Use of computer tomography imaging for analyzing bone remodeling around a percutaneous osseointegrated implant.

Osseointegration (OI) is being used for the direct skeletal attachment of prosthetic limbs using an intramedullary stem that extends percutaneously from the subject's residual limb. For this technology to be successful, bone ingrowth and remodeling around the implant must occur. Physicians need an effective way to assess bone remodeling to make informed treatment and rehabilitation decisions. Previous studies utilizing two-dimensional imaging X-ray as a tool to monitor bone-remodeling around OI devices have limitations. This study describes methodology that was developed utilizing computed tomography (CT) imaging as a tool for analyzing bone remodeling around a percutaneous OI implant. Six transfemoral amputees implanted with a percutaneous osseointegrated prosthesis (POP) had CT scans taken of their residual femur at 6 and 52 weeks postoperatively. Three-dimensional femoral models were processed using custom MATLAB script to collect cortical and medullary morphology measurements. Morphology data from 6- and 52-week scans were compared to quantify bone remodeling around the POP implant. Fifty-two weeks after implantation of the POP device, increases in cortical bone area and thickness were observed around the porous-coated stem. Minimal changes were observed in the medullary canal parameters within the periprosthetic regions. This study successfully utilized CT imaging and three-dimensional modeling techniques to analyze longitudinal data of bone remodeling around a transfemoral percutaneous implant. These methods have the potential to be used as a clinical tool for evaluating orthopedic implants in vivo. Data collected suggests that the POP device achieved the desired bone remodeling around the porous-coated region of the implanted stem.

Upper extremity prosthetic selection influences loading of transhumeral osseointegrated systems.

Percutaneous osseointegrated (OI) implants are increasingly viable as an alternative to socket suspension of prosthetic limbs. Upper extremity prostheses have also become more complex to better replicate hand and arm function and attempt to recreate pre-amputation functional levels. With more functionality comes heavier devices that put more stress on the bone-implant interface, which could be an issue for implant stability. This study quantified transhumeral loading at defined amputation levels using four simulated prosthetic limb-types: (1) body powered hook, (2) myoelectric hook, (3) myoelectric hand, and (4) advanced prosthetic limb. Computational models were constructed to replicate the weight distribution of each prosthesis type, then applied to motion capture data collected during Advanced Activities of Daily Living (AADLs). For activities that did not include a handheld weight, the body powered prosthesis bending moments were 13-33% (range of means for each activity across amputation levels) of the intact arm moments (reference 100%), torsional moments were 12-15%, and axial pullout forces were 30-40% of the intact case (p≤0.001). The myoelectric hook and hand bending moments were 60-99%, torsional moments were 44-97%, and axial pullout forces were 62-101% of the intact case. The advanced prosthesis bending moments were 177-201%, torsional moments were 164-326%, and axial pullout forces were 133-185% of the intact case (p≤0.001). The addition of a handheld weight for briefcase carry and jug lift activities reduced the overall impact of the prosthetic model itself, where the body powered forces and moments were much closer to those of the intact model, and more complex prostheses further increased forces and moments beyond the intact arm levels. These results reveal a ranked order in loading magnitude according to complexity of the prosthetic device, and highlight the importance of considering the patient's desired terminal device when planning post-operative percutaneous OI rehabilitation and training.

Robbery in progress: Historical museum collections bring to light a mitochondrial capture within a bird species widespread across southern Australia, the Copperback Quail-thrush Cinclosoma clarum.

