Biomechanically superior treatments do not translate into improved outcomes in randomized controlled trials.

PURPOSE: Significant time and resources are devoted to conducting orthopaedic biomechanics research; however, it is not known how these studies relate to their subsequent clinical studies. The purpose of the present study was to determine whether biomechanically superior treatments were associated with improved clinical outcomes as determined by analogous randomized controlled trials (RCTs). METHODS: A systematic review was conducted to find RCTs that tested a research question based on a prior biomechanical study. PubMed and SCOPUS databases were queried for orthopaedic randomized controlled trials, and full text articles were reviewed to find RCTs which cited biomechanical studies with analogous comparison groups. A random-effects multi-level logistic regression model was conducted examining the association between RCT outcome and biomechanics outcome, adjusting for multiple outcomes nested within study. RESULTS: In total, 20,261 articles were reviewed yielding 21 RCTs citing a total of 43 analogous biomechanical studies. In 7 instances (16.2%), the RCT and a cited biomechanical study showed concordant results (i.e. the superior treatment in the RCT was also the superior construct in the biomechanical study). RCT outcome was not associated with biomechanical outcome (ß = -1.50, standard error = 0.78, p = .05). CONCLUSION: This study assessed 21 orthopaedic RCTs with 43 corresponding biomechanical studies and found no association between superior biomechanical properties of a given orthopaedic treatment and improved clinical outcomes. Favourable biomechanical properties alone should not be the primary reason for selecting one treatment over another. Furthermore, RCTs based on biomechanical studies should be carefully designed to maximize the chance of providing clinically relevant insights.

Bennett Fractures: A Biomechanical Model and Relevant Ligamentous Anatomy.

PURPOSE: This study examined a palmar beak fracture model to determine which thumb carpometacarpal (CMC) joint ligament is the primary ligament relevant to the pattern of injury. METHODS: Six fresh-frozen cadaveric wrists were used. The radius, ulna, and first metacarpal were secured and tested with a materials testing system, holding the wrist in 20° extension, 20° ulnar deviation, and 30° palmar abduction of the first metacarpal. Testing consisted of preconditioning cycles followed by compressive loading at 100 mm/s. We confirmed fractures with fluoroscopy and dissected the specimens to examine the CMC joint ligaments. The metacarpal was stressed through a range of motion to determine which maneuvers reduced or displaced the fractures. RESULTS: Our model successfully created palmar beak fractures in all cadaveric specimens. All fractures were displaced and intra-articular. The anterior oblique ligament (AOL) was thin and partially attached to the palmar beak fracture fragment. The ulnar collateral ligament was attached in its entirety to the fracture fragment and represented a thicker, more robust ligament compared with the AOL. Radial abduction and pronation of the metacarpal reduced fracture displacement. Extension of the CMC joint or tensioning the AOL did not decrease fracture displacement. CONCLUSIONS: This model successfully created a reproducible and clinically relevant palmar beak fracture in a biomechanical setting. The primary ligament attached to the palmar beak fracture fragment was the ulnar collateral ligament, and not the AOL as previously described. These findings suggest that the AOL may not be a substantial contributor to palmar beak fracture morphology. CLINICAL RELEVANCE: A refined description of the ligamentous anatomy of the palmar break fracture enhances opportunities for improved reduction and treatment of this common hand injury.

Primary reverse shoulder arthroplasty using contemporary implants is associated with very low reoperation rates.

BACKGROUND: The early results of reverse shoulder arthroplasty (RSA) were influenced to some extent by the use of first-generation implants and surgeons' learning curves, resulting in relatively high reoperation rates. The purpose of this study was to quantify the burden of and identify the indications for reoperation after primary RSA using contemporary implants and techniques. METHODS: A retrospective review of 1649 primary RSAs implanted consecutively between 2009 and 2015 at a single institution was conducted. All arthroplasties were performed by 5 fellowship-trained shoulder surgeons at a tertiary referral center. Demographic characteristics, indications for primary RSA, and reoperations were analyzed and categorized for trends associated with each type of reoperation performed. RESULTS: A total of 39 reoperations (2.37%) were performed for a variety of indications. Overall, only a few patients with infection or instability required reoperation (0.55%). The most common indications for reoperation were related to the humeral component (1.03%); the majority of humeral component complications were related to a specific design flaw of 1 implant system. RSAs performed for proximal humeral fracture sequelae more commonly underwent reoperation owing to instability or humeral component-related issues; all 4 cases of aseptic humeral stem loosening occurred in the setting of proximal humeral fracture sequela treatment. Only 0.36% of all primary RSAs required reoperation because of glenoid complications. CONCLUSIONS: Primary RSA performed with contemporary implants and surgical techniques seems to be associated with a very low rate of reoperation. The most common reasons for reoperation were humeral component fracture for 1 particular implant, humeral loosening, dislocation, infection, and glenoid failure, each occurring at a rate under 1%.

Mechanisms of fatty degeneration in massive rotator cuff tears.

