Bilateral first metatarsophalangeal joint arthrodesis: An investigation of functional, surgical and radiological outcomes.

BACKGROUND: First metatarsophalangeal joint (MTPJ) arthrodesis is a commonly utilised procedure. In this study, the authors aim to explore functional outcomes of patients undergoing nonsynchronous bilateral first MTPJ arthrodesis under the care of a single surgeon using a compression screw/locking plate construct. METHODS: This is a prospectively collected, retrospectively analysed case series of fifty five patients who underwent bilateral nonsynchronous first MTPJ arthrodesis. Clinical and radiological outcomes were assessed preoperatively and at a minimum of two years postoperatively. Clinical outcomes were assessed using the Foot and Ankle Outcome Score (FAOS), the Self-Reported Foot and Ankle Score (SEFAS) and the Sports Questionnaire version 1 (SQ). Postoperative radiographs were used to assess evidence of union and compare both hallux valgus and intermetatarsal angles. Removal of hardware, revision surgery and correction of deformities were also recorded. RESULTS: Fifty five patients were included in the study. There was statistically significant improvements in all five facets of the FAOS (p value < 0.05). The mean postoperative SEFAS was 45.1. In total, patients participated in thirteen different sporting activities. This represented 92 patient specific activities preoperatively and 104 postoperatively. The most common activities were walking, cycling and swimming. Overall, 94.5% (N = 52) of the cohort were satisfied with their return to sport while 98.2% (N = 54) would recommend bilateral first MTPJ arthrodesis. Mean reductions in hallux valgus angles and intermetatarsal angles were noted at 18.87 and 4.69 degrees respectively. There was one non-union in the cohort which required revision surgery. One patient required removal of hardware. CONCLUSIONS: Bilateral first MTPJ arthrodesis is a safe and effective surgical option for patients with bilateral first MTPJ pathology. It has a high union rate, low complication rate and significantly improves clinical outcomes and allows patients reliably return to physical activities.

Outcomes following tibiotalocalcaneal arthrodesis using a solid posterior offset intramedullary nail in 44 patients with a minimum 30-month follow-up.

BACKGROUND: Tibiotalocalcaneal arthrodesis is frequently performed by foot and ankle surgeons in the management of complex ankle and hindfoot pathology. In this study, the authors describe the clinical and radiological outcomes of tibiotalocalcaneal arthrodesis using a solid posterior offset hindfoot arthrodesis nail. METHODS: Forty-four consecutive patients underwent tibiotalocalcaneal arthrodesis by a single surgeon operating in two centers. Clinical and radiological outcomes were assessed preoperatively and at 6-month, 12-month and final follow-up (mean 47 months). Clinical outcomes were assessed with VAS, AOFAS and MOXFQ scores. Serial radiographs were used to assess union at each follow-up visit. RESULTS: Forty-four patients attended 12-month and final follow-up (mean 47 months). A total of 44 (100%) ankle joints and 44 (100%) subtalar joints were completely united at 12-month follow-up. The VAS score improved significantly from a mean of 6.5 preoperatively to a mean of 0.98 at final follow-up (P = <0.0001). AOFAS score improved significantly from a mean of 36.4 preoperatively to a mean of 73 at final follow-up (P = <0.0001). MOXFQ score improved significantly from a mean of 44.5 preoperatively to a mean of 12.7 at final follow-up (P = <0.0001). The mean change in frontal plane alignment was 5.7 degrees (P = 0.005). A total of 6 patients (13.6%) had an adverse event during the course of the study. CONCLUSIONS: Tibiotalocalcaneal arthrodesis with a solid posterior offset hindfoot arthrodesis nail is a safe and effective surgical option for patients with severe ankle and hindfoot pathology. It has a high union rate, low complication rate and significantly improves clinical outcomes.

Reducing deaths and injury from road traffic crashes through multisectoral collaboration.

