Trends in functional outcome measures in orthopedic oncology.

The purpose of this study was to identify trends in the use of functional outcome measures within orthopedic oncology. The search engine, PubMed, was reviewed for all articles over an 11-year period from 2011 to 2021 from five major journals that publish in the field of orthopedic oncology. The functional outcome measures used in the articles were recorded along with study date, study design, clinical topic/pathology, and level of evidence. Out of 5968 musculoskeletal tumor-focused articles reviewed, 293 (4.9%) included at least one outcome measure. A total of 28 different outcome tools were identified. The most popular were Musculoskeletal Tumor Society (MSTS) score (61.1%) and Toronto Extremity Salvage (TESS) score (14.0%), followed by 36-Item Short Form Survey (SF-36) (4.1%) and Patient-Reported Outcomes Measurement Information System (PROMIS) (3.8%). The use of MSTS scores decreased by 0.7% each year, whereas PROMIS increased by 1.2% each year. Seventy-four articles used more than one outcome measure. Of these 74 articles, 61 had the MSTS as one of the outcome measures. Orthopedic oncology utilizes functional outcome measures less commonly in comparison to other orthopedic subspecialties. However, this may be due in large part to orthopedic oncologists putting more emphasis on outcomes such as local recurrence, implant failure, and mortality. MSTS score is the most widely used functional outcome measure, but the utilization of PROMIS has increased recently, and could be the next step in evaluating outcomes in orthopedic oncology as it is patient-derived rather than physician-derived.

Mesenchymal stem cells enhance targeted bone growth from injectable hydrogels with BMP-2 peptides.

Osteoporosis is the most common chronic metabolic bone disease, and the prevalence of osteoporotic fractures is rapidly increasing with the aging population. While bisphosphonates can reduce bone loss and risk of fracture, these drugs are systemic, rely on long-term use, and patient compliance is low. Recombinant human bone morphogenetic protein-2 (BMP-2) is an FDA-approved protein that can offer a more targeted therapeutic than systemic treatments. DWIVA is a peptide sequence corresponding to the wrist epitope of BMP-2, and DWIVA-functionalized hydrogels feature osteoinductive propertiesin vitro and in vivo. This study reports that self-forming DWIVA-functionalized hydrogels injected into the intramedullary canal of rat femurs induce a local increase in trabecular bone in as little as 2 weeks. Increases in bone volume, trabecular thickness, and trabeculae count from DWIVA-laden hydrogels persist for at least 4 weeks, and the inclusion of mesenchymal stem cells (MSCs) significantly enhances the development of mineralized bone. Histological analysis of decalcified femurs also shows that hydrogel injections containing DWIVA peptide and MSCs stimulate unmineralized bone tissue formation and induce an increased count of osteoblasts and osteoclasts at the injection site after 4 weeks. Overall, the MSC-laden DWIVA peptide-functionalized hydrogels presented rapidly induce targeted bone formation and have the potential to form nascent bone within bones in jeopardy of an osteoporotic fracture such as the femur.

Self-Forming Norbornene-Tetrazine Hydrogels with Independently Tunable Properties.

Although photopolymerization reactions are commonly used to form hydrogels, these strategies rely on light and may not be suitable for delivering therapeutics in a minimally invasive manner. Here, hyaluronic acid (HA) macromers are modified with norbornene (Nor) or tetrazine (Tet) and upon mixing click into covalently crosslinked Nor-Tet hydrogels via a Diels-Alder reaction. By incorporating a high degree of Nor and Tet substitution, Nor-Tet hydrogels with a broad range in elastic moduli (5 to 30 kPa) and fast gelation times (1 to 5 min) are achieved. By pre-coupling methacrylated HANor macromers with thiolated peptides via a Michael addition reaction, Nor-Tet hydrogels are peptide-functionalized without affecting their physical properties. Mesenchymal stem cells (MSCs) on RGD-functionalized Nor-Tet hydrogels adhere and exhibit stiffness-dependent differences in matrix mechanosensing. Fluid properties of Nor-Tet hydrogel solutions allow for injections through narrow syringe needles and can locally deliver viable cells and peptides. Substituting HA with enzymatically degradable gelatin also results in cell-responsive Nor-Tet hydrogels, and MSCs encapsulated in Nor-Tet hydrogels preferentially differentiate into adipocytes or osteoblasts, based on 3D cellular spreading regulated by stable (HA) and degradable (gelatin) macromers.

