PeerJ Preprints: Orthopedicshttps://peerj.com/preprints/index.atom?journal=peerj&subject=5900Orthopedics articles published in PeerJ PreprintsFracture Table vs. Lateral Positioning for Intramedullary Fixation of Femur Fractures (The FLiP Study): A protocol for a pilot randomized controlled trialhttps://peerj.com/preprints/278752019-10-222019-10-22Daniel AxelrodHerman JohalKim MaddenFrancesc MarcanoCarlos Prada
Background: Femoral Shaft fractures are devastating and life threatening injuries. Femoral shaft fractures are most commonly treated with intramedullary fixation. Malrotation of the injured limb after fixation is a common and significant complication following femoral shaft fractures. During the operation, patients can be positioned either supine or in a lateral position. Additionally, patients can be placed on a standard radiolucent operating room table, or placed on a fracture table with traction statically applied to the operative limb throughout the case. Previous case series and cohort studies have shown equivalence between study groups, but choice between positioning options remains controversial.
Methods: This represents a protocol for a randomized controlled pilot trial. We will be compared lateral positioning with use of manual traction to supine positioning with use of a fracture table. Primary outcomes will be in assessment for feasibility for a future full scale randomized trial, including evaluating patient recruitment, patient compliance with followup, contamination between treatment arms and others.
Results: The primary outcome will be feasibility for a future trial. Secondary outcomes will include malrotation as measured through postoperative computed tomography scans and gait analysis at 6 months.
Background: Femoral Shaft fractures are devastating and life threatening injuries. Femoral shaft fractures are most commonly treated with intramedullary fixation. Malrotation of the injured limb after fixation is a common and significant complication following femoral shaft fractures. During the operation, patients can be positioned either supine or in a lateral position. Additionally, patients can be placed on a standard radiolucent operating room table, or placed on a fracture table with traction statically applied to the operative limb throughout the case. Previous case series and cohort studies have shown equivalence between study groups, but choice between positioning options remains controversial.Methods: This represents a protocol for a randomized controlled pilot trial. We will be compared lateral positioning with use of manual traction to supine positioning with use of a fracture table. Primary outcomes will be in assessment for feasibility for a future full scale randomized trial, including evaluating patient recruitment, patient compliance with followup, contamination between treatment arms and others.Results: The primary outcome will be feasibility for a future trial. Secondary outcomes will include malrotation as measured through postoperative computed tomography scans and gait analysis at 6 months.Opposite asymmetries of face and trunk and of kissing and hugging, as predicted by the axial twist hypothesishttps://peerj.com/preprints/275932019-03-162019-03-16Marc HE de Lussanet
The contralateral organization of the forebrain and the crossing of the optic nerves in the optic chiasm represent a long-standing conundrum. According to the Axial Twist Hypothesis (ATH) the rostral head and the rest of the body are twisted with respect to each other to form a left-handed half turn. This twist is the result, mainly, of asymmetric, twisted growth in the early embryo. Evolutionary selection tends to restore bilateral symmetry. Since selective pressure will decrease as the organism approaches symmetry, we expected a small control error in the form of a small, residual right-handed twist. We found that the mouth-eyes-nose (rostral head) region shows a left-offset with respect to the ears (posterior head) by up to 0.8° (P<0.01, Bonferroni-corrected). Moreover, this systematic aurofacial asymmetry was larger in young children (on average up to 3°) and reduced with age. Finally, we predicted and found a right-sided bias for hugging (78%) and a left-sided bias for kissing (69%). Thus, all predictions were confirmed by the data. These results are all in support of the ATH, whereas the pattern of results is not explained by existing alternative theories. As of the present results, the ATH is the first theory for the contralateral forebrain and the optic chiasm whose predictions have been tested empirically. We conclude that humans (and all other vertebrates) are fundamentally asymmetric, both in their anatomy and their behavior. This supports the thesis that the approximate bilateral symmetry of vertebrates is a secondary feature, despite their being bilaterians.
