Publications by Year: 2022

2022

Rozental, T. D., Merchan, N., Johannesdottir, F., Lechtig, A., Earp, B. E., Harper, C. M., & Bouxsein, M. L. (2022). Longitudinal Changes in Serum Markers of Bone Metabolism and Bone Material Strength in Premenopausal Women with Distal Radial Fracture.. The Journal of Bone and Joint Surgery. American Volume, 104(1), 15-23. https://doi.org/10.2106/JBJS.21.00540 (Original work published 2022)

BACKGROUND: Markers of bone metabolism (MBM) play an important role in fracture evaluation, and changes have been associated with increased fracture risk. The purpose of the present study was to describe changes in MBM in premenopausal women with distal radial fractures.

METHODS: Premenopausal women with distal radial fractures (n = 34) and without fractures (controls) (n = 39) were recruited. Serum MBM in patients with distal radial fractures were obtained at the time of the initial presentation, 6 weeks, and 3, 6, and 12 months. MBM included 25(OH) vitamin D, PTH, osteocalcin, P1NP, BSAP, CTX, sclerostin, DKK1, periostin, and TRAP5b. Areal bone mineral density (aBMD) was assessed with dual x-ray absorptiometry, and the bone material strength index (BMSi) was assessed with microindentation.

RESULTS: Most MBM reached peak levels at 6 weeks after the injury, including osteocalcin (+17.7%), sclerostin (+23.5%), and DKK1 (12.6%). Sclerostin was lower (-27.4%) and DKK1 was higher (+22.2%) at 1 year after the fracture. CTX declined below baseline levels at 6 and 12 months, whereas TRAP5b, BSAP, and periostin did not significantly change. At 12 months, sclerostin was lower (p = 0.003) and DKK1 was higher (p = 0.03) in the distal radial fracture group than in the control group. Greater fracture severity was associated with greater increases in P1NP and BSAP. aBMD and BMSi were not associated with fracture.

CONCLUSIONS: Distal radial fractures caused increases in several MBM, which typically peaked at 6 weeks after injury and gradually decreased over 6 months. Sclerostin and DKK1 remained below and above baseline at 1 year, respectively. Increasing fracture severity resulted in larger changes in MBM. aBMD and BMSi did not discriminate between patients with distal radial fractures and controls. Continued efforts to identify markers of skeletal fragility in young women are warranted to mitigate future fracture risk.

LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Stupay, K. L., Miller, C. P., Staffa, S., McTague, M. F., Weaver, M. J., & Kwon, J. Y. (2022). Risk Factors for Aseptic Revision of Operatively Treated Ankle Fractures.. Foot & Ankle International, 43(3), 378-388. https://doi.org/10.1177/10711007211050876 (Original work published 2022)

BACKGROUND: Early revision rates within 12 months after ankle fracture open reduction internal fixation (AF-ORIF) are fairly low; however, they remain relevant given the volume of ankle fractures occurring annually. Understanding these rates is complex because reoperation due to technical or mechanical complications is typically reported alongside soft tissue-related problems such as symptomatic hardware, wound dehiscence, or infection. There are limited data identifying risk factors specifically for revision of ankle fracture fixation in the absence of soft tissue complications. Understanding variables that predispose to aseptic technical and mechanical failure without this confounder may provide insight and improve patient care.

METHODS: A retrospective cohort study was performed at 2 large academic medical centers. Research Patient Data Registry (RPDR) data available from 2002 to 2019 were used to identify patients who underwent aseptic revision of AF-ORIF within 12 months (n = 33). A control group (n = 100) was selected by identifying sequential patients who underwent AF-ORIF not requiring revision within 12 months. Multiple factors were recorded for all patients in both cohorts. Each fracture was also evaluated according to the Ankle Reduction Classification System (ARCS) of Chien et al,8 which categorizes biplanar talar displacement in relation to a central tibial plumb line into 1 of 3 grades: A (0-2 mm), B (3-10 mm), and C (>10 mm). Adapted from its original purpose of grading reduction quality, we applied ARCS to pre-reduction radiographs to assess initial fracture displacement. All variables collected were compared in univariate analysis. Variables that achieved significance in univariate comparisons were included as candidates for multivariable analysis.

RESULTS: Final multivariable logistic regression modeling demonstrated the following factors to independently predict the need for aseptic revision surgery: documented falls in the early postoperative period (aOR, 298; 95% CI, 15.4, 5759; P < .001), movement-altering disorders (aOR, 81.7; 95% CI, 4.12, 1620; P = .004), a nonanatomic mortise (medial clear space [MCS] > superior clear space [SCS]) on immediate postoperative imaging (aOR, 38.4; 95% CI, 5.53, 267; P < .001), initial coronal plane tibiotalar displacement >10 mm and sagittal plane tibiotalar dislocation (ARCS-C) (aOR vs ARCS-A, 25.8; 95% CI, 2.81, 237; P = .004), substance abuse (aOR, 15.7; 95% CI, 2.66, 92.8; P = .002), and polytrauma (aOR, 12.3; 95% CI, 2.02, 74.8; P = .006).

