Tranexamic acid in trauma: After 3 hours from injury, when is it safe and effective to use again?

Tranexamic acid (TXA) has proven mortality benefit if used early after traumatic injury, likely related to a combination of bleeding reduction and other non-bleeding effects. If TXA is given more than 3 h after traumatic injury, there is a significant and paradoxical increased risk of death due to bleeding. TXA has level 1 evidence for use as a bleeding reduction agent in isolated orthopedic operations, but in polytrauma patients undergoing orthopedic operations, it is not clear if and when TXA is safe or effective once outside the 3-h window of proven trauma efficacy.

Clinical Outcomes and Associated Pathologies Following Pediatric Traumatic Hip Dislocations: A Systematic Review of the Literature.

INTRODUCTION: Pediatric traumatic hip dislocations are a rare condition that can have devastating short and/or long-term outcomes and associated pathologies (APs), including associated injuries (AIs) and long-term adverse events (LTAEs), with negative long-term sequelae. Currently, there are little data that exist on the rate of APs, with the most notable being avascular necrosis (AVN), for pediatric traumatic hip dislocations. The purpose of this systematic review is to evaluate the outcome relative frequency of dislocation direction, reduction type, and rate of APs for traumatic hip dislocations in the pediatric population. METHODS: A systematic review on the topic of traumatic hip dislocations in the pediatric population was performed using PubMed, ScienceDirect, Web of Science, CINAHL, and MEDLINE databases from database inception to March 30, 2023. Inclusion criteria was full-text English articles, addressed traumatic hip dislocations, and pediatric patients (<18 y old). RESULTS: A total of 24 articles (n=575 patients) met final inclusion criteria from a total of 219 articles retrieved from the initial search. For the average age of the included patients with reported age (n=433 patients), the frequency weighted mean was 9.50 years±1.75 years with a frequency weighted mean follow-up time of 74.05 months ±45.97 months (n=399 patients). The most common dislocation direction was posterior (86.4%), the most common treatment type was closed reduction (84.5%), AVN was the most common type of LTAEs (15.5% of APs), and labral/capsular injuries and acetabular fractures were the most common type of AIs (14.0% and 9.4% of APs, respectively). There were a combined total of 414 APs (72%) out of 575 total patients. CONCLUSION: Pediatric traumatic hip dislocations are associated with a high rate of AIs and LTAEs (72%, 414 APs out of 575 patients). AVN, labral/capsular injuries, and acetabular fractures are the most common APs after pediatric traumatic hip dislocations. Pediatric hip dislocations are usually posterior and commonly managed through closed reduction. LEVEL OF EVIDENCE: III, Systematic Review.

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.

Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study.

BACKGROUND: Fibrinolysisis is essential for vascular blood flow maintenance and is triggered by endothelial and platelet release of tissue plasminogen activator (t-PA). In certain critical conditions, e.g. sepsis, acute respiratory failure (ARF) and trauma, the fibrinolytic response is reduced and may lead to widespread thrombosis and multi-organ failure. The mechanisms underpinning fibrinolysis resistance include reduced t-PA expression and/or release, reduced t-PA and/or plasmin effect due to elevated inhibitor levels, increased consumption and/or clearance. This study in critically ill patients with fibrinolysis resistance aimed to evaluate the ability of t-PA and plasminogen supplementation to restore fibrinolysis with assessment using point-of-care ClotPro viscoelastic testing (VET). METHODS: In prospective, observational studies, whole-blood ClotPro VET evaluation was carried out in 105 critically ill patients. In 32 of 58 patients identified as fibrinolysis-resistant (clot lysis time > 300 s on the TPA-test: tissue factor activated coagulation with t-PA accelerated fibrinolysis), consecutive experimental whole-blood VET was carried out with repeat TPA-tests spiked with additional t-PA and/or plasminogen and the effect on lysis time determined. In an interventional study in a patient with ARF and fibrinolysis resistance, the impact of a 24 h intravenous low-dose alteplase infusion on coagulation and fibrinolysis was prospectively monitored using standard ClotPro VET. RESULTS: Distinct response groups emerged in the ex vivo experimental VET, with increased fibrinolysis observed following supplementation with (i) t-PA only or (ii) plasminogen and t-PA. A baseline TPA-test lysis time of > 1000 s was associated with the latter group. In the interventional study, a gradual reduction (25%) in serial TPA-test lysis times was observed during the 24 h low-dose alteplase infusion. CONCLUSIONS: ClotPro viscoelastic testing, the associated TPA-test and the novel experimental assays may be utilised to (i) investigate the potential mechanisms of fibrinolysis resistance, (ii) guide corrective treatment and (iii) monitor in real-time the treatment effect. Such a precision medicine and personalised treatment approach to the management of fibrinolysis resistance has the potential to increase treatment benefit, while minimising adverse events in critically ill patients. TRIAL REGISTRATION: VETtiPAT-ARF, a clinical trial evaluating ClotPro-guided t-PA (alteplase) administration in fibrinolysis-resistant patients with ARF, is ongoing (ClinicalTrials.gov NCT05540834 ; retrospectively registered September 15th 2022).

