Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this study is to compare medium to long term patient reported outcomes to one-year data for patients treated surgically for an aseptic fracture nonunion. METHODS:305 patients surgically treated for a fracture-nonunion were prospectively followed. Data collected included pain scores measured by the Visual Analog Scale (VAS), clinical outcomes assessed by the Short Musculoskeletal Functional Assessment (SMFA), and range of motion. 75% of patients in this study had lower extremity fracture nonunions and 25% had upper extremity fracture nonunions. Femur fracture nonunions were the most common. Data at latest follow-up was compared to one-year follow-up using the independent t-test. RESULTS:Sixty-two patients were available for follow-up data at an average of eight years. There were no differences in patient reported outcomes between one and eight years according to the standardized total SMFA (p = 0.982), functional index SMFA (p = 0.186), bothersome index SMFA (p = 0.396), activity index SMFA (p = 0.788), emotional index SMFA (p = 0.923), or mobility index SMFA (p = 0.649). There was also no difference in reported pain (p = 0.534). Range of motion data was collected for patients who followed up in clinic for an average of eight years after their surgical treatment. 58% of these patients reported a slight increase in range of motion at an average of eight years. CONCLUSION/CONCLUSIONS:Patient functional outcomes, range of motion, and reported pain all normalize after one year following surgical treatment for fracture nonunion and do not change significantly at an average of eight years. Surgeons can feel confident in counseling patients that their results will last and they do not need to follow up beyond one year, barring pain or other complications. LEVEL OF EVIDENCE/METHODS:Level IV.

Cannabis has a rich history as a therapeutic tool with wide ranging applications. The efficacy of cannabidiol (CBD), the non-psychoactive component of cannabis, has been well demonstrated for pain management. Further, recent orthopedic studies have demonstrated positive effects of CBD on wound healing, inflammation, bone marrow density, and fracture healing. Despite the growing interest in CBD, there is a paucity of research on its impact on fracture risk and bone density in human clinical trials and the existing literature has significant limitations. As the rate of cannabis consumption increases, further research is essential to delineate the therapeutic qualities of CBD and its long-term effects on fracture healing and bone metabolism in order to optimize patient outcomes.

OBJECTIVE:To determine if a peri-operative pain cocktail injection improves post-operative pain, ambulation distance and long-term outcomes in hip fracture patients. DESIGN/METHODS:Prospective, single-blinded, randomized controlled trial. SETTING/METHODS:Academic Medical Center. PATIENTS/PARTICIPANTS/METHODS:Patients with OTA/AO 31A1-3 and 31B1-3 fractures undergoing operative fixation, excluding arthroplasty. INTERVENTION/METHODS:Multimodal local injection of bupivacaine (Marcaine), morphine sulfate (Duramorph), ketorolac (Toradol) given at the fracture site at the time of hip fracture surgery (Hip Fracture Injection, HiFI). MAIN OUTCOME MEASUREMENTS/METHODS:Patient-reported pain, American Pain Society Patient Outcome Questionnaire (APS-POQ), narcotic usage, length of stay, post-operative ambulation, Short Musculoskeletal Function Assessment (SMFA). RESULTS:75 patients were in the treatment group and 109 in the control group. Patients in the HiFI group had a significant reduction in pain and narcotic usage compared to the control group on post-operative day (POD) 0 (p<0.01). Based on the APS-POQ, patients in the control group had a significantly harder time falling asleep, staying asleep, and experienced increased drowsiness on POD 1 (p<0.01). Patient ambulation distance was greater on POD 2 (p<0.01) and POD 3 (p<0.05) in the HiFI group. The control group experienced more major complications (p<0.05). At six-weeks post-op, patients in the treatment group reported significantly less pain, better ambulatory function, less insomnia, less depression, and better satisfaction than the control group as measured by the APS-POQ. The SMFA bothersome index was also significantly lower for patients in the HiFI group, p<0.05. CONCLUSIONS:Intraoperative HiFI not only improved early pain management and increased ambulation in patients undergoing hip fracture surgery while in the hospital, it was also associated with early improved health related quality of life following discharge. LEVEL OF EVIDENCE/METHODS:Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Musculoskeletal development and later post-natal homeostasis are highly dynamic processes, marked by rapid structural and functional changes across very short periods of time. Adult anatomy and physiology are derived from pre-existing cellular and biochemical states. Consequently, these early developmental states guide and predict the future of the system as a whole. Tools have been developed to mark, trace, and follow specific cells and their progeny either from one developmental state to the next or between circumstances of health and disease. There are now many such technologies alongside a library of molecular markers which may be utilized in conjunction to allow for precise development of unique cell 'lineages'. In this review, we first describe the development of the musculoskeletal system beginning as an embryonic germ layer and at each of the key developmental stages that follow. We then discuss these structures in the context of adult tissues during homeostasis, injury, and repair. Special focus is given in each of these sections to the key genes involved which may serve as markers of lineage or later in post-natal tissues. We then finish with a technical assessment of lineage tracing and the techniques and technologies currently used to mark cells, tissues, and structures within the musculoskeletal system.

Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance and repair. Deciphering the molecular mechanisms that regulate their function is crucial for the successful generation and application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary and sufficient for periosteal stem cell function. Hox genes are transcriptionally enriched in periosteal stem cells and their overexpression in more committed progenitors drives reprogramming to a naïve, self-renewing stem cell-like state. Crucially, individual Hox family members are expressed in a location-specific manner and their stem cell-promoting activity is only observed when the Hox gene is matched to the anatomical origin of the PSPC, demonstrating a role for the embryonic Hox code in adult stem cells. Finally, we demonstrate that Hoxa10 overexpression partially restores the age-related decline in fracture repair. Together, our data highlight the importance of Hox genes as key regulators of PSPC identity in skeletal homeostasis and repair.

Cannabidiol (CBD), the non-psychoactive component of the Cannabis sativa plant, is marketed as a potential therapeutic agent and has been studied for its roles in reducing inflammation and managing neuropathic pain. Some studies have reported that CB1 and CB2 receptor activation can attenuate and reverse bone loss in experimental animal models. Despite this, little is known about the impact of CBD on fracture healing. We investigated the effects of CBD in vitro using human osteoprogenitor cells and in vivo via murine femur fracture and osteoporosis models. In vitro mesenchymal stem cells were treated with increasing concentrations of crystalized pharmaceutical grade CBD or vehicle solution. Cell viability and proliferation were significantly increased in cells treated with CBD compared to vehicle control. Osteocalcin expression was also significantly higher in the CBD-treated human stem cells compared to vehicle control. In vivo the effect of CBD on bone mineral density and fracture healing in mice was examined using a two-phase experimental approach. Fluoxetine was used for pharmacologic induction of osteoporosis and surgical oophorectomy (OVX) was used for hormonal induction of osteoporosis. X-ray and microCT analysis showed that CBD prevented both fluoxetine- and OVX-induced osteoporosis. We found that while OVX resulted in delayed bone healing in control mice, CBD-pretreated mice exhibited normal bone healing. Collectively these in vitro and in vivo findings suggest that CBD exerts cell-specific effects which can be exploited to enhance bone metabolism. These findings also indicate that CBD usage in an osteoporotic population may positively impact bone morphology, warranting further research.

BACKGROUND/UNASSIGNED:The posterolateral approach to the ankle allows for reduction and fixation of the posterior and lateral malleoli through the same surgical incision. This can be accomplished via 1 or 2 surgical "windows." The purpose of this study is to compare outcomes including wound complications following direct fixation of unstable rotational ankle fracture through the posterolateral approach using either 1 or 2 surgical windows. METHODS/UNASSIGNED:One hundred sixty-four patients with bi- or trimalleolar ankle fractures treated using the single-window posterolateral approach (between the peroneal tendons and the flexor hallucis longus [FHL]) or the 2-window technique (between the peroneal tendons and the FHL for posterior malleolus fixation; lateral to the peroneal tendons for fibula fixation) were reviewed for demographics, radiographic details, and clinical outcomes. We were able to review these 164 at the 3-month follow-up and a subset of 104 at a minimum of 12-month follow-up. RESULTS/UNASSIGNED: = .021). We did not find a significant difference in nerve complications for these 2 cohorts. CONCLUSION/UNASSIGNED:In our study, we found the single-window posterolateral approach to be associated with fewer wound complications and better postoperative range of ankle motion when compared to the 2-window approach. LEVEL OF EVIDENCE/UNASSIGNED:Level III, retrospective cohort study.

