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Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti-programmed death-ligand 1/anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen 4). This evidence is supported in numerous in vitro, animal, and clinical studies that highlight the importance of microbial mechanisms in defining therapeutic responses. The microbiome therefore shapes oncologic outcomes and is now being leveraged for the development of novel personalized therapeutic approaches in cancer treatment. However, if the microbiome is to be successfully translated into next-generation oncologic treatments, a new multimodal model of the oncomicrobiome must be conceptualized that incorporates gut microbial cometabolism of pharmacologic agents into cancer care. The objective of this review is therefore to outline the current knowledge of oncologic pharmacomicrobiomics and to describe how the multiparametric functions of the gut microbiome influence treatment response across cancer types. The secondary objective is to propose innovative approaches for modulating the gut microbiome in clinical environments that improve therapy efficacy and diminish toxic effects derived from antineoplastic agents for patient benefit.
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Antineoplásicos , Microbioma Gastrointestinal , Microbiota , Neoplasias , Animais , Imunoterapia/efeitos adversos , Antineoplásicos/efeitos adversosRESUMO
BACKGROUND: Routine surgical video recording has multiple benefits. Video acts as an objective record of the operative record, allows video-based coaching and is integral to the development of digital technologies. Despite these benefits, adoption is not widespread. To date, only questionnaire studies have explored this failure in adoption. This study aims to determine the barriers and provide recommendations for the implementation of routine surgical video recording. MATERIALS AND METHODS: A pre- and post-pilot questionnaire surrounding a real-world implementation of a C-SATS©, an educational recording and surgical analytics platform, was conducted in a university teaching hospital trust. Usage metrics from the pilot study and descriptive analyses of questionnaire responses were used with the non-adoption, abandonment, scale-up, spread, sustainability (NASSS) framework to create topic guides for semi-structured interviews. Transcripts of interviews were evaluated in an inductive thematic analysis. RESULTS: Engagement with the C-SATS© platform failed to reach consistent levels with only 57 videos uploaded. Three attending surgeons, four surgical residents, one scrub nurse, three patients, one lawyer, and one industry representative were interviewed, all of which perceived value in recording. Barriers of 'change,' 'resource,' and 'governance,' were identified as the main themes. Resistance was centred on patient misinterpretation of videos. Participants believed availability of infrastructure would facilitate adoption but integration into surgical workflow is required. Regulatory uncertainty was centred around anonymity and data ownership. CONCLUSION: Barriers to the adoption of routine surgical video recording exist beyond technological barriers alone. Priorities for implementation include integration recording into the patient record, engaging all stakeholders to ensure buy-in, and formalising consent processes to establish patient trust.
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OBJECTIVE: Rapid evaporative ionization mass spectrometry (REIMS) is a metabolomic technique analyzing tissue metabolites, which can be applied intraoperatively in real-time. The objective of this study was to profile the lipid composition of colorectal tissues using REIMS, assessing its accuracy for real-time tissue recognition and risk-stratification. SUMMARY BACKGROUND DATA: Metabolic dysregulation is a hallmark feature of carcinogenesis; however, it remains unknown if this can be leveraged for real-time clinical applications in colorectal disease. METHODS: Patients undergoing colorectal resection were included, with carcinoma, adenoma and paired-normal mucosa sampled. Ex vivo analysis with REIMS was conducted using monopolar diathermy, with the aerosol aspirated into a Xevo G2S QToF mass spectrometer. Negatively charged ions over 600 to 1000 m/z were used for univariate and multivariate functions including linear discriminant analysis. RESULTS: A total of 161 patients were included, generating 1013 spectra. Unique lipidomic profiles exist for each tissue type, with REIMS differentiating samples of carcinoma, adenoma, and normal mucosa with 93.1% accuracy and 96.1% negative predictive value for carcinoma. Neoplasia (carcinoma or adenoma) could be predicted with 96.0% accuracy and 91.8% negative predictive value. Adenomas can be risk-stratified by grade of dysplasia with 93.5% accuracy, but not histological subtype. The structure of 61 lipid metabolites was identified, revealing that during colorectal carcinogenesis there is progressive increase in relative abundance of phosphatidylglycerols, sphingomyelins, and mono-unsaturated fatty acid-containing phospholipids. CONCLUSIONS: The colorectal lipidome can be sampled by REIMS and leveraged for accurate real-time tissue recognition, in addition to riskstratification of colorectal adenomas. Unique lipidomic features associated with carcinogenesis are described.
