RESUMO
Aims: Total knee arthroplasty (TKA) with a highly congruent condylar-stabilized (CS) articulation may be advantageous due to increased stability versus cruciate-retaining (CR) designs, while mitigating the limitations of a posterior-stabilized construct. The aim was to assess ten-year implant survival and functional outcomes of a cemented single-radius TKA with a CS insert, performed without posterior cruciate ligament sacrifice. Methods: This retrospective cohort study included consecutive patients undergoing TKA at a specialist centre in the UK between November 2010 and December 2012. Data were collected using a bespoke electronic database and cross-referenced with national arthroplasty audit data, with variables including: preoperative characteristics, intraoperative factors, complications, and mortality status. Patient-reported outcome measures (PROMs) were collected by a specialist research team at ten years post-surgery. There were 536 TKAs, of which 308/536 (57.5%) were in female patients. The mean age was 69.0 years (95% CI 45.0 to 88.0), the mean BMI was 32.2 kg/m2 (95% CI 18.9 to 50.2), and 387/536 (72.2%) survived to ten years. There were four revisions (0.7%): two deep infections (requiring debridement and implant retention), one aseptic loosening, and one haemosiderosis. Results: Kaplan-Meier analysis demonstrated no difference in implant survival according to sex, age, or obesity status. Ten-year PROMs were available for 196/387 (50.6%) surviving patients and were excellent: mean Oxford Knee Score 34.4 (95% CI 32.7 to 36.1); mean Forgotten Joint Score (FJS) 51.2 (95% CI 16.1 to 86.3); mean EuroQol five-dimension five-level questionnaire score 69.9 (95% CI 46.8 to 93.0); 141/196 (71.9%) achieved the 22-point FJS patient-acceptable symptom state (PASS); and 156/196 (79.6%) were "very satisfied or satisfied". Conclusion: This is the only large study reporting ten-year implant survival and functional outcomes of TKA using a cemented single-radius design and with a CS tibial bearing construct. The findings of excellent implant survival, safety, and functional outcomes indicate that this combination is a safe and effective option in routine TKA. Further investigation of this single-radius design TKA with CS tibial bearings with well-matched patient study groups will allow further insight into the performance of these implants.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Medidas de Resultados Relatados pelo Paciente , Ligamento Cruzado Posterior , Desenho de Prótese , Falha de Prótese , Humanos , Artroplastia do Joelho/métodos , Feminino , Masculino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Ligamento Cruzado Posterior/cirurgia , Cimentos Ósseos/uso terapêutico , Osteoartrite do Joelho/cirurgia , Resultado do Tratamento , CimentaçãoRESUMO
The synthesis and characterization of a novel trinuclear rhodamine-Gd(III) complex, along with two analogous mononuclear rhodamine-Gd(III) complexes, are reported. All complexes displayed good selectivity in a human glioma cell line (T98G) when compared to a glial cell line (SVG p12), with low cytotoxicities. Superior tumor cell uptake for these Gd(III) complexes was observed at lower incubation concentrations compared to previously-reported delocalized lipophilic cations such as a rhodamine-lanthanoid (III) probe and Gd(III)-arylphosphonium complexes, with ca. 150% and 250% increases in Gd uptake, respectively.
RESUMO
The synthesis, characterisation, and tumour cell uptake of six novel Gd(III)-diphenylphosphoryl-diphenylphosphonium complexes are reported. The propyl-linked Gd(III) complexes can accumulate inside human glioma cells at prodigious levels, approaching 1200%, over the parent triphenylphosphonium salts. DFT and quantum chemical topology analyses support a new type of conformationally-dependent tumour cell targeting vector.