Introduction: road traffic injuries are the eighth cause of mortality globally, killing about 1.35 million people and leaving more than 50 million others with permanent injuries and disabilities yearly. In Tanzania, the impact of road traffic crashes is still high despite a noticeable reduction in the number of associated injuries. This paper seeks to lay the foundation for promoting multisectoral actions and collaborations in dealing with public health concerns due to increased consequences caused by road traffic deaths and injuries. Methods: in 2015, a multisectoral approach was adopted to implement a 5-year (2015-2020) road safety program that aimed to advocate for amendment of the Road Traffic Act of 1973, Chapter 168 Revised Edition 2002. A series of consultative sessions were held between government and non-state actors, including different committees formed to feed each other on the agenda. The program was implemented through the Ministry of Health and the Ministry of Home Affairs in collaboration with World Health Organisation and civil society organisations. Results: it has been noted that there is a direct relation with a set of combined policy-level interactions seeking to improve the legal environment for road safety. The program committee, civil society organisations, and parliamentarians' forum were solicited as essential stakeholders in advancing policy reform. Together they conducted a series of consultative meetings, resulting in having a Bill tabled in the Parliament as a first draft. This informed policymakers and raised their attention to the magnitude of road traffic crashes and the country's social and economic burden. Conclusion: efforts still need to be expanded to analyse the existing data to understand the extent to which risk factors contribute to road crashes, injuries, and deaths. There is a need to have a strong Government involvement in strengthening ownership and sustainability of any public health intervention, such as road safety.

Battle of the titans: Survivorship analysis of the 3 most common types of uncemented femoral stems used across national registries.

Background: Although many institutions utilize uncemented stems as routine in performing total hip arthroplasty (THA), many surgeons continue to rely on outcomes reported in the literature in the form of small cohorts and patient series when analyzing survivorship for specific implants. The purpose of this study was to identify and analyze the survivorship of the 3 most common uncemented stem types (as opposed to brands) used across multiple national joint registries. Methods: A review of data available from all national joint registries was carried out in July 2022. Analysis of each individual registry and classified uncemented implants into the seven different uncemented stem types. The 3 most common stem types were identified, and average cumulative revision rates calculated. Metal on metal bearings surface implants were excluded from this study due to high revision rates across all implant types. Results: Our detailed review identified 6 out of 13 (NJR, AOANJRR, LROI, EPRD, MARCQI and the NZJR) international registries reporting implant specific survivorship on uncemented femoral stems; including 960,328 uncemented stems across all registries. The most common type of stem used was type 3c, accounting for 61% (583,724), followed by type 1 stems with 23% (217,897) and type 2 stems with 8% (79,257). Cumulative revision rates at 13 years follow-up for these stems ranged from 6.9% to 7.9%. Conclusion: Although all stem types have comparable revision rates across all registries, the most common uncemented stem reported was the type 3c, tapered rectangular fully coated stem. Furthermore, out of all type 3c, the Müller design philosophy with full hydroxyapatite coating seems to be the most sought after worldwide. In this study we can conclude, thus far, that there does not appear to clinical or statistical differences in revision rates between the different stem types. Level of evidence: III.

Does previous fragility fracture impact upon mortality in a hip fracture cohort? a retrospective study.

BACKGROUND: Fragility fractures are described as fractures resulting from low-energy trauma and are considered diagnostic of reduced bone mineral density or osteoporosis. They often present as hip fractures with hip fractures remaining a common but devastating injury among older patients. Many factors influence a patient's risk of hip fracture and their subsequent risk of death. AIM: In this study, we examined if previous fragility fracture impacts upon mortality after hip fracture. METHODS: This was a retrospective single-center cohort study of patients included in the Irish Hip Fracture registry over a 5-year time period. Epidemiological data including gender, age, type of fracture, type of surgery, bone protection medication, American Society of Anesthetics (ASA) grade, and post-fracture outcomes including death at 30 days and death at 1 year were recorded. The presence or absence of a previous fragility fracture was examined to explore if a previous fragility fracture was an independent predictor of mortality. RESULTS: There were 964 patients included, and 290 of whom had sustained a previous fragility fracture; 289 patients were males and 675 females, 33 patients had died in the 30 days following their surgery, and 180 patients had died within 1 year. We found statistically significant results for gender and age but not for previous fragility fracture influencing mortality (p value 0.230). CONCLUSION: We found that previous fragility fracture does not impact upon mortality in a hip fracture cohort. However, gender and age did impact upon mortality in this study.

