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1.
Nat Commun ; 14(1): 5333, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660049

RESUMO

Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.


Assuntos
Imunoterapia , Neoplasias , Feminino , Animais , Camundongos , Glicólise , Adjuvantes Imunológicos/farmacologia , Frutose , Poli I-C , Células Dendríticas
2.
J Plast Reconstr Aesthet Surg ; 86: 211-213, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37769482

RESUMO

This study explores how novices could effectively evaluate the quality of microsurgical suturing. That would be enhanced with using a novel Manual Suture Parameters for Training and Assessment (M-SParTA), which supported novices with guidance on the objective parameters, in order to increased the accuracy of scoring ability. We also propose the following initial framework to train novices in microsuturing using a standardised task: 1) Exposure; 2) Assessment; 3) Hands-on and self-assessment. The independent learning cycle with targeted supervision provides novices with greater autonomy and a less stressful environment that could enhance skills training.


Assuntos
Microcirurgia , Treinamento por Simulação , Humanos , Microcirurgia/educação , Competência Clínica , Procedimentos Neurocirúrgicos , Técnicas de Sutura , Suturas
3.
Biomaterials ; 301: 122292, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37643489

RESUMO

Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAFV600E mutated YUMM1.1 melanoma decreased tumor volume three-fold. PES MPs in the TME also led to maintenance of M1 macrophages with up-regulation of TSLP and type 1 interferon pathway. Impressively, this led to generation of pro-inflammatory adaptive immune responses in the form of increased T helper type 1 and T helper type 17 cells in the TME. Overall, our findings from this challenging tumor model suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.


Assuntos
Melanoma , Ácido Succínico , Animais , Camundongos , Macrófagos Associados a Tumor , Microambiente Tumoral , Proteínas Proto-Oncogênicas B-raf , Succinatos
4.
J Control Release ; 358: 541-554, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37182805

RESUMO

Boosting the metabolism of immune cells while restricting cancer cell metabolism is challenging. Herein, we report that using biomaterials for the controlled delivery of succinate metabolite to phagocytic immune cells activates them and modulates their metabolism in the presence of metabolic inhibitors. In young immunocompetent mice, polymeric microparticles, with succinate incorporated in the backbone, induced strong pro-inflammatory anti-melanoma responses. Administration of poly(ethylene succinate) (PES MP)-based vaccines and glutaminase inhibitor to young immunocompetent mice with aggressive and large, established B16F10 melanoma tumors increased their survival three-fold, a result of increased cytotoxic T cells expressing RORγT (Tc17). Mechanistically, PES MPs directly modulate glutamine and glutamate metabolism, upregulate succinate receptor SUCNR1, activate antigen presenting cells through and HIF-1alpha, TNFa and TSLP-signaling pathways, and are dependent on alpha-ketoglutarate dehydrogenase for their activity, which demonstrates correlation of succinate delivery and these pathways. Overall, our findings suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.


Assuntos
Vacinas Anticâncer , Melanoma , Animais , Camundongos , Polímeros , Ácido Succínico/metabolismo , Imunoterapia , Transdução de Sinais , Células Dendríticas
5.
Postgrad Med J ; 99(1169): 127-138, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37222068

RESUMO

Self-reported questionnaires have become a widely adopted method of reviewing patients in clinical practice. This systematic review aimed to determine the reliability of patient-reported comorbidities and to identify which patient factors influence the reliability. Included studies assessed the reliability of at least one patient-reported comorbidity against their medical record or clinical assessment as gold standard. Twenty-four eligible studies were included in the meta-analysis. Only endocrine diseases (Cohen's Kappa Coefficient (CKC) 0.81 (95% CI 0.76 to 0.85)), consisting of diabetes mellitus (CKC 0.83 (95% CI 0.80 to 0.86)) and thyroid disease (CKC 0.68 (95% CI 0.50 to 0.86)), showed good-to-excellent reliability. Factors most frequently reported to influence concordance included age, sex and educational level. This systematic review demonstrated poor-to-moderate reliability for most systems, except for endocrine which showed good-to-excellent reliability. Although patient self-reporting can be a useful guide to clinical management, several patient factors were demonstrated to affect reliability therefore it should be avoided as a standalone measure.


