Aims. This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). Methods. A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). Results. SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. Conclusion. Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI. Cite this article: Bone Joint Res 2022;11(12):843–853

Adamantinoma is a rare low-grade malignant epithelial bone tumour. We report a case of an expansile, osteolytic mid-diaphyseal tibial lesion found in a 12 year-old girl. An initial histological diagnosis of basaloid-type adamantinoma was made. Following excision, further histology demonstrated basaloid cells and acellular matrix focally surrounded by osteoclast giant cells with calcium deposits, features consistent with pilomatrixoma. Several histological variants of adamantinoma have been documented; this case details a previously unreported histological adamantinoma variant – pilomatrixoma-adaminatinoma

Liposarcoma is the most common soft tissue sarcoma accounting for 20% of all mesenchymal malignancies.We report a rare histological variant arising from the dorsum of the foot. A 55 year old lady presented with a slow growing, well defined swelling on the dorsum of the foot. Histological examination following complete excision showed a tumor with zones of dense collagenous tissue containing pleomorphic spindle cells and scattered atypical adipocytes. A diagnosis of spindle cell sarcoma was made and referred to the local Sarcoma unit. Repeat excision and histology confirmed margins free of tumor. Four years after primary excision, patient is well with no evidence of recurrence or metastasis. Spindle cell liposarcoma is a rare variant of well differentiated liposarcoma characterized by prominent spindle cell component. Previously reported cases originated in the subcutaneous tissues of shoulder girdle and upper limb. Main differential diagnoses include benign lesions such as spindle cell lipoma, and diffuse neurofibroma as well as dermatofibrosarcoma pro-tuberans and other malignancies such as sclerosing liposarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumor and fibromyxoid sarcoma. Spindle cell Liposarcomas tend to recur locally and may dedifferentiate with a potential for metastasis. Wide excision and long term follow up looking for recurrence and metastasis is necesssary in these rare variants of liposarcoma especially those arising at atypical sites as in our case

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

Ewing sarcoma (ES) is an aggressive sarcoma, and is the second most common bone sarcoma in childhood. Disease specific t(11;22)(~85–90%), t(21;22)(~5–10%), or rarer variant translocations with the involvement of chromosome 22 (~5%) are present. At the gene level, the EWSR1 gene fuses with FLI1, ERG or other ETS transcription factor family members. So far, no ES has been identified with a fusion to transcription factors other than ETS. By using a panel of molecular tools such as multicolor FISH and array-CGH, a ring chromosome containing chromosomes 20 and 22 was identified in four ES cases. Molecular karyotyping showed the translocation and amplification of regions of chromosomes 20q13 and 22q12. Cloning of the breakpoint showed an in-frame fusion between the EWSR1 and NFATc2 genes. The translocation led to the loss of the N-terminal, calcineurin-dependent control region. Consequently, the remaining intact DNA binding domain of NFATc2 is under control of the EWSR1 promoter region permitting oncogenic activation. Intriguingly, in all cases a distinct histological feature was observed. In conclusion: a new translocation involving EWS and NFATc2 was cloned that is associated with a histological variant of ES. The NFATc2 transcription factor is not a member of the ETS family of transcription factors. NFTAC2 has well characterized functions in T-cell differentiation and immune response. For the first time a direct involvement of NFATc2 in oncogenesis has been shown

Aim: To assess the effectiveness of a physiotherapist led normal variant clinic for children. Method: The study comprised all children presenting to the physiotherapy clinic at the Royal Liverpool Children’s hospital between January 2000 and January 2006. The clinic is run by two specialist physiotherapists alongside a consultant led Orthopaedic clinic, providing support as required. Physiotherapy staff are able to request and interpret radiographs and order blood tests independently. The numbers of patients, the range of conditions seen in the clinic, and the outcome of the consultations recorded in the practitioner case-notes were examined for the purpose of this study. Complete data was available for the full period under review except for the year 2003. Results: During the five year study period 1594 children were seen, a mean of 318 patients annually (range 267–387). The age distribution of patients was 33.1% (527) under the age of 2, 38.9% (620) 2–5 years, 19.3% (307) 5–10 years and 8.8% (140) 10–16 years. The most common conditions seen were genu valgum 28.7% (458), genu varum 18.4% (293), in-toeing 14.7% (234) and toe walking 6.0% (96). Most patients (94.7% n=1509) were managed independent of consultant supervision by the physiotherapist. A minority of patients required consultant review in the clinic (4.2% n=67). Fewer still were referred to another medical clinic (1.1% n=18). Conclusions: Children with a spectrum of orthopaedic conditions can be appropriately managed by a trained physiotherapist independent of consultant input

