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This article examines a hybrid graduate history course called "Teaching Hidden History." Team-taught in Summer 2015 across two universities, the course fundamentally tasked graduate students in history and history education with creating online learning modules based on the idea that hidden within any artifact is a larger historical narrative. Course objectives and activities encouraged students to think about how this narrative might take shape and, more broadly, how they could present history to their intended audiences. The authors share the story of the course development, include findings from an evaluation of the course and student work, and consider ways in which the initial iteration of the course might evolve to focus on specific components of historical thinking and student collaboration. They hope that others interested in hybrid humanities classrooms and digital history education may find ideas and outcomes to support furthering these fields.

Objective: The objective of this study was to establish a zone of clinical equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial, which will compare resection and endoprosthetic reconstruction to internal fixation for skeletal metastases of the proximal femur., Methods: A survey was developed, piloted, and distributed to self-declared interested stakeholders in the PERFORM trial. The survey targeted orthopedic oncologists and was designed to assess patient and bone lesion characteristics that drive surgical decision-making in the treatment of skeletal metastases in the proximal femur. An Ethics Waiver was obtained at the lead academic institution and data was collected in the REDCap survey database., Results: Responses were complete from 76 surgeons across North America, South America, Europe, Asia, and Africa. Response rate from self-declared interested stakeholders was 70%, with additional responses collected from a broader international audience. Responses indicate that a study population for which either resection and endoprosthetic reconstruction or internal fixation are acceptable options include (1) life expectancy at least 6 months, (2) bone loss of no more than 75% and no less than 25%, and (3) minimal to moderate risk for perioperative complications. Ninety-three percent of respondents indicated that they would be interested in participating in the PERFORM trial., Conclusion: A preliminary zone of equipoise for the PERFORM trial includes patients with 25-75% bone loss, low to moderate risk of operative complications, and life expectancy of at least 6 months. Further stakeholder discussions have finalized the PERFORM trial protocol prior to study initiation., Competing Interests: Ethics approval and consent to participate An Ethics Waiver for this study was obtained at the lead academic institution. Consent for participation was inferred by survey completion. Consent for publication Consent for publication of survey data was inferred by survey completion. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

The actions of the retinoic acid nuclear receptor gamma (RARγ) agonist, palovarotene, on pre-existing osteochondromas were investigated using a mouse multiple osteochondroma model. This approach was based on the knowledge that patients often present to the clinic after realizing the existence of osteochondroma masses, and the findings from preclinical investigations are the effects of drugs on the initial formation of osteochondromas. Systemic administration of palovarotene, with increased doses (from 1.76 to 4.0 mg/kg) over time, fully inhibited tumor growth, keeping the tumor size (0.31 ± 0.049 mm 3 ) similar to the initial size (0.27 ± 0.031 mm 3 , p = 0.66) while the control group tumor grew (1.03 ± 0.23 mm 3 , p = 0.023 to the drug-treated group). Nanoparticle (NP)-based local delivery of the RARγ agonist also inhibited the growth of osteochondromas at an early stage (Control: 0.52 ± 0.11 mm 3 ; NP: 0.26 ± 0.10, p = 0.008). Transcriptome analysis revealed that the osteoarthritis pathway was activated in cultured chondrocytes treated with palovarotene (Z-score = 2.29), with the upregulation of matrix catabolic genes and the downregulation of matrix anabolic genes, consistent with the histology of palovarotene-treated osteochondromas. A reporter assay performed in cultured chondrocytes demonstrated that the Stat3 pathway, but not the Stat1/2 pathway, was stimulated by RARγ agonists. The activation of Stat3 by palovarotene was confirmed using immunoblotting and immunohistochemistry. These findings suggest that palovarotene treatment is effective against pre-existing osteochondromas and that the Stat3 pathway is involved in the antitumor actions of palovarotene.

