Elizabeth M. Polfer

Do Inflammatory Markers Portend Heterotopic Ossification and Wound Failure in Combat Wounds

BackgroundAfter a decade of war in Iraq and Afghanistan, we have observed an increase in combat-related injury survival and a paradoxical increase in injury severity, mainly because of the effects of blasts. These severe injuries have a devastating effect on each patient’s immune system resulting in massive upregulation of the systemic inflammatory response. By examining inflammatory mediators, preliminary data suggest that it may be possible to correlate complications such as wound failure and heterotopic ossification (HO) with distinct systemic and local inflammatory profiles, but this is a relatively new topic.Questions/purposesWe asked whether systemic or local markers of inflammation could be used as an objective means, independent of demographic and subjective factors, to estimate the likelihood of (1) HO and/or (2) wound failure (defined as wounds requiring surgical débridement after definitive closure, or wounds that were not closed or covered within 21 days of injury) in patients sustaining combat wounds.MethodsTwo hundred combat wounded active-duty service members who sustained high-energy extremity injuries were prospectively enrolled between 2008 and 2012. Of these 200 patients, 189 had adequate followups to determine the presence or absence of HO, and 191 had adequate followups to determine the presence or absence of wound failure. In addition to injury-specific and demographic data, we quantified 24 cytokines and chemokines during each débridement. Patients were followed clinically for 6 weeks, and radiographs were obtained 3 months after definitive wound closure. Associations were investigated between these markers and wound failure or HO, while controlling for known confounders.ResultsThe presence of an amputation (p < 0.001; odds ratio [OR], 6.1; 95% CI. 1.63–27.2), Injury Severity Score (p = 0.002; OR, 33.2; 95% CI, 4.2–413), wound surface area (p = 0.001; OR, 1.01; 95% CI, 1.002–1.009), serum interleukin (IL)-3 (p = 0.002; OR, 2.41; 95% CI, 1.5–4.5), serum IL-12p70 (p = 0.01; OR, 0.49; 95% CI, 0.27–0.81), effluent IL-3 (p = 0.02; OR, 1.75; 95% CI, 1.2–2.9), and effluent IL-13 (p = 0.006; OR, 0.67; 95% CI, 0.50–0.87) were independently associated with HO formation. Injury Severity Score (p = 0.05; OR, 18; 95% CI, 5.1–87), wound surface area (p = 0.05; OR, 28.7; 95% CI, 1.5–1250), serum procalcitonin ([ProCT] (p = 0.03; OR, 1596; 95% CI, 5.1–1,758,613) and effluent IL-6 (p = 0.02; OR, 83; 95% CI, 2.5–5820) were independently associated with wound failure.ConclusionsWe identified associations between patients’ systemic and local inflammatory responses and wound-specific complications such as HO and wound failure. However, future efforts to model these data must account for their complex, time dependent, and nonlinear nature.Level of Evidence Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Raman spectroscopic analysis of combat-related heterotopic ossification development☆

Over 60% of our severely combat-injured patient population develops radiographically apparent heterotopic ossification. Nearly a third of these require surgical excision of symptomatic lesions, a procedure that is fraught with complications, and delays or regresses functional rehabilitation in many cases. Unfortunately, for the combat injured, medical contraindications and logistical limitations limit widespread use of conventional means of primary prophylaxis. Better means of risk stratification are needed to both mitigate the risk of current means of primary prophylaxis as well as to evaluate novel preventive strategies currently in development. We asked whether Raman spectral changes, measured ex vivo, correlated with histologic evidence of the earliest signs of HO formation using tissue biopsies from the wounds of combat casualties. In doing so, we compared normal muscle tissue to injured muscle tissue, unmineralized HO tissue, and mineralized HO tissue. The Raman spectra of these tissues demonstrate clear differences in the amide I and amide III spectral regions of HO tissue compared to normal tissue, denoted by changes in the 1640/1445cm(-1)(p<0.01), and 1340/1270cm(-1) (p<0.01) band area ratios (BARs). Additionally, analysis of the bone mineral in HO by Raman spectroscopy appears capable of determining bone maturity by measuring both the 945/960cm(-1) and the 1070/1445cm(-1) BARs. Raman may therefore prove a useful, non-invasive, and early diagnostic modality to detect HO formation prior to it becoming evident clinically or radiographically. This technique could ostensibly be utilized as a non-invasive means to risk stratify individual wounds at a time thought to be amenable to various means of primary prophylaxis.

The development of a rat model to investigate the formation of blast-related post-traumatic heterotopic ossification

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification.

A decade of conflict: flap coverage options and outcomes in traumatic war-related extremity reconstruction.

