Reduced sister chromatid cohesion acts as a tumor penetrance modifier.

Sister chromatid cohesion (SCC) is an important process in chromosome segregation. ESCO2 is essential for establishment of SCC and is often deleted/altered in human cancers. We demonstrate that esco2 haploinsufficiency results in reduced SCC and accelerates the timing of tumor onset in both zebrafish and mouse p53 heterozygous null models, but not in p53 homozygous mutant or wild-type animals. These data indicate that esco2 haploinsufficiency accelerates tumor onset in a loss of heterozygosity (LOH) sensitive background. Analysis of The Cancer Genome Atlas (TCGA) confirmed ESCO2 deficient tumors have elevated number of LOH events throughout the genome. Further, we demonstrated heterozygous loss of sgo1, important in maintaining SCC, also results in reduced SCC and accelerated tumor formation in a p53 heterozygous background. Surprisingly, while we did observe elevated levels of chromosome missegregation and micronuclei formation in esco2 heterozygous mutant animals, this chromosomal instability did not contribute to the accelerated tumor onset in a p53 heterozygous background. Interestingly, SCC also plays a role in homologous recombination, and we did observe elevated levels of mitotic recombination derived p53 LOH in tumors from esco2 haploinsufficient animals; as well as elevated levels of mitotic recombination throughout the genome of human ESCO2 deficient tumors. Together these data suggest that reduced SCC contributes to accelerated tumor penetrance through elevated mitotic recombination.

Dysfunction of the Lateral Branch of the Superficial Radial Nerve Associated with Radial Collateral Ligament Injuries of the Thumb Metacarpophalangeal Joint: A Case Series with Cadaveric Dissections.

The lateral branch of the superficial radial nerve (SRN) may undergo a neuropraxic stretch injury following radial collateral ligament (RCL) injury to the thumb metacarpophalangeal joint. This case series presents seven athletes who sustained a previously undescribed injury pattern combining dysfunction of the lateral branch of the SRN associated with RCL injury. Successful stabilization of the joint as well as relief of pain was obtained with surgical repair of the RCL, neurolysis and wrapping of the nerve with a tissue engineered allograft product, and, when necessary, excision of a post-traumatic osteophyte. Diagnostic workup along with surgical treatment is presented. Additionally, cadaveric dissections confirmed the course of this nerve, proximity to surrounding structures, and its innervation of the MP capsule. (Journal of Surgical Orthopaedic Advances 29(4):195-198, 2020).

Designing patient-specific solutions using biomodelling and 3D-printing for revision lumbar spine surgery.

PURPOSE: Despite the variety of "off-the-shelf" implants and instrumentation, outcomes following revision lumbosacral surgery are inconstant. Revision fusion surgery presents a unique set of patient-specific challenges that may not be adequately addressed using universal kits. This study aims to describe how patient-specific factors, surgeon requirements, and healthcare efficiencies were integrated to design and manufacture anatomically matched surgical tools and implants to complement a minimally invasive posterior approach for revision lumbar fusion surgery. METHODS: A 72-year-old woman presented with sciatica and a complex L5-S1 pseudoarthrosis 12 months after L2-S1 fixation surgery for symptomatic degenerative scoliosis. Patient computed tomography data were used to develop 1:1 scale biomodels of the bony lumbosacral spine for pre-operative planning, patient education, and intraoperative reference. The surgeon collaborated with engineers and developed a patient-specific 3D-printed titanium lumbosacral fixation implant secured by L2-L5, S2, and iliac screws. Sizes and trajectories for the S2 and iliac screws were simulated using biomodelling to develop a stereotactic 3D-printed drill guide. Self-docking 3D-printed nylon tubular retractors specific to patient tissue depth and bony anatomy at L5-S1 were developed for a minimally invasive transforaminal approach. The pre-selected screws were separately sourced, bundled with the patient-specific devices, and supplied as a kit to the hospital before surgery. RESULTS: At 6-month follow-up, the patient reported resolution of symptoms. No evidence of implant dysfunction was observed on radiography. CONCLUSION: Pre-operative planning combined with biomodelling and 3D printing is a viable process that enables surgical techniques, equipment, and implants to meet patient and surgeon-specific requirements for revision lumbar fusion surgery.

