Contemporary modern total ankle arthroplasty (TAA): A systematic review and meta-analysis of indications, survivorship and complication rates.

BACKGROUND: This study evaluates the clinical outcomes of contemporary total ankle arthroplasty (TAAs) to primarily establish the current benefits and risks to facilitate informed decision making to secondarily establish if improvements are seen between subsequent generations of implants, bearing philosophy, and associated surgical technique. METHODS: A systematic review and meta-analysis of published data from January 2000 to January 2020 was conducted following PRISMA guidelines. INCLUSION CRITERIA: English language papers, adult population, ≥20 ankles with a minimum follow up ≥24 months, pre- and post-operative functional scores available. Ankle implants were characterised by generations, which were determined from the original studies and confirmed based on literature set definitions. RESULTS: A total of 4642 TAAs in 4487 patients from 51 studies were included. The mean age was 61.9-years and follow up 57.8-months. Overall, 10-year survivorship rates were 77.63 %, with mobile bearing designs showing a small but significant advantage. Improved survivorship favoured the most modern implants at both two (p < 0.05), and 10-years (p < 0.01). The relative risk of a complication occurring improved with the evolution of implants e.g., nerve injury, and post-operative complications such as fracture, wound complications (e.g., dehiscence or heamatoma) and radiological abnormalities (e.g., radiolucencies, heterotopic bone formation and aseptic loosening). However, surgical site infection, and intra-operative fracture rates remain implant independent. CONCLUSIONS: Modern TAA offers improved survivorship, even with a trend to lower mean implantation age, similar complexity and ever changing indications. It would appear that implant evolution has reduced risks, especially those associated with revision, without affecting functional outcomes.

Acute musculoskeletal infection in children: assessment and management.

Musculoskeletal infection in children is challenging to treat, and includes septic arthritis, deep tissue infection, osteomyelitis, discitis and pyomyositis. Delays to diagnosis and management, and under-treatment can be life-threatening and result in chronic disability. The British Orthopaedic Association Standards for Trauma include critical steps in the timely diagnosis and management of acute musculoskeletal infection in children, the principles of acute clinical care and the service delivery requirements to appropriately manage this cohort of patients. Orthopaedic and paediatric services are likely to encounter cases of acute musculoskeletal infection in children and thus an awareness and thorough understanding of the British Orthopaedic Association Standards for Trauma guidelines is essential. This article reviews these guidelines and associated published evidence for the management of children with acute musculoskeletal infection.

Assessment and management of adult ankle fractures: understanding the evidence.

Ankle fractures are a common injury. Assessment should include looking at the mechanism of injury, comorbidities, associated injuries, soft tissue status and neurovascular status. Emergent reduction is required for clinically deformed ankles. Investigations should include plain radiographs and a computed tomography scan for more complex injuries or those with posterior malleolus involvement. An assessment of ankle stability determines treatment, taking into account comorbidities and preoperative mobility which need special consideration. Non-operative management includes splint or cast, allowing for early weightbearing when the ankle is stable. Operative management includes open reduction and internal fixation, intramedullary nailing (of the fibula and hindfoot) and external fixation. Syndemosis stabilisation includes suture button or screw fixation. The aim of treatment is to restore ankle stability and this article explores the current evidence in best practice.

Outcomes of orthopaedic trauma patients undergoing surgery during the peak period of COVID-19 infection at a UK major trauma centre.

BACKGROUND: To review the clinical outcomes of all patients undergoing emergency orthopaedic trauma surgery at a UK major trauma centre during the first 6 weeks of the COVID-19 related lockdown. METHODS: A retrospective review was performed of all patients who underwent emergency orthopaedic trauma surgery at a single urban major trauma centre over the first six-week period of national lockdown. Demographics, co-morbidities, injuries, injury severity scores, surgery, COVID-19 status, complications and mortalities were analysed. RESULTS: A total of 76 patients were included for review who underwent multiple procedures. Significant co-morbidity was present in 72%. The overall COVID-19 infection rate of the study population at any time was 22%. Sub-group analysis indicated 13% had active COVID-19 at the time of surgery. Only 4% of patients developed COVID-19 post surgery with no mortalities in this sub-group. The overall mortality rate was 4%. The overall complication rate was 14%. However mortality and complications rates were higher if the patients had active COVID-19 at surgery, if they were over 70 years and had sustained life-threatening injuries. CONCLUSION: The overall survival rate for patients undergoing emergency orthopaedic trauma surgery during the COVID-19 peak was 96%. The rate of any complication was more significant in those presenting with active COVID-19 infections who had sustained potentially life threatening injuries and were over 70 years of age. Conversely those without active COVID-19 infection and who lacked significant co-morbidities experienced a lower complication and mortality rate.

