Chancellor F. Gray

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.

Arthrodesis Should Be Strongly Considered After Failed Two-stage Reimplantation TKA

BackgroundA two-stage reimplantation procedure is a well-accepted procedure for management of first-time infected total knee arthroplasty (TKA). However, there is a lack of consensus on the treatment of subsequent reinfections.Questions/purposesThe purpose of this study was to perform a decision analysis to determine the treatment method likely to yield the highest quality of life for a patient after a failed two-stage reimplantation.MethodsWe performed a systematic review to estimate the expected success rates of a two-stage reimplantation procedure, chronic suppression, arthrodesis, and amputation for treatment of infected TKA. To determine utility values of the various possible health states that could arise after two-stage revision, we used previously published values and methods to determine the utility and disutility tolls for each treatment option and performed a decision tree analysis using the TreeAgePro 2012 software suite (Williamstown, MA, USA). These values were subsequently varied to perform sensitivity analyses, determining thresholds at which different treatment options prevailed.ResultsOverall, the composite success rate for two-stage reimplantation was 79.1% (range, 33.3%–100%). The utility (successful outcome) and disutility toll (cost for treatment) for two-stage reimplantation were determined to be 0.473 and 0.20, respectively; the toll for undergoing chronic suppression was set at 0.05; the utility for arthrodesis was 0.740 and for amputation 0.423. We set the utilities for subsequent two-stage revision and other surgical procedures by subtracting the disutility toll from the utility each time another procedure was performed. The two-way sensitivity analysis varied the utility status after an additional two-stage reimplantation (0.47–0.99) and chance of a successful two-stage reimplantation (45%–95%). The model was then extended to a three-way sensitivity analysis twice: once by setting the variable arthrodesis utility at a value of 0.47 and once more by setting utility of two-stage reimplantation at 0.05 over the same range of values on both axes. Knee arthrodesis emerged as the treatment most likely to yield the highest expected utility (quality of life) after initially failing a two-stage revision. For a repeat two-stage revision to be favored, the utility of that second two-stage revision had to substantially exceed the published utility of primary TKA of 0.84 and the probability of achieving infection control had to exceed 90%.ConclusionsBased on best available evidence, knee arthrodesis should be strongly considered as the treatment of choice for patients who have persistent infected TKA after a failed two-stage reimplantation procedure. We recognize that particular circumstances such as severe bone loss can preclude or limit the applicability of fusion as an option and that individual clinical circumstances must always dictate the best treatment, but where arthrodesis is practical, our model supports it as the best approach.

Disruption of the anterior-posterior rotator cuff force balance alters joint function and leads to joint damage in a rat model.

The rotator cuff assists in shoulder movement and provides dynamic stability to the glenohumeral joint. Specifically, the anterior–posterior (AP) force balance, provided by the subscapularis anteriorly and the infraspinatus and teres minor posteriorly, is critical for joint stability and concentric rotation of the humeral head on the glenoid. However, limited understanding exists of the consequences associated with disruption of the AP force balance (due to tears of both the supraspinatus and infraspinatus tendons) on joint function and joint damage. We investigated the effect of disrupting the APforce balance on joint function and joint damage in an overuse rat model. Twenty‐eight rats underwent 4 weeks of overuse to produce a tendinopathic condition and were then randomized into two surgical groups: Detachment of the supraspinatus only or detachment of the supraspinatus and infraspinatus tendons. Rats were then gradually returned to their overuse protocol. Quantitative ambulatory measures including medial/lateral, propulsion, braking, and vertical forces were significantly different between groups. Additionally, cartilage and adjacent tendon properties were significantly altered. These results identify joint imbalance as a mechanical mechanism for joint damage and demonstrate the importance of preserving rotator cuff balance when treating active cuff tear patients.

