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Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and facilitate comparisons between studies. To determine the penetrance of these documents in the field, we synthesized the recommendations of the American Society for Testing and Materials, U.S. Food and Drug Administration, and European Medicines Agency into a scoring system and performed a systematic review of the past 20 years of preclinical cartilage repair studies. Our hypothesis was that the guidance documents would have a significant impact on how large animal cartilage repair studies were performed. A total of 114 publications meeting our inclusion criteria were reviewed for adherence to 24 categories extracted from the guidance documents, including 11 related to study design and description and 13 related to study outcomes. Overall, a weak positive trend was observed over time (P = 0.004, R(2) = 0.07, slope = 0.63%/year), with overall adherence (the sum of study descriptors and outcomes) ranging from 32 ± 16% to 58 ± 14% in any individual year. There was no impact of the publication of the guidance documents on adherence (P = 0.264 to 0.50). Given that improved adherence would expedite translation, we discuss the reasons for poor adherence and outline approaches to increase and promote their more widespread adoption., (Copyright © 2015, American Association for the Advancement of Science.)

Background: Shoulder instability is a common cause of pain and dysfunction in young, active patients. While studies have analyzed risk factors for recurrent instability and failure after instability surgery, few have examined which variables are associated with initial surgery in this patient population., Purpose: To identify variables that may be associated with surgical intervention in patients with shoulder instability in the context of the FEDS (frequency, etiology, direction, severity) classification, a system that may be useful in the surgical treatment of shoulder instability patients., Study Design: Cohort study (prognosis); Level of evidence, 2., Methods: A database of patients treated for shoulder instability from 3 separate institutions from 2005 to 2010 was generated using International Classification of Diseases-9th Revision data. Data were collected via retrospective review. Injury data were categorized according to the FEDS system. Data were analyzed for significance, with the primary outcome of surgical intervention. Summary statistics were used to assess which variables were associated with eventual surgery. To test the unadjusted bivariate associations between shoulder surgery and each data point, Pearson chi-square tests were used for categorical variables and Wilcoxon tests were used for continuous variables., Results: Over the study time period, 377 patients were treated for shoulder instability. Patients who had surgery were more likely younger, had recurrent instability, and had their initial injury while playing a sport. Most patients had anterior instability; however, there was a greater proportion of posterior instability patients in the operative group. Severity of dislocation, measured by whether the patient required help to relocate the shoulder, was not significantly associated with eventual surgery. While imaging was not available for all patients, surgical patients were more likely to have magnetic resonance imaging findings of anterior labral injury and less likely to have a supraspinatus or subscapularis tear., Conclusion: Patients who underwent surgery for shoulder instability were younger, more likely to have experienced recurrent instability, and more likely to have sustained their original injury while playing sports. The FEDS classification, particularly the frequency and etiology of the patient's shoulder instability, may be helpful in identifying patients with a higher likelihood of undergoing surgical treatment.

A 13-year-old right-hand-dominant skeletally immature boy presented to the authors' clinic after being blocked during an overhead dodgeball throw and hearing an abrupt "pop" in the shoulder. He had pain in the subdeltoid region that was most prominent during sports-related activity, particularly throwing. The patient had nonoperative management of a lesser tuberosity avulsion fracture 1 year earlier after a similar injury that occurred during a basketball game. He had returned to normal sporting activity 2 months before the most recent injury. Repeat advanced imaging showed an avulsion fracture of the subscapularis tendon, with a significantly retracted 2-cm component as well as a less retracted component, suggesting acute-on-chronic injury. Given this retraction and the symptoms during throwing, the patient was counseled that surgical management would best facilitate an asymptomatic return to sports-related activity. This case showed acute-on-chronic subscapularis tendon insufficiency with avulsion of the lesser tuberosity and significant retraction of the subscapularis tendon without tearing, a rare injury pattern in adolescents. For fixation of the avulsed lesser tuberosity fracture, an open approach technique was used in which SpeedBridge (Arthrex, Naples, Florida) sutures were passed behind the bone fragment. Four anchors were placed medial and lateral to the subscapularis insertion points to create a knotless double-row footprint. Compared with the published literature, this method of subscapularis fixation offered secure anatomic repair in a time-efficient, user-friendly manner., (Copyright 2015, SLACK Incorporated.)

Background: Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options., Methods: We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1:1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189., Findings: We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22·4 months (95% CI 19·0-25·2) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months (10·6-13·8) in the group assigned to chlorambucil only (hazard ratio 0·57, 95% CI 0·45-0·72; p<0·0001). Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group (109 [50%] patients; vs 98 [43%] given chlorambucil alone), with neutropenia being the most common event (56 [26%] vs 32 [14%]). Grade 3 or greater infections had similar frequency in both groups. Grade 3 or greater infusion-related adverse events were reported in 22 (10%) patients given chlorambucil plus ofatumumab. Five (2%) patients died during treatment in each group., Interpretation: Addition of ofatumumab to chlorambucil led to clinically important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities. Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who cannot tolerate more intensive therapy., Funding: GlaxoSmithKline, Genmab A/S., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Management of Anterior Cruciate Ligament Injuries: Evidence-Based Guideline is based on a systematic review of the current scientific and clinical research. This guideline has been endorsed by the National Academy of Sports Medicine, the American Orthopaedic Society for Sports Medicine, the National Athletic Trainers' Association, and the American Academy of Physical Medicine and Rehabilitation. The guideline contains 20 recommendations, including both diagnosis and treatment. In addition, the work group highlighted the need for better research in the treatment of anterior cruciate ligament injuries., (Copyright 2015 by the American Academy of Orthopaedic Surgeons.)