Introduction: Megaprostheses provide a reconstructive option for patients with bone loss after musculoskeletal tumor resection. However, the postoperative surgical site infection (SSI) risk is significant. This study aims to evaluate outcomes of extended postoperative antibiotic regimens in patients after megaprosthesis surgery and gather insight into strategies to minimize SSI., Methods: This retrospective cohort study evaluated patients who underwent megaprosthesis surgery by a single surgeon at a single center from 2014 to 2022. Patient demographics, comorbidities, cancer treatment details, and antibiotic regimens were collected. Excluded were patients with less than 1 year of follow-up, active infection at time of surgery, non-healing wounds unrelated to SSI, and preoperative antibiotic regimens secondary to being immunocompromised. Measures of interest included the development of SSI within 1 year of surgery and development of antibiotic-related complications., Results: Included were 49 patients, with a mean age of 61.2 ± 2.0 years and a mean BMI of 29.4 ± 7.0. The mean drain duration was 6.5 days (standard deviation [SD], 6.9 days), and the mean intravenous antibiotic administration duration was 6.4 days (SD, 6.9 days). The median time to drain removal was five days, and the median time for intravenous antibiotic cessation was five days. The mean total antibiotic administration duration (intravenous and oral) was 25.4 days (SD, 13.4 days). Only 1 patient in the included cohort (2.04 %) developed an SSI requiring operative intervention. No other patient within the cohort experienced an antibiotic-related complication., Discussion: This study suggests that the site's current protocol for managing post-megaprosthesis antibiotic prophylaxis based on drain duration and incision healing status has resulted in a low rate of SSI and antibiotic-related complications. Further research is needed to validate these findings and gain additional insights into managing antibiotic prophylaxis after megaprosthesis surgery., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Osteochondromas are cartilage-capped tumors that arise near growing physes and are the most common benign bone tumor in children. Osteochondromas can lead to skeletal deformity, pain, loss of motion, and neurovascular compression. Currently, surgery is the only available treatment for symptomatic osteochondromas. Osteochondroma mouse models have been developed to understand the pathology and the origin of osteochondromas and develop therapeutic drugs. Several cartilage regulatory pathways have been implicated in the development of osteochondromas, such as bone morphogenetic protein, hedgehog, and WNT/β-catenin signaling. Retinoic acid receptor-γ is an important regulator of endochondral bone formation. Selective agonists for retinoic acid receptor-γ, such as palovarotene, have been investigated as drugs for inhibition of ectopic endochondral ossification, including osteochondromas. This review discusses the signaling pathways involved in osteochondroma pathogenesis and their possible interactions with the retinoid pathway., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The number of arthroplasties conducted annually continues to increase; however, approximately 1%-2% of all knee and hip arthroplasties will become infected. These prosthetic joint infections are costly, difficult to treat, and cause significant morbidity and mortality as a direct result of conventional surgical and medical managements. In this perspective, we discuss factors that make these infections arduous to treat as well as the potential use of adjuvant bacteriophage therapy with debridement, antibiotics, and implant retention surgery to cure these infections without removing the infected prosthesis. We also provide rationale as to why future clinical trials evaluating this novel therapeutic will need to be designed as noninferiority trials, and we compare this approach to 2-stage revision surgery. If bacteriophage therapy continues to show effectiveness, this could revolutionize the treatment of prosthetic joint infections and pioneer new treatments for similar infections., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Spatially fractionated radiotherapy (GRID) has been utilized primarily in the palliative and definitive treatment of bulky tumors. Delivered in the modern era primarily with megavoltage photon therapy, this technique offers the promise of safe dose escalation with potential immunogenic, bystander and microvasculature effects that can augment a conventionally fractionated course of radiotherapy. At the University of Maryland, an institutional standard has arisen to incorporate a single fraction of GRID radiation in large (>8 cm), high-risk soft tissue and osteosarcomas prior to a standard fractionated course. Herein, we report on the excellent pathologic responses and apparent safety of this regimen in 26 consecutive patients., (©2020 by Radiation Research Society. All rights of reproduction in any form reserved.)

Objective: Most cutaneous squamous cell carcinomas (cSCC) are low risk and can be treated with simple excision or ablation. High-risk cSCC require invasive treatment, including radical surgery. We present our experience in treating invasive cSCC of the pelvis and extremities., Method: A retrospective review of the data of patients with invasive cSCC, indicated for surgery between 2014 and 2018, from a single institution was carried out., Results: A total of 19 patients (nine men, 10 women) were included in the study. Mean age was 62 years; mean tumour size was 8.6cm). Of the 19 patients, five patients with paraplegia with cSCC arising from hard-to-heal ulcers died of infection or bleeding after surgery or systemic therapy. Also, nine patients with localised cSCC underwent margin-negative resection with or without radiation; one patient experienced disease relapse. Of the participants, two patients with previous transplants and multifocal aggressive cSCC underwent numerous resections but succumbed to disease, and two patients who presented with locally recurrent disease after previous positive margin resection and radiation underwent re-resection but developed recurrent disease., Conclusions: Prognosis for invasive cSCC largely depends on clinical setting. Tumours arising from ulcers in patients with paraplegia have a poor prognosis regardless of treatment. Invasive cSCC in transplant patients are often multifocal and often recur. Debulking procedures are associated with local recurrence despite radiation. Patients presenting with localised disease have a favourable prognosis with wide resection, flap coverage and adjuvant therapy.