Assuntos
Prontuários Médicos , Medidas de Resultados Relatados pelo Paciente , Humanos , Reprodutibilidade dos Testes , Comorbidade , Escolaridade
6.
Eur J Orthop Surg Traumatol ; 33(5): 1635-1640, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35794424

RESUMO

PURPOSE: Positive ulnar variance following a distal radius malunion can lead to ulnar-sided wrist pain, loss of grip strength, and distal radioulnar joint impingement. The primary aim of this study is to describe upper limb-specific functional outcomes following ulnar shortening osteotomy (USO) for ulnar-sided wrist pain associated with malunion of the distal radius. METHODS: We retrospectively identified 40 adult patients from a single centre over a 9-year period that had undergone an USO for symptomatic malunion of the distal radius. The primary outcome was the patient-rated wrist evaluation (PRWE). Secondary outcomes were the QuickDASH, EQ-5D-5L, complications, and net promoter score (NPS). RESULTS: Outcomes were available for 37 patients (93%). The mean age was 56 years and 25 patients were female (68%). At a mean follow-up of 6 years (range 1-10 years) the median PRWE was 11 (IQR 0-29.5), the median QuickDASH 6.8 (IQR 0-29.5), and the median EQ-5D-5L index was 0.88 (IQR 0.71-1). The NPS was 73. Complications occurred in nine patients (24%) and included non-union (n = 4), early loss of fixation requiring revision surgery (n = 1), superficial wound infection (n = 2), neurological injury (n = 1), and further surgery for symptomatic hardware removal (n = 1). CONCLUSIONS: For patients with a symptomatic distal radius malunion where the predominant deformity is ulnar positive variance, this study has demonstrated that despite 1 in 4 patients experiencing a complication, USO can result in excellent patient reported outcomes with high levels of satisfaction. LEVEL OF EVIDENCE: III (Cohort Study).


Assuntos
Fraturas Mal-Unidas , Fraturas do Rádio , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Estudos de Coortes , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Estudos Retrospectivos , Fraturas Mal-Unidas/cirurgia , Amplitude de Movimento Articular , Ulna/cirurgia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/cirurgia , Osteotomia/efeitos adversos , Artralgia , Resultado do Tratamento
7.
EClinicalMedicine ; 51: 101541, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35813093

RESUMO

Background: For clinical decision making, it is crucial to identify patients with stage IV non-small cell lung cancer (NSCLC) who may benefit from tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). In this study, a deep learning-based system was designed and validated using pre-therapy computed tomography (CT) images to predict the survival benefits of EGFR-TKIs and ICIs in stage IV NSCLC patients. Methods: This retrospective study collected data from 570 patients with stage IV EGFR-mutant NSCLC treated with EGFR-TKIs at five institutions between 2010 and 2021 (data of 314 patients were from a previously registered study), and 129 patients with stage IV NSCLC treated with ICIs at three institutions between 2017 and 2021 to build the ICI test dataset. Five-fold cross-validation was applied to divide the EGFR-TKI-treated patients from four institutions into training and internal validation datasets randomly in a ratio of 80%:20%, and the data from another institution was used as an external test dataset. An EfficientNetV2-based survival benefit prognosis (ESBP) system was developed with pre-therapy CT images as the input and the probability score as the output to identify which patients would receive additional survival benefit longer than the median PFS. Its prognostic performance was validated on the ICI test dataset. For diagnosing which patient would receive additional survival benefit, the accuracy of ESBP was compared with the estimations of three radiologists and three oncologists with varying degrees of expertise (two, five, and ten years). Improvements in the clinicians' diagnostic accuracy with ESBP assistance were then quantified. Findings: ESBP achieved positive predictive values of 80·40%, 75·40%, and 77·43% for additional EGFR-TKI survival benefit prediction using the probability score of 0·2 as the threshold on the training, internal validation, and external test datasets, respectively. The higher ESBP score (>0·2) indicated a better prognosis for progression-free survival (hazard ratio: 0·36, 95% CI: 0·19-0·68, p<0·0001) in patients on the external test dataset. Patients with scores >0·2 in the ICI test dataset also showed better survival benefit (hazard ratio: 0·33, 95% CI: 0·18-0·55, p<0·0001). This suggests the potential of ESBP to identify the two subgroups of benefiting patients by decoding the commonalities from pre-therapy CT images (stage IV EGFR-mutant NSCLC patients receiving additional survival benefit from EGFR-TKIs and stage IV NSCLC patients receiving additional survival benefit from ICIs). ESBP assistance improved the diagnostic accuracy of the clinicians with two years of experience from 47·91% to 66·32%, and the clinicians with five years of experience from 53·12% to 61·41%. Interpretation: This study developed and externally validated a preoperative CT image-based deep learning model to predict the survival benefits of EGFR-TKI and ICI therapies in stage IV NSCLC patients, which will facilitate optimized and individualized treatment strategies. Funding: This study received funding from the National Natural Science Foundation of China (82001904, 81930053, and 62027901), and Key-Area Research and Development Program of Guangdong Province (2021B0101420005).