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

Evidence has accumulated in recent years that programmed cell death (PCD) is not necessarily synonymous with the classical apoptosis, as defined by Kerr & Wyllie (J Path, 1973, 111:255–261), but that cells use a variety of pathways to undergo cell death, which are reflected by different morphologies. Although chondrocytes with the hallmark features of classical apoptosis have been demonstrated in culture, such cells are extremely rare in vivo. We have examined the morphological differences between dying chondrocytes and classical apoptotic cells in growth plate and osteoarthritic chondrocytes. Unlike classical apoptosis, chondrocyte death involves an increase in the endoplasmic reticulum and Golgi apparatus. This is likely to reflect an increase in protein synthesis with retention of proteins in the ER leading to expansion of the ER lumen, whose membranes surround and compartmentalise organelles and parts of cytoplasm. The final removal of apoptotic remains does not involve phagocytosis, but a combination of three routes: 1) auto-digestion of cellular material within compartments formed by ER membranes; 2) autophagic vacuoles and 3) extrusion of cell remnants into the lacunae. Together these processes lead to complete self-destruction of the chondrocyte as evidenced by the presence of empty lacunae. The involvement of ER suggests that the endoplasmic reticulum pathway of apoptosis may play a greater role in chondroptosis than receptor-mediated and mitochondrial pathways. Lysosomal proteases, present in autophagic digestion, are likely to be as important as caspases in the programmed cell death of chondrocytes in vivo. We propose the term ‘chondroptosis’ to reflect the fact that such cells are undergoing apoptosis, albeit in a non-classical manner, but one that appears to be typical of programmed chondrocyte death in vivo. Chondroptosis may serve to eliminate cells that are not phagocytosed by neighboring cells, which constitutes a crucial advantage for chondrocytes that are typically embedded in an extracellular matrix. Classical apoptosis in that situation is likely to lead to secondary necrosis with all its disadvantages. This may be the reason why most programmed cell death of chondrocytes in vivo appears to follow a chondroptotic pattern and not the classical apoptotic pattern. At present the initiation factors or the molecular pathways involved in chondroptosis remain unclear.

We present a review of our Specialist Physiotherapy clinic for normal physiological variations of the lower limb (SPNV) clinics, demonstrating them to be clinically effective and cost effective.

Children with normal variation of rotational profile and limb angulation present much anxiety to parents and primary care. Providing consultation: to eliminate significant pathology and reassure families, is an important service that a Paediatric Orthopaedic department provides. In our tertiary referral department we have a Specialist Physiotherapy led clinics into which primary care practitioners refer children with whom there are concerns about lower limb development variation.

The (SPNV) Clinic was first set up by a Consultant and Senior Physiotherapist in 1999. The aim of the clinic was to reduce the waiting times for incoming referrals but ensuring they are seen in an appropriate environment by an experienced health care professional. Clinics are run by Senior Specialist Physiotherapists, alongside Consultant clinics who are available for advice and direction. This provides security for the physios, the Trust and the patient.

Over 15 years there have been more than 4000 patient visits to this clinic. Over 80% were new patient visits. 70% of these visits were discharged in one or two reviews. 97.4% of new referrals were discharged without subsequent review by an orthopaedic surgeon. The most common conditions reviewed were Genu valgum (25%), Genu Varum (16%), intoeing (17%) and flexible flat feet (11%).

The clinic has proven to be cost effective as well in drawing in up to £500,000 revenue into the trust in a single year. The department has been approached by other trusts to assist in the implementation of similar clinics.

We present this review of the patients, as a template for supporting the work of Paediatric Orthopaedic Departments. This service has facilitated the streamlining of our Consultant Paediatric Orthopaedic clinics.

Purpose: The bifoliated vascularised fibula graft is an attractive alternative for reconstruction of large bone segments. The purpose of this work was to evaluate mid-term results and the usefulness of two surgical techniques: skin island flap monitoring and the arterio-venous loop.