Chondrosarcoma is the second most common primary bone sarcoma. Treatment of chondrosarcoma is limited to surgery due to radiation and chemotherapy resistance of this cancer. An ideal treatment for chondrosarcoma would be a well-tolerated, minimally invasive local or systemic treatment modality to halt or slow tumor growth prior to resection of local, unresectable local, or metastatic disease. Palovarotene, an agonist of nuclear retinoic acid receptor γ (RARγ) has shown therapeutic action for treatment of heterotopic ossification and osteochondroma without serious adverse effects in animal models. We hypothesized that selective agonists of RARγ would have an inhibitory effect on chondrosarcoma. All human chondrosarcoma specimens expressed RARγ as determined by immunohistochemical staining. The ΗCS-2/8 chondrosarcoma cell line, established from low-grade human chondrosarcoma, was used to examine the actions of RARγ agonists. In ΗCS2/8 pellet cultures, RARγ agonist treatment reduced the mass size and significantly decreased total glycosaminoglycan, protein amounts, and gene expression levels of cartilage matrix molecules when compared with control groups. Systemic treatment with RARγ agonists significantly inhibited the growth of ΗCS-2/8 cell transplants in vivo. Furthermore, local injection of RARγ agonist-loaded poly-lactic acid nanoparticles induced regression of the mass size of the transplants. Histologic analysis demonstrated that RARγ agonist treatment inhibited cell proliferation activity and stimulated encapsulation of the tumor. These findings indicate that RARγ agonists, including palovarotene, may have an anti-tumor effect on low-grade chondrosarcomas. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1045-1051, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

A series of cis-dioxorhenium(V) complexes containing chiral tetradentate N 4 ligands, including cis-[Re V (O) 2 (pyxn)] + (1; pyxn = N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)cyclohexane-1,2-diamine), cis-[Re V (O) 2 (6-Me 2 pyxn)] + (cis-2), cis-[Re V (O) 2 (R,R-pdp)] + (3; R,R-pdp = 1,1'-bis((R,R)-2-pyridinylmethyl)-2,2'-bipyrrolidine), cis-[Re V (O) 2 (R,R-6-Me 2 pdp)] + (4), and cis-[Re V (O) 2 (bqcn)] + (5; bqcn = N,N'-dimethyl-N,N'-di(quinolin-8-yl)cyclohexane-1,2-diamine), were synthesized. Their structures were established by X-ray crystallography, showing Re-O distances in the range of 1.740(3)-1.769(8) Å and O-Re-O angles of 121.4(2)-124.8(4)°. Their cyclic voltammograms in MeCN (0.1 M [NBu 4 ]PF 6 ) display a reversible Re VI/V couple at E 1/2 = 0.39-0.49 V vs SCE. In aqueous media, three proton-coupled electron transfer reactions corresponding to Re VI/V , Re V/III , and Re III/II couples were observed at pH 1. The Pourbaix diagrams of 1·OTf, 3·OTf, and 5·OTf have been examined. The electronic absorption spectra of the cis-dioxorhenium(V) complexes show three absorption bands at around 800 nm (600-1730 dm 3 mol -1 cm -1 ), 580 nm (1700-5580 dm 3 mol -1 cm -1 ), and 462-523 nm (3170-6000 dm 3 mol -1 cm -1 ). Reaction of 1 with Lewis acids (or protic acids) gave cis-[Re V (O)(OH)(pyxn)] 2+ (1·H + ), in which the Re-O distances are lengthened to 1.788(5) Å. Complex cis-2 resulted from isomerization of trans-2 at elevated temperature. cis-[Re VI (O) 2 (pyxn)](PF 6 ) 2 (1'·(PF 6 ) 2 ) was obtained by constant-potential electrolysis of 1·PF 6 in MeCN (0.1 M [NBu 4 ]PF 6 ) at 0.56 V vs SCE; it displays shorter Re-O distances (1.722(4), 1.726(4) Å) and a smaller O-Re-O angle (114.88(18)°) relative to 1 and shows a d-d transition absorption band at 591 nm (ε = 77 dm 3 mol -1 cm -1 ). With a driving force of ca. 75 kcal mol -1 , 1' oxidizes hydrocarbons with weak C-H bonds (75.5-76.3 kcal mol -1 ) via hydrogen atom abstraction. DFT and TDDFT calculations on the electronic structures and spectroscopic properties of the cis-dioxorhenium(V/VI) complexes were performed.