8.
Bone Joint J ; 104-B(5): 541-548, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35491572

RESUMO

AIMS: This systematic review aims to compare the precision of component positioning, patient-reported outcome measures (PROMs), complications, survivorship, cost-effectiveness, and learning curves of MAKO robotic arm-assisted unicompartmental knee arthroplasty (RAUKA) with manual medial unicompartmental knee arthroplasty (mUKA). METHODS: Searches of PubMed, MEDLINE, and Google Scholar were performed in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta--Analysis statement. Search terms included "robotic", "unicompartmental", "knee", and "arthroplasty". Published clinical research articles reporting the learning curves and cost-effectiveness of MAKO RAUKA, and those comparing the component precision, functional outcomes, survivorship, or complications with mUKA, were included for analysis. RESULTS: A total of 179 articles were identified from initial screening, of which 14 articles satisfied the inclusion criteria and were included for analysis. The papers analyzed include one on learning curve, five on implant positioning, six on functional outcomes, five on complications, six on survivorship, and three on cost. The learning curve was six cases for operating time and zero for precision. There was consistent evidence of more precise implant positioning with MAKO RAUKA. Meta-analysis demonstrated lower overall complication rates associated with MAKO RAUKA (OR 2.18 (95% confidence interval (CI) 1.06 to 4.49); p = 0.040) but no difference in re-intervention, infection, Knee Society Score (KSS; mean difference 1.64 (95% CI -3.00 to 6.27); p = 0.490), or Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (mean difference -0.58 (95% CI -3.55 to 2.38); p = 0.700). MAKO RAUKA was shown to be a cost-effective procedure, but this was directly related to volume. CONCLUSION: MAKO RAUKA was associated with improved precision of component positioning but was not associated with improved PROMs using the KSS and WOMAC scores. Future longer-term studies should report functional outcomes, potentially using scores with minimal ceiling effects and survival to assess whether the improved precision of MAKO RAUKA results in better outcomes. Cite this article: Bone Joint J 2022;104-B(5):541-548.


Assuntos
Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho/cirurgia , Curva de Aprendizado , Ontário , Procedimentos Cirúrgicos Robóticos/métodos
9.
J Hand Surg Eur Vol ; 47(2): 197-205, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34525852

RESUMO

The primary aim of this study was to identify factors associated with nonresponse to routinely collected patient-reported outcome measures (PROMs) after hand surgery. The secondary aim was to investigate the impact of nonresponder bias on postoperative PROMs. We identified 4357 patient episodes for which the patients received pre- and 1-year postoperative questionnaires. The response rate was 55%. Univariate and regression analyses were undertaken to determine factors predicting nonresponse. We developed a predictive model for the postoperative Quick version of the Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores for nonresponders using imputation. Younger age, increasing deprivation, higher comorbidity, worse preoperative QuickDASH scores and unemployment predicted nonresponse. No significant difference in mean postoperative QuickDASH score was observed between the responders, and the scores for the responders combined with the predicted scores for the nonresponders. Preoperative function was the primary predictor of postoperative outcome. These results challenge the dogma that 'loss to follow-up' automatically invalidates the results of a study.Level of evidence: III.


