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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Aim: A total of 15–20% of patients with rectal cancer have liver metastases on presentation. The management of these patients is controversial. Heterogeneity in management strategies is considerable, with management often being dependent on local resources and available expertise. Method: Members of the PelvEx Collaborative were invited to participate in the generation of a consensus statement on the optimal management of patients with advanced rectal cancer with liver involvement. Fifteen statements were created for topical discussion on diagnostic and management issues. Panellists were asked to vote on statements and anonymous feedback was given. A collaborative meeting was used to discuss any nuances and clarify any obscurity. Consensus was considered when > 85% agreement on a statement was achieved. Results: A total of 135 participants were involved in the final round of the Delphi questionnaire. Nine of the 15 statements reached consensus regarding the management of patients with advanced rectal cancer and oligometastatic liver disease. Routine use of liver MRI was not recommended for patients with locally advanced rectal cancer, unless there was concern for metastatic disease on initial computed tomography staging scan. Induction chemotherapy was advocated as first‐line treatment in those with synchronous liver metastases in locally advanced rectal cancer. In the presence of symptomatic primary disease, a diverting stoma may be required to facilitate induction chemotherapy. Overall, only one‐quarter of the panellists would consider simultaneous pelvic exenteration and liver resection. Conclusion: This Delphi process highlights the diverse treatment of advanced rectal cancer with liver metastases and provides recommendations from an experienced international group regarding the multidisciplinary management approach. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cryptococcus neoformans and Cryptococcus gattii are both known urease producers and have the potential to cause hyperammonemia. We hypothesized that the risk of hyperammonemia is increased by renal failure, burden of cryptococcal infection, and fungal strain characteristics. We performed a retrospective review of plasma ammonia levels in patients with cryptococcal infections. Risk factors for hyperammonemia were statistically compared between patients with and without hyperammonemia (>53 µmol/L). Cryptococcal cells from three patients included in the study were recovered from our biorepository. Strain characteristics including urease activity, ammonia production, growth curves, microscopy, melanin production, and M13 molecular typing were analyzed and compared with a wild-type (WT) C. neoformans strain. We included 29 patients, of whom 37.9% had hyperammonemia, 59% had disseminated cryptococcal infection (DCI), and 41% had isolated central nervous system infection. Thirty-eight percent of patients had renal failure and 28% had liver disease. Renal failure was associated with 4.4 times (95% confidence interval [CI] 1.5, 13.0) higher risk of hyperammonemia. This risk was higher in DCIs (RR 6.2, 95% CI 1.0, 40.2) versus isolated cryptococcal meningitis (RR 2.5, 95% CI, 0.40, 16.0). Liver disease and cryptococcal titers were not associated with hyperammonemia. C. neoformans from one patient with extreme hyperammonemia demonstrated a 4- to 5-fold increase in extracellular urease activity, slow growth, enlarged cell size phenotypes, and diminished virulence factors. Hyperammonemia was strongly associated with renal failure in individuals with DCI, surpassing associations with liver failure or cryptococcal titers. However, profound hyperammonemia in one patient was attributable to high levels of urease secretion unique to that cryptococcal strain. Prospective studies are crucial to exploring the significance of this association.IMPORTANCE Cryptococcus produces and secretes the urease enzyme to facilitate its colonization of the host. Urease breaks down urea into ammonia, overwhelming the liver's detoxification process and leading to hyperammonemia in some hosts. This underrecognized complication exacerbates organ dysfunction alongside the infection. Our study investigated this intricate relationship, uncovering a strong association between the development of hyperammonemia and renal failure in patients with cryptococcal infections, particularly those with disseminated infections. We also explore mechanisms underlying increased urease activity, specifically in strains associated with extreme hyperammonemia. Our discoveries provide a foundation for advancing research into cryptococcal metabolism and identifying therapeutic targets to enhance patient outcomes., Competing Interests: The authors declare no conflict of interest.

Aim: The aim of this study was to determine whether patients treated with a caged reconstruction for metastatic acetabular disease would have a construct survival superior to that of their life expectancy., Patients and Methods: We undertook a retrospective study, in a single centre in the United Kingdom, reviewing outcomes for 19 patients (20 hips) treated with a cage reconstruction for metastatic disease of their acetabulum over 6 years. Inclusion criteria were those with an impending fracture of the acetabulum, metastatic dissociation, fracture of the acetabulum and or femur and those whose life expectancy was considered by the oncology team to be >6 months., Results: In all patients the Restoration GAP II acetabular cage (Stryker, Howmedica Osteonics Corp, NJ, USA) was used in conjunction with a cemented acetabular cup and cemented femoral stem. The mean age at the time of surgery was 68 (44-87) years with breast cancer being the most common primary malignancy (31%) followed by prostate cancer (26%).Radiological survivorship estimates were 94.1% (95% CI, 99.2-65.0) at 12 and 24 months, 70.6% (95% CI, 93.6-16.0) at 36 months and 35.3% (95% CI, 78.2-1.2) at 48 months. There were 3 radiological failures of the implant due to disease progression. Complications occurred in 3 patients with 2 developing deep infection which was treated with suppressive antibiotic therapy following aspiration of the hip. 1 patient suffered a hip dislocation following trauma which was successfully reduced closed and no further intervention was required., Conclusions: This study represents the first published case series of the use of the GAP II cage in patients with metastatic acetabular disease. The construct generally outlives the patient and hence is suitable for the treatment of acetabular metastases.