Background: War trauma patients who have sustained extremity trauma often exhibit extensive zones of injury with multiple concomitant injuries that can contribute to limited coverage options. Thus, flap availability and choice can become critical in the reconstruction algorithm of these severely traumatized patients. The authors’ purpose was to analyze the outcomes of muscle and fasciocutaneous flaps during their extremity reconstructive experience to determine which option had better flap and limb salvage outcomes. Methods: A retrospective review of servicemembers treated with flap-based limb salvage from 2003 through 2012 at the National Capital Consortium was completed. Patients were divided into cohorts of patients who underwent muscle or fasciocutaneous flaps. Results: Three hundred fifty-nine flap procedures were performed. Of these procedures, 197 were muscle (55 percent) and 152 were fasciocutaneous flaps (42 percent). There was no difference in overall flap complications between groups (30 percent versus 26 percent; p = 0.475). However, there was a significantly higher flap failure rate in the muscle compared with the fasciocutaneous group (13 percent versus 6 percent; p = 0.030). Although there were more overall extremity complications in the muscle group (59 percent versus 47 percent; p = 0.030), there were no significant differences in soft-tissue infection, osteomyelitis, or amputation rates. Conclusions: There are many flap options that provide adequate coverage in extremity salvage. Complication rates did not differ significantly between muscle and fasciocutaneous flaps, with one exception—flap failure rates were significantly higher in our muscle-based flap cohort of patients. Nonetheless, each of these flap types has utility in our patients based on individual wounding patterns, flap availability for reconstruction, and rehabilitation goals. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Neurovascular entrapment due to combat-related heterotopic ossification in the lower extremity.

BACKGROUND Heterotopic ossification is the ectopic formation of mature lamellar bone in nonosseous tissue. The prevalence of heterotopic ossification following combat injuries is much higher than civilian data would suggest. In certain cases, the aberrant bone formation can envelop major neurovascular structures in the lower extremity, leading to symptomatic neurovascular entrapment. METHODS We describe five consecutive cases of heterotopic ossification leading to symptomatic neurovascular entrapment in the lower extremity as a result of blast trauma and present our method of patient assessment, preoperative planning, and surgical excision. RESULTS Heterotopic bone was successfully excised without neurovascular injury in all patients. At a mean of twenty months (range, eight to forty-five months) postoperatively, all patients demonstrated continued improvement of their pre-excision function. All patients who had neuropathic pain had a decrease in the pain. Those with decreased joint motion regained motion once their wounds were stable. Sensory deficits resolved before motor deficits did. There was no recurrence of clinically relevant heterotopic ossification in this series. CONCLUSIONS Excision of heterotopic bone, particularly with concurrent neurovascular entrapment, can be associated with major short-term and long-term complications. With use of our treatment algorithm, involving careful preoperative planning and meticulous operative excision, heterotopic bone entrapping major neurovascular structures following severe extremity trauma can be safely excised with subsequent clinical improvement.

Fluid Collections in Amputations Are Not Indicative or Predictive of Infection

BackgroundIn the acute postoperative period, fluid collections are common in lower extremity amputations. Whether these fluid collections increase the risk of infection is unknown.Questions/purposesThe purposes of this study were to determine (1) the percentage of patients who develop postoperative fluid collections in posttraumatic amputations and the natural course of the collection; (2) whether patients who develop these collections are at increased risk for infection; and to ask (3) are there objective clinical or radiologic signs that are associated with likelihood of infection when a fluid collection is present?MethodsWe performed a review of all 300 patients injured in combat operations who sustained at least one major lower extremity amputation (at or proximal to the tibiotalar joint) and were treated definitively at our institution between March 2005 and April 2009. We segregated the groups based on whether cross-sectional imaging was performed less than 3 months (early group) after closure, greater than 3 months (late group) after closure, or not at all (control group, baseline frequency of infection). Our primary study cohort where those patients with a fluid collection in the first three months. The clinical course was reviewed and the primary outcome was a return to the operating room for irrigation and débridement with positive cultures. For those patients with cross-sectional imaging, we also collected objective clinical parameters within 24 hours of the scan (white blood cell count, maximum temperature, presence of bacteremia, tachycardia, oxygen desaturation), extremity examination (presence of erythema, warmth, and/or drainage), and characteristics of the fluid collections seen (size of the fluid collection, enhancement, complexity (simple versus loculated), surrounding edema, skin changes, tract formation, presence of air, and changes within the bone itself). The presence of a fluid collection on imaging was analyzed to determine whether it was associated with infection. We further analyzed clinical parameters, objective physical examination findings at the extremity, and characteristics of the fluid collection to determine if there were other parameters associated with infection.ResultsOver half (55%) of the limbs demonstrated fluid collection in the early postoperative period and the prevalence decreased in the late group (11%; p = 0.001). There was no association between the presence of a fluid collection and infection. However, there was an association between objective clinical signs at the extremity (erythema and/or drainage) and infection (p < 0.001) in our primary study cohort.ConclusionsFluid collections are common in combat-related amputations in the immediate postoperative period and become smaller and less frequent over time. In the absence of extremity erythema and wound drainage, imaging of a residual limb to evaluate for the presence of a fluid collection appears to be of little clinical use.Level of EvidenceLevel III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Skin Grafts for Residual Limb Coverage and Preservation of Amputation Length.