The contralateral organization of the forebrain and the crossing of the optic nerves in the optic chiasm represent a long-standing conundrum. According to the Axial Twist Hypothesis (ATH) the rostral head and the rest of the body are twisted with respect to each other to form a left-handed half turn. This twist is the result, mainly, of asymmetric, twisted growth in the early embryo. Evolutionary selection tends to restore bilateral symmetry. Since selective pressure will decrease as the organism approaches symmetry, we expected a small control error in the form of a small, residual right-handed twist. We found that the mouth-eyes-nose (rostral head) region shows a left-offset with respect to the ears (posterior head) by up to 0.8° (P<0.01, Bonferroni-corrected). Moreover, this systematic aurofacial asymmetry was larger in young children (on average up to 3°) and reduced with age. Finally, we predicted and found a right-sided bias for hugging (78%) and a left-sided bias for kissing (69%). Thus, all predictions were confirmed by the data. These results are all in support of the ATH, whereas the pattern of results is not explained by existing alternative theories. As of the present results, the ATH is the first theory for the contralateral forebrain and the optic chiasm whose predictions have been tested empirically. We conclude that humans (and all other vertebrates) are fundamentally asymmetric, both in their anatomy and their behavior. This supports the thesis that the approximate bilateral symmetry of vertebrates is a secondary feature, despite their being bilaterians.An automatic fascicle tracking algorithm quantifying gastrocnemius architecture during maximal effort contractionshttps://peerj.com/preprints/274752019-01-102019-01-10John F DrazanTodd J HullfishJosh R Baxter
Background. Ultrasound has become the gold-standard for making dynamic measurements of muscle structure during functional movements in biomechanical studies. Manual measurements of fascicle length and pennation angle are time intensive which limits the clinical utility of this approach while also limiting sample sizes. The purpose of this study was to develop a novel tracking paradigm to quantify individual fascicle length and pennation measurements during maximal voluntary contractions and demonstrate is repeatability between days and reproducibility between different examiners.
Methods. Five healthy young adults performed maximal isokinetic contractions at 0, 30, 120, 210, and 500 degrees about their ankle on an isokinetic dynamometer while their gastrocnemius muscle was observed using ultrasound. Individual muscle fascicles were identified in the first frame, and tracked using the automatic fascicle tracking algorithm and a manual approach by three observers on three separate days. Repeatability within examiners across days and reproducibility across examiners and days was evaluated using intraclass correlation coefficients. Agreement between manual and automatic tracking was evaluated using the coefficient of multiple correlations. Supervised automatic tracking was performed on all videos by one examiner to evaluate the fidelity of automatic tracking in practice.
Results. We found both manual and automatic measurements of fascicle length and pennation angle to be strongly repeatable within examiners and strongly reproducible across examiners and days (ICCs>0.76). There was greater agreement between manual and automatic measurements of fascicle length than pennation angle, however the mean CMC value for both was still found to be strong in both cases (CMC>0.8). Supervision of automatic tracking greatly showed very strong agreement between manual and automatic measurements of fascicle length and pennation angle (CMC>0.94).
Conclusions. We have developed a novel automatic fascicle tracking algorithm that quantifies fascicle length and pennation angle of individual muscle fascicles during dynamic contractions across a range of velocities. We demonstrated that this fascicle tracking algorithm is repeatable and reproducible across different examiners and different days and showed strong agreement with manual measurements, especially when tracking is supervised by the user so that tracking can be reinitialized if poor tracking fidelity is observed.
