excision was performed as a partial excision (p = 0.03; odds ratio [OR], 5.0; 95% confidence interval [CI], 1.2-29.6) or when the initial excision was performed within 180 days of injury (p = 0.047; OR, 4.1; 95% CI, 1.02-16.6). There was no association between symptomatic recurrence and HO grade, central nervous system injury, experience of the attending surgeon, or postoperative prophylaxis. Radiographic recurrence was observed when partial excisions (eight of 30 [27%]) were done compared with complete excisions (five of 77 [7%]; p = 0.008). CONCLUSIONS: HO is common after combat-related amputations, and patients undergoing surgical excision of HO for this indication often have complications that result in repeat surgical procedures. Partial excisions of immature lesions more often resulted in both symptomatic and radiographic recurrence. The likelihood of a patient undergoing reexcision can be minimized by performing a complete excision at least 180 days from injury to surgery with no evidence of a reduced risk of reexcision by waiting longer than 270 days. LEVEL OF EVIDENCE: Level III, therapeutic study.

Bioburden Increases Heterotopic Ossification Formation in an Established Rat Model.

BACKGROUND: Heterotopic ossification (HO) develops in a majority of combat-related amputations wherein early bacterial colonization has been considered a potential early risk factor. Our group has recently developed a small animal model of trauma-induced HO that incorporates many of the multifaceted injury patterns of combat trauma in the absence of bacterial contamination and subsequent wound colonization. QUESTIONS/PURPOSES: We sought to determine if (1) the presence of bioburden (Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus [MRSA]) increases the magnitude of ectopic bone formation in traumatized muscle after amputation; and (2) what persistent effects bacterial contamination has on late microbial flora within the amputation site. METHODS: Using a blast-related HO model, we exposed 48 rats to blast overpressure, femur fracture, crush injury, and subsequent immediate transfemoral amputation through the zone of injury. Control injured rats (n = 8) were inoculated beneath the myodesis with phosphate-buffered saline not containing bacteria (vehicle) and treatment rats were inoculated with 1 × 10(6) colony-forming units of A baumannii (n = 20) or MRSA (n = 20). All animals formed HO. Heterotopic ossification was determined by quantitative volumetric measurements of ectopic bone at 12-weeks postinjury using micro-CT and qualitative histomorphometry for assessment of new bone formation in the residual limb. Bone marrow and muscle tissue biopsies were collected from the residual limb at 12 weeks to quantitatively measure the bioburden load and to qualitatively determine the species-level identification of the bacterial flora. RESULTS: At 12 weeks, we observed a greater volume of HO in rats infected with MRSA (68.9 ± 8.6 mm(3); 95% confidence interval [CI], 50.52-85.55) when compared with A baumannii (20.9 ± 3.7 mm(3); 95% CI, 13.61-28.14; p < 0.001) or vehicle (16.3 ± 3.2 mm(3); 95% CI, 10.06-22.47; p < 0.001). Soft tissue and marrow from the residual limb of rats inoculated with A baumannii tested negative for A baumannii infection but were positive for other strains of bacteria (1.33 × 10(2) ± 0.89 × 10(2); 95% CI, -0.42 × 10(2)-3.08 × 10(2) and 1.25 × 10(6) ± 0.69 × 10(6); 95% CI, -0.13 × 10(6)-2.60 × 10(6) colony-forming units in bone marrow and muscle tissue, respectively), whereas tissue from MRSA-infected rats contained MRSA only (4.84 × 10(1) ± 3.22 × 10(1); 95% CI, -1.47 × 10(1)-11.1 × 10(1) and 2.80 × 10(7) ± 1.73 × 10(7); 95% CI, -0.60 × 10(7)-6.20 × 10(7) in bone marrow and muscle tissue, respectively). CONCLUSIONS: Our findings demonstrate that persistent infection with MRSA results in a greater volume of ectopic bone formation, which may be the result of chronic soft tissue inflammation, and that early wound colonization may be a key risk factor. CLINICAL RELEVANCE: Interventions that mitigate wound contamination and inflammation (such as early débridement, systemic and local antibiotics) may also have a beneficial effect with regard to the mitigation of HO formation and should be evaluated with that potential in mind in future preclinical studies.

An Analysis of Research from Faculty at U.S. Adult Reconstruction Fellowships.

