Background: Reported infection rates following anterior cruciate ligament (ACL) reconstruction are low, but infections are associated with high morbidity including reoperations and inferior clinical outcomes. The purpose of the current study was to investigate the rate of infection after ACL reconstruction with and without graft preparation with a vancomycin irrigant. Methods: All ACL reconstructions performed between May 2009 and August 2018 at a single academic institution were reviewed and categorized based on vancomycin use. Patients with <90-day follow-up, intraoperative graft preparation with an antibiotic other than vancomycin, or previous ipsilateral knee infection were excluded. Infection was defined as a return to the operating room for irrigation and debridement within 90 days after ACL reconstruction. Descriptive and inferential statistical analysis using t tests and Poisson regression were performed, with significance defined as p < 0.05. Results: In total, 1,640 patients (952 males; 58.0%) with a mean age (and standard deviation) of 27.7 ± 11.4 years underwent ACL reconstruction (1,379 primary procedures; 84.1%) and were included for analysis. Intraoperative vancomycin was used in 798 cases (48.7%), whereas 842 ACL reconstructions (51.3%) were performed without intraoperative vancomycin. In total, 11 reconstructions (0.7%) were followed by infection, which occurred in 10 (1.2%) of the patients in whom the graft was not soaked in vancomycin and in 1 (0.1%) of the patients in whom the graft was soaked in vancomycin (p = 0.032). Age (p = 0.571), sex (p = 0.707), smoking (p = 0.407), surgeon (p = 0.124), and insurance type (p = 0.616) were not associated with postoperative infection risk. Autograft use was associated with decreased infections (p = 0.045). There was an 89.4% relative risk reduction with the use of intraoperative vancomycin. An increased body mass index (BMI) (p = 0.029), increased operative time (p = 0.001), and the absence of ACL graft preparation with vancomycin (p = 0.032) independently predicted postoperative infection. Conclusions: The use of vancomycin-soaked grafts was associated with a 10-fold reduction in infection after ACL reconstruction (0.1% versus 1.2%; p = 0.032). Other risk factors for infection after ACL reconstruction included increased BMI and increased operative time. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
BackgroundIdentification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized as a tumor suppressor gene in B lymphocytes. The present study aimed to identify novel oncogenes involved in malignant transformation of TRAF3-deficient B cells.MethodsWe used microarray analysis to identify genes differentially expressed in TRAF3−/− mouse splenic B lymphomas. We employed lentiviral vector-mediated knockdown or overexpression to manipulate gene expression in human multiple myeloma (MM) cell lines. We analyzed cell apoptosis and proliferation using flow cytometry, and performed biochemical studies to investigate signaling mechanisms. To delineate protein-protein interactions, we applied affinity purification followed by mass spectrometry-based sequencing.ResultsWe identified mutated in colorectal cancer (MCC) as a gene strikingly up-regulated in TRAF3-deficient mouse B lymphomas and human MM cell lines. Aberrant up-regulation of MCC also occurs in a variety of primary human B cell malignancies, including non-Hodgkin lymphoma (NHL) and MM. In contrast, MCC expression was not detected in normal or premalignant TRAF3−/− B cells even after treatment with B cell stimuli, suggesting that aberrant up-regulation of MCC is specifically associated with malignant transformation of B cells. In elucidating the functional roles of MCC in malignant B cells, we found that lentiviral shRNA vector-mediated knockdown of MCC induced apoptosis and inhibited proliferation in human MM cells. Experiments of knockdown and overexpression of MCC allowed us to identify several downstream targets of MCC in human MM cells, including phospho-ERK, c-Myc, p27, cyclin B1, Mcl-1, caspases 8 and 3. Furthermore, we identified 365 proteins (including 326 novel MCC-interactors) in the MCC interactome, among which PARP1 and PHB2 were two hubs of MCC signaling pathways in human MM cells.ConclusionsOur results indicate that in sharp contrast to its tumor suppressive role in colorectal cancer, MCC functions as an oncogene in B cells. Our findings suggest that MCC may serve as a diagnostic marker and therapeutic target in B cell malignancies, including NHL and MM.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0056-6) contains supplementary material, which is available to authorized users.