Background. Ultrasound has become the gold-standard for making dynamic measurements of muscle structure during functional movements in biomechanical studies. Manual measurements of fascicle length and pennation angle are time intensive which limits the clinical utility of this approach while also limiting sample sizes. The purpose of this study was to develop a novel tracking paradigm to quantify individual fascicle length and pennation measurements during maximal voluntary contractions and demonstrate is repeatability between days and reproducibility between different examiners.Methods. Five healthy young adults performed maximal isokinetic contractions at 0, 30, 120, 210, and 500 degrees about their ankle on an isokinetic dynamometer while their gastrocnemius muscle was observed using ultrasound. Individual muscle fascicles were identified in the first frame, and tracked using the automatic fascicle tracking algorithm and a manual approach by three observers on three separate days. Repeatability within examiners across days and reproducibility across examiners and days was evaluated using intraclass correlation coefficients. Agreement between manual and automatic tracking was evaluated using the coefficient of multiple correlations. Supervised automatic tracking was performed on all videos by one examiner to evaluate the fidelity of automatic tracking in practice.Results. We found both manual and automatic measurements of fascicle length and pennation angle to be strongly repeatable within examiners and strongly reproducible across examinersand days (ICCs>0.76). There was greater agreement between manual and automatic measurements of fascicle length than pennation angle, however the mean CMC value for both was still found to be strong in both cases (CMC>0.8). Supervision of automatic tracking greatly showed very strong agreement between manual and automatic measurements of fascicle length and pennation angle (CMC>0.94).Conclusions. We have developed a novel automatic fascicle tracking algorithm that quantifies fascicle length and pennation angle of individual muscle fascicles during dynamic contractions across a range of velocities. We demonstrated that this fascicle tracking algorithm is repeatable and reproducible across different examiners and different days and showed strong agreement with manual measurements, especially when tracking is supervised by the user so that tracking can be reinitialized if poor tracking fidelity is observed.A protocol for a survey of patient perceptions about outpatient joint replacement surgery (The RAAPID survey)https://peerj.com/preprints/274642019-01-032019-01-03Taylor WoolnoughKim MaddenAnthony AdiliVickas KhannaJustin deBeerMitchell WinemakerThomas WoodDaniel Tushinski
Background: Total knee arthroplasty (TKA) and total hip arthroplasty (THA), are the second and third most common surgical procedures performed in Canada, accounting for more than 600,000 acute care bed days and over $1 billion CAD in healthcare spending. The demand for these procedures, both in Canada and internationally, is only expected to increase. Same-day discharge has been demonstrated to be safe and effective in properly selected patients and has the potential to greatly decrease the cost of THA and TKA, collectively referred to as total joint arthroplasty (TJA). The existing literature focuses on implementing outpatient TJA from the physician’s perspective. However, patient opinions do not always align with physician opinions. To date, only one study has explored patients’ perspectives regarding outpatient TJA; many questions remain unanswered. To effectively implement or expand outpatient joint replacement programs, detailed exploration of the patient perspective is necessary.
Methods: This study is a multicentre cross-sectional survey to primarily determine the proportion of patients who are open to outpatient TJA. Adult patients scheduled for primary TJA surgery or those who have received TJA surgery in the past year will be included in the survey. The secondary objectives of this survey are to determine patient characteristics associated with openness to outpatient TJA, describe patient concerns regarding outpatient TJA, and identify potential methods to increase patient comfort with outpatient TJA.
Discussion: Resource expenditure and clinical practice are increasingly guided by subjective patient outcomes, especially in the area of joint replacement. With the current focus on cost-efficiency in healthcare, there is increasing interest in outpatient TJA. By exploring how patients perceive outpatient TJA, this study may serve to guide the development of educational resources and programs to enhance and support outpatient TJA. Addressing concerns identified by patients in an evidence-based manner has the potential to improve patient satisfaction and outcomes in the growing trend of outpatient TJA.