Assuntos
Gadolínio , Neoplasias , Humanos , Gadolínio/farmacologia , Gadolínio/química , Neoplasias/patologiaRESUMO
Aims: National hip fracture registries audit similar aspects of care but there is variation in the actual data collected; these differences restrict international comparison, benchmarking, and research. The Fragility Fracture Network (FFN) published a revised minimum common dataset (MCD) in 2022 to improve consistency and interoperability. Our aim was to assess compatibility of existing registries with the MCD. Methods: We compared 17 hip fracture registries covering 20 countries (Argentina; Australia and New Zealand; China; Denmark; England, Wales, and Northern Ireland; Germany; Holland; Ireland; Japan; Mexico; Norway; Pakistan; the Philippines; Scotland; South Korea; Spain; and Sweden), setting each of these against the 20 core and 12 optional fields of the MCD. Results: The highest MCD adherence was demonstrated by the most recently established registries. The first-generation registries in Scandinavia collect data for 60% of MCD fields, second-generation registries (UK, other European, and Australia and New Zealand) collect for 75%, and third-generation registries collect data for 85% of MCD fields. Five of the 20 core fields were collected by all 17 registries (age; sex; surgery date/time of operation; surgery type; and death during acute admission). Two fields were collected by most (16/17; 94%) registries (date/time of presentation and American Society of Anesthesiologists grade), and five more by the majority (15/17; 88%) registries (type, side, and pathological nature of fracture; anaesthetic modality; and discharge destination). Three core fields were each collected by only 11/17 (65%) registries: prefracture mobility/activities of daily living; cognition on admission; and bone protection medication prescription. Conclusion: There is moderate but improving compatibility between existing registries and the FFN MCD, and its introduction in 2022 was associated with an improved level of adherence among the most recently established programmes. Greater interoperability could be facilitated by improving consistency of data collection relating to prefracture function, cognition, bone protection, and follow-up duration, and this could improve international collaborative benchmarking, research, and quality improvement.
Assuntos
Atividades Cotidianas , Fraturas do Quadril , Humanos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Cognição , Prática Clínica Baseada em Evidências , Padrões de ReferênciaRESUMO
AIM: The aims were to assess the utility of: 1) virtual reality-mediated simulation, and 2) a multi-modality 'Bootcamp' in the delivery of total knee arthroplasty (TKA) teaching to orthopaedic surgical trainees. BACKGROUND: Surgical training opportunities are diminished as a result of the COVID-19 pandemic which may result in delays to training completion and gaps in the permanent workforce. Modern and technology-enhanced learning methods have been identified as having the potential to support high-quality and sustainable education. METHODS: This mixed-methods study assessed the educational benefit of two activities designed to teach TKA to junior (ST1-3) orthopaedic trainees. A multi-modality training Bootcamp was delivered that included: virtual reality (VR) and saw-bone simulation; tutorials, and case-based symposia. The VR component was delivered to different participants (surgical trainees, scrub nurses, and consultants) on a further two separate occasions. Qualitative and quantitative data were collected pertaining to utility and performance. RESULTS: Trainees reported that the Bootcamp improved comprehension of arthroplasty principles including component alignment, knee balancing, and intraoperative strategies. Case-based discussions helped develop diagnostic and decision-making skills. The VR activity improved understanding of the surgical process map, increased ability to anticipate steps, and consider the procedure strategically. All staff groups found the VR activity beneficial and would recommend it as a useful addition to a surgical department. CONCLUSION: VR-mediated simulation could augment the education of surgical trainees and scrub team staff by improving comprehension of the surgical process map. Integrated multi-modality 'Bootcamp-style' training activities constructed around trainees' needs may provide a sustainable solution to bridge the experience gap related to reduced exposure to elective orthopaedic practice.
Assuntos
COVID-19 , Ortopedia , Treinamento por Simulação , Cirurgiões , Realidade Virtual , Humanos , Ortopedia/educação , Pandemias , COVID-19/epidemiologia , Tecnologia , Competência Clínica , Treinamento por Simulação/métodosRESUMO
Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies. Cite this article: Bone Joint Res 2022;11(6):342-345.