Age and CRP Associated With Improved Tissue Pathogen Identification in Children With Blood Culture Negative Osteomyelitis: Results From the CORTICES Multicenter Database.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a relatively common condition in children, and identifying the offending pathogen with blood or tissue cultures aids in diagnosis and medical management while reducing treatment failure. Recent 2021 AHO clinical practice guidelines from the Pediatric Infectious Disease Society recommend obtaining routine tissue cultures, particularly in cases with negative blood cultures. The purpose of this study was to identify variables associated with positive tissue cultures when blood cultures are negative. METHODS: Children with AHO from 18 pediatric medical centers throughout the United States through the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study were evaluated for predictors of positive tissue cultures when blood cultures were negative. Cutoffs of predictors were determined with associated sensitivity and specificity. RESULTS: One thousand three children with AHO were included, and in 688/1003 (68.6%) patients, both blood cultures and tissue cultures were obtained. In patients with negative blood cultures (n=385), tissue was positive in 267/385 (69.4%). In multivariate analysis, age ( P <0.001) and C-reactive protein (CRP) ( P =0.004) were independent predictors. With age >3.1 years and CRP >4.1 mg/dL as factors, the sensitivity of obtaining a positive tissue culture when blood cultures were negative was 87.3% (80.9-92.2%) compared with 7.1% (4.4-10.9%) if neither of these factors was present. There was a lower ratio of methicillin-resistant Staphylococcus aureus in blood culture-negative patients who had a positive tissue culture 48/188 (25.5%), compared with patients who had both positive blood and tissue cultures 108/220 (49.1%). CONCLUSION: AHO patients with CRP ≤ 4.1 mg/dL and age under 3.1 years are unlikely to have clinical value from tissue biopsy that exceeds the morbidity associated with this intervention. In patients with CRP > 4.1 mg/dL and age over 3.1 years, obtaining a tissue specimen may add value; however, it is important to note that effective empiric antibiotic coverage may limit the utility of positive tissue cultures in AHO. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-ß1 responses: insights into cardiac fibrosis and function following myocardial infarction.

Extracellular purine nucleotides and nucleosides released from activated or injured cells influence multiple aspects of cardiac physiology and pathophysiology. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; CD39) hydrolyzes released nucleotides and thereby regulates the magnitude and duration of purinergic signaling. However, the impact of CD39 activity on post-myocardial infarction (MI) remodeling is incompletely understood. We measured the levels and activity of ectonucleotidases in human left ventricular samples from control and ischemic cardiomyopathy (ICM) hearts and examined the impact of ablation of Cd39 expression on post-myocardial infarction remodeling in mice. We found that human CD39 levels and activity are significantly decreased in ICM hearts (n = 5) compared with control hearts (n = 5). In mice null for Cd39, cardiac function and remodeling are significantly compromised in Cd39-/- mice following myocardial infarction. Fibrotic markers including plasminogen activator inhibitor-1 (PAI-1) expression, fibrin deposition, α-smooth muscle actin (αSMA), and collagen expression are increased in Cd39-/- hearts. Importantly, we found that transforming growth factor ß1 (TGF-ß1) stimulates ATP release and induces Cd39 expression and activity on cardiac fibroblasts, constituting an autocrine regulatory pathway not previously appreciated. Absence of CD39 activity on cardiac fibroblasts exacerbates TGF-ß1 profibrotic responses. Treatment with exogenous ectonucleotidase rescues this profibrotic response in Cd39-/- fibroblasts. Together, these data demonstrate that CD39 has important interactions with TGF-ß1-stimulated autocrine purinergic signaling in cardiac fibroblasts and dictates outcomes of cardiac remodeling following myocardial infarction. Our results reveal that ENTPD1 (CD39) regulates TGF-ß1-mediated fibroblast activation and limits adverse cardiac remodeling following myocardial infarction.NEW & NOTEWORTHY We show that CD39 is a critical modulator of TGF-ß1-mediated fibroblast activation and cardiac remodeling following myocardial infarction via modulation of nucleotide signaling. TGF-ß1-induced CD39 expression generates a negative feedback loop that attenuates cardiac fibroblast activation. In the absence of CD39 activity, collagen deposition is increased, elastin expression is decreased, and diastolic dysfunction is worsened. Treatment with ecto-apyrase attenuates the TGF-ß1-induced profibrotic cardiac fibroblast phenotype, revealing a novel approach to combat post-myocardial infarction cardiac fibrosis.