Background: Although a sex-based balance in US graduate medical education has been well-documented, a discrepancy remains in orthopaedic surgery. In orthopaedic sports medicine, the representation of women as team physicians has not previously been characterized. Purpose: To quantify the sex-related composition of team physicians of select National Collegiate Athletic Association (NCAA) Division I collegiate and professional teams. Additionally, the authors assess the sex-related composition of orthopaedic surgeon team physicians specifically and compare these proportions to the sex-related composition of orthopaedic surgeon membership of the American Orthopaedic Society for Sports Medicine (AOSSM). Study Design: Cross-sectional study. Methods: Publicly available sex-related data were collected for team physicians in select NCAA Division I collegiate conferences and professional sports organizations. Subspecialty characteristics and sex distribution were described by use of percentages. Chi-square tests were used to assess whether sex distributions of team physicians in collegiate and professional sports were (1) representative between the populations of female and male physicians compared with the general public and (2) representative of the sex-based composition of orthopaedic surgeons nationally. Results: Women represented 12.7% (112/879) of all team physicians and 6.8% (30/443) of all orthopaedic surgeons ( P < .0001). More than half (53.9%; 413/767) of male and 26.8% (30/112) of female team physicians were orthopaedic surgeons. In collegiate athletics, women comprised 18.1% of all team physicians and 7.7% of orthopaedic surgeon team physicians. In professional sports, women comprised 6.7% of all team physicians and 6.3% of orthopaedic surgeon team physicians, with the greatest proportion in the Women’s National Basketball Association (31.3%). Conclusion: Women comprise a minority of team physicians in select NCAA Division I collegiate and professional sports organizations. When compared with the composition of AOSSM orthopaedic surgeon membership, expected female orthopaedic surgeon representation varies between conferences and leagues with little statistical significance. Although efforts have been made to increase sex-based diversity in orthopaedic surgery, results of this study suggest that barriers affecting female orthopaedic surgeons as team physicians should be identified and addressed.
Bortezomib, a clinical drug for multiple myeloma (MM) and mantle cell lymphoma, exhibits complex mechanisms of action, which vary depending on the cancer type and the critical genetic alterations of each cancer. Here we investigated the signaling mechanisms of bortezomib in mouse B lymphoma and human MM cells deficient in a new tumor suppressor gene, TRAF3. We found that bortezomib consistently induced up-regulation of the cell cycle inhibitor p21(WAF1) and the pro-apoptotic protein Noxa as well as cleavage of the anti-apoptotic protein Mcl-1. Interestingly, bortezomib induced the activation of NF-κB1 and the accumulation of the oncoprotein c-Myc, but inhibited the activation of NF-κB2. Furthermore, we demonstrated that oridonin (an inhibitor of NF-κB1 and NF-κB2) or AD 198 (a drug targeting c-Myc) drastically potentiated the anti-cancer effects of bortezomib in TRAF3-deficient malignant B cells. Taken together, our findings increase the understanding of the mechanisms of action of bortezomib, which would aid the design of novel bortezomib-based combination therapies. Our results also provide a rationale for clinical evaluation of the combinations of bortezomib and oridonin (or other inhibitors of NF-κB1/2) or AD 198 (or other drugs targeting c-Myc) in the treatment of lymphoma and MM, especially in patients containing TRAF3 deletions or relevant mutations.