Background: Total knee arthroplasty (TKA) and total hip arthroplasty (THA), are the second and third most common surgical procedures performed in Canada, accounting for more than 600,000 acute care bed days and over $1 billion CAD in healthcare spending. The demand for these procedures, both in Canada and internationally, is only expected to increase. Same-day discharge has been demonstrated to be safe and effective in properly selected patients and has the potential to greatly decrease the cost of THA and TKA, collectively referred to as total joint arthroplasty (TJA). The existing literature focuses on implementing outpatient TJA from the physician’s perspective. However, patient opinions do not always align with physician opinions. To date, only one study has explored patients’ perspectives regarding outpatient TJA; many questions remain unanswered. To effectively implement or expand outpatient joint replacement programs, detailed exploration of the patient perspective is necessary.Methods: This study is a multicentre cross-sectional survey to primarily determine the proportion of patients who are open to outpatient TJA. Adult patients scheduled for primary TJA surgery or those who have received TJA surgery in the past year will be included in the survey. The secondary objectives of this survey are to determine patient characteristics associated with openness to outpatient TJA, describe patient concerns regarding outpatient TJA, and identify potential methods to increase patient comfort with outpatient TJA.Discussion: Resource expenditure and clinical practice are increasingly guided by subjective patient outcomes, especially in the area of joint replacement. With the current focus on cost-efficiency in healthcare, there is increasing interest in outpatient TJA. By exploring how patients perceive outpatient TJA, this study may serve to guide the development of educational resources and programs to enhance and support outpatient TJA. Addressing concerns identified by patients in an evidence-based manner has the potential to improve patient satisfaction and outcomes in the growing trend of outpatient TJA.Trochanteric pain in patients undergoing total hip arthroplasty: A protocol for a systematic reviewhttps://peerj.com/preprints/272932018-10-222018-10-22Daniel AxelrodKim MaddenLaura BanfieldMitchell WinemakerJustin deBeerThomas Wood
Background: Total hip arthroplasty (THA) is one of the most common surgical procedures. Although THA surgeries are typically very successful, between 3% and 17% of all patients experience trochanteric pain after surgery. Unfortunately, there remains little high quality and reproducible evidence surrounding this disorder, especially following total hip replacement. The objectives of this review are to describe, among pre-operative or post-operative primary THA patients the prevalence, treatments, prognosis, risk factors, and diagnostic methods available for trochanteric pain.
Methods: This is a protocol for a descriptive systematic review of trochanteric pain among THA patients. We will include studies of all study designs, with the exception of non-systematic reviews and expert opinion, with no date limits. We will search Medline, Embase, CINAHL, and the Cochrane Library using the Ovid search interface. We will also search the reference lists of included studies for possible missed studies. We will use the systematic review management software Rayyan to assist with study screening. Two reviewers will independently review studies for inclusion and extract data into a study-specific database.
Discussion: This study will add to the literature by comprehensively and systematically evaluating the available literature on trochanteric pain after THA. Previous studies have been conducted on the topic but they were not comprehensive or did not review the literature systematically. Additionally, our study will critically evaluate the methodological quality of the included studies, adding an evidence-based component to the review. This review will help orthopaedic surgeons better care for patients with trochanteric pain after THA, and will identify knowledge gaps for future research.
Registration: This protocol will be registered on PROSPERO
Background: Total hip arthroplasty (THA) is one of the most common surgical procedures. Although THA surgeries are typically very successful, between 3% and 17% of all patients experience trochanteric pain after surgery. Unfortunately, there remains little high quality and reproducible evidence surrounding this disorder, especially following total hip replacement. The objectives of this review are to describe, among pre-operative or post-operative primary THA patients the prevalence, treatments, prognosis, risk factors, and diagnostic methods available for trochanteric pain.Methods: This is a protocol for a descriptive systematic review of trochanteric pain among THA patients. We will include studies of all study designs, with the exception of non-systematic reviews and expert opinion, with no date limits. We will search Medline, Embase, CINAHL, and the Cochrane Library using the Ovid search interface. We will also search the reference lists of included studies for possible missed studies. We will use the systematic review management software Rayyan to assist with study screening. Two reviewers will independently review studies for inclusion and extract data into a study-specific database.Discussion: This study will add to the literature by comprehensively and systematically evaluating the available literature on trochanteric pain after THA. Previous studies have been conducted on the topic but they were not comprehensive or did not review the literature systematically. Additionally, our study will critically evaluate the methodological quality of the included studies, adding an evidence-based component to the review. This review will help orthopaedic surgeons better care for patients with trochanteric pain after THA, and will identify knowledge gaps for future research.Registration: This protocol will be registered on PROSPEROProspective abuse and intimate partner violence surgical evaluation (PRAISE-2 pilot): Statistical analysis plan for a pilot prospective cohort studyhttps://peerj.com/preprints/269182018-05-072018-05-07Kim MaddenDiane Heels-AnsdellSheila SpragueHerman JohalMichelle GhertMohit BhandariLehana Thabane