The fungus Cryptococcus neoformans is the causative agent of cryptococcosis, a disease that is uniformly lethal unless treated with antifungal drugs, yet current regimens are hindered by host toxicity and pathogen resistance. An attractive alternative approach to combat this deadly disease is the direct targeting of pathogen-derived virulence mechanisms. C. neoformans expresses multiple virulence factors that have been studied previously as isolated entities. Among these, are urease, which increases phagosomal pH and promotes brain invasion, and melanization, which protects against immune cells and antifungal treatments. Here we report a reciprocal interdependency between these two virulence factors. Cells hydrolyzing urea release ammonia gas which acts at a distance to raise pH and increase melanization rates for nearby cells, which in turn reduces secretion of urease-carrying extracellular vesicles. This reciprocal relationship manifests as an emergent property that may explain why targeting isolated virulence mechanisms for drug development has been difficult and argues for a more holistic approach that considers the virulence composite., (© 2023. The Author(s).)

A pet cockatoo was the suspected source of Cryptococcus neoformans recovered from an immunocompromised patient with cryptococcosis based on molecular analyses available in 2000. Here, we report whole genome sequence analysis of the clinical and cockatoo strains. Both are closely related MATα strains belonging to the VNII lineage, confirming that the human infection likely originated from pet bird exposure. The two strains differ by 61 single nucleotide polymorphisms, including eight nonsynonymous changes involving seven genes. To ascertain whether changes in these genes are selected for during mammalian infection, we passaged the cockatoo strain in mice. Remarkably, isolates obtained from mouse tissue possess a frameshift mutation in one of the seven genes altered in the human sample (LQVO5_000317), a gene predicted to encode an SWI-SNF chromatin-remodeling complex protein. In addition, both cockatoo and patient strains as well as mouse-passaged isolates obtained from brain tissue had a premature stop codon in a homologue of ZFC3 (LQVO5_004463), a predicted single-zinc finger containing protein, which is associated with larger capsules when deleted and reverted to a full-length protein in the mouse-passaged isolates obtained from lung tissue. The patient strain and mouse-passaged isolates show variability in virulence factors, with differences in capsule size, melanization, rates of nonlytic expulsion from macrophages, and amoeba predation resistance. Our results establish that environmental strains undergo genomic and phenotypic changes during mammalian passage, suggesting that animal virulence can be a mechanism for genetic change and that the genomes of clinical isolates may provide a readout of mutations acquired during infection.

Introduction: Hip resurfacing remains a valid option in young male patients. The creation of the optimum cement mantle aids fixation of the femoral component. If the cement mantle is too thick the prosthesis can remain proud leading to early failure or if it penetrates too far into the femoral head, it may cause osteonecrosis., Method: 18 of 96 femoral heads collected from patients undergoing total hip arthroplasty were matched for their surface porosity. They were randomly allocated into 2 different cementing groups. Group 1 had the traditional bolus of cement technique, while group 2 had a modified cementing technique (swirl) where the inside of the femoral component was lined with an even layer of low viscosity cement., Results: The traditional bolus technique had significantly greater cement mantle thickness in 3 of 4 zones of penetration ( p  = 0.002), greater and larger air bubble formation (6 of 9 in bolus technique vs. 1 in 9 in swirl technique, p  = 0.05) and more incomplete cement mantles compared with the swirl technique. There was no relationship to femoral head porosity., Conclusion: The swirl technique should be used to cement the femoral component in hip resurfacing. Long-term clinical studies would conform if this translates into increased survivorship of the femoral component.

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning. This review will focus on patients who have been recommended for surgery by the MDT and have completed neoadjuvant therapy. Other important considerations beyond the scope of this review are the various neoadjuvant strategies employed which in this patient group include Total Neo-adjuvant Therapy and reirradiation. Critical to improving perioperative outcomes is the dual aim of achieving a negative resection margin in a patient fit enough for extended surgery. Advanced, realistic communication is required pre-operatively and should be maintained throughout recovery. Optimising patient's physiological and psychological reserve with a preoperative prehabilitation programme is important, with physiotherapy, psychological and nutritional input. From a surgical perspective, image based technical preoperative planning is important to identify risk points and ensure correct surgical strategy. Careful attention to the entire patient journey through these 5 preoperative phases can optimise outcomes with the accumulation of marginal gains at multiple timepoints., Competing Interests: Declaration of competing interest The authors whose names are listed below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021. Published by Elsevier Ltd.)

Aims: We compared the risks of re-revision and mortality between two-stage revision surgery and single-stage revision surgery among patients with infected primary knee arthroplasty., Methods: Patients with a periprosthetic joint infection (PJI) of their primary knee arthroplasty, initially revised with a single-stage or a two-stage procedure in England and Wales between 2003 and 2014, were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HR) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies., Results: A total of 489 primary knee arthroplasties were revised with single-stage procedure (1,390 person-years) and 2,377 with two-stage procedure (8,349 person-years). The adjusted incidence rates of all-cause re-revision and for infection were comparable between these strategies (HR overall five years, 1.15 (95% confidence interval (CI) 0.87 to 1.52), p = 0.308; HR overall five years, 0.99 (95% CI 0.70 to 1.39), p = 0.949, respectively). Patients initially managed with single-stage revision received fewer revision procedures overall than after two-stage revision (1.2 vs 2.2, p < 0.001). Mortality was lower for single-stage revision between six and 18 months postoperative (HR at six months, 0.51 (95% CI 0.25 to 1.00), p = 0.049 HR at 18 months, 0.33 (95% CI 0.12 to 0.99), p = 0.048) and comparable at other timepoints., Conclusion: The risk of re-revision was similar between single- and two-stage revision for infected primary knee arthroplasty. Single-stage group required fewer revisions overall, with lower or comparable mortality at specific postoperative periods. The single-stage revision is a safe and effective strategy to treat infected knee arthroplasties. There is potential for increased use to reduce the burden of knee PJI for patients, and for the healthcare system.Cite this article: Bone Joint Res  2022;11(10):690-699.