Aim: To evaluate the local treatment-seeking behaviors of diabetics with a focus on the root causes of culture-specific barriers to treatment compliance and define targets for intervention., Methods: A cross-sectional survey was administered in the local language to 204 diabetic adults in rural and urban clinical settings. Fasting blood glucose level was measured in all participants prior to the survey. Questions included sociodemographic characteristics, treatment-seeking behavior, and perceptions of obstacles., Results: Out of 204 participants, predictors of at target status included age (OR 1.06, 95% CI 1.02-1.11) and rural living area (OR 1.92, 92% CI 1.02-3.60). Participants were commonly diagnosed with symptoms of diabetes (44.6%). Participants demonstrated frequent healthcare provider contact (51% in last one month, 74.5% in last three months). Accidental or purposeful deviation from the recommended medications or treatment plan was reported by 18.7% and 12.8%, respectively. From the sample, 111 participants (54.4%) were capable of receiving SMS messages and 79 (71.1%) were willing to receive messages about diabetes. The most frequently self-reported obstacles to diabetes management were: medication costs (49.3%), treatment costs (46.6%), diabetic diet (33.8%), lack of relief on current treatment (17.4%), and transportation (16.7%)., Conclusion: Though most diabetics have frequent encounters with healthcare providers and report compliant behaviors, the majority do not meet recommended diabetes management guidelines. Screening of at-risk populations, targeted SMS campaigns, or diabetes-specific training for healthcare providers may improve clinical outcomes., (Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Synovial chondromatosis (SCh) can undergo malignant transformation. Pathologic diagnosis of secondary synovial chondrosarcoma (SChS) is challenging and misdiagnosis may result in over- or undertreatment., Method: A systematic review revealed 48 cases of SChS published in 27 reports since 1957. Data was collected to identify findings indicative of SChS and outcomes of treatment., Results: At median follow-up of 18 months, patients were reported as alive (10%), alive without disease (22%), alive with disease (15%), dead of disease (19%), dead of pulmonary embolism (4%), and unknown (29%). Initial diagnosis of SChS (grade: low/unknown 48%, intermediate/high 52%) was after biopsy in 58%, local resection in 29%, and amputation in 13%. Seventy-four percent of patients underwent 1.8 (mean) resections. Patients treated prior to 1992 were managed with amputation in 79% of cases compared to 48% after 1992. Symptoms were present for 72 mos prior to diagnosis of SChS. Synovial chondrosarcoma demonstrated symptom progression over several months (82%), rapid recurrence after complete resection (30%), and medullary canal invasion (43%). The SChS tumor dimensions were seldom quantified., Conclusion: Malignant degeneration of synovial chondromatosis is rare but can necessitate morbid surgery or result in death. Pathognomonic signs for SChS including intramedullary infiltration are present in the minority of cases. Progression of symptoms, quick local recurrence, and muscle infiltration are more suggestive of SChS. Periarticular cortical erosion, extra-capsular extension, and metaplastic chondroid features are non-specific. Although poorly documented for SChS, tumor size is a strong indicator of malignancy. Biopsy and partial resection are prone to diagnostic error. Surgical decisions are frequently based on size and clinical appearance and may be in conflict with pathologic diagnosis.