RESUMO
AIMS: The aim of this study was to explore current use of the Global Fragility Fracture Network (FFN) Minimum Common Dataset (MCD) within established national hip fracture registries, and to propose a revised MCD to enable international benchmarking for hip fracture care. METHODS: We compared all ten established national hip fracture registries: England, Wales, and Northern Ireland; Scotland; Australia and New Zealand; Republic of Ireland; Germany; the Netherlands; Sweden; Norway; Denmark; and Spain. We tabulated all questions included in each registry, and cross-referenced them against the 32 questions of the MCD dataset. Having identified those questions consistently used in the majority of national audits, and which additional fields were used less commonly, we then used consensus methods to establish a revised MCD. RESULTS: A total of 215 unique questions were used across the ten registries. Only 72 (34%) were used in more than one national audit, and only 32 (15%) by more than half of audits. Only one registry used all 32 questions from the 2014 MCD, and five questions were only collected by a single registry. Only 21 of the 32 questions in the MCD were used in the majority of national audits. Only three fields (anaesthetic grade, operation, and date/time of surgery) were used by all ten established audits. We presented these findings at the Asia-Pacific FFN meeting, and used an online questionnaire to capture feedback from expert clinicians from different countries. A draft revision of the MCD was then presented to all 95 nations represented at the Global FFN conference in September 2021, with online feedback again used to finalize the revised MCD. CONCLUSION: The revised MCD will help aspirant nations establish new registry programmes, facilitate the integration of novel analytic techniques and greater multinational collaboration, and serve as an internationally-accepted standard for monitoring and improving hip fracture services. Cite this article: Bone Joint J 2022;104-B(6):721-728.
Assuntos
Fraturas do Quadril , Benchmarking , Alemanha , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Sistema de Registros , EspanhaRESUMO
AIMS: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. METHODS: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1st March-31st May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. RESULTS: A total of 7090 patients were included, with a mean age of 82.2 (range 50-104) years and 4959 (69.9%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) were positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p = 0.001), residential care (OR 2.15, p < 0.001), inpatient fall (OR 2.23, p = 0.003), cancer (OR 0.63, p = 0.009), ASA grades 4 (OR 1.59, p = 0.008) or 5 (OR 8.28, p < 0.001), and longer admission (OR 1.06 for each increasing day, p < 0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p < 0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p < 0.001). Increasing age (HR 1.03, p = 0.028), male sex (HR 2.35, p < 0.001), renal disease (HR 1.53, p = 0.017), and pulmonary disease (HR 1.45, p = 0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. CONCLUSION: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher 30-day mortality risk.
Assuntos
COVID-19 , Infecção Hospitalar , Fraturas do Quadril , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Pandemias , Infecção Hospitalar/complicações , Infecção Hospitalar/epidemiologia , Mortalidade Hospitalar , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Estudos RetrospectivosRESUMO
AIMS: The aim of this study was to determine the impact of hospital-level service characteristics on hip fracture outcomes and quality of care processes measures. METHODS: This was a retrospective analysis of publicly available audit data obtained from the National Hip Fracture Database (NHFD) 2018 benchmark summary and Facilities Survey. Data extraction was performed using a dedicated proforma to identify relevant hospital-level care process and outcome variables for inclusion. The primary outcome measure was adjusted 30-day mortality rate. A random forest-based multivariate imputation by chained equation (MICE) algorithm was used for missing value imputation. Univariable analysis for each hospital level factor was performed using a combination of Tobit regression, Siegal non-parametric linear regression, and Mann-Whitney U test analyses, dependent on the data type. In all analyses, a p-value < 0.05 denoted statistical significance. RESULTS: Analyses included 176 hospitals, with a median of 366 hip fracture cases per year (interquartile range (IQR) 280 to 457). Aggregated data from 66,578 patients were included. The only identified hospital-level variable associated with the primary outcome of 30-day mortality was hip fracture trial involvement (no trial involvement: median 6.3%; trial involvement: median 5.7%; p = 0.039). Significant key associations were also identified between prompt surgery and presence of dedicated hip fracture sessions; reduced acute length of stay and both a higher number of hip fracture cases per year and more dedicated hip fracture operating lists; Best Practice Tariff attainment and greater number of hip fracture cases per year, more dedicated hip fracture operating lists, presence of a dedicated hip fracture ward, and hip fracture trial involvement. CONCLUSION: Exploratory analyses have identified that improved outcomes in hip fracture may be associated with hospital-level service characteristics, such as hip fracture research trial involvement, larger hip fracture volumes, and the use of theatre lists dedicated to hip fracture surgery. Further research using patient level data is warranted to corroborate these findings. Cite this article: Bone Joint J 2021;103-B(10):1627-1632.