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Adenoma , Carcinoma , Neoplasias Colorretais , Humanos , Lipidômica , Espectrometria de Massas , Neoplasias Colorretais/patologia , Lipídeos , Carcinogênese , Adenoma/diagnóstico , Adenoma/cirurgia , Adenoma/metabolismoRESUMO
PURPOSE OF REVIEW: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related deaths. Of the various established risk factors for this aggressive condition, diet is a notable modifiable risk factor. This review aims to summarize the mounting evidence to suggest the role of diet, the microbiota and their cross-talk in modulating an individual's risk of developing CRC. RECENT FINDINGS: Specifically, the metabolism of bile acids and its symbiosis with the microbiota has gained weight given its basis on a high meat, high fat, and low fibre diet that is present in populations with the highest risk of CRC. Bacteria modify bile acids that escape enterohepatic circulation to increase the diversity of the human bile acid pool. The production of microbial bile acids contributes to this as well. Epidemiological studies have shown that changing the diet results in different levels and composition of bile acids, which has in turn modified the risk of CRC at a population level. Evidence to identify underlying mechanisms have tied into the microbiota-led digestions of various foods into fatty acids that feedback into bile acid physiology as well as modulation of endogenous receptors for bile acids. SUMMARY: There is adequate evidence to support the role of microbiota in in the metabolism of bile acids, and how this relates to colorectal cancer. Further work is necessary to identify specific bacteriome involved and their underlying mechanistic pathways.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Ácidos e Sais Biliares , Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal/fisiologia , HumanosRESUMO
OBJECTIVES: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. BACKGROUND: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. METHODS: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. RESULTS: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. CONCLUSION: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.
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COVID-19/epidemiologia , Emergências/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Cirurgia Geral/estatística & dados numéricos , SARS-CoV-2 , Inquéritos e Questionários , Adulto , Idoso , Comorbidade , Feminino , Seguimentos , Saúde Global , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , PandemiasRESUMO
BACKGROUND: This is an analysis of the first 50 in-human uses of a novel digital rigid sigmoidoscope. The technology provides digital image capture, telemedicine capabilities, improved ergonomics, and the ability to biopsy under pneumorectum while maintaining the low cost of conventional rigid sigmoidoscopy. The primary outcome was adverse events, and the secondary outcome was diagnostic view. PRELIMINARY RESULTS: Fifty patients underwent outpatient (n = 25) and surgical rectal assessment (n = 25), with a mean age of 60 years. This included 31 men and 19 women with 12 different clinical use indications. No adverse events were reported, and no defects were reported with the instrumentation. Satisfactory diagnoses were obtained in 48 (96%) of 50 uses, images were captured in 48 (96%) of 50 uses, and biopsies were successfully taken in 13 uses (26%). No adverse events were recorded. Independent reviewers of recorded videos agreed on the quality and diagnostic value of the images with a κ of 0.225 (95% CI, 0.144-0.305) when assessing whether the target pathology was adequately visualized. IMPACT OF INNOVATION: The improved views afforded by digital rectoscopy facilitated a satisfactory clinical diagnosis in 96% of uses. The device was successfully deployed in the operating room and outpatients irrespective of bowel preparation method, where it has the potential to replace flexible sigmoidoscopy for specific use cases. The technology provides a high-quality image and video that can be securely recorded for documentation and medicolegal purposes with agreement between blinded users despite a lack of standardized training and heterogenous pathology. We perceive significant impact of this technology for the assessment of colorectal anastomoses, the office management of colitis, "watch and wait," and for diagnostic support in rectal cancer diagnosis. The technology has significant potential to facilitate proctoring and training, and it now requires prospective trials to validate its diagnostic accuracy against more costly flexible sigmoidoscopy systems.