Material and methods: This retrospective analysis included fourteen patients (eleven men and three women) treated between 1992 and 2002. Mean age was 30 years (10–54). Indications were complications of open fractures in nine patients, major bone loss in two, septic nonunion in four, and aseptic nonunion in three. Reconstruction was performed after bone tumour resection in five patients involving immediate reconstruction after failure of an infected massive allograft in four of them. Localisations were: tibia (n=6), femur (n=5), humerus (n=2), and pelvis (n=1). Average bone loss was 10 cm (7–15 cm). Minimal pinning, cerclage or screwing was used to stabilise the flap completed by internal fixation in four patients and external fixation in ten. A monitoring skin island was used for twelve patients (the island was technically impossible in two patients). Vascular anastomoses were performed in seven patients using an arteriovenous loop, performed as a preliminary measure in six.

Results: Mean follow-up was 35 months. One patient died early from tumour progression. Among the seven patients who had an arteriovenous loop, one required revision for a vascular complication. For the seven “classical” bypasses, there were three intraoperative or early complications requiring revision of the anastomoses. Nonunion developed despite early revision in the four patients whose monitoring skin island suffered. Consolidation was achieved without revision in all patients who skin island did not suffer; time to bone healing was eleven months for seven of them.

Conclusion: Bone healing was related to the quality of graft vacularisation. Clinical observation of the monitoring island was the best way to identify vascular complications early and initiate treatment. Use of a preliminary arteriovenous loop decreased the risk of vascular insufficiency inherent with long bypasses and shortened operative time.

Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154

The regenerative capacity of hyaline cartilage is greatly limited. To prevent the onset of osteoarthritis, cartilage defects have to be properly treated. Cartilage, tissue engineered by mean of bioactive glass (BG) scaffolds presents a promising approach. Until now, conventional BGs have been used mostly for bone regeneration, as they are able to form a hydroxyapatite (HA) layer and are therefore, less suited for cartilage reconstruction. The aim of this study is to compare two BGs based on a novel BG composition tailored specifically for cartilage (CAR12N) and patented by us with conventional BG (BG1393) with a similar topology. The highly porous scaffolds consisting of 100% BG (CAR12N, CAR12N with low Ca2+/Mg2+ and BG1393) were characterized and dynamically seeded with primary porcine articular chondrocytes (pACs) or primary human mesenchymal stem cells (hMSCs) for up to 21 days. Subsequently, cell viability, DNA and glycosaminoglycan contents, cartilage-specific gene and protein expression were evaluated. The manufacturing process led to a comparable high (over 80%) porosity in all scaffold variants. Ion release and pH profiles confirmed bioactivity for them. After both, 7 and 21 days, more than 60% of the total surfaces of all three glass scaffold variants was densely colonized by cells with a vitality rate of more than 80%. The GAG content was significantly higher in BG1393 colonized with pACs. In general, the GAG content was higher in pAC colonized scaffolds in comparison to those seeded with hMSCs. The gene expression of cartilage-specific collagen type II, aggrecan, SOX9 and FOXO1 could be detected in all scaffold variants, irrespectively whether seeded with pACs or hMSCs. Cartilage-specific ECM components could also be detected at the protein level. In conclusion, all three BGs allow the maintenance of the chondrogenic phenotype or chondrogenic differentiation of hMSCs and thus, they present a high potential for cartilage regeneration

Aims. The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two variants: single and twin peg OUKA. The purpose of this study was to assess the stability of both variants in a worst-case scenario of bone defects and suboptimal cementation. Methods. Single and twin pegs were implanted randomly allocated in 12 pairs of human fresh-frozen femora. We generated 5° bone defects at the posterior condyle. Relative movement was simulated using a servohydraulic pulser, and analyzed at 70°/115° knee flexion. Relative movement was surveyed at seven points of measurement on implant and bone, using an optic system. Results. At the main fixation zone, the twin peg shows less relative movement at 70°/115°. At the transition zone, relative movements are smaller for the single peg for both angles. The single peg shows higher compression at 70° flexion, whereas the twin peg design shows higher compression at 115°. X-displacement is significantly higher for the single peg at 115°. Conclusion. Bony defects should be avoided in OUKA. The twin peg shows high resilience against push-out force and should be preferred over the single peg. Cite this article: Bone Joint Res 2022;11(2):82–90