Genetic heterogeneity of heritable ectopic mineralization disorders in a large international cohort.

PURPOSE: Heritable ectopic mineralization disorders comprise a group of conditions with a broad range of clinical manifestations in nonskeletal connective tissues. We report the genetic findings from a large international cohort of 478 patients afflicted with ectopic mineralization. METHODS: Sequence variations were identified using a next-generation sequencing panel consisting of 29 genes reported in association with ectopic mineralization. The pathogenicity of select splicing and missense variants was analyzed in experimental systems in vitro and in vivo. RESULTS: A total of 872 variants of unknown significance as well as likely pathogenic and pathogenic variants were disclosed in 25 genes. A total of 159 distinct variants were identified in 425 patients in ABCC6, the gene responsible for pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder. The interpretation of variant pathogenicity relying on bioinformatic predictions did not provide a consensus. Our in vitro and in vivo functional assessment of 14 ABCC6 variants highlighted this dilemma and provided unambiguous interpretations to their pathogenicity. CONCLUSION: The results expand the ABCC6 variant repertoire, shed new light on the genetic heterogeneity of heritable ectopic mineralization disorders, and provide evidence that functional characterization in appropriate experimental systems is necessary to determine the pathogenicity of genetic variants.

Blood Loss and Transfusion in a Pediatric Scoliosis Surgery Cohort in the Antifibrinolytic Era.

Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is one key strategy to decrease blood loss and transfusion in pediatric scoliosis surgery. Here we review 172 pediatric scoliosis patients (birth to 21 y) who underwent posterior spinal fusion at our institution from 2017 to 2018. We reported rates of blood loss and transfusion, compared patients receiving tranexamic acid to a ε-aminocaproic acid, and evaluated antifibrinolytic agent and laboratory parameters as predictors of blood loss and transfusion. Intraoperatively, 62% received tranexamic acid and 38% received ε-aminocaproic acid. Overall, blood loss (mean intraoperative estimated blood loss=14.9±9.7 mL/kg, 22% with clinically significant blood loss [>20 mL/kg], and mean calculated hemoglobin mass loss=175.9±70.1 g) and transfusion rates (15% with intraoperative allogeneic red blood cell transfusion and mean intraoperative allogeneic red blood cell transfusion volume=12.5±7.1 mL/kg) were similar to previous cohorts studying intraoperative antifibrinolytics. There was no difference in intraoperative estimated blood loss, clinically significant blood loss, calculated hemoglobin mass loss, or transfusion rates between the antifibrinolytic groups. Antifibrinolytic choice was not predictive of blood loss or transfusion. Routine hematologic laboratory parameters and antifibrinolytic choice were insufficient to predict blood loss or other outcomes. Future prospective laboratory-based studies may provide a more comprehensive model of surgical-induced coagulopathy in scoliosis surgery and provide a better tool for predicting blood loss and improving outcomes.

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.

Practice Variation in the Surgical Management of Children With Acute Hematogenous Osteomyelitis.

