Faculty Bibliography

To determine if radiographic evidence of posttraumatic osteoarthritis (PTOA) following tibial plateau fracture correlates with poorer clinical and functional outcomes, patients with tibial plateau fractures were followed at 3, 6, and 12 months. All patients had baseline radiographs and computed tomography scan. Radiographs obtained at each follow-up were reviewed for healing, articular incongruence, hardware positional changes, and the development of postinjury arthritic change. Cohorts were determined based on the presence (PTOA) or absence (NPTOA) of radiographic evidence of PTOA. Demographics, fracture classification, complications, additional procedures, and functional status were compared between cohorts. Sixty patients had radiographic evidence of PTOA on follow-up radiographs at a mean final follow-up of 24.2 months. The NPTOA cohort was composed of 210 patients who were matched to the PTOA cohort based on age and Charlson comorbidity index. Mean time to fracture union for the overall cohort was 4.86 months. Cohorts did not differ in Schatzker classification, time to healing, injury mechanism, or baseline Short Musculoskeletal Function Assessment (SMFA). Patients with PTOA had a greater degree of initial depression and postoperative step-off, higher incidence of initial external fixator usage, higher rates of reoperation for any reason, and higher rates of wound complications. Associated soft tissue injury and meniscal repair did not coincide with the development of PTOA. Range of motion and SMFA scores were significantly worse at all time points in patients with PTOA. Although fracture patterns are similar, patients who required an initial external fixator, had a greater degree of initial depression or residual articular incongruity, underwent more procedures, and developed an infection were found to have increased incidence of PTOA. Radiographic evidence of osteoarthritis correlated with worse functional status in patients. The goal of surgery should be restoration of articular congruity and stability to mitigate the risk of PTOA, although this alone may not prevent degenerative changes. Patients with early loss of range of motion should be aggressively treated as this may precede the development of PTOA.

The field of additive manufacturing, 3D printing (3DP), has experienced an exponential growth over the past four decades, in part due to increased accessibility. Developments including computer-aided design and manufacturing, incorporation of more versatile materials, and improved printing techniques/equipment have stimulated growth of 3DP technologies within various industries, but most specifically the medical field. Alternatives to metals including ceramics and polymers have been garnering popularity due to their resorbable properties and physiologic similarity to extracellular matrix. 3DP has the capacity to utilize an assortment of materials and printing techniques for a multitude of indications, each with their own associated benefits. Within the field of medicine, advances in medical imaging have facilitated the integration of 3DP. In particular, the field of orthopedics has been one of the earliest medical specialties to implement 3DP. Current indications include education for patients, providers, and trainees, in addition to surgical planning. Moreover, further possibilities within orthopedic surgery continue to be explored, including the development of patient-specific implants. This review aims to highlight the use of current 3DP technology and materials by the orthopedic community, and includes comments on current trends and future direction(s) within the field.

BACKGROUND:Multiple techniques have been developed for the repair of acute quadriceps and patellar tendon ruptures with the goal of optimizing clinical outcomes while minimizing complications and costs. The purpose of this study was to evaluate the biomechanical properties of transosseous tunnels and suture anchors for the repair of quadriceps and patellar tendon ruptures. METHODS:≥25%). RESULTS:A total of 392 studies were identified from the initial literature search with 7 studies meeting the eligibility criteria for quadriceps tendon repair and 8 studies meeting the eligibility criteria for patellar tendon repair. Based on the random-effects model for total gap formation and load to failure for quadriceps tendon repair, the mean difference was 8.88 mm (95% CI, -8.31 mm to 26.06 mm; p = 0.31) in favor of a larger gap with transosseous tunnels and -117.25N (95%CI, -242.73N to 8.23N; p = 0.07) in favor of a larger load to failure with suture anchors. A similar analysis for patellar tendon repair demonstrated a mean difference of 2.86 mm (95% CI, 1.08 mm to 4.64 mm; p = 0.002) in favor of a larger gap with transosseous tunnels and -56.34N (95% CI, -226.75 to 114.07N; p = 0.52) in favor of a larger load to failure with suture anchor repair. CONCLUSIONS:Transosseous tunnels are biomechanically similar to suture anchors for quadriceps tendon repair. Patellar tendon repair may benefit from reduced gap formation after cycling with suture anchor repair, but the load to failure for both techniques is biomechanically similar. Additional studies are necessary to evaluate these and alternative repair techniques. LEVEL OF EVIDENCE/METHODS:Systematic review and meta-analysis of biomechanical studies, Level V.