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Neoplasias Retais/diagnóstico , Sigmoidoscopia/efeitos adversos , Sigmoidoscopia/métodos , Telemedicina/instrumentação , Adulto , Idoso , Anastomose Cirúrgica , Biópsia/métodos , Colite/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preceptoria/métodos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/diagnóstico por imagem , Reto/patologia , Sigmoidoscopia/economia , Avaliação da Tecnologia Biomédica/estatística & dados numéricos , Gravação em Vídeo/instrumentação , Conduta Expectante/métodosRESUMO
This viewpoint explores the ethical and regulatory consequences of the digital transformation of the operating room. Surgical robotics is undergoing significant change and future advances will center around the capture and use of data. The consequences of creating this surgical data pipeline must be understood and digital surgical systems must prioritize the safeguarding of patient data. Moreover, data protection laws and frameworks must adapt to the changing nature of surgical data. Finally, digital surgeons must understand changing data legislation and best practice on data governance to act as guardians not only for their own but also for their patients' data.
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Cirurgiões , Humanos , Salas CirúrgicasRESUMO
OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis. DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research. RESULTS: Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis. CONCLUSION: Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.
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Carcinogênese , Microbiota , Neoplasias/microbiologia , Animais , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Carcinogênese/genética , Carcinogênese/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/microbiologia , Dano ao DNA , Disbiose/complicações , Disbiose/imunologia , Disbiose/microbiologia , Microbioma Gastrointestinal , Humanos , Inflamação/microbiologia , Neoplasias/genética , Neoplasias/imunologiaRESUMO
OBJECTIVES: Accurate, real-time, endoscopic risk stratification of colorectal polyps would improve decision-making and optimize clinical efficiency. Technologies to manipulate endoscopic optical outputs can be used to predict polyp histology in vivo; however, it remains unclear how accuracy has progressed and whether it is sufficient for routine clinical implementation. METHODS: A meta-analysis was conducted by searching MEDLINE, Embase, and the Cochrane Library. Studies were included if they prospectively deployed an endoscopic optical technology for real-time in vivo prediction of adenomatous colorectal polyps. Polyposis and inflammatory bowel diseases were excluded. Bayesian bivariate meta-analysis was performed, presenting 95% confidence intervals (CI). RESULTS: One hundred two studies using optical technologies on 33,123 colorectal polyps were included. Digital chromoendoscopy differentiated neoplasia (adenoma and adenocarcinoma) from benign polyps with sensitivity of 92.2% (90.6%-93.9% CI) and specificity of 84.0% (81.5%-86.3% CI), with no difference between constituent technologies (narrow-band imaging, Fuji intelligent Chromo Endoscopy, iSCAN) or with only diminutive polyps. Dye chromoendoscopy had sensitivity of 92.7% (90.1%-94.9% CI) and specificity of 86.6% (82.9%-89.9% CI), similarly unchanged for diminutive polyps. Spectral analysis of autofluorescence had sensitivity of 94.4% (84.0%-99.1% CI) and specificity of 50.9% (13.2%-88.8% CI). Endomicroscopy had sensitivity of 93.6% (85.3%-98.3% CI) and specificity of 92.5% (81.8%-98.1% CI). Computer-aided diagnosis had sensitivity of 88.9% (74.2%-96.7% CI) and specificity of 80.4% (52.6%-95.7% CI). Prediction confidence and endoscopist experience alone did not significantly improve any technology. The only subgroup to demonstrate a negative predictive value for adenoma above 90% was digital chromoendoscopy, making high confidence predictions of diminutive recto-sigmoid polyps. Chronologic meta-analyses show a falling negative predictive value over time. A significant publication bias exists. DISCUSSION: This novel approach to meta-analysis demonstrates that existing optical technologies are increasingly unlikely to allow safe "resect and discard" strategies and that step-change innovation may be required. A "diagnose and leave" strategy may be supported for diminutive recto-sigmoid polyps diagnosed with high confidence; however, limitations exist in the evidence base for this cohort.
