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Urinary volatolomics offers a noninvasive approach for disease detection and monitoring. Herein we present an improved methodology for global volatolomic profiling. Wide coverage was achieved by utilizing a multiphase sorbent for volatile organic compound (VOC) extraction. A single, midpolar column gas chromatography (GC) assay yielded substantially higher numbers of monitored VOCs compared to our previously reported single-sorbent method. Multidimensional GC (GC×GC) enhanced further biomarker discovery while data analysis was simplified by using a tile-based approach. At the same time, the required urine volume was reduced 5-fold from 2 to 0.4 mL. The applicability of the methodology was demonstrated in a pancreatic ductal adenocarcinoma cohort where previous findings were confirmed while a series of additional VOCs with diagnostic potential were discovered.
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Compostos Orgânicos Voláteis , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Gasosa , Compostos Orgânicos Voláteis/análiseRESUMO
Analysis of volatile organic compounds (VOC) within exhaled breath is subject to numerous sources of methodological and physiological variability. Whilst breathing pattern is expected to influence the concentrations of selected exhaled VOCs, it remains challenging to investigate respiratory rate and depth accurately in awake subjects. Online breath sampling was performed in 20 mechanically ventilated patients using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). The effect of variation in respiratory rate (RR) and tidal volume (TV) on the VOC release profiles was examined. A panel of nineteen VOCs were selected, including isoprene, acetone, propofol, volatile aldehydes, acids and phenols. Variation in RR had the greatest influence on exhaled isoprene levels, with maximum and average concentrations being inversely correlated with RR. Variations in RR had a statistically significant impact on acetone, C3-C7 linear aldehydes and acetic acid. In comparison, phenols (including propofol), C8-C10 aldehydes and C3-C6 carboxylic acids were not influenced by RR. Isoprene was the only compound to be influenced by variation in TV. These findings, obtained under controlled conditions, provide useful guidelines for the optimisation of breath sampling protocols to be applied on awake patients.
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Propofol , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Respiração Artificial , Acetona/análise , Testes Respiratórios/métodos , Aldeídos , FenóisRESUMO
OBJECTIVE: Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer remains poorly understood. DESIGN: A systematic search identified studies assessing the oesophagogastric cancer microbiome. The primary outcome was to identify bacterial enrichment specific to oesophagogastric cancer. Secondary outcomes included appraisal of the methodology, diagnostic performance of cancer bacteria and the relationship between oral and tissue microbiome. RESULTS: A total of 9295 articles were identified, and 87 studies were selected for analysis. Five genera were enriched in gastric cancer: Lactobacillus, Streptococcus, Prevotella, Fusobacterium and Veillonella. No clear trends were observed in oesophageal adenocarcinoma. Streptococcus, Prevotella and Fusobacterium were abundant in oesophageal squamous cell carcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways mediating carcinogenesis. STORMS reporting assessment identified experimental deficiencies, considering batch effects and sources of contamination prevalent in low-biomass samples. CONCLUSIONS: Functional analysis of cancer pathways can infer tumorigenesis within the cancer-microbe-immune axis. There is evidence that study design, experimental protocols and analytical techniques could be improved to achieve more accurate and representative results. Whole-genome sequencing is recommended to identify key metabolic and functional capabilities of candidate bacteria biomarkers.
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Volatolomics offers an opportunity for noninvasive detection and monitoring of human disease. While gas chromatography-mass spectrometry (GC-MS) remains the technique of choice for analyzing volatile organic compounds (VOCs), barriers to wider adoption in clinical practice still exist, including: sample preparation and introduction techniques, VOC extraction, throughput, volatolome coverage, biological interpretation, and quality control (QC). Therefore, we developed a complete pipeline for untargeted urinary volatolomic profiling. We optimized a novel extraction technique using HiSorb sorptive extraction, which exhibited high analytical performance and throughput. We achieved a broader VOC coverage by using HiSorb coupled with a set of complementary chromatographic methods and time-of-flight mass spectrometry. Furthermore, we developed a data preprocessing strategy by evaluating internal standard normalization, batch correction, and we adopted strict QC measures including removal of nonlinearly responding, irreproducible, or contaminated metabolic features, ensuring the acquisition of high-quality data. The applicability of this pipeline was evaluated in a clinical cohort consisting of pancreatic ductal adenocarcinoma (PDAC) patients (n = 28) and controls (n = 33), identifying four urinary candidate biomarkers (2-pentanone, hexanal, 3-hexanone, and p-cymene), which can successfully discriminate the cancer and noncancer subjects. This study presents an optimized, high-throughput, and quality-controlled pipeline for untargeted urinary volatolomic profiling. Use of the pipeline to discriminate PDAC from control subjects provides proof of principal of its clinical utility and potential for application in future biomarker discovery studies.