Prosthetic femoral interposition arthroplasty with adult humeral implant, for children with cerebral palsy and symptomatic hips.

BACKGROUND: Immobile patients with cerebral palsy can suffer with painful dislocated hips. Decision-making and surgical management can prove challenging in this cohort of patients, with hips that cannot be reconstructed. METHODS: We conduced a retrospective chart review of all patients who underwent prosthetic femoral interposition arthroplasty (PFIA) by two surgeons from 2013 to 2021, for unreconstructable hips. We compared pain and range of motion in preoperative period to the postoperative period. Caregiver reported outcomes were used to assess satisfaction post operatively. During the follow up, radiographs of the PFIA were obtained to assess for proximal migration, heterotopic ossification and loosening of implants. RESULTS: Eleven index surgeries, which met the inclusion criteria, were included in this study. These were performed in eleven patients with an average follow up of 45 months. Regarding pain and range of motion post-operatively an excellent or good result was seen in nine cases. Two patients were classified as having a fair result with none having a poor result. Most caregivers reported being satisfied or very satisfied with the post-operative outcomes. CONCLUSION: A prescriptive operative solution to the painful dislocated hip in children with spastic cerebral palsy remains elusive. In this study, we have demonstrated both clinically and radiologically satisfactory results post proximal femoral interposition arthroplasty, for those patients with unreconstructable hips. Patient caregiver reported outcomes, show that the majority of caregivers were satisfied or very satisfied with the outcome of the surgery.

Modern Internet Search Analytics and Osseointegration: What are Patients Asking and Reading Online?

Background: Osseointegration (OI) limb has been performed for over 30 years and is an example of an advance in technology and surgical technique which has led to improvements in patient mobility and quality of life. An increasing number of patients seek information about osseointegration. The aim of this study was to categorise the most frequently asked questions by patients using the Google search engine and the most frequently accessed websites with the highest return on answers. The secondary aims of this study were to assess the quality of the information provided on those websites and to stratify, by category, which websites provide the best quality information. Materials and methods: Ten permutations and conjugations of the word 'osseointegration' were entered into Google. The first fifty 'People also ask' and associated websites by Google's machine learning and natural language processing engine were collected for each search term. The Rothwell classification system of questions by topic (Fact, Value, Policy) and websites by category was used (Commercial, Academic, Medical Practice, Single Surgeon Personal, Government, Social Media). Website quality was assessed using the Journal of the American Medical Association (JAMA) benchmark criteria (Likert-style rating 0-4). Pearson's Chi-squared and Student's t-tests were performed for statistical analysis as appropriate (significance, p < 0.05). Results: The 10 search terms generated 454 questions and referenced 408 websites. Of the 454 questions generated, the most common question categories were fact (70.8%), value (19.2%), and policy (10%). The most common website type was social media (37.4%). The most common question types were technical details (30.4%), specific activity (20.6%), and cost (14.1%). Only 1.6% of questions related to risks and complications. Generally, website quality was poor with 64.1% having a JAMA score of 0 or 1. Websites that were categorised as 'Government' had the highest overall JAMA scores: 71.4% had a score of 4. Conclusion: Based on Google search engine's results, the most commonly asked questions about osteointegration related to technical details, specific activities and cost; only 1.6% related to risks and complications. Interestingly, social media websites represented the highest volume of search result referrals. Overall, the quality of websites was poor with the most factual information coming from governmental websites. How to cite this article: Murphy EP, Sheridan GA, Page BJ, et al. Modern Internet Search Analytics and Osseointegration: What Are Patients Asking and Reading Online? Strategies Trauma Limb Reconstr 2023;18(3):163-168.

