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Breast cancer is the most common cancer among women worldwide. It is a major cause of cancer death, and its incidence rate has been gradually increasing in the Arab world, Saudi Arabia has a higher proportion of young females getting breast cancer than other countries. This study was conducted to investigate the knowledge, attitude, and practice regarding breast self-examination among females from 20 to 60 years old in Jazan Region, Saudi Arabia. Using A Community-based descriptive cross-sectional approach, data were gathered from 567 Saudi and non-Saudi women using structured interviews and then analyzed using the Statistical Package for Social Sciences (IBM) version 21.0 software program. Where the study indicated that around half of the participants (55.7%) had good total knowledge scores regarding breast self-examination, and most had positive attitudes. However, only 205 (36.2%) respondents practice it regularly. Moreover, the study reveals a significant association between respondents' knowledge and attitudes toward breast self-examination (P = 0.05). These findings indicate moderate knowledge, poor breast self-examination practices, and a significant association between knowledge and attitudes. Therefore, conducting health education programs is necessary to raise awareness about breast self-examination (BSE) among Jazan women.
Le cancer du sein est le cancer le plus répandu chez les femmes dans le monde. Il s'agit d'une cause majeure de décès par cancer et son taux d'incidence augmente progressivement dans le monde arabe. L'Arabie saoudite compte une proportion plus élevée de jeunes femmes atteintes d'un cancer du sein que les autres pays. Cette étude a été menée pour étudier les connaissances, l'attitude et la pratique concernant l'auto-examen des seins chez les femmes de 20 à 60 ans dans la région de Jazan, en Arabie Saoudite. À l'aide d'une approche transversale descriptive communautaire, les données ont été recueillies auprès de 567 femmes saoudiennes et non saoudiennes à l'aide d'entretiens structurés, puis analysées à l'aide du logiciel Statistical Package for Social Sciences (IBM) version 21.0. L'étude a indiqué qu'environ la moitié des participantes (55,7 %) avaient de bons scores totaux de connaissances concernant l'auto-examen des seins et que la plupart avaient des attitudes positives. Cependant, seuls 205 (36,2%) répondants le pratiquent régulièrement. De plus, l'étude révèle une association significative entre les connaissances et les attitudes des répondants à l'égard de l'auto-examen des seins (P = 0,05). Ces résultats indiquent des connaissances modérées, de mauvaises pratiques d'auto-examen des seins et une association significative entre les connaissances et les attitudes. Par conséquent, il est nécessaire de mener des programmes d'éducation sanitaire pour sensibiliser les femmes de Jazan à l'auto-examen des seins (ESB).
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Neoplasias de la Mama , Autoexamen de Mamas , Conocimientos, Actitudes y Práctica en Salud , Humanos , Femenino , Autoexamen de Mamas/estadística & datos numéricos , Autoexamen de Mamas/psicología , Arabia Saudita , Adulto , Estudios Transversales , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico , Adulto Joven , Encuestas y Cuestionarios , Detección Precoz del CáncerRESUMEN
Among the range of severe plant diseases, bacterial soft rot caused by Erwinia carotovora is a significant threat to crops. This study aimed to examine the varying response patterns of distinct potato cultivars to the influence of E. carotovora. Furthermore, it seeks to highlight the potential role of salicylic acid (SA) and methyl jasmonate (MeJA) in stimulating the antioxidant defence system. We collected eight bacterial isolates from diseased and rotted tubers which were morphologically and physiologically identified as E. carotovora subsp. carotovora. We conducted a greenhouse experiment to analyse the antioxidant responses of three different potato cultivars (Diamont, Kara, and Karros) at various time intervals (2, 4, 6, 8, 12, and 24 h) after bacterial infection (hpi). We assessed the extent of disease damage by applying a foliar spray of 0.9 mM salicylic acid (SA) and 70 µM methyl jasmonate (MeJA). Inoculating with Ecc led to an increase in total phenolic levels, as well as the activities and gene expression of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POX) as time progressed. Additionally, the application of SA and MeJA resulted in a further increase relative to the diseased treatments. The Karros cultivar, unlike the Diamont and Kara cultivars, demonstrated the highest expression levels of PAL, PPO and POX through inoculation, reflecting its higher levels of activity and resistance. Furthermore, the genetic response of potato cultivars to infection at 0 hpi varied depending on their susceptibility. The examination of the rate of PAL activity upregulation following SA or MeJA stimulation clarifies the cultivars' susceptibility over time. In conclusion, the study identified E. carotovora subsp. carotovora as the most virulent isolate causing soft rot disease in potato tubers. It further revealed that the Karros cultivar displayed superior resistance with high activities and gene expression of PAL, PPO and POX, while the cv. Diamont exhibited sensitivity. Additionally, foliar exposure to SA and MeJA induced antioxidant responses, enhancing the potato plants' resistance against Ecc pathogenesis and overall plant defence.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
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Enfisema , Fibrosis Pulmonar Idiopática , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/complicaciones , Pulmón , Fibrosis , Enfisema/complicaciones , Progresión de la Enfermedad , Estudios RetrospectivosRESUMEN
We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.