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Compostos Orgânicos Voláteis , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Espectrometria de Massas , BiomarcadoresRESUMO
Prehabilitation aims to optimize a patient's functional capacity in preparation for surgery. Esophageal cancer patients have a high incidence of sarcopenia and commonly undergo neoadjuvant therapy, which is associated with loss of muscle mass. This study examines the effects of prehabilitation on body composition during neoadjuvant therapy in esophageal cancer patients. In this cohort study, changes in body composition were compared between esophageal cancer patients who participated in prehabilitation during neoadjuvant therapy and controls who did not receive prehabilitation. Assessment of body composition was performed from CT images acquired at the time of diagnosis and after neoadjuvant therapy. Fifty-one prehabilitation patients and 28 control patients were identified. There was a significantly greater fall in skeletal muscle index (SMI) in the control group compared with the prehabilitation patients (Δ SMI mean difference = -2.2 cm2/m2, 95% CI -4.3 to -0.1, p=0.038). Within the prehabilitation cohort, there was a smaller decline in SMI in patients with ≥75% adherence to exercise in comparison to those with lower adherence (Δ SMI mean difference = -3.2, 95% CI -6.0 to -0.5, P = 0.023). A greater decrease in visceral adipose tissue (VAT) was seen with increasing volumes of exercise completed during prehabilitation (P = 0.046). Loss of VAT during neoadjuvant therapy was associated with a lower risk of post-operative complications (P = 0.017). By limiting the fall in SMI and promoting VAT loss, prehabilitation may have multiple beneficial effects in patients with esophageal cancer. Multi-center, randomized studies are needed to further explore these findings.
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Neoplasias Esofágicas , Exercício Pré-Operatório , Humanos , Estudos de Coortes , Terapia Combinada , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/complicações , Composição CorporalRESUMO
The interest around analysis of volatile organic compounds (VOCs) within breath has increased in the last two decades. Uncertainty remains around standardisation of sampling and whether VOCs within room air can influence breath VOC profiles. To assess the abundance of VOCs within room air in common breath sampling locations within a hospital setting and whether this influences the composition of breath. A secondary objective is to investigate diurnal variation in room air VOCs. Room air was collected using a sampling pump and thermal desorption (TD) tubes in the morning and afternoon from five locations. Breath samples were collected in the morning only. TD tubes were analysed using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF-MS). A total of 113 VOCs were identified from the collected samples. Multivariate analysis demonstrated clear separation between breath and room air. Room air composition changed throughout the day and different locations were characterized by specific VOCs, which were not influencing breath profiles. Breath did not demonstrate separation based on location, suggesting that sampling can be performed across different locations without affecting results.
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Poluentes Atmosféricos , Líquidos Corporais , Compostos Orgânicos Voláteis , Ar/análise , Poluentes Atmosféricos/análise , Líquidos Corporais/química , Testes Respiratórios/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análiseRESUMO
The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from human skin can be signatures of health and disease is unknown. This systematic review summarises the published literature concerning the methodology, application, and volatile profiles of skin VOC studies. An online literature search was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis, to identify human skin VOC studies using untargeted mass spectrometry (MS) methods. The principal outcome was chemically verified VOCs detected from the skin. Each VOC was cross-referenced using the CAS number against the Human Metabolome and KEGG databases to evaluate biological origins. A total of 29 studies identified 822 skin VOCs from 935 participants. Skin VOCs were commonly sampled from the hand (n = 9) or forearm (n = 7) using an absorbent patch (n = 15) with analysis by gas chromatography MS (n = 23). Twenty-two studies profiled the skin VOCs of healthy subjects, demonstrating a volatolome consisting of aldehydes (18%), carboxylic acids (12%), alkanes (12%), fatty alcohols (9%), ketones (7%), benzenes and derivatives (6%), alkenes (2%), and menthane monoterpenoids (2%). Of the VOCs identified, 13% had putative endogenous origins, 46% had tentative exogenous origins, and 40% were metabolites from mixed metabolic pathways. This review has comprehensively profiled the human skin volatolome, demonstrating the presence of a distinct VOC signature of healthy skin, which can be used as a reference for future researchers seeking to unlock the clinical potential of skin volatolomics. As significant proportions of identified VOCs have putative exogenous origins, strategies to minimise their presence through methodological refinements and identifying confounding compounds are discussed.