Tumor-to-Tumor Metastasis: Renal Cell Carcinoma Metastasizing to a Lipoma of the Thigh: A Case Report.

CASE: A 73-year-old man with a medical history significant for renal cell carcinoma (RCC) presented with widespread osseous metastases and imaging suspicious for RCC metastasizing to a lipoma interdigitated within the right vastus lateralis. The patient's pathological fractures were surgically addressed, and the lipoma excised. Final histology revealed a thigh lipoma involved by metastatic RCC without direct extension. CONCLUSION: Tumor-to-tumor metastasis is a rare occurrence, with RCC typically being the most common "recipient" tumor. This is the first case to the best of our knowledge of RCC metastasizing to a lipoma, highlighting a rare phenomena in a patient with metastatic disease.

Intraosseous hibernoma: Two case reports and a review of the literature.

Intraosseous hibernomas are exceedingly rare tumors with only 35 cases reported worldwide. They are composed of vestigial brown adipose tissue and require biopsy and pathologic analysis for definitive diagnosis. Given their propensity to mimic more insidious malignant neoplasms, early and accurate identification may spare the patient both anxiety and invasive therapeutic interventions. In this report, we present two cases of intraosseous hibernomas and provide a review of current literature to further characterize the clinical, radiographic, and histopathologic parameters of these lesions. Clinicians should consider the diagnosis of intraosseous hibernoma when evaluating patients with characteristic presentations as it may be more prevalent than currently reported.

Injectable hydrogel with immobilized BMP-2 mimetic peptide for local bone regeneration.

Osteoporosis is a disease characterized by a decrease in bone mineral density, thereby increasing the risk of sustaining a fragility fracture. Most medical therapies are systemic and do not restore bone in areas of need, leading to undesirable side effects. Injectable hydrogels can locally deliver therapeutics with spatial precision, and this study reports the development of an injectable hydrogel containing a peptide mimic of bone morphogenetic protein-2 (BMP-2). To create injectable hydrogels, hyaluronic acid was modified with norbornene (HANor) or tetrazine (HATet) which upon mixing click into covalently crosslinked Nor-Tet hydrogels. By modifying HANor macromers with methacrylates (Me), thiolated BMP-2 mimetic peptides were immobilized to HANor via a Michael addition reaction, and coupling was confirmed with 1H NMR spectroscopy. BMP-2 peptides presented in soluble and immobilized form increased alkaline phosphatase (ALP) expression in MSCs cultured on 2D and encapsulated in 3D Nor-Tet hydrogels. Injection of bioactive Nor-Tet hydrogels into hollow intramedullary canals of Lewis rat femurs showed a local increase in trabecular bone density as determined by micro-CT imaging. The presented work shows that injectable hydrogels with immobilized BMP-2 peptides are a promising biomaterial for the local regeneration of bone tissue and for the potential local treatment of osteoporosis.

Intraosseous Lipoma: An Elusive Cause of Long Bone Pain: A Case Series.

Introduction: Intraosseous lipomas are benign tumors composed of mature fat that reside within the intramedullary canal. Although many cases are asymptomatic, some patients report pain that interferes with daily living. For patients presenting with refractory pain, surgical excision may be performed. These tumors were once thought to be rare, but a recent increase in awareness and diagnostic capability may contradict this. Case Presentations: A 27-year-old female presented with a 3-month history of deep and aching pain in her left shoulder. The second patient was a 24-year-old female who presented with a 3-year history of pain in her right tibia. The third was a 50 year old female who presented with a 4-month history of deep pain in her right humerus. The fourth patient was a 34-year-old female who presented with a 6-month history of the left heel pain. All were found to have intraosseous lipomas and were treated with excisional curettage, achieving resolution of symptoms. Conclusion: These cases may help orthopedists better understand the presentation and treatment of intraosseous lipomas due to several shared characteristics. We also hope that this report may lead clinicians to include this pathology in their differential diagnosis when patients present with similar symptoms. As the prevalence of these tumors appears to be increasing, efficient diagnosis and treatment will become increasingly valuable to orthopedists and patients.