We surveyed mitochondrial, autosomal, and Z chromosome diversity within and between the Copperback Quail-thrush Cinclosoma clarum and Chestnut Quail-thrush C. castanotum, which together span the arid and semi-arid zones of southern Australia, and primarily from specimens held in museum collections. We affirm the recent taxonomic separation of the two species and then focus on diversity within the more widespread of the two species, C. clarum. To guide further study of the system and what it offers to understanding the genomics of the differentiation and speciation processes, we develop and present a hypothesis to explain mitonuclear discordance that emerged in ourdata. Following a period of historical allopatry, secondary contact has resulted in an eastern mitochondrial genome replacing the western mitochondrial genome in western populations. This is predicted under a population-level invasion in the opposite direction, that of the western population invading the range of the eastern one. Mitochondrial captures can be driven by neutral, demographic processes, or adaptive mechanisms, and we favor the hypothesized capture being driven by neutral means. We cannot fully reject the adaptive process but suggest how these alternatives may be further tested. We acknowledge an alternative hypothesis, which finds some support in phenotypic data published elsewhere, namely that outcomes of secondary contact have been more complex than our current genomic data suggest. Discriminating and reconciling these two alternative hypotheses, which may not be mutually exclusive, could be tested with closer sampling at levels of population, individual, and nucleotide than has so far been possible. This would be further aided by knowledge of the genetic basis to phenotypic variation described elsewhere.

Initial stability of a percutaneous osseointegrated endoprosthesis with proximal interlocking screws for transhumeral amputees.

BACKGROUND: Percutaneous osseointegrated devices for skeletal fixation of prosthetic limbs have the potential to improve clinical outcomes in the transhumeral amputee population. Initial endoprosthesis stability is paramount for long-term osseointegration and safe clinical introduction of this technology. We evaluated an endoprosthetic design featuring a distally porous coated titanium stem with proximal slots for placement of bicortical interlocking screws. METHODS: Yield load, ultimate failure load, and construct stiffness were measured in 18 pairs of fresh-frozen and thawed cadaver humeri, at distal and proximal amputation levels, without and with screws, under axial pull-out, torsion, and bending loads. Paired statistical comparisons were performed without screws at the two resection levels, and at distal and proximal levels with and without screws. FINDINGS: Without screws, the location of the amputation influenced the stability only in torsional yield (p = 0.032) and torsional ultimate failure (p = 0.033). Proximally, the torsional yield and the torsional ultimate failure were 44% and 47% of that distally. Screws improved stability. In axial pull-out, screws increased the distal ultimate failure 3.2 times (p = 0.003). In torsion, screws increased the yield at the proximal level 1.9 times (p = 0.035), distal ultimate failure load 3.3 times (p = 0.016) and proximal ultimate failure 6.4 times (p = 0.013). In bending, screws increased ultimate failure at the proximal level 1.6 times (p = 0.026). INTERPRETATION: Proximal slots and bicortical interlocking screws may find application in percutaneous osseointegrated devices for patients with amputations, especially in the less stable proximal bone of a short residual limb.

Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes.

INTRODUCTION: Dystonia is a clinically and genetically heterogeneous disorder and a genetic cause is often difficult to elucidate. This is the first study to use whole genome sequencing (WGS) to investigate dystonia in a large sample of affected individuals. METHODS: WGS was performed on 111 probands with heterogenous dystonia phenotypes. We performed analysis for coding and non-coding variants, copy number variants (CNVs), and structural variants (SVs). We assessed for an association between dystonia and 10 known dystonia risk variants. RESULTS: A genetic diagnosis was obtained for 11.7% (13/111) of individuals. We found that a genetic diagnosis was more likely in those with an earlier age at onset, younger age at testing, and a combined dystonia phenotype. We identified pathogenic/likely-pathogenic variants in ADCY5 (n = 1), ATM (n = 1), GNAL (n = 2), GLB1 (n = 1), KMT2B (n = 2), PRKN (n = 2), PRRT2 (n = 1), SGCE (n = 2), and THAP1 (n = 1). CNVs were detected in 3 individuals. We found an association between the known risk variant ARSG rs11655081 and dystonia (p = 0.003). CONCLUSION: A genetic diagnosis was found in 11.7% of individuals with dystonia. The diagnostic yield was higher in those with an earlier age of onset, younger age at testing, and a combined dystonia phenotype. WGS may be particularly relevant for dystonia given that it allows for the detection of CNVs, which accounted for 23% of the genetically diagnosed cases.

Variation in bone response to the placement of percutaneous osseointegrated endoprostheses: A 24-month follow-up in sheep.