Cryptococcus neoformans is a facultative intracellular pathogen that can replicate and disseminate in mammalian macrophages. In this study, we analyzed fungal proteins identified in murine macrophage-like cells after infection with C. neoformans . To accomplish this, we developed a protocol to identify proteins released from cryptococcal cells inside macrophage-like cells; we identified 127 proteins of fungal origin in infected macrophage-like cells. Among the proteins identified was urease, a known virulence factor, and others such as transaldolase and phospholipase D, which have catalytic activities that could contribute to virulence. This method provides a straightforward methodology to study host-pathogen interactions. We chose to study further Yeast Oligomycin Resistance (Yor1), a relatively uncharacterized protein belonging to the large family of ATP binding cassette transporter (ABC transporters). These transporters belong to a large and ancient protein family found in all extant phyla. While ABC transporters have an enormous diversity of functions across varied species, in pathogenic fungi they are better studied as drug efflux pumps. Analysis of C. neoformans yor1Δ strains revealed defects in nonlytic exocytosis, capsule size, and dimensions of extracellular vesicles, when compared to wild-type strains. We detected no difference in growth rates and cell body size. Our results indicate that C. neoformans releases a large suite of proteins during macrophage infection, some of which can modulate fungal virulence and are likely to affect the fungal-macrophage interaction., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, suggesting uptake of additional catecholamines. Probing the biosynthesis of melanin using radiolabeled catecholamines revealed that C. neoformans melanization simultaneously incorporated more than one catecholamine, implying that the pigment was polytypic in nature. Nonetheless, melanin derived from individual or mixed catecholamines had comparable ability to protect C. neoformans against ultraviolet light and oxidants. Our results indicate that melanin produced during infection differs depending on the catecholamine composition of tissue and that melanin pigment synthesized in vivo is likely to accrue from the polymerization of a mixture of precursors. From a practical standpoint, our results strongly suggest that using dopamine as a polymerization precursor is capable of producing melanin pigment comparable to that produced during infection. On a more fundamental level, our findings uncover additional structural complexity for natural cryptococcal melanin by demonstrating that pigment produced during human infection is likely to be composed of polymerized moieties derived from chemically different precursors., Competing Interests: Conflict of interest Dr Arturo Casadevall reports financial support provided by the National Institutes of Health. The remaining authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The porosity of the femoral head prepared for hip resurfacing has not been previously described. This is important as greater pore size increases the penetration of bone cement and excessive cement penetration can cause osteonecrosis., Methods: 96 osteoarthritic femoral heads were harvested at total hip arthroplasty and prepared for hip resurfacing. The porosity of the bone cement interface in hip resurfacing was calculated from digitised black and white photographs using MatLab software., Results: The mean porosity was 0.63. Increased porosity was associated with larger femoral heads in both the coronal and sagittal dimensions and cysts in the femoral head. It was not associated with gender, age, body mass index (BMI), smoking, alcohol or corticosteroid consumption., Conclusion: The porosity of the femoral head has been shown to be 0.63. Future studies of cementing techniques in hip resurfacing should include this porosity in their designs. The surgeon prior to hip resurfacing should consider altering his cementing technique when cysts are present on the preoperative radiographs.

Rhomboid intramembrane proteases regulate pathophysiological processes, but their targeting in a disease context has never been achieved. We decoded the atypical substrate specificity of malaria rhomboid PfROM4, but found, unexpectedly, that it results from "steric exclusion": PfROM4 and canonical rhomboid proteases cannot cleave each other's substrates due to reciprocal juxtamembrane steric clashes. Instead, we engineered an optimal sequence that enhanced proteolysis >10-fold, and solved high-resolution structures to discover that boronates enhance inhibition >100-fold. A peptide boronate modeled on our "super-substrate" carrying one "steric-excluding" residue inhibited PfROM4 but not human rhomboid proteolysis. We further screened a library to discover an orthogonal alpha-ketoamide that potently inhibited PfROM4 but not human rhomboid proteolysis. Despite the membrane-immersed target and rapid invasion, ultrastructural analysis revealed that single-dosing blood-stage malaria cultures blocked host-cell invasion and cleared parasitemia. These observations establish a strategy for designing parasite-selective rhomboid inhibitors and expose a druggable dependence on rhomboid proteolysis in non-motile parasites., Competing Interests: Declaration of Interests S.G., S.C., and S.U. are listed as inventors on US patent US20190144498 for using tetrahedral-mimicking groups as rhomboid inhibitors in parasites. K.S. and S.S. are inventors on a patent for the general use of alpha-ketoamides as rhomboid protease inhibitors registered in the United Kingdom, EU, and USA (publications GB2563396, EP3638686, and US20200095278, respectively)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hypertension among young people is common, affecting 1 in 8 adults aged between 20 and 40 years. This number is likely to increase with lifestyle behaviors and lowering of hypertension diagnostic thresholds. Early-life factors influence blood pressure (BP) although the mechanisms are unclear; BP tracks strongly within individuals from adolescence through to later life. Higher BP at a young age is associated with abnormalities on heart and brain imaging and increases the likelihood of cardiovascular events by middle age. However, diagnosis rates are lower, and treatment is often delayed in young people. This reflects the lack of high-quality evidence that lowering BP in young adults improves cardiovascular outcomes later in life. In this review, we evaluate the current evidence regarding the association between BP in young adult life and adverse cardiovascular outcomes later in life. Following this, we discuss which young people with raised BP should be investigated for secondary causes of hypertension. Third, we assess the current models to assess cardiovascular risk and show a lack of validation in the younger age group. Fourth, we evaluate the evidence for lifestyle interventions in this age group and demonstrate a lack of persistence in BP lowering once the initial intervention has been delivered. Fifth, we address the pros and cons of drug treatment for raised BP in young people. Finally, there are unique life events in young people, such as pregnancy, that require specific advice on management and treatment of BP.

