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Ten-year follow-up of fracture risk in a systematic population-based screening program: the risk-stratified osteoporosis strategy evaluation (ROSE) randomised trial.
BACKGROUND: Osteoporotic fractures pose a growing public health concern. Osteoporosis is underdiagnosed and undertreated, highlighting the necessity of systematic screening programs. We aimed to evaluate the effectiveness of a two-step population-based osteoporotic screening program. METHODS: This ten-year follow-up of the Risk-stratified Osteoporosis Strategy Evaluation (ROSE) randomized trial tested the effectiveness of a screening program utilizing the Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOF) to select women for dual-energy x-ray absorptiometry (DXA) scan following standard osteoporosis treatment. Women residing in the Region of Southern Denmark, aged 65-80, were randomised (single masked) into a screening or a control group by a computer program prior to inclusion and subsequently approached with a mailed questionnaire. Based on the questionnaire data, women in the screening group with a FRAX value ≥15% were invited for DXA scanning. The primary outcome was MOF derived from nationwide registers. ClinicalTrials.gov: NCT01388244, status: Completed. FINDINGS: All randomised women were included February 4, 2010-January 8, 2011, the same day as approached to participate. During follow-up, 7355 MOFs were observed. No differences in incidences of MOF were identified, comparing the 17,072 women in the screening group with the 17,157 controls in the intention-to-treat analysis (IRR 1.01, 0.95; 1.06). However, per-protocol, women DXA-scanned exhibited a 14% lower incidence of MOF (IRR 0.86, 0.78; 0.94) than controls with a FRAX value ≥15%. Similar trends were observed for hip fractures, all fractures, and mortality. INTERPRETATION: While the ROSE program had no overall effect on osteoporotic fracture incidence or mortality it showed a preventive effect for women at moderate to high risk who underwent DXA scans. Hence the overall effect might have been diluted by those who were not at an intervention level threshold risk or those who did not show up for DXA. Using self-administered questionnaires as screening tools may be inefficient for systematic screening due to the low and differential screening uptake. FUNDING: INTERREG and the Region of Southern Denmark.
Novel La1−xCaxMnO3 perovskite materials for chemical looping combustion applications
Novel customized lanthanum calcium manganese (LCM) perovskite structures were synthesized as candidate materials for chemical looping combustion (CLC) following the coprecipitation method and varying the Ca percentage (0, 30, 50, 70, 100 wt%). Their ability either to offer oxygen and thus oxidize CH4 during the fuel oxidation stage, and/or to reversibly receive oxygen during the solid oxidation stage was explored performing pulse reaction experiments in a lab scale, fixed-bed reactor at 1000°C. Their stability in multiple redox cycles was also further explored in a larger, fluid-bed reactor unit, where the stability of the optimum oxygen carrier material (OCM) sample was further investigated (up to 100 redox cycles). All materials were physicochemically characterized before and after their use (porosity characteristics by N2 adsorption-desorption isotherms, identification of crystalline phases by X-ray diffraction, morphological observation by scanning electron microscopy, investigation of the redox properties by H2-TPR, TPD-O2, and TPO), in an effort to track down any alterations in their textural and morphological characteristics, as a result of Ca doping and multiple reduction-oxidation cycles. All materials exhibited varying efficiency concerning their oxygen transfer capacity (OTC), their CH4 oxidation ability, their selectivity to CO2 and CO, and their stability in multiple reduction-oxidation cycles, a behavior depending on the Ca content and derived physicochemical properties. The reducibility and the oxygen adsorption capacity of the as synthesized LCM samples is enhanced with increasing Ca content with CaMnO3 (LCM100) presenting the best redox properties and suggested as the most promising OCM among the studied perovskites, reaching a maximum OTC of 7.73 wt% at 1000°C. Further evaluation of the CaMnO3 perovskite at lower temperatures (720°C, 820°C, and 920°C) showed great redox potential, while the spongy morphology and the reduction-oxidation ability of the sample was retained after multiple redox cycles.
Engineering the Catalytic Properties of HZSM5 by Cobalt Modification and Post-synthetic Hierarchical Porosity Development
Hierarchical zeolites have been identified as special catalytic materials with improved catalytic properties. In this study, hierarchical bifunctional ZSM5 based catalysts were prepared by desilication for controlled mesoporosity development and have been modified by Co doping. Their performance in the catalytic pyrolysis of oak in a lab scale reactor was evaluated. Desilicated counterparts were proven more active in deoxygenation of bio oil, while carbon deposition on the catalysts reduced compared to non-desilicated counterparts. Increased Lewis acidity favors decarboxylation reactions, while higher olefins as well as PAH content indicate easier diffusion within and from the porous network and interactions in the mesopores. The conversion of bulky lignin molecules (alkoxy phenols) is enhanced by the mesopores, while acidity is of secondary importance. Coke deposition inside the pores is more profound in the desilicated catalysts due to larger pore size. Carbon deposition on the catalysts is reduced in the following order: HZSM5 > Co/HZSM5 > Ds-HZSM5 > Co/Ds-HZSM5. GC–MS characterization of the CH2Cl2 soluble coke indicated that for the desilicated counterparts the main coke precursors are the bulky lignin molecules which are partially deoxygenated.