NR4A1-3 nuclear receptor activity and immune cell dysregulation in rheumatic diseases.

The development and progression of immune-mediated rheumatic disease (IMRD) involves dysfunction of innate and adaptive immune cell populations leading to altered responses including inflammasome activation, dysregulated cytokine networks, increased immune cell numbers and multifaceted cell-cell communication. Several rheumatic diseases are further characterized by the presence of autoantibodies, immune complex mediated complement activation and the deficit of peripheral immune tolerance due to reduced regulatory T-lymphocyte cell function. Ultimately, in rheumatic disease the loss in cellular and tissue homeostasis culminates in the advancement of chronic inflammation. The three members of the NR4A subfamily of nuclear receptors are immediate early genes, and act as potent transcriptional responders to changes in the cellular and tissue microenvironment. Subfamily members are rapidly expressed in diseases characterized by inflammation and function to control the differentiation and activity of innate and adaptive immune cells in a cell-type and cell-context specific manner. Rheumatic disease including rheumatoid-, psoriatic-, osteo-arthritis and systemic sclerosis display altered NR4A1-3 activity in controlling immune cell migration and function, production of paracrine signaling molecules, synovial tissue hyperplasia, and regulating cartilage turn-over in vivo. Additionally, NR4A1-3 activities mediate cytokine, prostanoid and growth factor signaling to control angiogenesis, modulate the regulatory functions of mesenchymal stromal cells, alter the activation status of dendritic cells, influence the generation of peripheral myeloid and T-lymphocyte lineages and promote the maintenance of functional regulatory T-cells. Further reports uncover the potential of moderating NR4A 1-3 receptors as therapeutic targets in altering immune tolerance, pathological angiogenesis and controlling inflammation in several models of disease.

Children's Hip Predictive (CHiP) Score: A Triage Tool for Hip Dislocation in Children Referred With Suspected Hip Dysplasia.

BACKGROUND: A fundamental tenent of treating developmental dysplasia of the hip is to identify patients with dislocated hips early so as to avoid the long-term sequelae of late diagnosis. The aim of this study was to develop a readily useable triage tool for patients with suspected hip dislocation, based on the clinical history and examination findings of the referring practitioner. METHODS: All primary care referrals (n=934) over a 3-year period for suspected developmental dysplasia of the hip to a tertiary pediatric center were evaluated. Defined parameters with respect to history and clinical examination were evaluated. Multivariable logistic regression was used to establish predictors of hip dislocation, and from this a predictive model was derived which incorporated significant predictors of dislocation. An illustrative nomogram translated this predictive model into a usable numerical scoring system called the Children's Hip Prediction score, which estimates probability of hip dislocation. RESULTS: There were 97 dislocated hips in 85 patients. The final predictive model included age, sex, family history, breech, gait concerns, decreased abduction, leg length discrepancy, and medical/neurological syndrome. The area under receiver operating curve for the model is 0.761. A Children's Hip Prediction score of≥5 corresponds to a sensitivity of 76.3% and a score of≥15 has a specificity of 97.8%, corresponding to an odds ratio of 27.3 for increased risk of dislocation. CONCLUSION: We found that a novel clinical prediction score, based on readily available history and examination parameters strongly predicted risk of dislocations in hip dysplasia referral. It is hoped that this tool could be utilized to optimize resource allocation and may be of particular benefit in less well-resourced health care systems. LEVEL OF EVIDENCE: Level II.

Review of the Role of Intraoperative Neurophysiological Monitoring in Spinal Surgery With a Focus on the True and False Positives and a Clinical Correlation.