Assuntos
Mãos , Perda de Seguimento , Viés , Mãos/cirurgia , Humanos , Ombro , Inquéritos e Questionários
10.
Knee Surg Sports Traumatol Arthrosc ; 30(8): 2677-2695, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33547914

RESUMO

This systematic review and meta-analysis were conducted to compare the accuracy of component positioning, alignment and balancing techniques employed, patient-reported outcomes, and complications of robotic-arm assisted total knee arthroplasty (RATKA) with manual TKA (mTKA) and the associated learning curve. Searches of PubMed, Medline and Google Scholar were performed in October 2020 using PRISMA guidelines. Search terms included "robotic", "knee" and "arthroplasty". The criteria for inclusion were published clinical research articles reporting the learning curve for RATKA and those comparing the component position accuracy, alignment and balancing techniques, functional outcomes, or complications with mTKA. There were 198 articles identified, following full text screening, 16 studies satisfied the inclusion criteria and reported the learning curve of rTKA (n=5), component positioning accuracy (n=6), alignment and balancing techniques (n=7), functional outcomes (n=7), or complications (n=5). Two studies reported the learning curve using CUSUM analysis to establish an inflexion point for proficiency which ranged from 7 to 11 cases and there was no learning curve for component positioning accuracy. The meta-analysis showed a significantly lower difference between planned component position and implanted component position, and the spread was narrower for RATKA compared with the mTKA group (Femur coronal: mean 1.31, 95% confidence interval (CI) 1.08-1.55, p<0.00001; Tibia coronal: mean 1.56, 95% CI 1.32-1.81, p<0.00001). Three studies reported using different alignment and balancing techniques between mTKA and RATKA, two studies used the same for both group and two studies did not state the methods used in their RATKA groups. RATKA resulted in better Knee Society Score compared to mTKA in the short-to-mid-term follow up (95%CI [- 1.23, - 0.51], p=0.004). There was no difference in arthrofibrosis, superficial and deep infection, wound dehiscence, or overall complication rates. RATKA demonstrated improved accuracy of component positioning and patient-reported outcomes. The learning curve of RATKA for operating time was between 7 and 11 cases. Future well-powered studies on RATKAs should report on the knee alignment and balancing techniques utilised to enable better comparisons on which techniques maximise patient outcomes.Level of evidence III.


Assuntos
Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho/cirurgia , Medidas de Resultados Relatados pelo Paciente , Procedimentos Cirúrgicos Robóticos/métodos , Tíbia/cirurgia
12.
NPJ Digit Med ; 4(1): 157, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773071

RESUMO

Complications following surgery are common and frequently occur the following discharge. Mobile and wearable digital health interventions (DHI) provide an opportunity to monitor and support patients during their postoperative recovery. Lack of high-quality evidence is often cited as a barrier to DHI implementation. This review captures and appraises the current use, evidence base and reporting quality of mobile and wearable DHI following surgery. Keyword searches were performed within Embase, Cochrane Library, Web of Science and WHO Global Index Medicus databases, together with clinical trial registries and Google scholar. Studies involving patients undergoing any surgery requiring skin incision where postoperative outcomes were measured using a DHI following hospital discharge were included, with DHI defined as mobile and wireless technologies for health to improve health system efficiency and health outcomes. Methodological reporting quality was determined using the validated mobile health evidence reporting and assessment (mERA) guidelines. Bias was assessed using the Cochrane Collaboration tool for randomised studies or MINORS depending on study type. Overall, 6969 articles were screened, with 44 articles included. The majority (n = 34) described small prospective study designs, with a high risk of bias demonstrated. Reporting standards were suboptimal across all domains, particularly in relation to data security, prior patient engagement and cost analysis. Despite the potential of DHI to improve postoperative patient care, current progress is severely restricted by limitations in methodological reporting. There is an urgent need to improve reporting for DHI following surgery to identify patient benefit, promote reproducibility and encourage sustainability.

