Sequestration and Involucrum: Understanding Bone Necrosis and Revascularization in Pediatric Orthopedics.

Sequestration, a condition where a section of bone becomes necrotic due to a loss of vascularity or thrombosis, can be a challenging complication of osteomyelitis. This review explores the pathophysiology of sequestration, highlighting the role of the periosteum in forming involucrum and creeping substitution which facilitate revascularization and bone formation. The authors also discuss the induced membrane technique, a two-stage surgical procedure for cases of failed healing of sequestration. Future directions include the potential use of prophylactic anticoagulation and novel drugs targeting immunocoagulopathy, as well as the development of advanced imaging techniques and single-stage surgical procedures.

Navigating the Enigma of Pediatric Musculoskeletal Infections: A Race Against Time.

Musculoskeletal infection (MSKI) in children is a critical condition in pediatric orthopedics due to the potential for serious adverse outcomes, including multiorgan dysfunction syndrome, which can lead to death. The diagnosis and treatment of MSKI continue to evolve with advancements in infectious organisms, diagnostic technologies, and pharmacologic treatments. It is imperative for pediatric orthopedic surgeons and medical teams to remain up to date with the latest MSKI practices.

CRP Predicts the Need to Escalate Care After Initial Debridement for Musculoskeletal Infection.

BACKGROUND: Musculoskeletal infections (MSKIs) are a major cause of morbidity in the pediatric population and account for nearly 1 in every 10 consultations with a pediatric orthopaedic provider at a tertiary care center. To prevent or deescalate the risk of adverse medical and musculoskeletal outcomes, timely medical intervention in the form of antibiotics and potential surgical debridement is required. While there have been numerous studies indicating the value of laboratory testing during the initial workup of a child with MSKI, few studies to date have examined the utility of longitudinal assessment of laboratory measures in the acute setting to monitor the efficacy of antibiotic therapy and/or surgical intervention. The purpose of this investigation was to retrospectively determine whether measuring changes in the inflammatory response could indicate the need for escalated care. Specifically, this study examined the hypothesis that serial measurements of C-reactive protein (CRP), immediately preoperatively and 2 days after surgical debridement, could predict the need for medical (change in antibiotics) or surgical (additional debridement) escalation. METHODS: Retrospective review of pediatric patients undergoing operative debridement for the treatment of MSKI between September 2009 and December 2015 from whom laboratory data (CRP) was obtained preoperatively and at postoperative day (POD) 2. Patient demographics, the need for escalated care, and patient outcomes were evaluated. RESULTS: Across 135 pediatric patients, preoperative CRP values >90 mg/L and a positive change in CRP at POD2 effectively predicted the need for escalation of care after initial surgical debridement (Area under the Receiver Operator Curve: 0.883). For each 10-unit increase in preoperative CRP or postoperative change in CRP, there was a 21% or 22% increased risk of needing escalated care, respectively. Stratification by preoperative CRP >90 mg/L and change in CRP postoperatively likewise correlated with increased rates of disseminated disease, percent tissue culture positivity, length of stay, and rate of adverse outcomes. CONCLUSIONS: This study demonstrates the utility of serial CRP to assess the need for escalated care in patients being treated for MSKI. As serial CRP measurements become standard of practice in the acute setting, future prospective studies are needed to optimize the timing of CRP reassessment during inpatient hospitalization to prognosticate patient outcomes, weighing both improvements of patient care and clinical burden. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Growth factor free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia.

Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or de novo growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both ex vivo and in vivo assays. In a murine femoral artery ligation model of CLI, delivery of in situ crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.

Head and Neck Necrotizing Fasciitis: Abbreviated SOFA Score Associated With Death and Infection Spread.