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776

Abstract. Introduction. In cementless UKR, early post-operative tibial fractures are 7x more common in very small tibias. A smaller keel has been shown to reduce this fracture risk, but its effect on fixation is unassessed. This mechanical study assesses the effect of keel interference and size on sagittal micromotion of the tibial component in physiological loading positions. Method. A high-resolution Digital Image Correlation setup was developed and validated to an accuracy of 50 micrometres. Variants of tibial components were 3D-printed: standard, no-interference, no-keel, and a new small keel. Components were implanted into bone-analogue foam which was machined to a CT-reconstructed small tibia, using surgical technique. Tibias were loaded to 200N in physiological loading positions: 8mm (step-up) and 15mm (lunge) posterior to midpoint, and micromotion was assessed. Results. In all tests, anterior lift-off was the largest micromotion observed. In ‘step-up’, a standard keel moved more than the no-interference and no-keel variants (340μm-vs-63μm-vs-30μm, p=0.002). In ‘lunge’ loading, the no-interference and no-keel variants moved more than the standard (826μm-vs-1003μm-vs-521μm, p=0.039). The small keel experienced less micromotion in ‘step-up’ (245μm-vs-340μm p=0.233, overall p=0.009) and ‘lunge’ (378μm-vs-521μm p=0.265, overall p=0.006) than the standard keel. Conclusion. The keel protects against large tibial micromotion during lunge movement. Counterintuitively, interference increases micromotion during step-up movement, likely due to implant pivoting around the bone-keel interface. Results suggest patients should be advised against lunge movements early post-operatively. The new smaller keel fixes similarly or better than the standard keel, making it viable for replacing the standard keel to potentially reduce fracture risk

Dual Mobility (DM) Total Hip Replacements (THRs), are becoming widely used but function in-vivo is not fully understood. The aim of this study was to compare the incidence of impingement of a modular dual mobility with that of a standard cup. A geometrical model of one subject's bony anatomy \[1\] was developed, a THR was implanted with the cup at a range of inclination and anteversion positions (Corail® stem, Pinnacle® cup (DePuy Synthes)). Two DM variants and one STD acetabular cup were modelled. Joint motions were taken from kinematic data of activities of daily living associated with dislocation \[2\] and walking. The occurrence of impingement was assessed for each component combination, orientation and activity. Implant-implant impingement can occur between the femoral neck and the metal or PE liner (DM or STD constructs respectively) or neck-PE mobile liner (DM only). The results comprise a colour coded matrix which sums the number of impingement events for each cup position and activity and for each implant variant. Neck-PE mobile liner impingement, occurred for both DM sizes, for all activities, and most cup placement positions indicating that the PE mobile liner is likely to move at the start of all activities including walking. For all constructs no placement positions avoided neck-metal (DM) or neck-PE liner (STD) impingementevents in all activities. The least number of events occurred at higher inclination and anteversion component positions. In addition to implant-implant impingement, some instances of bone-bone and implant-bone impingement were also observed. Consistent with DM philosophy, neck-PE mobile liner impingement and liner motion occurred for all activities including walking. Neck-liner impingement frequency was comparable between both DM sizes (metal liner) and a standard cup (PE liner)

Background. Intervertebral disc degeneration (DD) is a complex age-related condition that constitutes the main risk factor for disabling back pain. DD is assessed using different traits extracted from MR imaging (MRI), normally combined to give summary measures (e.g. Pfirmann score). The aetiology of DD is poorly understood and despite its high heritability (75%), the precise genetic predisposition is yet to be defined. Genome wide association study (GWAS) is used to discover genetic variants associated with a disease or phenotype. It tests variants across the whole genome. It requires large samples to provide adequate but unfortunately there is poor availability of spine imaging data due to the high cost of MRI. We have adopted new methods to examine different MRI traits independently and use the information of those traits to boost GWAS power using specialized statistical software for jointly analyse correlated traits. Methods/Results. We examined DD MRI features disc narrowing, disc bulge, disc signal intensity and osteophyte formation in the TwinsUK cohort who had undergone T2-weighted sagittal spine MRI. GWAS were performed on the four traits. MTAG software was used to boost single trait GWAS power using the information in the other trait GWAS. 9 different loci were identified. Conclusions. Preliminary results suggest genes GDF6, SP1/SP7 are associated with individual trait signal intensity. In addition, novel associated genes with potential for shedding new light on pathogenic mechanisms are identified. Additional cohorts will be included in the design as a replication to test reproducibility of the results. Conflicts of interest: No conflicts of interest. Sources of funding: Funded by Disc4All, EU Horizon 2020, MSCA-2020-ITN-ETN GA: 955735