Untargeted analysis of plasma samples from pre-eclamptic women reveals polar and apolar changes in the metabolome.

INTRODUCTION: Pre-eclampsia is a hypertensive gestational disorder that affects approximately 5% of all pregnancies. OBJECTIVES: As the pathophysiological processes of pre-eclampsia are still uncertain, the present case-control study explored underlying metabolic processes characterising this disease. METHODS: Maternal peripheral plasma samples were collected from pre-eclamptic (n = 32) and healthy pregnant women (n = 35) in the third trimester. After extraction, high-resolution mass spectrometry-based untargeted metabolomics was used to profile polar and apolar metabolites and the resulting data were analysed via uni- and multivariate statistical approaches. RESULTS: The study demonstrated that the metabolome undergoes substantial changes in pre-eclamptic women. Amongst the most discriminative metabolites were hydroxyhexacosanoic acid, diacylglycerols, glycerophosphoinositols, nicotinamide adenine dinucleotide metabolites, bile acids and products of amino acid metabolism. CONCLUSIONS: The putatively identified compounds provide sources for novel hypotheses to help understanding of the underlying biochemical pathology of pre-eclampsia.

Pharmacological profile of vascular activity of human stem villous arteries.

INTRODUCTION: The function of the placental vasculature differs considerably from other systemic vascular beds of the human body. A detailed understanding of the normal placental vascular physiology is the foundation to understand perturbed conditions potentially leading to placental dysfunction. METHODS: Behaviour of human stem villous arteries isolated from placentae at term pregnancy was assessed using wire myography. Effects of a selection of known vasoconstrictors and vasodilators of the systemic vasculature were assessed. The morphology of stem villous arteries was examined using IHC and TEM. RESULTS: Contractile effects in stem villous arteries were caused by U46619, 5-HT, angiotensin II and endothelin-1 (p ≤ 0.05), whereas noradrenaline and AVP failed to result in a contraction. Dilating effects were seen for histamine, riluzole, nifedipine, papaverine, SNP and SQ29548 (p ≤ 0.05) but not for acetylcholine, bradykinin and substance P. DISCUSSION: Stem villous arteries behave differently to vessels of the systemic vasculature and results indicate that the placenta is cut off from the systemic maternal vascular regulation. Particularly, endothelium-dependent processes were attenuated in the placental vasculature, creating a need to determine the role of the endothelium in the placenta in future studies.

Evaluation of extraction and normalisation strategies for the analysis of lipids in placental vessels.

The analysis of lipids in tough or fibrous biological tissues can be challenging due to difficulties in obtaining a representative sample following homogenisation of the tissue. Furthermore, the choice of normalisation method can have a major effect on the quality of quantitative results. Therefore, a range of mechanical homogenisation techniques and normalisation strategies were evaluated for application to human placental vessels. The findings showed that rotor-stator homogenisation in a suitable solvent and wet weight normalisation were the best combination of procedures for quantitative analysis of lipids in placental blood vessels.

Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer.

The use of reference genes is the most common method of controlling the variation in mRNA expression during quantitative polymerase chain reaction, although the use of traditional reference genes, such as ß­actin, glyceraldehyde­3­phosphate dehydrogenase or 18S ribosomal RNA, without validation occasionally leads to unreliable results. Therefore, the present study aimed to evaluate a set of five commonly used reference genes to determine the most suitable for gene expression studies in normal ovarian tissues, borderline ovarian and ovarian cancer tissues. The expression stabilities of these genes were ranked using two gene stability algorithms, geNorm and NormFinder. Using geNorm, the two best reference genes in ovarian cancer were ß­glucuronidase and ß­actin. Hypoxanthine phosphoribosyltransferase­1 and ß­glucuronidase were the most stable in ovarian borderline tumours, and hypoxanthine phosphoribosyltransferase­1 and glyceraldehyde­3­phosphate dehydrogenase were the most stable in normal ovarian tissues. NormFinder ranked ß­actin the most stable in ovarian cancer, and the best combination of two genes was ß­glucuronidase and ß­actin. In borderline tumours, hypoxanthine phosphoribosyltransferase­1 was identified as the most stable, and the best combination was hypoxanthine phosphoribosyltransferase­1 and ß­glucuronidase. In normal ovarian tissues, ß­glucuronidase was recommended as the optimum reference gene, and the most optimum pair of reference genes was hypoxanthine phosphoribosyltransferase­1 and ß­actin. To the best of our knowledge, this is the first study to investigate the selection of a set of reference genes for normalisation in quantitative polymerase chain reactions in different ovarian tissues, and therefore it is recommended that ß­glucuronidase, ß­actin and hypoxanthine phosphoribosyltransferase­1 are the most suitable reference genes for such analyses.