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Adenocarcinoma/diagnóstico por imagem , Pólipos Adenomatosos/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Adenocarcinoma/patologia , Adenoma/diagnóstico por imagem , Adenoma/patologia , Pólipos Adenomatosos/patologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Diagnóstico por Computador , Humanos , Microscopia , Imagem de Banda Estreita , Imagem Óptica , Sensibilidade e EspecificidadeRESUMO
Health based games have significant potential as therapeutic interventions due to the inherent mechanisms associated with social and individual game play and their capacity for sensor integration, data capture analysis and patient feedback. Moreover, they are low cost and they can be deployed at the point of care across an evolving digital ecosystem. However, a robust evidence base to support their wider adoption as a clinical intervention for chronic diseases is lacking and significant methodological barriers exist for health games developers creating efficacious 'digital medicines'. Game design is complex and it must utilise validated game mechanics balanced with a creative and engaging game design. The aim of this review is therefore to outline the fundamental steps of game development for health professionals and to critically appraise the methodology for assessing health games as medical interventions. This requires (1) The adoption of clearly defined global language for health games development based on a targeted function as therapeutic agents. (2) The development of multidisciplinary teams with a broad portfolio of development and clinical skill sets. (3) The creation of health game engines specifically built to facilitate clinical game development. (4) Robust trial design and assessment of translational impact: If games are to be prescribed, their efficacy and toxicity must be based on a rigorous assessment of their use within a real world clinical environment. Trials for precision health games have specific challenges around blinding, learning curves, bias and confounding that are particularly problematic. We propose the adoption of the IDEAL-GAMES framework for game development that systematically assess and validates games through open registries. In conclusion we propose a new framework for assessing the robustness and clinical efficacy of games for health as clinical interventions in the clinical environment.
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Terapia Comportamental/métodos , Doença Crônica/terapia , Jogos de Vídeo , HumanosRESUMO
Metabolic phenotyping involves the comprehensive analysis of biological fluids or tissue samples. This analysis allows biochemical classification of a person's physiological or pathological states that relate to disease diagnosis or prognosis at the individual level and to disease risk factors at the population level. These approaches are currently being implemented in hospital environments and in regional phenotyping centres worldwide. The ultimate aim of such work is to generate information on patient biology using techniques such as patient stratification to better inform clinicians on factors that will enhance diagnosis or the choice of therapy. There have been many reports of direct applications of metabolic phenotyping in a clinical setting.
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Líquidos Corporais/química , Cirurgia Geral/métodos , Metaboloma , Fenótipo , Animais , Biomarcadores/análise , Líquidos Corporais/metabolismo , Células/metabolismo , Humanos , Doenças Metabólicas/diagnóstico , Medicina de PrecisãoRESUMO
BACKGROUND: Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile. METHODS: Adults patients undergoing elective laparoscopic or open colorectal resections were included. Primary outcomes were serum oxylipin profile quantified by ultra high-performance liquid chromatography-mass spectrometry, serum white cell count and C-reactive protein concentration. Serum samples were taken at three time-points: pre-operative (day zero), early post-operative (day one) and late post-operative (day four/five). RESULTS: Some 55 patients were included, of which 33 (60%) underwent surgery that was completed laparoscopically. Pre-operative oxylipin profiles were characterised by marked heterogeneity but surgery induced a common shift resulting in more homogeneity at the early post-operative time-point. By the late post-operative phase, oxylipin profiles were again highly variable. This evolution was driven by time-dependent changes in specific oxylipins. Notably, the levels of several oxylipins with anti-inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at the early post-operative point before returning to baseline by the late post-operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the early post-operative phase while levels of anti-thrombotic mediators (9-HODE and 13-HODE) fell; concentrations of all three oxylipins then remained fairly static from early to late post-operative phases. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had lower levels of some anti-inflammatory oxylipins (8,9-DHET and 17-HDoHE) in addition to reduced concentrations of anti-thrombotic mediators (9-HODE and 13-HODE) with increased concentration of their pro-thrombotic counterpart (TxB2). CONCLUSIONS: Serum oxylipin profile is modified by surgical intervention and may even be sensitive to the degree of surgical trauma and therefore represents a novel descriptor of the surgical systemic inflammatory response.