INTRODUCTION: The surgical indications to manage children with acute hematogenous osteomyelitis (AHO) remain poorly defined. The purpose of this study was to identify if practice pattern variation exists in the surgical management of pediatric AHO among tertiary pediatric medical centers across the United States. A secondary purpose was to evaluate variables that may impact the rate of surgical intervention among these institutions. METHODS: Children with AHO were retrospectively analyzed between January 1, 2010, and December 31, 2016, from 18 pediatric medical centers throughout the United States. The rates of surgery were identified. Admission vitals, labs, weight-bearing status, length of stay, and readmission rates were compared between those who did and did not undergo surgery. Multivariate regression and classification and regression tree analyses were performed to identify the variables that were associated with surgical intervention. RESULTS: Of the 1003 children identified with AHO in this retrospective, multicenter database, 619/1003 (62%) were treated surgically. Multivariate analysis revealed institution, inability to ambulate, presence of multifocal infection, elevated admission C-reactive protein, increased admission platelet count, and location of the osteomyelitis were significant predictors of surgery (P<0.01). Patients who underwent surgery were more than twice as likely to have a recurrence or readmission and stayed a median of 2 days longer than those who did not have surgery. In the classification and regression tree analysis, 2 distinct patterns of surgical intervention were identified based on institution, with 12 institutions operating in most cases (72%), regardless of clinical factors. A second cohort of 6 institutions operated less routinely, with 47% receiving surgery overall. At these 6 institutions, patients without multifocal infection only received surgery 26% of the time, which increased to 74% with multifocal infection and admission erythrocyte sedimentation rate >37.5 mm/h. CONCLUSIONS: This study is the first to objectively identify significant differences in the rates of surgical management of pediatric AHO across the United States. Variation in the surgical management of AHO appears to be driven primarily based on institutional practice. Twelve institutions operated on 72% of patients, regardless of the severity of disease, indicating that the institution custom or dogma may drive the surgical indications. Six institutions relied more on clinical judgment with significant variability in rates of surgical intervention (26% vs. 74%), depending on the severity of the disease. Surgical intervention is associated with increased recurrence, readmission, and hospital length of stay. As a result of these findings, it is essential to prospectively study the appropriate surgical indications and measure the outcomes in children with pediatric AHO. LEVEL OF EVIDENCE: Level III.

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.

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.

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.

The multifaceted role of fibrinogen in tissue injury and inflammation.

The canonical role of the hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological end points of hemorrhage or thrombosis with vessel occlusion. However, fibrin(ogen) and proteases controlling its deposition and clearance, including (pro)thrombin and plasmin(ogen), have powerful roles in driving acute and reparative inflammatory pathways that affect the spectrum of tissue injury, remodeling, and repair. Indeed, fibrin(ogen) deposits are a near-universal feature of tissue injury, regardless of the nature of the inciting event, including injuries driven by mechanical insult, infection, or immunological derangements. Fibrin can modify multiple aspects of inflammatory cell function by engaging leukocytes through a variety of cellular receptors and mechanisms. Studies on the role of coagulation system activation and fibrin(ogen) deposition in models of inflammatory disease and tissue injury have revealed points of commonality, as well as context-dependent contributions of coagulation and fibrinolytic factors. However, there remains a critical need to define the precise temporal and spatial mechanisms by which fibrinogen-directed inflammatory events may dictate the severity of tissue injury and coordinate the remodeling and repair events essential to restore normal organ function. Current research trends suggest that future studies will give way to the identification of novel hemostatic factor-targeted therapies for a range of tissue injuries and disease.

Financial and Clinical Ramifications of Introducing a Novel Pediatric Enhanced Recovery After Surgery Pathway for Pediatric Complex Hip Reconstructive Surgery.

BACKGROUND: Enhanced recovery after surgery pathways confer significant perioperative benefits to patients and are currently well described for adult patients undergoing a variety of surgical procedures. Robust data to support enhanced recovery pathway use in children are relatively lacking in the medical literature, though clinical benefits are reported in targeted pediatric surgical populations. Surgery for complex hip pathology in the adolescent patient is painful, often requiring prolonged courses of opioid analgesia. Postoperative opioid-related side effects may lead to prolonged recovery periods and suboptimal postoperative physical function. Excessive opioid use in the perioperative period is also a major risk factor for the development of opioid misuse in adolescents. Perioperative opioid reduction strategies in this vulnerable population will help to mitigate this risk. METHODS: A total of 85 adolescents undergoing complex hip reconstructive surgery were enrolled into an enhanced recovery after surgery pathway (October 2015 to December 2018) and were compared with 110 patients undergoing similar procedures in previous years (March 2010 to September 2015). The primary outcome was total perioperative opioid consumption. Secondary outcomes included hospital length of stay, postoperative nausea, intraoperative blood loss, and other perioperative outcomes. Total cost of care and specific charge sectors were also assessed. Segmented regression was used to assess the effects of pathway implementation on outcomes, adjusting for potential confounders, including the preimplementation trend over time. RESULTS: Before pathway implementation, there was a significant downward trend over time in average perioperative opioid consumption (-0.10 mg total morphine equivalents/90 days; 95% confidence interval [CI], -0.20 to 0.00) and several secondary perioperative outcomes. However, there was no evidence that pathway implementation by itself significantly altered the prepathway trend in perioperative opioid consumption (ie, the preceding trend continued). For postanesthesia care unit time, the downward trend leveled off significantly (pre: -5.25 min/90 d; 95% CI, -6.13 to -4.36; post: 1.04 min/90 d; 95% CI, -0.47 to 2.56; Change: 6.29; 95% CI, 4.53-8.06). Clinical, laboratory, pharmacy, operating room, and total charges were significantly associated with pathway implementation. There was no evidence that pathway implementation significantly altered the prepathway trend in other secondary outcomes. CONCLUSIONS: The impacts of our pediatric enhanced recovery pathway for adolescents undergoing complex hip reconstruction are consistent with the ongoing improvement in perioperative metrics at our institution but are difficult to distinguish from the impacts of other initiatives and evolving practice patterns in a pragmatic setting. The ERAS pathway helped codify and organize this new pattern of care, promoting multidisciplinary evidence-based care patterns and sustaining positive preexisting trends in financial and clinical metrics.