Assuntos
Benchmarking , Fixação de Fratura/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Fraturas do Quadril/cirurgia , Hospitais/normas , Avaliação de Processos e Resultados em Cuidados de Saúde , Algoritmos , Auditoria Clínica , Bases de Dados Factuais , Fraturas do Quadril/mortalidade , Hospitais/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Lineares , Análise Multivariada , Guias de Prática Clínica como Assunto , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
AIMS: The primary aim was to assess the rate of postoperative COVID-19 following hip and knee arthroplasty performed in March 2020 in the UK. The secondary aims were to assess whether there were clinical factors associated with COVID-19 status, the mortality rate of patients with COVID-19, and the rate of potential COVID-19 in patients not presenting to healthcare services. METHODS: A multicentre retrospective study was conducted of patients undergoing hip or knee arthroplasty during the first wave of the COVID-19 pandemic (1 March 2020 to 31 March 2020) with a minimum of 60 days follow-up. Patient demographics, American Society of Anesthesiologists grade, procedure type, primary or revision, length of stay (LOS), COVID-19 test status, and postoperative mortality were recorded. A subgroup of patients (n = 211) who had not presented to healthcare services after discharge were contacted and questioned as to whether they had symptoms of COVID-19. RESULTS: Five (0.5%) of 1,073 patients who underwent hip or knee arthroplasty tested positive for SARS-CoV-2 postoperatively. When adjusting for confounding factors, increasing LOS (p = 0.022) was the only significant factor associated with developing COVID-19 following surgery and a stay greater than three days was a reliable predictor with an area under the curve of 81% (p = 0.018). There were three (0.3%) deaths in the study cohort and the overall mortality rate attributable to COVID-19 was 0.09% (n = 1/1,073), with one (20%) of the five patients with COVID-19 dying postoperatively. Of the 211 patients contacted, two had symptoms within two to 14 days postoperatively with a positive predictive value of 31% and it was therefore estimated that one patient may have had undiagnosed COVID-19. CONCLUSION: The rate of postoperative COVID-19 was 0.5% and may have been as high as 1% when accounting for those patients not presenting to healthcare services, which was similar to the estimated population prevalence during the study period. The overall mortality rate secondary to COVID-19 was low (0.09%), however the mortality rate for those patients developing COVID-19 was 20%. Cite this article: Bone Joint J 2021;103-B(4):681-688.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , COVID-19/epidemiologia , Procedimentos Cirúrgicos Eletivos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/etiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Auditoria Clínica , Feminino , Seguimentos , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Reino Unido/epidemiologiaRESUMO
The synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported. Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. The in vitro cytotoxicity of all complexes was determined to be low at therapeutically-relevant concentrations. Selected Gd(III) complexes are potential candidates for further investigation as theranostic agents.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Gadolínio/química , Glioblastoma/tratamento farmacológico , Compostos Organofosforados/síntese química , Compostos Organofosforados/farmacologia , Antineoplásicos/farmacocinética , Proliferação de Células , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Compostos Organofosforados/farmacocinética , Distribuição Tecidual , Células Tumorais CultivadasRESUMO
