Investigation of the short-term in vivo performance of metal-on-carbon fibre reinforced poly ether ether ketone Motec wrists: an explant analysis.

Total wrist arthroplasty (TWA) aims to restore pain-free motion to diseased joints. One such TWA, the Motec, has demonstrated good results with acceptable complication rates. It has recently been suggested that the metal-on-carbon fibre reinforced poly ether ether ketone (Mo-CFR-PEEK) version of the Motec TWA be implanted instead of the metal-on-metal version. An explant analysis was undertaken on seven Motec Mo-CFR-PEEK TWAs, revised for a variety of reasons, after a mean time of 2 years in vivo. Compared to a new Motec implant, five of the explanted metal heads and three of the CFR-PEEK cups became smoother in vivo, suggesting self-polishing and negative skewness, indicating some material loss in vivo. Two explanted cups showed indentation marks on their rims and one of these was from component impingement with embedded metallic debris. In the short-term, the articulating surfaces of Motec Mo-CFR-PEEK TWAs did not show major damage.Level of evidence: IV.

MGMT ProFWise: Unlocking a New Application for Combined Feature Selection and the Rank-Based Weighting Method to Link MGMT Methylation Status to Serum Protein Expression in Patients with Glioblastoma.

Glioblastoma (GBM) is a fatal brain tumor with limited treatment options. O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is the central molecular biomarker linked to both the response to temozolomide, the standard chemotherapy drug employed for GBM, and to patient survival. However, MGMT status is captured on tumor tissue which, given the difficulty in acquisition, limits the use of this molecular feature for treatment monitoring. MGMT protein expression levels may offer additional insights into the mechanistic understanding of MGMT but, currently, they correlate poorly to promoter methylation. The difficulty of acquiring tumor tissue for MGMT testing drives the need for non-invasive methods to predict MGMT status. Feature selection aims to identify the most informative features to build accurate and interpretable prediction models. This study explores the new application of a combined feature selection (i.e., LASSO and mRMR) and the rank-based weighting method (i.e., MGMT ProFWise) to non-invasively link MGMT promoter methylation status and serum protein expression in patients with GBM. Our method provides promising results, reducing dimensionality (by more than 95%) when employed on two large-scale proteomic datasets (7k SomaScan® panel and CPTAC) for all our analyses. The computational results indicate that the proposed approach provides 14 shared serum biomarkers that may be helpful for diagnostic, prognostic, and/or predictive operations for GBM-related processes, given further validation.

Impingement-related osteolysis in Motec total wrist arthroplasty: an explant analysis and review of the literature.

We present five cases of osteolysis in the Motec total wrist prosthesis, three around the radial implant, one around the metacarpal implant and one around both. Three of these were progressive and required revision, and biomechanical explant analyses of these revised prostheses were performed. Ex vivo testing of the contact points of the Motec implants was also performed at maximum extension. Here, impingement occurs between the metacarpal screw and the dorsal rim of the cup (non-articulating surfaces) with the short-necked prosthesis, leading to metacarpal screw damage, titanium debris formation and osteolysis. An analysis of three previously published cases suggests that this may have been the likely mode of failure in those cases. This complication is preventable by avoiding use of the short-neck prosthesis.Level of evidence: IV.

Long-term results and explant analysis of the ReMotion total wrist arthroplasty.

The ReMotion wrist replacement has good short- to medium-term survival with an acceptable complication profile as we previously reported in a cohort of patients with rheumatoid arthritis. We now report the long-term results of the same cohort and details of explant analysis of revisions undertaken for aseptic loosening. A total of 16 wrists were reviewed. Seven prostheses remain in situ with no obvious signs of wear or radiological loosening at a mean follow-up of 15.5 years. Three wrists had been revised: one for infection and two for aseptic loosening. Five patients (six wrists) died 2-9 years after operation from unrelated causes. Explant analysis demonstrated relatively minor wear compared with the published results of the Universal-2 prosthesis. We hypothesize that this may be explained by differences in polyethylene sterilization and prosthetic design. The ReMotion wrist replacement has favourable long-term results in patients with rheumatoid arthritis with a 16-year survival rate of 78%-86%.Level of evidence: IV.

An Overview of CD133 as a Functional Unit of Prognosis and Treatment Resistance in Glioblastoma.

Biomarkers for resistance in Glioblastoma multiforme (GBM) are lacking, and progress in the clinic has been slow to arrive. CD133 (prominin-1) is a membrane-bound glycoprotein on the surface of cancer stem cells (CSCs) that has been associated with poor prognosis, therapy resistance, and tumor recurrence in GBM. Due to its connection to CSCs, to which tumor resistance and recurrence have been partially attributed in GBM, there is a growing field of research revolving around the potential role of CD133 in each of these processes. However, despite encouraging results in vitro and in vivo, the biological interplay of CD133 with these components is still unclear, causing a lack of clinical application. In parallel, omic data from biospecimens that include CD133 are beginning to emerge, increasing the importance of understanding CD133 for the effective use of these highly dimensional data sets. Given the significant mechanistic overlap, prioritization of the most robust findings is necessary to optimize the transition of CD133 to clinical applications using patient-derived biospecimens. As a result, this review aims to compile and analyze the current research regarding CD133 as a functional unit in GBM, exploring its connections to prognosis, the tumor microenvironment, tumor resistance, and tumor recurrence.

