The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNFα and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.

Role of vitamin D supplementation in modifying outcomes after surgery: a systematic review of randomised controlled trials.

BACKGROUND: There is increasing evidence to suggest vitamin D plays a role in immune and vascular function; hence, it may be of biological and clinical relevance for patients undergoing major surgery. With a greater number of randomised studies being conducted evaluating the impact of vitamin D supplementation on surgical patients, it is an opportune time to conduct further analysis of the impact of vitamin D on surgical outcomes. METHODS: MEDLINE, EMBASE and the Cochrane Trials Register were interrogated up to December 2023 to identify randomised controlled trials of vitamin D supplementation in surgery. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. A narrative synthesis was conducted for all studies. The primary outcome assessed was overall postoperative survival. RESULTS: We screened 4883 unique studies, assessed 236 full-text articles and included 14 articles in the qualitative synthesis, comprising 1982 patients. The included studies were highly heterogeneous with respect to patient conditions, ranging from open heart surgery to cancer operations to orthopaedic conditions, and also with respect to the timing and equivalent daily dose of vitamin D supplementation (range: 0.5-7500 mcg; 20-300 000 IU). No studies reported significant differences in overall survival or postoperative mortality with vitamin D supplementation. There was also no clear evidence of benefit with respect to overall or intensive care unit length of stay. DISCUSSION: Numerous studies have reported the benefits of vitamin D supplementation in different surgical settings without any consistency. However, this systematic review found no clear evidence of benefit, which warrants the supposition that a single biological effect of vitamin D supplementation does not exist. The observed improvement in outcomes in low vitamin D groups has not been convincingly proven beyond chance findings. TRIAL REGISTRATION NUMBER: CRD42021232067.

Paediatric emergency front-of-neck airway: issues of ethics, law, and philosophy.

Practitioners can face significant challenges when managing the airways of infants and neonates because of their unique anatomical and physiological features. The requirement for emergency airway management in this age group is rare. Details of emergency airway techniques in paediatric practice guidelines are missing or lack consensus, and it is known that outcomes for affected children can be poor. Ideally, these children should be managed by experienced paediatric airway practitioners working in a team. However, situations can arise where practitioners, unfamiliar and inexperienced with infants, find themselves in charge. So, what happens when such a practitioner encounters this life-or-death scenario and feels ill-equipped to act? The ethical and legal issues surrounding the management of this emergency are clearly defined, but they can be unknown or misunderstood by doctors. Compounding the extreme stress of the scenario is the moral and ethical dilemma of whether to act or not. The following discussion explores these issues and examines the philosophical and psychological perspectives.

Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis.

OBJECTIVE: The p.E148Q variant in pyrin is present in different populations at a frequency of up to 29%, and has been associated with diseases, including vasculitis and FMF. The pathogenicity of p.E148Q in FMF is unclear, even when observed in cis or in trans to a single, typically recessive, pathogenic mutation. We performed functional validation to determine whether p.E148Q increases the ability of pyrin to form an active inflammasome complex in cell lines. METHODS: We interrogated the Australian Autoinflammatory Disease RegistrY (AADRY) to find candidate inheritance patterns for the p.E148Q variant in pyrin. Different pyrin variant combinations were tested in HEK293T cells stably expressing the adaptor protein apoptosis-associated speck-like (ASC), which were analysed by flow cytometry to visualize inflammasome formation, with and without stimulation by Clostridioides difficile toxin B (TcdB). Inflammasome-dependent cytokine secretion was also quantified by ELISA of supernatants from THP-1 cells transduced with lentiviral expression vectors. RESULTS: In AADRY, we observed the p.E148Q allele in individuals with autoinflammatory diseases alone or in conjunction with other pyrin variants. Two FMF families harboured the allele p.E148Q-M694I in cis with dominant heritability. In vitro, p.E148Q pyrin could spontaneously potentiate inflammasome formation, with increased IL-1ß and IL-18 secretion. p.E148Q in cis to classical FMF mutations provided significant potentiation of inflammasome formation. CONCLUSION: The p.E148Q variant in pyrin potentiates inflammasome activation in vitro. In cis, this effect is additive to known pathogenic FMF mutations. In some families, this increased effect could explain why FMF segregates as an apparently dominant disease.

