Matthew J. Kraeutler

Bone–Patellar Tendon–Bone Autograft Versus Allograft in Outcomes of Anterior Cruciate Ligament Reconstruction A Meta-analysis of 5182 Patients

Background: Bone–patellar tendon–bone (BPTB) is a common autograft and allograft source used for anterior cruciate ligament (ACL) reconstruction. Although the failure rate is generally higher for allografts, donor site morbidity and anterior knee pain can be issues with BPTB autografts. Controversy exists regarding the functional outcomes, complications, and knee stability of these grafts, previous comparisons of which have been based on smaller samples of case series. Purpose: To compare BPTB autografts to allografts for ACL reconstruction, specifically with regard to patient satisfaction, return to preinjury activity level, and postoperative functional outcomes. Study Design: Meta-analysis. Methods: A total of 76 studies published between 1998 and 2012, including a total of 5182 patients, were reviewed. It was not required for studies to be comparative in nature. Outcomes evaluated were graft rupture rate, return to preinjury activity level, overall and subjective International Knee Documentation Committee (IKDC), Lysholm, Tegner activity, Cincinnati Knee Rating System, pivot shift, and single-legged hop tests, as well as KT-1000 arthrometer side-to-side difference and presence of anterior knee pain. Summary odds ratios with 95% confidence intervals were calculated to compare BPTB autografts to allografts for each outcome. Results: Outcomes on subjective IKDC, Lysholm, Tegner, single-legged hop, and KT-1000 arthrometer were statistically significantly in favor of autografts. Return to preinjury activity level, overall IKDC, pivot shift, and anterior knee pain were significantly in favor of allografts, although allograft BPTB demonstrated a 3-fold increase in rerupture rates compared with autograft (12.7% vs 4.3%). There was no significant difference between the 2 groups for Cincinnati Knee scores. Conclusion: Patients undergoing ACL reconstruction with BPTB autografts demonstrate lower rates of graft rupture, lower levels of knee laxity, and improved single-legged hop test results and are more generally satisfied postoperatively compared with patients undergoing reconstruction with allograft BPTB.

Network Reconstruction and Systems Analysis of Cardiac Myocyte Hypertrophy Signaling

Background: Little is known about how global signaling network properties influence cardiac myocyte hypertrophy. Results: New 106 species computational model exhibited enriched cross-talk motifs and modular organization, predicting Ras as the most influential hub. Conclusion: Multiple levels of network organization modulate hypertrophic outcomes. Significance: Rather than acting through isolated pathways, cardiac hypertrophy signaling is a highly integrated network. Cardiac hypertrophy is managed by a dense web of signaling pathways with many pathways influencing myocyte growth. A quantitative understanding of the contributions of individual pathways and their interactions is needed to better understand hypertrophy signaling and to develop more effective therapies for heart failure. We developed a computational model of the cardiac myocyte hypertrophy signaling network to determine how the components and network topology lead to differential regulation of transcription factors, gene expression, and myocyte size. Our computational model of the hypertrophy signaling network contains 106 species and 193 reactions, integrating 14 established pathways regulating cardiac myocyte growth. 109 of 114 model predictions were validated using published experimental data testing the effects of receptor activation on transcription factors and myocyte phenotypic outputs. Network motif analysis revealed an enrichment of bifan and biparallel cross-talk motifs. Sensitivity analysis was used to inform clustering of the network into modules and to identify species with the greatest effects on cell growth. Many species influenced hypertrophy, but only a few nodes had large positive or negative influences. Ras, a network hub, had the greatest effect on cell area and influenced more species than any other protein in the network. We validated this model prediction in cultured cardiac myocytes. With this integrative computational model, we identified the most influential species in the cardiac hypertrophy signaling network and demonstrate how different levels of network organization affect myocyte size, transcription factors, and gene expression.

Modeling cardiac β-adrenergic signaling with normalized-Hill differential equations: comparison with a biochemical model

BackgroundNew approaches are needed for large-scale predictive modeling of cellular signaling networks. While mass action and enzyme kinetic approaches require extensive biochemical data, current logic-based approaches are used primarily for qualitative predictions and have lacked direct quantitative comparison with biochemical models.ResultsWe developed a logic-based differential equation modeling approach for cell signaling networks based on normalized Hill activation/inhibition functions controlled by logical AND and OR operators to characterize signaling crosstalk. Using this approach, we modeled the cardiac β1-adrenergic signaling network, including 36 reactions and 25 species. Direct comparison of this model to an extensively characterized and validated biochemical model of the same network revealed that the new model gave reasonably accurate predictions of key network properties, even with default parameters. Normalized Hill functions improved quantitative predictions of global functional relationships compared with prior logic-based approaches. Comprehensive sensitivity analysis revealed the significant role of PKA negative feedback on upstream signaling and the importance of phosphodiesterases as key negative regulators of the network. The model was then extended to incorporate recently identified protein interaction data involving integrin-mediated mechanotransduction.ConclusionsThe normalized-Hill differential equation modeling approach allows quantitative prediction of network functional relationships and dynamics, even in systems with limited biochemical data.

