Faculty Bibliography

BACKGROUND:The quality of evidence of the orthopedic literature has been often called into question. The fragility index (FI) has emerged as a means to evaluate the robustness of a significant result. Similarly, reverse fragility index (RFI) can be used for nonsignificant results to evaluate whether one can confidently conclude that there is no difference between groups. The analysis of FI and RFI in proximal humerus fracture (PHF) management is of particular interest, given ongoing controversy regarding optimal management and patient selection. The aim of this study was to report the FI, RFI and quality of the evidence in the proximal humerus fracture literature. METHODS:A systematic review was conducted based on the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, which utilized EMBASE, MEDLINE and Cochrane Library databases. Inclusion criteria included randomized controlled clinical trials related to the management of proximal humerus fractures, published from 2000 to 2020 with dichotomous outcome measures and 1:1 allocation. The FI and RFI were calculated by successively changing one nonevent to an event for each outcome measure until the result was made nonsignificant or significant, respectively. The fragility quotient, (FQ), calculated by dividing the FI by the total sample size, was calculated as well. RESULTS:There were 25 studies that met our criteria with 48 outcome measures recorded. A total of 21 studies had at least one fragile result, with ten studies including a fragile result in the conclusion of the abstract. A total of 31 outcome measures had nonsignificant results and the median RFI was found to be 4, with 71% greater than number of patients lost to follow up. Seventeen outcomes had significant results, with a median FI of 1, with 65% greater than or equal to the number patients lost to follow up. A total of 18 of 25 studies (72%) included a power analysis. In particular, ten studies reported a statistical analysis of complication rates, 90% of which were fragile. The median FQ was found to be 0.037. CONCLUSIONS:The literature on PHF management is frequently fragile. Outcome measures are often fragile, particularly with regards to comparing complication rates and reoperation rates in treatment arms. Comparing to the studies in other subspecialties PHF RCTs are relatively more fragile and underpowered. Standardized reporting of FI, FQ and RFI can help the reader to reliably draw conclusions based on the fragility of outcome measures.

BACKGROUND:Tibial nonunion remains a considerable burden for patients and the surgeons who treat them. In recent years, alternatives to autogenous grafts for the treatment of tibial nonunions have been sought. The purpose of this study was to evaluate the efficacy of autogenous iliac crest bone graft (ICBG) in the treatment of tibial shaft nonunions. MATERIAL AND METHODS/METHODS:Sixty-nine patients were identified who underwent ICBG for repair of atrophic or oligotrophic tibial nonunion and had complete data with at least one year of follow-up (mean 27.9 months). Surgical treatments consisted of revision/supplemental fixation ± ICBG. Surgical approaches for graft placement were either posterolateral (PL), anterolateral (AL), or direct medial (DM). Healing status, time to union, postoperative pain, and functional outcomes were assessed. RESULTS:Bony union was achieved by 97.1% (67/69) of patients at a mean time of 7.8 ± 3.2 months postoperatively. There was no significant difference in mean time to union between the three surgical approach groups: (PL (44.9%) = 7.3 months, AL (20.3%) = 9.2 months, DM (34.8%) = 7.6 months; p = 0.22). Intraoperative cultures obtained at the time of nonunion surgery were positive in 27.5% of patients (19/69). Positive cultures were associated with need for secondary surgery as 8/19 patients (42.1%) with positive cultures required re-operation. Two out of four patients that developed iliac donor site hematomas/infections requiring washout had positive intraoperative cultures as well. There was no difference in final SMFA among the three surgical approach groups. CONCLUSIONS:Autogenous ICBG remains the gold standard in the management of persistent tibial nonunions regardless of surgical approach. There is a small risk for complication at the iliac crest donor site. Given the high union rate, autogenous iliac crest bone grafting for tibial nonunion remains the gold standard for this difficult condition. LEVEL OF EVIDENCE/METHODS:Level III.

Although distal radius fractures are quite common, bilateral distal radius fractures seldomly occur. Due to this, treatment is primarily based on surgeon experience with unilateral fractures, however bi- lateral fractures add a level of complexity : loss of functional independence. The purpose of this study was to examine a cohort of patients with bilateral distal radius fractures to identify differences in demographics, mechanism of injury, and outcomes to further our understanding of these rare injuries. 23 patients were identified retrospectively over a 5-year period that met inclusion criteria. The medical records were reviewed with multiple demographic and clinical parameters recorded and analyzed. Males were more likely to sustain high-energy mechanisms (80% vs. 53%). Patients <50 years old were more likely to sustain high-energy mechanisms (90% vs. 46%) and were more likely to be treated operatively (80% vs. 62%). The most commonly associated injury was a head injury (30%). All patients treated non-operatively reported minimal/no pain upon final follow-up where 57% of patients treated operatively noted regular pain. 75% of patients with medical comorbidities had minimal/no pain upon final follow- up. Conclusions : Patients with bilateral fractures were more likely to be younger males who suffered from higher energy mechanisms. Age was a critical factor in determining treatment strategy. Rates of associated head injuries were elevated, which is an important factor for the clinician to keep in mind when treating this population. As we further our understanding of this unique population, we can improve our treatment approaches and subsequently attain better outcomes.