BACKGROUND: Spinal surgery is a technically challenging endeavor with potentially devastating complications. Intraoperative neurophysiological monitoring (IONM) is a method of preventing and identifying damage to the spinal cord. OBJECTIVE: The aim of our study was to examine the clinical utility of IONM in spinal surgeries performed at our institution and what effect, if any, subsequent interventions had on postoperative patient outcomes. METHODS: This is a retrospective cohort study of 169 patients who underwent spinal surgery with IONM at 2 institutions between 2013 and 2018. Signal changes detected were recorded as well as the surgeon's response to these changes. Neurological status was recorded using a standard neurological examination and characterized as per the McCormick Neurological Scale. Patients were followed up for 12 months after surgery. RESULTS: A total of 169 spinal surgery cases with concurrent use of spinal cord monitoring were carried out in our institution between 2013 and 2018. The youngest patient was 14 years old, and the oldest was 92 years old (mean, 51.9 ± 19.6 years). There were 100 female patients and 69 male patients. Most patients (n = 124) had no signal changes. Signal changes were observed in 26.6% of the cases (n = 45). Most of these signal changes were rectified through repositioning of the patient (n = 24). The other 21 patients saw no improvement in their signals before the end of their procedures; however, these 21 patients had no postoperative deficits (grade I). This brought the false positive rate to 38% (21/55); the false negative rate was 1.8% (3/169). CONCLUSION: This study showed similar outcomes in patients whether IONM signals were recovered or not. The false positive and false negative rates were high. Our study helps to raise awareness about IONM's strengths and weaknesses to inform future clinical practice. We recommend prioritizing clinical judgment in spinal surgery cases and using IONM with caution.

Collagenase and the Treatment of Dupuytren Contracture: Efficacy of Treatment and Patient Satisfaction.

Background: Collagenase clostridium histolyticum has become a widely used treatment in the management of Dupuytren disease. The aims of this study are to assess the immediate success of treatment of Dupuytren contracture with collagenase injection, to measure long-term patient-rated outcomes, to determine whether the risk factors for the disease impacted outcomes and to report complications of collagenase treatment. Methods: A prospective study was performed in a tertiary referral centre. Measurements were recorded pre-treatment, day 1 and day 90. Patient-rated outcome scores were measured using Disability of the Arm, Shoulder and Hand questionnaire (DASH) and the Michigan Hand Questionnaire (MHQ) at minimum 36 months post-injection. Results: The study included 45 patients with 53 hands with a mean age of 65.7 years. The treatment was successful in 62% of patients with the greatest improvement in the metacarpal-phalangeal joint of the little finger. Diabetes, epilepsy, gender, alcohol intake and positive family history had no statistically significant predictive value on successful outcomes. Patient satisfaction at 41 months was high with mean MHQ score of 97.3. Conclusions: Collagenase is effective in the treatment of Dupuytren contracture, with disease involving the little finger showing the greatest benefit. Risk factors for development of Dupuytren disease had no effect on successful outcome and long-term satisfaction rates are high. Level of Evidence: Level III (Therapeutic).

Functional Capabilities After First Metatarsal Phalangeal Joint Arthrodesis Using a Locking Plate and Compression Screw Construct.