Objectives. Congenital cruciate ligament deficiency is a rare condition that may occur in isolation or in association with longitudinal limb deficiencies such as fibular hemimelia or proximal femoral focal deficiency. Often anomalies of the menisci and their attachments can be very abnormal and impact on surgical management by standard techniques. Arthroscopic surgical knee reconstruction is undertaken to improve symptomatic instability and/or to stabilise and protect the knee for future planned limb lengthening surgery. The aim of this study is to evaluate the arthroscopic findings of patients undergoing surgery for congenital cruciate ligament deficiency, and specifically to determine the frequency and types of meniscal anatomical variations seen in these cases. Methods. Patients undergoing surgery for congenital cruciate ligament deficiency were identified from a prospectively collated database. Diagnosis was confirmed through review of the clinical notes and imaging. Operative notes and 4K saved arthroscopic images and video recordings for these cases were reviewed. Results. Over a six-year period (July 2017 – September 2023), 42 patients underwent surgery for congenital ligament deficiency and tibiofemoral instability (45 surgical episodes). Median age of patients at time of surgery was 10 years (range 4 – 17 years). The most frequent diagnosis was congenital longitudinal limb deficiency syndromes in 27 cases, with the most frequent being fibular hemimelia. Isolated congenital ligament deficiency without any other associated extra-articular manifestations occurred in 11 cases. Absence of meniscal root attachments or hypertrophy of meniscofemoral ligaments acting as ‘pseudo-cruciates’ were seen in over 25% of patients. In isolated ACL deficiency these were injured causing onset of instability symptoms and pain following trauma. Often these abnormal structures required addressing to allow surgical reconstruction. Conclusions. Our findings demonstrate that there are often meniscal variations seen in association with congenital absence or hypoplasia of the cruciate ligaments. In these patients hypertrophied meniscofemoral ligaments may act as cruciate-like structures and play a role in providing a degree of sagittal plane stability to the knee. However, when the knee becomes unstable to the point that cruciate ligament reconstruction is indicated, these meniscal variants may often require stabilisation using complex meniscal root repair techniques or variations to standard cruciate ligament reconstruction techniques to accommodate the variant anatomy

Osteoarthritis (OA) is the most common form of arthritis and one of the ten most disabling diseases in developed countries. Total joint replacement (TJR) is considered by far as the most effective treatment for end-stage OA patients. The majority of patients achieve symptomatic improvement following TJR. However, about 22% of the TJR patients either do not improve or deteriorate after surgery. Several potential non-genetic predictors for the TJR outcome have been investigated. However, the results were either inconclusive or had very limited predictive power. The aim of this study was to identify genetic variants for the poor outcome of TJR in primary OA patients by a genome-wide association study (GWAS). Study participants were total knee or hip replacement patients due to primary OA who were recruited to the Newfoundland Osteoarthritis Study (NFOAS) before 2017. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess pain and functional impairment pre- and 3.99±1.38 years post-surgery. Two non-responder classification criteria were used in our study. One was defined by an absolute WOMAC change score. Participants with a change score less than 7/20 points for pain were considered as pain non-responders; and those with less than 22/68 points for function were classified as function non-responders. The second one was the Outcome Measures in Arthritis Clinical Trials and the Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Blood DNA samples were genotyped using the Illumina GWAS microarrays genotyping platform. The quality control (QC) filtering was performed on GWAS data before the association of the genetic variants with non-responders to TJR was tested using the GenABEL package in R with adjustment for the relatedness of the study population and using the commonly accepted GWAS significance threshold p < 5*10. −8. to control multiple testing. In total, 316 knee and 122 hip OA patients (mean age 65.45±7.62 years, and 58% females) passed the QC check. These study participants included 368 responders and 56 non-responders to pain, and 364 responders and 68 non-responders to function based on the absolute WOMAC point score change classification. While 377 responders and 56 non-responders to pain, and 366 responders and 71 non-responders to function were identified by the OMERACT-OARSI classification criteria. Interestingly, the same results were obtained by both classification methods, and we found that the G allele of rs4797006 was significantly associated with pain non-responders with odds ratio (OR) of 5.12 (p<7.27×10. -10. ). This SNP is in intron one of the melanocortin receptor 5 (MC5R) gene on chr18. This gene plays central roles in immune response, pain sensitivity, and negative regulation of inflammatory response to antigenic stimulus. The A allele of rs200752023 was associated with function non-responders with OR of 4.41 (p<3.29×10. -8. ). The SNP is located in intron three of the RNA Binding Fox-1 Homolog 3 (RBFOX3) gene on chr17 which has been associated with numerous neurological disorders. Our data suggested that two chromosomal regions are associated with TJR poor outcomes and could be the novel targets for developing strategies to improve the outcome of the TJR

Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies. Cite this article: Bone Joint Res 2022;11(6):342–345