Background: The most common modes of failure for megaprostheses are aseptic loosening followed by periprosthetic infection and stem fracture. Surgical technique for bone and implant exposure is controversial and may influence the success of revision and the need for additional future revisions. The purpose of this study was to evaluate the effectiveness of cortical fenestration for megaprosthesis revision, particularly for stem fracture., Methods: From 1985-2014, 196 adult and pediatric patients underwent limb salvage with a distal femoral or proximal tibial megaprosthesis (109 cemented, 87 pressfit). A retrospective chart review was performed to assess the rate of revision based on cemented or pressfit fixation and the use of a cortical window to extract the failed stem. Results: 27% (29 of 109) of cemented and 18% (16 of 87) of pressfit implants were revised for stem failure. The reasons for revision in the cemented group were loosening (62%), infection (24%), and stem fracture (13%). In the pressfit group, the reasons were loosening (43%), infection (31%), stem fracture (6%), limb-length discrepancy (6%), malrotation (6%), and local recurrence (6%). A cortical window was used in 10 of 45 initial revisions (7 cemented, 3 pressfit) including all of the stem fractures, and in 2 of 15 subsequent re-revisions., Conclusion: Cortical fenestration is an effective, bone-preserving method of implant extraction, particularly for broken or cemented stems. It is associated with low rates of loosening and no increase in periprosthetic fractures.

Background: Allograft reconstruction of oncologic resections involving the tibia can have unpredictable results. Prior studies have reported a high rate of complications and a long recovery period involving prolonged bracing, repeated procedures and extended periods of antibiotics., Methods: The case details of 30 tibial allografts (12 adults, 18 children; 20 intercalary, 7 hemicortical, 3 other) were reviewed retrospectively. Based on factors including function, pain, healing and infection, clinical outcomes were stratified into three categories: excellent, moderate, and poor., Results: The overall survival rate of the allografts was 66% at a mean follow-up of 42 mos (adults) and 63 mos (children). Healing for metaphyseal junctions was successful in 73% at a mean of 44 weeks and for diaphyseal junctions, 64% at 41 weeks. Intercalary allografts in adults (4 of 20) all became infected and none had excellent results. All hemicortical allografts were performed in adults and 6 of 7 had excellent results. Distal intercalary allografts in children (6 of 20) had either excellent or moderate results with no infections, but had 3 nonunions and 2 fractures. Proximal intercalary allografts in children (8 of 20) had 2 excellent results, but had 6 infections requiring a cement spacer. Five of the six spacers were ultimately revised to another allograft or an arthroplasty., Conclusion: For tibial allograft reconstruction, surgeons and patients should prepare for a prolonged treatment course that may include multiple complications and surgeries. Excellent or moderate results can be achieved eventually in most, but amputation may be necessary in 15-20% of cases.

Purpose: The proximal humerus is a common location for both primary and metastatic bone tumors. There are numerous reconstruction options after surgical resection. There is no consensus on the ideal method of reconstruction., Methods: A systematic review was performed with a focus on the surgical reconstructive options for lesions involving the proximal humerus., Results: A total of 50 articles and 1227 patients were included for analysis. Reoperation rates were autograft arthrodesis (11%), megaprosthesis (10%), RSA (17%), hemiarthroplasty (26%), and osteoarticular allograft (34%). Mechanical failure rates, including prosthetic loosening, fracture, and dislocation, were highest in allograft-containing constructs (APC, osteoarticular allograft, arthrodesis) followed by arthroplasty (hemiarthroplasty, RSA, megaprosthesis) and lowest for autografts (vascularized fibula, autograft arthrodesis). Infections involving RSA (9%) were higher than hemiarthroplasty (0%) and megaprosthesis (4%). Postoperative function as measured by MSTS score were similar amongst all prosthetic options, ranging from 66% to 74%, and claviculo pro humeri (CPH) was slightly better (83%). Patients were generally limited to active abduction of approximately 45° and no greater than 90°. With resection of the rotator cuff, deltoid muscle or axillary nerve, function and stability were compromised even further. If the rotator cuff was sacrificed but the deltoid and axillary nerve preserved, active forward flexion and abduction were superior with RSA., Discussion: Various reconstruction techniques for the proximal humerus lead to relatively similar functional results. Surgical choice should be tailored to anatomic defect and functional requirements.

Background: Severe postoperative knee contractures after arthroplasty or megaprosthesis reconstruction occur rarely, but are devastating complications. Management of preoperative flexion contractures is well-described, but there is a paucity of literature for surgical treatment of postoperative contractures. A retrospective chart review was performed for a single surgeon of cases between 1996 and 2014., Results: Nine patients (5 of 66 for pediatrics; 4 of 95 for adults) underwent surgical release for severe stiffness after implantation of knee megaprosthesis. The total arc of motion was improved from a preoperative mean of 34° (range, 10° to 70°) to a postoperative mean 89° (63° to 125°). The amount of extension improved by a mean of 27° (range, -3° to +70°) and the amount of flexion improved by a mean of 28° (range, -10° to +75°)., Conclusion: Surgical release of severe postoperative knee contracture is a challenging procedure, but in most cases, the amount of extension and flexion can be improved, yielding a greater total arc of motion.