Background: Treatment of osteochondritis dissecans (OCD) of the knee is challenging, and evidence for stage-dependent treatment options is lacking. Basic science approaches utilizing animal models have provided insight into the etiology of OCD but have yet to produce a reliable and reproducible large animal model of the disease on which to test new surgical strategies., Purpose/hypotheses: The purpose of this study was to develop an animal model featuring an OCD-like lesion in terms of size, location, and International Cartilage Repair Society (ICRS) grading. The hypothesis was that surgical creation of an osteochondral defect followed by placement of a barrier between parent bone and progeny fragment would generate a reproducible OCD-like lesion., Study Design: Controlled laboratory study., Methods: Bilateral osteochondral lesions were created in the medial femoral condyles of 9 Yucatan minipigs. After lesion creation, a biodegradable membrane was interposed between the progeny and parent bone. Five different treatment groups were evaluated at 2 weeks: a control with no membrane (ctrl group; n = 4), a slowly degrading nanofibrous poly(∊-caprolactone) membrane (PCL group; n = 4), a fenestrated PCL membrane with 1.5-mm holes covering 25% of surface area (fenPCL group; n = 4), a collagen membrane (Bio-Gide) (CM group; n = 3), and a fenestrated CM (fenCM group; n = 3). Five unperturbed lateral condyles (1 from each treatment group) served as sham controls. After euthanasia on day 14, the lesion was evaluated by gross inspection, fluoroscopy, micro-computed tomography (micro-CT), and histology. To quantify changes between groups, a scoring system based on gross appearance (0-2), fluoroscopy (0-2), and micro-CT (0-6) was established. Micro-CT was used to quantify bone volume per total volume (BV/TV) in a defined region surrounding and inclusive of the defect., Results: The no scaffold group showed healing of the subchondral bone at 2 weeks, with continuity of subchondral bone elements. Conversely, condyles treated with PCL or CM showed substantial remodeling, with loss of bone in both the progeny fragment and surrounding parent bone. When these membranes were fenestrated (fenPCL and fenCM groups), bone loss was less severe. Histological analysis showed no integration in the cartilage layer in any treatment group, while fibrous tissue formed between the parent and progeny fragments. Micro-CT showed significant differences in mean BV/TV between the PCL (27.4% ± 2.3%) and the sham (47.7% ± 1.4%) or no scaffold (54.9% ± 15.1%) groups (P < .01 and P < .05, respectively). In addition, a significant difference in bone loss was evident between the PCL and fenPCL groups (mean BV/TV, 46.6% ± 15.2%; P < .05), as well as between the PCL and fenCM (mean BV/TV, 50.9% ± 3.5%) and fenPCL groups (P < .01). Grading by 6 blinded reviewers using an OCD scoring system with 3 subcategories showed a significant difference between control and PCL groups., Conclusion: This study successfully developed a large animal model of OCD-like lesions in the knee joint of Yucatan minipigs. The lesions generated matched characteristics of an ICRS grade 3 OCD lesion in humans. These findings set the stage for ongoing model refinement as well as exploration of novel interventional therapies to restore function and bone and cartilage patency in individuals affected by this rare but significant disease., Clinical Relevance: This developed model will serve as a platform on which to further investigate the natural course as well as emerging treatment options for OCD.

Background: Anterior cruciate ligament (ACL) reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. Limited data are available regarding the agreement among orthopaedic surgeons regarding the causes of primary ACL reconstruction failure and accuracy of graft tunnel placement., Hypothesis: Experienced knee surgeons have a high level of interobserver reliability in the agreement about the causes of primary ACL reconstruction failure, anatomic graft characteristics, and tunnel placement., Study Design: Cohort study (diagnosis); Level of evidence, 3., Methods: Twenty cases of revision ACL reconstruction were randomly selected from the Multicenter ACL Revision Study (MARS) database. Each case included the patient's history, standardized radiographs, and a concise 30-second arthroscopic video taken at the time of revision demonstrating the graft remnant and location of the tunnel apertures. All 20 cases were reviewed by 10 MARS surgeons not involved with the primary surgery. Each surgeon completed a 2-part questionnaire dealing with each surgeon's training and practice, as well as the placement of the femoral and tibial tunnels, condition of the primary graft, and the surgeon's opinion as to the causes of graft failure. Interrater agreement was determined for each question with the kappa coefficient and the prevalence-adjusted, bias-adjusted kappa (PABAK)., Results: The 10 reviewers have been in practice an average of 14 years and have performed at least 25 ACL reconstructions per year, and 9 were fellowship trained in sports medicine. There was wide variability in agreement among knee experts as to the specific causes of ACL graft failure. When participants were specifically asked about technical error as the cause for failure, interobserver agreement was only slight (PABAK = 0.26). There was fair overall agreement on ideal femoral tunnel placement (PABAK = 0.55) but only slight agreement on whether a femoral tunnel was too anterior (PABAK = 0.24) and fair agreement on whether it was too vertical (PABAK = 0.46). There was poor overall agreement for ideal tibial tunnel placement (PABAK = 0.17)., Conclusion: This study suggests that more objective criteria are needed to accurately determine the causes of primary ACL graft failure as well as the ideal femoral and tibial tunnel placement in patients undergoing revision ACL reconstruction., (© 2014 The Author(s).)

Background: Osteochondritis dissecans (OCD) is a vexing condition for patients, parents, and physicians because of the frequent slow healing and nonhealing that leads to prolonged treatment. Several features on plain radiographs have been identified as predictors of healing, but the reliability of their measurement has not been established., Purpose: To determine the inter- and intrarater reliability of several radiographic features used in the diagnosis, treatment, and prognosis of OCD femoral condyle lesions., Study Design: Cohort study (Diagnosis); Level of evidence, 3., Methods: Pretreatment anteroposterior, lateral, and notch radiographs of 45 knees containing OCD lesions of the medial or lateral femoral condyle were reviewed in blinded fashion by 7 orthopaedic physician raters from different institutions over a secure web portal at 2 time points over a month apart. Classification variables included lesion location, growth plate maturity, parent bone radiodensity, progeny bone fragmentation, progeny bone displacement, progeny bone contour, lesion boundary, and radiodensity of the lesion center and rim. Condylar width and lesion size were measured on all views. Interrater reliability was assessed using free-marginal kappa and intraclass correlations. Intrarater reliability was assessed using the Cohen kappa, linear-weighted kappa, and intraclass correlations based on measurement type., Results: Raters had excellent reliability for differentiating medial and lateral lesions and growth plate maturity and for measuring condylar width and lesion size. In the subset of knees with visible bone in the lesion, the fragmentation, displacement, boundary, central radiodensity, and contour (concave/nonconcave) of the lesion bone were classified with moderate to substantial reliability. The radiodensity of the lesion rim and surrounding epiphyseal bone were classified with poor to fair reliability., Conclusion: Many diagnostic features of femoral condyle OCD lesions can be reliably classified on plain radiographs, supporting their future testing in multifactorial classification systems and multicenter research to develop prognostic algorithms. Other radiographic features should be excluded, however, because of poor reliability., (© 2015 The Author(s).)

The authors' preferred treatment algorithm for osteochondritis dissecans (OCD) of the knee is based on skeletal maturity, OCD lesion stability, and OCD lesion salvageability. For unstable yet salvageable OCD lesions, the senior author's preferred treatment is fixation with bone grafting. For unstable and unsalvageable OCD lesions, the senior author's preferred treatment is autologous chondrocyte implantation with bone grafting., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Multiple systems for classifying osteochondritis dissecans (OCD) of the knee have been reported. These existing classification systems have some similar characteristics, such as stable lesion/intact articular cartilage and presence of a loose body. However, variations are found in the number of stages and specific lesion characteristics assessed. Currently, no system has been universally accepted. A future classification system should be developed that reconciles the discrepancies among the current systems and provides a clear, consistent, and reliable method for classifying OCD lesions of the knee during arthroscopy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Several aetiological theories have been proposed for the development of osteochondritis dissecans. Cartilage toxicity after fluoroquinolone use has been well documented in vitro. We present a case report of a 10-year-old child who underwent a prolonged 18-month course of ciprofloxacin therapy for chronic urinary tract infections. This patient later developed an osteochondritis dissecans lesion of the medial femoral condyle. We hypothesise that the fluoroquinolone therapy disrupted normal endochondral ossification, resulting in development of osteochondritis dissecans. The aetiology of osteochondritis dissecans is still unclear, and this case describes an association between fluoroquinolone use and osteochondritis dissecans development., (2014 BMJ Publishing Group Ltd.)