Aim: To compare the long-term clinical and radiological results of metal-on-polyethylene hybrid total hip replacement (THA) with metal-on-metal Birmingham hip resurfacing (BHR) in young, active patients., Patients and Methods: From the 1st consecutive 63 hips in young, active patients who underwent BHR by the senior author, 54 (51 patients) were matched to patients who had undergone THA with regard to age, gender, body mass index and preoperative levels of activity. Radiologically, all hips were assessed for migration and osteolysis, THAs for polyethylene wear and BHRs for a pedestal sign. Patient-reported outcomes, mortality and revision rates were compared., Results: The mean follow-up of the patients with a hybrid THR was 19.9 years and for those with a BHR, 17.6 years. 13 patients with a hybrid THR and 5 with a BHR had died. 1 hybrid THR and 3 BHRs were lost to follow-up. The revision rate of the hybrid THRs was 14/54 and of the BHRs 6/54. Log rank comparison of Kaplan-Meier survival estimates demonstrated a significantly lower mortality in the BHR group ( p = 0.039; hazard ratio [HR] = 0.37 [95% CI, 0.15-0.95]) but a non-significant difference in revision rates ( p = 0.067; HR = 0.43 [95% CI, 0.18-1.06]). The BHRs recorded superior OHS ( p = 0.03), UCLA ( p = 0.0096), and EuroQol visual analogue scores ( p = 0.03). Significantly more BHRs had run, played sport and undertaken heavy manual labour in the month preceding follow-up., Conclusion: After 18 years, patients with BHRs remained more active with a lower mortality rate but demonstrated no significant difference in revision rates. Both groups demonstrated progressive radiological changes at long-term follow-up.

Protein cleavage inside the cell membrane triggers various pathophysiological signaling pathways, but the mechanism of catalysis is poorly understood. We solved ten structures of the Escherichia coli rhomboid protease in a bicelle membrane undergoing time-resolved steps that encompass the entire proteolytic reaction on a transmembrane substrate and an aldehyde inhibitor. Extensive gate opening accompanied substrate, but not inhibitor, binding, revealing that substrates and inhibitors take different paths to the active site. Catalysis unexpectedly commenced with, and was guided through subsequent catalytic steps by, motions of an extracellular loop, with local contributions from active site residues. We even captured the elusive tetrahedral intermediate that is uncleaved but covalently attached to the catalytic serine, about which the substrate was forced to bend dramatically. This unexpectedly stable intermediate indicates rhomboid catalysis uses an unprecedented reaction coordinate that may involve mechanically stressing the peptide bond, and could be selectively targeted by inhibitors.

Introduction: Curettage with cement augmentation is a technique used in the treatment of bone tumours. Thermal energy released during the cement polymerisation process can damage surrounding tissues. This study aims to record temperature changes at various sites on and around bone during the cementing process. We hypothesised that adjacent structures, such as the radial nerve, may be threatened by this process in the clinical setting., Materials and Methods: Using 18 porcine femurs as a model of the human humerus, we used thermocouples and a thermal imaging camera to measure changes in temperature during the cementing process. Fractures were created in nine samples to establish whether a discontinuity of the cortex had an effect on thermal conduction., Results: Significantly higher temperatures were recorded in samples with a fracture compared to those without a fracture. The site overlying the centre of the cement bolus (hypothetical site of the radial nerve) demonstrated higher temperatures than all other sites on the same cortex. When considering the radial nerve site, over half the samples demonstrated temperatures exceeding 47 °C for over a minute. When a threshold of 50 °C for more than 30 s was considered, three samples without a fracture exceeded this value compared to two with a fracture., Conclusion: The temperatures recorded were sufficient to cause damage to neural tissue. Limiting thermal exposure to soft tissues is recommended. Increased attention is required when using larger cement boluses, or where bone quality is poor or a fracture, iatrogenic or preexisting, is present.

Background: Prosthetic joint infection is a rare, but devastating complication of primary total hip arthroplasty (THA). Postoperative wound discharge and deep infection are related. We examined whether barbed sutures were associated with a decrease in the incidence of postoperative wound discharge when compared with skin closure using metal staples., Methods: Prospective nonrandomized comparison between two groups (35 barbed suture closures vs. 49 staple closures). Wounds were assessed daily for postoperative wound discharge until dry. Hemoglobin and hematocrit were recorded at the preoperative assessment and on day 3 postoperative., Results: There were no significant differences between the groups with regard to age, body mass index, gender, preoperative hemoglobin, preoperative hematocrit, or estimated blood volume. The number of days elapsed until the wound was dry was significantly lower in the barbed suture group than the staples group ( p < 0.0001). In the staples cohort, ongoing wound ooze resulted in delayed hospital discharge in three (6%) patients, six bed days total., Conclusion: Barbed sutures reliably reduce the period of postoperative wound ooze following primary THA compared to staple closure. The use of barbed sutures may prevent delayed patient discharge from hospital, decreasing the bed burden.