Fatty degeneration of chronically injured muscle is a commonly recognized consequence of massive rotator cuff tears. Current surgical treatments are unable to alter or reverse the progression of fatty degeneration and are associated with poor functional outcomes in these patients. Therefore, a better understanding of the pathophysiology of fatty degeneration is required. As such, recent discoveries in stem cell biology and new animal models have significantly advanced our understanding of the cellular and molecular basis of fatty degeneration. Future studies will facilitate development of novel treatments to prevent the progression of fatty degeneration and improve muscle regeneration in patients with massive rotator cuff tears.

Limb salvage with major nerve injury: current management and future directions.

Major peripheral nerve injuries are often associated with devastating functional deficits. Current management techniques fail to achieve adequate functional neural regeneration, and the development of adjunct therapies is necessary to improve outcomes. Recent efforts at enhancing the regeneration rate of peripheral nerves and developing axonal guidance channels or conduits have had limited success. The neuromuscular junction serves as the interface between the peripheral nerves and muscle. This critical area undergoes significant changes following peripheral nerve injury and induces end-organ atrophy after denervation, which limits the chance of true functional regeneration. Stabilization of the neuromuscular junction may be an important adjunct in peripheral nerve repair and should be explored as a method of managing major nerve injuries.

The router bit extraction technique for removing a well-fixed humeral stem in revision shoulder arthroplasty.

AIMS: A number of methods have been described to remove a well-fixed humeral implant as part of revision shoulder arthroplasty. These include the use of cortical windows and humeral osteotomies. The router bit extraction technique uses a high-speed router bit to disrupt the bone-implant interface. The implant is then struck in a retrograde fashion with a square-tip impactor and mallet. The purpose of this study was to determine the characteristics and frequency of the different techniques needed for the removal of a well-fixed humeral stem in revision shoulder arthroplasty. PATIENTS AND METHODS: Between 2010 and 2018, 288 revision shoulder arthroplasty procedures requiring removal of a well-fixed humeral component were carried out at a tertiary referral centre by a single surgeon. The patient demographics, indications for surgery, and method of extraction were collected. RESULTS: Of the 288 revisions, 284 humeral stems (98.6%) were removed using the router bit extraction technique alone. Four humeral stems (1.39%) required an additional cortical window. Humeral osteotomy was not necessary in any procedure. Most of the humeral stems removed (78.8%) were cementless. Of the four humeral stems that required a cortical window, three involved removal of a hemiarthroplasty. Two were cemented and two were cementless. CONCLUSION: The router bit extraction technique removed a well-fixed humeral component in a very high proportion of patients (98.6%). This method allows surgeons to avoid more invasive approaches involving a cortical window or humeral osteotomy, and their associated complications. Cite this article: Bone Joint J 2019;101-B:1280-1284.

What Makes Journal Club Effective?-A Survey of Orthopaedic Residents and Faculty.

BACKGROUND: Journal clubs play an important role in the education of orthopaedic surgery residents; however, there are sparse data available on the characteristics that make journal clubs effective. OBJECTIVE: The primary goal of this study was to determine the characteristics of effective journal clubs as identified by orthopaedic residents and faculty. We sought to compare the opinions of residents and faculty in order to identify areas that may benefit from future research and discussion. DESIGN: Orthopaedic surgery residents and faculty at residency programs around the country were surveyed anonymously. The survey was designed to determine the contribution of various journal club characteristics on the effectiveness of journal club. Nonparametric statistics were used to test for goodness-of-fit, and to compare responses between faculty and residents. RESULTS: A total of 204 individuals participated. The most important goals of journal clubs were teaching the skillset of evaluating scientific papers (2.0 ± 1.2 [mean rank ± standard deviation, on a scale of 6, with 1 being most important]), encouraging participants to read current orthopaedic literature, (2.4 ± 1.1), and instilling career-long habits of reading the orthopaedic literature among residents (3.1 ± 1.3). Mandatory attendance (71.8%), monthly journal clubs (80.9%), resident presentation of articles (86.7%), and discussion of 3 to 5 papers (78.7%) were thought to lead to more effective clubs. The most clinically relevant articles published within the last year (63.8%), and classic articles that have influenced practice (68.1%) were preferred. Participation and attendance (2.4 ± 1.5) and paper selection (2.6 ± 1.5) were the most important characteristics overall. CONCLUSIONS: In orthopaedics, journal clubs fulfill the role of encouraging reading of the literature, as well as educating residents and faculty. There are many possible club formats, but some are clearly felt to be more effective. Particular attention should be paid to attendance, participation, and paper selection.

Treatment of Massive Irreparable Rotator Cuff Tears: A Cost-effectiveness Analysis.