Background: Quadriceps dysfunction after anterior cruciate ligament (ACL) reconstruction is common and may affect return to sport due to resulting muscle atrophy and muscle weakness. Purpose: To systematically review the available literature regarding the impact of perioperative and postoperative interventions on quadriceps atrophy and loss of strength after ACL reconstruction. Study Design: Systematic review; Level of evidence, 3. Methods: A systematic review was performed in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed, CINAHL, Cochrane Central, and Embase. The quality of evidence was evaluated using the Modified Coleman Methodology Score to determine consensus scores. Eligible level 1 or level 2 studies included interventions of perioperative nerve block, intraoperative tourniquet use, postoperative nutritional supplementation, and postoperative blood flow restriction training. Additionally, the included studies quantified postoperative quadriceps measurements such as thigh circumference, quadriceps cross-sectional area (CSA), isokinetic quadriceps strength, and/or quadriceps electromyographic (EMG) testing. Results: In total, 15 studies met stated inclusion and exclusion criteria with the following intervention types: perioperative nerve block (n = 4), intraoperative tourniquet use (n = 5), postoperative nutritional supplementation (n = 3), and postoperative blood flow restriction (n = 3). Intraoperative tourniquet use resulted in decreased thigh circumference and detrimental EMG changes in quadriceps function in 3 of the 5 included studies. Perioperative femoral nerve blocks were associated with transient decreases in postoperative quadriceps strength, persisting up to 6 weeks after surgery, in 2 of the 4 studies. Postoperative blood flow restriction training augmented quadriceps size and function after ACL reconstruction in 2 of 3 studies. Postoperative nutritional supplementation was associated with increased quadriceps volume and strength in 1 of the 3 studies examined. Conclusion: The peri- and postoperative factors reviewed here may influence quadriceps atrophy and strength after ACL reconstruction. Our results tentatively indicated that blood flow restriction training may be beneficial to the quadriceps after ACL reconstruction and that intraoperative tourniquet use and nerve block administration may be detrimental; however, the strongest finding was that all of these interventions would benefit from further level 1 and 2 evidence studies, including multicenter, randomized controlled trials with extended follow-up, to definitively determine their impact on return to activity.
Background: The Patient-Reported Outcome Measurement Information System (PROMIS) was developed to improve patient-reported outcome measures (PROMs) and administration through a computer adaptive test (CAT). The PROMIS physical function-CAT (PF-CAT) has not been investigated in patients with patellofemoral instability (PFI). Purpose/Hypothesis: The purpose of this study was to evaluate the construct validity of the PROMIS PF-CAT with previously validated tools for measuring PROMs in patients with a diagnosis of PFI. We hypothesized that the PF-CAT will have the strongest correlations with other PROMs that evaluated PF as well as moderate correlations with PROMs that measured other health domains. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Patients enrolled in this study who underwent operative intervention for PFI completed the following evaluations preoperatively: PROMIS PF-CAT, 36-Item Short Form Health Survey (SF-36), Knee injury and Osteoarthritis Outcome Score (KOOS), EuroQol-5 dimensions (EQ-5D), and Kujala Anterior Knee Pain Scale (AKPS). Correlation coefficients and the percentage of patients achieving the highest and lowest possible outcome score of each instrument were calculated to assess floor and ceiling effects. Statistical significance was defined as P < .05. Results: In total, 91 participants (63.7% females; mean age, 20.1 ± 7.2 years) completed the questionnaires. PF-CAT had the lowest number of questions (4.3 ± 1.1). The strongest correlations were between the PF-CAT and SF-36 PF subscale ( r = 0.78; P < .01), AKPS ( r = 0.68; P < .01), and KOOS Activities of Daily Living subscale ( r = 0.68; P < .01). Correlation was moderate between the PF-CAT and the KOOS subscales of Sports/Recreation ( r = 0.58; P < .01), Quality of Life ( r = 0.53; P < .01), and Symptoms ( r = 0.47; P < .01). The PROMIS PF-CAT demonstrated no floor or ceiling effects. Conclusion: In patients with PFI, construct validity of the PROMIS PF-CAT was supported by strong correlations demonstrated between the PF-CAT and PROMs evaluating PF and moderate correlations with those assessing other health domains. Our results demonstrated a low respondent burden and no floor or ceiling effects associated with the PROMIS PF-CAT. The PROMIS PF-CAT may be considered a beneficial alternative to previously established PF PROMs for preoperative evaluation of patients with PFI.
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