Treatment of Femoral Shaft Fractures in Patients with Klippel-Trénaunay Syndrome: A Report of 2 Cases.

CASES: Long-bone fractures in patients with Klippel-Trénaunay syndrome (KTS), a rare disorder of the venous, lymphatic, and capillary system, are difficult to treat with many complications. Two patients diagnosed with KTS presented with closed femoral shaft fractures after low-energy falls. Conservative treatment, open reduction internal fixation, and intramedullary nailing resulted in painful nonunions. Ultimately, both patients achieved pain relief and the ability to ambulate after en bloc resection and reconstruction. CONCLUSIONS: These cases demonstrate the challenges in achieving bony union when treating long-bone fractures in KTS. The feasibility of undergoing extensive resection and reconstruction to regain function is best approached with a multidisciplinary team.

Outcomes after antibiotic megaspacer implantation in patients with severe chronic periprosthetic infections.

Periprosthetic joint infection (PJI) is a rare postoperative complication that is treated with antibiotic spacers. Some patients develop severe, treatment-resistant, chronic PJI despite multiple attempts at salvaging the joint. Permanent resection of the joint or amputation may be the only definitive treatment. The purpose of this study is to describe the outcomes, infection resolution rate, and complications of two-stage revision, utilizing extensive resection of the affected bone and application of antibiotic megaspacers as a modality for limb-salvage. A review of 12 patients, initially referred for amputation due to chronically failed PJI, was conducted. All patients underwent extensive resection of the bone and surgical implantation of a custom-made antibiotic megaspacer between December 2016 and June 2019. Thirteen megaspacers were placed in 13 infected joints in 12 patients with a history of chronic PJI. Six patients (50%) had a diagnosis of osteomyelitis. Eradication of the infection leading to limb-salvage was successful in nine patients. Visual Analog Scale pain scores improved by 3.5, or 50%, after two-stage revision with megaprosthesis reimplantation (p = .008), and six patients (54.5%) had improvement in ambulation. Complication rates, not including reinfection or recurrence, following megaspacer and megaprosthesis reimplantation were 58.3% and 27.3%, respectively. One patient underwent amputation due to a life-threatening infection while two other patients underwent amputation due to debilitating complications following limb-salvage surgery. Statement of Clinical Significance: In patients whose PJI becomes treatment-resistant after multiple failed attempts at traditional two-stage exchange, performing extensive boney resection with placement of an antibiotic-laden megaspacer can be an effective method of achieving limb-salvage.

Team Approach: Rehabilitation Strategies for Patients After Osteosarcoma Reconstructive Surgery.

The multimodal treatment of osteosarcoma with chemotherapy, surgical resection, and reconstruction has improved outcomes after a limb-salvage surgical procedure. Physical rehabilitation considerations after surgical resection vary, depending on the location of the tumor. Physical medicine and rehabilitation physicians incorporate lymphedema specialists, orthotists, and prosthetists to help to improve limb function. Beyond physical rehabilitation, psychological or behavioral interventions and nutritional rehabilitation are necessary to maximize a patient's return to function.

Effect of temperature and ultraviolet light on the bacterial kill effectiveness of antibiotic-infused 3D printed implants.