Background: Emergency department (ED) patients frequently undergo chest x-ray (CXR) to evaluate for pneumonia. The rate of false-negative CXR in patients with pneumonia is unclear., Objectives: Identify patients admitted with pneumonia who were diagnosed by CT despite nondiagnostic CXR., Methods: Retrospective analysis of quality improvement data on adult ED patients admitted with pneumonia over 21 months. Primary outcome was percent of patients diagnosed by CT despite normal CXR. Patients were classified as CXR-diagnosed if they had CXR and no CT, or if antibiotics were ordered after CXR and before CT. CT-based diagnosis was indicated by administration of antibiotics only after CT was completed., Results: 49 patients (11.4%) were diagnosed by CT (p<0.001). These patients were younger (p<0.001) and more often complained of chest pain (p<0.001)., Conclusions: Patients with pneumonia may present with normal or nondiagnostic CXR, although false negatives may be less common than previously reported.

Background: Research has associated adhesive capsulitis with diabetes mellitus but suggests that glucose-mediated injury may begin before diabetes is diagnosed. The period preceding diabetes is often marked by metabolic syndrome., Methods: We investigated the relationship between metabolic syndrome components (insulin resistance, hypertension, dyslipidemia, and obesity) and the development of adhesive capsulitis using a case-control study. We retrospectively reviewed 150 consecutive adhesive capsulitis patient charts to determine the prevalence of obesity and of medications used for treating metabolic syndrome elements and compared these with previously reported nationwide values., Results: The prevalence of anti-hyperglycemia medications in the adhesive capsulitis cohort was 18.4% (95% confidence interval [CI], 12.9%-25.7%), twice the national rate of diagnosed diabetes of 7.6% (95% CI, 6.7%-8.5%). In the 20- to 39-year-old group, the prevalence of anti-hyperglycemic medications, 26.3% (95% CI, 11.8%-48.8%), was over 10 times the nationwide rate. The overall prevalence of hypertensive medication use in the adhesive capsulitis group, 33.1% (95% CI, 25.9%-41.2%), was notably higher than the nationwide rate, 21.6% (95% CI, 19.8%-23.4%). In the 40- to 64-year-old group, the prevalence of hypertensive medication use, 36.8% (95% CI, 28.6%-46.0%), was notably higher than the nationwide rate of 24.5% (95% CI, 22.2%-27.0%). The prevalence of anti-lipid medications and obesity was similar between the groups., Conclusions: The relationship between adhesive capsulitis and metabolic syndrome remains unclear. Our results confirm previous work associating hyperglycemia with adhesive capsulitis. We have also shown a possible association of hypertension, part of metabolic syndrome and a proinflammatory condition, with adhesive capsulitis, which has not been previously described., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Hypothesis: The purpose of this cross-sectional study is to determine whether the duration of symptoms influences the features seen in patients with atraumatic, full-thickness rotator cuff tears. Our hypothesis is that an increasing duration of symptoms will correlate with more advanced findings of rotator cuff tear severity on magnetic resonance imaging, worse shoulder outcome scores, more pain, decreased range of motion, and less strength., Methods: We enrolled 450 patients with full-thickness rotator cuff tears in a prospective cohort study to assess the effectiveness of nonoperative treatment and factors predictive of success. The duration of patient symptoms was divided into 4 groups: 3 months or less, 4 to 6 months, 7 to 12 months, and greater than 12 months. Data collected at patient entry into the study included (1) demographic data, (2) history and physical examination data, (3) radiographic imaging data, and (4) validated patient-reported measures of shoulder status. Statistical analysis included a univariate analysis with the Kruskal-Wallis test and Pearson test to identify statistically significant differences in these features for different durations of symptoms., Results: A longer duration of symptoms does not correlate with more severe rotator cuff disease. The duration of symptoms was not related to weakness, limited range of motion, tear size, fatty atrophy, or validated patient-reported outcome measures., Conclusions: There is only a weak relationship between the duration of symptoms and features associated with rotator cuff disease., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: For many orthopaedic disorders, symptoms correlate with disease severity. The objective of this study was to determine if pain level is related to the severity of rotator cuff disorders., Methods: A cohort of 393 subjects with an atraumatic symptomatic full-thickness rotator-cuff tear treated with physical therapy was studied. Baseline pretreatment data were used to examine the relationship between the severity of rotator cuff disease and pain. Disease severity was determined by evaluating tear size, retraction, superior humeral head migration, and rotator cuff muscle atrophy. Pain was measured on the 10-point visual analog scale (VAS) in the patient-reported American Shoulder and Elbow Surgeons (ASES) score. A linear multiple regression model was constructed with use of the continuous VAS score as the dependent variable and measures of rotator cuff tear severity and other nonanatomic patient factors as the independent variables. Forty-eight percent of the patients were female, and the median age was sixty-one years. The dominant shoulder was involved in 69% of the patients. The duration of symptoms was less than one month for 8% of the patients, one to three months for 22%, four to six months for 20%, seven to twelve months for 15%, and more than a year for 36%. The tear involved only the supraspinatus in 72% of the patients; the supraspinatus and infraspinatus, with or without the teres minor, in 21%; and only the subscapularis in 7%. Humeral head migration was noted in 16%. Tendon retraction was minimal in 48%, midhumeral in 34%, glenohumeral in 13%, and to the glenoid in 5%. The median baseline VAS pain score was 4.4., Results: Multivariable modeling, controlling for other baseline factors, identified increased comorbidities (p = 0.002), lower education level (p = 0.004), and race (p = 0.041) as the only significant factors associated with pain on presentation. No measure of rotator cuff tear severity correlated with pain (p &gt; 0.25)., Conclusions: Anatomic features defining the severity of atraumatic rotator cuff tears are not associated with the pain level. Factors associated with pain are comorbidities, lower education level, and race., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

