Mara L. Schenker

Angiogenesis in Bone Regeneration

Angiogenesis is a key component of bone repair. New blood vessels bring oxygen and nutrients to the highly metabolically active regenerating callus and serve as a route for inflammatory cells and cartilage and bone precursor cells to reach the injury site. Angiogenesis is regulated by a variety of growth factors, notably vascular endothelial growth factor (VEGF), which are produced by inflammatory cells and stromal cells to induce blood vessel in-growth. A variety of studies with transgenic and gene-targeted mice have demonstrated the importance of angiogenesis in fracture healing, and have provided insights into regulatory processes governing fracture angiogenesis. Indeed, in animal models enhancing angiogenesis promotes bone regeneration, suggesting that modifying fracture vascularization could be a viable therapeutic approach for accelerated/improved bone regeneration clinically.

Does timing to operative debridement affect infectious complications in open long-bone fractures? A systematic review

BACKGROUND Existing guidelines recommend emergency surgical debridement of open fractures within six hours after injury. The aim of this study was to systematically review the association between time to operative debridement of open fractures and infection. METHODS Searches of the MEDLINE, EMBASE, and Cochrane computerized literature databases and manual searches of bibliographies were performed. Randomized controlled trials and cohort studies (retrospective and prospective) evaluating the association between time to operative debridement and infection after open fractures were included. Descriptive and quantitative data were extracted. A meta-analysis of patient cohorts who underwent early or delayed debridement was performed with use of a random effects model. RESULTS The initial search identified 885 references. Of the 173 articles inspected further on the basis of the title, sixteen (six prospective and ten retrospective cohort studies with a total of 3539 open fractures) were included. No significant difference in the infection rate was detected between open fractures debrided early or late according to any of the time thresholds used in the included studies. Sensitivity analyses demonstrated no difference in infection rate between early and late debridement in subgroups defined according to the Gustilo-Anderson classification, level of evidence, depth of infection, or anatomic location. CONCLUSIONS The data did not indicate an association between delayed debridement and higher infection rates when all infections were considered, when only deep infections were considered, or when only more severe open fracture injuries were considered. On the basis of this analysis, the historical “six-hour rule” has little support in the available literature. It is important to realize that additional carefully conducted studies are needed and that elective delay of treatment of patients with open fractures is not recommended

Pathogenesis and prevention of posttraumatic osteoarthritis after intra-articular fracture.

Posttraumatic osteoarthritis (PTOA) occurs after traumatic injury to the joint. It is most common following injuries that disrupt the articular surface or lead to joint instability. The reported risk of PTOA following significant joint trauma is as high as 75%; articular fractures can increase the risk more than 20‐fold. Despite recent advances in surgical management, the incidence of PTOA following intra‐articular fractures has remained relatively unchanged over the last few decades. Pathogenesis of PTOA after intra‐articular fracture is likely multifactorial and may be associated with acute cartilage injury as well as chronic joint overload secondary to instability, incongruity, and malalignment. Additional studies are needed to better elucidate how these factors contribute to the development of PTOA and to develop advanced treatment algorithms that consist of both acute biologic interventions targeted to decrease inflammation and cellular death in response to injury and improved surgical methods to restore stability, congruity, and alignment.

The cost of after-hours operative debridement of open tibia fractures.

Objectives: The aim of this study was to evaluate the additional cost associated with performing after-hours operative debridement of open fractures within 6 hours of injury. Data Sources: The economic model is based on population estimates obtained from the National Trauma Database and the National Inpatient Sample on the number of open tibia fractures that occur annually in the United States and the number that present after-hours (between 6 PM and 2 AM) that undergo operative debridement within 6 hours. This model estimates incremental cost for after-hours surgery based on overtime wages for on-call personnel (nurses and surgical technicians) required to staff after-hours cases as published by the US Department of Labor and data from our own institution. As many level 1 hospitals are capable of performing after-hours cases without additional cost, a sensitivity analysis was performed to determine the effect of designated level of care of the trauma hospital. Data Extraction and Synthesis: A total of 17,414 open tibia fractures were recorded in the National Inpatient Sample for 2009, and an estimated 7485 open tibia fractures presented after-hours, 4242 of which underwent operative debridement within 6 hours of presentation. Based on wage statistics from the US Department of Labor and our own institution, the estimated total additional cost for after-hours operative debridement of open tibia fractures within 6 hours is from