13.
Bone Joint J ; 103-B(6): 1009-1020, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34058875

RESUMO

AIMS: The aims of this systematic review were to assess the learning curve of semi-active robotic arm-assisted total hip arthroplasty (rTHA), and to compare the accuracy, patient-reported functional outcomes, complications, and survivorship between rTHA and manual total hip arthroplasty (mTHA). METHODS: Searches of PubMed, Medline, and Google Scholar were performed in April 2020 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included "robotic", "hip", and "arthroplasty". The criteria for inclusion were published clinical research articles reporting the learning curve for rTHA (robotic arm-assisted only) and those comparing the implantation accuracy, functional outcomes, survivorship, or complications with mTHA. RESULTS: There were 501 articles initially identified from databases and references. Following full text screening, 17 articles that satisfied the inclusion criteria were included. Four studies reported the learning curve of rTHA, 13 studies reported on implant positioning, five on functional outcomes, ten on complications, and four on survivorship. The meta-analysis showed a significantly greater number of cases of acetabular component placement in the safe zone compared with the mTHA group (95% confidence interval (CI) 4.10 to 7.94; p < 0.001) and that rTHA resulted in a significantly better Harris Hip Score compared to mTHA in the short- to mid-term follow-up (95% CI 0.46 to 5.64; p = 0.020). However, there was no difference in infection rates, dislocation rates, overall complication rates, and survival rates at short-term follow-up. CONCLUSION: The learning curve of rTHA was between 12 and 35 cases, which was dependent on the assessment goal, such as operating time, accuracy, and team working. Robotic arm-assisted total hip arthroplasty was associated with improved accuracy of component positioning and functional outcome, however no difference in complication rates or survival were observed at short- to mid-term follow-up. Overall, there remains an absence of high-quality level I evidence and cost analysis comparing rTHA and mTHA. Cite this article: Bone Joint J 2021;103-B(6):1009-1020.


Assuntos
Artroplastia de Quadril/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Curva de Aprendizado , Duração da Cirurgia , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias , Sobrevivência
14.
J Child Neurol ; 36(10): 894-900, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34048307

RESUMO

Children with neurofibromatosis type 1 (NF1) often report cognitive challenges, though the etiology of such remains an area of active investigation. With the advent of treatments that may affect white matter microstructure, understanding the effects of age on white matter aberrancies in NF1 becomes crucial in determining the timing of such therapeutic interventions. A cross-sectional study was performed with diffusion tensor imaging from 18 NF1 children and 26 age-matched controls. Fractional anisotropy was determined by region of interest analyses for both groups over the corpus callosum, cingulate, and bilateral frontal and temporal white matter regions. Two-way analyses of variance were done with both ages combined and age-stratified into early childhood, middle childhood, and adolescence. Significant differences in fractional anisotropy between NF1 and controls were seen in the corpus callosum and frontal white matter regions when ages were combined. When stratified by age, we found that this difference was largely driven by the early childhood (1-5.9 years) and middle childhood (6-11.9 years) age groups, whereas no significant differences were appreciable in the adolescence age group (12-18 years). This study demonstrates age-related effects on white matter microstructure disorganization in NF1, suggesting that the appropriate timing of therapeutic intervention may be in early childhood.


Assuntos
Imagem de Tensor de Difusão/métodos , Neurofibromatose 1/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Fatores Etários , Anisotropia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
15.
Bone Joint J ; 103-B(5): 951-957, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33934646

RESUMO

AIMS: The aim of this study was to define the complications and long-term outcome following adolescent mid-shaft clavicular fracture. METHODS: We retrospectively reviewed a consecutive series of 677 adolescent fractures in 671 patients presenting to our region (age 13 to 17 years) over a ten-year period (2009 to 2019). Long-term patient-reported outcomes (abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score and EuroQol five-dimension three-level (EQ-5D-3L) quality of life score) were undertaken at a mean of 6.4 years (1.2 to 11.3) following injury in severely displaced mid-shaft fractures (Edinburgh 2B) and angulated mid-shaft fractures (Edinburgh 2A2) at a minimum of one year post-injury. The median patient age was 14.8 years (interquartile range (IQR) 14.0 to 15.7) and 89% were male (n = 594/671). RESULTS: The majority of fractures were mid-shaft (n = 606) with angulation (Edinburgh 2A2, n = 241/606, 39.8%) or displacement (Edinburgh 2B1/2, n = 263/606, 43.4%). Only 7% of the displaced mid-shaft fractures underwent acute fixation (n = 18/263). The incidence of refracture over ten years following nonoperative management of mid-shaft fractures was 3.2% (n = 19/588) and all united without surgery. Fracture type, severity of angulation, or displacement were not associated with refracture. One nonunion occurred following nonoperative management in a displaced mid-shaft fracture (0.4%, n = 1/245). Of the angulated fractures, 61 had angulation > 30°, of which 68.9% (n = 42/61) completed outcome scores with a median QuickDASH of 0.0 (IQR 0.0 to 0.6), EQ-5D-3L 1.0 (1.0 to 1.0), and 98% satisfaction with shoulder function. For the displaced fractures, 127 had displacement beyond one cortical width of bone for which completed outcome scores were provided in 72.4% (n = 92/127). Of these 15 had undergone acute fixation. Following nonoperative treatment, the median QuickDASH was 0.0 (IQR 0.0 to 2.3), EQ-5D-3L 1.0 (1.0 to 1.0), and satisfaction with shoulder function was 95%. There were no significant differences in the patients' demography or functional outcomes between operative and nonoperative treatments. CONCLUSION: Nonoperative management of adolescent mid-shaft clavicle fractures results in excellent functional outcomes at long-term follow-up. Nonunion is exceptionally rare following nonoperative management and the relative indications for surgical intervention in adults do not appear to be applicable to adolescents. Cite this article: Bone Joint J 2021;103-B(5):951-957.