A recent randomized trial from the Finnish Degenerative Meniscal Lesion Study Group was published in the New England Journal of Medicine and attempted to determine the efficacy of partial meniscectomy without osteoarthritis. Patients were randomized to either arthroscopic partial meniscectomy or sham surgery. The authors concluded that the clinical outcomes after arthroscopic partial meniscectomy were no better than those after the sham surgical procedure. However, there are several important limitations of this trial that make it difficult to generalize to the 700,000 arthroscopic partial meniscectomies performed in the United States each year. In this small sample of 146 patients, patients with traumatic meniscal tears and locking symptoms-those most likely to benefit from a partial meniscectomy-were excluded. In addition, although patients with radiographic arthritis were excluded, most of the patients in the study had degenerative changes at the time of arthroscopy. Therefore it is difficult to determine whether the patients were symptomatic from their chondral degeneration or their degenerative meniscal tear. In our opinion this study does not change the role of surgery in current clinical practice. The primary indication for arthroscopic partial meniscectomy remains symptoms of well-localized joint line pain with acute onset and mechanical symptoms such as catching or locking that have failed comprehensive nonoperative management., (Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The authors' preferred treatment algorithm for osteochondritis dissecans (OCD) of the knee is based on skeletal maturity, OCD lesion stability, and OCD lesion salvageability. For unstable yet salvageable OCD lesions, the senior author's preferred treatment is fixation with bone grafting. For unstable and unsalvageable OCD lesions, the senior author's preferred treatment is autologous chondrocyte implantation with bone grafting., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Multiple systems for classifying osteochondritis dissecans (OCD) of the knee have been reported. These existing classification systems have some similar characteristics, such as stable lesion/intact articular cartilage and presence of a loose body. However, variations are found in the number of stages and specific lesion characteristics assessed. Currently, no system has been universally accepted. A future classification system should be developed that reconciles the discrepancies among the current systems and provides a clear, consistent, and reliable method for classifying OCD lesions of the knee during arthroscopy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Organophosphate (OP) pesticide poisoning is a global health problem with over 250,000 deaths per year. OPs affect neuronal signaling through acetylcholine (Ach) neurotransmission via inhibition of acetylcholinesterase (AChE), leading to accumulation of Ach at the synaptic cleft and excessive stimulation at post-synaptic receptors. Mortality due to OP agents is attributed to respiratory dysfunction, including central apnea. Cholinergic circuits are integral to many aspects of the central control of respiration, however it is unclear which mechanisms predominate during acute OP intoxication. A more complete understanding of the cholinergic aspects of both respiratory control as well as neural modification of pulmonary function is needed to better understand OP-induced respiratory dysfunction. In this article, we review the physiologic mechanisms of acute OP exposure in the context of the known cholinergic contributions to the central control of respiration. We also discuss the potential central cholinergic contributions to the known peripheral physiologic effects of OP intoxication., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: To assess the effectiveness of a specific nonoperative physical therapy program in treating atraumatic full-thickness rotator cuff tears using a multicenter prospective cohort study design., Materials and Methods: Patients with atraumatic full-thickness rotator cuff tears who consented to enroll provided data via questionnaire on demographics, symptom characteristics, comorbidities, willingness to undergo surgery, and patient-related outcome assessments (Short Form 12 score, American Shoulder and Elbow Surgeons score, Western Ontario Rotator Cuff score, Single Assessment Numeric Evaluation score, and Shoulder Activity Scale). Physicians recorded physical examination and imaging data. Patients began a physical therapy program developed from a systematic review of the literature and returned for evaluation at 6 and 12 weeks. At those visits, patients could choose 1 of 3 courses: (1) cured (no formal follow-up scheduled), (2) improved (continue therapy with scheduled reassessment in 6 weeks), or (3) no better (surgery offered). Patients were contacted by telephone at 1 and 2 years to determine whether they had undergone surgery since their last visit. A Wilcoxon signed rank test with continuity correction was used to compare initial, 6-week, and 12-week outcome scores., Results: The cohort consists of 452 patients. Patient-reported outcomes improved significantly at 6 and 12 weeks. Patients elected to undergo surgery less than 25% of the time. Patients who decided to have surgery generally did so between 6 and 12 weeks, and few had surgery between 3 and 24 months., Conclusion: Nonoperative treatment using this physical therapy protocol is effective for treating atraumatic full-thickness rotator cuff tears in approximately 75% of patients followed up for 2 years., (Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Arthroscopic partial meniscectomy can be complicated by excessive resection, damage to articular cartilage, neurovascular injury, persistent drainage from portals, and infection; the procedure can be rendered more difficult, and the outcome less certain, if the surgeon fails to recognize concomitant injuries, malpositions the portals, or misidentifies the components of a meniscus tear. We review the problems that can occur as a result of errors made before, during, and after surgery.

Background: Osteochondritis dissecans (OCD) has been defined as a localized process in which a focus of subchondral bone and adjacent articular cartilage separates from the surrounding bone. With the knee being the most common location for OCD development and the propensity for this lesion to be found in those who participate in sports, a repetitive microtrauma hypothesis for its cause has gained favor. However, the cause of OCD remains controversial, as does the most appropriate treatment for the varying degrees of OCD lesions., Case Description: We present a unique case of three OCD lesions in one knee. The patient was a young, athletic boy who developed three separate OCD lesions in his right knee over the course of 4 years. Temporally, the OCD lesions developed first in the lateral femoral condyle, then in the medial femoral condyle, and finally in the trochlea., Literature Review: Our literature review yielded a few reports of bicondylar OCD lesions. We identified no previous reports of three separate OCD lesions found in a single joint., Purposes and Clinical Relevance: This report illustrates how a uniquely affected knee with three OCD lesions was treated in three different ways with resolution of symptoms. Each of the OCD lesions was evaluated individually and treatment for each based on the severity of the lesion from the physical examination, imaging studies, and arthroscopic findings.

Background: Early diagnosis and successful treatment of juvenile osteochondritis dissecans (JOCD) is essential in preventing articular degeneration at a young age. Surgical treatment of stable JOCD lesions failing nonoperative treatment involves retroarticular or transarticular drilling to induce revascularization and healing. Multiple case series report high healing rates and infrequent complications for both retroarticular and transarticular drilling modalities; however, it is unclear from these individual reports whether one mode of drilling provides higher healing rates., Questions/purposes: We asked whether transarticular or retroarticular drilling of stable JOCD lesions results in differing patient-oriented outcomes, rates of radiographic healing, time to radiographic healing, and complication rates., Methods: We systematically reviewed the short-term clinical outcomes of retroarticular and transarticular drilling of stable OCD lesions. PubMed and additional sources identified 65 studies; 12 studies met inclusion criteria., Results: Heterogeneity and quality of studies limited review to qualitative analysis. No clear differences were seen in patient-oriented outcomes after treatment with either drilling modality. Radiographic healing for JOCD lesions drilled retroarticularly occurred in 96 of 111 (86%) lesions in an average of 5.6 months. Transarticular drilling of JOCD lesions resulted in 86 of 94 (91%) lesions healing by radiography in an average of 4.5 months. No complications were reported for either drilling modality., Conclusions: Retroarticular and transarticular drilling of stable lesions results in comparable short-term patient-oriented outcomes and radiographic healing. Further high-quality comparative studies are required to adequately compare drilling modalities, clearly define radiographic healing, and patient-oriented outcomes after nonoperative treatment.

Background: Although many etiological theories have been proposed for osteochondritis dissecans (OCD), its etiology remains unclear. Histological analysis of the articular cartilage and subchondral bone tissues of OCD lesions can provide useful information about the cellular changes and progression of OCD. Previous research is predominantly comprised of retrospective clinical studies from which limited conclusions can be drawn., Questions/purposes: The purposes of this study were threefold: (1) Is osteonecrosis a consistent finding in OCD biopsy specimens? (2) Is normal articular cartilage a consistent finding in OCD biopsy specimens? (3) Do histological studies propose an etiology for OCD based on the tissue findings?, Methods: We searched the PubMed, Embase, and CINAHL databases for studies that conducted histological analyses of OCD lesions of the knee and identified 1560 articles. Of these, 11 met our inclusion criteria: a study of OCD lesions about the knee, published in the English language, and performed a histological analysis of subchondral bone and articular cartilage. These 11 studies were assessed for an etiology proposed in the study based on the study findings., Results: Seven of 11 studies reported subchondral bone necrosis. Four studies reported normal articular cartilage, two studies reported degenerated or irregular articular cartilage, and five studies found a combination of normal and degenerated or irregular articular cartilage. Five studies proposed trauma or repetitive stress and two studies proposed poor blood supply as possible etiologies., Conclusions: We found limited research on histological analysis of OCD lesions of the knee. Future studies with consistent methodology are necessary to draw major conclusions about the histology and progression of OCD lesions. Inconsistent histologic findings have resulted in a lack of consensus regarding the presence of osteonecrosis, whether the necrosis is primary or secondary, the association of cartilage degeneration, and the etiology of OCD. Such studies could use a standardized grading system to allow better comparison of findings.

