Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Tenosynovial giant cell tumours: experience at an Australian tertiary referral centre for musculoskeletal tumours with minimum two-year follow-up.

Aims: Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates. Methods: A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis. Results: There were 111 total cases included in the study; 71 (64%) were female, the mean age was 36 years (SD 13.6), and the knee (n = 64; 57.7%) was the most commonly affected joint. In all, 60 patients (54.1%) had diffuse-type (D-TGCT) disease, and 94 patients (84.7%) presented therapy-naïve as "primary cases" (PC). The overall recurrence rate was 46.8% for TGCT. There was a statistically significant difference in recurrence rates between D-TGCT and localized disease (75.0% vs 13.7%, relative risk (RR) 3.40, 95% confidence interval (CI) 2.17 to 5.34; p < 0.001), and for those who were referred in the "revision cases" (RC) group compared to the PC group (82.4% vs 48.9%, RR 1.68, 95% CI 1.24 to 2.28; p = 0.011). Age, sex, tumour volume, and mean duration of symptoms were not associated with recurrence (p > 0.05). Conclusion: Recurrence rates remain high even at a tertiary referral hospital. Highest rates are seen in D-TGCT and "revision cases". Due to the risks of recurrence, the complexity of surgery, and the need for adjuvant therapy, this paper further supports the management of TGCT in a tertiary referral multi-disciplinary orthopaedic oncology service.

Eukaryogenesis and oxygen in Earth history.

The endosymbiotic origin of mitochondria during eukaryogenesis has long been viewed as an adaptive response to the oxygenation of Earth's surface environment, presuming a fundamentally aerobic lifestyle for the free-living bacterial ancestors of mitochondria. This oxygen-centric view has been robustly challenged by recent advances in the Earth and life sciences. While the permanent oxygenation of the atmosphere above trace concentrations is now thought to have occurred 2.2 billion years ago, large parts of the deep ocean remained anoxic until less than 0.5 billion years ago. Neither fossils nor molecular clocks correlate the origin of mitochondria, or eukaryogenesis more broadly, to either of these planetary redox transitions. Instead, mitochondria-bearing eukaryotes are consistently dated to between these two oxygenation events, during an interval of pervasive deep-sea anoxia and variable surface-water oxygenation. The discovery and cultivation of the Asgard archaea has reinforced metabolic evidence that eukaryogenesis was initially mediated by syntrophic H2 exchange between an archaeal host and an α-proteobacterial symbiont living under anoxia. Together, these results temporally, spatially and metabolically decouple the earliest stages of eukaryogenesis from the oxygen content of the surface ocean and atmosphere. Rather than reflecting the ancestral metabolic state, obligate aerobiosis in eukaryotes is most probably derived, having only become globally widespread over the past 1 billion years as atmospheric oxygen approached modern levels.

Survival of the Systems.

Since Darwin, individuals and more recently genes, have been the focus of evolutionary thinking. The idea that selection operates on nonreproducing, higher-level systems including ecosystems or societies, has met with scepticism. But research emphasising that natural selection can be based solely on differential persistence invites reconsideration of their evolution. Self-perpetuating feedback cycles involving biotic as well as abiotic components are critical to determining persistence. Evolution of autocatalytic networks of molecules is well studied, but the principles hold for any 'self-perpetuating' system. Ecosystem examples include coral reefs, rainforests, and savannahs. Societal examples include agricultural systems, dominant belief systems, and economies. Persistence-based selection of feedbacks can help us understand how ecological and societal systems survive or fail in a changing world.

Uranium isotopes distinguish two geochemically distinct stages during the later Cambrian SPICE event.

Anoxic marine zones were common in early Paleozoic oceans (542-400 Ma), and present a potential link to atmospheric pO2 via feedbacks linking global marine phosphorous recycling, primary production and organic carbon burial. Uranium (U) isotopes in carbonate rocks track the extent of ocean anoxia, whereas carbon (C) and sulfur (S) isotopes track the burial of organic carbon and pyrite sulfur (primary long-term sources of atmospheric oxygen). In combination, these proxies therefore reveal the comparative dynamics of ocean anoxia and oxygen liberation to the atmosphere over million-year time scales. Here we report high-precision uranium isotopic data in marine carbonates deposited during the Late Cambrian 'SPICE' event, at ca. 499 Ma, documenting a well-defined -0.18‰ negative δ238U excursion that occurs at the onset of the SPICE event's positive δ13C and δ34S excursions, but peaks (and tails off) before them. Dynamic modelling shows that the different response of the U reservoir cannot be attributed solely to differences in residence times or reservoir sizes - suggesting that two chemically distinct ocean states occurred within the SPICE event. The first ocean stage involved a global expansion of euxinic waters, triggering the spike in U burial, and peaking in conjunction with a well-known trilobite extinction event. During the second stage widespread euxinia waned, causing U removal to tail off, but enhanced organic carbon and pyrite burial continued, coinciding with evidence for severe sulfate depletion in the oceans (Gill et al., 2011). We discuss scenarios for how an interval of elevated pyrite and organic carbon burial could have been sustained without widespread euxinia in the water column (both non-sulfidic anoxia and/or a more oxygenated ocean state are possibilities). Either way, the SPICE event encompasses two different stages of elevated organic carbon and pyrite burial maintained by high nutrient fluxes to the ocean, and potentially sustained by internal marine geochemical feedbacks.