Drug eluting 3D printed polymeric implants have great potential in orthopaedic applications since they are relatively inexpensive and can be designed to be patient specific thereby providing quality care. Fused Deposition Modeling (FDM) and Stereolithography (SLA) are among the most popular techniques available to print such polymeric implants. These techniques facilitate introducing antibiotics into the material at microscales during the manufacturing stage and subsequently, the printed implants can be engineered to release drugs in a controlled manner. However, FDM uses high temperature to melt the filament as it passes through the nozzle and SLA relies on exposure to nanoscale wavelength ultraviolet (UV) light which can adversely affect the anti-bacterial effectiveness of the antibiotics. The focus of this article is two-fold: i) Examine the effect of high temperature on the bacterial kill-effectiveness of eluted antibiotics through Polycaprolactone (PCL) based femoral implants and ii) Examine the effect of exposure to ultraviolet (UV) light on the bacterial kill-effectiveness of eluted antibiotics through femoral implants made up of a composite resin with various weight fractions of Polyethylene Glycol (PEG) and Polyethylene Glycol Diacrylate (PEGDA). Results indicate that even after exposing doxycycline, vancomycin and cefazolin at different temperatures between 20oC and 230oC, the antibiotics did not lose their effectiveness (kill radius of at least 0.85 cm). For doxycycline infused implants exposed to UV light, it was seen that a resin with 20 % PEGDA and 80 % PEG had the highest efficacy (1.8 cm of kill radius) and the lowest efficacy was found in an implant with 100 % PEGDA (1.2 cm of kill radius).

The Efficacy of Medical Marijuana in the Treatment of Cancer-Related Pain.

Background: The opioid epidemic has spurred investigations for nonopioid options, yet limited research persists on medical marijuana's (MMJ) efficacy in managing cancer-related symptoms. Objective: We sought to characterize MMJ's role on symptomatic relief and opioid consumption in the oncologic population. Design: Retrospective chart review of MMJ-certified oncology patients was performed. Divided patients into MMJ use [MMJ(+)] versus no use [MMJ(-)], and Edmonton Symptom Assessment System (ESAS)-reported pain cohorts: "mild-moderate" versus "severe." Measurements: Medical records were reviewed for ESAS, to measure physical and emotional symptoms, and opiate consumption, converted into morphine milligram equivalents (MME). Minimal clinically important differences were determined. Wilcoxon signed-rank tests determined statistical significance between MMJ-certification and most recent palliative care visit. Results: Identified 232 patients [95/232 MMJ(-); 137/232 MMJ(+)]. Pain, physical and total ESAS significantly improved for total MMJ(-) and MMJ(+); however, only MMJ(+) significantly improved emotional ESAS. MMJ(-) opioid consumption increased by 23% (97.5-120 mg/day MME, p = 0.004), while it remained constant (45-45 mg/day MME, p = 0.522) in MMJ(+). Physical and total ESAS improved in mild-moderate-MMJ(-) and MMJ(+). Pain and emotional symptoms worsened in MMJ(-); while MMJ(+)'s pain remained unchanged and emotional symptoms improved. MMJ(-) opioid consumption increased by 29% (90-126 mg/day MME, p = 0.012); while MMJ(+)'s decreased by 33% (45-30 mg/day MME, p = 0.935). Pain, physical, emotional, and total ESAS scores improved in severe-MMJ(-) and MMJ(+); opioid consumption reduced by 22% in MMJ(-) (135-106 mg/day MME, p = 0.124) and 33% in MMJ(+) (90-60 mg/day MME, p = 0.421). Conclusions: MMJ(+) improved oncology patients' ESAS scores despite opioid dose reductions and should be considered a viable adjuvant therapy for palliative management.

The Changing Nature of the Oncology Section of the Orthopaedic In-Training Examination.