Platelet-rich plasma (PRP) has garnered widespread and increasing attention in recent years. We aimed to characterize the most influential articles in PRP research while clarifying controversies surrounding its use and clinical efficacy and identifying important areas on which to focus future research efforts. The Science Citation Index Expanded subsection of the Web of Science Core Collection was systematically searched to identify the top 50 cited publications on orthopedic PRP research. Publication and study characteristics were extracted, and Spearman's correlations were calculated to assess the relationship between citation data and level of evidence. The top 50 articles were published between the years 2005 and 2016, with 68% published in the year 2010 or later. Of the 33 studies for which level of evidence was assessed, the majority were of level I or II (18, 54.5%). Seventeen articles (34%) were classified as basic science. All clinical studies were prospective, and most (12 studies, 60%) included a high number of metrics related to the PRP preparation protocol and composition. Knee osteoarthritis was the most common topic among clinical studies in the top 50 cited articles (11 studies, 34%). More recent articles were associated with higher citation rates (ρ = 0.46, p < 0.001). The most influential articles on orthopaedic PRP research are recent and consist of high-level of evidence studies mostly. Randomized controlled trials were the most common study type, while basic science articles were relatively less common. The most influential clinical studies reported a high number of metrics related to their PRP preparation protocol and the final PRP composition. These results suggest a rapidly evolving field with the potential to better explain inconsistent clinical results with improved understanding and documentation of basic science concepts such as PRP composition, preparation, and combination techniques.

AIMS/OBJECTIVE:Acute myocardial infarction rapidly increases blood neutrophils (<2 hours). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 hours after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 minutes) release of extracellular vesicles (EVs), which have emerged as an important means of cell-cell signalling and are thus a potential mechanism for communicating with remote tissues. METHODS AND RESULTS/RESULTS:Here, we show that injury to the myocardium rapidly mobilises neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilised splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilisation of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model. CONCLUSIONS:Our findings show a novel EV-dependent mechanism for the rapid mobilisation of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells. TRANSLATIONAL PERSPECTIVE/UNASSIGNED:Peripheral blood neutrophils are rapidly elevated following acute myocardial infarction (AMI) and prior to alterations in systemic cytokines. Extracellular vesicles (EVs) are membrane enclosed particles that carry protein and miRNAs and are rapidly liberated from endothelial cells (EC). Here, we show that following AMI EC-derived-EVs (EC-EVs) mediate neutrophil mobilisation from the spleen via EC-EV-VCAM-1 and induce transcriptional activation of neutrophils in the blood to favour miRNA-126-mRNA targets; miRNA-126 antagomir treatment lowers infarct size. EC-EV-VCAM-1 and EC-EV-miRNA-126 are novel mechanisms that mobilise splenic reserve of neutrophils, a previously unidentified source of neutrophils in sterile ischaemic injury.

BACKGROUND:Type 2 diabetes mellitus (T2DM) afflicts about six percent of the global population, and these patients suffer from a two-fold increased fracture risk. Thiazolidinediones (TZDs), including rosiglitazone, are commonly used medications in T2DM because they have a low incidence of monotherapy failure. It is known that rosiglitazone is associated with secondary osteoporosis, further increasing the fracture risk in an already susceptible population. However, it is not yet understood how rosiglitazone impacts endochondral bone healing after fracture. The aim of this study is to elucidate how rosiglitazone treatment impacts endochondral fracture healing, and how rosiglitazone influences the differentiation of skeletal stem and progenitor cells from the bone marrow and the periosteum. METHODS:An in-vivo mouse femur fracture model was employed to evaluate differences in fracture healing between mice treated with and without rosiglitazone chow. Fracture healing was assessed with histology and micro computed tomography (μCT). In-vitro assays utilized isolated mouse bone marrow stromal cells and periosteal cells to investigate how rosiglitazone impacts the osteogenic capability and adipogenicity of these cells. RESULTS:The in-vivo mouse femur fracture model showed that fracture callus in mice treated with rosiglitazone had significantly more adipose content than those of control mice that did not receive rosiglitazone. In addition, μCT analysis showed that rosiglitazone treated mice had significantly greater bone volume, but overall greater porosity when compared to control mice. In-vitro experimentation showed significantly less osteogenesis and more adipogenesis in bone marrow derived progenitor cells that were cultured in osteogenic media. In addition, rosiglitazone treatment alone caused significant increases in adipogenesis in both bone marrow and periosteum derived cells. CONCLUSION/CONCLUSIONS:Rosiglitazone impairs endochondral fracture healing in mice by increasing adipogenesis and decreasing osteogenesis of both bone marrow and periosteum derived skeletal progenitor cells.

The aim of this study was to compare outcomes of tibial plateau fracture dislocations (FD) with tibial plateau fractures alone. This study was an analysis of a series of tibial plateau fractures, in which FD was defined as a fracture of the tibial plateau with an associated loss of congruent joint reduction and stability of the knee, and classified by the Moore system. Patient data collected included demographics, injury information, and functional outcomes (short musculoskeletal function assessment [SMFA] score and Pain by the visual analog scale). Clinical outcomes at follow-up were recorded including knee range of motion, knee stability and development of complications. There were a total of 325 tibial plateau fracture patients treated operatively, of which 22.2% were identified as FD (n = 72). At injury presentation there was no difference with regard to nerve injury or compartment syndrome (both p > 0.05). FD patients had a higher incidence of arterial injury and acute ligament repair (both p < 0.005). At a mean follow-up of 17.5 months, FD patients were similar with regard to pain, total SMFA scores, and return to sports than their non-FD counterparts (p = 0.884, p = 0.531, p = 0.802). FD patients were found to have decreased knee flexion compared with non-FD patients by 5 degrees (mean: 120 and 125 degrees) (p < 0.05). FD patients also had a higher incidence of late knee instability and subsequent surgery for ligament reconstruction (p < 0.005 & p < 0.05). However, there was no difference in neurological function between groups at follow-up (p = 0.102). Despite the higher incidence of ligamentous instability and decreased range of motion, FD patients appear to have similar long-term functional outcomes compared with non-FD of the tibial plateau. While FD patients initially presented with a higher incidence of arterial injury, neurovascular outcomes at final follow-up were similar to those without a dislocation.