The frail fail: Increased mortality and post-operative complications in orthopaedic trauma patients

2,210,895 to

Building better bone: the weaving of biologic and engineering strategies for managing bone loss†

4,046,648 annually, respectively. For level 2 hospitals and below, the cost of performing after-hours operative debridement of open tibia fractures is calculated as from

Delivery of Active FGF-2 From Mechanically-Stable Biological Nanofibers Accelerates Cell Ingress Into Multifiber Composites

1,532,980 to

Use of a 5-Item Modified Frailty Index for Risk Stratification in Patients Undergoing Surgical Management of Distal Radius Fractures

2,805,846 annually. Conclusions: The data indicated an increased overall financial cost of performing after-hours operative debridement of open tibia fractures. Given that there is minimal documented benefit to this practice, and with increased pressure to practice cost containment, elective delay of operative debridement of open fractures and/or transfer to a higher level of care trauma hospital may be an acceptable way to address these issues. Level of Evidence: Economic Analysis Level III. See Instructions for Authors for a complete description of levels of evidence.

Disparities in follow-up care for ballistic and non-ballistic long bone lower extremity fractures

OBJECTIVE The burgeoning elderly population calls for a robust tool to identify patients with increased risk of mortality and morbidity. This paper investigates the utility of the MFI as a predictor of morbidity and mortality in orthopaedic trauma patients. DESIGN Retrospective review of the NSQIP database to identify patients age 60 and above who underwent surgery for pelvis and lower extremity fractures between 2005 and 2014. MAIN OUTCOMES AND MEASURES For each patient, an MFI score was calculated using NSQIP variables. The relationship between the MFI score and 30-day mortality and morbidity was determined using chi-square analysis. MFI was compared to age, American Society of Anesthesiologists physical status classification, and wound classifications in multiple logistic regression. RESULTS Study sample consisted of 36,424 patients with 27.8% male with an average age of 79.5 years (SD 9.3). MFI ranged from 0 to 0.82 with mean MFI of 0.12 (SD 0.09). Mortality increased from 2.7% to 13.2% and readmission increased from 5.5% to 18.8% with increasing MFI score. The rate of any complication increased from 30.1% to 38.6%. Length of hospital stay increased from 5.3days (±5.5days) to 9.1days (±7.2days) between MFI score 0 and 0.45+. There was a stronger association between 30-day mortality and MFI (aOR for MFI 0.45+: 2.6, 95% CI: 1.7-3.9) compared to age (aOR for age: 1.1, 95% CI: 1.1-1.1) and ASA (aOR 2.5, 95% CI: 2.3-2.7). CONCLUSIONS AND RELEVANCE MFI was a significant predictor of morbidity and mortality in orthopaedic trauma patients. The use of MFI can provide an individualized risk assessment tool that can be used by an interdisciplinary team for perioperative counseling and to improve outcomes.

Frailty predicts mortality and complications in chronologically young patients with traumatic orthopaedic injuries

Segmental bone loss remains a challenging clinical problem for orthopaedic trauma surgeons. In addition to the missing bone itself, the local tissues (soft tissue, vascular) are often highly traumatized as well, resulting in a less than ideal environment for bone regeneration. As a result, attempts at limb salvage become a highly expensive endeavor, often requiring multiple operations and necessitating the use of every available strategy (autograft, allograft, bone graft substitution, Masquelet, bone transport, etc.) to achieve bony union. A cost‐sensitive, functionally appropriate, and volumetrically adequate engineered substitute would be practice‐changing for orthopaedic trauma surgeons and these patients with difficult clinical problems. In tissue engineering and bone regeneration fields, numerous research efforts continue to make progress toward new therapeutic interventions for segmental bone loss, including novel biomaterial development as well as cell‐based strategies. Despite an ever‐evolving literature base of these new therapeutic and engineered options, there remains a disconnect with the clinical practice, with very few translating into clinical use. A symposium entitled “Building better bone: The weaving of biologic and engineering strategies for managing bone loss,” was presented at the 2016 Orthopaedic Research Society Conference to further explore this engineering‐clinical disconnect, by surveying basic, translational, and clinical researchers along with orthopaedic surgeons and proposing ideas for pushing the bar forward in the field of segmental bone loss.