Aims Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. Methods A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia. Results GIK treatment resulted in a significant protection of skeletal muscle with increased viability (GIK 22.07% (SD 15.48%)) compared to saline control (control 3.14% (SD 3.29%)) (p = 0.005). Additionally, GIK led to a statistically significant reduction in gene expression markers of cell death (CASP3, p < 0.001) and inflammation (NOS2, p < 0.001; IGF1, p = 0.007; IL-1β, p = 0.002; TNFα, p = 0.012), and a significant reduction in serum creatine kinase (p = 0.004) and creatinine (p < 0.001). GIK led to a significant reduction in IR-related pain (p = 0.030). Conclusion Systemic GIK infusion during and after limb ischaemia protects murine skeletal muscle from cell death, kidneys from reperfusion metabolites, and reduces pain by reducing post-ischaemic inflammation.

PURPOSE/OBJECTIVE:To determine if the DTS decreases radiation exposure (primary outcome measure), fluoroscopy time (secondary outcome measure), and time to distal screw placement (secondary outcome measure) compared to the freehand "perfect circles" method when used for locking of cephalomedullary nails in the treatment of femur fractures METHODS: Fifty-eight patients with hip or femoral shaft fractures that were treated with a long cephalomedullary nail were enrolled in this study. Cohorts were determined based on the method of distal interlocking screw placement into either the "Perfect Circles" or "Distal Targeting" cohort. Time from cephalad screw placement to placement of final distal interlocking screw (seconds), radiation exposure (mGy), and fluoroscopy time (seconds) were compared between groups. Hospital quality measures were compared between cohorts. RESULTS:Use of the DTS resulted in 77% (4.3x) lower radiation exposure (p < 0.001), 64% (2.7x) lower fluoroscopy time (p < 0.001), and 60% (1.7x) lower intraoperative time from end of cephalad screw placement to end of distal interlocking screw placement (p < 0.001) compared to the freehand "perfect circles" method. There was no difference in 30-day or 90-day complication rates between cohorts. CONCLUSION/CONCLUSIONS:The Stryker Gamma3® Distal Targeting System is a safe, effective and efficient alternative to the freehand "perfect circles" method.

OBJECTIVES/OBJECTIVE:To examine the efficacy of regional anesthesia with sedation only for a variety of hip fractures using the newly described lateral femoral cutaneous with over the hip Block (LOH Block). DESIGN/METHODS:Retrospective. SETTING/METHODS:Level-I Trauma CenterPatients/Participants: 40 patients who presented between 11/2021 and 02/2022 for fixation of OTA/AO 31.A1-3 and 31.B1-3 fractures. Matched cohorts of 40 patients who received general anesthesia and 40 patients who received spinal anesthesia for hip fracture fixation were also used. INTERVENTION/METHODS:Operative fixation under LOH block and sedation only. The LOH block is a regional hip analgesic that targets the lateral femoral cutaneous nerve, articular branches of femoral nerve (FN) and accessory obturator nerve (AON). MAIN OUTCOME MEASUREMENTS/METHODS:Demographics, intraoperative characteristics, anesthesia-related complications, hospital quality metrics, and short-term mortality and reoperation rates. RESULTS:A total of 120 patients (40 each: general, spinal, LOH block) were compared. The cohorts were similar in age, race, BMI, gender, CCI, trauma risk score, ambulatory status at baseline, fracture type, and surgical fixation technique performed. Physiologic parameters during surgery were more stable in the LOH block group (p<0.05). Total OR time and anesthesia time were shortest for the LOH block cohort (p<0.05). Patients in the LOH block cohort also had lower post-operative pain scores (p<0.05). Length of hospital stay was shortest for patients in the LOH block cohort (p<0.05), and at time of discharge, patients in the LOH block cohort ambulated the furthest (p<0.05). No differences were found in regards to anesthesia-related complications, palliative care consults, major and minor hospital complications, discharge disposition, reoperation and readmission rates, and mortality rates. CONCLUSIONS:The LOH block is safe and effective anesthesia for the treatment of all types of hip fractures in the elderly requiring surgery. In addition, this block may decrease post-operative pain and length of hospital stay, and also allow for greater ambulation in the early post-operative period for hip fracture patients. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.