BACKGROUND:The purpose of this study is to determine if a standardized protocol for radial nerve handling during humeral shaft repair reduces the incidence of iatrogenic nerve palsy post operatively. METHODS:Seventy-three patients were identified who underwent acute or reconstructive humeral shaft repair with radial nerve exploration as part of the primary procedure for either humeral shaft fracture or nonunion. All patients exhibited intact radial nerve function pre-operatively. A retrospective chart review and analysis identified patients who developed a secondary radial nerve palsy post-operatively. In each case, the radial nerve was identified and mobilized for protection, regardless of whether the implant necessitated the extensile exposure. RESULTS:Fractures were classified according to AO/OTA guidelines and included 23 Type 12A, 11 Type 12B, and 3 Type 12C. Eight patients had periprosthetic fractures and 28 fractures could not be classified. All patients in the cohort were fixed with locking plates. Surgery was indicated for 36 patients with humeral nonunions and 37 patients with acute humeral shaft fractures. Of the 73 patients, 2 (2.7%) developed radial nerve palsy following surgery, one from the posterior approach and one from the anterolateral approach. Both patients exhibited complete recovery of radial nerve function by 6-month follow-up. No significant differences (p > 0.05) were found in any demographic or surgical details between those with and without radial nerve injury. CONCLUSIONS:Nerve exploration identification and protection leads to a low incidence of transient radial nerve palsy compared to the rate reported in the current literature (2.7% compared to 6-24%). Thus, radial nerve exploration and mobilization should be considered when approaching the humeral shaft for acute fracture and nonunion repairs. LEVEL OF EVIDENCE/METHODS:Level III.

OBJECTIVE:mice. METHODS:mice were fed a typical Western-style diet for 22 weeks and injected with a nontargeting locked nucleic acid (LNA; LNA control) or miR-148a LNA (LNA 148a) for the last 10 weeks. At the end of the treatment, the mice were sacrificed, and circulating lipids, hepatic gene expression, and atherosclerotic lesions were analyzed. RESULTS:Examination of atherosclerotic lesions revealed a significant reduction in plaque size, with marked remodeling of the lesions toward a more stable phenotype. Mechanistically, miR-148a levels influenced macrophage cholesterol efflux and the inflammatory response. Suppression of miR-148a in murine primary macrophages decreased mRNA levels of proinflammatory M1-like markers (Nos2, Il6, Cox2, and Tnf) and increased the expression of anti-inflammatory genes (Arg1, Retlna, and Mrc1). CONCLUSIONS:Therapeutic silencing of miR148a mitigated the progression of atherosclerosis and promoted plaque stability. The antiatherogenic effect of miR-148a antisense therapy is likely mediated by the anti-inflammatory effects observed in macrophages treated with miR-148 LNA and independent of significant changes in circulating low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).

Brown adipose tissue (BAT), a crucial heat-generating organ, regulates whole-body energy metabolism by mediating thermogenesis. BAT inflammation is implicated in the pathogenesis of mitochondrial dysfunction and impaired thermogenesis. However, the link between BAT inflammation and systematic metabolism remains unclear. Herein, we use mice with BAT deficiency of thioredoxin-2 (TRX2), a protein that scavenges mitochondrial reactive oxygen species (ROS), to evaluate the impact of BAT inflammation on metabolism and thermogenesis and its underlying mechanism. Our results show that BAT-specific TRX2 ablation improves systematic metabolic performance via enhancing lipid uptake, which protects mice from diet-induced obesity, hypertriglyceridemia, and insulin resistance. TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mechanistically, loss of TRX2 induces excessive mitochondrial ROS, mitochondrial integrity disruption, and cytosolic release of mitochondrial DNA, which in turn activate aberrant innate immune responses in BAT, including the cGAS/STING and the NLRP3 inflammasome pathways. We identify NLRP3 as a key converging point, as its inhibition reverses both the thermogenesis defect and the metabolic benefits seen under nutrient overload in BAT-specific Trx2-deficient mice. In conclusion, we identify TRX2 as a critical hub integrating oxidative stress, inflammation, and lipid metabolism in BAT, uncovering an adaptive mechanism underlying the link between BAT inflammation and systematic metabolism.