Light sheet fluorescence microscopy enables fast, minimally phototoxic, three-dimensional imaging of live specimens, but is currently limited by low throughput and tedious sample preparation. Here, we describe an automated high-throughput light sheet fluorescence microscope in which specimens are positioned by and imaged within a fluidic system integrated with the sheet excitation and detection optics. We demonstrate the ability of the instrument to rapidly examine live specimens with minimal manual intervention by imaging fluorescent neutrophils over a nearly 0.3 mm3 volume in dozens of larval zebrafish. In addition to revealing considerable inter-individual variability in neutrophil number, known previously from labor-intensive methods, three-dimensional imaging allows assessment of the correlation between the bulk measure of total cellular fluorescence and the spatially resolved measure of actual neutrophil number per animal. We suggest that our simple experimental design should considerably expand the scope and impact of light sheet imaging in the life sciences., Competing Interests: The authors have declared that no competing interests exist.

Background: Normal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Previous image analysis approaches have successfully extracted properties related to the temporal frequency of motility modes, but robust measures of contraction magnitude, especially from in vivo image data, remain challenging to obtain., Methods: We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motion., Key Results: We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild types., Conclusions & Inferences: Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements., (© 2018 John Wiley & Sons Ltd.)

Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain Aeromonas veronii was displaced by V. cholerae expressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of A. veronii , driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident microbiota by the host. Deleting an actin cross-linking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening V. cholerae 's ability to kill A. veronii in vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering., Competing Interests: The authors declare no conflict of interest.

Patients presenting with skeletal metastatic lesions requiring surgery are increasing, this is due to an ageing population and improved oncological survival following advances in medical management. Furthermore, patients are living longer with skeletal metastatic disease. The majority of bone metastases occur in the proximal femur. Robust diagnosis (Biopsy) and treatment is required to ensure that patients can mobilise fully weight bearing immediately post-surgery and that the construct should outlive the patients expected survival. We review the changing management of metastatic disease in the proximal femur.

Intramembrane proteases are an ancient and diverse group of multispanning membrane proteins that cleave transmembrane substrates inside the membrane to effect a wide range of biological processes. As proteases, a clear understanding of their function requires kinetic dissection of their catalytic mechanism, but this is difficult to achieve for membrane proteins. Kinetic measurements in detergent systems are complicated by micelle fusion/exchange, which introduces an additional kinetic step and imposes system-specific behaviors (e.g., cooperativity). Conversely, kinetic analysis in proteoliposomes is hindered by premature substrate cleavage during coreconstitution, and lack of methods to quantify proteolysis in membranes in real time. In this chapter, we describe a method for the real-time kinetic analysis of intramembrane proteolysis in model liposomes. Our assay is inducible, because the enzyme is held inactive by low pH during reconstitution, and fluorogenic, since fluorescence emission from the substrate is quenched near lipids but restored upon proteolytic release from the membrane. The precise measurement of initial reaction velocities continuously in real time facilitates accurate steady-state kinetic analysis of intramembrane proteolysis and its inhibition inside the membrane environment. Using real data we describe a step-by-step strategy to implement this assay for essentially any intramembrane protease., (© 2017 Elsevier Inc. All rights reserved.)

The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this "microbial organ" for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this issue, we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within a vertebrate gut. We observed that the interplay between each population and the gut environment produces distinct spatiotemporal patterns. As a consequence, one species dominates while the other experiences sudden drops in abundance that are well fit by a stochastic mathematical model. Modeling revealed that direct bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to a mutation in the ret locus, which in humans is associated with the intestinal motility disorder known as Hirschsprung disease. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities can drive bacterial population dynamics within the gut, and it reveals a new facet of the intestinal host-microbe interface by demonstrating the capacity of the enteric nervous system to influence the microbiota. Ultimately, these findings suggest that therapeutic strategies targeting the intestinal ecosystem should consider the dynamic physical nature of the gut environment.

Objective: Although opioids have substantial efficacy for acute pain management, escalation to opioid misuse and abuse is a persistent concern. This report assesses the current status of the opioid epidemic in Maine using three complementary data sets., Method: A representative sample of pharmacists (N = 275) completed an online survey regarding the extent that opioids affected their practice. A county-level analysis of opioid prescriptions (N = 1.22 million) reported to the Maine Prescription Monitoring Program (M-PMP) in 2014 and the agents implicated in arrests as reported to the Maine Diversion Alert Program (DAP, N = 2,700) in 2014/15 also was completed., Results: A significantly greater number of pharmacists agreed that opioid misuse (85.9%), rather than diversion (76.8%) or access (54.2%), was a concern. Only half (56.2%) reported use of the M-PMP. Opioids were dispensed to 22.4% of residents (37.7% of women in their 80s). This was enough to supply everyone in Maine with a 16.1-day supply. Buprenorphine accounted for almost half of opioid prescriptions to young adults (46.3% women, 49.3% men). Arrests increased by 13.3% from 2014 to 2015, and the proportion of arrests that involved prescription opioids decreased while those involving stimulants and heroin were elevated., Conclusions: Pharmacists are very aware of the potential for opioid misuse, but many do not consistently use the M-PMP. There continues to be substantial legitimate use, as well as criminal activity, involving oxycodone and other prescription opioids. Continued vigilance and use of tools like the PMP and DAP are necessary to minimize nonmedical use of opioids in Maine.