Percutaneous osseointegrated (OI) devices for amputees are metallic endoprostheses, that are surgically implanted into the residual stump bone and protrude through the skin, allowing attachment of an exoprosthetic limb. In contrast to standard socket suspension systems, these percutaneous OI devices provide superior attachment platforms for artificial limbs. However, bone adaptation, which includes atrophy and/or hypertrophy along the extent of the host bone-endoprosthetic interface, is seen clinically and depends upon where along the bone the device ultimately transfers loading forces to the skeletal system. The goal of this study was to determine if a percutaneous OI device, designed with a porous coated distal region and an end-loading collar, could promote and maintain stable bone attachment. A total of eight, 18 to 24-month old, mixed-breed sheep were surgically implanted with a percutaneous OI device. For 24-months, the animals were allowed to bear weight as tolerated and were monitored for signs of bone remodelling. At necropsy, the endoprosthesis and the surrounding tissues were harvested, radiographically imaged, and histomorphometrically analyzed to determine the periprosthetic bone adaptation in five animals. Bone growth into the porous coating was achieved in all five animals. Serial radiographic data showed stress-shielding related bone adaptation occurs based on the placement of the endoprosthetic stem. When collar placement and achieved end-bearing against the transected bone, distal bone conservation/hypertrophy was observed. The results supported the use of a distally loading and distally porous coated percutaneous OI device to achieve distal host bone maintenance.

Sex and Laterality Differences in Medullary Humerus Morphology.

Percutaneous osseointegrated (OI) prosthetic limb attachment holds promise for transhumeral amputees. Understanding humeral medullary morphology is necessary for informed design of upper extremity OI systems, and is beneficial to the field of megaprosthetic reconstruction of the distal humerus where diaphyseal fixation is desired. The purpose of this study was to quantify the sex and laterality differences in humerus morphology, specifically over the diaphysis. Three-dimensional surface reconstructions of 58 pairs of cadaveric humeri (43 male, 15 female) were generated from CT data. Measures describing periosteal and medullary morphology were collected relative to an anatomic coordinate system. Sex and laterality differences in biomechanical length (BML) were observed (P ≤ 0.001 and 0.022, respectively). Head radius was larger in males than females (P ≤ 0.001). Retroversion was increased in right humeri relative to left (P ≤ 0.001). Canal orientation exhibited a conformational shift from anteversion to retroversion distally at approximately 65% BML. Right humeri exhibited larger medullary diameters than left in the 1st and 2nd principal directions (P ≤ 0.024). Males displayed larger diameter medullary canals proximally (P ≤ 0.029) and an increased rate of divergence of the endosteal cortex in the proximal diaphysis (P ≤ 0.009). Females exhibited higher canal aspect ratios at mid-shaft (P ≤ 0.014) and lower mean cortical thickness (P ≤ 0.001). Human humeral diaphysis morphology exhibits sex and laterality differences, which are dependent on position along the diaphysis. Understanding humeral morphology is necessary to achieve adequate primary stability and bone apposition in design of endoprosthetic stems for percutaneous OI implants, and distal humerus replacement. Anat Rec, 302:1709-1717, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association for Anatomy.

Dissection by genomic and plumage variation of a geographically complex hybrid zone between two Australian non-sister parrot species, Platycercus adscitus and Platycercus eximius.

The study of hybrid zones advances understanding of the speciation process, and approaches incorporating genomic data are increasingly used to draw significant conclusions about the impact of hybridisation. Despite the progress made, the complex interplay of factors that can lead to substantially variable hybridisation outcomes are still not well understood, and many systems and/or groups remain comparatively poorly studied. Our study aims to broaden the literature on avian hybrid zones, investigating a potentially geographically and temporally complex putative hybrid zone between two native Australian non-sister parrot species, the pale-headed and eastern rosellas (Platycercus adscitus and Platycercus eximius, respectively). We analysed six plumage traits and >1400 RADseq loci and detected hybrid individuals and an unexpectedly complex geographic structure. The hybrid zone is larger than previously described due to either observer bias or its movement over recent decades. It comprises different subregions where genetic and plumage signals of admixture vary markedly in their concordance. Evidence of contemporary hybridisation (later generation and backcrossed individuals) both within and beyond the previously defined zone, when coupled with a lack of F1 hybrids and differential patterns of introgression among potentially diagnostic loci, indicates a lack of post-zygotic barriers to gene flow between species. Despite ongoing gene flow, species boundaries are likely maintained largely by strong pre-mating barriers. These findings are discussed in detail and future avenues for research into this system are proposed, which would be of benefit to the speciation and hybrid zone literature.