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BACKGROUND: Malnutrition commonly affects patients with esophageal cancer and has the potential to negatively influence treatment outcomes. The aim of this study was to investigate the impact of early (preoperative) jejunostomy tube feeding (JTF) in nutritionally 'high risk' patients receiving multimodal therapy for esophageal cancer. METHODS: Patients were selected to undergo early JTF during neoadjuvant chemoradiotherapy (nCRT) in accordance with European Society for Clinical Nutrition and Metabolism (ESPEN) and Enhanced Recovery after Surgery (ERAS®) Society guidelines. Clinical outcomes were compared with patients who received routine JTF from the time of esophagectomy. Body composition was determined from computed tomography (CT) images acquired at diagnosis, after nCRT, and ≥ 3 months after surgery. RESULTS: In total, 81 patients received early JTF and 91 patients received routine JTF. Patients who received early JTF had lower body mass index (BMI; 26.1 ± 4.6 vs. 28.4 ± 4.9; p = 0.002), greater weight loss, and worse performance status at diagnosis. Groups were otherwise well-matched for baseline characteristics. Rate of re-intubation (8.8% vs. 1.1%; p = 0.027), pulmonary embolism (5.0% vs. 0.0%; p = 0.046), and 90-day mortality (10.0% vs. 1.1%; p = 0.010) were worse in the early JTF group; however, overall survival was equivalent for both the early and routine JTF groups (p = 0.053). Wide variation in the degree of preoperative muscle loss and total adipose tissue loss was observed across the entire study cohort. Relative preoperative muscle and adipose tissue loss in patients with early and routine JTF was equivalent. CONCLUSIONS: In patients determined to be at 'high risk' of malnutrition, early JTF may prevent excess morbidity after esophagectomy with an associated relative preservation of parameters of body composition.
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Neoplasias Esofágicas , Desnutrição , Composição Corporal , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Humanos , Jejunostomia/efeitos adversos , Jejunostomia/métodos , Desnutrição/etiologia , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND: Oesophageal adenocarcinoma poses a significant global health burden, yet the staging used to predict survival has limited ability to stratify patients by outcome. This study aimed to identify published clinical models that predict survival in oesophageal adenocarcinoma and to evaluate them using an independent international multicentre dataset. METHODS: A systematic literature search (title and abstract) using the Ovid Embase and MEDLINE databases (from 1947 to 11 July 2020) was performed. Inclusion criteria were studies that developed or validated a clinical prognostication model to predict either overall or disease-specific survival in patients with oesophageal adenocarcinoma undergoing surgical treatment with curative intent. Published models were validated using an independent dataset of 2450 patients who underwent oesophagectomy for oesophageal adenocarcinoma with curative intent. RESULTS: Seventeen articles were eligible for inclusion in the study. Eleven models were suitable for testing in the independent validation dataset and nine of these were able to stratify patients successfully into groups with significantly different survival outcomes. Area under the receiver operating characteristic curves for individual survival prediction models ranged from 0.658 to 0.705, suggesting poor-to-fair accuracy. CONCLUSION: This study highlights the need to concentrate on robust methodologies and improved, independent, validation, to increase the likelihood of clinical adoption of survival predictions models.