Objective: Describe features unique to head and neck (H&N) necrotizing fasciitis (NF) compared to other anatomic regions and specify a prognostic score associated with death and descending necrotizing mediastinitis (DNM). Study Design: Retrospective cohort. Setting: Tertiary care, level 1 trauma center. Methods: A single-institution database identified 399 confirmed cases of NF between 2006 and 2021, 33 of which involved the H&N. Patients with confirmed H&N NF were sorted into cohorts based on clinical outcomes, with the "poor" outcomes group defined by death and/or DNM. Results: Thirty-three patients with H&N NF were included. Compared to NF of other regions, patients with H&N NF had a significantly lower mortality rate (6.06% vs 20.8%, p = .041) and significantly lower rates of obesity (27.3% vs 63.7%, p < .001) and hypertension (42.4% vs 60.9%, p = .038). Within the H&N group, there were 2 deaths (6.06%) and 8 cases of DNM (24.2%). Diabetes was associated with poor outcomes (p = .047), as was an abbreviated sequential organ failure assessment score for necrotizing fasciitis (nfSOFA) of 2 or greater (p = .015). Conclusion: H&N NF is unique among other forms of NF, with a lower mortality rate and lower rates of obesity and hypertension in affected patients. Within the H&N cohort, worse outcomes were associated with diabetes as well as a nfSOFA score of 2 or greater. Timely surgical debridement alongside broad-spectrum antibiotics remains the mainstay of treatment for NF; however, this simple prognostic score may play a role during the early stages of care for patients with H&N NF.

Maintaining the balance: the critical role of plasmin activity in orthopedic surgery injury response.

The musculoskeletal system plays vital roles in the body, facilitating movement, protecting vital structures, and regulating hematopoiesis and mineral metabolism. Injuries to this system are common and can cause chronic pain, loss of range of motion, and disability. The acute phase response (APR) is a complex process necessary for surviving and repairing injured musculoskeletal tissue. To conceptualize the APR, it is useful to divide it into 2 distinct phases, survival and repair. During the survival-APR, a "damage matrix" primarily composed of fibrin, via thrombin activity, is produced to contain the zone of injury. Once containment is achieved, the APR transitions to the repair phase, where reparative inflammatory cells use plasmin to systematically remove the damage matrix and replace it with new permanent matrices produced by differentiated mesenchymal stem cells. The timing of thrombin and plasmin activation during their respective APR phases is crucial for appropriate regulation of the damage matrix. This review focuses on evidence indicating that inappropriate exuberant activation of plasmin during the survival-APR can result in an overactive APR, leading to an "immunocoagulopathy" that may cause "immunothrombosis" and death. Conversely, preclinical data suggest that too little plasmin activity during the repair-APR may contribute to failed tissue repair, such as a fracture nonunion, and chronic inflammatory degenerative diseases like osteoporosis. Future clinical studies are required to affirm these findings. Therefore, the temporal-spatial functions of plasmin in response to musculoskeletal injury and its pharmacologic manipulation are intriguing new targets for improving orthopedic care.

Growth factor-free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia.

Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or de novo growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both ex vivo and in vivo assays. In a murine femoral artery ligation model of CLI, delivery of in situ crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.

Measures of Admission Immunocoagulopathy as an Indicator for In-Hospital Mortality in Patients with Necrotizing Fasciitis: A Retrospective Study.

Necrotizing fasciitis is a rapidly progressive infection with a high mortality rate. Pathogens evade the host containment and bactericidal mechanisms by hijacking the coagulation and inflammation signaling pathways, leading to their rapid dissemination, thrombosis, organ dysfunction, and death. This study examines the hypothesis that measures of immunocoagulopathy upon admission could aid in the identification of patients with necrotizing fasciitis at high risk for in-hospital mortality. Methods: Demographic data, infection characteristics, and laboratory values from 389 confirmed necrotizing fasciitis cases from a single institution were analyzed. A multivariable logistic regression model was built on admission immunocoagulopathy measures (absolute neutrophil, absolute lymphocyte, and platelet counts) and patient age to predict in-hospital mortality. Results: The overall in-hospital mortality rate was 19.8% for the 389 cases and 14.6% for the 261 cases with complete measures of immunocoagulopathy on admission. A multivariable logistic regression model indicated that platelet count was the most important predictor of mortality, followed by age and absolute neutrophil count. Greater age, higher neutrophil count, and lower platelet count led to significantly higher risk of mortality. The model discriminated well between survivors and non-survivors, with an overfitting-corrected C-index of 0.806. Conclusions: This study determined that measures of immunocoagulopathy and patient age at admission effectively prognosticated the in-hospital mortality risk of patients with necrotizing fasciitis. Given the accessibility of neutrophil-to-lymphocyte ratio and platelet count measurements determined from a simple complete blood-cell count with differential, future prospective studies examining the utility of these measures are warranted. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sterility of Miniature C-arm Fluoroscopy in Hand and Upper Extremity Surgery.