AIMS: The primary aim was to assess the independent influence of coronavirus disease (COVID-19) on 30-day mortality for patients with a hip fracture. The secondary aims were to determine whether: 1) there were clinical predictors of COVID-19 status; and 2) whether social lockdown influenced the incidence and epidemiology of hip fractures. METHODS: A national multicentre retrospective study was conducted of all patients presenting to six trauma centres or units with a hip fracture over a 46-day period (23 days pre- and 23 days post-lockdown). Patient demographics, type of residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, operation, American Society of Anesthesiologists (ASA) grade, anaesthetic, length of stay, COVID-19 status, and 30-day mortality were recorded. RESULTS: Of 317 patients with acute hip fracture, 27 (8.5%) had a positive COVID-19 test. Only seven (26%) had suggestive symptoms on admission. COVID-19-positive patients had a significantly lower 30-day survival compared to those without COVID-19 (64.5%, 95% confidence interval (CI) 45.7 to 83.3 vs 91.7%, 95% CI 88.2 to 94.8; p < 0.001). COVID-19 was independently associated with increased 30-day mortality risk adjusting for: 1) age, sex, type of residence (hazard ratio (HR) 2.93; p = 0.008); 2) Nottingham Hip Fracture Score (HR 3.52; p = 0.001); and 3) ASA (HR 3.45; p = 0.004). Presentation platelet count predicted subsequent COVID-19 status; a value of < 217 × 109/l was associated with 68% area under the curve (95% CI 58 to 77; p = 0.002) and a sensitivity and specificity of 63%. A similar number of patients presented with hip fracture in the 23 days pre-lockdown (n = 160) and 23 days post-lockdown (n = 157) with no significant (all p ≥ 0.130) difference in patient demographics, residence, place of injury, Nottingham Hip Fracture Score, time to surgery, ASA, or management. CONCLUSION: COVID-19 was independently associated with an increased 30-day mortality rate for patients with a hip fracture. Notably, most patients with hip fracture and COVID-19 lacked suggestive symptoms at presentation. Platelet count was an indicator of risk of COVID-19 infection. These findings have implications for the management of hip fractures, in particular the need for COVID-19 testing. Cite this article: Bone Joint J 2020;102-B(9):1219-1228.
Assuntos
Causas de Morte , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Fraturas do Quadril/epidemiologia , Mortalidade Hospitalar , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Estudos de Coortes , Feminino , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/cirurgia , Humanos , Incidência , Masculino , Pandemias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Centros de TraumatologiaRESUMO
Purpose: Neurosurgical patients are often complex and require high quality, attentive care in the immediate postoperative period. We identified a number of issues in our department pertaining to patient safety and the assessment and management of patients following handover of care to the neurosurgical ward, and intervened with an aim to provide safe, timely, patient-centred, and procedure-specific care in the postoperative period. Method: We reviewed the records of 50 patients between (Aug-Oct 2015) and analysed quality of postoperative assessment, prescriptions, and adherence to national standards of postoperative care. We identified barriers to effective practice and intervened by introducing a bespoke Neurosurgical Postoperative Checklist which provided a framework for the assessment and management of patients in the immediate postoperative period. We reviewed the records of 50 patients (Oct-Nov 2016) to assess adherence to the new protocol and its effect on the quality of postoperative care, and reaudited a further 50 patients after one year (Sep-Nov 2016). Results: Prior to intervention 37/50 (74.0%) patients were reviewed postoperatively and quality was poor. This improved to 49/50 (98.0%) post-Checklist and was associated with a dramatic improvement in quality of care compared to pre-Checklist: appropriate analgesia and anti-emetics prescribed in 98.0% and 98.0% versus 26.0% and 18.0%; appropriate antibiotic and corticosteroid prescription in 100.0% and 100.0% versus 26.0% and 18.0%; and timely prescription of an appropriate VTE prophylaxis plan in 98.0% versus 2.0% pre-Checklist. Improvements were sustained after one year. Conclusions: The introduction of our Neurosurgery Postoperative Checklist yielded dramatic improvements in patient safety and quality of postoperative care, as indicated by improved adherence to national standards of postoperative clinical assessment, and the quality and safety of medication prescriptions which are so vital in complex neurosurgical patients. We recommend the use of a neurosurgical Postoperative Checklist as a simple, cheap, reproducible tool to improve patient care.