Hinge prostheses in the revision of unicompartmental knee replacement: a descriptive analysis of data from the national joint registry for England, Wales and Northern Ireland.

INTRODUCTION: Unicompartmental knee replacement (UKR) is an effective surgical strategy in patients with isolated medial or lateral compartment osteoarthritis. Study aims were to (1) describe the epidemiology of patients undergoing revision of UKR to a hinge knee replacement (HKR); (2) identify factors influencing time to revision; (3) evaluate HKR survival. MATERIALS AND METHODS: An analysis of National Joint Registry data was undertaken, exploring revision of UKR to HKR between 2007 and April 2021. Descriptive analysis of eligible patients and Cox Regression to identify key determinants of time to revision were performed. Failure of HKR post-revision was assessed using survival analysis. RESULTS: 111 patients underwent revision of UKR to HKR. Median age at revision was 70 years and most common indications were instability (n = 42) and infection (n = 22). The most common implant was a rotating HKR. Significant independent factors associated with earlier revision were periprosthetic fracture (p = 0.03) and malalignment (p = 0.03). Progressive osteoarthritis (p = 0.01) and higher ASA grades (3: p = 0.01, 4: p < 0.01) delayed time to revision; patient sex and age were not significant factors. Ten patients required subsequent re-revision; median age at re-revision was 61 years. HKR revised from UKR had an 89.3% revision-free risk at 5 years. Male sex (p < 0.01) and younger age (p < 0.01) were associated with re-revision. CONCLUSIONS: Factors associated with time to revision may be used to counsel patients prior to UKR. The survivorship of the HKR of 89.3% at 5 years is concerning and careful consideration should be given when using this level of constraint when revising UKR in younger or male patients.

The left ventricular assist device: a literature review and guidelines for dental care.

About 6.2 million adults in the United States suffer from heart failure (HF). For patients with advanced HF refractory to medical therapy, an orthotopic heart transplant or a ventricular assist device (VAD) is the only long-term survival option. The most commonly used form of these devices is the left VAD (LVAD), implanted to support the left ventricle. As many as 2754 LVADs were implanted annually between 2006 and 2015, allowing recipients to maintain a relatively normal lifestyle, including both elective and emergency dental care in the ambulatory setting. As more LVADs are implanted, oral healthcare providers (OHCPs) are more likely to encounter these patients in an outpatient clinical setting. This study aims to educate OHCPs on the specific needs of these patients and to begin development of clinical guidelines for their dental management. A literature review using electronic resources was conducted to identify all literature relevant to the clinical topic. Appropriate literature was selected based on established inclusion and exclusion criteria, and 3 articles published between 2015 and 2020 were identified. None offered clinical practice guidelines for the care of patients with implanted LVADs. However, it is known that patients supported by an LVAD are at higher risk of thrombotic complications, which can lead to pump system failure and embolic stroke. To reduce the risk of complications, these patients are treated with anticoagulation therapy. Interruption of these drugs prior to dental treatment is not recommended. Due to the side effects of anticoagulation therapy and acquired coagulopathy, patients with an LVAD are also at increased risk of bleeding events. Thus, perioperative hemorrhagic risk during routine oral surgical procedures must be considered. While most dental care can be done in an outpatient setting, OHCPs should be aware of the special needs of these patients and provide appropriate care through close coordination with the LVAD/transplant team.

Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2.

Type-1 and type-3 interferons (IFNs) are important for control of viral replication; however, less is known about the role of Type-2 IFN (IFNγ) in anti-viral immunity. We previously observed that lung infection with Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 in mice yet drives low levels of type-1 IFNs but robust IFNγ. Here we examine the role of ongoing IFNγ responses to pre-established bacterial infection on SARS-CoV-2 disease outcomes in two murine models. We report that IFNγ is required for iv BCG induced reduction in pulmonary viral loads, an outcome dependent on IFNγ receptor expression by non-hematopoietic cells. Importantly, we show that BCG infection prompts pulmonary epithelial cells to upregulate IFN-stimulated genes with reported anti-viral activity in an IFNγ-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirm the anti-viral properties of IFNγ by demonstrating that the recombinant cytokine itself provides strong protection against SARS-CoV-2 challenge when administered intranasally. Together, our data show that a pre-established IFNγ response within the lung is protective against SARS-CoV-2 infection, suggesting that concurrent or recent infections that drive IFNγ may limit the pathogenesis of SARS-CoV-2 and supporting possible prophylactic uses of IFNγ in COVID-19 management.