Long-term outcomes of the Universal 2 total wrist replacement: revision and loosening at 10 years and beyond.

The aim of this study was to ascertain the long-term revision rates of the Universal 2 wrist prosthesis in a previously published cohort of patients with rheumatoid arthritis. The time to, and reasons for revision were determined. Radiographs were analysed to determine whether loosening had occurred in the long-term according to the Wrightington zonal classification of loosening. Seventy-eight wrists from the original cohort of 85 wrists could be identified for analysis. The longest follow-up was 16 years and 29 wrists had follow-up beyond 10 years. Seventeen wrists had been revised or were on the waiting list for revision, an overall revision rate of 22%. The 10-year survivorship was 78%. Long-term revision was commonly for periprosthetic loosening with pain and component subsidence. In those with more than 10-year follow-up, significant lucency was seen in 16 carpal components and 15 radial components. Explant analysis showed significant polyethylene wear and we postulate this is the principal reason for component loosening.Level of evidence: IV.

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

Background: Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed-type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods: At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype, and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time-dependent receiver operator curves. Results: Using next-generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure, and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1% for pre-operative and post-operative models respectively. Conclusions: The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient's genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient-specific responses to different biomaterials.

Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells.

We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.

Metallosis is commonly associated with magnetically controlled growing rods; results from an independent multicentre explant database.

PURPOSE: Determine the incidence of metallosis around MAGEC rods. METHODS: A multicentre explant database was searched to identify cases with complete intraoperative findings at rod removal. Surgeons removing rods detailed the presence or absence of tissue metallosis associated with rods. More recently surgeons measured the 'length' of tissue metallosis. Prior to rod disassembly, the majority underwent testing with an external remote controller (ERC). The impact of clinical and explant variables on metallosis was assessed. RESULTS: Sixty-six cases were identified. Mean age at insertion was 8.1 ± 2.3 years with mean duration of implantation 37.6 ± 15.1 months. Tissue metallosis was noted at revision surgery in 52/66 cases (79%). Metallosis was noted more commonly when rods were removed during fusion surgery than rod removal/exchange (97% vs. 58% (p = < 0.01)). The mass at insertion was greater in cases with metallosis (25.9 ± 7.8 kg vs. 21.1 ± 6.2 kg, p = 0.04). Length of tissue metallosis was reported for 45 rods, median 9 cm (range 1-25). Metallosis was noted in 43/59 (73%) rods that produced no force and 22/30 (73%) rods that produced some force on ERC activation (p = 0.96). Wear debris was found within the actuator in all rods, and all but 3 rods had damaged O-rings. CONCLUSION: MAGEC rods are associated with tissue metallosis in the majority of cases. It is seen with functional rods as well as failed rods and appears related to wear debris within the actuator and high rates of O-ring failure. Until the implications of metal debris in children are known, we urge caution with the use of this implant.

Malignant mitral valve prolapse: an uncommon variation of a common condition.

Mitral valve prolapse affects up to 3% of the population, with an annual risk of death of up to 2% a year. Presentation is often in the third to fourth decade of life. This report details an adolescent with mitral valve prolapse with non-specific symptoms but investigative findings of ventricular ectopy at higher heart rates. These patients warrant close surveillance to monitor for progressive arrhythmias and may progress to need an ICD.

Sites of fractures in explanted NeuFlex® silicone metacarpophalangeal joint prostheses.

Single-piece silicone implants dominate metacarpophalangeal joint arthroplasty. The NeuFlex® implant was introduced to improve on the clinical performance of other silicone implants by having a pre-flexed hinge. By visually examining a cohort of 30 explanted NeuFlex® metacarpophalangeal joint prostheses we sought to identify the failure modes of these implants. Seven were not fractured, 11 had fractured across the hinge, nine had fractured at the junction of the distal stem and the hinge, and three showed fractures at both the hinge and at the junction of the distal stem and the hinge. These data may prove helpful in identifying how the performance of single-piece silicone implant designs can be improved.

Investigation of Taper Failure in a Contemporary Metal-on-Metal Hip Arthroplasty System Through Examination of Unused and Explanted Prostheses.

