The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research.

The Extracellular RNA Communication Consortium (ERCC) was launched to accelerate progress in the new field of extracellular RNA (exRNA) biology and to establish whether exRNAs and their carriers, including extracellular vesicles (EVs), can mediate intercellular communication and be utilized for clinical applications. Phase 1 of the ERCC focused on exRNA/EV biogenesis and function, discovery of exRNA biomarkers, development of exRNA/EV-based therapeutics, and construction of a robust set of reference exRNA profiles for a variety of biofluids. Here, we present progress by ERCC investigators in these areas, and we discuss collaborative projects directed at development of robust methods for EV/exRNA isolation and analysis and tools for sharing and computational analysis of exRNA profiling data.

The NanoFlow Repository.

MOTIVATION: Extracellular particles (EPs) are the focus of a rapidly growing area of exploration due to the widespread interest in understanding their roles in health and disease. However, despite the general need for EP data sharing and established community standards for data reporting, no standard repository for EP flow cytometry data captures rigor and minimum reporting standards such as those defined by MIFlowCyt-EV (https://doi.org/10.1080/20013078.2020.1713526). We sought to address this unmet need by developing the NanoFlow Repository. RESULTS: We have developed The NanoFlow Repository to provide the first implementation of the MIFlowCyt-EV framework. AVAILABILITY AND IMPLEMENTATION: The NanoFlow Repository is freely available and accessible online at https://genboree.org/nano-ui/. Public datasets can be explored and downloaded at https://genboree.org/nano-ui/ld/datasets. The NanoFlow Repository's backend is built using the Genboree software stack that powers the ClinGen Resource, specifically the Linked Data Hub (LDH), a REST API framework written in Node.js, developed initially to aggregate data within ClinGen (https://ldh.clinicalgenome.org/ldh/ui/about). NanoFlow's LDH (NanoAPI) is available at https://genboree.org/nano-api/srvc. NanoAPI is supported by a Node.js Genboree authentication and authorization service (GbAuth), a graph database called ArangoDB, and an Apache Pulsar message queue (NanoMQ) to manage data inflows into NanoAPI. The website for NanoFlow Repository is built with Vue.js and Node.js (NanoUI) and supports all major browsers.

INFIX versus plating for pelvic fractures with disruption of the symphysis pubis.

PURPOSE: The purpose of this study is to compare INFIX to plating in the treatment of unstable pelvic ring injuries with disruption of the symphysis. METHODS: Twenty-four patients treated with INFIX were compared to 28 patients fixed by plating. All patients had anterior and posterior fixation. Injuries were classified using the Young and Burgess and AO/OTA classification systems. Reductions of the pelvic ring were assessed using the pelvic deformity index (PDI) and symphyseal widening. Patients were contacted to get functional outcomes using the Majeed scoring system and complications were tabulated . RESULTS: INFIX was inferior to plating at reducing symphyseal widening (INFIX 10.72± 5.0 Plates 6.97 ± 3.39 P = 0.012) but similar in reducing the pelvic deformity index. (INFIX 0.0221± .015 Plates 0.0190 ± .0105 P = 0 .38). Majeed scores were similar 83.95 ± 15.2 (median 89, range 51-100) for INFIX and 77.67± 16.7 (median 79, range 54-100) for plating. Complications included infection (1 (4%) INFIX , 4 (14%) plates), improper hardware placement or failure (2 (8%) INFIX, 3 (11%) plates), and heterotopic ossification (11 (46%) INFIX, 16 (57.1%) plates). Infection in the plated patients was related to urological injury in 3/4 cases. CONCLUSIONS: Plating provides better reduction of the pubic symphysis and requires only one surgery. Outcomes scores were similar. INFIX may be preferable in obese patients, young women of childbearing age or those with urological injury.

Wellness Among Interventional Radiologists: Results From a Multidimensional Survey.