Background. Intimate partner violence (IPV) is a prevalent social issue that affects the health and well-being of women globally. In orthopaedics, the prevalence of women who have experienced abuse in the past year is as high as 1 in 6. PRAISE-2 is a multi-centre pilot prospective cohort study of 250 women with musculoskeletal injuries to determine how IPV experiences affect injury-related outcomes, and how patterns of IPV change over a 12 month period of time following a musculoskeletal injury. The current report is a description of the statistical analysis plan for the PRAISE-2 pilot study. Methods. This study is a pilot multicentre prospective cohort study to primarily assess feasibility of our recruitment, retention and data collection strategies, and to collect preliminary data on orthopaedic outcomes after experiencing IPV, as well as changes in IPV patterns following an injury. Included participants will be adult females presenting to participating fracture clinics for a fracture and/or dislocation requiring orthopaedic care. Participants will be followed for one year. The primary analysis will be descriptive. We will report recruitment, missed visits, out of window visits, participant completion data, and completed form data as counts and percentages with 95% confidence intervals. Based on the primary analyses, we will report whether the feasibility criteria have been met, and recommend modifications to the protocol for any planned definitive studies, if needed. All secondary (clinical) analyses are exploratory. Discussion. In order for surgeons to be as effective as possible in assisting and advocating for women who have experienced abuse, we need more information on how IPV experiences are associated with musculoskeletal outcomes. Both the feasibility and clinical information gained from this pilot study will be instrumental in informing future observational and interventional IPV studies. By reporting our statistical analysis plan before the study ends, we hope to improve the transparency, integrity, and reproducibility of our study findings. Trial registration. This study is registered on clinicaltrials.gov NCT02529267 on 20 August 2015, before the first participant was enrolled
Background. Intimate partner violence (IPV) is a prevalent social issue that affects the health and well-being of women globally. In orthopaedics, the prevalence of women who have experienced abuse in the past year is as high as 1 in 6. PRAISE-2 is a multi-centre pilot prospective cohort study of 250 women with musculoskeletal injuries to determine how IPV experiences affect injury-related outcomes, and how patterns of IPV change over a 12 month period of time following a musculoskeletal injury. The current report is a description of the statistical analysis plan for the PRAISE-2 pilot study. Methods. This study is a pilot multicentre prospective cohort study to primarily assess feasibility of our recruitment, retention and data collection strategies, and to collect preliminary data on orthopaedic outcomes after experiencing IPV, as well as changes in IPV patterns following an injury. Included participants will be adult females presenting to participating fracture clinics for a fracture and/or dislocation requiring orthopaedic care. Participants will be followed for one year. The primary analysis will be descriptive. We will report recruitment, missed visits, out of window visits, participant completion data, and completed form data as counts and percentages with 95% confidence intervals. Based on the primary analyses, we will report whether the feasibility criteria have been met, and recommend modifications to the protocol for any planned definitive studies, if needed. All secondary (clinical) analyses are exploratory. Discussion. In order for surgeons to be as effective as possible in assisting and advocating for women who have experienced abuse, we need more information on how IPV experiences are associated with musculoskeletal outcomes. Both the feasibility and clinical information gained from this pilot study will be instrumental in informing future observational and interventional IPV studies. By reporting our statistical analysis plan before the study ends, we hope to improve the transparency, integrity, and reproducibility of our study findings. Trial registration. This study is registered on clinicaltrials.gov NCT02529267 on 20 August 2015, before the first participant was enrolledDetection of linear features including bone and skin areas in ultrasound images of jointshttps://peerj.com/preprints/35192018-01-102018-01-10Artur BąkJakub SegenKamil WereszczyńskiPawel MielnikMarcin FojcikMarek Kulbacki
Identifying the separate parts in ultrasound images such as bone and skin plays the crucial role in synovitis detection task. This paper presents a detector of bone and skin regions in the form of a classifier which is trained on a set of annotated images. Selected regions have labels: skin or bone or none. Feature vectors used by the classifier are assigned to image pixels as a result of passing the image through the bank of linear and nonlinear filters. The filters include Gaussian blurring filter, its first and second order derivatives, Laplacian as well as positive and negative threshold operations applied to the filtered images. We compared multiple supervised learning classifiers including Naive Bayes, k-Nearest Neighbour, Decision Trees, Random Forest, AdaBoost and Support Vector Machines (SVM) with various kernels, using four classification performance scores and computation time. The Random Forest classifier was selected for the final use, as it gives the best overall evaluation results.