Assuntos
Lista de Checagem/métodos , Procedimentos Neurocirúrgicos/métodos , Segurança do Paciente , Cuidados Pós-Operatórios/métodos , Qualidade da Assistência à Saúde , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Prescrições de Medicamentos , Fidelidade a Diretrizes , Humanos , Dor Pós-Operatória/tratamento farmacológico , Melhoria de QualidadeRESUMO
Pseudouridine (Ψ) is an important urinary cancer biomarker, especially in human colorectal cancer (CRC). Disclosed herein is the first Ψ molecularly imprinted polymer (Ψ-MIP) material obtained from tailor-engineered functional monomers. The resulting MIP imprint exhibits a remarkable imprinting factor greater than 70. It is successfully used for the selective recognition of Ψ in spiked human urine. This selective functionalized material opens the route to the development of inexpensive disposable chemosensors for noninvasive CRC diagnosis and prognosis.
Assuntos
Biomarcadores Tumorais/urina , Cromatografia Líquida de Alta Pressão/métodos , Polímeros/síntese química , Pseudouridina/urina , Humanos , Espectroscopia de Ressonância Magnética , Impressão Molecular/métodos , Polimerização , Polímeros/química , Extração em Fase Sólida/instrumentação , Extração em Fase Sólida/métodos , Solventes/químicaRESUMO
Molecularly imprinted polymers (MIPs) targeting tegafur, an anti-cancer 5-fluorouracil pro-drug, have been prepared by stoichiometric imprinting using 2,6-bis(acrylamido)pyridine (BAAPy) as the functional monomer. Solution association between tegafur and BAAPy was studied by (1)H NMR titration, which confirmed the formation of 1:1 complexes with an affinity constant of 574±15M(-1) in CDCl3. Evaluation of the synthesised materials by HPLC and equilibrium rebinding experiments revealed high selectivity of the imprinted polymer for the pro-drug vs. 5-fluorouracil and other competing analytes, with maximum imprinting factors of 25.3 and a binding capacity of 45.1µmolg(-1). The synthesised imprinted polymer was employed in solid-phase extraction of the pro-drug using an optimised protocol that included a simple wash with the porogen used in the preparation of the material. Tegafur recoveries of up to 96% were achieved from aqueous samples and 92% from urine samples spiked with the template and three competing analytes. The results demonstrate the potential of the prepared polymers in the pre-concentration of tegafur from biological samples, which could be an invaluable tool in the monitoring of patient compliance and drug uptake and excretion.
Assuntos
Antineoplásicos/análise , Impressão Molecular/métodos , Tegafur/análise , Antineoplásicos/química , Cromatografia Líquida , Humanos , Extração em Fase Sólida , Tegafur/químicaRESUMO
BACKGROUND & AIMS: Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity. METHODS: The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63). RESULTS: HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04). CONCLUSIONS: Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.
Assuntos
Ordem de Nascimento , Carcinoma Hepatocelular/epidemiologia , Portador Sadio/epidemiologia , Antígenos de Superfície da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/virologia , Estudos de Casos e Controles , Feminino , Gâmbia/epidemiologia , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/transmissão , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: To estimate the seroprevalence of cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella zoster virus (VZV) among pregnant women in Bradford by ethnic group and country of birth. METHODS: A stratified random sample of 949 pregnant women enrolled in the Born in Bradford birth cohort was selected to ensure sufficient numbers of White UK born women, Asian UK born women and Asian women born in Asia. Serum samples taken at 24-28 weeks' gestation were tested for CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included socio-demographic information. RESULTS: CMV seroprevalence was 49% among the White British women, 89% among South Asian UK born women and 98% among South Asian women born in South Asia. These differences remained after adjusting for socio-demographic factors. In contrast, VZV seroprevalence was 95% among women born in the UK but significantly lower at 90% among South Asian women born in Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country of birth. CONCLUSIONS: Although about half of White British women are at risk of primary CMV infection in pregnancy and the associated increased risk of congenital infection, most congenital CMV infections are likely to be in children born to South Asian women with non-primary infection during pregnancy. South Asian women born in South Asia are at risk of VZV infection during pregnancy which could produce congenital varicella syndrome or perinatal chickenpox. Differences in CMV and VZV seroprevalence by ethnic group and country of birth must be taken into account when universal immunisation against these viruses is contemplated.