Guidelines for humeral subluxation cutoff values: a comparative study between conventional, reoriented, and three-dimensional computed tomography scans of healthy shoulders.

BACKGROUND: The humeral subluxation index (HSI) is frequently assessed on computed tomography (CT) scans in conditions of the shoulder characterized by humeral displacement. An arbitrarily set HSI cutoff value of 45% for anterior subluxation and 55% for posterior subluxation has been widely accepted. We studied whether mean values and thresholds of humeral subluxation, in relation to the glenoid and scapula, were influenced by different imaging modalities. METHODS: The HSIs referenced to the scapula (SHSI) and glenoid (GHSI) were compared between conventional CT scans, CT scans reoriented into the corresponding reference plane (ie, scapular plane for the SHSI and glenoid center plane for the GHSI), and 3-dimensional (3D) CT reconstructions of 120 healthy shoulders. The 95% normal range determined the cutoff values of humeral subluxation. RESULTS: The SHSI thresholds for conventional, reoriented, and 3D CT scans were 33%-61%, 44%-68%, and 49%-61%, respectively. A different mean SHSI was found for each imaging modality (conventional, 47%; reoriented, 56%; 3D, 55%; P ≤ .014), with the conventional SHSI showing an underestimation in 89% of the cases. GHSI thresholds for conventional, reoriented, and 3D CT scans were 40%-61%, 44%-56%, and 46%-54%, respectively. The mean GHSI did not differ between each imaging modality (conventional, 51%; reoriented, 50%; 3D, 50%; P = .146). CONCLUSIONS: The SHSI and GHSI are susceptible to different imaging modalities with consequently different cutoff values. The redefined HSI cutoff values guide physicians in the evaluation of humeral subluxation in conditions characterized by humeral displacement, depending on the available image data.

Transhumeral loading during advanced upper extremity activities of daily living.

Percutaneous osseointegrated (OI) implants for direct skeletal attachment of upper extremity prosthetics represent an alternative to traditional socket suspension that may yield improved patient function and satisfaction. This is especially true in high-level, transhumeral amputees where prosthetic fitting is challenging and abandonment rates remain high. However, maintaining mechanical integrity of the bone-implant interface is crucial for safe clinical introduction of this technology. The collection of population data on the transhumeral loading environment will aid in the design of compliance and overload protection devices that mitigate the risk of periprosthetic fracture. We collected marker-based upper extremity kinematic data from non-amputee volunteers during advanced activities of daily living (AADLs) that applied dynamic loading to the humerus. Inverse dynamic analysis was applied to calculate the axial force, bending and torsional moments at three virtual amputation levels representing 25, 50, and 75% residual humeral length. The influences of amputation level, elbow flexion constraint, gender and anthropometric scaling were assessed. Results indicate that the proximal (25%) amputation level experienced significantly higher axial forces and bending moments across all subjects when compared to distal amputation levels (p≤0.030). Constraining elbow flexion had a limited influence on peak transhumeral loads. Male subjects experienced higher axial forces during all evaluated activities (p≤0.023). Peak axial force for all activities occurred during jumping jacks (174.5N). Peak bending (57.6Nm) and torsional (57.2Nm) moments occurred during jumping jacks and rapid internal humeral rotation, respectively. Calculated loads fall within the range of implant fixation failure loads reported in cadaveric investigations of humeral stem fixation; indicating that periprosthetic fracture may occur during non-contact AADLs. These kinematic data, collected over a range of AADLs, will aid in the development of overload protection devices and appropriate post-operative rehabilitation protocols that balance return to an active lifestyle with patient safety.