Laser Sintering Approaches for Bone Tissue Engineering.

The adoption of additive manufacturing (AM) techniques into the medical space has revolutionised tissue engineering. Depending upon the tissue type, specific AM approaches are capable of closely matching the physical and biological tissue attributes, to guide tissue regeneration. For hard tissue such as bone, powder bed fusion (PBF) techniques have significant potential, as they are capable of fabricating materials that can match the mechanical requirements necessary to maintain bone functionality and support regeneration. This review focuses on the PBF techniques that utilize laser sintering for creating scaffolds for bone tissue engineering (BTE) applications. Optimal scaffold requirements are explained, ranging from material biocompatibility and bioactivity, to generating specific architectures to recapitulate the porosity, interconnectivity, and mechanical properties of native human bone. The main objective of the review is to outline the most common materials processed using PBF in the context of BTE; initially outlining the most common polymers, including polyamide, polycaprolactone, polyethylene, and polyetheretherketone. Subsequent sections investigate the use of metals and ceramics in similar systems for BTE applications. The last section explores how composite materials can be used. Within each material section, the benefits and shortcomings are outlined, including their mechanical and biological performance, as well as associated printing parameters. The framework provided can be applied to the development of new, novel materials or laser-based approaches to ultimately generate bone tissue analogues or for guiding bone regeneration.

Variable phenotypes and penetrance between and within different zebrafish ciliary transition zone mutants.

Meckel syndrome, nephronophthisis, Joubert syndrome and Bardet-Biedl syndrome are caused by mutations in proteins that localize to the ciliary transition zone (TZ). The phenotypically distinct syndromes suggest that these TZ proteins have differing functions. However, mutations in a single TZ gene can result in multiple syndromes, suggesting that the phenotype is influenced by modifier genes. We performed a comprehensive analysis of ten zebrafish TZ mutants, including mks1, tmem216, tmem67, rpgrip1l, cc2d2a, b9d2, cep290, tctn1, nphp1 and nphp4, as well as mutants in ift88 and ift172. Our data indicate that variations in phenotypes exist between different TZ mutants, supporting different tissue-specific functions of these TZ genes. Further, we observed phenotypic variations within progeny of a single TZ mutant, reminiscent of multiple disease syndromes being associated with mutations in one gene. In some mutants, the dynamics of the phenotype became complex with transitory phenotypes that are corrected over time. We also demonstrated that multiple-guide-derived CRISPR/Cas9 F0 'crispant' embryos recapitulate zygotic null phenotypes, and rapidly identified ciliary phenotypes in 11 cilia-associated gene candidates (ankfn1, ccdc65, cfap57, fhad1, nme7, pacrg, saxo2, c1orf194, ttc26, zmynd12 and cfap52).

Ulnar nerve dysfunction at the elbow after platelet-rich plasma treatment for partial ulnar collateral ligament injuries.

Background: Platelet-rich plasma (PRP) has been used for the treatment of partial ulnar collateral ligament (UCL) tears of the elbow in throwing athletes. Very few studies have focused on the complication profile of PRP in this application.The purpose of this study was to discuss the complication of ulnar nerve fibrosis and resulting cubital tunnel syndrome after a PRP injection for a partial UCL injury. Methods: A retrospective review of 3 high-level baseball players who underwent a PRP injection for treatment of their partial UCL injury was completed. All 3 were noted to have an asymptomatic subluxing ulnar nerve at time of presentation. Their postinjection course is discussed, and the complication of cubital tunnel syndrome highlighted. Results: All 3 players developed cubital tunnel syndrome with significant fibrosis surrounding their ulnar nerve. Conclusion: PRP injections for the treatment of partial UCL injuries of the elbow may place some patients at risk of developing postinjection cubital tunnel syndrome from increased fibrosis around the ulnar nerve. This complication may be more likely to develop in patients who present with a subluxing ulnar nerve.