Introduction: The gender-specific total knee arthroplasty (TKA) debate focuses on differences in distal femoral mediolateral to anteroposterior aspect ratio between males and females. However, randomized studies have been unable to demonstrate significant differences in outcomes utilizing gender-specific implants. No studies have examined the effect of intermediate femoral component sizes on outcome. We compared outcomes before and after intermediate sizing availability., Materials and Methods: We identified 331 patients (413 knees) who underwent primary TKA between 2003 and 2004 with a single complete knee system. There were 121 males and 210 females. Three intermediate femoral sizes were added in March 2004 to the six initial options. Patients before March 2004 were assigned to group 1 (n=178), and after to group 2 (n=235)., Results: Follow-up averaged 8.5 years. Preoperative demographics and clinical scores were similar between groups. Knee Society (KS) clinical and functional scores improved in females in both groups, but there was no significant difference. Male patients in group 2 had a significant improvement in KS clinical scores compared to male patients in group 1 (group 1: 33.9, group 2: 41.1; p=0.01). Females in group 2 had significantly less need for manipulation, 1.9%, versus females in group 1, 8.7% (p=0.01). MUA rates were similar for men between groups. Overall, there were 19 revisions (4.6%) with no differences between groups or by genders. Once intermediate sizes were available, they were used in 48% of females and 13% of males. The average femoral component size for females in group 1 was 65 mm and decreased in group 2 to 62.5 mm. The average size of femoral components in males was 70 mm in both groups., Conclusions: Availability of intermediate size femoral component sizes was associated with a lower rate of manipulation in female patients. Greater KS clinical score improvement was observed in men after availability of additional femoral sizes.

Background: Pelvic Ewing sarcoma (ES) has poorer outcomes than extremity-based lesions and the method of local control is controversial., Methods: A retrospective review was performed of 40 primary pelvic or sacral ES treated by a single surgeon. All received modern chemotherapy and those that received radiation were treated with modern dosages., Results: Fifty-five percent were disease-free at latest follow-up (median, 83.1 mos). Sixty-one percent had ≥ 99% necrosis, which was associated with 65% disease-free survival. Larger size (P = 0.016) and the absence of metastatic disease (P = 0.005) was predictive of survival. Eighty-three percent of relapsed patients were DOD. Half of patients who received surgery alone or RT alone have NED while 57% of those who received S/RT have NED. Complication rates were 69% (S/RT), 75% (surgery alone), 10% (RT alone). Functional outcomes were similar., Conclusion: Primary pelvic ES is localized at presentation in 50% and the absence of metastases is the strongest predictor for survival. Chemotherapy is key, but excellent histologic response is neither a guarantee nor a necessity for survival. More than one-third die despite an excellent histologic response and at least one-third with lung metastases survive. With chemotherapy, radiation, and surgery, reasonable control of disease can be achieved., Level of Evidence Iii: Case-control or retrospective cohort study., (© 2015 Wiley Periodicals, Inc.)

Purpose: There is conflicting evidence whether custom instrumentation for total knee arthroplasty (TKA) improves component position compared to standard instrumentation. Studies have relied on long-limb radiographs limited to two-dimensional (2D) analysis and subjected to rotational inaccuracy. We used postoperative computed tomography (CT) to evaluate preoperative three-dimensional templating and CI to facilitate accurate and efficient implantation of TKA femoral and tibial components., Methods: We prospectively evaluated a single-surgeon cohort of 78 TKA patients (51 custom, 27 standard) with postoperative CT scans using 3D reconstruction and contour-matching technology to preoperative imaging. Component alignment was measured in coronal, sagittal and axial planes., Results: Preoperative templating for custom instrumentation was 87 and 79 % accurate for femoral and tibial component size. All custom components were within 1 size except for the tibial component in one patient (2 sizes). Tourniquet time was 5 min longer for custom (30 min) than standard (25 min). In no case was custom instrumentation aborted in favour of standard instrumentation nor was original alignment of custom instrumentation required to be adjusted intraoperatively. There were more outliers greater than 2° from intended alignment with standard instrumentation than custom for both components in all three planes. Custom instrumentation was more accurate in component position for tibial coronal alignment (custom: 1.5° ± 1.2°; standard: 3° ± 1.9°; p = 0.0001) and both tibial (custom: 1.4° ± 1.1°; standard: 16.9° ± 6.8°; p < 0.0001) and femoral (custom: 1.2° ± 0.9°; standard: 3.1° ± 2.1°; p < 0.0001) rotational alignment, and was similar to standard instrumentation in other measurements., Conclusions: When evaluated with CT, custom instrumentation performs similar or better to standard instrumentation in component alignment and accurately templates component size. Tourniquet time was mildly increased for custom compared to standard.