Massive irreparable rotator cuff tears cause significant shoulder pain and dysfunction. Physical therapy (PT), arthroscopic debridement with biceps tenotomy (AD-BT), and hemiarthroplasty (HA) are treatments shown to reduce pain and improve quality of life. Reverse total shoulder arthroplasty (RTSA) is a newer surgical treatment option that may offer improved function. A cost-effectiveness analysis of these interventions has never been performed, and no head-to-head comparative effectiveness trials currently exist. A Markov decision analytic model was used to compare RTSA, HA, AD-BT, and PT as treatments for elderly patients with massive irreparable rotator cuff tears. Probabilities for complications, perioperative death, conversion procedures, and reoperations were derived from the literature, and costs were determined by average Medicare reimbursement rates from 2011. Reverse total shoulder arthroplasty yielded the most quality-adjusted life years (QALY) with 7.69, but greater benefits came at higher costs compared with other treatments. Sensitivity analyses showed that PT was the most cost-effective intervention at a health utility of 0.75 or greater (QALY 7.35). The health utility of RTSA was 0.72 or less (QALY 7.48) or RTSA probability of no complications was 0.83 or less (QALY 7.48 at cost of $23,830). Reverse total shoulder arthroplasty yielded benefits at a cost considered good value for money compared with other treatments. Reverse total shoulder arthroplasty is the preferred and most cost-effective treatment option for elderly patients with massive irreparable rotator cuff tears. For patients seeking pain relief without functional gains, AD-BT can be considered a cost-effective and cheaper alternative. The cost-effectiveness analysis approach can help guide clinical practice as well as the policies of health care systems and insurers. [Orthopedics. 2017; 40(1):e65-e76.].

Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice.

Influenza-related complications continue to be a major cause of mortality worldwide. Due to unclear mechanisms, a substantial number of influenza-related deaths result from bacterial superinfections, particularly secondary pneumococcal pneumonia. Here, we report what we believe to be a novel mechanism by which influenza-induced type I IFNs sensitize hosts to secondary bacterial infections. Influenza-infected mice deficient for type I IFN-alpha/beta receptor signaling (Ifnar-/- mice) had improved survival and clearance of secondary Streptococcus pneumoniae infection from the lungs and blood, as compared with similarly infected wild-type animals. The less effective response in wild-type mice seemed to be attributable to impaired production of neutrophil chemoattractants KC (also known as Cxcl1) and Mip2 (also known as Cxcl2) following secondary challenge with S. pneumoniae. This resulted in inadequate neutrophil responses during the early phase of host defense against secondary bacterial infection. Indeed, influenza-infected wild-type mice cleared secondary pneumococcal pneumonia after pulmonary administration of exogenous KC and Mip2, whereas neutralization of Cxcr2, the common receptor for KC and Mip2, reversed the protective phenotype observed in Ifnar-/- mice. These data may underscore the importance of the type I IFN inhibitory pathway on CXC chemokine production. Collectively, these findings highlight what we believe to be a novel mechanism by which the antiviral response to influenza sensitizes hosts to secondary bacterial pneumonia.

Specificity of TRAF3 in its negative regulation of the noncanonical NF-kappa B pathway.

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are critical signaling adaptors downstream of many receptors in the TNF receptor and interleukin-1 receptor/Toll-like receptor superfamilies. Whereas TRAF2, 5, and 6 are activators of the canonical NF-kappaB signaling pathway, TRAF3 is an inhibitor of the noncanonical NF-kappaB pathway. The contribution of the different domains in TRAFs to their respective functions remains unclear. To elucidate the structural and functional specificities of TRAF3, we reconstituted TRAF3-deficient cells with a series of TRAF3 mutants and assessed their abilities to restore TRAF3-mediated inhibition of the noncanonical NF-kappaB pathway as measured by NF-kappaB-inducing kinase (NIK) protein levels and processing of p100 to p52. We found that a structurally intact RING finger domain of TRAF3 is required for inhibition of the noncanonical NF-kappaB pathway. In addition, the three N-terminal domains, but not the C-terminal TRAF domain, of the highly homologous TRAF5 can functionally replace the corresponding domains of TRAF3 in suppression of the noncanonical NF-kappaB pathway. This functional specificity correlates with the specific binding of TRAF3, but not TRAF5, to the previously reported TRAF3 binding motif in NIK. Our studies suggest that both the RING finger domain activity and the specific binding of the TRAF domain to NIK are two critical components of TRAF3 suppression of NIK protein levels and the processing of p100 to p52.

Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif.

Upon recognition of viral infection, RIG-I and Helicard recruit a newly identified adapter termed Cardif, which induces type I interferon (IFN)-mediated antiviral responses through an unknown mechanism. Here, we demonstrate that TRAF3, like Cardif, is required for type I interferon production in response to intracellular double-stranded RNA. Cardif-mediated IFNalpha induction occurs through a direct interaction between the TRAF domain of TRAF3 and a TRAF-interaction motif (TIM) within Cardif. Interestingly, while the entire N-terminus of TRAF3 was functionally interchangeable with that of TRAF5, the TRAF domain of TRAF3 was not. Our data suggest that this distinction is due to an inability of the TRAF domain of TRAF5 to bind the TIM of Cardif. Finally, we show that preventing association of TRAF3 with this TIM by mutating two critical amino acids in the TRAF domain also abolishes TRAF3-dependent IFN production following viral infection. Thus, our findings suggest that the direct and specific interaction between the TRAF domain of TRAF3 and the TIM of Cardif is required for optimal Cardif-mediated antiviral responses.