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Adenocarcinoma , Neoplasias Esofágicas , Bases de Dados Factuais , Esofagectomia/métodos , Humanos , PrognósticoRESUMO
OBJECTIVE: The aim of this study was to investigate long-term HRQOL and symptom evolution in disease free patients up to 20 years after esophagectomy. BACKGROUND: Esophagectomy has been associated with decreased HRQOL and persistent gastrointestinal symptoms. METHODS: The study cohort was identified from 2 high volume centers for the management of esophageal cancer. Patients completed HRQOL and symptom questionnaires, including: Digestive Symptom Questionnaire, EORTC QLQ-C30, EORTC QLQ-OG25 Euro QoL 5D, and SF36. Patients were assessed in 3 cohorts: <1 year; 1-5 years, and; >5 years after surgery. RESULTS: In total 171 of 222 patients who underwent esophagectomy between 1991 and 2017 who met inclusion criteria and were contactable, responded to the questionnaires, corresponding to a response rate of 77%. Median age was 66.2 years, and median time from operation to survey was 5.6 years (range 0.3-23.1). Early satiety was the most commonly reported symptom in all patients irrespective of timeframe (87.4%; range 82%-92%). Dysphagia was seen to decrease over time (58% at <2 years; 28% at 2-5 years; 20% at >5 years; P = 0.013). Weight loss scores demonstrated nonstatistical improvement over time. All other symptom scores including heartburn, regurgitation, respiratory symptoms, and pain scores remained constant over time. Average HRQOL did not improve from levels 1 year after surgery compared to patients up to 23 years after esophagectomy. CONCLUSION: With the exception of dysphagia, which improved over time, esophagectomy was associated with decreased HRQOL and lasting gastrointestinal symptoms up to 20 years after surgery. Pertinently however long-term survivors after oesophagectomy demonstrated comparable to improved HRQOL compared to the general population. The impact of esophagectomy on gastrointestinal symptoms and long-term HRQOL should be considered when counseling and caring for patients undergoing esophagectomy.
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Neoplasias Esofágicas/cirurgia , Esofagectomia , Junção Esofagogástrica/cirurgia , Qualidade de Vida , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Sobreviventes , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.Trial registration number: ISRCTN59036820, ISRCTN10386621.
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Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagectomia/normas , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Ensaios Clínicos Controlados Aleatórios como Assunto , Técnica Delphi , Humanos , Excisão de Linfonodo , Fotografação , Projetos Piloto , Complicações Pós-Operatórias , Garantia da Qualidade dos Cuidados de Saúde/métodos , Gravação em VídeoRESUMO
INTRODUCTION: Three-dimensional (3D) reconstruction describes the generation of either virtual or physically printed anatomically accurate 3D models from two-dimensional medical images. Their implementation has revolutionised medical practice. Within surgery, key applications include growing roles in operative planning and procedures, surgical education and training, as well as patient engagement and education. In comparison to other surgical specialties, oesophagogastric surgery has been slow in their adoption of this technology. Herein the authors outline a scoping review protocol that aims to analyse the current role of 3D modelling in oesophagogastric surgery and highlight any unexplored avenues for future research. METHODS AND ANALYSIS: The protocol was generated using internationally accepted methodological frameworks. A succinct primary question was devised, and a comprehensive search strategy was developed for key databases (MEDLINE, Embase, Elsevier Scopus and ISI Web of Science). These were searched from their inception to 1 June 2020. Reference lists will be reviewed by hand and grey literature identified using OpenGrey and Grey Literature Report. The protocol was registered to the Open Science Framework (osf.io/ta789).Two independent reviewers will screen titles, abstracts and perform full-text reviews for study selection. There will be no methodological quality assessment to ensure a full thematic analysis is possible. A data charting tool will be created by the investigatory team. Results will be analysed to generate descriptive numerical tabular results and a thematic analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was not required for the collection and analysis of the published data. The scoping review report will be disseminated through a peer-reviewed publication and international conferences. REGISTRATION DETAILS: The scoping review protocol has been registered on the Open Science Framework (https://osf.io/ta789).