A prenatal skin atlas reveals immune regulation of human skin morphogenesis.
Human prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7-17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated in scarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin1. The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells.
Threaded rods versus arthrodesis nail as a static spacer for two-stage revision total knee arthroplasty.
INTRODUCTION: A spacer is required to maintain limb length and alignment and to provide a stable limb for mobilisation in two-stage revision total knee arthroplasty (rTKA) for periprosthetic joint infection (PJI). Static spacers are indicated in cases of massive bone loss, compromised soft tissues, and ligamentous and/or extensor mechanism insufficiency. The aim of this study was to compare the use of Ilizarov rods to arthrodesis nails for static spacer constructs in first-stage rTKA for PJI. METHODS: This was a retrospective cohort study of 40 patients who underwent two-stage rTKA for PJI between 2019 and 2022. Static spacers were used in all cases, constructed from Ilizarov rods 20 patients and nails in 20 patients. Data collected included number of previous revisions, patient age at first revision, comorbidities and identified organisms. Groups were compared based on outcome measures including complications, reoperations, length of stay and re-revision rates. RESULTS: The use of Ilizarov rods showed higher rates of intraoperative complications (5% vs. 0%), readmissions (55% vs. 5%), and interstage re-operations (50% vs. 10%). Spacer-related complications occurred in 10 of 20 cases (50%) in the Ilizarov rod group, all due to spacer fractures, compared to none in the nail group (0%) (p
External femoral rotation of 2 degrees is associated with the lowest stuffing rates around the femur in functionally aligned TKA.
PURPOSE: Modifying femoral morphology after total knee arthroplasty (TKA) poses a potential risk for ligament-imbalances and patella mal-tracking. The purpose of this study was primarily to quantify TKA-induced stuffing around the femur and secondarily assess the effect of femoral rotation (FR) on trochlear and condylar anatomy-changes. METHODS: Knee anatomy-modification was quantified in 69 robotic-assisted TKAs utilising tibia-based functional alignment (FA). Caliper-measurements were performed on the medial (Med), central (Ctr), and lateral (Lat) sides of the following resection planes: anterior trochlea (AT), oblique trochlea (OT), distal condyles (DC), posterior condyles (PC) and tibia (TIB). The same caliper-measurements were performed on the femoral components used to calculate bone-implant differences and analyse possible patterns of postoperative trochlear anatomy-modifications (TAM) and condylar anatomy-modifications (CAM). Over- or understuffing analysis for different FRs and regression analysis were conducted to assess the effect of FR on CAM and TAM. RESULTS: TAM results were Lat-AT -3.2 mm ([95% confidence interval [CI]: -3.71 to -2.63], p 2 mm in 60.9%, 39.1%, and 39.1%, respectively. CAM results were Med-DC -3.6 mm ([95%CI: -4.14 to -3.05], p 0.001) with stuffing > 2 mm in 78.3% and 63.8%. FR (3.8 ± 2.6°, range: -1.6° to 8.5°) affected mostly the anterior (r = -0.40, p 2 mm and ≥ 4 mm. CONCLUSIONS: FA-typical modification-pattern was a TAM with lateral facet understuffing, and CAM with medial distal understuffing and lateral posterior overstuffing. Trochlear groove height was non-significantly affected by FR. FA with the current off-the-shelf implant induces the lowest stuffing rates when set in 2° external femoral rotation. LEVEL OF EVIDENCE: Level II.
Low confidence in the cumulative evidence for the existence of a volume-outcome relationship after revision total knee replacement: A systematic review and meta-analysis.
PURPOSE: This systematic review and meta-analysis aimed to establish the relationship between the number of procedures a hospital or surgeon performs with outcomes following revision knee replacement (RevKR). METHODS: MEDLINE and Embase were searched using Ovid silver platter up to December 2024 for randomised controlled trials and cohort studies that reported RevKR volumes, in at least two categories, performed by hospitals and surgeons and their relationship to patient and provider level outcomes. The primary outcome was re-revision rate. Secondary outcomes included mortality, post-operative complications, patient-reported outcomes measures (PROMs), emergency readmissions and hospital length of stay. The effect estimates were pooled and plotted using a random-effects, non-linear dose-response meta-analysis (DRMA). Where limitations in the data prohibited DRMA, a narrative approach was utilised. ROBINS-I and the GRADE approach were used to assess the risk of bias and the confidence in the cumulative evidence, respectively. RESULTS: A total of 10 cohort studies with data from 1993 to 2021 were included. The confidence in the cumulative evidence exploring the relationship between surgeon/hospital volume and all outcomes after RevKR was very low. An inconsistent relationship was seen between hospital and surgeon volume and re-revision at any point. There was a non-linear dose-response relationship between higher hospital volume and lower odds of adverse post-operative events (p
Indications for lateral unicompartmental knee arthroplasty - A systematic review.