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Inflamação/sangue , Laparoscopia , Oxilipinas/sangue , Idoso , Proteína C-Reativa/metabolismo , Demografia , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Contagem de Leucócitos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Fatores de TempoRESUMO
BACKGROUND: Surgical Site Infection (SSI) occurs in 9 % of laparoscopic colorectal surgery. Warming and humidifying carbon dioxide (CO2) used for peritoneal insufflation may protect against SSI by avoiding postoperative hypothermia (itself a risk factor for SSI). This study aimed to assess the impact of CO2 conditioning on postoperative hypothermia and SSI and to perform a cost-effectiveness analysis. METHODS: A retrospective cohort study of patients undergoing elective laparoscopic colorectal resection was performed at a single UK specialist centre. The control group (n = 123) received peritoneal insufflation with room temperature, dry CO2, whereas the intervention group (n = 123) received warm, humidified CO2 (using HumiGard™, Fisher & Paykel Healthcare). The outcomes were postoperative hypothermia, SSI and costs. Multivariate analysis was performed. RESULTS: A total of 246 patients were included in the study. The mean age was 68 (20-87) and mean BMI 28 (15-51). The primary diagnosis was cancer (n = 173), and there were no baseline differences between the groups. CO2 conditioning significantly decreased the incidence of postoperative hypothermia (odds ratio 0.10, 95 % CI 0.04-0.23), with hypothermic patients found to be at increased risk of SSI (odds ratio 4.0, 95 % CI 1.25-12.9). Use of conditioned CO2 significantly decreased the incidence of SSI by 66 % (p = 0.04). The intervention group incurred costs of £155 less per patient. The incremental cost-effectiveness ratio was negative. CONCLUSION: CO2 conditioning during laparoscopic colorectal surgery is a safe, feasible and a cost-effective intervention. It improves the quality of surgical care relating to SSI and postoperative hypothermia.
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Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Temperatura Alta , Umidade , Hipotermia/epidemiologia , Laparoscopia/métodos , Pneumoperitônio Artificial/métodos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dióxido de Carbono , Estudos de Casos e Controles , Estudos de Coortes , Colite Ulcerativa/cirurgia , Cirurgia Colorretal , Análise Custo-Benefício , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/economia , Doença Diverticular do Colo/cirurgia , Procedimentos Cirúrgicos Eletivos , Estudos de Viabilidade , Feminino , Humanos , Hipotermia/economia , Insuflação , Laparoscopia/economia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peritônio , Pneumoperitônio Artificial/economia , Período Pós-Operatório , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/economia , Reino Unido/epidemiologia , Adulto JovemRESUMO
Rapid evaporative ionization mass spectrometry (REIMS) technology allows real time intraoperative tissue classification and the characterization and identification of microorganisms. In order to create spectral libraries for training the classification models, reference data need to be acquired in large quantities as classification accuracy generally improves as a function of number of training samples. In this study, we present an automated high-throughput method for collecting REIMS data from heterogeneous organic tissue. The underlying instrumentation consists of a 2D stage with an additional high-precision z-axis actuator that is equipped with an electrosurgical diathermy-based sampling probe. The approach was validated using samples of human liver with metastases and bacterial strains, cultured on solid medium, belonging to the species P. aeruginosa, B. subtilis, and S. aureus. For both sample types, spatially resolved spectral information was obtained that resulted in clearly distinguishable multivariate clustering between the healthy/cancerous liver tissues and between the bacterial species.