Assuntos
Clavícula/lesões , Fixação de Fratura/métodos , Fraturas Ósseas/terapia , Fraturas não Consolidadas/terapia , Adolescente , Avaliação da Deficiência , Feminino , Seguimentos , Consolidação da Fratura , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Estudos Retrospectivos
16.
Sensors (Basel) ; 21(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801002

RESUMO

Machine learning (ML)-based algorithms are playing an important role in cancer diagnosis and are increasingly being used to aid clinical decision-making. However, these commonly operate as 'black boxes' and it is unclear how decisions are derived. Recently, techniques have been applied to help us understand how specific ML models work and explain the rational for outputs. This study aims to determine why a given type of cancer has a certain phenotypic characteristic. Cancer results in cellular dysregulation and a thorough consideration of cancer regulators is required. This would increase our understanding of the nature of the disease and help discover more effective diagnostic, prognostic, and treatment methods for a variety of cancer types and stages. Our study proposes a novel explainable analysis of potential biomarkers denoting tumorigenesis in non-small cell lung cancer. A number of these biomarkers are known to appear following various treatment pathways. An enhanced analysis is enabled through a novel mathematical formulation for the regulators of mRNA, the regulators of ncRNA, and the coupled mRNA-ncRNA regulators. Temporal gene expression profiles are approximated in a two-dimensional spatial domain for the transition states before converging to the stationary state, using a system comprised of coupled-reaction partial differential equations. Simulation experiments demonstrate that the proposed mathematical gene-expression profile represents a best fit for the population abundance of these oncogenes. In future, our proposed solution can lead to the development of alternative interpretable approaches, through the application of ML models to discover unknown dynamics in gene regulatory systems.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Algoritmos , Difusão , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética
17.
J Hand Surg Asian Pac Vol ; 26(2): 152-157, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33928856

RESUMO

Upper extremity trauma is one of the most common types of injuries, accounting for 20 to 40 percent of injured patients presenting to the emergency department. In severe upper extremity injury, the likelihood of secondary procedures to improve function and resolve outstanding clinical problems is high. Secondary procedures are performed later than initial primary surgery, usually after wound healing and with a discernible time gap of days, weeks or occasionally longer. They should be considered as separate procedures from the primary surgery, with due diligence given to planning for it. When approaching secondary procedures, the key principles are anchored in early preparation, patient engagement, optimal timing and sequencing, reviewing and considering alternatives, and finally knowing when to stop. Although secondary procedures after upper extremity injuries can be a complex undertaking, the careful application of these principles and considerations will optimise outcomes.


Assuntos
Tomada de Decisão Compartilhada , Procedimentos Ortopédicos , Participação do Paciente , Extremidade Superior/lesões , Extremidade Superior/cirurgia , Humanos , Fatores de Tempo
18.
Bone Joint J ; 103-B(2): 309-320, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517729