Content Factor: A Measure of a Journal’s Contribution to Knowledge

Impact Factor, the pre-eminent performance metric for medical journals, has been criticized for failing to capture the true impact of articles; for favoring methodology papers; for being unduly influenced by statistical outliers; and for examining a period of time too short to capture an article’s long-term importance. Also, in the era of search engines, where readers need not skim through journals to find information, Impact Factor’s emphasis on citation efficiency may be misplaced. A better metric would consider the total number of citations to all papers published by the journal (not just the recent ones), and would not be decremented by the total number of papers published. We propose a metric embodying these principles, “Content Factor”, and examine its performance among leading medical and orthopaedic surgery journals. To remedy Impact Factor’s emphasis on recent citations, Content Factor considers the total number of citations, regardless of the year in which the cited paper was published. To correct for Impact Factor’s emphasis on efficiency, no denominator is employed. Content Factor is thus the total number of citations in a given year to all of the papers previously published in the journal. We found that Content Factor and Impact Factor are poorly correlated. We further surveyed 75 experienced orthopaedic authors and measured their perceptions of the “importance” of various orthopaedic surgery journals. The correlation between the importance score and the Impact Factor was only 0.08; the correlation between the importance score and Content Factor was 0.56. Accordingly, Content Factor better reflects a journal’s “importance”. In sum, while Content Factor cannot be defended as the lone metric of merit, to the extent that performance data informs journal evaluations, Content Factor– an easily obtained and intuitively appealing metric of the journal’s knowledge contribution, not subject to gaming– can be a useful adjunct.

Effect of return to overuse activity following an isolated supraspinatus tendon tear on adjacent intact tendons and glenoid cartilage in a rat model.

Rotator cuff tears are common conditions that can alter shoulder mechanics and may lead to damage of intact joint tissues. These injuries are of particular concern in populations who perform tasks requiring repetitive overhead activity (e.g., athletes and laborers) and who are likely to return to aggressive pre‐injury activity levels despite limited understanding of the potentially damaging effects on the remaining tissues. Therefore, we investigated the effect of returning to overuse activity following a supraspinatus tear on shoulder function and the mechanical properties of the remaining intact tendons and glenoid cartilage. Forty rats underwent 4 weeks of overuse activity to create a tendinopathic condition followed by detachment of the supraspinatus tendon and were then randomized into two groups: continued overuse or cage activity. Ambulatory measurements were performed throughout the 8 weeks prior to euthaniasia, and properties of the adjacent tendons and cartilage were evaluated. Results demonstrated that shoulder function was not compromised in the return to overuse group. However, alterations of the glenoid cartilage and biceps tendon properties occurred. Our results help define the contributory roles of common mechanical injury mechanisms and provide a framework by which physicians could better prescribe long‐term treatment strategies for patients.

Periprosthetic fractures around loose femoral components.

The development of periprosthetic fractures around loose femoral components can be a devastating event for patients who have undergone total hip arthroplasty (THA). As indications for THA expand in an aging population and to use in younger patients, these fractures are increasing in incidence. This review covers the epidemiology, risk factors, prevention, and clinical management of periprosthetic femoral fractures. Treatment principles and reconstructive options are discussed, along with outcomes and complications. Femoral revision with a long-stem prosthesis or a modular tapered stem is the mainstay of treatment and has demonstrated good outcomes in the literature. Other reconstruction options are available, depending on bone quality. Surgeons must have a sound understanding of the diagnosis and treatment of periprosthetic femoral fractures.

Returning to overuse activity following a supraspinatus and infraspinatus tear leads to joint damage in a rat model

Large rotator cuff tears (supraspinatus and infraspinatus) are common in patients who perform overhead activities (laborers, athletes). In addition, following large cuff tears, these patients commonly attempt to return to pre-injury activity levels. However, there is a limited understanding of the damaging effects on the uninjured joint tissues when doing so. Therefore, the objective of this study was to investigate the effect of returning to overuse activity following a supraspinatus and infraspinatus tear on shoulder function and the structural and biological properties of the intact tendons and glenoid cartilage. Forty rats underwent 4 weeks of overuse followed by detachment of the supraspinatus and infraspinatus tendons and were then randomized into two groups: return to overuse or cage activity. Ambulatory measurements were performed over time and structural and biological properties of the adjacent tendons and cartilage were evaluated. Results demonstrated that animals returning to overuse activity did not have altered shoulder function but despite this, did have altered cartilage and tendon properties. These mechanical changes corresponded to altered transcriptional regulation of chondrogenic genes within cartilage and tendon. This study helps define the mechanical and biological mechanisms leading to joint damage and provides a framework for treating active cuff tear patients.