Bone penetrance of locally administered vancomycin powder in a rat femur fracture model.

INTRODUCTION: Locally delivered, crystalline vancomycin has been suggested as a potential prophylactic measure against the development of deep and superficial surgical site infection. Clinical expectations regarding the duration and peak of drug concentration in local tissues following administration are unknown. Our goal was to develop concentration vs time curves for locally administered vancomycin powder in a high-energy, open femur fracture rat model in local tissues and to compare that data to two well performed similar, systemic administration studies. METHODS: After approval for animal research, 24 adult Sprague-Dawley rats sustained closed, midshaft femoral fracture under anesthesia. Fractures were caused via blunt guillotine with 750g metal rod dropped 50cm. Injured hindlimbs were surgically opened at fracture to simulate open injury and stabilized using 0.054 Kirschner wires. Vancomycin powder was administered using weight-based protocol (goal: 25mg/kg). Rats were sacrificed in groups of 4 at 4, 8, 24, 48, 72, 96h. Samples harvested included rat-tail venous blood prior to sacrifice, and femoral bone and anterior thigh soft-tissue were harvested post-mortem. High Performance Liquid Chromatography (HPLC) was performed on all samples. RESULTS: Concentration vs. time curves demonstrated that the surrounding soft-tissues demonstrated highest maximum concentration (1.5mg vancomycin/g muscle). Bone reached maximum average of 199µg vancomycin/g femur: approximately 13% of maximal soft-tissue absorption. Plasma reached maximum concentration of 1.8µg/mL plasma. All peaks at t=4h. Within 48h, average muscle vancomycin concentration dropped to 3µg/g muscle (0.2% maximum muscle concentration) and the average bone concentration dropped to 1.9µg/g femur (0.9% maximum bone concentration). Vancomycin was undetectable on all samples at 96h. Comparison to classical animal studies suggest local delivery to bone exceeds that of IV dosing for approximately 48h and may peak near concentrations of 102 multiples. CONCLUSIONS: Locally administered vancomycin provides drug delivery in excess of IV dosing for approximately 48h after intervention. Exponential decay demonstrates rapid removal of drug to near undetectable levels in bone, plasma, and local soft tissue thereafter in a rat model. Local delivery may generate concentrations exceeding that achievable by steady state systemic dosing for 48h.

Accuracy of 3D dual echo steady state (DESS) MR arthrography to quantify acetabular cartilage thickness.

PURPOSE: To deploy and quantify the accuracy of 3D dual echo steady state (DESS) MR arthrography with hip traction to image acetabular cartilage. Clinical magnetic resonance imaging (MRI) sequences used to image hip cartilage often have reduced out-of-plane resolution and may lack adequate signal-to-noise to image cartilage. MATERIALS AND METHODS: Saline was injected into four cadaver hips placed under traction. 3D DESS MRI scans were obtained before and after cores of cartilage were harvested from the acetabulum; the two MRIs were spatially aligned to reference core positions. The thickness of cartilage cores was measured under microscopy to serve as the reference standard. 3D reconstructions of cartilage and subchondral bone were generated using automatic and semiautomatic image segmentation. Cartilage thickness estimated from the 3D reconstructions was compared to physical measurements using Bland-Altman plots. RESULTS: As revealed by the automatic segmentation mask, saline imbibed the joint space throughout the articulating surface, with the exception of the posteroinferior region in two hips. Locations where air bubbles were introduced and regions of suspected low density bone disrupted an otherwise smooth automatic segmentation mask. Automatic and semiautomatic segmentation yielded a bias ± repeatability coefficient (95% limits of agreement) of 0.10 ± 0.51 mm (-0.41 to 0.61 mm) and 0.06 ± 0.43 mm (-0.37 to 0.49 mm), respectively. CONCLUSION: Cartilage thickness can be estimated to within ∼0.5 mm of the physical value with 95% confidence using 3D reconstructions of 3D DESS MR arthrography images. Manual correction of the automatic segmentation mask may improve reconstruction accuracy.