INTRODUCTION: The Orthopaedic In-Training Examination (OITE) assesses orthopaedic resident knowledge over 275 multiple-choice questions.Since the first publication examining the contents of the pathology section was published over ten years ago, the pathology content has been renamed (oncology) and revamped. As the overall extent of these alterations is currently unknown, the efficacy of current orthopaedic oncology educational practices for optimal OITE performance should be questioned. To determine how the oncology (pathology) material has changed, we compared the following characteristics from previous examinations (2002 to 2006) to current examinations (2012 to 2016): (1) What are the average number of oncology questions being asked? (2) What are the specific imaging modalities presented for examinee interpretation? (3) Which pathologic diagnoses are commonly examined? (4) What is the pattern of taxonomic question classifications? METHODS: The 2012 to 2016 OITE study guides were reviewed, and each oncology question was categorized into one of the following: benign or malignant, imaging modality grouping, common pathologic diagnosis, question type, and taxonomic classification. The aforementioned information was extrapolated from the previous pathology publication published in 2010 to create the previous examination cohort (2002 to 2006). The current examination characteristics were then compared with those of the previous examinations. RESULTS: The current number of oncology OITE questions significantly decreased from previous years (27.2 versus 21.2; P = 0.015). Current examinations displayed a significant increase in testing the interpretation of diagnostic imaging modalities compared with previous examinations (78.3% versus 55.8%; P < 0.001). The current examinations examined a wide spectrum of pathologic diagnoses, including previously untested pathologies. The number of taxonomy 1 questions on current examinations significantly decreased (36.8% versus 24.5%; P = 0.032), whereas the number of taxonomy 3 questions significantly increased from previous examinations (48.1% versus 32.4%; P = 0.032). DISCUSSION: This study demonstrated that the nature of the orthopaedic oncology (pathology) section has changed over the past 10 years. Although the overall number of pathology-related questions decreased, the difficulty level of these questions increased, demanding a higher level of knowledge and critical thinking. A formal orthopaedic oncology rotation may be the best method to educate and improve OITE oncology performance. LEVEL OF EVIDENCE: Prognostic study, level III.

Novel policing techniques decrease gun-violence and the cost to the healthcare system.

The objective was to investigate the effects of novel policing techniques on hospital-observed incidence, healthcare utilization, mortality and costs associated with gun violence, from the perspective of a level-1 trauma center. An eight-year retrospective review evaluating the clinical and financial effects of gunshot wound (GSW) encounters between January 1st, 2010 and December 31st, 2017. Individuals who presented to the emergency department (Level-1 trauma center in Camden, NJ) between January 1, 2010 and December 31, 2017 with GSW (995 encounters) were included; however, patients with incomplete financial or medical record data were excluded (55 encounters). Patients were subdivided into two cohorts: before and after changes in policing tactics (May 1st, 2013). 940 total firearm-related encounters were included in the study. Following the policing changes, the hospital-observed quarterly incidence of GSW encounters decreased by 22% post-policing changes, 44.3 to 34.6 (p = 0.038). Average quarterly days spent in-house for GSW treatment decreased 220.7 to 151.3 (31%) days. Hospital observed mortality increased from 13.5% of presentations to 17.3% of presentations (p = 0.106). Total cost savings associated with the policing change was roughly $254,000 per quarter (p = 0.023). In areas susceptible to high rates of gun violence, similar novel policing tactics could significantly decrease hospital-observed incidence, costs and healthcare utilization demanded by firearm-related injury.

Efficacy of eluted antibiotics through 3D printed femoral implants.

Costs associated with musculoskeletal diseases in the United States account for 5.7% of the Gross Domestic Product (GDP) (Weinstein et al. 2018). As such, there is a need to pursue new ideas in orthopaedic implants that can decrease cost and improve patient care. In the recent years, 3D printing of polymers using Fused Deposition Modeling (FDM) and metals using Direct Metal Laser Sintering (DMLS) has opened several exciting possibilities to create customized orthopaedic implants. Such implants can be engineered to release antibiotics in a controlled manner by infusing the drug into the material during manufacturing stage. However, the prevalence of high temperature could impact the anti-bacterial effectiveness of the eluted antibiotics in such implants. An alternative approach to circumvent this issue would be to modify the implant geometry to incorporate built-in design features such as micro-channels and reservoirs in which antibiotics can be introduced prior to the surgical procedure. Irrespective of the approach used, the ability of 3D printed orthopaedic implants to elute antibiotics, and the rate of elution are not well understood. The purpose of this article is to study the elution of doxycycline through 3D printed femoral implants using three different materials: Poly-Lactic Acid (PLA), Poly-Caprolactone (PCL) and Titanium grade Ti-6Al-4V. The PLA and Ti-6Al-4V implants were designed with built-in reservoirs and micro-channels in which doxycycline was introduced post the manufacturing stage. However, the PCL implants were printed from a PCL spool that was infused with doxycycline using an extruder. The PLA and Ti-6Al-4V experiments were run for a period of 31 days and the PCL experiment for one day. The antibacterial ability of eluted doxycycline from all implants were examined using Kirby-Bauer test on the bacteria E.coli k-12. The results show that most of doxycycline eluted through the three materials in the first 24 hours. After the initial spike, a steady release was achieved for the PLA and Ti-6Al-4V implants for 30 days. During this timeframe, Ti-6Al-4V implants released more doxycycline than the PLA implant. The eluted antibiotics through all the implants demonstrated the ability to kill bacteria in the subsequent Kirby-Bauer test. These outcomes show that irrespective of how the antibiotics were introduced, 3D printed polymeric and metallic implants have great potential in orthopaedic applications.