A gingival crevice model (epithelial cell-Porphyromonas gingivalis-neutrophil) was established and used to profile gingipain, matrix metalloproteinase (MMP), MMP mediators [neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinases 1 (TIMP-1)] and cytokine networks. Smoking is the primary environmental risk factor for periodontitis. Therefore, the influence of cigarette smoke extract (CSE) was also monitored in the same model. Porphyromonas gingivalis alone induced low levels of interleukin-1β and interleukin-8 from epithelial cells, but high levels of both cytokines were produced on the addition of neutrophils. Exposure to CSE (100 and 1000 ng ml(-1) nicotine equivalency) significantly compromised P. gingivalis-induced cytokine secretion (both P < 0.05). P. gingivalis induced impressive secretion of NGAL (P < 0.05) that was not influenced by CSE. The influence of CSE on gingipain production was strain-specific. Purified gingipains effectively and rapidly degraded both TIMP-1 and MMP-9. Induction of large amounts of NGAL, degradation of TIMP-1, and increased gingipain activity would each be expected to prolong collagen degradation and promote disease progression. However, gingipains also degrade MMP-9. Hence, P. gingivalis exerts a complex influence on the proteolytic balance of a gingival crevice model. Exposure to CSE reduces the proinflammatory cytokine burden, which may be expected to promote P. gingivalis survival. In addition to novel findings that provide mechanistic insight into periodontal disease progression, these results are in keeping with the recognized clinical dogma of decreased inflammation/increased disease in smokers. This straightforward gingival crevice model is established as a suitable vehicle for the elucidation of mechanisms that contribute to susceptibility to periodontitis., (© 2012 John Wiley & Sons A/S.)

Background: Knee injury prevention programs have been developed to address the epidemic of knee injuries in young athletes. These programs include exercises that focus on balance, proprioception, and neuromuscular control. Some studies have suggested such specialized exercise programs may reduce the risk of knee injury., Questions/purposes: We conducted a systematic review of randomized controlled trials (RCTs) of knee injury prevention programs and evaluated the risks of bias in these studies., Methods: We performed a systematic search using MEDLINE (from 1966), CINAHL (from 1982), Cochrane (CENTRAL), and EMBASE (from 1974) in April 2011. The searches were limited to RCTs. Two reviewers independently assessed the internal validity of the included studies using the van Tulder critical appraisal tool for RCTs. Authors were contacted when internal validity was unclear in the methodology. Ten Level I studies (RCTs) met the inclusion criteria. The average risk of bias score for these studies was 7 of 11 (range, 5-10)., Results: Two of the 10 studies reported a reduction in knee injuries. Of the three studies that provided ACL injuries as an outcome measure, none showed a reduction in overall ACL injury., Conclusions: Current evidence suggests most (eight of 10) well-designed RCTs show no difference of treatment benefit. Perhaps refinements of interventions may lead to a reduction in knee and ACL injuries in future trials. Limitations in the number and heterogeneity of currently published RCTs of injury prevention programs place restraints on quantifying intervention efficacy with a meta-analytic approach. Future research articles should more clearly describe the different elements of their methodology, consistent with the standards set forth by the CONSORT statement.

Background: Little is known about surgeon agreement and accuracy using arthroscopic evaluation of anterior cruciate ligament (ACL) tunnel positioning., Purpose: To investigate agreement on ACL tunnel position evaluated arthroscopically between operating surgeons and reviewing surgeons. We hypothesized that operating and evaluating surgeons would characterize tunnel positions significantly differently., Study Design: Controlled laboratory study., Methods: Twelve surgeons drilled ACL tunnels on 72 cadaveric knees using transtibial (TT), medial portal (MP), or 2-incision (TI) techniques and then completed a detailed assessment form on tunnel positioning. Then, 3 independent blinded surgeon reviewers each arthroscopically evaluated tunnel position and completed the assessment form. Statistical comparisons of tunnel position evaluation between operating and reviewing surgeons were completed. Three-dimensional (3D) computed tomography (CT) scans were performed and compared with arthroscopic assessments. Arthroscopic assessments were compared with CT tunnel location criteria., Results: Operating surgeons were significantly more likely to evaluate femoral tunnel position (92.6% vs 69.2%; P = .0054) and femoral back wall thickness as "ideal" compared with reviewing surgeons. Tunnels were judged ideal by reviewing surgeons more often when the TI technique was used compared with the MP and TT techniques. Operating surgeons were more likely to evaluate tibial tunnel position as ideal (95.5% vs 57.1%; P < .0001) and "acceptable" compared with reviewers. The ACL tunnels drilled using the TT technique were least likely to be judged as ideal on the tibia and the femur. Agreement among surgeons and observers was poor for all parameters (κ = -0.0053 to 0.2457). By 3D CT criteria, 88% of femoral tunnels and 78% of tibial tunnels were placed within applied criteria., Conclusion: Operating surgeons are more likely to judge their tunnels favorably than observers. However, independent surgeon reviewers appear to be more critical than results of 3D CT imaging measures. When subjectively evaluated arthroscopically, the TT technique yields more subjectively poorly positioned tunnels than the TI and MP techniques. Surgeons do not agree on the ideal placement for single-bundle ACL tunnels., Clinical Relevance: This study demonstrates that surgeons do not currently uniformly agree on ideal single-bundle tunnel placement and that the TT technique may yield more poorly placed tunnels.

Background: The adverse effects of smoking on various health conditions such as cancer, diabetes, and cardiovascular disease have been well documented. Many orthopaedic conditions, such as fracture healing, wound repair, and bone mineral density, have been reported to be adversely affected by smoking. However, no known systematic reviews have investigated the effects of smoking on ligament and cartilage knee surgery., Purpose: We hypothesized that smoking would have a negative influence from both a basic science and clinical outcome perspective on these types of knee surgeries., Study Design: Systematic review., Methods: A systematic review of multiple medical databases was performed evaluating clinical and basic science studies to determine the effects of smoking on ligament and cartilage knee surgery., Results: Fourteen studies were found for inclusion and analysis. Eight of these studies addressed the relationship between smoking and knee ligaments, and 6 investigated the relationship between smoking and articular cartilage. With the exception of 1, all of the basic science and clinical studies exploring the relationship between smoking and knee ligaments found a negative association of smoking, either molecularly, biomechanically, or clinically. One basic science and 3 clinical studies found a negative influence of smoking on articular cartilage of the knee. No studies were found that investigated the relationship of smoking and menisci., Conclusion: The current literature reveals a negative influence of smoking on the results of knee ligament surgery, both from a basic science and clinical perspective, implying that smoking cessation would benefit patients undergoing these procedures. The association between smoking and knee articular cartilage was less clear, although the literature still suggests an overall negative influence and highlights the need for further investigation.

