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1.
Hum Mol Genet ; 28(14): 2427-2448, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30972415

RESUMO

Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , MicroRNAs/metabolismo , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Contusões/tratamento farmacológico , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Feminino , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/metabolismo , Bainha de Mielina/metabolismo , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Ratos , Ratos Sprague-Dawley
2.
J Orthop ; 56: 32-39, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38784946

RESUMO

Background: There is an accepted variation in the financial cost of total knee arthroplasty (TKA) implants but it is not known whether this cost is reflected by the evidence in support of their use. A cost analysis study was carried out to determine the total cost of consumables of a TKA, and whether this was related to the supporting evidence and survivorship data. Methods: Intra-operative data for all unilateral, cemented, primary TKA over a 13 month period at a high-volume Orthopaedic Centre was collected. Level of evidence for each model was taken from the Orthopaedic Data Evaluation Panel (ODEP) website, and data from the UK National Joint Registry was used to assign survivorship (failure rates). Correlation was calculated using the Spearman rank correlation (r). Results: A total of 1301 TKA were performed at the study centre during the data collection period. The mean cost of consumables for a TKA with patella resurfacing (n = 816) was £1969.08 (range of £1061.46 and £5143.89), and without resurfacing (n = 485) was £1846.62 (range of £1118.98 and £4196.81). There was a negative correlation between price of implant and ODEP rating (r = -0.47), with increasing level of evidence being associated with a lower cost. There was a positive correlation between price of implant and rate of implant failure at the1-, 3- and 5-year time-points (r = 0.55, 0.44, 0.28 respectively), with increasing cost being associated with a higher failure rate. Conclusion: Higher financial cost of TKA prostheses was associated with a weaker level of supporting evidence and a higher failure rate. The increased financial cost of new implants may be justified as more data and evidence becomes available to support an advantage in its use over currently established implants.

3.
Health Informatics J ; 30(3): 14604582241249929, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39048524

RESUMO

Using data from two ED. departments of 773 patients admitted with SARS-CoV-2, ICD-10 codes derived from the General Practitioner - Summary Care Record (GP-SCR) and Emergency Department (ED.) records were analysed for code discrepancies and whether this related to increased mortality. The average number of ICD-10 codes in both GP-SCR and ED. records was higher for patients who died than patients who survived (all p < .0001). Pre-existing GP digital data provides a better prediction of mortality than data collected manually during admission clerking in the ED. Up to 78.47% of GP-SCR codes were missed in the ED. records and up to 45.49% of the ED. record codes were not in the GP-SCR. A subset of missed ICD-10 codes were identified as being able to predict outcome; a trend towards increasing death rate as the proportion of missed codes increases. Initiatives to make the GP-SCR available to the wider healthcare community should improve patient care and reduce bias during development of machine learning based algorithms.


Assuntos
COVID-19 , Atenção Primária à Saúde , SARS-CoV-2 , Atenção Secundária à Saúde , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Atenção Secundária à Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Feminino , Masculino , Classificação Internacional de Doenças , Registros Eletrônicos de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/organização & administração , Idoso
4.
Bone Jt Open ; 3(1): 42-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35037765

RESUMO

AIMS: There is little published on the outcomes after restarting elective orthopaedic procedures following cessation of surgery due to the COVID-19 pandemic. During the pandemic, the reported perioperative mortality in patients who acquired SARS-CoV-2 infection while undergoing elective orthopaedic surgery was 18% to 20%. The aim of this study is to report the surgical outcomes, complications, and risk of developing COVID-19 in 2,316 consecutive patients who underwent elective orthopaedic surgery in the latter part of 2020 and comparing it to the same, pre-pandemic, period in 2019. METHODS: A retrospective service evaluation of patients who underwent elective surgical procedures between 16 June 2020 and 12 December 2020 was undertaken. The number and type of cases, demographic details, American society of Anesthesiologists (ASA) grade, BMI, 30-day readmission rates, mortality, and complications at one- and six-week intervals were obtained and compared with patients who underwent surgery during the same six-month period in 2019. RESULTS: A total of 2,316 patients underwent surgery in 2020 compared to 2,552 in the same period in 2019. There were no statistical differences in sex distribution, BMI, or ASA grade. The 30-day readmission rate and six-week validated complication rates were significantly lower for the 2020 patients compared to those in 2019 (p < 0.05). No deaths were reported at 30 days in the 2020 group as opposed to three in the 2019 group (p < 0.05). In 2020 one patient developed COVID-19 symptoms five days following foot and ankle surgery. This was possibly due to a family contact immediately following discharge from hospital, and the patient subsequently made a full recovery. CONCLUSION: Elective surgery was safely resumed following the cessation of operating during the COVID-19 pandemic in 2020. Strict adherence to protocols resulted in 2,316 elective surgical procedures being performed with lower complications, readmissions, and mortality compared to 2019. Furthermore, only one patient developed COVID-19 with no evidence that this was a direct result of undergoing surgery. Level of evidence: III Cite this article: Bone Jt Open 2022;3(1):42-53.

5.
Br J Hosp Med (Lond) ; 82(8): 1-10, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34431342

RESUMO

Patella dislocation is one of the most common knee injuries, accounting for 3% of acute knee injuries. Despite its prevalence, patella dislocation is often missed, with a haemarthrosis often the only sign, albeit a non-specific one. A thorough history and examination are necessary to identify patella dislocation and its potential causes. Investigations should include cross-sectional imaging to evaluate both osseous and soft tissue structures in order to guide management. Management in the acute setting is normally non-operative, but damage to structural supports, osteochondral defects or recurrent dislocation should prompt consideration of operative treatment. Operative treatment should address the soft tissue stabilisers and/or osseus deformities that predispose to, or occur secondary to, patella dislocation.


Assuntos
Luxações Articulares , Traumatismos do Joelho , Luxação Patelar , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/terapia , Articulação do Joelho , Patela/diagnóstico por imagem , Luxação Patelar/diagnóstico por imagem , Luxação Patelar/epidemiologia , Prevalência
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