Natural selection for costly nutrient recycling in simulated microbial metacommunities.

Recycling of essential nutrients occurs at scales from microbial communities to global biogeochemical cycles, often in association with ecological interactions in which two or more species utilise each others' metabolic by-products. However, recycling loops may be unstable; sequences of reactions leading to net recycling may be parasitised by side-reactions causing nutrient loss, while some reactions in any closed recycling loop are likely to be costly to participants. Here we examine the stability of nutrient recycling loops in an individual-based ecosystem model based on microbial functional types that differ in their metabolism. A supplied nutrient is utilised by a "source" functional type, generating a secondary nutrient that is subsequently used by two other types-a "mutualist" that regenerates the initial nutrient at a growth rate cost, and a "parasite" that produces a refractory waste product but does not incur any additional cost. The three functional types are distributed across a metacommunity in which separate patches are linked by a stochastic diffusive migration process. Regions of high mutualist abundance feature high levels of nutrient recycling and increased local population density leading to greater export of individuals, allowing the source-mutualist recycling loop to spread across the system. Individual-level selection favouring parasites is balanced by patch-level selection for high productivity, indirectly favouring mutualists due to the synergistic productivity benefits of the recycling loop they support. This suggests that multi-level selection may promote nutrient cycling and thereby help to explain the apparent ubiquity and stability of nutrient recycling in nature.

Symbiotic physiology promotes homeostasis in Daisyworld.

A connection is hypothesized between the physiological consequences of mutualistic symbiosis and life's average long-term impact on certain highly biologically conserved environmental variables. This hypothesis is developed analytically and with a variant of the Daisyworld model. Biological homeostasis is frequently effective due to co-ordination between opposing physiological "rein" functions, which buffer an organism in response to an external (often environmental) perturbation. It is proposed that during evolutionary history the pooling of different species' physiological functions in mutualistic symbioses increased the range of suboptimal environmental conditions that could be buffered against--a mutual tolerance benefit sometimes sufficient to outweigh the cost of cooperation. A related argument is that for a small number of biologically-crucial physical variables (i) the difference between organism interiors and the life-environment interface is relatively low, and (ii) the biologically optimum level of that variable is relatively highly conserved across different species. For such variables, symbiosis tends to cause (at a cost) an increase in the number of environmental buffering functions per unit of selection, which in turn biases the overall impact of the biota on the state of the variable towards the biological optimum. When a costly but more temperature-tolerant and physiologically versatile symbiosis between one black (warming) and one white (cooling) "daisy" is added to the (otherwise unaltered) Daisyworld parable, four new results emerge: (1) The extension of habitability to a wider luminosity range, (2) resistance to the impact of "cheater" white daisies with cold optima, that derive short-term benefit from environmental destabilisation, (3) the capacity to maintain residual, oscillatory regulation in response to forcings that change more rapidly than allele frequencies and (crucially) (4) "succession"-type dynamics in which the tolerant symbiosis colonises and to an extent makes habitable an otherwise lifeless environment, but is later displaced by free-living genotypes that have higher local fitness once conditions improve. The final result is arguably analogous to lichen colonisation of the Neoproterozoic land surface, followed by the Phanerozoic rise of vascular plants. Caution is necessary in extrapolating from the Daisyworld parable to real ecology/geochemistry, but sufficiently conserved variables may be water potential, macronutrient stoichiometry and (to a lesser extent) the temperature window for metabolic activity.

A comparison of conventional guidewire alignment jigs with imageless computer navigation in hip resurfacing arthroplasty.