Recurrent Adolescent Giant-Cell Tumor of the Scaphoid: Scaphoid Excision with Intracarpal Fusion after Failed Curettage and Bone Grafting.

We present a case of the giant-cell tumor of bone in the scaphoid of a 17-year-old female. Imaging revealed an expansile lytic lesion of her scaphoid, and the diagnosis was confirmed with open biopsy. She was treated with curettage and iliac crest bone graft, in an effort to spare reconstruction of her wrist. After one year, she developed increasing tightness and pain. Local recurrence was apparent on radiographs, and CT revealed increased lucency with bony destruction in the area of prior excision. She was successfully treated, without recurrence to date, with complete scaphoid excision and a four-corner wrist fusion. Local recurrence of the giant-cell tumor of bone is high, especially in carpal bones. When treating patients with advanced lesions, more aggressive initial options should be considered.

Candida albicans Sacral Osteomyelitis Causing Necrosis of a Sacral Nerve Root: A Case Report.

CASE: A 31-year-old immunocompetent woman presented with a large sacral mass on the left side, concerning for a neoplastic process. A biopsy specimen demonstrated fungal osteomyelitis. Intraoperatively, the left S1 sacral nerve root was found to be necrotic, consistent with the symptoms of numbness and weakness. The infection was resolved with aggressive surgical debridement and long-term therapy with antifungal medication. CONCLUSION: Fungal osteomyelitis of the sacrum is rare, especially in an immunocompetent patient, and untreated infections can cause nerve root necrosis. We recommend aggressive surgical and antifungal management to avoid neurologic compromise.

Aspirin for Prophylaxis Against Venous Thromboembolism After Orthopaedic Oncologic Surgery.

BACKGROUND: Patients who undergo orthopaedic oncologic surgical procedures are at increased risk of developing a venous thromboembolism (VTE). Guidelines from surgical societies are shifting to include aspirin as a postoperative VTE prophylactic agent. The purpose of this study was to review our experience using aspirin as postoperative VTE prophylaxis for orthopaedic oncologic surgical procedures. METHODS: This study was a retrospective review of patients diagnosed with a primary malignant soft-tissue or bone tumor or metastatic carcinoma. Demographic information, histopathologic diagnosis, VTE history, surgical procedure, and VTE prophylaxis were analyzed. VTE rates in the overall and prophylactic-specific cohorts were recorded and compared. RESULTS: A total of 142 distinct surgical procedures in 130 patients were included. VTE prophylaxis with aspirin was used after 103 procedures, and non-aspirin prophylaxis was used after 39. In 33 cases, imaging was used to investigate for VTE because of clinical signs and symptoms. VTE developed after 7 (4.9%) of the 142 procedures. There were 6 deep venous thromboses (DVTs) and 1 pulmonary embolism, and 2 of the VTEs presented in patients with a VTE history. VTE developed in 2.9% (3) of the 103 aspirin cases and 10.3% (4) of the 39 non-aspirin cases. No patient in the aspirin group who had been diagnosed with metastatic carcinoma, malignant soft-tissue sarcoma, lymphoma, or multiple myeloma developed a VTE. Risk factors for VTE development included diabetes mellitus (odds ratio [OR] = 10.40, 95% confidence interval [CI] = 1.61 to 67.30), a history of VTE (OR = 7.26, 95% CI = 1.19 to 44.25), postoperative transfusion (OR = 34.50, 95% CI = 3.94 to 302.01), and estimated blood losses of 250 mL (OR = 1.50, 95% CI = 1.11 to 2.03), 500 mL (OR = 2.26, 95% CI = 1.23 to 4.13), and 1,000 mL (OR = 5.10, 95% CI = 1.52 to 17.04). CONCLUSIONS: Aspirin may be a suitable and effective option for VTE chemoprophylaxis in patients treated with orthopaedic oncologic surgery, especially those diagnosed with a soft-tissue sarcoma. Research with a more advanced study design is required. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