Background: Maine is a rural state with an aging population located in the northeastern United States. Pharmacists play an important role in serving the public's health as they are often the most available point-of-contact within a community., Objective: To assess the current pharmacy practice needs as viewed by licensed pharmacists across our rural state, and to distinguish issues that are unique to rural pharmacy practice., Methods: An online survey was sent to all licensed pharmacists in the state in the fall of 2014 (n=1,262) to assess their pharmacy practice needs, and specify an rural-specific needs, within the categories of (1) opioid misuse, abuse, and diversion, (2) challenges associated with access to healthcare, (3) poly-pharmacy use, (4) meeting the needs of special populations, (5) lack of antibiotic stewardship, and (6) resources, such as staffing., Results: The response rate was 22.1 % (n=279). We found the most agreed upon issue facing pharmacists' in Maine is opioid use, misuse and diversion, followed closely by shortages in staffing. We also learned that pharmacists' view pharmaceutical care for older adults, those with low health literacy, and those with mental disabilities more time-consuming. Some urban-rural differences were discovered in with regard to the pharmacists' views; such as the magnitude of the distance barrier, and limited transportation options available to rural residents. Issues related to polypharmacy were viewed as more problematic by pharmacists practicing in urban versus rural sites., Conclusions: Pharmaceutical care in Maine must focus on meeting the needs of the elderly, those with disabilities, and those with limited health literacy. As with the rest of the nation, opioids challenge pharmacy practice in a variety of ways. These findings clarify areas that present opportunities for pharmacists to focus more specifically on Maine's largely rural population.

Intramembrane proteases catalyse the signal-generating step of various cell signalling pathways, and continue to be implicated in diseases ranging from malaria infection to Parkinsonian neurodegeneration. Despite playing such decisive roles, it remains unclear whether or how these membrane-immersed enzymes might be regulated directly. To address this limitation, here we focus on intramembrane proteases containing domains known to exert regulatory functions in other contexts, and characterize a rhomboid protease that harbours calcium-binding EF-hands. We find calcium potently stimulates proteolysis by endogenous rhomboid-4 in Drosophila cells, and, remarkably, when rhomboid-4 is purified and reconstituted in liposomes. Interestingly, deleting the amino-terminal EF-hands activates proteolysis prematurely, while residues in cytoplasmic loops connecting distal transmembrane segments mediate calcium stimulation. Rhomboid regulation is not orchestrated by either dimerization or substrate interactions. Instead, calcium increases catalytic rate by promoting substrate gating. Substrates with cleavage sites outside the membrane can be cleaved but lose the capacity to be regulated. These observations indicate substrate gating is not an essential step in catalysis, but instead evolved as a mechanism for regulating proteolysis inside the membrane. Moreover, these insights provide new approaches for studying rhomboid functions by investigating upstream inputs that trigger proteolysis.

Hip joint replacement is 1 of the most successful surgical procedures of the last century and the number of replacements implanted is steadily growing. An infected hip arthroplasty is a disaster, it leads to patient suffering, surgeon's frustration and significant costs to the health system. The treatment of an infected hip replacement is challenging, healing rates can be low, functional results poor with decreased patient satisfaction. However, if a patient-adapted treatment of infected hip joints is used a success rate of above 90% can be obtained.Patient-adapted treatment is based on 5 important concepts: teamwork; understanding the biofilm; diagnostic accuracy; correct definition and classification of PJI; and patient-tailored treatment.This review presents a patient-adapted treatment strategy to prosthetic hip infection. It incorporates the best aspects of the single and staged surgical strategies and promotes the short interval philosophy for the 2-stage approach.

Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2-3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3-6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state-level structure in the transition state. We propose that loops 1-3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated.

We describe a microscope capable of both light sheet fluorescence microscopy and differential interference contrast microscopy (DICM). The two imaging modes, which to the best of our knowledge have not previously been combined, are complementary: light sheet fluorescence microscopy provides three-dimensional imaging of fluorescently labelled components of multicellular systems with high speed, large fields of view, and low phototoxicity, whereas differential interference contrast microscopy reveals the unlabelled neighbourhood of tissues, organs, and other structures with high contrast and inherent optical sectioning. Use of a single Nomarski prism for differential interference contrast microscopy and a shared detection path for both imaging modes enables simple integration of the two techniques in one custom microscope. We provide several examples of the utility of the resulting instrument, focusing especially on the digestive tract of the larval zebrafish, revealing in this complex and heterogeneous environment anatomical features, the behaviour of commensal microbes, immune cell motions, and more., (© 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.)

Cement-in-cement femoral component revision is a useful and commonly practised technique. Onerous and hazardous re-shaping of the original cement mantle is required if the new stem does not seat easily. Furthermore, without removing the entirety of the original cement mantle, the freedom to alter anteversion or leg length is difficult to predict preoperatively. We present data from in vitro experiments testing the compatibility of the top cemented stems according to UK registry figures (NJR 2013). This data augments preoperative planning by indicating which revision stems require minimal or no cement reshaping when being inserted into another stem's mantle. We also present the maximum shortening and anteversion that can be achieved without reshaping the original cement mantle.

The histological specimens from 29 failed metal-on-metal (MoM) hip arthroplasties treated at our institution were reviewed. Five patients had a failed MoM total hip arthroplasty (THA), and 24 patients a failed hip resurfacing. Clinical and radiographic features of each hip were correlated with the histological findings. We report three major histological subtypes. Patients either have a macrophage response to metal debris, a lymphocytic response (ALVAL) or a mixed picture of both. In addition we observe that the ALVAL response is located deep within tissue specimens, and can occur in environments of low wear debris. The macrophage response is limited to the surface of tissue specimens, with normal underlying tissue. Patients with subsequently confirmed ALVAL underwent revision surgery sooner than patients whose histology confirms a macrophage response (3.8 vs. 6.9 years p<0.05). Both histological subtypes (ALVAL and macrophage dominant) are responsible for abnormal soft tissue swellings.