The impact of Longitudinal Integrated Foundation Training: preliminary experiences in the United Kingdom.

BACKGROUND: The United Kingdom health system is challenged with retaining doctors entering specialty training directly after their second foundation year. Improving doctors' training experience during the foundation programme may aid such retention. The Longitudinal Integrated Foundation Training (LIFT) pilot scheme aimed to provide a programme that improves the quality of their foundation training experience, advance patient-centred care and provide doctors with more experience in the primary care settings. METHODS: During this pilot study, three methods were employed to evaluate and compare doctors' experiences across their 2-year foundation training programme: Horus ePortfolio assessment of six domains for good medical practice analysed using a T-test, online survey assessments analysed using a 2-tailed chi-square test, and focus group feedback sessions with thematic analysis. RESULTS: Doctors completing LIFT (n = 47) scored a higher but non-significant mean score on all six domains for good medical practice versus doctors completing traditional foundation training (n = 94). By the end of foundation training, 100% of LIFT doctors rated their understanding of how primary and secondary care work together as high versus 78.7% of traditional doctors (p < 0.05). Improvements in wellbeing were observed among LIFT doctors, along with a reduction in the proportion of doctors considering leaving medical training. A significantly greater number of LIFT doctors versus traditional doctors rated their compassion for patients as high (100% versus 86.8%; p < 0.05), intended to become general practitioners (23.1% versus 13.5%; p < 0.05) and rated the extent to which they felt well informed and able to consider a general practice career rather than a hospital career as high (91.7% versus 72.3%, respectively; p < 0.05). Some LIFT doctors felt they had reduced exposure to secondary care, received less on-call experience and considered working a half-day to be problematic; challenges ameliorated by the end of the 2-year foundation programme. CONCLUSION: The LIFT programme enhanced the quality of foundation training and improved doctors' experiences and competencies, generating valuable insights for the future of education and healthcare delivery. Applying the principles of LIFT to foundation training helps doctors to be more compassionate and patient-centred, leading to enhanced individualised patient care.

Cognitive ability and voting behaviour in the 2016 UK referendum on European Union membership.

On June 23rd 2016 the UK voted to leave the European Union. The period leading up to the referendum was characterized by a significant volume of misinformation and disinformation. Existing literature has established the importance of cognitive ability in processing and discounting (mis/dis) information in decision making. We use a dataset of couples within households from a nationally representative UK survey to investigate the relationship between cognitive ability and the propensity to vote Leave / Remain in the 2016 UK referendum on European Union membership. We find that a one standard deviation increase in cognitive ability, all else being equal, increases the likelihood of a Remain vote by 9.7%. Similarly, we find that an increase in partner's cognitive ability further increases the respondent's likelihood of a Remain vote (7.6%). In a final test, restricting our analysis to couples who voted in a conflicting manner, we find that having a cognitive ability advantage over one's partner increases the likelihood of voting Remain (10.9%). An important question then becomes how to improve individual and household decision making in the face of increasing amounts of (mis/dis) information.

Synthesis and Thermal Oxidation Resistance of Boron-Rich Boron-Carbide Material.