Factors That Drive Annual Variation in Pediatric Elbow Fracture Occurrence, Severity, and Resource Utilization.

BACKGROUND: Elbow fractures are the most common pediatric fractures requiring operative treatment. To date, few studies have examined what annual factors drive pediatric elbow fracture incidence and no studies have examined which annual factors drive elbow fracture severity or resource utilization. The goal of this study was to not only document the annual patterns of pediatric elbow fracture incidence and severity but also the impact of these patterns on resource utilization in the emergency department, emergency medical service transportation, and the operating room (OR). METHODS: Retrospective cohort study of 4414 pediatric elbow fractures from a single tertiary hospital (2007 to 2017). Exclusion criteria included outside treatment or lack of diagnosis by an orthopaedist. Presentation information, injury patterns, transport, and treatment requirements were collected. Pearson correlations were used to analyze factors influencing fracture incidence, severity, and resource utilization. RESULTS: Pediatric elbow fracture incidence positively correlated with monthly daylight hours, but significantly fewer elbow fractures occurred during summer vacation from school compared with surrounding in school months. While fewer overall fractures occurred during summer break, the fractures sustained were greater in severity, conferring higher rates of displacement, higher risk of neurovascular injury, and greater needs for emergency transportation and operative treatment. Yearly, elbow fractures required 320.6 OR hours (7.7% of all pediatric orthopaedic OR time and 12.3% of all pediatric orthopaedic operative procedures), 203.4 hospital admissions, and a total of 4753.7 miles traveled by emergency medical service transportation to manage. All-cause emergency department visits were negatively correlated with daylight hours, inversing the pattern seen in elbow fractures. CONCLUSION: Increased daylight, while school was in session, was a major driver of the incidence of pediatric elbow fractures. While summer vacation conferred fewer fractures, these were of higher severity. As such, increased daylight correlated strongly with monthly resource utilization, including the need for emergency transportation and operative treatment. This study provides objective data by which providers and administrators can more accurately allocate resources. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

The Heterogeneity of Pediatric Knee Infections: A Retrospective Analysis.

BACKGROUND: Musculoskeletal infection is a major cause of morbidity in the pediatric population. Despite the canonical teaching that an irritable joint and signs of infection likely represent an infected joint space, recent evidence in the pediatric hip has demonstrated that alternative diagnoses are equally or more likely and that combinations of pathologies are common. The knee is the second most commonly infected joint in children, yet there remains a paucity of available data regarding the epidemiology and workup of the infected pediatric knee. The authors hypothesize that there is heterogeneity of pathologies, including combinations of pathologies, that presents as a potentially infected knee in a child. The authors aim to show the utility of magnetic resonance imaging and epidemiologic and laboratory markers in the workup of these patients. METHODS: A retrospective review of all consults made to the pediatric orthopaedic surgery team at a single tertiary care center from September 2009 through December 2015 regarding a concern for potential knee infection was performed. Excluded from the study were patients with penetrating trauma, postoperative infection, open fracture, no C-reactive protein (CRP) within 24 hours of admission, sickle cell disease, an immunocompromised state, or chronic osteomyelitis. RESULTS: A total of 120 patients were analyzed in this study. There was marked variability in pathologies. Patients with isolated osteomyelitis or osteomyelitis+septic arthritis were older, had an increased admission CRP, were more likely to be infected with Staphylococcus aureus, required an increased duration of antibiotics, and had an increased incidence of musculoskeletal complications than patients with isolated septic arthritis. CONCLUSIONS: When considering a child with an irritable knee, a heterogeneity of potential underlying pathologies and combinations of pathologies are possible. Importantly, the age of the patient and CRP can guide a clinician when considering further workup. Older patients with a higher admission CRP value warrant an immediate magnetic resonance imaging, as they are likely to have osteomyelitis, which was associated with worse outcomes when compared with patients with isolated septic arthritis. LEVEL OF EVIDENCE: Level III-retrospective research study.