Caspase-1-mediated cytokine release from gestational tissues, placental, and cord blood.

Distinguishing between fetal and maternal inflammatory responses is necessary for understanding the immune interplay either side of the placenta. Fetal immunity reaches maturity during extrauterine life and while basic inflammatory responses afford a certain degree of protection, fetuses are vulnerable to infection. With the discovery of inflammasomes-intracellular scaffolds that facilitate the elaboration of reactions resulting in the release of mature interleukin-1ß (IL-1ß)-it is necessary to consider how inflammatory stimuli are processed. The purinergic P2X7 receptor located on haematopoietic cells is a key intermediary in signal transduction initiated at Toll-like receptors (TLR) terminating in release of the mature IL-1ß product. We demonstrate herein that IL-1ß release from fetal membranes and mononuclear cells isolated from cord, placental, and maternal blood, obtained at term, is P2X7- and caspase-1 dependent. The P2X7-dependent release of the cytokine, which was highest from choriodecidua, was attenuated by progesterone (P4), prolactin and an NFkB inhibitor. The NLRP3 inflammasome appears necessary for the processing of IL-1ß in gestational tissues and leukocytes.

A clear and present danger: inflammasomes DAMPing down disorders of pregnancy.

BACKGROUND: When the normal progression of pregnancy is threatened, inflammatory processes are often amplified in order to minimize detrimental effects and eliminate noxious agents. Inflammasomes are unique, intracellular, multiprotein assemblies that enable caspase-1 mediated proteolytic processing of the proinflammatory cytokine interleukin-1ß, levels of which are elevated in some forms of preterm birth and maternal metabolic disorders. METHODS: A comprehensive review based on a search of PubMed and Medline for terms and combinations of terms incorporating 'inflammation', 'inflammasome', 'pregnancy', 'preterm birth', 'pre-eclampsia', 'interleukin-1', 'caspase-1' and others selected to capture key articles. RESULTS: In the decade since the discovery of the inflammasome, between January 2002 and June 2014 over 2200 articles have been published. Articles in the reproductive field are scarce but there is clear evidence for a role of the inflammasome axis in pregnancy, preterm birth and the maternal metabolic syndrome. CONCLUSION: Further investigations on the inflammasome in pregnancy are needed in order to elucidate the biology of this unique structure in reproduction. Coordination of maternal, fetal and placental aspects of inflammasome function will potentially yield new information on the detection and transduction of host and non-host signals in the inflammatory response.

Current status and effectiveness of mentorship programmes in urology: a systematic review.

The objectives of this review were to identify and evaluate the efficacy of mentorship programmes for minimally invasive procedures in urology and give recommendations on how to improve mentorship. A systematic literature search of the PubMed/Medline databases was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In all, 21 articles were included in the review and divided into four categories: fellowships, mini-fellowships, mentored skills courses and novel mentorship programmes. Various structures of mentorship programme were identified and in general, mentorship programmes were found to be feasible, having content validity and educational impact. Perioperative data showed equally good outcomes when comparing trainees and specialists. Mentorship programmes are effective and represent one of the best current methods of training in urology. However, participation in such programmes is not widespread. The structure of mentorship programmes is highly variable, with no clearly defined 'best approach' for postgraduate training. This review offers recommendations as to how this 'best approach' can be established.

Expression and prognostic significance of the oncogenic K2P potassium channel KCNK9 (TASK-3) in ovarian carcinoma.

BACKGROUND/AIMS: The TWIK-related acid sensitive K(+) channel-3 (TASK-3) is an oncogenic potassium channel. We investigated the expression of TASK-3 in human ovaries, examined its prognostic significance, and determined effects of TASK-3 blockers on cell proliferation and apoptosis. MATERIALS AND METHODS: Immunofluorescence and western blotting were used to investigate TASK-3 expression in two ovarian cancer cell lines, normal ovarian surface epithelium and cancer. Immunohistochemistry quantified expression in an ovarian cancer tissue microarray. The effect of TASK-3 blocking agents on cell proliferation was investigated with the CellTiter 96® Aqueous Non-Radioactive Cell Proliferation assay and on apoptosis with flow cytometry. RESULTS: TASK-3 expression was confirmed by immunofluorescence in the SKOV-3 and OVCAR-3 cell lines, normal ovaries (n=4) and ovarian tumours (n=4) and by western blotting in normal ovaries (n=6) and ovarian tumours (n=22). Immunohistochemistry demonstrated immunostaining in 99% of tumours (n=230). Increased immunostaining conferred a survival advantage (p=0.002; median survival of >24 months). TASK-3 blockers caused a significant reduction in cell proliferation and an increase in apoptosis in the SKOV-3 and OVCAR-3 cell lines. CONCLUSION: TASK-3 is expressed in epithelial ovarian cancer, conferring a significant survival advantage on patients with increased expression. TASK-3-modulating agents have a significant effect on cell proliferation and apoptosis. Based on these results, we propose that TASK-3 could prove to be both a novel tumour marker and a new therapeutic target in ovarian cancer, but further investigation is required.