RATIONALE AND OBJECTIVES: To evaluate wellness among interventional radiologists using a multidimensional survey. MATERIALS AND METHODS: An anonymous 53-item survey, including 36 Perceived Wellness Survey (PWS) prompts, was created in Qualtrics (an online survey tool) to assess wellness among interventional radiology attendings and residents. The survey was open from June to September, 2022, 2 years into the COVID-19 Pandemic. The survey was distributed via Society of Interventional Radiology Forums, social media (Twitter, LinkedIn, and Facebook), and personal correspondence. PWS scores were categorized into Wellness Composite and subscores (physical, emotional, intellectual, psychological, social, and spiritual). RESULTS: 367 surveys were completed. 300 (81.7%) respondents were male and 67 (18.3%) were female. Respondents included attending physicians (297; 81.0%) and residents (70; 19.0%). Practice settings included academic (174; 47.4%), private (114; 31.0%), private-academic hybrid (62; 16.9%), and others (17; 4.7%). Mean Wellness Composite at academic centers (14.74 ± 3.16; range: 5.42-23.50) was significantly lower than at private (15.22 ± 3.37; range: 6.13-23.51) and hybrid (16.14 ± 2.47; range: 10.20-23.50) practices (p = 0.01). Respondents < 40 years old had significantly lower emotional wellness subscores compared to those ≥ 40 years old (4.34 ± 0.86 vs. 4.60 ± 0.87; p = 0.006). There were no significant differences between geographic regions in the United States, however, International respondents had significantly lower social and intellectual wellness (INT) subscores. Physical wellness subscore (4.00 ± 0.9) was significantly lower than the other subscores (4.59 ± 0.81) (p < .001). Overall mean Wellness Composite was 15.11 ± 3.13 (range: 5.42-23.51). CONCLUSION: Overall self-reported wellness was lower among interventional radiologists practicing at academic centers. Interventional Radiologists < 40 years old and residents had lower emotional wellness, while international respondents had lower social and INT. Overall wellness scores were lower than prior PWS studies.

Seminar: Extracellular Vesicles as Mediators of Environmental Stress in Human Disease.

BACKGROUND: Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress. OBJECTIVES: This seminar addresses the application of new tools and approaches for EV research, developed in part through the National Institutes of Health (NIH) Extracellular RNA Communication Program, and reflects presentations and discussions from a workshop held 27-28 September 2021 by the National Institute of Environmental Health Sciences (NIEHS) and the National Center for Advancing Translational Sciences (NCATS) on "Extracellular Vesicles, Exosomes, and Cell-Cell Signaling in Response to Environmental Stress." The panel of experts discussed current research on EVs and environmental exposures, highlighted recent advances in EV isolation and characterization, and considered research gaps and opportunities toward identifying and characterizing the roles for EVs in environmentally related diseases, as well as the current challenges and opportunities in this field. DISCUSSION: The authors discuss the application of new experimental models, particularly organ-on-chip (OOC) systems and in vitro approaches and how these have the potential to extend findings in population-based studies of EVs in exposure-related diseases. Given the complex challenges of identifying cell-specific EVs related to environmental exposures, as well as the general heterogeneity and variability in EVs in blood and other accessible biological samples, there is a critical need for rigorous reporting of experimental methods and validation studies. The authors note that these efforts, combined with cross-disciplinary approaches, would ensure that future research efforts in environmental health studies on EV biomarkers are rigorous and reproducible. https://doi.org/10.1289/EHP12980.

exRNA-eCLIP intersection analysis reveals a map of extracellular RNA binding proteins and associated RNAs across major human biofluids and carriers.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

MPAPASS software enables stitched multiplex, multidimensional EV repertoire analysis and a standard framework for reporting bead-based assays.

Extracellular vesicles (EVs) of various types are released or shed from all cells. EVs carry proteins and contain additional protein and nucleic acid cargo that relates to their biogenesis and cell of origin. EV cargo in liquid biopsies is of widespread interest owing to its ability to provide a retrospective snapshot of cell state at the time of EV release. For the purposes of EV cargo analysis and repertoire profiling, multiplex assays are an essential tool in multiparametric analyte studies but are still being developed for high-parameter EV protein detection. Although bead-based EV multiplex analyses offer EV profiling capabilities with conventional flow cytometers, the utilization of EV multiplex assays has been limited by the lack of software analysis tools for such assays. To facilitate robust EV repertoire studies, we developed multiplex analysis post-acquisition analysis (MPAPASS) open-source software for stitched multiplex analysis, EV database-compatible reporting, and visualization of EV repertoires.

Open Problems in Extracellular RNA Data Analysis: Insights From an ERCC Online Workshop.

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19-20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop presentations and discussions are available (https://exRNA.org/exRNAdata2021-videos/). There were three target audiences: experimentalists who generate exRNA sequencing data, computational and data scientists who work with those groups to analyze their data, and experimental and data scientists new to the field. Here we summarize issues explored during the workshop, including progress on an effort to develop an exRNA data analysis challenge to engage the community in solving some of these open problems.

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells.

Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To further elucidate EV-mediated mechanisms of neovascularization in vitro, we perform RNA-seq and DNA methylation profiling of human brain endothelial cells exposed to GSC-EVs. To correlate these results to tumors in vivo, we perform histoepigenetic analysis of GBM molecular profiles in the TCGA collection. Remarkably, GSC-EVs and normal vascular growth factors stimulate highly distinct gene regulatory responses that converge on angiogenesis. The response to GSC-EVs shows a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Our results provide insights into targetable angiogenesis pathways in GBM and miRNA candidates for liquid biopsy biomarkers.

Expression profiling using a hexamer-based universal microarray.

We describe a transcriptional analysis platform consisting of a universal micro-array system (UMAS) combined with an enzymatic manipulation step that is capable of generating expression profiles from any organism without requiring a priori species-specific knowledge of transcript sequences. The transcriptome is converted to cDNA and processed with restriction endonucleases to generate low-complexity pools (approximately 80-120) of equal length DNA fragments. The resulting material is amplified and detected with the UMAS system, comprising all possible 4,096 (4(6)) DNA hexamers. Ligation to the arrays yields thousands of 14-mer sequence tags. The compendium of signals from all pools in the array-of-universal arrays comprises a full-transcriptome expression profile. The technology was validated by analysis of the galactose response of Saccharomyces cerevisiae, and the resulting profiles showed excellent agreement with the literature and real-time PCR assays. The technology was also used to demonstrate expression profiling from a hybrid organism in a proof-of-concept experiment where a T-cell receptor gene was expressed in yeast.

Midterm Radiographic and Functional Outcomes of the Anterior Subcutaneous Internal Pelvic Fixator (INFIX) for Pelvic Ring Injuries.

OBJECTIVE: To describe our experience using the anterior internal pelvic fixator (INFIX) for treating pelvic ring injuries. DESIGN: Case Series. SETTING: Level 1 Trauma Center. PATIENTS: Eighty-three patients with pelvic ring injuries were treated with INFIX. Follow-up average was 35 months (range 12-80.33). INTERVENTION: Surgical treatment of pelvic ring injuries included reduction, appropriate posterior fixation, and INFIX placement. OUTCOME MEASUREMENTS: Reduction using the pelvic deformity index and pubic symphysis widening, Majeed functional scores, complications; infection, implant failure, heterotopic ossification (HO), nerve injury, and pain. RESULTS: All patients healed in an appropriate time frame (full weight bearing 12 weeks postoperation). The average pelvic deformity index reduction (injury = 0.0420 ± 0.0412, latest FU = 0.0254 ± 0.0243) was 39.58%. The average reduction of pubic symphysis injuries was 56.92%. The average Majeed score of patients at latest follow-up was 78.77 (range 47-100). Complications were 3 infections, 1 case of implant failure, 2 cases implantation too deep, 7 cases of lateral femoral cutaneous nerve irritation, and 3 cases of pain associated with the device. HO was seen in >50% of the patients, correlated with increased age (P < 0.007), injury severity score (P < 0.05) but only 1 case was symptomatic. CONCLUSIONS: The pelvic injuries had good functional and radiological outcomes with INFIX and the appropriate posterior fixation. The downside is removal requiring a second anesthetic, there is a learning curve, HO often occurs, the lateral femoral cutaneous nerve may get irritated which often resolves once the implants are removed. Surgery-specific implants need to be developed. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Adult Native Septic Arthritis in an Inner City Hospital: Effects on Length of Stay.

The objective of this retrospective study was to assess what factors affected length of stay (LOS) in 183 adult patients with native septic arthritis. Diagnosis was based on a representative physical examination, fluid cell count/Gram stain, and organisms isolated from joint fluid culture. Data included demographics, comorbidities, laboratory results, treatment, and discharge times. Joint fluid cultures were positive in 55% (100 of 183) of the patients, and these patients were the subjects of this study. Blood cultures were taken for 65 patients and were positive in 54%; when positive, they were found to be the same as isolates from joint fluid analysis 91% of the time. Pathogens found in joint fluid analysis were as follows: methicillin-susceptible Staphylococcus aureus (MSSA), 44%; methicillin-resistant S aureus (MRSA), 21%; Streptococcus species, 14%; Pseudomonas, 10%; and other organisms, 11%. Surgical washout less than 24 hours from diagnosis affected LOS (12.25 vs 16.96 days for >24 hours; P<.05), but pathogen type and comorbid conditions did not. Average time for culture sensitivities was 4±1 days. Almost half of the patients had MSSA. Delays that could be controlled were getting an early diagnosis and expedient surgical washout of the joint. A lack of insurance and a requirement of intravenous antibiotics prolonged stay, whereas age, sex, and ethnicity did not. Waiting for bacterial sensitivities was a factor that could not be controlled. The authors believe that polymerase chain reaction or other technologies could lead to early diagnosis and expedient surgery. Effective oral antibiotics against resistant organisms would help the patients leave the hospital earlier. [Orthopedics. 2016; 39(4):e674-e679.].