Patient-specific implants for craniomaxillofacial surgery: A manufacturer's experience.

Additive manufacturing technologies have enabled the development of customised implants for craniomaxillofacial applications using biomaterials such as polymethylmethacrylate (PMMA), porous high-density polyethylene (pHDPE), and titanium mesh. This study aims to report an Australian manufacturer's experience in developing, designing and supplying patient-specific craniomaxillofacial implants over 23 years and summarise feedback received from clinicians. The authors conducted a retrospective review of the manufacturer's implant database of orders placed for custom craniomaxillofacial implants between 1996 and 2019. The variables collected included material, country of order, gender, patient age, and reported complications, which included a measure of custom implant "fit" and adverse events. The development of critical checkpoints in the custom manufacturing process that minimise clinical or logistical non-conformities is highlighted and discussed. A total of 4120 patient-specific implants were supplied, of which 2689 were manufactured from PMMA, 885 from titanium mesh, and 546 from pHDPE. The majority of the implants were used in Australia (2260), United Kingdom (412), Germany (377), and New Zealand (338). PMMA was the preferred material for cranial implants whereas pHDPE was preferred for maxillofacial applications. Age or gender did not influence the material choice. Implant "fit" and adverse outcomes were used as a metric of implant performance. Between 2007 and 2019 there were 37 infections (0.98%) and 164 non-conformities recorded of which 75 (1.8%) were related to implant 'fit'. Our experience demonstrates a safe, reliable, and clinically streamlined manufacturing process which supports surgeons that require bespoke craniomaxillofacial solutions for reconstruction surgery.

Cubital tunnel syndrome: a surgical modification to in situ decompression to improve results.

BACKGROUND: The gold standard for surgical treatment of cubital tunnel syndrome is in situ decompression. However, this procedure does not come without complications. Subluxation of the ulnar nerve and ulnar nerve neuritis from adhesion formation remain 2 potential complications after this procedure. It has been shown in the literature that young, active, male patients are most likely to have these complications postoperatively. We have developed a modification to in situ decompression by developing a fascial turnover flap and using a porcine submucosa extracellular matrix (Axogen) to help reduce both ulnar nerve subluxation and adhesion formation postoperatively. METHODS: Thirteen patients underwent cubital tunnel surgery by the highlighted technique to prevent postoperative ulnar nerve subluxation and adhesion formation. Patient outcomes including elbow range of motion, functional status, paresthesia, and grip strength were recorded. RESULTS: Of the 13 patients, 10 had excellent results, 1 had a good result, and 2 required revision with anterior transposition of the nerve. The mean Mayo Elbow Performance Score of the 11 patients not needing revision was 92.7. CONCLUSION: The described surgical technique provides surgeons with the ability to directly decompress the ulnar nerve while decreasing postoperative complications such as instability and adhesion formation.

Patient-specific processes for occipitocervical fixation using biomodelling and additive manufacturing.

This report describes a novel method for occipitocervical fixation using a patient-specific, 3D-printed implant and tools. A 79-year-old female presented with progressive neck pain due to a pathologic fracture of C1. DICOM data was used to 3D-print 1:1 scale biomodels of the occipitocervical spine for pre-operative planning, patient education, and intraoperative reference. The surgeon collaborated with engineers to design and 3D-print a titanium patient-specific implant (PSI) and a stereotactic drill guide for occipitocervical screw fixation. The surgical plan specified the occipitocervical "neutral" position, screw sizes, entry points, and trajectories. The PSI was pre-contoured to match the posterior occipitocervical bony spine and reproduce the planned occipitocervical "neutral" position. Stereotactic portholes for screw fixation were integrated into the PSI. The planned "neutral" position was achieved by intraoperatively matching the occipitocervical alignment to the PSI. Screw placement under fluoroscopy was simplified using the stereotactic drill guide. There were no intraoperative or postoperative complications. At 6-month follow up, our patient reported resolution of symptoms and demonstrated satisfactory occipitocervical alignment without evidence of implant dysfunction. Our experience demonstrates that preoperative planning can be combined with biomodelling and 3D-printing to develop patient-specific tools and implants that are viable for occipitocervical fixation surgery.