We reviewed all articles published in three major orthopaedic journals from January 2010 to December 2014. Any article focusing on adult reconstruction of the hip or knee was reviewed for first and last authorship, institution, and level of evidence. Three institutions had authored work from arthroplasty faculty that fell within the top five most published institutions in all three journals, while one institution ranked first in all three journals. 43 of 67 (64.2%) reconstruction fellowships had at least one publication included in this study. The majority of the adult reconstruction literature published by faculty at U.S. reconstruction fellowships stems from a few academic centers with the ten most prolific institutions accounting for 65.9% of all U.S. fellowship publications.

Successful Closed Reduction of Distal Radius Volar Locking Plate Plastic Deformation with Associated Fracture: A Case Report.

CASE: Distal radius fractures are among the most common orthopaedic injuries. The volar locking plate is now the most utilized internal fixation method for these fractures. There are few reports of mechanical failure of volar locking plates within the literature. In this case report, we describe successful closed reduction of traumatic volar locking plate plastic deformation with associated fracture. In addition, we discuss existing literature regarding plastic deformation of distal radius plates. CONCLUSION: Traumatic, plastic deformation of distal radius volar locking plates with associated fracture may be managed nonoperatively with closed reduction.

Contemporary Management of Appendicular Skeletal Metastasis by Primary Tumor Type.

Skeletal metastases exert a profound effect on patients and society, and will be encountered by most orthopedic surgeons. Once a primary malignancy is diagnosed, multidisciplinary management should focus on maximizing the quality of life while minimizing disease- and treatment-related morbidity. This may be best achieved with discerning attention to the unique characteristics of primary cancer types, including pathologic fracture healing rates, longevity, and efficacy of adjuvant therapies. Some lesions may respond well to nonsurgical measures, whereas others may require surgery. A single surgical intervention should allow immediate unrestricted activity and outlive the patient. In certain scenarios, a therapeutic benefit may be provided by excision with a curative intent. In these scenarios, or when endoprosthetic reconstruction is necessary, patients may be best referred to an orthopedic oncologist.

Heterotopic ossification and lessons learned from fifteen years at war: A review of therapy, novel research, and future directions for military and civilian orthopaedic trauma.

Heterotopic ossification, the formation of bone in soft tissues, is a common complication of the high-energy extremity trauma sustained in modern armed conflict. In the past 15years, military treatment facilities and aligned laboratories have been in a unique position to study and treat this process due to the high volume of patients with these injuries secondary to blast trauma. The devastating nature of these wounds has limited traditional therapeutic options, necessitating alternative solutions to prophylaxis and initial treatment producing substantial advances in modeling, prophylaxis, detection, and therapy. Specific developments include establishment of an animal model that reproduces the systemic and local tissue injury of blast injuries, the use of molecular assays and predictive modeling in clinical decision making, advances in early detection including Raman spectroscopy, and investigation of prophylactic and therapeutic pharmacotherapy targeting the molecular pathways of aberrant bone formation. In this review article, we will present the literature to date, ongoing studies, and future directions for investigation of heterotopic ossification, with a focus on military-specific research.

Has the Proportion of Combat-Related Amputations That Develop Heterotopic Ossification Increased?

OBJECTIVES: To determine what proportion of residual limbs formed heterotopic ossification (HO) in amputations sustained by US service members, the injury profile of these amputations, and what effect the number of limb amputations sustained has on resource utilization. DESIGN: Retrospective review. SETTING: A tertiary military medical center. PATIENTS: Four-hundred seventy-one consecutive patients with 714 combat-related amputations were treated at our institution between September 2009 and August 2014. Four-hundred thirty-nine amputations had radiographic follow-up beyond 2 months of injury and met the criteria for study inclusion. MAIN OUTCOME MEASURE: Formation and grade of HO. RESULTS: HO was present in 399 of 439 (91%) residual limbs, including 211 of 216 (98%) transfemoral amputations. Dismounted improvised explosive device blast injury resulted in HO development in 346 of 372 (93%) residual limbs compared with 36 of 44 (82%) in mounted improvised explosive device blast injury [P = 0.014; odds ratio (OR) 2.96, 95% confidence interval (CI), 1.25-7.04]. As the number of amputations per patient increased, so too did blood product utilization [including packed red blood cells (P < 0.001), fresh frozen plasma (P < 0.001), and platelets (P < 0.001)]; the number of days on a ventilator (P < 0.001), in the intensive care unit (P < 0.001), and in the hospital (P = 0.007). CONCLUSIONS: HO prevalence in the traumatic amputations of war wounded has increased compared with earlier studies, which is temporally associated with higher rates of increasingly severe injuries due to dismounted blast. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma-induced heterotopic ossification.