Application of Circumferential Compression Device (Binder) in Pelvic Injuries: Room for Improvement.

INTRODUCTION: The use of a noninvasive pelvic circumferential compression device (PCCD) to achieve pelvic stabilization by both decreasing pelvic volume and limiting inter-fragmentary motion has become commonplace, and is a well-established component of Advanced Trauma Life Support (ATLS) protocol in the treatment of pelvic ring injuries. The purpose of this study was to evaluate the following: 1) how consistently a PCCD was placed on patients who arrived at our hospital with unstable pelvic ring injuries; 2) if they were placed in a timely manner; and 3) if hemodynamic instability influenced their use. METHODS: We performed an institutional review board-approved retrospective study on 112 consecutive unstable pelvic ring injuries, managed over a two-year period at our Level I trauma center. Our hospital electronic medical records were used to review EMT, physician, nurses', operative notes and radiographic images, to obtain information on the injury and PCCD application. The injuries were classified by an orthopaedic trauma surgeon and a senior orthopaedic resident. Proper application of a pelvic binder using a sheet is demonstrated. RESULTS: Only 47% of unstable pelvic fractures received PCCD placement, despite being the standard of care according to ATLS. Lateral compression mechanism pelvic injuries received PCCDs in 33% of cases, while anterior posterior compression (APC) and vertical shear (VS) injuries had applications in 63% of cases. Most of these PCCD devices were applied after imaging (72%). Hemodynamic instability did not influence PCCD application. CONCLUSION: PCCD placement was missed in many (37%) of APC and VS mechanism injuries, where their application could have been critical to providing stability. Furthermore, to provide rapid stability, pelvic circumferential compression devices should be applied after secondary examination, rather than after receiving imaging results. Better education on timing and technique of PCCD placement at our institution is required to improve treatment of pelvic ring injuries.

Investigating the Universality of Preoperative Health-Related Quality of Life (HRQoL) for Surgically Treated Spinal Deformity in Young Adults: A Propensity Score-Matched Comparison Between African and US Populations.

STUDY DESIGN: Retrospective analysis of propensity score-matched (PSM) observational cohorts. OBJECTIVES: To evaluate and compare preoperative health-related quality of life (HRQoL) scores and radiographic measurements of young African and US adults with spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: Young ASD patients in the United States are motivated more to correct coronal and sagittal plane deformities than to alleviate pain. Motivations for surgical correction in young ASD patients in Africa have not been previously investigated. METHODS: Retrospective review of two large databases of African and US patients with ASD. African patients who underwent ASD surgery were PSM by age, gender, and pelvic tilt with US patients. Preoperative radiographic parameters and HRQoL scores (ODI, SRS-22r, back/leg pain) were compared between cohorts. Pearson correlations used to evaluate relationships between radiographic parameters and HRQoL scores. RESULTS: Fifty-four US patients (average age 22.9 ± 4.9 years; 0% African American) and 54 African patients (24.6 ± 7.2 years) met inclusion criteria. Compared to the United States, African patients had significantly lower body mass index (21.1 ± 3.3 vs. 24.6 ± 7.2) and more severe scoliosis, coronal malalignment, and sagittal malalignment (p < .05). Africans also had significantly better Oswestry Disability Index (12.8 vs. 17.7), worse Scoliosis Research Society questionnaire (SRS-22r)-Appearance (2.5 vs. 3.2), SRS-Function (3.3 vs. 3.9), and SRS-Total (3.2 vs. 3.5) scores than US patients (p < .05). SRS-Appearance scores correlated with Cobb angles of the upper thoracic (r = -0.321), thoracic (r = -0.277), and thoracolumbar (r = -0.300) curves for US patients. For African patients, global sagittal alignment and C7 inclination correlated with SRS-Appearance (r = -0.347, -0.346, respectively). CONCLUSIONS: Young African ASD patients have significantly more severe deformity, less disability, and worse SRS-22r scores preoperatively than a matched cohort of US patients. Spinal deformity and associated poor self-image appear to be the major drivers of surgical intervention in this cohort. Global malalignment in African patients is most closely correlated with appearance scores and should be surgically addressed accordingly. LEVEL OF EVIDENCE: Level III.