A boron-rich boron-carbide material (B4+δC) was synthesized by spark plasma sintering of a ball-milled mixture of high-purity boron powder and graphitic carbon at a pressure of 7 MPa and a temperature of 1930 °C. This high-pressure, high-temperature synthesized material was recovered and characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, Vickers hardness measurements, and thermal oxidation studies. The X-ray diffraction studies revealed a single-phase rhombohedral structure (space group R-3m) with lattice parameters in hexagonal representation as a = 5.609 ± 0.007 Å and c = 12.082 ± 0.02 Å. The experimental lattice parameters result in a value of δ = 0.55, or the composition of the synthesized compound as B4.55C. The high-resolution scans of boron binding energy reveal the existence of a B-C bond at 188.5 eV. Raman spectroscopy reveals the existence of a 386 cm-1 vibrational mode representative of C-B-B linear chain formation due to excess boron in the lattice. The measured Vickers microhardness at a load of 200 gf shows a high hardness value of 33.8 ± 2.3 GPa. Thermal gravimetric studies on B4.55C were conducted at a temperature of 1300 °C in a compressed dry air environment, and its behavior is compared to other high-temperature ceramic materials such as high-entropy transition metal boride. The high neutron absorption cross section, high melting point, high mechanical strength, and thermal oxidation resistance make this material ideal for applications in extreme environments.

Development of a targeted hydrophilic interaction liquid chromatography-tandem mass spectrometry based lipidomics platform applied to a coronavirus disease severity study.

The importance of lipids seen in studies of metabolism, cancer, the recent COVID-19 pandemic and other diseases has brought the field of lipidomics to the forefront of clinical research. Quantitative and comprehensive analysis is required to understand biological interactions among lipid species. However, lipidomic analysis is often challenging due to the various compositional structures, diverse physicochemical properties, and wide dynamic range of concentrations of lipids in biological systems. To study the comprehensive lipidome, a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS)-based screening method with 1200 lipid features across 19 (sub)classes, including both nonpolar and polar lipids, has been developed. HILIC-MS/MS was selected due to its class separation property and fatty acyl chain level information. 3D models of class chromatographic retention behavior were established and evaluations of cross-class and within-class interferences were performed to avoid over-reporting these features. This targeted HILIC-MS/MS method was fully validated, with acceptable analytical parameters in terms of linearity, precision, reproducibility, and recovery. The accurate quantitation of 608 lipid species in the SRM 1950 NIST plasma was achieved using multi-internal standards per class and post-hoc correction, extending current databases by providing lipid concentrations resolved at fatty acyl chain level. The overall correlation coefficients (R2) of measured concentrations with values from literature range from 0.64 to 0.84. The applicability of the developed targeted lipidomics method was demonstrated by discovering 520 differential lipid features related to COVID-19 severity. This high coverage and targeted approach will aid in future investigations of the lipidome in various disease contexts.

Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads.

Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or concurrent influenza A virus infection in Mycobacterium tuberculosis (Mtb)-infected mice resulted in increased pulmonary bacterial burden, partly through type I interferon (IFN-I)-dependent mechanisms. Here we investigated whether SARS-CoV-2 (SCV2) co-infection could also negatively affect bacterial control of Mtb. Importantly, we found that K18-hACE2 transgenic mice infected with SCV2 one month before, or months after aerosol Mtb exposure did not display exacerbated Mtb infection-associated pathology, weight loss, nor did they have increased pulmonary bacterial loads. However, pre-existing Mtb infection at the time of exposure to the ancestral SCV2 strain in infected K18-hACE2 transgenic mice or the beta variant (B.1.351) in WT C57Bl/6 mice significantly limited early SCV2 replication in the lung. Mtb-driven protection against SCV2 increased with higher bacterial doses and did not require IFN-I, TLR2 or TLR9 signaling. These data suggest that SCV2 co-infection does not exacerbate Mtb infection in mice, but rather the inflammatory response generated by Mtb infection in the lungs at the time of SCV2 exposure restricts viral replication.

Endogenous and Therapeutic 25-Hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice.

Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-Hydroxycholesterol (25HC), a product of the activity of cholesterol-25-hydroxylase (CH25H) on cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, 25HC can also amplify inflammation and be converted by CYP7B1 (cytochrome P450 family 7 subfamily B member 1) to 7α,25-dihydroxycholesterol, a lipid with chemoattractant activity, via the G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2)/GPR183 (G protein-coupled receptor 183). Here, using in vitro studies and two different murine models of SARS-CoV-2 infection, we investigate the effects of these two oxysterols on SARS-CoV-2 pneumonia. We show that although 25HC and enantiomeric-25HC are antiviral in vitro against human endemic coronavirus-229E, they did not inhibit SARS-CoV-2; nor did supplemental 25HC reduce pulmonary SARS-CoV-2 titers in the K18-human ACE2 (angiotensin-converting enzyme 2) mouse model in vivo. Treatment with 25HC also did not alter immune cell influx into the airway, airspace cytokines, lung pathology, weight loss, symptoms, or survival but was associated with increased airspace albumin, an indicator of microvascular injury, and increased plasma proinflammatory cytokines. Conversely, mice treated with the EBI2/GPR183 inhibitor NIBR189 displayed a modest increase in lung viral load only at late time points but no change in weight loss. Consistent with these findings, although Ch25h and 25HC were upregulated in the lungs of SARS-CoV-2-infected wild-type mice, lung viral titers and weight loss in Ch25h-/- and Gpr183-/- mice infected with the ß variant were similar to those in control animals. Taken together, endogenous 25HCs do not significantly regulate early SARS-CoV-2 replication or pathogenesis, and supplemental 25HC may have proinjury rather than therapeutic effects in SARS-CoV-2 pneumonia.

G-CSF drives autoinflammation in APLAID.

Missense mutations in PLCG2 can cause autoinflammation with phospholipase C gamma 2-associated antibody deficiency and immune dysregulation (APLAID). Here, we generated a mouse model carrying an APLAID mutation (p.Ser707Tyr) and found that inflammatory infiltrates in the skin and lungs were only partially ameliorated by removing inflammasome function via the deletion of caspase-1. Also, deleting interleukin-6 or tumor necrosis factor did not fully prevent APLAID mutant mice from autoinflammation. Overall, these findings are in accordance with the poor response individuals with APLAID have to treatments that block interleukin-1, JAK1/2 or tumor necrosis factor. Cytokine analysis revealed increased granulocyte colony-stimulating factor (G-CSF) levels as the most distinct feature in mice and individuals with APLAID. Remarkably, treatment with a G-CSF antibody completely reversed established disease in APLAID mice. Furthermore, excessive myelopoiesis was normalized and lymphocyte numbers rebounded. APLAID mice were also fully rescued by bone marrow transplantation from healthy donors, associated with reduced G-CSF production, predominantly from non-hematopoietic cells. In summary, we identify APLAID as a G-CSF-driven autoinflammatory disease, for which targeted therapy is feasible.

The value of national arthroplasty registry data in 2023.

The importance of registries has been brought into focus by recent UK national reports focusing on implant (Cumberlege) and surgeon (Paterson) performance. National arthroplasty registries provide real-time, real-world information about implant, hospital, and surgeon performance and allow case identification in the event of product recall or adverse surgical outcomes. They are a valuable resource for research and service improvement given the volume of data recorded and the longitunidal nature of data collection. This review discusses the current value of registry data as it relates to both clinical practice and research.

Building reflective spaces for junior doctors to promote ethical, legal and professional learning relating to clinical practice.

BACKGROUND: Concerns have been raised surrounding the training of Foundation Doctors on the ethical, legal and professionalism (ELP) aspects of clinical practice, leading to some to claim a degree of educational neglect. Foundation Doctors are junior doctors in the United Kingdom within the first 2 years of their medical career since graduating from medical school. APPROACH: Lancaster University and Health Education England North West (HEE NW) introduced a series of training materials specially created to meet the ELP training needs of Foundation Doctors, which were piloted by Foundation Schools. EVALUATION: The training was delivered to Foundation Doctors in first and second year of their training either online or in person. The facilitators were clinical senior doctors and did not have an academic qualification in ELP. Some large Foundation Schools used two training packs to provide an optional ELP day for their Foundation Doctors, while individual hospitals within a Foundation School used the training packs to provide training as part of their mandatory weekly training for Foundation Doctors. Feedback was gathered from Foundation Doctors and training facilitators when a training pack was piloted. IMPLICATIONS: Foundation Doctors were able to make links between the messages delivered in the training to their own clinical practice. Foundation Schools have incorporated the training packs into the 2-year Foundation Programme, which creates the possibility for ELP training to become standardised across Foundation Schools.