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Adenocarcinoma/secundário , Bactérias/classificação , Neoplasias Colorretais/patologia , Meios de Cultura/análise , Diagnóstico por Imagem , Neoplasias Hepáticas/secundário , Espectrometria de Massas por Ionização por Electrospray/métodos , Bactérias/química , Bactérias/crescimento & desenvolvimento , Humanos , Processamento de Imagem Assistida por Computador , Análise de Componente PrincipalRESUMO
We have investigated the urinary and plasma metabolic phenotype of acute pancreatitis (AP) patients presenting to the emergency room at a single center London teaching hospital with acute abdominal pain using (1)H NMR spectroscopy and multivariate modeling. Patients were allocated to either the AP (n = 15) or non-AP patients group (all other causes of abdominal pain, n = 21) on the basis of the national guidelines. Patients were assessed for three clinical outcomes: (1) diagnosis of AP, (2) etiology of AP caused by alcohol consumption and cholelithiasis, and (3) AP severity based on the Glasgow score. Samples from AP patients were characterized by high levels of urinary ketone bodies, glucose, plasma choline and lipid, and relatively low levels of urinary hippurate, creatine and plasma-branched chain amino acids. AP could be reliably identified with a high degree of sensitivity and specificity (OPLS-DA model R(2) = 0.76 and Q(2)Y = 0.59) using panel of discriminatory biomarkers consisting of guanine, hippurate and creatine (urine), and valine, alanine and lipoproteins (plasma). Metabolic phenotyping was also able to distinguish between cholelithiasis and colonic inflammation among the heterogeneous non-AP group. This work has demonstrated that combinatorial biomarkers have a strong diagnostic and prognostic potential in AP with relevance to clinical decision making in the emergency unit.
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Metaboloma , Metabolômica/métodos , Pancreatite/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Aminoácidos/sangue , Aminoácidos/química , Biomarcadores/sangue , Biomarcadores/urina , Colelitíase/complicações , Creatina/urina , Serviço Hospitalar de Emergência , Feminino , Humanos , Corpos Cetônicos/urina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreatite/diagnóstico , Pancreatite/etiologia , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVE: To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy. BACKGROUND: Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. This study sought to characterize metabolic properties in CRC using HR-MAS NMR spectroscopy. METHODS: Between November 2010 and January 2012, 44 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and acquired spectral data were imported into SIMCA and MATLAB statistical software packages for unsupervised and supervised multivariate analysis. RESULTS: A total of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n = 83). Cancer tissue contained significantly increased levels of lactate (P < 0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y = 0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition unique metabolic profiles were observed for tumors of differing T-stage. CONCLUSIONS: HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between colonic and rectal cancers. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeutic approaches.
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Biópsia/métodos , Neoplasias Colorretais/diagnóstico , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Estadiamento de Neoplasias/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Colectomia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The present review describes commonly employed metabolic profiling platforms and discusses the current and likely future application of these technologies in surgery. BACKGROUND: The metabolic adaptations that occur in response to surgical illness and trauma are incompletely understood. Evaluating these will be critical to the development of personalized surgical health solutions. Metabonomics is an advancing field in systems biology, which provides a means of interrogating these metabolic shifts. METHODS: Recent literature regarding metabolic profiling technologies and their applications in surgical practice are discussed. Future strategies are proposed for the incorporation of these and next-generation technologies in the evaluation of all steps in the patient surgical pathway. RESULTS: Metabolite-based profiling has provided valuable insights into the metabolic irregularities that occur in cancer development and progression across a variety of cancer subclasses including colorectal, breast, prostate, and lung cancers. In addition, metabolic modeling has shown considerable promise in other surgical conditions including trauma and sepsis and in the assessment of pharmacotherapeutic efficacy. DISCUSSION: Metabonomics offers a posttranscriptional view of system activity providing functional information downstream of the genome and proteome. Information at this level will provide the surgeon with a novel means of evaluating major socioeconomic problems such as cancer and sepsis. In addition, the rapid nature of emerging next generation profiling platforms provides a viable means of "real-time" perioperative metabolic assessment and optimization.