Giant cell tumor of bone is a locally aggressive lesion with a predilection for local recurrence, and in a small proportion of patients, metastatic disease can develop. Surgery is the mainstay of management for extremity-based lesions. For tumors located in challenging anatomical locations such as the sacrum and spine however, surgery may be associated with unacceptable functional morbidity. There are limited data regarding other treatment modalities such as radiation therapy, cytotoxic chemotherapy, interferon and bisphosphonates. Serial arterial embolization can be effective in some cases. Recent evidence has demonstrated denosumab to be a promising agent in the treatment of unresectable or metastatic disease.

Systemic lupus erythematosus (SLE) is a multisystem chronic disease with a multitude of clinical presentations. We review and synthesize how an environmental insult (exposure to extreme cold for a short duration) and endogenous (antiphospholipid antibody syndrome, SLE vasculitis) insults in a susceptible young female with lupus (peripheral arterial disease, smoking, SLE) led to a perfect storm resulting in catastrophic injuries (frostbite)., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background/aim: The purpose of this study was to analyze the incidence and survival in all sarcomas based on year of diagnosis, anatomical site, grade, stage, and age of patient., Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for the years 1975 to 2009 and included 18 registries across the United States representing 28% of the national population. Incidence rates for 2005-2009 and five-year survival rates for 2000-2004 were calculated for all categories of sarcomas for multiple key variables., Results: Sarcomas are rare, with most occurring in fewer than 5 per 1,000,000. The most common were leiomyosarcoma, Kaposi sarcoma, malignant fibrous histiocytoma, liposarcoma and fibrosarcoma. Survival was poorer for those with more advanced grade, stage, and age at-diagnosis. Most sarcomas affected the lower extremities, followed by the upper extremities and torso. Pelvic tumors were less common, but generally led lower survival than lesions of the extremities., Conclusion: The epidemiology of sarcomas varies widely by type and other variables. Incidence and survival data provide valuable information for patient counseling and may have implications in understanding the natural history of sarcoma. This study represents the most recently updated comprehensive report on all types of sarcomas in the United States.

Background: Current cartilage transplantation techniques achieve suboptimal restoration and rely on patient donor cells or living grafts of chondrocytes., Purpose: We sought to enhance allogeneic grafts by testing mosaics of genetically engineered and naïve juvenile human chondrocytes (jCh)., Methods: We obtained specimens from three humans and performed three experiments (two in vitro, one in vivo). We compared neocartilage with and without (1) supplemented serum-free medium (chondrocyte differentiation medium [CDM]), (2) adenoviral BMP-2 (AdBMP-2) transduction, and (3) varying ratios (0.1-1) of transduced and naïve jCh. We compared (4) healing with mosaic grafts with naïve neocartilage or marrow stimulation in immunosuppressed rats. For each of 10 in vitro treatment groups, we had six replicates for each human, and for each of three in vivo treatment groups, we had four replicates for one human. We scored the histology with the semiquantitative Bern score., Results: AdBMP-2 and naïve neocartilage growth in CDM were histologically superior (Bern score, 5.2 versus 3.7; 8.0 versus 1.8) and size (8.0 versus 6.1; 7.9 versus 2.2 mg) to standard medium. In CDM, AdBMP-2 decreased viability (76% versus 90%), but increased BMP-2 production (619 ng/mL versus 43 pg/mL). Ten percent and 25% AdBMP-2 transduction had Bern scores of 6.8 and 6.5 and viability of 84% and 83%, respectively. Twenty-five percent mosaic grafts provided better healing histologically than marrow stimulation or naive neocartilage., Conclusions: Low-level AdBMP-2 and CDM augment neocartilage parameters in vitro and vivo., Clinical Relevance: Genetic augmentation of jCh and creation of mosaic neocartilage may improve graft viability and articular healing compared with naïve neocartilage.