Arthrodesis of the first metatarsal phalangeal joint (MTPJ) is a widely utilized surgical procedure for a wide array of metatarsal pathologies. This study aims to explore the functional limitations following first MTPJ arthrodesis, overall satisfaction and patient's abilities to achieve activities of daily living (ADL). This prospective cohort study assessed functional limitations as well as footwear and lifestyle restrictions using several questionnaires. One hundred and three participants who had a first MTPJ arthrodesis under the care of a single surgeon were recruited. Pre- and postoperative patient-reported outcome measures were recorded. The American Orthopaedic Foot and Ankle Score (AOFAS) and the Manchester-Oxford Foot Questionnaire were also used to further examine functional status. Hallux valgus angle (HVA) and intermetatarsal angle (IMA) were compared using preoperative and postoperative weightbearing radiographs and successful fusion was recorded. Complications were documented and are discussed in detail. The duration of follow-up was more than 12 months. There was one nonunion in the cohort while 2 patients experienced delay to fusion. Approximately 97% of patients were very satisfied with the procedure and their ability to achieve ADLs post operatively. A further 82.5% of patients were able to return to wearing nonadaptive footwear. The mean reduction in HVA and IMA was 21.78° and 6.84°, respectively. This study demonstrates the safe and successful use of a compression screw/locking plate construct for arthrodesis of the first MTPJ. Furthermore, the study provides clear evidence of high levels of functionality after the procedure with statistically significant differences (p value <.05) in all 4 facets of the AOFAS questionnaire as well as several notable differences in activity levels and footwear restrictions pre and postoperatively.

Total Knee Arthroplasty in Hemophilia: Survivorship and Outcomes-A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with hemophilia (PWHs) may experience spontaneous or traumatic bleeding episodes. Recurrent bleeding can lead to end-stage hemophilic arthropathy and total knee replacement (TKR) provides an effective treatment. The aim of this study is to investigate outcomes in PWHs who undergo TKR. METHODS: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study outcomes included patient-reported functional outcomes, implant survivorship, and complications. Subgroup analysis was performed assessing the effect of recombinant prophylaxis medication by comparing studies that included only TKRs performed after the year 2000 (period A), to those that included TKRs before 2000 (period B). RESULTS: Twenty-eight studies were included, with a total of 1210 TKRs performed in 917 PWHs. The mean age of patients was 38.5 years (standard deviation 5.1) with a mean length of follow-up of 7.1 years (standard deviation 2.9). The total complication rate was 28.7%, with 19.3% requiring a further procedure. Hospital for Special Surgery Knee Score improved by 44.6 points (confidence interval 38.9-50.4) and Knee Society Score function improved by 35.9 points (confidence interval 30.1-41.8). Total range of motion improved by 22.3°. The most common complication was post-operative hemarthrosis (7.6%, 92 TKRs). Deep infection (6.2% vs 3.9%) and aseptic loosening (3.8% vs 2.1%) rates fell between period B and period A. CONCLUSION: TKR in PWHs is a successful procedure improving function, reducing pain, and improving range of motion. PWHs undergo TKR at a younger age and have a higher risk of complications, though contemporary treatment has reduced these risks. PWHs can expect similar survivorship to the general population.

Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 Reveals Distinct Signalling Roles Related to Antigen Presentation and Viral Response.

The nuclear receptor sub-family 4 group A (NR4A) family are early response genes that encode proteins that are activated in several tissues/cells in response to a variety of stressors. The NR4A family comprises NR4A1, NR4A2 and NR4A3 of which NR4A2 and NR4A3 are under researched and less understood, particularly in the context of immune cells. NR4A expression is associated with multiple diseases e.g. arthritis and atherosclerosis and the development of NR4A-targetting molecules as therapeutics is a current focus in this research field. Here, we use a combination of RNA-sequencing coupled with strategic bioinformatic analysis to investigate the down-stream effects of NR4A2 and NR4A3 in monocytes and dissect their common and distinct signalling roles. Our data reveals that NR4A2 and NR4A3 depletion has a robust and broad-reaching effect on transcription in both the unstimulated state and in the presence of LPS. Interestingly, many of the genes affected were present in both the unstimulated and stimulated states revealing a previously unappreciated role for the NR4As in unstimulated cells. Strategic clustering and bioinformatic analysis identified both distinct and common transcriptional roles for NR4A2 and NR4A3 in monocytes. NR4A2 notably was linked by both bioinformatic clustering analysis and transcription factor interactome analysis to pathways associated with antigen presentation and regulation of MHC genes. NR4A3 in contrast was more closely linked to pathways associated with viral response. Functional studies further support our data analysis pointing towards preferential/selective roles for NR4A2 in the regulation of antigen processing with common roles for NR4A2 and NR4A3 evident with respect to cell migration. Taken together this study provides novel mechanistic insights into the role of the enigmatic nuclear receptors NR4A2 and NR4A3 in monocytes.