Assuntos
Citomegalovirus/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Adulto , Estudos de Coortes , Etnicidade , Feminino , Humanos , Estudos Longitudinais , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Soroepidemiológicos , Reino Unido , Adulto JovemRESUMO
Age at infection with hepatitis B virus (HBV) is a known risk factor for chronic HBV infection. However, in addition, there is some evidence that early age at infection further increases the risk of primary liver cancer beyond its association with increased risk of chronic infection. This systematic review of observational studies assesses the association between age at initiation of chronic HBV infection and liver cirrhosis, hepatocellular carcinoma, and their predictors including indicators of ongoing viral replication and hepatic damage. The review includes birth order and maternal HBV serology as proxies for age at infection. Electronic searches in two English-language (Medline and Embase, until Jan 2012) and two Chinese-language (CNKI and SinoMed, until Sep 2012) databases without language restriction and manual search through reference lists identified 7,077 papers, of which 19 studies of 21 outcomes (8 primary liver cancer, 1 liver cirrhosis, 10 viral replication and 2 liver inflammation) are included. One study directly examined the age at infection in a longitudinal cohort, 12 assessed maternal sero-status and 6 investigated birth order. The direction of associations in all studies was in accordance with our hypothesis that earlier age at infection is associated with worse outcomes in addition to its effect of increasing the probability of chronic HBV infection. This has implications for the control of hepatitis B.
Assuntos
Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Replicação Viral , Fatores Etários , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Exposição Materna , Razão de Chances , Viés de Publicação , Fatores de TempoRESUMO
The Gambia National Cancer Registry (GNCR) is one of the few nationwide population-based cancer registries in sub-Saharan Africa. Most registries in sub-Saharan Africa are limited to cities; therefore, the GNCR is important in providing estimates of cancer incidence in rural Africa. Our study assesses the quality of its data. The methods proposed by Bray and Parkin, and Parkin and Bray (Eur J Cancer 2009;45:747-64) were applied to the registry data from 1990 to 2009 to assess comparability, validity and completeness. The system used for classification and coding of neoplasms followed international standards. The percentage of cases morphologically verified was 18.1% for men and 33.1% for women, and that of death certificate only cases was 6.6 and 3.6%, respectively. Incidence rates in rural regions were lower than in the urban part of the country, except amongst young male adults. Comparison with other West African registries showed that the incidences of liver and uterine cervical cancer were comparable, but those of prostate and breast in The Gambia were relatively low. The overall completeness was estimated at 50.3% using the capture-recapture method. The GNCR applies international standard practices to data collection and handling, providing valuable data on cancer incidence in sub-Saharan Africa. However, the data are incomplete in the rural and elderly populations probably because of health care access and use.
Assuntos
Neoplasias/epidemiologia , Sistema de Registros/normas , Coleta de Dados , Feminino , Gâmbia/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , Sistemas de Informação , Masculino , Gradação de Tumores , Sistema de Registros/estatística & dados numéricos , População RuralRESUMO
Several novel fluorogenic N-aminoacylnaphthyridine substrates were synthesized in good yield and tested for their ability to detect pathogenic bacteria in agar-based cell culture. Simple 2-N-(ß-alanyl)amino-5,7-dialkylnaphthyridine substrates were selectively hydrolysed by ß-alanylaminopeptidase expressing bacteria, but were subject to diffusion in the agar medium. Diffusion was reduced in the 2-N-(ß-alanyl)amino-7-alkylnaphthyridine substrates with longer alkyl chains, but inhibition of growth was increased. 2-N-(ß-Alanyl)amino-7-octylnaphthyridine inhibited the growth of all species tested, except for strains resistant to colistin/polymyxin, providing a rationale for the development of substrates for the selective detection of drug resistant species in clinical samples.