Background: Patellofemoral instability affects activities of daily living and hinders athletic participation. Over the past 2 decades, more attention has been paid to medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocations/subluxations. Numerous techniques have been reported; however, there is no consensus regarding optimal reconstruction., Purpose: This study sought to report on the various techniques for MPFL reconstruction described in the literature and to assess the rate of complications associated with the procedure., Study Design: Meta-analysis., Methods: A systematic review of the literature was performed in early October 2010 using keywords "medial patellofemoral ligament," "MPFL," "reconstruction," "complication(s)," and "failure(s)." Articles meeting the inclusion criteria were reviewed. Graft choice, surgical technique, outcome measures, and complications were recorded and organized in a database. Descriptive statistical analysis was performed on the data collected., Results: Twenty-five articles were identified and reviewed. A total of 164 complications occurred in 629 knees (26.1%). These adverse events ranged from minor to major including patellar fracture, failures, clinical instability on postoperative examination, loss of knee flexion, wound complications, and pain. Twenty-six patients returned to the operating room for additional procedures., Conclusion: Medial patellofemoral ligament reconstruction has a high rate of success for patients with patellofemoral instability; however, the complication rate of 26.1% associated with this procedure is not trivial. This study quantified complications and documented the variety of complications reported in outcomes-based literature.

Colonoscopy is generally a safe and effective means to detect, diagnose, and treat colonic abnormalities. Although the overall complication rate is low, the morbidity and mortality following perforation approach 50%. Here we present a case of a 49-year-old woman undergoing routine colonoscopy when she suffered bowel perforation and tension pneumoperitoneum. This is a seldom occurrence and may result following bowel perforation with the rapid accumulation of free air into the peritoneal cavity. It is a life-threatening complication and a surgical emergency.

Background: Although the reliability of determining acromial morphology has been examined, to date, there has not been an analysis of interobserver and intraobserver reliability on determining the presence and measuring the size of an acromial enthesophyte., Questions/purposes: The hypothesis of this study was that there will be poor intraobserver and interobserver reliability in the (1) determination of the presence of an acromial enthesophyte, (2) determination of the size of an acromial enthesophyte, and (3) determination of acromial morphology., Patients and Methods: Fifteen fellowship-trained orthopedic shoulder surgeons reviewed the radiographs of 15 patients at two different intervals. Measurement of acromial enthesophytes was performed using two techniques: (1) enthesophyte length and (2) enthesophyte-humeral distance. Acromial morphology was also determined. Interobserver and intraobserver agreement was determined using intraclass correlation and kappa statistical methods., Results: The interobserver reliability was fair to moderate and the intraobserver reliability moderate for determining the presence of an acromial enthesophyte. The measurement of the enthesophyte length showed poor interobserver and intraobserver reliability. The measurement of the enthesophyte-humeral distance showed poor interobserver reliability and moderate intraobserver reliability. The interobserver and intraobserver reliability in determining acromial morphology was found to be moderate and good, respectively., Conclusions: There is fair to moderate reliability among fellowship-trained shoulder surgeons in determining the presence of an acromial enthesophyte. However, there is poor reliability among observers in measuring the size of the enthesophyte. This study suggests that the enthesophyte-humeral distance may be more reliable than the enthesophyte length when measuring the size of the enthesophyte.

Purpose: Many clinical studies and systematic reviews have compared the short-term (2 years) outcomes of ACL reconstruction with hamstring and patellar tendon autograft. Few differences have been observed, with the exception of increased kneeling pain with patellar tendon grafts. The goal of this systematic review is to determine whether there are differences in clinical, patient-reported, or radiographic outcomes based on graft choice at a minimum of 5 years after ACL reconstruction., Methods: A systematic review was performed to identify all prospective outcome studies comparing patellar tendon and hamstring autograft ACL reconstruction with minimum follow-up of at least 5 years. Seven studies were identified and meta-analysis of select data determined to be sufficiently homogenous was performed (failure and laxity)., Results: Five randomized controlled trials and two prospective cohorts comparing hamstring and patellar tendon autografts were identified. Clinical assessment [failure rate, International Knee Documentation Committee (IKDC) class, Lachman, pivot shift, and KT 1000 testing] showed no difference between grafts. Patient-reported outcomes (Lysholm, Cincinnati, and IKDC) showed no difference. Both anterior knee pain (3/3 studies) and kneeling pain (4/4 studies) were more frequent in the patellar tendon group. However, the patient-reported outcomes in these studies were not different. Radiographic evidence of osteoarthritis was inconsistent between autograft choices., Conclusion: This level II systematic review demonstrates no difference in major clinical results between graft types with the exception of increased anterior knee and kneeling pain. There exists a potential for increased incidence of osteoarthritis in the patellar tendon group but increased sample size is required. These longer-term outcomes are similar to results of prior systematic reviews with two-year follow-up.

The CALAXO osteoconductive interference screw was recalled in August 2007 due to reports of increased numbers of postoperative complications associated with screw swelling and prominence leading to the need for surgical debridement. This study reviews complications associated with CALAXO screw use in a consecutive cohort of patients undergoing anterior cruciate ligament reconstruction surgery by the senior author at the authors' institution. Over a 12-month period, 226 CALAXO interference screws, either of 20 mm length or 25 mm length, were implanted in 112 patients, and postoperative complications were noted. The 25-mm tibial screw was over 5 times (RR 5.2, 95% CI 1.8 to 15.3) more likely to be prominent than the 20-mm screw (p value=.002). Four surgical debridements were required in the 25-mm tibial screw group; none were required in the 20-mm group. The authors hypothesize that the inability to bury the longer screw length into the bone tunnel is associated with postoperative complications associated with the CALAXO screw.

Data from large prospectively collected anterior cruciate ligament (ACL) cohorts are being utilized to address clinical questions regarding ACL injury demographics and outcomes of ACL reconstruction. These data are affected by patient and injury factors as well as surgical factors associated with the site of data collection. The aim of this article is to compare primary ACL reconstruction data from patient cohorts in the United States and Norway, demonstrating the similarities and differences between two large cohorts. Primary ACL reconstruction data from the Multicenter Orthopaedic Outcomes Network (MOON) in the United States and the Norwegian National Knee Ligament Registry (NKLR) were compared to identify similarities and differences in patient demographics, activity at injury, preoperative Knee injury and Osteoarthritis Outcome Score (KOOS), time to reconstruction, intraarticular pathology, and graft choice. Seven hundred and thirteen patients from the MOON cohort were compared with 4,928 patients from the NKLR. A higher percentage of males (NKLR 57%, MOON 52%; P < 0.01) and increased patient age (NKLR 27 years, MOON 23 years; P\0.001) were noted in the NKLR population. The most common sports associated with injury in the MOON cohort were basketball (20%), soccer (17%), and American football (14%); while soccer (42%), handball (26%), and downhill skiing (10%) were most common in the NKLR. Median time to reconstruction was 2.4 (Interquartile range [IQR] 1.2-7.2) months in the MOON cohort and 7.9 (IQR 4.2-17.8) months in the NKLR cohort (P < 0.001). Both meniscal tears (MOON 65%, NKLR 48%; P < 0.001) and articular cartilage defects (MOON 46%, NKLR 26%; P < 0.001) were more common in the MOON cohort. Hamstring autografts (MOON 44%, NKLR 63%) and patellar tendon autografts (MOON 42%, NKLR 37%) were commonly utilized in both cohorts. Allografts were much more frequently utilized in the MOON cohort (MOON 13%, NKLR 0.04%; P < 0.001). Significant diversity in patient, injury, and surgical factors exist among large prospective cohorts collected in different locations. Surgeons should investigate and consider the characteristics of these cohorts when applying knowledge gleaned from these groups to their own patient populations.