Enzymatic cleavage of transmembrane anchors to release proteins from the membrane controls diverse signaling pathways and is implicated in more than a dozen diseases. How catalysis works within the viscous, water-excluding, two-dimensional membrane is unknown. We developed an inducible reconstitution system to interrogate rhomboid proteolysis quantitatively within the membrane in real time. Remarkably, rhomboid proteases displayed no physiological affinity for substrates (K(d) ~190 μM/0.1 mol%). Instead, ~10,000-fold differences in proteolytic efficiency with substrate mutants and diverse rhomboid proteases were reflected in k(cat) values alone. Analysis of gate-open mutant and solvent isotope effects revealed that substrate gating, not hydrolysis, is rate limiting. Ultimately, a single proteolytic event within the membrane normally takes minutes. Rhomboid intramembrane proteolysis is thus a slow, kinetically controlled reaction not driven by transmembrane protein-protein affinity. These properties are unlike those of other studied proteases or membrane proteins but are strikingly reminiscent of one subset of DNA-repair enzymes, raising important mechanistic and drug-design implications., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Purpose: Previously, we have documented surface temperatures recorded by thermography great enough to cause osteonecrosis of the femoral head during hip resurfacing. We now performed an in vitro investigation with 3 questions: (1) whether water irrigation reduced bone surface temperature, (2) whether external bone temperatures were similar to core temperatures, and (3) whether blunting of the reamer affected temperature generation., Methods: Using an ox-bone model, 57 femoral heads were peripherally reamed. The surface temperatures of bone were measured using a thermal camera and internal bone temperatures were measured using 2 theromocouples. We measured the effects of cooling with water at room temperature and with ice-cooled water. Progressive blunting of reamers was assessed over the 57 experiments., Results: Mean and maximum temperatures generated during peripheral reaming were greater when no irrigation was used. Ice-cold saline protected femoral heads from thermal damage. External bone temperatures were much greater than internal temperatures, which were not sufficiently elevated to cause osteonecrosis regardless of lavage. Blunting of the reamer was not found to have a statistically significant effect in this study., Interpretation: Cooling with ice-cooled water is recommended. Internal bone temperatures are not elevated despite the high surface temperatures reached during femoral head resurfacing.

Study Design: Retrospective longitudinal cohort., Objective: To evaluate the different patterns of stenosis with lateral subluxation in degenerative lumbar scoliosis (DLS)., Summary of Background Data: Lateral subluxation of the vertebra is commonly seen in DLS. Different patterns of subluxation occur at different levels of the spine and are often associated with neurological compression that can be symptomatic requiring treatment. The pattern and location of the stenosis are variable in DLS. No study to date has evaluated the site of stenosis seen on magnetic resonance imaging with respect to the different patterns or locations of lateral subluxation., Methods: The standing radiographs and supine magnetic resonance imaging scans of 35 consecutive patients with DLS were analyzed and demonstrated lateral listhesis on standing radiographs (average age, 70.2 years). Subluxation level, amount of listhesis, subluxation angle, axial rotation, and pattern or location of spinal stenosis were noted., Results: There were 60 subluxations in 35 patients. Open subluxations resulted in predominantly contralateral lateral recess and foraminal stenosis (71%; 17 of 24 patients). Closed dislocations demonstrated an ipsilateral pattern of stenosis (82%; 14 of 17 patients). Open subluxations were most commonly present at L3-4 toward the convex apex, whereas closed subluxations were identified on the concavity of the curve, with L1-2 most frequently involved (53%; 9 of 17 patients). An association was identified with open dislocations involving the mid-lumbar spine and closed subluxations at L1-2 (p < .001)., Conclusions: Open and closed subluxations in DLS result in different patterns of spinal stenosis. The presence of unilateral stenosis should alert the clinician to the possibility of spinal deformity and lateral subluxation. After careful review of the anteroposterior standing radiograph, any lateral subluxation and its type can be determined. This may assist decision making in how to treat the stenosis when deformity is present., (Copyright © 2013 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Total shoulder resurfacing (TSR) provides a reliable solution for the treatment of glenohumeral arthritis. It confers a number of advantages over traditional joint replacement with stemmed humeral components, in terms of bone preservation and improved joint kinematics. This study aimed to determine if humeral reaming instruments produce a thermal insult to subchondral bone during TSR., Patients and Methods: This was tested in vivo on 13 patients (8 with rheumatoid arthritis and 5 with osteoarthritis) with a single reaming system and in vitro with three different humeral reaming systems on saw bone models. Real-time infrared thermal video imaging was used to assess the temperatures generated., Results: Synthes (Epoca) instruments generated average temperatures of 40.7°C (SD 0.9°C) in the rheumatoid group and 56.5°C (SD 0.87°C) in the osteoarthritis group (P = 0.001). Irrigation with room temperature saline cooled the humeral head to 30°C (SD 1.2°C). Saw bone analysis generated temperatures of 58.2°C (SD 0.79°C) in the Synthes (Epoca) 59.9°C (SD 0.81°C) in Biomet (Copeland) and 58.4°C (SD 0.88°C) in the Depuy Conservative Anatomic Prosthesis (CAP) reamers (P = 0.12)., Conclusion: Humeral reaming with power driven instruments generates considerable temperatures both in vivo and in vitro. This paper demonstrates that a significant thermal effect beyond the 47°C threshold needed to induce osteonecrosis is observed with humeral reamers, with little variation seen between manufacturers. Irrigation with room temperature saline cools the reamed bone to physiological levels and should be performed regularly during this step in TSR.