BACKGROUND: While evidence-based indications are established for medial UKA, the optimal indications for lateral UKA have not received as much attention. There exists significant anatomical, osteoarthritis phenotype, kinematic, and surgical technique differences between medial and lateral UKA. The indications for the two procedures may therefore not be identical. Hence, this review aims to access the indications and contraindications in published cohort studies on lateral UKA, to assess if consensus exists. METHODS: In May 2024, a systematic review was carried out following the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort studies on lateral UKA with a clear report of indications were included. Data on indications and contraindications were extracted to evaluate consensus. Furthermore, outcomes related to expanding or testing indications for lateral UKA were obtained. RESULTS: 38 studies were included. Lateral UKA was mostly performed for primary lateral osteoarthritis. The most reported indications were moderate to severe lateral osteoarthritis, with full-thickness cartilage in the medial compartment, intact ligaments, a correctable valgus deformity, and a flexion contracture
Higher hospital volume reduces early failure rates in single-stage revision TKR for infection: An analysis of the United Kingdom National Joint Registry and National Administrative Databases.
PURPOSE: Revision knee replacement (RevKR) for infection is rare but increasing. It is hypothesised that higher hospital volume reduces adverse outcomes. The aim was to estimate the association of surgical unit volume with outcomes following first, single-stage RevKR for infection. METHODS: This population-based cohort study merged data from the United Kingdom National Joint Registry, Hospital Episode Statistics, National Patient Reported Outcome Measures and the Civil Registrations of Death. Patients undergoing procedures between 1 January 2009 and 30 June 2019 were included. Early outcomes were chosen to reflect the quality of the surgical provision and included re-revision at 2 years, mortality, serious medical complications, length of stay and patient-reported outcome measures (PROMs). Adjusted fixed effect multivariable regression models were used to examine the association between surgical unit mean annual caseload and the risk of adverse outcomes. RESULTS: A total of 1477 patients underwent first-time single-stage RevKRs for infection across 267 surgical units and 716 surgeons. Following adjustment for age, gender, American Society of Anaesthesiologists grade, surgeon volume, year of surgery and operation funder and modelling surgical unit volume with restricted cubic spline, a greater mean annual volume was associated with a lower risk of re-revision at 2 years. The odds of re-revision in hospitals performing fewer than or equal to 12 cases per year was 2.53 (95% confidence interval = 1.50-4.31) times more likely than hospitals performing three to four cases per month. Annual variation in surgical unit volume was not associated with mortality and serious medical complications within 90 days. Only 99 out of 1477 (7%) of patients had linked PROMs which precluded subsequent analysis. CONCLUSION: Overall, higher volume surgical units had lower rates of early re-revision following the first RevKR for infection. We were unable to provide recommended specific volume thresholds for units; however, the probability of re-revision appears to be lowest in the highest volume units. LEVEL OF EVIDENCE: Level III, retrospective cohort study of prospectively collected data.
'Obviously, because it's a tear it won't necessarily mend itself': a qualitative study of patient experiences and expectations of treatment for a meniscal tear.
OBJECTIVES: There is a paucity of qualitative research exploring the patient experience of living with a meniscal tear, vital to effective patient management. The aim of this study was to explore the experiences and expectations of treatment of patients aged 18-55 years with a meniscal tear of the knee. DESIGN: Qualitative study involving semistructured interviews. SETTING: Participants were selected from nine secondary care centres in England. PARTICIPANTS: 10 participants diagnosed with a meniscal tear were recruited from the Meniscal Tear Outcome cohort study using a purposive sampling strategy until data saturation was achieved. Semistructured interviews were conducted between April and May 2021 and thematic analysis was used to identify key patient experiences. RESULTS: Themes identified relate to the broad areas of symptoms, clinical consultation and experience of treatment. Meniscal tears have a profound impact on pain and many patients experience effects on their family and financial life in addition to physical symptoms. Participants expected most of their management to occur in secondary care and most thought surgery would be a definitive treatment, while they believed the effectiveness of physiotherapy could not be guaranteed as it would not fix the physical tear. CONCLUSION: This study is one of the first to explore patient experiences of a meniscal tear and their perceptions of treatment options. Patient experiences and perceptions are important for clinicians to understand in order to provide the best possible care. It is important to elicit these experiences, listen to the patient, discuss their perspectives and build these experiences and expectations into clinical care. TRIAL REGISTRATION NUMBER: ISRCTN11534691.