BACKGROUND: Large-diameter (≥36-mm) metal-on-metal (MoM) total hip replacements have been shown to fail at an unacceptably high rate. Globally, the DePuy Pinnacle prosthesis was the most widely used device of this type. There is evidence to suggest that one of the main reasons for the poor clinical performance of large-diameter MoM prostheses is the metal debris released from the head-stem taper junction-i.e., taper junction failure. The aim of this study was to investigate variation in the as-manufactured finish of the female taper surface and to determine its influence on material loss. We hypothesized that rougher surfaces with higher relative material peaks would be significantly associated with greater taper wear rates. METHODS: We analyzed 93 Articul/eze femoral head tapers with a 36-mm bearing diameter that had been used in combination with a Corail titanium uncemented stem. The influence of the surface topography of the as-manufactured female taper surface on taper wear was examined by means of a multiple regression model, taking into account other known variables. RESULTS: We identified great variation in the as-manufactured surface finish of the female taper surface, with a range of measured Ra values from 0.14 to 4.20 µm. The roughness of the female taper surface appeared to be the most important variable associated with taper wear (p < 0.001). The best-fitting regression model, including duration in vivo, head offset, reduced peak height (Rpk) value, stem shaft angle, and bearing surface wear rate, explained approximately 44% of the variation in taper wear rates. CONCLUSIONS: We concluded that the roughness of the female taper surface appears to be a significant factor in metal debris release from head-stem taper junctions. CLINICAL RELEVANCE: This study shows evidence that previously unappreciated variations in manufacturing processes may have a major impact on the clinical outcomes of patients.

Surgical criteria for femoroacetabular impingement syndrome: a scoping review.

BACKGROUND: The purpose of this review was to analyse and report criteria used for open and arthroscopic surgical treatment of femoroacetabular impingement syndrome (FAIS). METHODS: A librarian-assisted computer search of Medline, CINAHL and Embase for studies related to criterion for FAIS surgery was used in this study. Inclusion criteria included studies with the primary purpose of surgery or surgical outcomes for treatment of FAIS with and without labral tear, and reporting criteria for FAIS surgery. RESULTS: Diagnostic imaging was a criterion for surgery in 92% of the included studies, with alpha angle the most frequently reported (68% of studies) criterion. Reporting of symptoms was a criterion for surgery in 75%, and special tests a criterion in 70% of studies. Range-of-motion limitations were only a required criterion in 30%, only 12% of studies required intra-articular injection and 44% of studies described previously failed treatment (non-surgical or physiotherapist-led rehabilitation) as a criterion for surgery. Only 56% of included studies utilised the combination of symptoms, clinical signs and diagnostic imaging combined for diagnosis of FAIS as suggested by the Warwick Agreement on FAIS meeting. CONCLUSION: Diagnostic imaging evidence of FAIS was the most commonly reported criterion for surgery. Only 56% of included studies utilised the combination of symptoms, clinical signs and diagnostic imaging for diagnosis of FAIS as suggested by the Warwick Agreement on FAIS meeting, and only 44% of studies had failed non-surgical treatment (and 18% a failed trial of physiotherapy) as a criterion for surgery.

Retrospective cohort study of the performance of the Pinnacle metal on metal (MoM) total hip replacement: a single-centre investigation in combination with the findings of a national retrieval centre.

OBJECTIVES: To determine risk factors for revision in patients implanted with a commonly used metal on metal (MoM) hip replacement. DESIGN: Retrospective cohort study in combination with a prospective national retrieval study (Northern Retrieval Registry (NRR)). SETTING: Combined orthopaedic unit in combination with the NRR. PARTICIPANTS: All patients implanted with a DePuy Pinnacle MoM hip prostheses by the 2 senior authors were invited to attend for a review which included clinical examination, blood metal ion measurements, radiographs and targeted imaging. Explanted components underwent wear analysis using validated methodology and these results were compared with those obtained from the NRR. RESULTS: 489 MoM Pinnacle hips were implanted into 434 patients (243 females and 191 males). Of these, 352 patients attended the MoM recall clinics. 64 patients had died during the study period. For the purposes of survival analysis, non-attendees were assumed to have well-functioning prostheses. The mean follow-up of the cohort as a whole was 89 months. 71 hips were revised. Prosthetic survival for the whole cohort was 83.6% (79.9-87.3) at 9 years. The majority of explanted devices exhibited signs of taper junction failure. Risk factors for revision were bilateral MoM prostheses, smaller Pinnacle liners, and implantation in 2006 and later years. A significant number of devices were found to be manufactured out of their specifications. This was confirmed with analysis of the wider data set from the NRR. CONCLUSIONS: This device was found to have an unacceptably high revision rate. Bilateral prostheses, those implanted into female patients and devices implanted in later years were found to be at greater risk. A significant number of explanted components were found to be manufactured with bearing diameters outside of the manufacturer's stated tolerances. Our findings highlight the clinical importance of hitherto unrecognised variations in device production.

Topographical analysis of the femoral components of ex vivo total knee replacements.

With greater numbers of primary knee replacements now performed in younger patients there is a demand for improved performance. Surface roughness of the femoral component has been proposed as a causative mechanism for premature prosthesis failure. Nineteen retrieved total knee replacements were analysed using a non-contacting profilometer to measure the femoral component surface roughness. The Hood technique was used to analyse the wear and surface damage of the matching ultra-high molecular weight polyethylene (UHMWPE) tibial components. All femoral components were shown to be up to 11× rougher after their time in vivo while 95 % showed a change in skewness, further indicating wear. This increase in roughness occurred relatively soon after implantation (within 1 year) and remained unchanged thereafter. Mostly, this roughness was more apparent on the lateral condyle than the medial. This increased femoral surface roughness likely led to damage of the UHMWPE tibial component and increased Hood scores.