Trauma-Induced Nanohydroxyapatite Deposition in Skeletal Muscle is Sufficient to Drive Heterotopic Ossification.

Heterotopic ossification (HO), or the pathologic formation of bone within soft tissues, is a significant complication following severe injuries as it impairs joint motion and function leading to loss of the ability to perform activities of daily living and pain. While soft tissue injury is a prerequisite of developing HO, the exact molecular pathology leading to trauma-induced HO remains unknown. Through prior investigations aimed at identifying the causative factors of HO, it has been suggested that additional predisposing factors that favor ossification within the injured soft tissues environment are required. Considering that chondrocytes and osteoblasts initiate physiologic bone formation by depositing nanohydroxyapatite crystal into their extracellular environment, we investigated the hypothesis that deposition of nanohydroxyapatite within damaged skeletal muscle is likewise sufficient to predispose skeletal muscle to HO. Using a murine model genetically predisposed to nanohydroxyapatite deposition (ABCC6-deficient mice), we observed that following a focal muscle injury, nanohydroxyapatite was robustly deposited in a gene-dependent manner, yet resolved via macrophage-mediated regression over 28 days post injury. However, if macrophage-mediated regression was inhibited, we observed persistent nanohydroxyapatite that was sufficient to drive the formation of HO in 4/5 mice examined. Together, these results revealed a new paradigm by suggesting the persistent nanohydroxyapatite, referred to clinically as dystrophic calcification, and HO may be stages of a pathologic continuum, and not discrete events. As such, if confirmed clinically, these findings support the use of early therapeutic interventions aimed at preventing nanohydroxyapatite as a strategy to evade HO formation.

Comparison of different dosage regimes of epsilon aminocaproic acid on blood loss in children undergoing craniosynostosis surgery.

BACKGROUND: Open cranial vault reconstruction is frequently performed for craniosynostosis. These procedures often involve high volume blood loss that requires blood transfusion. Antifibrinolytics have been shown to decrease blood loss during these procedures but the optimal dose that maximizes benefits is not known. AIMS: The primary aim was to evaluate the differences in calculated blood loss between a high infusion rate (40 mg/kg/h) and a low infusion rate (≤30 mg/kg/h) of epsilon aminocaproic acid after a 100 mg/kg loading dose. Secondary aims were to determine if a high infusion rate of epsilon aminocaproic acid was associated with decreased packed red cell transfusion volume and to determine the factors associated with blood loss. METHODS: This was a retrospective study of children who underwent open cranial vault reconstruction. Using an electronic medical record, we identified patients that fit the inclusion criteria. Demographic, laboratory, transfusion, and perioperative data were collected and statistical analysis was performed. RESULTS: Fifty-three patients were included into the study with twenty-three receiving higher infusion rate (40 mg/kg/h) epsilon aminocaproic acid. There was a 14.3 mL/kg (95% CI 6.6-23.9) decrease in calculated blood loss in the high-dose cohort. CONCLUSION: An EACA bolus of 100 mg/kg followed by an infusion of 40 mg/kg was associated with a lower calculated blood loss compared to the group who received 100 mg/kg EACA and ≤ 30 mg/kg infusion.

Developmental Dysplasia of the Hip From Birth to Arthroplasty: Clear Indications and New Controversies.

Developmental dysplasia of the hip is the all-encompassing term used to describe the wide spectrum of disorders of the development of the hip that manifest in various forms and at different ages. Developmental dysplasia of the hip often evolves over time because the structures of the hip are normal during embryogenesis but gradually become abnormal. Such variability in pathology is associated with a similarly wide range in management options and recommendations aimed at preventing hip joint arthrosis. These options may be instituted at any time between birth and adulthood as techniques aimed at preserving the native hip or replacing the arthritic hip. Many of these management options are clearly indicated and considered standard practice. However, with the evolution of the understanding of hip biomechanics, better knowledge of the long-term outcomes of hip joint-preserving surgeries, and ever-improving technology influencing hip arthroplasty come new controversies, especially whether to preserve or replace the mature hip.