Extending gene ontology in the context of extracellular RNA and vesicle communication.

BACKGROUND: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. METHODS: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. RESULTS: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. CONCLUSIONS: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.

Low-Velocity Knee Dislocations in Obese and Morbidly Obese Patients.

BACKGROUND: Knee dislocations from minor trauma have been reported sparsely in the literature. The consensus is that these injuries tend not to be associated with neurovascular compromise. PURPOSE: To present a series of atraumatic knee dislocations in obese and morbidly obese patients and to compare operative versus conservative treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study included 19 patients (21 knees) who presented with knee dislocation from a low-velocity or ultra low-velocity incident. Charts, radiographs, and magnetic resonance images (MRIs) were reviewed, and patients were reviewed based on their latest follow-up. We included patients in our database from 2001 to 2011 and compared knees of patients who had ligament repair or reconstruction (9 total knees) verses nonoperative treatment (12 total knees). Range of motion, activity levels, and knee laxity information were collected as outcome measures to compare operative and nonoperative results. RESULTS: The mean age at presentation was 30.3 years (range, 15-74 years), with 5 men and 14 women. The average body mass index (BMI) was 41.4 kg/m(2) (range, 30-64.4 kg/m(2)), with an average follow-up of 31 months (range, 12-72 months). Five patients (27%) had a popliteal artery injury, and 7 (44.4%) had a peroneal nerve injury at presentation. Four had a vascular repair, 1 had an amputation, and 3 of 7 patients had return of peroneal nerve. Ligament reconstruction was performed on 9 individuals. The average operating time for ligament reconstruction was 183% of that with injury-matched normal-weight patients. Eight operative patients who complied with therapy had an average range of motion of 91.4° (range, 60°-110°). The nonoperative patients had an average range of motion of 60.45° (range, 0°-120°). Two of these patients later required a total knee arthroplasty (3 total knee arthroplasties overall). CONCLUSION: Knee dislocations from minor falls occur in obese patients and are often accompanied by neurovascular complications. While surgical reconstruction is more time consuming and more difficult than that in normal-weight individuals, it may be preferable to nonoperative treatment.

Integration of extracellular RNA profiling data using metadata, biomedical ontologies and Linked Data technologies.

The large diversity and volume of extracellular RNA (exRNA) data that will form the basis of the exRNA Atlas generated by the Extracellular RNA Communication Consortium pose a substantial data integration challenge. We here present the strategy that is being implemented by the exRNA Data Management and Resource Repository, which employs metadata, biomedical ontologies and Linked Data technologies, such as Resource Description Framework to integrate a diverse set of exRNA profiles into an exRNA Atlas and enable integrative exRNA analysis. We focus on the following three specific data integration tasks: (a) selection of samples from a virtual biorepository for exRNA profiling and for inclusion in the exRNA Atlas; (b) retrieval of a data slice from the exRNA Atlas for integrative analysis and (c) interpretation of exRNA analysis results in the context of pathways and networks. As exRNA profiling gains wide adoption in the research community, we anticipate that the strategies discussed here will increasingly be required to enable data reuse and to facilitate integrative analysis of exRNA data.

Monoaxial pedicle screws are superior to polyaxial pedicle screws and the two pin external fixator for subcutaneous anterior pelvic fixation in a biomechanical analysis.

Purpose. Comparison of monoaxial and polyaxial screws with the use of subcutaneous anterior pelvic fixation. Methods. Four different groups each having 5 constructs were tested in distraction within the elastic range. Once that was completed, 3 components were tested in torsion within the elastic range, 2 to torsional failure and 3 in distraction until failure. Results. The pedicle screw systems showed higher stiffness (4.008 ± 0.113 Nmm monoaxial, 3.638 ± 0.108 Nmm Click-x; 3.634 ± 0.147 Nmm Pangea) than the exfix system (2.882 ± 0.054 Nmm) in distraction. In failure testing, monoaxial pedicle screw system was stronger (360 N) than exfixes (160 N) and polyaxial devices which failed if distracted greater than 4 cm (157 N Click-x or 138 N Pangea). The exfix had higher peak torque and torsional stiffness than all pedicle systems. In torsion, the yield strengths were the same for all constructs. Conclusion. The infix device constructed with polyaxial or monoaxial pedicle screws is stiffer than the 2 pin external fixator in distraction testing. In extreme cases, the use of reinforcement or monoaxial systems which do not fail even at 360 N is a better option. In torsional testing, the 2 pin external fixator is stiffer than the pedicle screw systems.