Does Proximal Femoral Morphology Impact Morbidity and Mortality? A Cohort Study of Uncemented Hemiarthroplasties in the Treatment of Femoral Neck Fractures.

BACKGROUND: To assess outcomes after uncemented hemiarthroplasty stems in the treatment of intracapsular femoral neck fractures over an 11-year period. Mortality rates were assessed, and whether proximal femoral geometry and stem alignment were factors in intraoperative or postoperative periprosthetic fracture (PPF) needs to be identified. MATERIALS AND METHODS: A retrospective single-center observational study was conducted of all patients who underwent intracapsular femoral neck fracture treatment using an uncemented prosthesis between January 2008 and December 2018. Primary endpoints included mortality rate, Dorr classification, prosthesis alignment, intraoperative fracture, and reoperation rate for any reason. Subanalysis on collared and uncollared implants was also conducted. Multivariate logistic regression was performed based on Dorr classification for stem alignment, fracture incidence, reoperation rate, implant sizing, and patient mortality. RESULTS: A total of 536 patients received an uncemented hemiarthroplasty in the study period. The mean patients age was 80.4 years, of which 71% were female. The 30-day mortality rate was 5.2%, with no deaths on day zero or day one. Twenty patients (3.7%) sustained an intraoperative calcar fracture, and 14 patients a PPF (2.6%) at a mean of 1.3 years from surgery. Dorr C type femurs were more likely to develop a PPF (P = .001), while valgus stem alignment was associated with PPF (P = .049). CONCLUSIONS: This implant has low reoperation rates, low early postoperative mortality, and low 30-day mortality. This large single-center study provides up-to-date information using a contemporary stem in patients with multiple comorbidities. Dorr C femoral morphology and valgus stem malalignment were risk factors for postoperative fractures.

Intermediate to Long-Term Follow-up of Distal Femoral Replacements in the Treatment of Neoplastic Disease About the Knee.

BACKGROUND: Limb salvage procedures have become more prevalent in orthopedic oncology. Endoprostheses have been used successfully to reconstruct large skeletal deficits. The aim was to review intermediate to long-term follow-up of distal femoral replacements in the setting of neoplastic disease about the knee. METHODS: This was a single-center retrospective cohort study from 1997 to 2018 in a national referral center for oncology. The secondary objectives were to describe morbidity and mortality in this cohort. We recorded the modes of failure using Henderson classification system, complications, revisions, and all further operations. RESULTS: Seventy-two distal femoral replacements were performed. Osteosarcoma was the most common indication (55 patients). Other indications included chondrosarcoma (7 patients), giant cell tumor (5 patients), Ewing's sarcoma (2 patients), metastatic spread (2 patients), and leiomyosarcoma (1 patient). One-year mortality was 1.38% with an overall mortality of 13.8%, at the end of the study period. The 1-year revision rate was 4.2%, 30.5% for 10 years, and 38.8% for more than 15 years. The overall implant survival rate was 63.8%. The most common reasons for failure included aseptic loosening (16.6%), infection (16.6%), and local recurrence (9.7%) with an amputation rate of 6.9% in the cohort. CONCLUSION: Neoplastic disease of the lower limb is associated with significant morbidity. Aseptic loosening (16.6%) and infection (16.6%) were the most common reasons for failure in this cohort.

The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo.

Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Here, we demonstrate concentrations up 100 µM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/chemokine array, ELISA and qRT-PCR analysis that multiple pro-inflammatory mediators were significantly increased in CRC tissue compared to control tissue, which were then attenuated with the addition of CsnB (such as IL-1ß, IL-8 and TNFα). Lastly, stratification of the data revealed that CsnB especially alters the inflammatory profile of tumours derived from males who had not undergone chemoradiotherapy. Thus, this study demonstrates that NR4A agonist CsnB does not adversely affect colon tissue structure or functionality and can attenuate the pro-inflammatory state of human CRC tissue ex vivo.

Protein kinase D, ubiquitin and proteasome pathways are involved in adenosine receptor-stimulated NR4A expression in myeloid cells.

Adenosine is a purine nucleoside pivotal for homeostasis in cells and tissues. Stimulation of the adenosine receptors (AR) has been shown to regulate the nuclear orphan receptor 4A (NR4A1-3) family, resulting in attenuation of hyper-inflammatory responses in myeloid cells. The NR4A1-3 orphan receptors are early immediate response genes and transcriptional regulators of cell and tissue homeostasis. The signal transduction and transcriptional mechanism(s) of how AR-stimulation promotes NR4A expression in myeloid cells is unknown and is the focus of this study. We confirm that adenosine and the stable analogue, 5'-N-Ethylcarboxamidoadenosine (NECA), enhance NR4A1-3 expression in THP-1 cells. Pharmacological approaches identified that protein kinase D (PKD) mediates AR-stimulated NR4A expression in myeloid cells and reveals no involvement of PKA nor PKC. The role of NF-κB, a principal regulator of NR4A expression in myeloid cells, was examined as a possible transcriptional regulator downstream of PKD. Utilising BAY11-7082 and MG-132, inhibitors of the respective ubiquitin and proteasome pathways essential for NF-κB activation, suggested a prospective role for NF-κB, or more specifically signalling via IKKα/ß. However, biological interventional studies using overexpression of IκBα in myeloid cells and MEF cells lacking IKKα and IKKß (IKKα/ß-/-) revealed the NF-κB pathway is not utilised in mediating AR-stimulated NR4A expression. Thus, this study contributes mechanistic insight into how AR signalling modulates the expression of NR4A receptors, pivotal regulators of inflammatory responses in myeloid cells.

Perioperative Mortality and Periprosthetic Fracture: A Single-Center Experience of 857 Uncemented Hemiarthroplasties for Displaced Femoral Neck Fractures.

BACKGROUND: Uncemented hemiarthroplasty (UHA) for displaced femoral neck fracture (FNF) is favored by some surgeons because of the reduced rate of perioperative mortality and operative time. However higher rates of intraoperative and postoperative periprosthetic fractures (PPFs) have been reported. The aim of the study was to review day-0, day-1, day-2, day-30, and one-year mortality as well as intraoperative and postoperative PPF after UHA for displaced FNF and compare this with cemented hemiarthroplasties (CHAs) performed. Secondary objectives were to assess whether femoral stem geometry and alignment were associated with PPF in UHA. METHODS: A retrospective observational study was conducted of patients treated with a hemiarthroplasty for a displaced FNF over an eleven-year period. Radiographic analysis was conducted of femoral geometry and stem alignment. RESULTS: Over the 11-year study period, 857 UHAs and 247 CHAs were performed. There were no on-table, day-0, day-1, or day-2 deaths in UHA. Intraoperative PPF occurred in 3.6% UHA and 2% CHA and postoperative PPF in 2.4% UHA and 4.8% CHA. Intraoperative PPF was not associated with increased mortality (P = .15), postoperative PPF, or all-cause revision in UHA. Valgus stem alignment was a risk factor for a postoperative PPF and additional surgery in UHA (P = .004). CONCLUSION: UHA was associated with no perioperative deaths and a 30-day mortality rate of 5% in this series. It can be considered in patients with multiple medical comorbidities. Careful surgical planning and technique is important to optimize stem alignment particularly in Dorr C type femurs.