BACKGROUND: Correct positioning of the initial femoral guidewire is vital in order to prepare the femoral head properly for hip resurfacing. The purpose of the present investigation was to determine the accuracy and precision of the placement of the initial femoral guidewire with use of conventional alignment jigs and to compare the results with those of imageless computer navigation. METHODS: Five commercially available jigs (two lateral pin jigs, two neck centering jigs, and one head planing jig) were obtained. Four surgeons used each jig and navigation three times to insert a guidewire in 10 degrees of relative valgus and neutral version into individual synthetic femora. A single surgeon then used each jig three times to align the initial guidewire in 10 degrees of relative valgus and neutral version in each of ten human cadaver femora. Radiographs of the synthetic and human femora were made to assess and compare guidewire inclination and version between conventional instrumentation and navigation. RESULTS: Navigation provided ranges of error in the coronal guidewire alignment of up to eight times less than the conventional jigs, but both methods provided similar ranges of error for version. In both arms of the study, there were significant differences in coronal alignment accuracy between the two neck centering jigs. Next to navigation, one lateral pin jig provided the most accurate coronal placement of the initial guidewire whereas one neck centering jig provided the most precise coronal placement of the guidewire. Navigation was similar to conventional jigs in terms of the accuracy and precision of guidewire version. CONCLUSIONS: In hip resurfacing arthroplasty, the choice of a femoral alignment device may influence the accuracy and precision of guidewire insertion, ultimately impacting femoral component placement. Imageless computer navigation can facilitate accurate and precise coronal alignment of the initial femoral guidewire, superior to that of conventional instrumentation. CLINICAL RELEVANCE: The results of this study may aid surgeons in the selection of alignment instruments for placement of the initial femoral guidewire during hip resurfacing.

Assessment of accuracy and reliability in preoperative templating for hip resurfacing arthroplasty.

The current study investigated the accuracy and reliability of hip resurfacing component selection based on digital preoperative templating. Four surgeons made a template of preoperative radiographs on 2 occasions for acetabular and femoral components in 50 randomly selected hip resurfacing patients. Component selection reliability was variable among surgeons (kappa = 0.16-0.73) and fair between surgeons (kappa = 0.23-0.32). The average percentage of agreement for the acetabular component was 47% (range, 32%-64%) and for the femoral component was 54% (range, 38%-70%). Surgeons tended to underestimate implant size if the correct implant was not chosen (acetabular, 29%; femoral, 32%). Selection of an undersized femoral component may lead to femoral neck notching or varus implant alignment. This study emphasizes the need for intraoperative verification of preoperative templating results to ensure optimal implant selection in hip resurfacing.

Bilateral total hip arthroplasty in Severe Hereditary Multiple Exostosis: a report of two cases.

Staged bilateral hip arthroplasties were carried out in two patients with osteoarthritis of the hip secondary to the development of hip dysplasia in Hereditary Multiple Exostosis (HME).Both patients had near ankylosis of their hips with pain and difficulty in performing activities of daily living. A proximal femur replacing prosthesis was implanted through an extended trochanteric osteotomy, with preservation of as much proximal bone stock as possible. At latest followup (two to five years), there was a sustained improvement in range of motion and symptoms. The Harris Hip Scores improved from 25 and 31 to 83 and 78. The Toronto Extremity Salvage Scores improved from 49% and 55% to 88% and 75%. Radiographs show bony ingrowth and healing of the trochanteric fragments. In severe HME, hip arthroplasty with replacement of the proximal femur provides good symptomatic relief and return of hip joint movement.

Fluctuation in the physical environment as a mechanism for reinforcing evolutionary transitions.

We hypothesize a mechanism for reinforcing transitions between levels of selection, involving physiological homeostasis and amplification of variation in the physical environment. Groups experience a stronger selection pressure than individuals for homeostasis with respect to reproductively limiting variables, because their greater longevity exposes them more often to suboptimal physical conditions, and greater physical size means they encompass a larger fraction of any resource/nutrient gradient. Groups achieve homeostasis by differentiation into microcosms with specialist functions, e.g. cell types. Such differentiation is more limited in individuals due to their smaller size and shorter lifespan. Hence tolerance of fluctuation in certain physical variables is proposed to be weaker in individuals than in groups. We show that a trait providing increased tolerance (alpha) to fluctuation (V-V(opt)) in a limiting abiotic variable (V), at relative fitness cost (C), can increase from rarity if the condition alpha.mid R:V-V(opt)|>C is met. Groups also sequester larger absolute quantities of resource than individuals, and group death is less frequent, hence the population dynamics of groups cause resource/nutrient availability to fluctuate with greater amplitude than that of individuals. Increasing the amplitude of fluctuation in a reproductively limiting environmental variable is proposed as a mechanism by which a group can limit reproduction of parasitic "cheat" individuals. Enhancing physical fluctuation is frequency dependent, hence only an increase in tolerance to fluctuation can explain the group's increase from rarity. However, once groups reach intermediate frequencies, a positive feedback process can be initiated in which a differentiated group enhances physical fluctuation beyond the tolerance of any "cheat", and in so doing enhances the selection pressure it experiences for homeostasis. This may help explain the persistence of transitions in individuality, and the coincidence of some such transitions with periods of change and oscillation in global scale environmental variables.