A growing interest exists in the diagnosis and treatment of femoroacetabular impingement. Although cam morphology of the proximal femur may conceptually appear to be a relatively simple topographical aberrancy, it is actually positioned amid a complex developmental, kinematic, and biomechanical region of the human body. The authors introduce a new classification scheme and review the historical and anthropological considerations, biomechanics, and genetic factors involved in cam morphology., (Copyright 2012, SLACK Incorporated.)

Background: Coronal malalignment occurs frequently in TKA and may affect implant durability and knee function. Designed to improve alignment accuracy and precision, the patient-specific positioning guide is predicated on restoration of the overall mechanical axis and is a multifaceted new tool in achieving traditional goals of TKA., Questions/purposes: We compared the effectiveness of patient-specific positioning guides to manual instrumentation with intramedullary femoral and extramedullary tibial guides in restoring the mechanical axis of the extremity and achieving neutral coronal alignment of the femoral and tibial components., Methods: We retrospectively reviewed 569 TKAs performed with patient-specific positioning guides and 155 with manual instrumentation by two surgeons using postoperative long-leg radiographs. For all patients, we assessed the zone in which the overall mechanical axis passed through the knee, and for one surgeon's cases (105 patient-specific positioning guide, 55 manual instrumentation), we also measured the hip-knee-ankle angle and the individual component angles with respect to their mechanical axes., Results: The overall mechanical axis passed through the central third of the knee more often with patient-specific positioning guides (88%) than with manual instrumentation (78%). The overall mean hip-knee-ankle angle for patient-specific positioning guides (180.6°) was similar to manual instrumentation (181.1°), but there were fewer ± 3° hip-knee-ankle angle outliers with patient-specific positioning guides (9%) than with manual instrumentation (22%). The overall mean tibial (89.9° versus 90.4°) and femoral (90.7° versus 91.3°) component angles were closer to neutral with patient-specific positioning guides than with manual instrumentation, but the rate of ± 2° outliers was similar for both the tibia (10% versus 7%) and femur (22% versus 18%)., Conclusions: Patient-specific positioning guides can assist in achieving a neutral mechanical axis with reduction in outliers.

Understanding acetabular cup orientation is important in all aspects of total hip arthroplasty including preoperative planning, intraoperative positioning, and postoperative analysis. New concepts in ideal cup orientation such as 'combined anteversion' have emerged. Using computer navigation and three-dimensional imaging, the potential for accuracy and precision of implantation have improved. Nevertheless, the varying manner in which the terms "anteversion" and "abduction" are often used in the literature is indicative of a nebulous understanding of the complex spatial anatomy of acetabular cup orientation.

Restoration of an overall neutral mechanical axis has been a long-held tenet in total knee arthroplasty (TKA). Numerous biomechanical, finite element, and clinical studies have demonstrated that coronal malalignment, particularly varus, is associated with increased strain, higher failure rates, and, in some cases, poorer outcomes. With advances in computer-assisted navigation, 3-dimensional imaging, and patient-specific positioning guides, the potential for greater precision in bone resection and component positioning has rekindled interest in this important issue. Several recently published studies demonstrating no difference in survivorship for malaligned TKAs have challenged the concept of an alignment safe zone. Some surgeons have discussed a paradigm shift in defining optimal alignment. While we agree that compared to several decades ago, there is greater understanding of TKA kinematics and that broad targets for alignment may not impart significant benefit as a dichotomous variable, there are multiple reasons why neutral alignment and classic bone cuts remain valid and important in delivering a successful TKA. In comparison to the preponderance of evidence advocating a neutral mechanical axis and approximately 5° to 7° valgus anatomic alignment, there is insufficient support for reasonably choosing any other target. Although technology has improved surgical precision, it has not eliminated the human factor, and aiming for neutral provides the safest margin for error. The foremost objective of TKA is a durable and well-functioning joint, not necessarily one that replicates normal or the patient's native condition. While the latter goal is certainly desirable, the priority of the former should never be overlooked., (Copyright 2011, SLACK Incorporated.)