Measuring the performance of patient-specific solutions for minimally invasive transforaminal lumbar interbody fusion surgery.

Pre-surgical planning using 3D-printed BioModels enables the preparation of a "patient-specific" kit to assist instrumented spinal fusion surgery. This approach has the potential to decrease operating time while also offering logistical benefits and cost savings for healthcare. We report our experience with this method in 129 consecutive patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) over 27 months at a single centre and performed by a single surgeon. Patient imaging and surgical planning software were used to manufacture a 3D-printed patient-specific MIS TLIF kit for each patient consisting of a 1:1 scale spine BioModel, stereotactic K-wire guide, osteotomy guide, and retractors. Pre-selected pedicle screws, rods, and cages were sourced and supplied with the patient-specific kit. Additional implants were available on-shelf to address a size discrepancy between the kit implant and intraoperative measurements. Each BioModel was used pre-operatively for surgical planning, patient consent and education. The BioModel was sterilised for intraoperative reference and navigation purposes. Efficiency measures included operating time (153 ±â€¯44 min), sterile tray usage (14 ±â€¯3), fluoroscopy screening time (57.2 ±â€¯23.7 s), operative waste (19 ±â€¯8 L contaminated, 116 ±â€¯30 L uncontaminated), and median hospital stay (4 days). The pre-selected kit implants exactly matched intraoperative measurements for 597/639 pedicle screws, 249/258 rods, and 46/148 cages. Pedicle screw placement accuracy was 97.8% (625/639) on postoperative CT. Complications included one intraoperative dural tear, no blood products administered, and six reoperations. Our experience demonstrates a viable application of patient-specific 3D-printed solutions and provides a benchmark for studies of efficiency in spinal fusion surgery.

Designing patient-specific 3D printed devices for posterior atlantoaxial transarticular fixation surgery.

Atlantoaxial transarticular screw fixation is an effective technique for arthrodesis. Surgical accuracy is critical due to the unique anatomy of the atlantoaxial region. Intraoperative aids such as computer-assisted navigation and drilling templates offer trajectory guidance but do not eliminate screw malposition. This study reports the operative and clinical performance of a novel process utilising biomodelling and 3D printing to develop patient specific solutions for posterior transarticular atlantoaxial fixation surgery. Software models and 3D printed 1:1 scale biomodels of the patient's bony atlantoaxial spine were developed from computed tomography data for surgical planning. The surgeon collaborated with a local medical device manufacturer using AnatomicsC3D to design patient specific titanium posterior atlantoaxial fixation implants using transarticular and posterior C1 arch screws. Software enabled the surgeon to specify screw trajectories, screw sizes, and simulate corrected atlantoaxial alignment allowing patient specific stereotactic drill guides and titanium posterior fixation implants to be manufactured using 3D printing. Three female patients with unilateral atlantoaxial osteoarthritis were treated using patient specific implants. Transarticular screws were placed using a percutaneous technique with fluoroscopy and neural monitoring. No screw malposition and no neural or vascular injuries were observed. Average operating and fluoroscopy times were 126.0 ±â€¯4.1 min and 36.7 ±â€¯11.5 s respectively. Blood loss was <50 ml per patient and length of stay was 4-6 days. Clinical and radiographic follow up data indicate satisfactory outcomes in all patients. This study demonstrates a safe, accurate, efficient, and relatively inexpensive process to stabilise the atlantoaxial spine using transarticular screws.

Teosinte inflorescence phytolith assemblages mirror Zea taxonomy.