We identified 45 knees in 42 patients who had an isolated tibial insert exchange for a failed primary knee arthroplasty with a minimum of 2 years of follow-up. The mean age at revision was 68 years, and the mean time to revision was 80 months. Thirty patients completed follow-up questionnaires (Oxford Knee Score, University Of California Activity Index score, Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], and Short Form 12) with a mean follow-up of 58 months. Patients' current scores were compared with preoperative scores in 14 knees. Four patients (9%) were subsequently revised. Significant improvement was seen in the Oxford Knee Score, Short Form 12 physical component, and all WOMAC domains, but only 58% of patients had a clinically successful result by global WOMAC score. When patients are selected appropriately, an isolated liner exchange can significantly improve the function of the knee., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Intramembrane proteases hydrolyze peptide bonds within the membrane as a signaling paradigm universal to all life forms and with implications in disease. Deciphering the architectural strategies supporting intramembrane proteolysis is an essential but unattained goal. We integrated new, quantitative and high-throughput thermal light-scattering technology, reversible equilibrium unfolding and refolding and quantitative protease assays to interrogate rhomboid architecture with 151 purified variants. Rhomboid proteases maintain low intrinsic thermodynamic stability (ΔG = 2.1-4.5 kcal mol(-1)) resulting from a multitude of generally weak transmembrane packing interactions, making them highly responsive to their environment. Stability is consolidated by two buried glycines and several packing leucines, with a few multifaceted hydrogen bonds strategically deployed to two peripheral regions. Opposite these regions lie transmembrane segment 5 and connected loops that are notably exempt of structural responsibility, suggesting intramembrane proteolysis involves considerable but localized protein dynamics. Our analyses provide a comprehensive 'heat map' of the physiochemical anatomy underlying membrane-immersed enzyme function at, what is to our knowledge, unprecedented resolution.

Ensuring the stability of a cemented PROSTALAC cup (Depuy, Warsaw, Ind) in the presence of severe superior acetabular segmental deficiency is critical to the success of the first-stage surgery. We present an illustrative case and the surgical technique required to achieve this., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We reviewed the seven- to ten-year results of our previously reported prospective randomised controlled trial comparing total hip replacement and hemiarthroplasty for the treatment of displaced intracapsular fracture of the femoral neck. Of our original study group of 81 patients, 47 were still alive. After a mean follow up of nine years (7 to 10) overall mortality was 32.5% and 51.2% after total hip replacement and hemiarthroplasty, respectively (p = 0.09). At 100 months postoperatively a significantly greater proportion of hemiarthroplasty patients had died (p = 0.026). Three hips dislocated following total hip replacement and none after hemiarthroplasty. In both the total hip replacement and hemiarthroplasty groups a deterioration had occurred in walking distance (p = 0.02 and p < 0.001, respectively). One total hip replacement required revision compared with four hemiarthroplasties which were revised to total hip replacements. All surviving patients with a total hip replacement demonstrated wear of the cemented polyethylene component and all hemiarthroplasties had produced acetabular erosion. There was lower mortality (p = 0.013) and a trend towards superior function in patients with a total hip replacement in the medium term.

The main objective of this study is to determine the prevalence of coronal abnormalities of the lumbar spine in a large population of patients with respect to their age and sex. Lumbar degenerative disease is associated with degenerative scoliosis. Degenerative scoliosis and lateral listhesis are important features to identify before decompressive surgery as deformity may not be seen on magnetic resonance imaging scans. Scoliosis and lateral listhesis may be important in the development of symptoms especially in an ageing population. All abdominal and plain kidney-ureter-bladder radiographs performed over a 10-month period were reviewed. 2,765 radiographs were assessed for scoliosis (Cobb angle greater then 10°), lateral listhesis and evidence of osteoarthritis. The prevalence of scoliosis, lateral listhesis and osteoarthritis of the lumbar spine increased with age. Scoliosis and lateral listhesis were significantly more prevalent in women. Deformity starts to occur after the age of 50 and steadily increases with age. By the ninth decade nearly a quarter of patients have evidence of scoliosis and lateral listhesis. As the adult lumbar spine ages, the prevalence of lateral listhesis and degenerative scoliosis increases. It is important to appreciate these coronal abnormalities in patients undergoing decompressive surgery for spinal stenosis. This increase in deformity may have a greater impact as the population continues to age.

We compared the medium-term clinical and radiological results of hybrid total hip replacement (THR) with metal-on-metal Birmingham hip resurfacing (BHR) in two groups of 54 young patients matched for age, gender, body mass index and pre-operative levels of activity. The clinical outcome was assessed by the University of California, Los Angeles (UCLA) activity score, the Oxford Hip Score (OHS) and the EuroQol scores. Radiologically, all hips were assessed for migration and osteolysis, the hybrid THRs for polyethylene wear and the BHRs for a pedestal sign. The mean follow-up of the patients with a hybrid THR was ten years and for those with a BHR, nine years. Four patients with a hybrid THR and one with a BHR had died. In each group five were lost to follow-up. The revision rate of the hybrid THRs was 16.7% (9 of 54) and of the BHRs 9.3% (5 of 54) (p = 0.195). Radiographs of a further eight hybrid THRs demonstrated wear and osteolysis, and they await revision (p = 0.008). Of the unrevised BHRs 90% had radiological changes, of which approximately 50% had progressed over the previous four years. All hybrid THRs demonstrated linear polyethylene wear with a mean of 1.24 mm (0.06 to 3.03). The BHRs recorded superior OHS (p = 0.013), UCLA (p = 0.008), and EuroQol visual analogue scores (p = 0.009). After nine years, patients with BHRs remained more active and had a lower rate of revision than those with hybrid THRs. Both groups demonstrated progressive radiological changes at medium-term follow-up.