Previous studies have demonstrated that sterile equipment is frequently contaminated intraoperatively, yet the incidence of miniature c-arm (MCA) contamination in hand and upper extremity surgery is unclear. To examine this incidence, a prospective study of MCA sterility in hand and upper extremity cases was performed in a hospital main operating room (MOR) ( n = 13) or an ambulatory surgery center operating room (AOR) ( n = 16) at a single tertiary care center. Case length, MCA usage parameters, and sterility of the MCA through the case were examined. We found that MOR surgical times trended toward significance ( p = 0.055) and that MOR MCAs had significantly more contamination prior to draping than AOR MCAs ( p < 0.001). In MORs and AORs, 46.2 and 37.5% of MCAs respectively were contaminated intraoperatively. In MORs and AORs, 85.7 and 80% of noncontaminated cases, respectively, used the above hand- table technique, while 50 and 83.3% of contaminated MOR and AOR cases, respectively, used a below hand-table technique. Similar CPT codes were noted in both settings. Thus, a high-rate of MCA intraoperative contamination occurs in both settings. MCA placement below the hand-table may impact intraoperative contamination, even to distant MCA areas. Regular sterilization of equipment and awareness of these possible risk factors could lower bacterial burden.

Impact of the COVID-19 Pandemic on Pediatric Elbow Fractures: Marked Change in Management and Resource Utilization, Without a Change in Incidence.

BACKGROUND: Elbow fractures are the most common pediatric fractures requiring operative treatment. Although recent reports have suggested that the COVID-19 pandemic has markedly reduced the incidence of pediatric fractures, no study has specifically evaluated the impact on pediatric elbow fractures. This study aimed to evaluate changes in the incidence, severity, and resource utilization for managing pediatric elbow fractures during the COVID-19 pandemic, compared with prepandemic years. METHODS: A prepandemic (2007 to 2017) cohort and a COVID-19 pandemic period (March 2020 to March 2021) cohort of pediatric elbow injuries from a single tertiary hospital were retrospectively examined and compared. Exclusion criteria included outside treatment or lack of diagnosis by an orthopedist. Presentation information, injury patterns, transport, and treatment requirements were collected. RESULTS: Although the incidence of pediatric elbow fractures and rate of neurovascular injury were comparable, seasonal patterns were not sustained and the rate of fracture displacement was found to be significantly elevated in the COVID-19 period compared with nonpandemic years. Likewise, marked changes to where patients first presented (emergency department vs. Clinic), how the patients were transported, and the distance traveled for care were observed. Specifically, patients were more likely to present to the clinic, were more likely to self-transport instead of using emergency medical service transportation, and traveled a greater distance for care, on average. Aligning with these changes, the resources utilized for the treatment of pediatric elbow fracture markedly changed during the COVID-19 period. This study found that there was an increase in the overall number of surgeries performed, the total operative time required to treat elbow fractures, and the number of patients requiring admission during the COVID-19 period. CONCLUSIONS: These data provide a contrasting viewpoint to prior reports, illustrating that the incidence of elbow fractures remained consistent during the COVID-19 period, whereas the operative volume and need for hospital admission increased compared with years prior. Furthermore, this study demonstrated how the COVID-19 pandemic altered the interface between pediatric patients with elbow fractures and our institution regarding the location of presentation and transportation. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Location of Initial Closed Reduction Attempt Significantly Increases Cost and Length of Stay in Total Hip Arthroplasty.