Notch signaling in mesenchymal stem cells harvested from geriatric mice.

Objectives: Morbidity associated with geriatric fractures may be attributed, in part, to compromised mesenchymal stem cell (MSC) function within the fracture callus. The Notch signaling pathway is important for the healing of nonskeletal tissues in an age-dependent manner, but the effect of Notch on age-dependent fracture healing and MSC dysfunction has not been substantiated. The objective of this study was to examine Notch signaling in MSCs obtained from young and geriatric mice. Methods: Marrow-derived MSCs were harvested from the femora of 5- and 25-month-old C57BL/6 mice. We assessed in vivo MSC number using CFU-F, proliferation using an Alamar Blue assay, osteoblast differentiation by Alizarin Red S staining, and adipogenic differentiation using Oil Red O staining. Notch receptor and ligand expression was assessed using quantitative PCR, and Notch signaling was assessed by evaluating Notch target gene expression (Hey and HES) under basal conditions and when cells were plated to Jagged-1 ligand. Results: MSC from geriatric mice exhibit reduced MSC number (CFU-F), proliferation, adipogenesis, and inconsistent osteogenesis. The highest expressed Notch receptor is Notch 2, and the highest expressed ligand is Jagged-1, but there were no differences in ligand and receptor gene expression between young and old MSCs. Interestingly, geriatric MSCs show decreased basal Notch signaling activity but are fully responsive to Jagged-1 stimulation. Conclusions: These data suggest that therapeutic targeting of Notch signaling should be explored in clinical therapies to improve geriatric fracture healing.

Biceps tenotomy in the presence of a supraspinatus tear alters the adjacent intact tendons and glenoid cartilage

A rotator cuff tear is a common injury in athletes and workers who repeatedly perform overhead movements, and it is not uncommon for this demographic to return to activity shortly after treatment. A biceps tenotomy is often performed in the presence of a rotator cuff tear to help reduce pain and improve joint function. However, the effect of this procedure on the surrounding tissues in the glenohumeral joint is unknown. Therefore, the purpose of this study was to investigate the effect of a biceps tenotomy in the presence of a supraspinatus rotator cuff tear followed by overuse activity on ambulatory function and mechanical and histologic properties of the remaining rotator cuff tendons and glenoid cartilage. 46 rats underwent 4weeks of overuse activity to create a tendinopathic condition, then were randomized into two groups: unilateral detachment of the supraspinatus tendon or detachment of the supraspinatus and long head of the biceps tendons. Ambulatory measurements were performed throughout the 8weeks prior to euthanasia, followed by analysis of the properties of the remaining intact tendons and glenoid cartilage. Results demonstrate that shoulder function was not effected in the biceps tenotomy group. However, the intact tendons and glenoid cartilage showed altered mechanical and histologic properties. This study provides evidence from an animal model that does not support the use of tenotomy in the presence of a supraspinatus tendon rotator cuff tear, and provides a framework for physicians to better prescribe long-term treatment strategies for patients.

Epidemiology, cost, and health policy related to total knee arthroplasty

Total knee arthroplasty (TKA) is a common procedure used in the United States to treat the pain associated with knee arthritis. Roughly 15% of Americans have symptomatic knee arthritis, and in 2010 roughly 600,000 TKAs were performed. The utilization of TKA is on the rise in the United States (US), and it is being performed in younger patients. Revision TKA also is increasingly being performed in the US, with infection being the most common reason. TKA is highly cost effective, with a cost per quality added life year (QALY) of