Thermoresponsive nanostructures by self-assembly of a poly(N-isopropylacrylamide)-lipid conjugate.

The synthesis and purification of a poly(N-isopropylacrylamide)-lipid conjugate and its use in the preparation of a thermoresponsive lipid mesophase is described. Specifically, poly(N-isopropylacrylamide) with a single carboxyl group at one end was activated with dicyclohexylcarbodiimide/N-hydroxysuccinimide to form an active ester. This N-hydroxysuccinimide ester was then used to form a dimyristoyl-sn-glycero-3-phosphoethanolamine conjugate with poly(N-isopropylacrylamide) via an amide bond, rendering the conjugate amphiphilic. Quaternary phases comprising the conjugate, a phosopholipid, dimyristoylphosphatidylcholine, and a cosurfactant, N,N-dimethyldodecylamine-N-oxide, dispersed in water were found to self-assemble at room temperature to form liquid crystalline gels, adopting an expanded lamellar structure. A modest increase in temperature triggered the reversible conversion of the aggregate to a collapsed lamellar structure, while a modest reduction in temperature resulted in its conversion to a nonlamellar phase. The phases were characterized by polarized optical microscopy and small-angle X-ray scattering (SAXS).

Low-temperature, high yield synthesis, and convenient isolation of the high-electron-density cluster compound Ta6Br14.8H2O for use in biomacromolecular crystallographic phase determination.

Reduction of TaBr(5) with Ga in the presence of KBr in a sealed borosilicate ampule at 400 degrees, followed by aqueous Soxhlet extraction and addition of stannous bromide and hydrobromic acid to the extract, yielded Ta(6)Br(14).8H(2)O in 80-84% yield. The new procedure provides a convenient, low temperature, high yield route to the synthesis of the title compound from inexpensive precursors.

Gallium and gallium dichloride, new solid-state reductants in preparative transition metal chemistry. New, lower temperature syntheses and convenient isolation of hexatantalum tetradecachloride octahydrate, Ta(6)(mu-Cl)(12)Cl(2)(OH(2))(4).4H(2)O, and synthesis and solid-state structure of a tetraalkylammonium derivative, [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)], of the reduced [Ta(6)(mu-Cl)(12)](2+) cluster core(1).

Reduction of TaCl(5) with either Ga or Ga(2)Cl(4), in the presence of NaCl, in a sealed borosilicate glass ampule at 500 degrees C, followed by aqueous Soxhlet extraction and treatment with SnCl(2) and hydrochloric acid, yielded Ta(6)(mu-Cl)(12)Cl(2)(OH(2))(4).4H(2)O in 92% (Ga) or 96% (Ga(2)Cl(4)) yield. Ga(2)Cl(4), a probable intermediate in the Ga-based reduction, is a more convenient reductant than Ga because it is readily dispersed in the reaction mixture, and these mixtures do not require homogenizations in order to afford high yields. Ta(6)(mu-Cl)(12)Cl(2)(OH(2))(4).4H(2)O was converted by ligand exchange to the first tetraalkylammonium derivative, [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)], of the reduced cluster core Ta(6)(mu-Cl)(12)(2+), in 88% yield. [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)] crystallizes from 1,2-dichloroethane/toluene mixtures in two crystalline morphologies, a nonsolvated cubic form and a solvated needle form. The solid-state molecular structures of both crystalline morphologies of [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)] consist of octahedral, 16 VEC hexatantalum cluster anions with an average Ta-Ta distance of 2.900[2] A, a Ta-Cl(bridge) distance of 2.463[2] A, a Ta-Cl(terminal) distance of 2.567[5] A, and a Ta-Cl-Ta angle of 72.1[1] degrees for the cubic form, and for the solvated needle morphology, an average Ta-Ta distance of 2.900[1] A, a Ta-Cl(bridge) distance of 2.461[1]A, a Ta-Cl(terminal) distance of 2.567[3] A, and a Ta-Cl-Ta angle of 72.19[7] degrees.