Background: Prosthetic hip dislocation remains one of the most frequent complications following total hip replacement. Dislocations are predominantly managed by a closed reduction in the emergency department (ED) or the operating room (OR). This study aimed to evaluate how the location of an initial closed reduction attempt impacts a patient's course of care including length of stay (LOS) and cost of care. Material and methods: A retrospective chart review was performed on all patients presenting to a single ED with a unilateral prosthetic hip dislocation from 2009 to 2019. A total of 108 patients were identified. Data collected included patient demographics, ED/hospital course, and hospital charges. Results: Seventy-four patients (69%) had initial reduction attempted in the ED (65/74, 88% were successful), while 34 patients (31%) went directly to OR (100% successful with closed reduction). Failed closed reduction in ED or direct to OR resulted in a greater LOS and rate of placement to a skilled nursing facility following discharge. Median hospital charges for successful ED reduction were $6,837, while failed ED closed reduction or direct to OR resulted in median charges of $27,317 and $20,481, respectively. Conclusion: Many patients successfully underwent closed reduction in the ED, and there was no difference in complications, independent of where the reduction was first performed. Patients undergoing reduction in the OR had greater LOS and cost of care, independent of whether a reduction attempt was performed and failed in the ED, than those successfully reduced in the ED.

Nonaccidental Trauma in Pediatric Elbow Fractures: When You Should Be Worried.

BACKGROUND: Nonaccidental trauma (NAT) is a rising source of morbidity and mortality in the pediatric population. Fractures are often the first cause for presentation to health care providers in the case of NAT but can be misidentified as accidental. Given that elbow fractures are the most common accidental injuries among pediatric patients, they are not traditionally associated with NAT. This study aims to determine the prevalence of NAT among elbow fractures and identify common features in nonaccidental elbow fractures. METHODS: Current Procedural Terminology (CPT) codes were used to retrospectively identify all pediatric (0 to 17) elbow fractures at a single, tertiary children's hospital between 2007 and 2017. Among these, all fractures for which an institutional child abuse evaluation team was consulted were identified. The medical record was then used to determine which of these fractures were due to NAT. Standard injury radiographs of all victims of NAT as well as all patients under 1 year of age were blinded and radiographically evaluated for fracture type by a pediatric orthopaedic surgeon. RESULTS: The prevalence of nonaccidental elbow fractures across the 10-year study period was 0.4% (N=18). However, the prevalence of nonaccidental elbow fractures in those patients below 1 year of age was markedly higher at 30.3% (10/33). Among all elbow fractures in patients below 1 year of age, supracondylar humerus fractures were the most common fracture type (19/33, 57.6%), yet transphyseal fractures (6/33, 18.1%) were most commonly the result of NAT (5/6, 83.3%). In children over 1 year of age, fracture type was not an indicator of NAT. CONCLUSIONS: The vast majority of pediatric elbow fractures (99.6%) are accidental. However, certain factors, namely age below 1 year and transphyseal fractures increase the likelihood that these fractures may be a result of NAT. LEVEL OF EVIDENCE: Level IV: retrospective case series.

Variable Response to Antifibrinolytics Correlates with Blood-loss and Transfusion in Posterior Spinal Fusion.