The development of premature osteoarthritis after anterior cruciate ligament (ACL) reconstruction is a significant cause of morbidity in young, active individuals. Meniscal injuries are frequently noted at the time of reconstruction, and the critical role of an intact meniscus in the prevention of osteoarthritis has been well documented. The purpose of this review is to evaluate the effects of meniscal status at ACL reconstruction on the subsequent development of osteoarthritis. A systematic review of the literature identified 11 studies with > or = 2 years of follow-up that compared patients' radiographic outcomes based on meniscus status at the time of ACL reconstruction. Patients undergoing partial meniscectomy at the time of ACL reconstruction were significantly more likely to develop radiographic evidence of osteoarthritis than those with normal menisci. Meniscal repair resulted in inconsistent findings. Virtually all patients who underwent complete meniscectomy at the time of ACL reconstruction had radiographic evidence of osteoarthritis at follow-up.

Background: Anterior cruciate ligament reconstruction can be performed with use of either autograft or allograft tissue. It is currently unclear if the outcomes of these two methods differ significantly. This systematic review and meta-analysis investigated whether the short-term clinical outcomes of anterior cruciate reconstruction with allograft were significantly different from those with autograft., Methods: A computerized search of the electronic databases MEDLINE and EMBASE was conducted. Only therapeutic studies with a prospective or retrospective comparative design were considered for inclusion in the present investigation. Two reviewers independently assessed the methodological quality and extracted relevant data from each included study. If a study failed the qualitative assessment and statistical tests of homogeneity, it was excluded from the meta-analysis. Furthermore, a study was withdrawn from the meta-analysis of a particular outcome if that outcome was not studied or was not reported adequately. A Mantel-Haenszel analysis utilizing a random-effects model allowed for pooling of results according to graft source while accounting for the number of subjects in individual studies., Results: Nine studies were determined to be appropriate for the systematic review. Eight studies compared bone-patellar tendon-bone grafts, and one study compared quadruple-stranded hamstring grafts. Five studies were prospective comparative studies, and four were retrospective comparative studies. One study, which investigated allografts that underwent a unique sterilization process, demonstrated an allograft failure rate of 45% (thirty-eight of eighty-five). That study failed the qualitative assessment and statistical tests of homogeneity and consequently was excluded from the meta-analysis. When the outcomes from the remaining studies were pooled according to graft source, the meta-analyses of the Lysholm score, instrumented laxity measurements, and the clinical failure rate estimated mean differences and odds ratios that were not significant. These findings were robust during the sensitivity analysis, which varied the included studies or variables on the basis of graft type, instrumented laxity cut-off value, secondary sterilization technique, duration of follow-up, mean patient age, and study methodology., Conclusions: In general, the short-term clinical outcomes of anterior cruciate reconstruction with allograft were not significantly different from those with autograft. However, it is important to note that none of these nonrandomized studies stratified outcomes according to age or utilized multivariable modeling to mathematically control for age (or any other possible confounder, such as activity level, that is not equally distributed in the two treatment groups). Understanding these limitations of the best available evidence, the surgeon may incorporate the results of the present systematic review into the informed-consent and shared-decision-making process in order to individualize optimum patient care.

Many anterior cruciate ligament (ACL) reconstructions have increased laxity postoperatively. We hypothesized that enhancing an ACL graft with a collagen-platelet composite (CPC) would improve knee laxity and graft structural properties. We also hypothesized the platelet concentration in the CPC would affect these parameters. Twelve goats underwent ACL reconstruction with autologous patellar tendon graft. In six goats, a collagen-platelet composite was placed around the graft (CPC group). In the remaining six goats, the collagen scaffold only was used (COLL group). Three goats were excluded due to complications. After 6 weeks in vivo, anterior-posterior (AP) laxity and tensile properties of the ACL reconstructed knees were measured and normalized against the contralateral intact knee. At a knee flexion angle of 30 degrees, the average increase in AP laxity was 40% less in the CPC group than the COLL group (p = 0.045). At 60 degrees, the AP laxity was 30% less in the CPC group, a difference that was close to statistical significance (p = 0.080). No differences were found between treatment groups with respect to the structural properties (p > 0.30). However, there were significant correlations between serum platelet concentration and AP laxity (R2 = 0.643; p = 0.009), maximum load (R2 = 0.691; p = 0.006), and graft stiffness (R2 = 0.840; p < 0.001). In conclusion, use of a CPC to enhance healing of an allograft ACL reconstruction inversely correlated with early sagittal plane laxity and the systemic platelet count was highly predictive of ACL reconstruction graft strength and stiffness at 6 weeks. These findings emphasize the importance of further research on delineating the effect of platelets in treating of ACL injuries., (Copyright 2008 Orthopaedic Research Society)

Background: Osteochondritis dissecans (OCD) can progress to loose body formation, resulting in a grade IV defect. The decision to fix versus excise the loose body is controversial. Published operative fixation outcomes are small case series with short follow-up., Hypothesis: Operative fixation (ORIF) of the loose body into the grade IV defect will heal and approximate "normal" knee function at long-term follow-up., Study Design: Case series; Level of evidence, 4., Methods: Twelve patients were identified who underwent ORIF of a knee OCD loose body into the grade IV osteochondral defects ranging in size from 2.0 to 8.0 cm(2) (mean, 3.5 cm(2)). After 12 weeks, hardware was removed, and healing was assessed. Long-term outcomes were assessed with a Knee injury and Osteoarthritis Outcome Score (KOOS) and a Marx activity score., Results: Arthroscopy for screw removal revealed stable healing in 92% (11 of 12) of patients. No patients required subsequent surgery for a loose body. At an average of 9.2 years' follow-up (range, 3.8-15.8 years), 83% (10 of 12) of patients completed the KOOS. The KOOS subscale scores for pain (mean, 87.8; range, 67-100), other symptoms (mean, 81.8; range, 61-96), function in activities of daily living (mean, 93.1; range, 72-100), and sports and recreation function (mean, 74.0; range, 40-100) were not significantly lower than those of published age-matched controls. However the KOOS subscale score for knee-related quality of life (mean, 61.9; range, 31-88) was significantly lower (P = .003)., Conclusion: Operative fixation of grade IV OCD loose bodies results in stable fixation. At an average 9 years after surgery, patients did not have symptoms of osteoarthritis pain and had normal function in activities of daily life. However, patients reported significantly lower knee-related quality of life. Operative fixation of OCD loose bodies is a better alternative to lesion excision.