FRCS Trauma and Orthopaedics Viva
Based on the highly successful Oxford revision course, this book helps candidates prepare for the viva section of the FRCS Trauma and Orthopaedics exam.
Glial-immune interactions in barrier organs.
Neuro-immune interactions within barrier organs, such as lung, gut, and skin, are crucial in regulating tissue homeostasis, inflammatory responses, and host defence. Our rapidly advancing understanding of peripheral neuroimmunology is transforming the field of barrier tissue immunology, offering a fresh perspective for developing therapies for complex chronic inflammatory disorders affecting barrier organs. However, most studies have primarily examined interactions between the peripheral nervous system and the immune system from a neuron-focused perspective, while glial cells, the nonneuronal cells of the nervous system, have received less attention. Glial cells were long considered as mere bystanders, only supporting their neuronal neighbours, but recent discoveries mainly on enteric glial cells in the intestine have implicated these cells in immune-regulation and inflammatory disease pathogenesis. In this review, we will highlight the bi-directional interactions between peripheral glial cells and the immune system and discuss the emerging immune regulatory functions of glial cells in barrier organs.
Higher surgeon volume reduces early failure in first time revision of non-infected total knee arthroplasty: An analysis using data from the United Kingdom National Joint Registry.
PURPOSE: Revision total knee replacement (RevKR) is an increasingly common procedure. It is hypothesised that higher surgical volume is linked to lower levels of adverse outcomes. The aim was to estimate the association of surgical volume on patient outcomes following first single-stage RevKR for non-infected indications. METHODS: This population-based cohort study used data from the United Kingdom National Joint Registry, Hospital Episode Statistics and National Patient Reported Outcome Measures. Patients undergoing procedures between 1 January 2009 and 30 June 2019 were included. The primary outcome measure was re-revision within 2 years; chosen to reflect the quality of the surgical provision. Fixed effect multivariable regression models were used to examine the association between surgeon and surgical unit annual caseload and the risk of adverse outcomes. RESULTS: A total of 8695 patients underwent first time single stage revision for aseptic loosening, instability, or malalignment across 389 surgical units and 1204 surgeons. Following adjustment for age, gender, ASA grade, year of surgery and operation funder, higher surgeon volume was associated with a lower risk of re-revision at 2 years. The risk of re-revision decreased amongst surgeons performing ≥9 annual revisions (OR 0.77, 95% CI 0.62-0.95, p-value = 0.02) compared to those performing <9 annual revisions. CONCLUSIONS: Annual surgeon case volume of ≥9 first single-stage RevKR for non-infected indications is independently associated with reductions in early re-revision. This evidence supports the setting of minimum volume targets to improve outcomes for patients. LEVEL OF EVIDENCE: Level III, retrospective cohort study of prospectively collected data.
What is the impact of longer patient travel distances and times on perioperative outcomes following revision knee replacement: a retrospective observational study using data for England from Hospital Episode Statistics.
OBJECTIVES: Patients undergoing revision total knee replacement (RevKR) surgery often have difficulties mobilising and increasingly rely on family support. Evolving practice in England aims to manage these patients in specialised centres with the intention of improving outcomes. This practice will result in longer travel distances and times in this frailer group of patients. We want to examine the types of distances and travel times patients can be expected to travel for this complex orthopaedic surgery and to explore concerns of how these impact patient outcomes. DESIGN: Retrospective observational study from the Hospital Episode Statistics. Multivariable adjusted logistic regression models were used to investigate the relationship between patient travel distances and times with perioperative outcomes. SETTING: Patients presenting to tertiary referral centres between 1 January 2016 and 31 December 2019. A tertiary referral centre was defined as a trust performing >49 revisions in the year prior. PARTICIPANTS: Adult patients undergoing RevKR procedures for any reason between 1 January 2016 ando 31 December 2019. EXPOSURE: The shortest patient level travel distance and time was calculated using the Department of Health Journey Time Statistics using Transport Accessibility and Connectivity Calculator software and Dijkstra's algorithm. MAIN OUTCOME MEASURES: The primary outcome is emergency readmission within 30 days. Secondary outcomes are mortality within 90 days and length of inpatient stay. RESULTS: 6880 patients underwent RevKR at 36 tertiary referral centres. There was a weak correlation between social deprivation and travel distance, with patients from the most deprived areas travelling longer distances. Overall, 30-day readmission was not statistically associated with longer driving distance (OR 1.00 95% CI 0.99 to 1.02) or peak driving times (OR 1.00 95% CI 0.99 to 1.01). CONCLUSIONS: There was no association between increasing travel distance and time on perioperative outcomes for RevKR patients.