CONCLUSION: In this investigation we found a notable increase in risk for revision surgery after AF-ORIF for patients who had one of the following: (1) falls in the early postoperative period, (2) movement-altering disorders, (3) a nonanatomic mortise (MCS > SCS) on immediate postoperative imaging, (4) more severe initial fracture displacement, (5) substance abuse, or (6) polytrauma. Identifying these factors may allow surgeons to better understand risk and counsel patients, and may serve as future targets for intervention aimed at improving patient safety and outcomes after ankle fracture ORIF.

LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Nassar, A. H., Maselli, A. M., Manstein, S., Shiah, E., Slatnick, B. L., Dowlatshahi, A. S., Cauley, R., & Lee, B. T. (2022). Comparison of Various Modalities Utilized for Preoperative Planning in Microsurgical Reconstructive Surgery.. Journal of Reconstructive Microsurgery, 38(3), 170-180. https://doi.org/10.1055/s-0041-1736316 (Original work published 2022)

BACKGROUND:  The benefits of preoperative perforator imaging for microsurgical reconstruction have been well established in the literature.

METHODS:  An extensive literature review was performed to determine the most commonly used modalities, and their applicability, advantages and disadvantages.

RESULTS:  The review demonstrated varioius findings including decreases in operative time and cost with the use of CT angiography to identification of perforators for inclusion in flap design with hand-held Doppler ultrasound. Modalities like MR angiography offer alternatives for patients with contrast allergies or renal dysfunction while maintaining a high level of clarity and fidelity. Although the use of conventional angiography has decreased due to the availability of less invasive alternatives, it continues to serve a role in the preoperative evaluation of patients for lower extremity reconstruction. Duplex ultrasonography has been of great interest recently as an inexpensive, risk free, and extraordinarily accurate diagnostic tool. Emerging technologies such as indocyanine green fluorescence angiography and dynamic infrared thermography provide real-time information about tissue vascularity and perfusion without requiring radiation exposure.

CONCLUSION:  This article presents an in-depth review of the various imaging modalities available to reconstructive surgeons and includes hand held Doppler ultrasound, CT angiography, MR angiography, conventional angiography, duplex ultrasonography, Indocyanine Green Fluorescence Angiography and Dynamic Infrared Thermography.

Harper, C. M., Johannesdottir, F., & Rozental, T. D. (2022). Prospective Fellows’ Appraisal of Hand Surgery Fellowships.. The Journal of Hand Surgery, 47(12), 1229.e1-1229.e8. https://doi.org/10.1016/j.jhsa.2021.09.013 (Original work published 2022)

PURPOSE: The nature and focus of hand surgery fellowships has been shown to vary. Compounding this issue is a paucity of information regarding the educational goals and desires of prospective fellows. The purpose of this study was to understand applicant motivation for pursuing a fellowship and the most important components of these fellowships.

METHODS: We performed an anonymous survey of all the candidates who applied for a hand surgery fellowship during the 2019-2020 academic year to establish general demographic information, preferences regarding fellowship size, and the importance of various educational and logistical components. We also recorded self-reported comfort level in treating pathologies encountered during a hand-focused subspecialty practice.

RESULTS: The most important motivation cited for pursuing a fellowship in hand surgery was the "complexity and variety of cases" (n = 55, 90%). The 5 most important desired components of a fellowship were the exposure to "bread and butter" hand surgery (n = 35, 57%), ability to take level 1 hand call (n = 26, 43%), exposure to complex wrist reconstruction (n = 26, 43%) or peripheral nerve surgery/transfers (n = 23, 38%), and soft tissue coverage including free flaps (n = 19, 31%). Further analysis revealed that the orthopedic surgery residents frequently rated exposure to level 1 call (n = 20, 45%) as 1 of their 3 most important characteristics, whereas the plastic/general surgery residents frequently ranked exposure to complex wrist reconstruction (n = 16, 38%) as 1 of their 3 most important characteristics. The components of a fellowship that received the fewest selections into an applicant's top 3 components were exposure to shoulder surgery (n = 1, 1.64%), education regarding practice building/billing (n = 2, 3.2%), and the ability to conduct research (n = 4, 6.5%).