PURPOSE: Posterior spinal fusion (PSF) activates the fibrinolytic protease plasmin, which is implicated in blood loss and transfusion. While antifibrinolytic drugs have improved blood loss and reduced transfusion, variable blood loss has been observed in similar PSF procedures treated with the same dose of antifibrinolytics. However, both the cause of this and the appropriate measures to determine antifibrinolytic efficacy during high-blood-loss spine surgery are unknown, making clinical trials to optimize antifibrinolytic dosing in PSF difficult. We hypothesized that patients undergoing PSF respond differently to antifibrinolytic dosing, resulting in variable blood loss, and that specific diagnostic markers of plasmin activity will accurately measure the efficacy of antifibrinolytics in PSF. METHODS: A prospective study of 17 patients undergoing elective PSF with the same dosing regimen of TXA was conducted. Surgery-induced plasmin activity was exhaustively analyzed in perioperative blood samples and correlated to measures of inflammation, bleeding, and transfusion. RESULTS: While markers of in vivo plasmin activation (PAP and D-dimer) suggested significant breakthrough plasmin activation and fibrinolysis (P < 0.01), in vitro plasmin assays, including TEG, did not detect plasmin activation. In vivo measures of breakthrough plasmin activation correlated with blood loss (R2 = 0.400, 0.264; P < 0.01), transfusions (R2 = 0.388; P < 0.01), and complement activation (R2 = 0.346, P < 0.05). CONCLUSIONS: Despite all patients receiving a high dose of TXA, its efficacy among patients was variable, indicated by notable intra-operative plasmin activity. Markers of in vivo plasmin activation best correlated with clinical outcomes. These findings suggest that the efficacy of antifibrinolytic therapy to inhibit plasmin in PSF surgery should be determined by markers of in vivo plasmin activation in future studies. LEVEL OF EVIDENCE: Level II-diagnostic.

Quantitative Analysis of Growth Factors From Cancellous Bone Graft Collected With a Reamer-Irrigator-Aspirator System From Native Long Bones Versus Previously Reamed Long Bones.

OBJECTIVE: Collection of bone graft with the Reamer-Irrigator-Aspirator (RIA) system has become common practice across the field of orthopaedic surgery. While RIA bone graft is typically obtained from native long bones, grafting material can likewise be harvested from long bones that have previously undergone the placement and removal of an intramedullary nail, a process termed re-reamed RIA (RRR). The purpose of this study was to evaluate the total protein and growth factor concentrations present in native-RIA (NR) compared with RRR samples. METHODS: NR and RRR bone grafts were collected intraoperatively with the RIA system and processed to evaluate both the aqueous and the hard tissue components. Total protein concentration and specific growth factors were analyzed using standard bicinchoninic acid and multiplex assays, respectively. Analyte levels were then normalized to the total amount of protein detected. RESULTS: Total protein levels were comparable between NR and RRR samples for both the aqueous filtrate and the hard tissue samples. When normalized, while levels of bone morphogenic protein-2 and vascular endothelial growth factor were comparable in the hard tissue component, the aqueous filtrate from the RRR sample was found to have elevated levels of growth factors, with bone morphogenic protein-2 reaching statistical significance. CONCLUSIONS: This study demonstrates that ample protein is found within both NR and RRR samples, with comparable or elevated levels of osteogenic growth factors found within RRR samples. Future, larger, prospective studies will be required to evaluate the osteogenic potential and clinical efficacy of NR and RRR cancellous bone grafts to validate their equivalency.

A Mini-Open Approach to Medial Pinning in Pediatric Supracondylar Humeral Fractures May Be Safer Than Previously Thought.