Recent work has suggested the transected anterior cruciate ligament (ACL) can heal and support reasonable loads if repaired with sutures and a bioactive scaffold; however, use of a traditional suture configuration results in knees with increased anterior-posterior (AP) laxity. The objective was to determine whether one of five different suture repair constructs when performed at two different joint positions would restore normal AP knee laxity. AP laxity of the porcine knee at 60 degrees of flexion was evaluated for five suture repair techniques. Femoral fixation for all repair techniques utilized a suture anchor. Primary repair was to either the tibial stump, one of three bony locations in the ACL footprint, or a hybrid bony fixation. All five repairs were tied with the knee in first 30 degrees and then 60 degrees of flexion for a total of 10 repair constructs. Suture repair to bony fixation points within the anterior half of the normal ACL footprint resulted in knee laxity values within 0.5 mm of the ACL-intact joint when the sutures were tied with the knee at 60 degrees flexion. Suture repair to the tibial stump, or with the knee at 30 degrees of flexion, did not restore normal AP laxity of the knee. Three specific suture repair techniques for the transected porcine ACL restored the normal AP laxity of the knee at the time of surgery. Additional studies defining the changes in laxity with cyclic loading and in vivo healing are indicated., ((c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Providing quality flow cytometric results requires more than monitoring quality control data. Laboratories should standardize all aspects of testing and evaluate each one critically for opportunities to improve. This article discusses a complete quality management system that includes assay validation and change control, specimen collection and delivery, ordering of flow cytometric testing, sample preparation, verification of specimen integrity, flow cytometry data acquisition, analysis and interpretation, reporting of results, document of standard operating procedures, proficiency testing, training, and documentation of ongoing competency.

This report describes the diagnosis, follow-up, and problems measuring serum immunoglobulin E (IgE) levels in a case of IgE myeloma with 20-yr survival. Serum and urine protein electrophoresis, immunofixation, and the N Latex IgE test were used to characterize the monoclonal proteins. The diagnosis of multiple myeloma in a 56-yr-old man was based on 5.4 g/24 h of monoclonal free lambda chain in urine and bone marrow findings of 23.5% plasma cells (19% mature and 4.5% atypical). IgE lambda monoclonal protein in serum measured 506,000 microg/L (210 833 IU/mL). The lack of other clinical findings of multiple myeloma places this case in the category of 'smoldering or indolent myeloma'. Measurement of serum IgE levels was complicated by the need to predilute serum to avoid antigen excess. Following chemotherapy, the patient went into clinical remission, eventually dying of complications of emphysema. This case expands the recognized clinical spectrum of IgE multiple myeloma.

Background: Anterior cruciate ligament injuries are common in professional football players, and their career impact is unclear., Purpose: To quantify the affect of anterior cruciate ligament injuries on professional football player performance., Study Design: Cohort study (prognosis); Level of evidence, 2., Methods: Anterior cruciate ligament injury data from the National Football League were collected during a 5-year period (1998-2002) for running backs and wide receivers. Recorded variables included player age, experience, position, time to return to competition, and yearly total yards and touchdowns. Power ratings (total yards divided by 10 plus touchdowns multiplied by 6) were calculated for the injury season as well as for the 3 seasons before and after injury. A control group consisted of all running backs and wide receivers without an identified anterior cruciate ligament injury who competed in the 2000 season., Results: Data were analyzed for 31 running backs and wide receivers with 33 anterior cruciate ligament injuries. More than one fifth of players never returned to a National Football League game. Returning players first competed in a game 55.8 +/- 5.4 weeks (mean +/- standard error) after injury. For the 24 anterior cruciate ligament-injured players with a minimum total power rating (sum of all 7 seasons) of 200 points, power rating per game played decreased from 9.9 +/- 1.1 preinjury to 6.5 +/- 0.9 postinjury. This decline in power rating per game played was statistically significant (P = .002) when compared with the change for the 146 control players., Conclusion: Nearly four fifths of National Football League running backs and wide receivers who sustain an anterior cruciate ligament injury return to play in a game. On return to competition, player performance of injured players is reduced by one third.

Mullerian inhibiting substance (MIS) inhibits breast cancer cell growth in vitro. To extend the use of MIS to treat breast cancer, it is essential to test the responsiveness of mammary tumor growth to MIS in vivo. Mammary tumors arising in the C3(1) T antigen mouse model expressed the MIS type II receptor, and MIS in vitro inhibited the growth of cells derived from tumors. Administration of MIS to mice was associated with a lower number of palpable mammary tumors compared with vehicle-treated mice (P=0.048), and the mean mammary tumor weight in the MIS-treated group was significantly lower compared with the control group (P=0.029). Analysis of proliferating cell nuclear antigen (PCNA) expression and caspase-3 cleavage in tumors revealed that exposure to MIS was associated with decreased proliferation and increased apoptosis, respectively, and was not caused by a decline in T antigen expression. The effect of MIS on tumor growth was also evaluated on xenografted human breast cancer cell line MDA-MB-468, which is estrogen receptor- and retinoblastoma-negative and expresses mutant p53, and thus complements the C3(1)Tag mouse mammary tumors that do not express estrogen receptor and have functional inactivation of retinoblastoma and p53. In agreement with results observed in the transgenic mice, MIS decreased the rate of MDA-MB-468 tumor growth and the gain in mean tumor volume in severe combined immunodeficient mice compared with vehicle-treated controls (P=0.004). These results suggest that MIS can suppress the growth of mammary tumors in vivo.

BTG2, a p53-inducible antiproliferative gene, is stimulated in breast cancer cells by activation of nuclear factor kappa B (NF-kappaB). In rat mammary glands, BTG2 is expressed in epithelial cells and levels decreased during pregnancy and lactation but recovered during involution. Estrogen and progestin suppress BTG2 expression, suggesting that these steroids, which stimulate proliferation and lobuloalveolar development of mammary epithelial cells, may downregulate BTG2 in the mammary gland during pregnancy. Consistent with the report that BTG2 inhibits cyclin D1 expression, suppression of BTG2 mRNA in the mammary gland during gestation, and by estrogen and progestin, correlated with stimulation of cyclin D1. Ectopic expression of BTG2 inhibited breast cancer cell growth by arresting cells in the G1 phase, an effect reversed by cyclin D1. BTG2 expression was very low or undetectable in human breast cancer cell lines compared with nontumorigenic mammary epithelial cells, and nuclear expression of BTG2 was absent in 65% of human breast tumors compared with adjacent matched normal glands. Spontaneous mammary tumors arising in a mouse model with targeted expression of the early region of the SV40 large tumor Ag demonstrated loss of BTG2 protein very early during the tumorigenic process. Thus deregulation of BTG2 may be an important step in the development of mammary tumors.