The Prevalence of Articular Cartilage Changes in the Knee Joint in Patients Undergoing Arthroscopy for Meniscal Pathology

PURPOSE The purposes of this study were to evaluate the prevalence of articular cartilage changes in the knee joint and to analyze predictive factors for these changes in patients undergoing arthroscopy for meniscal pathology. METHODS Between March 2005 and June 2009, 1,010 patients underwent arthroscopic meniscectomy or meniscal repair by the senior author. During surgery, a precise diagram was used to carefully note the presence, location, size, and Outerbridge grade of changes to the articular surfaces of the knee joint. The prevalence of articular cartilage changes was calculated for 6 age groups: younger than 20 years, 20 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 years or older. Demographic data including gender, ethnicity, smoking status, and body mass index (BMI) were acquired from patient charts. RESULTS Overall, 48% of patients showed changes to the medial compartment, 25% to the lateral compartment, and 45% to the patellofemoral compartment. Eighty-five percent of patients aged 50 to 59 years and 86% of patients aged 60 years or older showed articular cartilage changes to at least 1 knee compartment. In contrast, only 13% of patients aged younger than 20 years and 32% of patients aged 20 to 29 years showed changes to at least 1 compartment. A significant relation was found between age and the development of articular cartilage changes in each of the 3 compartments (P < .0001). BMI was also significantly related to articular cartilage changes in the medial and patellofemoral compartments (P < .0001) but not the lateral compartment (P = .08). CONCLUSIONS This study shows a high prevalence of articular cartilage damage as defined by the Outerbridge classification in patients undergoing arthroscopic surgery for meniscal pathology. Risk factors that correlate with articular cartilage damage include increasing age, elevated BMI, medial compartment pathology, and knee contractures. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Kerlan-Jobe Orthopaedic Clinic overhead athlete scores in asymptomatic professional baseball pitchers.

BACKGROUND The Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow score is a subjective questionnaire that has been validated and been shown to be more specific in overhead athletes than the American Shoulder and Elbow Surgeons scale. The purpose of this study was to determine a mean KJOC score and reasonable range of KJOC scores within which a healthy asymptomatic professional baseball pitcher will fall. It was hypothesized that healthy professional baseball pitchers would have very high KJOC scores. MATERIALS AND METHODS KJOC questionnaires were given to all healthy pitchers before the start of the season at all levels in 1 professional Minor League system. Pitchers were asked to complete the questionnaire upon reporting to their AAA, AA, or A affiliate team. Any pitcher starting the season on the disabled list was excluded from the study. RESULTS KJOC scores were returned by 44 pitchers. The mean score for all pitchers was 94.82 (95% confidence interval, 92.94-96.70). The mean score for each question was greater than 9 of 10. The mean score for the AAA affiliate was significantly higher than that for the AA affiliate (P = .015). No other significant differences in scores were found between class levels or groups based on professional playing experience. CONCLUSION Only 7 of 44 healthy asymptomatic pitchers (16%) had a KJOC score below 90. Therefore, we believe that the KJOC score is an accurate assessment for overhead athletes and normal values should be greater than 90. Anything below this value could be a potential cause for concern for team physicians. LEVEL OF EVIDENCE Basic Science, Survey Study, Healthy Subjects.

Repair of Pectoralis Major Ruptures: Single-surgeon Case Series

Rupture of the pectoralis major is an uncommon injury that can lead to pain, loss of strength, and cosmetic deformity. The purpose of this study was to analyze the outcome of pectoralis major repairs by a single surgeon. Twenty-four patients who underwent pectoralis major repair by the senior author (M.D.L.) between May 2005 and March 2011 were retrospectively identified. Patients were assessed at least 6 months postoperatively with the use of various questionnaires, including the Penn Shoulder Score, American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form, and Single Assessment Numeric Evaluation (SANE). All patients were men with an injury to the sternal head of the pectoralis. Most (16/24; 67%) patients sustained the injury while bench or incline bench pressing. Nineteen (79%) patients were successfully contacted for follow-up. Of these, an average preinjury bench press of 318 lb (range, 145-525 lb) was restored to an average of 264 lb (range, 100-500 lb) at follow-up. Average preoperative Penn Shoulder Score was 60 points (range, 33-77 points), improving to 94 points (range, 64-100 points) at last follow-up (P=.011). Average postoperative ASES and SANE scores were 96 points (range, 60-100 points) and 93 points (range, 50-100 points), respectively. All but 1 patient were rated excellent (14/19; 74%) or good (4/19; 21%) by the Bak criteria. Operative treatment of pectoralis major rupture yields high patient satisfaction and allows predictable return of comfort, range of motion, cosmesis, and overall limb strength, with a slightly less predictable return of maximum bench press strength.

Accuracy of intra-articular injections of the glenohumeral joint through an anterior approach: arthroscopic correlation.