BACKGROUND: Displaced pediatric supracondylar humeral fractures (SCHFs) are stabilized after reduction by smooth pins. Although some SCHFs are biomechanically stable after lateral-only entry pinning (lateral pinning), an additional medial entry pin (cross-pinning) confers superior stabilization in some SCHFs. There is a recognized risk of iatrogenic ulnar nerve injury with medial entry pinning. The best existing evidence has estimated an iatrogenic ulnar nerve injury rate of approximately 3.4% in cross-pinning. In similar studies, the rate of iatrogenic nerve injury (all nerves) in lateral pinning is estimated at 1.9%. This study aimed to use a large, single-center, single-technique (mini-open) retrospective case series to determine the rate of iatrogenic ulnar nerve injury in cross-pinning. METHODS: Patients undergoing percutaneous cross-pinning via the mini-open technique for SCHFs from 2007 to 2017 were retrospectively reviewed. Injury characteristics, operative variables, fixation technique, and complications, such as iatrogenic nerve injury, were recorded. Patients who underwent operative treatment at another hospital, had no postoperative follow-up, or died due to polytrauma were excluded. RESULTS: In this study, 698 patients undergoing cross-pinning during the study period were identified. Patients treated with cross-pinning had severe fractures, including a total of 198 preoperative neurovascular injuries (28.4%), 32 patients (4.6%) with skin tenting, and 19 patients (2.7%) with open fractures. Iatrogenic nerve injury was reported in 3 cases (0.43%), all of which affected the ulnar nerve. In 2 of 3 cases of iatrogenic nerve injury, the ulnar nerve symptoms resolved at a mean follow-up of 15 weeks. CONCLUSIONS: The mini-open approach for medial pin insertion is safer than previous estimates. Here, in the largest single-center study of cross-pinning for SCHFs, the iatrogenic ulnar nerve injury rate of 0.43% was nearly 10 times lower than estimated rates from recent meta-analyses. Considering all nerves, the iatrogenic injury rate for this cross-pinning cohort was also lower than the estimated iatrogenic nerve injury rate for lateral pinning. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Effect of Intramedullary Nailing Patterns on Interfragmentary Strain in a Mouse Femur Fracture: A Parametric Finite Element Analysis.

Delayed long bone fracture healing and nonunion continue to be a significant socioeconomic burden. While mechanical stimulation is known to be an important determinant of the bone repair process, understanding how the magnitude, mode, and commencement of interfragmentary strain (IFS) affect fracture healing can guide new therapeutic strategies to prevent delayed healing or nonunion. Mouse models provide a means to investigate the molecular and cellular aspects of fracture repair, yet there is only one commercially available, clinically-relevant, locking intramedullary nail (IMN) currently available for studying long bone fractures in rodents. Having access to alternative IMNs would allow a variety of mechanical environments at the fracture site to be evaluated, and the purpose of this proof-of-concept finite element analysis study is to identify which IMN design parameters have the largest impact on IFS in a murine transverse femoral osteotomy model. Using the dimensions of the clinically relevant IMN as a guide, the nail material, distance between interlocking screws, and clearance between the nail and endosteal surface were varied between simulations. Of these parameters, changing the nail material from stainless steel (SS) to polyetheretherketone (PEEK) had the largest impact on IFS. Reducing the distance between the proximal and distal interlocking screws substantially affected IFS only when nail modulus was low. Therefore, IMNs with low modulus (e.g., PEEK) can be used alongside commercially available SS nails to investigate the effect of initial IFS or stability on fracture healing with respect to different biological conditions of repair in rodents.

Bruise Location in Supracondylar Humerus Fractures Predicts Specific Neurovascular Injuries.

PURPOSE: The presence of soft tissue injury in pediatric supracondylar humerus fractures (SCHFs) has been shown to be an independent predictor of any neurovascular injury. Potentially expanding this concept, the specific neurovascular structure injured around the elbow is thought to be dependent upon the direction and magnitude of fracture displacement and subsequent soft tissue injury. Therefore, it was hypothesized that the bruise location following SCHF is indicative of the anatomic location of maximal soft tissue injury and therefore is a specific prognosticator of which neurovascular structure may be injured. METHODS: Retrospective chart review of all SCHFs treated at a tertiary pediatric hospital from 2007 to 2017 collected information on bruise location, neurovascular injury patterns, and outcomes. Bruise location was classified as anterior, anterolateral, anteromedial, or posterior. Injury radiographs were reviewed by a blinded pediatric orthopaedic surgeon to neurovascular structure injured. RESULTS: Of 2845 SCHFs identified, 267 (9.4%) had concomitant neurovascular injury-of which 128 (47.9%) met inclusion criteria. Among the vascular injuries, all bruising was anteromedial (28/45, 62.2%, P<0.05) or anterior (17/45, 37.8%, P>0.05). Fractures with anteromedial bruising correlated with median nerve injury (24/27, 88.9%, P<0.05), whereas fractures with anterolateral bruising correlated with radial nerve injuries (24/25, 96.0%, P<0.05). Bruising or radiographic evaluation correctly identified 60.2% and 64.1% of neurovascular injuries, respectively, whereas the combination identified 82.0% of neurovascular injuries correctly. Bruise location identified 23 neurovascular injuries not predicted by radiographic evaluation alone. CONCLUSION: Bruise location is an important physical examination finding that can be used as an adjunct to improve the diagnostic accuracy of neurovascular injury in SCHFs in conjunction with neurovascular physical examination and radiographic evaluation. SCHFs with anterior or anteromedial bruising should raise concern for vascular injury. In addition, anteromedial bruising is predictive of a median nerve injury and anterolateral bruising is predictive of radial nerve injury. This adjunct diagnostic is particularly helpful in a noncooperative child or if performed by a clinician with limited experience in diagnosing neurovascular injuries or interpreting pediatric elbow radiographs. LEVEL OF EVIDENCE: Level IV, case series.