Holocene variations in Lake Titicaca water level and their implications for sociopolitical developments in the central Andes.

Holocene climate in the high tropical Andes was characterized by both gradual and abrupt changes, which disrupted the hydrological cycle and impacted landscapes and societies. High-resolution paleoenvironmental records are essential to contextualize archaeological data and to evaluate the sociopolitical response of ancient societies to environmental variability. Middle-to-Late Holocene water levels in Lake Titicaca were reevaluated through a transfer function model based on measurements of organic carbon stable isotopes, combined with high-resolution profiles of other geochemical variables and paleoshoreline indicators. Our reconstruction indicates that following a prolonged low stand during the Middle Holocene (4000 to 2400 BCE), lake level rose rapidly ~15 m by 1800 BCE, and then increased another 3 to 6 m in a series of steps, attaining the highest values after ~1600 CE. The largest lake-level increases coincided with major sociopolitical changes reported by archaeologists. In particular, at the end of the Formative Period (500 CE), a major lake-level rise inundated large shoreline areas and forced populations to migrate to higher elevation, likely contributing to the emergence of the Tiwanaku culture.

First-time revision knee arthroplasty using a hinged prosthesis : temporal trends, indications, and risk factors associated with re-revision using data from the National Joint Registry for 3,855 patients.

AIMS: The aim of this study was to identify variables associated with time to revision, demographic details associated with revision indication, and type of prosthesis employed, and to describe the survival of hinge knee arthroplasty (HKA) when used for first-time knee revision surgery and factors that were associated with re-revision. METHODS: Patient demographic details, BMI, American Society of Anesthesiologists (ASA) grade, indication for revision, surgical approach, surgeon grade, implant type (fixed and rotating), time of revision from primary implantation, and re-revision if undertaken were obtained from the National Joint Registry data for England, Wales, Northern Ireland, and the Isle of Man over an 18-year period (2003 to 2021). RESULTS: There were 3,855 patient episodes analyzed with a median age of 73 years (interquartile range (IQR) 66 to 80), and the majority were female (n = 2,480, 64.3%). The median time to revision from primary knee arthroplasty was 1,219 days (IQR 579 to 2,422). Younger age (p < 0.001), decreasing ASA grade (p < 0.001), and indications for revision of sepsis (p < 0.001), unexplained pain (p < 0.001), non-polyethylene wear (p < 0.001), and malalignment (p < 0.001) were all associated with an earlier time to revision from primary implantation. The median follow-up was 4.56 years (range 0.00 to 17.52), during which there were 410 re-revisions. The overall unadjusted probability of re-revision for all revision HKAs at one, five, and ten years after surgery were 2.7% (95% confidence interval (CI) 2.2 to 3.3), 10.7% (95% CI 9.6 to 11.9), and 16.2% (95% CI 14.5 to 17.9), respectively. Male sex (p < 0.001), younger age (p < 0.001), revision for septic indications (p < 0.001) or implant fracture (p = 0.010), a fixed hinge (p < 0.001), or surgery performed by a non-consultant grade (p = 0.023) were independently associated with an increased risk of re-revision. CONCLUSION: There were several factors associated with time to first revision. The re-revision rate was 16.2% at ten years; however, the risk factors associated with an increased risk of re-revision could be used to counsel patients regarding their outcome.Cite this article: Bone Joint J 2023;105-B(1):47-55.

Structural Identification of Eicosanoids with Ring Structures Using Differential Mobility Spectrometry-Electron Impact Excitation of Ions from Organics Mass Spectrometry.

We developed a structural identification method for eicosanoids with various ring structures using mass spectrometry. We discovered that an electron beam with a kinetic energy of 10 eV, which is in the Electron Impact Excitation of Ions from Organics (EIEIO) regime, cleaved the fatty acids enough to distinguish constitutional and cis/trans isomers. In addition to EIEIO, a comparison to authentic standards using differential mobility spectrometry (DMS) can identify diastereomers, which was difficult by EIEIO. The combination of EIEIO and DMS can provide a high-throughput method to identify complete structures of eicosanoids in mixed samples, which is not allowed with conventional analytical methods though eicosanoids are important signaling molecules in biosystems.