BACKGROUND Intra-articular injections of the glenohumeral joint are an important tool for orthopedic surgeons who treat the spectrum of shoulder disorders. Previous studies, however, have suggested that these injections may not be reliably placed intra-articularly in the glenohumeral joint when performed in the office setting and that radiographic assistance may be necessary. This study assessed the accuracy of a glenohumeral injection through an anterior approach with arthroscopic confirmation. MATERIALS AND METHODS The study included 75 consecutive patients who were undergoing routine shoulder arthroscopy for a variety of shoulder disorders. All underwent anterior placement of a 1.5-inch, 21-gauge needle using a location just lateral to the coracoid and angled 45° toward the glenohumeral joint. After injection of sterile saline, a diagnostic arthroscopy was initiated through a standard posterior portal. The needle was considered intra-articular if fluid was expressed from the eyelet of the needle when the arthroscopy pump was turned on or with direct visualization of the needle with the arthroscope, or both. RESULTS The needle was visualized with the arthroscope in all 75 patients (100%). In 70 patients (93.3%), fluid was expressed through the eyelet of the needle when the arthroscopy pump was turned on. CONCLUSIONS The results of this study show that an anterior injection into the glenohumeral joint can be accurately placed without radiographic assistance using standard landmarks. The technique used is similar to making a standard rotator interval portal during shoulder arthroscopy; therefore, it is most successful in the hands of experienced shoulder arthroscopists.

Microfracture Versus Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Knee: A Systematic Review of 5-Year Outcomes:

Background: Microfracture (MFx) and autologous chondrocyte implantation (ACI) are 2 surgical treatment options used to treat articular cartilage injuries of the knee joint. Purpose: To compare the midterm to long-term clinical outcomes of MFx versus ACI for focal chondral defects of the knee. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to locate studies (level of evidence I-III) comparing the minimum average 5-year clinical outcomes of patients undergoing MFx versus ACI. Search terms used were “knee,” “microfracture,” “autologous chondrocyte implantation,” and “autologous chondrocyte transplantation.” Patients were evaluated based on treatment failure rates, magnetic resonance imaging, and patient-reported outcome scores (Lysholm, Knee Injury and Osteoarthritis Outcome Score [KOOS], and Tegner scores). Results: Five studies (3 level I evidence, 2 level II evidence) were identified that met the inclusion criteria, including a total of 210 patients (211 lesions) undergoing MFx and 189 patients (189 lesions) undergoing ACI. The average follow-up among all studies was 7.0 years. Four studies utilized first-generation, periosteum-based ACI (P-ACI), and 1 study utilized third-generation, matrix-associated ACI (M-ACI). Treatment failure occurred in 18.5% of patients undergoing ACI and 17.1% of patients undergoing MFx (P = .70). Lysholm and KOOS scores were found to improve for both groups across studies, without a significant difference in improvement between the groups. The only significant difference in patient-reported outcome scores was found in the 1 study using M-ACI in which Tegner scores improved to a significantly greater extent in the ACI group compared with the MFx group (P = .003). Conclusion: Patients undergoing MFx or first/third-generation ACI for articular cartilage lesions in the knee can be expected to experience improvement in clinical outcomes at midterm to long-term follow-up without any significant difference between the groups.

A Cost-Effectiveness Analysis of Surgical Treatment Modalities for Chondral Lesions of the Knee: Microfracture, Osteochondral Autograft Transplantation, and Autologous Chondrocyte Implantation

Background: Numerous surgical options exist to treat chondral lesions in the knee, including microfracture (MFx), osteochondral autograft transplantation (OAT), first-generation autologous chondrocyte implantation (ACI-1), and next-generation ACI (ACI-2). Purpose: To compare the cost-effectiveness of MFx, OAT, and ACI-1. The secondary purpose of this study was to compare the functional outcomes of MFx, OAT, ACI-1, and ACI-2. Study Design: Systematic review; Level of evidence, 2. Methods: Two independent reviewers conducted an online literature search of 2 databases for level 1 and 2 studies using the Lysholm, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), and/or Hospital for Special Surgery (HSS) Knee Score. A weighted mean difference in pre- to postoperative functional outcome score was calculated for each treatment. The mean per-patient costs associated with MFx, OAT, and ACI-1 were determined from a recent publication based on review of a national private insurance database. The cost for each procedure was then divided by the weighted mean difference in functional outcome score to give the cost-per-point change in outcome score. Results: A total of 12 studies (6 level 1, 6 level 2) met the inclusion criteria for the functional outcome analysis, including 730 knees (MFx, n = 300; OAT, n = 90; ACI-1, n = 68; ACI-2, n = 272). The mean follow-up was not significantly different between groups (MFx, 29.4 months; OAT, 38.3 months; ACI-1, 19.0 months; ACI-2, 26.7 months). The mean increase in functional outcome score was 23 for MFx, 19 for OAT, 20 for ACI-1, and 35 for ACI-2. The change in functional outcome score was significantly greater for ACI-2 when compared with all other treatments (P < .0001). The cost-per-point change in functional outcome score was

Additional x-ray views increase decision to treat clavicular fractures surgically

200.59 for MFx,