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Autogenous iliac crest bone grafting for tibial nonunions revisited: does approach matter?

Konda, Sanjit R; Littlefield, Connor P; Carlock, Kurtis D; Ganta, Abhishek; Leucht, Philipp; Egol, Kenneth A
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.
PMID: 33417030
ISSN: 1434-3916
CID: 4739432

The presence of 3D printing in orthopedics: A clinical and material review

Rodriguez Colon, Ricardo; Nayak, Vasudev Vivekanand; Parente, Paulo E L; Leucht, Philipp; Tovar, Nick; Lin, Charles C; Rezzadeh, Kevin; Hacquebord, Jacques H; Coelho, Paulo G; Witek, Lukasz
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.
PMID: 35634867
ISSN: 1554-527x
CID: 5235812

Transosseous tunnels versus suture anchors for the repair of acute quadriceps and patellar tendon ruptures: A systematic review and meta-analysis of biomechanical studies

Dankert, John F; Mehta, Devan D; Remark, Lindsey H; Leucht, Philipp
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.
PMID: 35490080
ISSN: 1436-2023
CID: 5217802

Influential Studies in Orthopaedic Platelet-Rich Plasma Research Are Recent and Consist of High Levels of Evidence: A Review of the Top 50 Most Cited Publications

Oeding, Jacob F; Lansdown, Drew A; Leucht, Philipp; Bosco, Joseph A; Konopka, Jaclyn; Lajam, Claudette M
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.
PMID: 35272369
ISSN: 1938-2480
CID: 5182332

Treatment of Segmental Bone Defects Biology and Treatment Options

Schultz, Blake J; McLaurin, Toni M; Leucht, Philipp
Segmental bone defects (SBD) are difficult to treat, requiring a comprehensive understanding of the bone and soft tissue injury. Defect size, fracture characteristics, and local and systemic biology all help dictate treatment options. Bone grafting with autograft or allograft, Masquelet technique, and bone transport with external or internal fixation can all be used successfully in the correct patient. When deciding on the best treatment option and addressing any complications throughout the process, it is important to always keep in mind the three principles of bone healing: sterility, stability, and biology. The goal of this review is to present the history of treatment for critical SBD, including the indications and challenges that have been addressed and current and emerging treatment options.
PMID: 35234587
ISSN: 2328-5273
CID: 5190222

Decreasing Post-Operative Opioid Prescriptions Following Orthopedic Trauma Surgery: The "Lopioid" Protocol

Landes, Emma K; Leucht, Philipp; Tejwani, Nirmal C; Ganta, Abhishek; McLaurin, Toni M; Lyon, Thomas R; Konda, Sanjit R; Egol, Kenneth A
OBJECTIVE:To assess the effectiveness of a multimodal analgesic regimen containing "safer" opioid and non-narcotic pain medications in decreasing opioid prescriptions following surgical fixation in orthopedic trauma. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:One urban, academic medical center. SUBJECTS/METHODS:Traumatic fracture patients from 2018 (848) and 2019 (931). METHODS:In 2019 our orthopedic trauma division began a standardized protocol of post-operative pain medications that included: 50 mg of tramadol four times daily, 15 mg of meloxicam once daily, 200 mg gabapentin twice daily, and 1 g of acetaminophen every 6 hours as needed. This multimodal regimen was dubbed the "Lopioid" protocol. We compared this protocol to all patients from the prior year who followed a standard protocol that included Schedule II narcotics. RESULTS:Greater mean MME were prescribed at discharge from fracture surgery under the standard protocol compared to the Lopioid protocol (252.3 vs 150.0; p < 0.001) and there was a difference in the type of opioid medication prescribed (p < 0.001). There was a difference in the number of refills filled for patients discharged with opioids after surgical treatment between standard and Lopioid cohorts (0.31 vs 0.21; p = 0.002). There was no difference in the types of medication-related complications (p = 0.710) or the need for formal pain management consults (p = 0.199), but patients in the Lopioid cohort had lower pain scores at discharge (2.2 vs 2.7; p = 0.001). CONCLUSIONS:The Lopioid protocol was effective in decreasing the amount of Schedule II narcotics prescribed at discharge and the number of opioid refills following orthopedic surgery for fractures.
PMID: 34999901
ISSN: 1526-4637
CID: 5112942

Modulating the systemic and local adaptive immune response after fracture improves bone regeneration during aging

Lopez, Emma Muiños; Leclerc, Kevin; Ramsukh, Malissa; Parente, Paulo El; Patel, Karan; Aranda, Carlos J; Josephson, Anna M; Remark, Lindsey H; Kirby, David J; Buchalter, Daniel B; Hadi, Tarik; Morgani, Sophie M; Ramkhelawon, Bhama; Leucht, Philipp
Tissue injury leads to the well-orchestrated mobilization of systemic and local innate and adaptive immune cells. During aging, immune cell recruitment is dysregulated, resulting in an aberrant inflammatory response that is detrimental for successful healing. Here, we precisely define the systemic and local immune cell response after femur fracture in young and aging mice and identify increased toll-like receptor signaling as a potential culprit for the abnormal immune cell recruitment observed in aging animals. Myd88, an upstream regulator of TLR-signaling lies at the core of this aging phenotype, and local treatment of femur fractures with a Myd88 antagonist in middle-aged mice reverses the aging phenotype of impaired fracture healing, thus offering a promising therapeutic target that could overcome the negative impact of aging on bone regeneration.
PMID: 34998981
ISSN: 1873-2763
CID: 5118182

A Comparative Study of Clinical Outcomes and Functional Status after Knee Fracture and Knee Fracture Dislocation

Bird, Mackenzie L; Chenard, Kristofer E; Gonzalez, Leah J; Konda, Sanjit R; Leucht, Philipp; Egol, Kenneth A
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.
PMID: 34952544
ISSN: 1938-2480
CID: 5109202

Rosiglitazone induces adipogenesis of both marrow and periosteum derived mesenchymal stem cells during endochondral fracture healing

Mehta, Devan; Dankert, John; Yim, Nury; Leclerc, Kevin; Leucht, Philipp
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.
PMID: 34879982
ISSN: 1436-2023
CID: 5110322

14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis

Fu, Wenyu; Hettinghouse, Aubryanna; Chen, Yujianan; Hu, Wenhuo; Ding, Xiang; Chen, Meng; Ding, Yuanjing; Mundra, Jyoti; Song, Wenhao; Liu, Ronghan; Yi, Young-Su; Attur, Mukundan; Samuels, Jonathan; Strauss, Eric; Leucht, Philipp; Schwarzkopf, Ran; Liu, Chuan-Ju
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.
PMID: 34226187
ISSN: 1468-2060
CID: 4932152