RESUMO

AIMS: The aim of this study was to determine whether fixation, as opposed to revision arthroplasty, can be safely used to treat reducible Vancouver B type fractures in association with a cemented collarless polished tapered femoral stem (the Exeter). METHODS: This retrospective cohort study assessed 152 operatively managed consecutive unilateral Vancouver B fractures involving Exeter stems; 130 were managed with open reduction and internal fixation (ORIF) and 22 with revision arthroplasty. Mean follow-up was 6.5 years (SD 2.6; 3.2 to 12.1). The primary outcome measure was revision of at least one component. Kaplan-Meier survival analysis was performed. Regression analysis was used to identify risk factors for revision following ORIF. Secondary outcomes included any reoperation, complications, blood transfusion, length of hospital stay, and mortality. RESULTS: Fractures (B1 n = 74 (49%); B2 n = 50 (33%); and B3 n = 28 (18%)) occurred at median of 4.2 years (interquartile range (IQR) 1.2 to 9.2) after primary total hip arthroplasty (THA) (n = 138) or hemiarthroplasty (n = 14). Rates of revision and reoperation were significantly higher following revision arthroplasty compared to ORIF for B2 (p = 0.001) and B3 fractures (p = 0.050). Five-year survival was significantly better following ORIF: 92% (95% confidence interval (CI) 86.4% to 97.4%) versus 63% (95% CI 41.7% to 83.3%), p < 0.001. ORIF was associated with reduced blood transfusion requirement and reoperations, but there were no differences in medical complications, hospital stay, or mortality between surgical groups. No independent predictors of revision following ORIF were identified: where the bone-cement interface was intact, fixation of B2 or B3 fractures was not associated with an increased risk of revision. CONCLUSION: When the bone-cement interface was intact and the fracture was anatomically reducible, all Vancouver B fractures around Exeter stems could be managed with fixation as opposed to revision arthroplasty. Fixation was associated with reduced need for blood transfusion and lower risk of revision surgery compared with revision arthroplasty. Cite this article: Bone Joint J 2021;103-B(2):309-320.


Assuntos
Artroplastia de Quadril , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas , Redução Aberta , Fraturas Periprotéticas/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação/métodos , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Cimentos Ósseos , Feminino , Fraturas do Fêmur/etiologia , Seguimentos , Prótese de Quadril , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reoperação/instrumentação , Estudos Retrospectivos , Resultado do Tratamento
19.
Hand Surg Rehabil ; 40(3): 343-346, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33401007

RESUMO

The primary aim was to determine the improvement in patient-reported functional outcomes (PROMs) following extensor indicis proprius (EIP) transfer for a closed rupture of the extensor pollicis longus (EPL) tendon. Secondary aims were to analyze the impact of this procedure on health-related quality of life (HRQoL) and satisfaction. Preoperative and one-year postoperative PROMs were collected prospectively at a single institution over a two-year period (2014-2016). The primary outcome measure was the QuickDASH score. Patients also completed satisfaction scores, and the EQ-5D-5L score was used to evaluate HRQoL. Paired data was available for 12 patients (92%) at mean 19 months following surgery. A statistically-significant improvement in mean QuickDASH score was observed from 29.7 (SD: 21.7) preoperatively to 15.2 (SD: 16.4) postoperatively (p?=?0.05). Nine patients reported an improvement, one patient reported no change, and the remaining two reported deterioration in QuickDASH score. Median EQ-5D-5L improved significantly from 0.82 (IQR: 0.71 - 1.0) to 0.93 (0.77 to 1.0) postoperatively (p?

Assuntos
Qualidade de Vida , Traumatismos dos Tendões , Estudos de Coortes , Humanos , Traumatismos dos Tendões/cirurgia , Transferência Tendinosa , Tendões
20.
Postgrad Med J ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37042521

RESUMO

Self-reported questionnaires have become a widely adopted method of reviewing patients in clinical practice. This systematic review aimed to determine the reliability of patient-reported comorbidities and to identify which patient factors influence the reliability. Included studies assessed the reliability of at least one patient-reported comorbidity against their medical record or clinical assessment as gold standard. Twenty-four eligible studies were included in the meta-analysis. Only endocrine diseases (Cohen's Kappa Coefficient (CKC) 0.81 (95% CI 0.76 to 0.85)), consisting of diabetes mellitus (CKC 0.83 (95% CI 0.80 to 0.86)) and thyroid disease (CKC 0.68 (95% CI 0.50 to 0.86)), showed good-to-excellent reliability. Factors most frequently reported to influence concordance included age, sex and educational level. This systematic review demonstrated poor-to-moderate reliability for most systems, except for endocrine which showed good-to-excellent reliability. Although patient self-reporting can be a useful guide to clinical management, several patient factors were demonstrated to affect reliability therefore it should be avoided as a standalone measure.

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