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Atenção à Saúde , Revisão por Pares , Humanos , Projetos de Pesquisa , Literatura de Revisão como AssuntoRESUMO
The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection and monitoring is an emergent research field that has the potential to reshape current clinical practice. However, adoption of breath testing has been limited by a lack of standardization. This protocol provides a comprehensive workflow for online and offline breath analysis using selected ion flow tube mass spectrometry (SIFT-MS). Following the suggested protocol, 50 human breath samples can be analyzed and interpreted in <3 h. Key advantages of SIFT-MS are exploited, including the acquisition of real-time results and direct compound quantification without need for calibration curves. The protocol includes details of methods developed for targeted analysis of disease-specific VOCs, specifically short-chain fatty acids, aldehydes, phenols, alcohols and alkanes. A procedure to make custom breath collection bags is also described. This standardized protocol for VOC analysis using SIFT-MS is intended to provide a basis for wider application and the use of breath analysis in clinical studies.
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Testes Respiratórios/métodos , Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Íons , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: To examine the feasibility and acceptability of breath research in primary care. DESIGN: Non-randomised, prospective, mixed-methods cross-sectional observational study. SETTING: Twenty-six urban primary care practices. PARTICIPANTS: 1002 patients aged 18-90 years with gastrointestinal symptoms. MAIN OUTCOME MEASURES: During the first 6 months of the study (phase 1), feasibility of patient enrolment using face-to-face, telephone or SMS-messaging (Short Message Service) enrolment strategies, as well as processes for breath testing at local primary care practices, were evaluated. A mixed-method iterative study design was adopted and outcomes evaluated using weekly Plan-Do-Study-Act cycles, focus groups and general practitioner (GP) questionnaires.During the second 6 months of the study (phase 2), patient and GP acceptability of the breath test and testing process was assessed using questionnaires. In addition a 'single practice' recruitment model was compared with a 'hub and spoke' centralised recruitment model with regards to enrolment ability and patient acceptability.Throughout the study feasibility of the collection of a large number of breath samples by clinical staff over multiple study sites was evaluated and quantified by the analysis of these samples using mass spectrometry. RESULTS: 1002 patients were recruited within 192 sampling days. Both 'single practice' and 'hub and spoke' recruitment models were effective with an average of 5.3 and 4.3 patients accrued per day, respectively. The 'hub and spoke' model with SMS messaging was the most efficient combined method of patient accrual. Acceptability of the test was high among both patients and GPs. The methodology for collection, handling and analysis of breath samples was effective, with 95% of samples meeting quality criteria. CONCLUSIONS: Large-scale breath testing in primary care was feasible and acceptable. This study provides a practical framework to guide the design of Phase III trials examining the performance of breath testing in primary care.
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Atenção Primária à Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
Volatile breath metabolites serve as potential disease biomarkers. Online mass spectrometry (MS) presents real-time quantification of breath volatile organic compounds (VOCs). The study aims to assess the relationship between two online analytical mass spectrometry techniques in the quantification of target breath metabolites: selected ion flow tube mass spectrometry (SIFT-MS) and proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). The two following techniques were employed: (i) direct injection with bag sampling using SIFT-MS and PTR-ToF-MS and (ii) direct injection and thermal desorption (TD) tube comparison using PTR-ToF-MS. The concentration of abundant breath metabolites, acetone and isoprene, demonstrated a strong positive linear correlation between both mass spectrometry techniques (r = 0.97, r = 0.89, respectively; p < 0.001) and between direct injection and TD tube (r = 0.97, r = 0.92, respectively; p < 0.001) breath sampling techniques. This was reflected for the majority of short chain fatty acids and alcohols tested (r > 0.80, p < 0.001). Analyte concentrations were notably higher with the direct injection of a sampling bag compared to the TD method. All metabolites produced a high degree of agreement in the detection range of VOCs between SIFT-MS and PTR-ToF-MS, with the majority of compounds falling within 95% of the limits of agreement with Bland-Altman analysis. The cross platform analysis of exhaled breath demonstrates strong positive correlation coefficients, linear regression, and agreement in target metabolite detection rates between both breath sampling techniques. The study demonstrates the transferability of using data outputs between SIFT-MS and PTR-ToF-MS. It supports the implementation of a TD platform in multi-site studies for breath biomarker research in order to facilitate sample transport between clinics and the laboratory.