Heterotopic ossification (HO) is a debilitating sequela of high-energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat-injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast-related, post-traumatic HO. Male Sprague-Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin-resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD-0, n = 34) or on postoperative day-3 (POD-3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12-weeks post-injury by micro-CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post-injury. Vancomycin treatment on POD-0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro-inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397-2406, 2017.

Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model.

Heterotopic ossification (HO) involves formation of endochondral bone at non-skeletal sites, is prevalent in severely wounded service members, and causes significant complications and delayed rehabilitation. As common prophylactic treatments such as anti-inflammatory drugs and irradiation cannot be used after multi-system combat trauma, there is an urgent need for new remedies. Previously, we showed that the retinoic acid receptor γ agonist Palovarotene inhibited subcutaneous and intramuscular HO in mice, but those models do not mimic complex combat injury. Thus, we tested Palovarotene in our validated rat trauma-induced HO model that involves blast-related limb injury, femoral fracture, quadriceps crush injury, amputation and infection with methicillin-resistant Staphylococcus aureus from combat wound infections. Palovarotene was given orally for 14days at 1mg/kg/day starting on post-operative day (POD) 1 or POD-5, and HO amount, wound dehiscence and related processes were monitored for up to 84days post injury. Compared to vehicle-control animals, Palovarotene significantly decreased HO by 50 to 60% regardless of when the treatment started and if infection was present. Histological analyses showed that Palovarotene reduced ectopic chondrogenesis, osteogenesis and angiogenesis forming at the injury site over time, while fibrotic tissue was often present in place of ectopic bone. Custom gene array data verified that while expression of key chondrogenic and osteogenic genes was decreased within soft tissues of residual limb in Palovarotene-treated rats, expression of cartilage catabolic genes was increased, including matrix metalloproteinase-9. Importantly, Palovarotene seemed to exert moderate inhibitory effects on wound healing, raising potential safety concerns related to dosing and timing. Our data show for the first time that Palovarotene significantly inhibits HO triggered by blast injury and associated complications, strongly indicating that it may prevent HO in patients at high risk such as those sustaining combat injuries and other forms of blast trauma.

Risk of Anterior Cruciate Ligament Injury in Athletes on Synthetic Playing Surfaces: A Systematic Review.

BACKGROUND: The effect of synthetic playing surfaces on the risk of injury in athletes is frequently debated in the orthopaedic literature. Biomechanical studies have identified increased frictional force at the shoe-surface interface, theoretically increasing the risk of injury relative to natural grass. This increase in frictional force is potentially relevant for the risk of anterior cruciate ligament (ACL) rupture, where noncontact mechanisms are frequent. However, clinical studies examining this issue have shown mixed results. HYPOTHESIS/PURPOSE: The purpose of this study was to systematically review the available literature on risk of ACL rupture on natural grass versus artificial turf. We hypothesized that the risk of ACL rupture on synthetic playing surfaces would not be higher than that of natural grass playing surfaces. STUDY DESIGN: Systematic review. METHODS: A systematic keyword search was performed of OVID, EMBASE, the Cochrane Library of Systematic Reviews, and the PROSPERO International Prospective Register of Systematic Reviews. Candidate articles were included if they reported the risk ratio of ACL rupture on natural grass versus synthetic playing surfaces, were of level 3 evidence or better, and included only ACL injuries sustained during organized athletic events. Exclusion criteria included a study with non-field-related sports and the use of historical cohorts for calculating risk ratios. RESULTS: A total of 10 studies with 963 ACL injuries met criteria for inclusion, all of which reported on soccer and football cohorts. Among these, 4 studies (753 ACL injuries) found an increased risk of ACL injury on artificial playing surfaces. All 4 of these articles were conducted using American football cohorts, and they included both earlier-generation surfaces (AstroTurf) and modern, 3rd-generation surfaces. Only 1 study in football players found a reduced risk of ACL injury on synthetic playing surfaces. No soccer cohort found an increased risk of ACL injury on synthetic surfaces. CONCLUSION: High-quality studies support an increased rate of ACL injury on synthetic playing surfaces in football, but there is no apparent increased risk in soccer. Further study is needed to clarify the reason for this apparent discrepancy.