Plasmin drives burn-induced systemic inflammatory response syndrome.

Severe injuries, such as burns, provoke a systemic inflammatory response syndrome (SIRS) that imposes pathology on all organs. Simultaneously, severe injury also elicits activation of the fibrinolytic protease plasmin. While the principal adverse outcome of plasmin activation in severe injury is compromised hemostasis, plasmin also possesses proinflammatory properties. We hypothesized that, following a severe injury, early activation of plasmin drives SIRS. Plasmin activation was measured and related to injury severity, SIRS, coagulopathy, and outcomes prospectively in burn patients who are not at risk of hemorrhage. Patients exhibited early, significant activation of plasmin that correlated with burn severity, cytokines, coagulopathy, and death. Burn with a concomitant, remote muscle injury was employed in mice to determine the role of plasmin in the cytokine storm and inflammatory cascades in injured tissue distant from the burn injury. Genetic and pharmacologic inhibition of plasmin reduced the burn-induced cytokine storm and inflammatory signaling in injured tissue. These findings demonstrate (a) that severe injury-induced plasmin activation is a key pathologic component of the SIRS-driven cytokine storm and SIRS-activated inflammatory cascades in tissues distant from the inciting injury and (b) that targeted inhibition of plasmin activation may be effective for limiting both hemorrhage and tissue-damaging inflammation following injury.

The Deleterious Effects of Impaired Fibrinolysis on Skeletal Development Are Dependent on Fibrin(ogen), but Independent of Interlukin-6.

Chronic diseases in growing children, such as autoimmune disorders, obesity, and cancer, are hallmarked by musculoskeletal growth disturbances and osteoporosis. Many of the skeletal changes in these children are thought to be secondary to chronic inflammation. Recent studies have likewise suggested that changes in coagulation and fibrinolysis may contribute to musculoskeletal growth disturbances. In prior work, we demonstrated that mice deficient in plasminogen, the principal protease of degrading and clearing fibrin matrices, suffer from inflammation-driven systemic osteoporosis and that elimination of fibrinogen resulted in normalization of IL-6 levels and complete rescue of the skeletal phenotype. Given the intimate link between coagulation, fibrinolysis, and inflammation, here we determined if persistent fibrin deposition, elevated IL-6, or both contribute to early skeletal aging and physeal disruption in chronic inflammatory conditions. Skeletal growth as well as bone quality, physeal development, and vascularity were analyzed in C57BL6/J mice with plasminogen deficiency with and without deficiencies of either fibrinogen or IL-6. Elimination of fibrinogen, but not IL-6, rescued the skeletal phenotype and growth disturbances in this model of chronic disease. Furthermore, the skeletal phenotypes directly correlated with both systemic and local vascular changes in the skeletal environment. In conclusion, these results suggest that fibrinolysis through plasmin is essential for skeletal growth and maintenance, and is multifactorial by limiting inflammation and preserving vasculature.