CONCLUSIONS: Most applicants pursue a subspecialty training in hand surgery because of the field's variety and breadth of cases. The applicants prioritize exposure to "bread and butter" cases in conjunction with both complex soft tissue and microsurgical reconstruction.

CLINICAL RELEVANCE: Assisting hand fellowships in understanding what is most important to prospective fellows will allow for appropriate recruitment and development of the field of hand surgery in general.

Hosseinzadeh, S., Egan, J., Shariat, M., Williamson, P. M., Momenzadeh, K., Van Dam, M., Rodriguez, E. K., Nazarian, A., & Luo, X. (2022). Plaster of Paris: Squeeze, But Not Too Hard!. Orthopedics, 45(1), e57-e61. https://doi.org/10.3928/01477447-20211101-01 (Original work published 2022)

Plaster of Paris (PoP) has been the predominant treatment option for most acute and chronic orthopedic conditions. Water immersion significantly decreases the PoP bandage strength. Moreover, concerns have been raised about the possibility of breaks in PoP splints and cast failures once solid. The current study was designed to account for the increase in weight associated with increased PoP layers. The authors hypothesized that by controlling for weight variation as layers increased, they could determine the number of layers of PoP bandage that truly results in optimal mechanical properties. They assessed whether adequate plaster weight control while increasing layers could improve the mechanical properties of the splint. [Orthopedics. 2022;45(1):e57-e61.].

Investigators, P. A. R. in T. S., Ghert, M., Schneider, P., Guyatt, G., Thabane, L., Vélez, R., O’Shea, T., Randall, L., Turcotte, R., Wilson, D., Wunder, J. S., Baptista, A. M., Cheng, E. Y., Doung, Y.-C., Ferguson, P. C., Giglio, V., Hayden, J., Heels-Ansdell, D., Khan, S. A., … Bhandari, M. (2022). Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial.. JAMA Oncology, 8(3), 345-353. https://doi.org/10.1001/jamaoncol.2021.6628 (Original work published 2022)

IMPORTANCE: The use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited.

OBJECTIVE: To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility.

INTERVENTIONS: A 1- or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen.

MAIN OUTCOMES AND MEASURES: The primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality.

RESULTS: Of the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01479283.

Gupta, A., Shamsi, F., Altemose, N., Dorlhiac, G. F., Cypess, A. M., White, A. P., Yosef, N., Patti, M. E., Tseng, Y.-H., & Streets, A. (2022). Characterization of transcript enrichment and detection bias in single-nucleus RNA-seq for mapping of distinct human adipocyte lineages.. Genome Research, 32(2), 242-257. https://doi.org/10.1101/gr.275509.121 (Original work published 2022)

Single-cell RNA sequencing (scRNA-seq) enables molecular characterization of complex biological tissues at high resolution. The requirement of single-cell extraction, however, makes it challenging for profiling tissues such as adipose tissue, for which collection of intact single adipocytes is complicated by their fragile nature. For such tissues, single-nucleus extraction is often much more efficient and therefore single-nucleus RNA sequencing (snRNA-seq) presents an alternative to scRNA-seq. However, nuclear transcripts represent only a fraction of the transcriptome in a single cell, with snRNA-seq marked with inherent transcript enrichment and detection biases. Therefore, snRNA-seq may be inadequate for mapping important transcriptional signatures in adipose tissue. In this study, we compare the transcriptomic landscape of single nuclei isolated from preadipocytes and mature adipocytes across human white and brown adipocyte lineages, with whole-cell transcriptome. We show that snRNA-seq is capable of identifying the broad cell types present in scRNA-seq at all states of adipogenesis. However, we also explore how and why the nuclear transcriptome is biased and limited, as well as how it can be advantageous. We robustly characterize the enrichment of nuclear-localized transcripts and adipogenic regulatory lncRNAs in snRNA-seq, while also providing a detailed understanding for the preferential detection of long genes upon using this technique. To remove such technical detection biases, we propose a normalization strategy for a more accurate comparison of nuclear and cellular data. Finally, we show successful integration of scRNA-seq and snRNA-seq data sets with existing bioinformatic tools. Overall, our results illustrate the applicability of snRNA-seq for the characterization of cellular diversity in the adipose tissue.

Yellin, J. L., Lu, L. Y., Bauer, A. S., Duane, J., Appleton, P. T., Berkson, E. M., Bluman, E. M., Bono, C. M., Drew, J. M., Duffy, K., Fogel, H. A., May, C., Ready, J. E., Weaver, M. J., Zarins, B., Dyer, G. S. M., & Committee, V. R. E. (2022). Selecting the Next Class: The "Virtual Orthopaedic Rotation".. Journal of the American Academy of Orthopaedic Surgeons. Global Research & Reviews, 6(1). https://doi.org/10.5435/JAAOSGlobal-D-21-00151 (Original work published 2022)

INTRODUCTION: When the COVID-19 pandemic forced the cancellation of visiting subinternships, we pivoted to create a virtual orthopaedic rotation (VOR). The purpose of this study was to assess the effect of the VOR on the residency selection process and determine the role of such a rotation in the future.