Molecular DNA analyses of the New World grass (Poaceae) genus Zea, comprising five species, has resolved taxonomic issues including the most likely teosinte progenitor (Zea mays ssp. parviglumis) of maize (Zea mays ssp. mays). However, archaeologically, little is known about the use of teosinte by humans both prior to and after the domestication of maize. One potential line of evidence to explore these relationships is opaline phytoliths produced in teosinte fruit cases. Here we use multidimensional scaling and multiple discriminant analyses to determine if rondel phytolith assemblages from teosinte fruitcases reflect teosinte taxonomy. Our results indicate that rondel phytolith assemblages from the various taxa, including subspecies, can be statistically discriminated. This indicates that it will be possible to investigate the archaeological histories of teosinte use pending the recovery of appropriate samples.

The use of physical biomodelling in complex spinal surgery.

Prior studies have suggested that biomodels enhance patient education, preoperative planning and intra-operative stereotaxy; however, the usefulness of biomodels compared to regular imaging modalities such as X-ray, CT and MR has not been quantified. Our objective was to quantify the surgeon's perceptions on the usefulness of biomodels compared to standard visualisation modalities for preoperative planning and intra-operative anatomical reference. Physical biomodels were manufactured for a series of 26 consecutive patients with complex spinal pathologies using a stereolithographic technique based on CT data. The biomodels were used preoperatively for surgical planning and customising implants, and intra-operatively for anatomical reference. Following surgery, a detailed biomodel utility survey was completed by the surgeons, and informal telephone interviews were conducted with patients. Using biomodels, 21 deformity and 5 tumour cases were performed. Surgeons stated that the anatomical details were better visible on the biomodel than on other imaging modalities in 65% of cases, and exclusively visible on the biomodel in 11% of cases. Preoperative use of the biomodel led to a different decision regarding the choice of osteosynthetic materials used in 52% of cases, and the implantation site of osteosynthetic material in 74% of cases. Surgeons reported that the use of biomodels reduced operating time by a mean of 8% in tumour patients and 22% in deformity procedures. This study supports biomodelling as a useful, and sometimes essential tool in the armamentarium of imaging techniques used for complex spinal surgery.

Biomodeling as an aid to spinal instrumentation.

STUDY DESIGN: Prospective trial. OBJECTIVE: To develop and validate a new method of spinal stereotaxy. SUMMARY OF BACKGROUND DATA: Biomodeling has been found to be helpful for complex skeletal surgery. Frameless stereotaxy has been used for spinal surgery but has significant limitations. A novel stereotactic technique using biomodels has been developed. METHODS: Twenty patients with complex spinal disorders requiring instrumentation were recruited. A three-dimensional CT scan of their spine was performed, and the data were transferred via a DICOM network to a computer workstation. ANATOMICS BIOBUILD software was used to generate the code required to manufacture exact acrylate biomodels of each spine using rapid prototyping. The biomodels were used to obtain informed consent from patients and to simulate surgery. Simulation was performed using a standard power drill to place trajectory pins into the spinal biomodel. Acrylate drill guides were manufactured using the biomodels and trajectory pins as templates. The biomodels and drill guides were sterilized and used intraoperatively to assist with surgical navigation and the placement of instrumentation. RESULTS: The biomodels were found to be highly accurate and of great assistance in the planning and execution of the surgery. The ability to drill optimum screw trajectories into the biomodel and then accurately replicate the trajectory was judged especially helpful. Accurate screw placement was confirmed with postoperative CT scanning. The design of the first two templates was suboptimal as the contact surface area was too great and complex. Approximately 20 minutes was spent before surgery preparing each biomodel and template. Operating time was reduced, as less reliance on intraoperative radiograph was necessary. Patients stated that the biomodels improved informed consent. CONCLUSIONS: The authors have developed a novel method of spinal stereotaxy using exact plastic copies of the spine manufactured using biomodeling technology. Biomodel spinal stereotaxy is a simple and accurate technique that may have advantages over frameless stereotaxy.