Assuntos
Cirurgia Geral/tendências , Metabolômica , Neoplasias/metabolismo , Medicina de Precisão/tendências , Neoplasias da Mama/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Análise dos Mínimos Quadrados , Neoplasias Pulmonares/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Metaboloma/fisiologia , Neoplasias/cirurgia , Período Perioperatório , Neoplasias da Próstata/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Estresse Fisiológico/fisiologia , Ferimentos e Lesões/metabolismoRESUMO
BACKGROUND: Surgeon specific outcome reports (SSOR) in the UK can be accessed freely by the general public to promote transparency and informed decision-making. However, the views amongst bariatric patients concerning these data are unknown. OBJECTIVES: The aims of this study were to determine patient awareness, views and priorities for outcome reporting in bariatric surgery, and to provide recommendations for future surgeon-specific outcome reporting through the United Kingdom National Bariatric Surgery Registry. SETTING: Bariatric surgical unit in a UK university teaching hospital. METHODS: We adapted a previously validated questionnaire and surveyed the views of 150 patients in a single bariatric surgical unit. We collected data concerning awareness, views, and future priorities for outcome reporting. RESULTS: A full 73% of participants were unaware they could access SSOR. Of the participants that were unaware, 75% stated that they would have accessed SSOR had they been aware they could. Of the participants that had previously accessed SSOR, 86% stated they understood the data, although 61% indicated it did not influence their choice of surgeon. The majority of participants favored public release of outcome reports at the surgeon-level (75%) and hospital-level (83%). The 3 main priorities indicated by participants for future outcome reporting were complication rates (91%), patient reported outcome measures (90%), and reoperation rate (89%), all at the surgeon level. CONCLUSION: Patient awareness of outcome reporting is poor. Efforts must be made to increase awareness of SSOR. Patients should be incorporated as key stakeholders in determining future outcome reporting in bariatric surgery.
Assuntos
Cirurgia Bariátrica , Cirurgiões , Humanos , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários , Reino Unido/epidemiologiaRESUMO
Accurate and objective performance assessment is essential for both trainees and certified surgeons. However, existing methods can be time consuming, labor intensive, and subject to bias. Machine learning (ML) has the potential to provide rapid, automated, and reproducible feedback without the need for expert reviewers. We aimed to systematically review the literature and determine the ML techniques used for technical surgical skill assessment and identify challenges and barriers in the field. A systematic literature search, in accordance with the PRISMA statement, was performed to identify studies detailing the use of ML for technical skill assessment in surgery. Of the 1896 studies that were retrieved, 66 studies were included. The most common ML methods used were Hidden Markov Models (HMM, 14/66), Support Vector Machines (SVM, 17/66), and Artificial Neural Networks (ANN, 17/66). 40/66 studies used kinematic data, 19/66 used video or image data, and 7/66 used both. Studies assessed the performance of benchtop tasks (48/66), simulator tasks (10/66), and real-life surgery (8/66). Accuracy rates of over 80% were achieved, although tasks and participants varied between studies. Barriers to progress in the field included a focus on basic tasks, lack of standardization between studies, and lack of datasets. ML has the potential to produce accurate and objective surgical skill assessment through the use of methods including HMM, SVM, and ANN. Future ML-based assessment tools should move beyond the assessment of basic tasks and towards real-life surgery and provide interpretable feedback with clinical value for the surgeon.PROSPERO: CRD42020226071.