AIMS/OBJECTIVE:Physician burnout and its consequences have been recognized as increasingly prevalent and important issues for both organizations and individuals involved in healthcare delivery. The purpose of this study was to describe and compare the patterns of self-reported wellness in orthopaedic surgeons and trainees from multiple nations with varying health systems. METHODS:A cross-sectional survey of 774 orthopaedic surgeons and trainees in five countries (Australia, Canada, New Zealand, UK, and USA) was conducted in 2019. Respondents were asked to complete the Mayo Clinic Well-Being Index and the Stanford Professional Fulfillment Index in addition to 31 personal/demographic questions and 27 employment-related questions via an anonymous online survey. RESULTS:A total of 684 participants from five countries (Australia (n = 74), Canada (n = 90), New Zealand (n = 69), UK (n = 105), and USA (n = 346)) completed both of the risk assessment questionnaires (Mayo and Stanford). Of these, 42.8% (n = 293) were trainees and 57.2% (n = 391) were attending surgeons. On the Mayo Clinic Well-Being Index, 58.6% of the overall sample reported feeling burned out (n = 401). Significant differences were found between nations with regards to the proportion categorized as being at risk for poor outcomes (27.5% for New Zealand (19/69) vs 54.4% for Canada (49/90) ; p = 0.001). On the Stanford Professional Fulfillment Index, 38.9% of the respondents were classified as being burned out (266/684). Prevalence of burnout ranged from 27% for Australia (20/74 up to 47.8% for Canadian respondents (43/90; p = 0.010). Younger age groups (20 to 29: RR 2.52 (95% confidence interval (CI) 1.39 to 4.58; p = 0.002); 30 to 39: RR 2.40 (95% CI 1.36 to 4.24; p = 0.003); 40 to 49: RR 2.30 (95% CI 1.35 to 3.9; p = 0.002)) and trainee status (RR 1.53 (95% CI 1.15 to 2.03 p = 0.004)) were independently associated with increased relative risk of having a 'at-risk' or 'burnout' score. CONCLUSIONS: 2021;2(11):932-939.

Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis due to its well-known anti-inflammatory role in immune cells but its impact on brown and beige adipose tissue biology has not yet been investigated. Here, we present the novel evidence that MTX treatment increases the gene expression of thermogenic genes in brown and beige adipose tissues in a fat cell autonomous manner. Furthermore, we show that treatment of mice with MTX is associated with cold resistance, improved glucose homeostasis, decreased inflammation, and reduced hepatosteatosis in high-fat diet states. Overall, our data provide novel evidence of a role of MTX on thermogenic tissues not previously appreciated.

SUMMARY/CONCLUSIONS:Operative management of sternoclavicular fracture-dislocations is recommended in the setting of symptomatic nonunion. Treatment options include open reduction internal fixation, fragment excision, and ligamentous reconstruction. We present a 29-year-old man with a medial clavicle fracture nonunion that previously failed open reduction internal fixation and was treated with sternoclavicular joint reconstruction using tendon allograft.

OBJECTIVES/OBJECTIVE:Osteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions. This study aims to decipher TNFR2 signalling in chondrocytes and OA. METHODS:Biochemical copurification and proteomics screen were performed to isolate the intracellular cofactors of TNFR2 complex. Bulk and single cell RNA-seq were employed to determine 14-3-3 epsilon (14-3-3ε) expression in human normal and OA cartilage. Transcription factor activity screen was used to isolate the transcription factors downstream of TNFR2/14-3-3ε. Various cell-based assays and genetically modified mice with naturally occurring and surgically induced OA were performed to examine the importance of this pathway in chondrocytes and OA. RESULTS:Signalling molecule 14-3-3ε was identified as an intracellular component of TNFR2 complexes in chondrocytes in response to progranulin (PGRN), a growth factor known to protect against OA primarily through activating TNFR2. 14-3-3ε was downregulated in OA and its deficiency deteriorated OA. 14-3-3ε was required for PGRN regulation of chondrocyte metabolism. In addition, both global and chondrocyte-specific deletion of 14-3-3ε largely abolished PGRN's therapeutic effects against OA. Furthermore, PGRN/TNFR2/14-3-3ε signalled through activating extracellular signal-regulated kinase (ERK)-dependent Elk-1 while suppressing nuclear factor kappa B (NF-κB) in chondrocytes. CONCLUSIONS:This study identifies 14-3-3ε as an inducible component of TNFR2 receptor complex in response to PGRN in chondrocytes and presents a previously unrecognised TNFR2 pathway in the pathogenesis of OA.

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment. Furthermore, biologic treatments may have potential devastating complications when proper methods or techniques are ignored. For these reasons, an association comprising several scientific societies, named the Biologic Association (BA), was created to foster coordinated efforts and speak with a unified voice, advocating for the responsible use of biologics in the musculoskeletal environment in clinical practice, spearheading the development of standards for treatment and outcomes assessment, and reporting on the safety and efficacy of biologic interventions. This article will introduce the BA and its purpose, provide a summary of the 2020 first annual Biologic Association Summit, and outline the future strategic plan for the BA.

»:The induced membrane technique (IMT) takes advantage of an osteoinductive environment that is created by the placement of a cement spacer into a bone defect. »:Most commonly, a polymethylmethacrylate (PMMA) spacer has been used, but spacers made from other materials have emerged and achieved good clinical outcomes. »:The IMT has demonstrated good results for long-bone repair; however, more research is required in order to optimize union rates as well as delineate more precise indications and surgical timing.

Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.