METHODS: A committee was convened to create a VOR to replace visiting orthopaedic rotations for medical students who are interested in pursuing a career in orthopaedic surgery. The VOR was reviewed and sanctioned by our medical school, but no academic credit was granted. We conducted three 3-week VOR sessions. During each session, virtual rotators participated in regularly scheduled educational conferences and attended an invitation-only daily conference in the evenings that was designed for a medical student audience. In addition, students were paired with faculty and resident mentors in a structured mentorship program. Students' orthopaedic knowledge was assessed using prerotation and postrotation tests.

RESULTS: From July to September 2020, 61 students from 37 distinct medical schools participated in the VOR. Notable improvements were observed in prerotation and postrotation orthopaedic knowledge test scores. In postrotation surveys, both students and faculty expressed high satisfaction with the curriculum but less certainty about how well they got to know each other. In the subsequent residency application cycle, 27.9% of the students who participated in the VOR were selected to interview, compared with 8.7% of the total application pool.

DISCUSSION: The VOR was a valuable substitute for in-person clinical rotations during the COVID-19 pandemic. Although not likely to be a replacement for conventional away rotations, the VOR is a possible adjunct to in-person clinical rotations in the future.

Abdeen, A., Valle, C. J. D., Kendoff, D., & Chen, A. F. (2022). The Paradox of Prosthetic Joint Infection and the Microbiome: Are Some Bacteria Actually Helpful?. Arthroplasty Today, 13, 116-119. https://doi.org/10.1016/j.artd.2021.11.011 (Original work published 2022)

Periprosthetic joint infection (PJI) is a potentially catastrophic complication of total joint arthroplasty of the lower extremity. PJI is associated with significant burden of illness and economic cost. There are a number of well-established modifiable risk factors for PJI. Myriad perioperative protocols are used with the intent of reducing the incidence of PJI. However, it remains unclear why infections occur despite correction of modifiable risk factors and/or adherence to prophylactic protocols. There is emerging evidence that the microbiome-the diverse population of commensal microorganisms that inhabit the human body-may play a role in the pathogenesis of musculoskeletal infections. The impact of the microbiome on PJI warrants further investigation and may change how we conceptualize, prevent, and treat PJI.

Kheir, N., Salvatore, G., Berton, A., Orsi, A., Egan, J., Mohamadi, A., DeAngelis, J. P., Ramappa, A. J., Longo, U. G., Denaro, V., & Nazarian, A. (2022). Lateral release associated with MPFL reconstruction in patients with acute patellar dislocation.. BMC Musculoskeletal Disorders, 23(1), 139. https://doi.org/10.1186/s12891-022-05013-5 (Original work published 2022)

OBJECTIVE: Medial patellofemoral ligament (MPFL) injury occurs in the majority of the cases of acute patellar dislocation. The role of concomitant lateral retinaculum release with MPFL reconstruction is not clearly understood. Even though the lateral retinaculum plays a role in both medial and lateral patellofemoral joint stability in MPFL intact knees, studies have shown mixed clinical outcomes following its release during MPFL reconstruction surgery. Better understanding of the biomechanical effects of the release of the lateral retinaculum during MPFL reconstruction is warranted. We hypothesize that performing a lateral release concurrent with MPFL reconstruction will disrupt the patellofemoral joint biomechanics and result in lateral patellar instability.

METHODS: A previously developed and validated finite element (FE) model of the patellofemoral joint was used to understand the effect of lateral retinaculum release following MPFL reconstruction. Contact pressure (CP), contact area (CA) and lateral patellar displacement were recorded. abstract.

RESULTS: FE modeling and analysis demonstrated that lateral retinacular release following MPFL reconstruction with tibial tuberosity-tibial groove distance (TT-TG) of 12 mm resulted in a 39% decrease in CP, 44% decrease in CA and a 20% increase in lateral patellar displacement when compared to a knee with an intact MPFL. In addition, there was a 45% decrease in CP, 44% decrease in CA and a 21% increase in lateral displacement when compared to a knee that only had an MPFL reconstruction.

CONCLUSION: This FE-based analysis exhibits that concomitant lateral retinaculum release with MPFL reconstruction results in decreased PF CA, CP and increased lateral patellar displacement with increased knee flexion, which may increase the risk of patellar instability.