3D printed liner for treatment of periprosthetic joint infections.

In the United States, long standing deep infections of joint arthroplasty, such as total knee and total hip replacements, are treated with two-stage exchange. This requires the removal of the prior implant, placement of an antibiotic eluting spacer block made of polymethylmethacrylate (PMMA), followed by re-implantation of a new implant after treatment with intravenous antibiotics for six to eight weeks. Unfortunately, the use of PMMA as a spacer material has limitations in terms of mechanical and drug-eluting properties. PMMA is brittle and elutes most of the antibiotics within the first few days. Furthermore, the polymerization reaction for PMMA is highly exothermic, thereby limiting the use to heat-stable antibiotics. We hypothesize that the use of a 3D printed polymeric liner made of polylactic acid (PLA) would overcome the limitations of PMMA because it is a stronger and a less brittle material than PMMA. Furthermore, the liner can also act as a controlled drug delivery vehicle by using built in reservoirs and a network of micro-channels as well as by incorporating antibiotics directly into the polymer during manufacturing stage. Finally, the liner can be 3D printed according to the anatomy of the patient and thereby has the potential to transform the manner in which periprosthetic joint infections are currently treated.

Retrospective Review of Atypical Femoral Fracture in Metastatic Bone Disease Patients Receiving Denosumab Therapy.

BACKGROUND: Denosumab therapy is used to reduce skeletal-related events in metastatic bone disease (MBD). There have been reports of atypical femoral fracture (AFF) in osteoporotic patients treated with denosumab but none in the context of higher dose and more frequent denosumab therapy for MBD. The goal of this study was to assess the incidence of AFF in MBD. PATIENTS AND METHODS: We conducted a retrospective review of 253 patients who received a minimum of 12 doses of denosumab at 120 mg each for MBD. To identify patients with asymptomatic atypical stress reactions in the lateral subtrochanteric femur (which precede fractures), we reviewed the skeletal images of 66 patients who had received at least 21 doses of denosumab for AFF features. RESULTS: These patients received a median of 17 doses, with a median treatment duration of 23 months. There was 1 case of undiagnosed clinical AFF detected after chart review and 2 cases of subclinical atypical femoral stress reaction observed on imaging review after 23 doses of denosumab over 33 months, 28 doses over 27 months, and 21 doses over 21 months, respectively. Scout computed tomography films showed diffuse cortical thickening of diaphysis with localized periosteal reaction of lateral femoral cortex. Bone scan and magnetic resonance imaging scan of 2 patients with stress reactions confirmed the diagnosis. CONCLUSION: The incidence of clinical AFF in this context is 0.4% (1/253; 95% confidence interval [CI] 0.1%-2.2%), and the incidence of atypical femoral stress reaction based on imaging review is 4.5% (3/66; 95% CI 1.6%-12.5%). Clinicians should be aware of the clinical prodrome (which may or may not be present) and antecedent imaging changes associated with AFF. The Oncologist 2017;22:438-444Implications for Practice: Among patients with metastatic bone disease treated with denosumab, cases of clinical and subclinical atypical femoral fracture (AFF) are rare. The one detected case of clinical fracture went unrecognized despite prodromic symptoms. Clinicians should be aware of (a) the potential prodrome of anterior thigh/groin pain and (b) subclinical imaging changes in the lateral femur, both of which may precede clinical AFF.