Identifying the separate parts in ultrasound images such as bone and skin plays the crucial role in synovitis detection task. This paper presents a detector of bone and skin regions in the form of a classifier which is trained on a set of annotated images. Selected regions have labels: skin or bone or none. Feature vectors used by the classifier are assigned to image pixels as a result of passing the image through the bank of linear and nonlinear filters. The filters include Gaussian blurring filter, its first and second order derivatives, Laplacian as well as positive and negative threshold operations applied to the filtered images. We compared multiple supervised learning classifiers including Naive Bayes, k-Nearest Neighbour, Decision Trees, Random Forest, AdaBoost and Support Vector Machines (SVM) with various kernels, using four classification performance scores and computation time. The Random Forest classifier was selected for the final use, as it gives the best overall evaluation results.The role of biomaterials in the treatment of meniscal tearshttps://peerj.com/preprints/31112017-07-262017-07-26Crystal O KeanRobert J BrownJames Chapman
Extensive investigations over the recent decades have established the anatomical, biomechanical and functional importance of the meniscus in the knee joint. As a functioning part of the joint, it serves to prevent the deterioration of articular cartilage and subsequent osteoarthritis. To this end, meniscus repair and regeneration is of particular interest from the biomaterial, bioengineering and orthopaedic research community. Even though meniscal research is previously of a considerable volume, the research community with evolving material science, biology and medical advances are all pushing toward emerging novel solutions and approaches to the successful treatment of meniscal difficulties.
Extensive investigations over the recent decades have established the anatomical, biomechanical and functional importance of the meniscus in the knee joint. As a functioning part of the joint, it serves to prevent the deterioration of articular cartilage and subsequent osteoarthritis. To this end, meniscus repair and regeneration is of particular interest from the biomaterial, bioengineering and orthopaedic research community. Even though meniscal research is previously of a considerable volume, the research community with evolving material science, biology and medical advances are all pushing toward emerging novel solutions and approaches to the successful treatment of meniscal difficulties.Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat modelhttps://peerj.com/preprints/27092017-01-082017-01-08Jinyong JuDu YuFeng XueYong ZhaoWeizhe ShiMingmang PanGuo TangHaijun Xiao
Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.
Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.BMPR1A signalling is linked to tumour progression in dedifferentiated liposarcomas: lessons for rhBMP2 use in spinal surgeryhttps://peerj.com/preprints/17192016-02-062016-02-06Hannah L O'NeillAmy P CassidyOlivia B HarrisJohn W Cassidy
Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. Because of BMP2’s osteogenic properties, a recombinant human version (rhBMP2) has found utility as an adjuvant therapy during surgery for spinal fusions. However, the results of large-scale meta-analysis has highlighted the potential of rhBMP2 to promote new tumour formation, leading to an FDA black box warning. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMPR1A-biased BMP2 signalling in soft tissue sarcomas. Using disease free survival as our primary endpoint, we find this BMPR1A-biased BMP2 signalling confers poor overall prognosis compared both to patients with BMPR1B-biased and to the sarcoma dataset as a whole. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link this effect to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2, the need for extensive patient follow-up and the potential disadvantages of rhBMP2 use. For the first time, we identify BMPR1A-biased BMP2 signalling as a biomarker of disease relapse in dedifferentiated liposarcomas.
Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. Because of BMP2’s osteogenic properties, a recombinant human version (rhBMP2) has found utility as an adjuvant therapy during surgery for spinal fusions. However, the results of large-scale meta-analysis has highlighted the potential of rhBMP2 to promote new tumour formation, leading to an FDA black box warning. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMPR1A-biased BMP2 signalling in soft tissue sarcomas. Using disease free survival as our primary endpoint, we find this BMPR1A-biased BMP2 signalling confers poor overall prognosis compared both to patients with BMPR1B-biased and to the sarcoma dataset as a whole. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link this effect to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2, the need for extensive patient follow-up and the potential disadvantages of rhBMP2 use. For the first time, we identify BMPR1A-biased BMP2 signalling as a biomarker of disease relapse in dedifferentiated liposarcomas.