Background: Split-thickness skin grafts have historically been used sparingly for amputation coverage when delayed primary closure is not feasible without substantial loss of length. The authors investigated the use of split-thickness skin grafts in the residual limbs of combat-related amputees. Methods: A retrospective review was completed on consecutive amputations of 300 lower and 100 upper extremities treated at Walter Reed National Military Medical Center from 2003 to 2009, comparing patients treated with split-thickness skin grafts with those treated with delayed primary closure. Principal outcomes measured included early (wound failure) and late (heterotopic ossification requiring excision and soft-tissue revisions) complications requiring surgery. Results: Statically significant differences were seen, with the split-thickness skin graft group having an increased incidence of wound failure (p < 0.022), heterotopic ossification requiring excision (p < 0.001), and soft-tissue revisions (p < 0.001) compared with controls. The risk of revision was higher for lower extremity than for upper extremity amputations undergoing skin grafting. However, amputation level salvage, maintaining the proximal joint, was successful for all residual limbs with split-thickness skin grafts. Conclusions: Split-thickness skin grafts for closure of amputations result in significantly increased reoperation rates, but they are ultimately successful in salvaging residual limb length and amputation levels. In carefully selected patients, they may be a successful means of achieving definitive coverage when performed over robust, healthy muscle. In many patients, however, they should be viewed as a staging procedure to maintain length and amputation level until swelling decreases and revision surgery for split-thickness skin graft excision with or without concurrent procedures can be performed without the need to substantially shorten the residual limb.

Turn-up Plasty for Salvage of Transtibial Amputations: An Illustrated Description of the Surgical Technique

Case: We present the operative technique for turn-up plasty with a transtibial amputation in three patients with combat-related open tibial fractures who ultimately required amputation. Unaugmented amputation would have resulted in residual limbs of 7 cm; however, with use of the turn-up plasty technique, resultant limbs averaged 14 cm. All three patients achieved union at the osteosynthesis site and regular ambulation with a below-the-knee prosthesis. Conclusion: Transtibial turn-up plasty for length and level salvage is a sound option to provide robust, sensate soft-tissue coverage with additional osseous length when limb salvage fails and primary amputation would result in either an extremely short transtibial amputation or a more proximal level amputation.

Zone I Flexor Digitorum Profundus Repair: A Surgical Technique

We present an all-inside technique for zone I flexor tendon repair that combines suture anchor fixation with buried back-up fixation. The back-up fixation uses transosseous tunnels and a dorsal counterincision to allow a suture tied dorsal to the distal phalanx and buried. This technique is strong and permits early active range of motion. The dorsal tie-over does not require a suture button and, therefore, does not imperil the nail matrix. The surgical technique is herein described including the proposed anesthesia (wide awake), the incisions (midlateral), the exposures, and the repair itself.

Anatomical Variation of the Radial Artery Associated With Clinically Significant Ischemia

PURPOSE The purpose of this retrospective review was to investigate the incidence of radial artery anatomical variations in patients with clinically significant distal upper extremity (UE) ischemia. Available anatomical studies report that high takeoff of the radial artery occurs in up to 15% of the population. We hypothesized that there is a higher incidence of high origin of the radial artery in patients with clinically significant ischemia compared with the reported frequency in the general population. METHODS We performed a retrospective review of all patients who underwent UE angiography for clinically significant hand and digital ischemia in our institution from 2012 to 2016. Data collected included patient age, sex, comorbidities, and modality of treatment. RESULTS Twenty-six angiograms were performed for UE ischemia meeting inclusion criteria. Eight patients had Raynaud disease or scleroderma. Ten patients (38%) had high radial artery takeoff with radial artery origin proximal to the antecubital fossa. The need for surgical intervention was similar in patients with normal anatomy and those with high takeoff of the radial artery. CONCLUSIONS Incidence of high radial artery takeoff was found more frequently in patients with distal UE ischemia requiring angiogram than in reported population data. TYPE OF STUDY/LEVEL OF EVIDENCE Diagnostic IV.