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Testes Respiratórios/métodos , Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Acetona/análise , Adulto , Testes Respiratórios/instrumentação , Butadienos/análise , Feminino , Hemiterpenos/análise , Humanos , Masculino , Espectrometria de Massas/instrumentaçãoRESUMO
This study seeks to define long-term variation in body composition in patients undergoing esophagectomy for cancer and to associate those changes with survival. Assessment of skeletal muscle, visceral (VAT) and subcutaneous adipose tissue (SAT) was performed using computed tomography (CT) images routinely acquired: at diagnosis; after neoadjuvant therapy, and; >6 months after esophagectomy. In cases where multiple CT scans were performed >6 months after surgery, all available images were assessed. Ninty-seven patients met inclusion criteria with a median of 2 (range 1-10) postoperative CT images acquired between 0.5 and 9.7 years after surgery. Following surgical treatment of esophageal cancer, patients lost on average 13.3% of their skeletal muscle, 64.5% of their VAT and 44.2% of their SAT. Sarcopenia at diagnosis was not associated with worse overall survival (66.3% vs. 68.5%; P = 0.331). Sarcopenia 1 year after esophagectomy was however associated with lower 5-year overall survival (53.8% vs. 87.5%; P = 0.019). Survival was lower in those patients who had >10% decrease in skeletal muscle index (SMI; 33.3% vs. 72.1%; P = 0.003) and >40% decrease in SAT 1 year after surgery (40.4% vs. 67.4%; P = 0.015). On multivariate analysis, a decline in SMI 1 year after surgery was predictive of worse survival (HR 0.38, 95%CI 0.20-0.73; P = 0.004). This study provides new insight relating to long-term variation in body composition in patients undergoing esophagectomy for cancer. Findings provide further evidence of the importance of body composition, in particular depletion of skeletal muscle, in predicting survival following esophagectomy.
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Esofagectomia , Sarcopenia , Adiposidade , Esofagectomia/efeitos adversos , Humanos , Músculo Esquelético/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologiaRESUMO
Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients' breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Aldeídos/metabolismo , Aldeídos/toxicidade , Biomarcadores Tumorais , Dano ao DNA/efeitos dos fármacos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Aldeído Desidrogenase/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Adutos de DNA , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Esôfago , Genes p53/genética , Humanos , MetforminaRESUMO
Where surgery forms the primary curative modality in surgical oncology trials the quality of this intervention has the potential to directly influence outcomes. Many trials however lack a robust framework to ensure surgical quality. We aim to report existing published challenges to quality assurance of surgical interventions within oncological trials. A systematic on-line literature search of Embase and Medline identified 34 relevant studies, including 19 RCTs, 11 further analyses of the primary RCTs, and 4 trial protocols. Inclusion criteria: oncological RCTs with a surgical intervention and/or associated publications relevant to the research question; 'Challenges to quality assurance of surgery in clinical oncology trials'. Selected articles were assessed by two reviewers to identify reported challenges to quality assurance of surgical intervention within these trials. Reported challenges to surgical quality could be classified as those affecting credentialing, standardisation and monitoring of surgical interventions. Constraints of using case volume for credentialing surgeons; inter-centre variation in the definition and execution of interventions; insufficient training, and monitoring of surgical quality, were the most commonly encountered challenges within each of these three domains. Findings confirmed an inadequacy in the implementation and reporting of effective surgical quality assurance measures. The surgical community should enable implementation of agreed upon mitigating strategies to overcome challenges to surgical quality in oncology trials.
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Neoplasias/cirurgia , Garantia da Qualidade dos Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Procedimentos Cirúrgicos Operatórios/normas , HumanosRESUMO
BACKGROUND: We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface and air contamination during the coronavirus disease 2019 (COVID-19) pandemic in London. METHODS: Prospective, cross-sectional, observational study in a multisite London hospital. Air and surface samples were collected from 7 clinical areas occupied by patients with COVID-19 and a public area of the hospital. Three or four 1.0-m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected using reverse-transcription quantitative polymerase chain reaction (PCR) and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114 of 218 (52.3%) surfaces and in 14 of 31 (38.7%) air samples, but no virus was cultured. Viral RNA was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67 of 105 [63.8%] vs 29 of 64 [45.3%]; odds ratio, 0.5; 95% confidence interval, 0.2-0.9; P = .025, χ2 test). The high PCR cycle threshold value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19 and the need for effective use of personal protective equipment, physical distancing, and hand/surface hygiene.