Identification of protective and 'at risk' HLA genotypes for the development of pseudotumours around metal-on-metal hip resurfacings.

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. 'Controls' were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two 'at risk' alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making.

Whole-body radiation exposure in Trauma and Orthopaedic surgery.

AIMS: The use of fluoroscopy in orthopaedic surgery creates risk of radiation exposure to surgeons. Appropriate personal protective equipment (PPE) can help mitigate this. The primary aim of this study was to assess if current radiation protection in orthopaedic trauma is safe. The secondary aims were to describe normative data of radiation exposure during common orthopaedic procedures, evaluate ways to improve any deficits in protection, and validate the use of electronic personal dosimeters (EPDs) in assessing radiation dose in orthopaedic surgery. METHODS: Radiation exposure to surgeons during common orthopaedic trauma operations was prospectively assessed using EPDs and thermoluminescent dosimeters (TLDs). Normative data for each operation type were calculated and compared to recommended guidelines. RESULTS: Current PPE appears to mitigate more than 90% of ionizing radiation in orthopaedic fluoroscopic procedures. There is a higher exposure to the inner thigh during seated procedures. EPDs provided results for individual procedures. CONCLUSION: PPE currently used by surgeons in orthopaedic trauma theatre adequately reduces radiation exposure to below recommended levels. Normative data per trauma case show specific anatomical areas of higher exposure, which may benefit from enhanced radiation protection. EPDs can be used to assess real-time radiation exposure in orthopaedic surgery. There may be a role in future medical wearables for orthopaedic surgeons.Cite this article: Bone Jt Open 2022;3(11):907-912.

The effect of indirect admission via hospital transfer on hip fracture patients in Ireland.

BACKGROUND AND AIMS: Current best practice states that hip fracture patients should undergo surgery within 48 hours to minimise perioperative complications. There are 10 emergency departments (EDs) in Ireland that receive hip fracture patients without a trauma and orthopaedic surgery unit on site. Idle periods and duplicated preoperative investigations can lead to a prolonged time to surgery. The aim of this study was to identify the effect of admission route on the time to surgery, length of stay and pressure ulcer development in patients who sustain a hip fracture in Ireland. METHODS: A retrospective cohort study was performed, using 2013 and 2014 data from the Irish Hip Fracture Database. Age, gender and ASA grade were identified as confounders and adjusted for accordingly. RESULTS: Of the 3893 hip fractures identified, indirect admissions via hospital transfer occurred in 8.6% of cases. Surgery was performed within 48 h in 72.0% of indirect admission and 73.7% of direct admission cases (p = 0.502). The length of stay was significantly prolonged for patients admitted via hospital transfer (25.6 compared to 19.6 days, p < 0.001). CONCLUSION: Delayed discharges post hip fracture have been shown to expose patients to increased perioperative morbidity and mortality rates, as well as reduced rehabilitation potential and less chance of returning home on discharge. This has significant cost implications for the health service and justifies the introduction of hospital bypass protocols for patients with hip fractures.

Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis.

BACKGROUND: Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. METHODS: In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. RESULTS: These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. CONCLUSION: The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.

3D Printing Aids Acetabular Reconstruction in Complex Revision Hip Arthroplasty.

Revision hip arthroplasty requires comprehensive appreciation of abnormal bony anatomy. Advances in radiology and manufacturing technology have made three-dimensional (3D) representation of osseous anatomy obtainable, which provide visual and tactile feedback. Such life-size 3D models were manufactured from computed tomography scans of three hip joints in two patients. The first patient had undergone multiple previous hip arthroplasties for bilateral hip infections, resulting in right-sided pelvic discontinuity and a severe left-sided posterosuperior acetabular deficiency. The second patient had a first-stage revision for infection and recurrent dislocations. Specific metal reduction protocols were used to reduce artefact. The images were imported into Materialise MIMICS 14.12®. The models were manufactured using selective laser sintering. Accurate templating was performed preoperatively. Acetabular cup, augment, buttress, and cage sizes were trialled using the models, before being adjusted, and resterilised, enhancing the preoperative decision-making process. Screw trajectory simulation was carried out, reducing the risk of neurovascular injury. With 3D printing technology, complex pelvic deformities were better evaluated and treated with improved precision. Life-size models allowed accurate surgical simulation, thus improving anatomical appreciation and preoperative planning. The accuracy and cost-effectiveness of the technique should prove invaluable as a tool to aid clinical practice.

The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density.

The Wnt/ß-catenin pathway is a major signaling cascade in bone biology, playing a key role in regulating bone development and remodeling, with aberrations in signaling resulting in disturbances in bone mass. The objectives of our study were to correlate serum Dkk1 expression with bone mineral density (BMD) and assess the potential role of Dkk1 as a serological marker of bone mass. Serum was collected from a cohort of patients (n = 36), 18 patients with a reduced BMD and 18 control patients. Serum Dkk1 expression as quantified by ELISA was correlated with lumbar and femoral t- and z-scores. Serum Dkk1 concentration in the osteoporosis group was significantly higher than control group (941 ± 116 vs. 558 ± 47 pg/ml, p < 0.01). Serum Dkk1 expression was highly correlated with bone mass variables with inverse associations found between serum Dkk1 expression and lumbar t-score (r = -0.34, p = 0.00433), lumbar z-score (r = -0.22, p = 0.1907), femur t-score (r = -0.42, p = 0.0101), and femur z-score (r = -0.43, p = 0.0089). Our data further emphasizes the pivotal role played by Wnt/ß-catenin signaling in bone mass regulation. Dkk1, a powerful antagonist of canonical Wnt signaling, may have a role to play as a serological marker for disorders of bone mass, warranting further evaluation.