Nous comparons l'hématocrite, l'hémoglobine, le besoin de transfusion, la photothérapie récurrente, le taux de bilirubine sérique et la ferritine sérique à différentes périodes pour la traite du cordon ombilical (UCM) et le clampage retardé du cordon (DCC) chez les nourrissons nés à terme et prématurés. Une recherche complète dans diverses bases de données visait à comparer les études UCM et DCC jusqu'au 2 mai 2023. Les outils Cochrane et NIH ont évalué les ECR et les cohortes, respectivement. La méta-analyse a utilisé le logiciel Review Manager 5.4, calculant le MD et le RR avec des IC à 95 % pour les données continues et dichotomiques. Nous avons inclus 20 études portant sur un total de 5 189 nourrissons. Concernant les nourrissons prématurés, le niveau d'hématocrite n'a montré aucune différence significative entre la traite du cordon ombilical intact (iUCM) et la DCC (DM = -0,24, IC à 95 % [-1,11, 0,64]). De plus, l'incidence des décès néonatals était significativement plus élevée avec la technique UCM qu'avec la technique DCC (RR = 1,28, IC à 95 % [1,01 à 1,62]). Concernant les nourrissons à terme et peu prématurés, le niveau = 0,21, IC à 95 % [-1,28 à 1,69]), (DM = 0,96, IC à 95 % [-1,02 à 2,95]), respectivement. L'UCM a entraîné un risque plus élevé de décès néonatal chez les nourrissons prématurés par rapport au DCC. Cependant, l'incidence de la polyglobulie était plus faible dans le groupe UCM. De plus, l'UCM était associée à des taux plus élevés d'événements IVH graves. Sur la base de ces résultats, le DCC peut être préféré en raison de sa plus faible incidence d'IVH grave et de décès néonatals. d'hématocrite n'a montré aucune différence significative entre les techniques iUCM ou cUCM par rapport à la technique DCC (DM.
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Recien Nacido Prematuro , Muerte Perinatal , Lactante , Embarazo , Femenino , Recién Nacido , Humanos , Clampeo del Cordón Umbilical , Cordón Umbilical , HematócritoRESUMEN
We aim to collect the evidence of efficacy of Gentle Guman Touch (GHT) and Yakson Touch in preterm neonates as pain relief, heart rate, oxygen saturation, and urine cortisol level. We made our search through PubMed, Web of Science, Scopus, and Cochrane by the mid of March 2023. Randomized control trials (RCTs) were included, and the Cochrane risk of bias tool was utilized to assess their quality. Using Review Manager software, a meta-analysis was conducted. We computed the mean difference (MD) with a 95% confidence interval (CI) for the continuous data. During the examination, the Neonatal Infant Pain Scale (NIPS) was significantly reduced in the touch group compared to the control group (MD = -3.40, 95% CI [-4.15 to -2.64], P-value= 0.00001). After the examination, the NIPS score was also reduced by both Yakson touch and GHT compared to the control (MD = -2.14, 95% CI [-3.42 to -0.85], P-value <0.00001). Yakson touch and GHT are non-pharmacological, easy, and safe methods that can be used for painful interventions to reduce the pain experience of preterm infants from variable interventions. Both methods improved infant sleep and behavior. Preterm infants' heart rates and oxygen saturation were unaffected by Yakson touch or GHT.
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Recien Nacido Prematuro , Tacto , Humanos , Lactante , Recién Nacido , Dolor/prevención & controlRESUMEN
Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods: Two CT scans 6-36â months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Results: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). Interpretation: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.
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Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.
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Carcinoma de Pulmón de Células no Pequeñas , Evolución Clonal , Células Clonales , Evolución Molecular , Neoplasias Pulmonares , Metástasis de la Neoplasia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Células Clonales/patología , Estudios de Cohortes , Progresión de la Enfermedad , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/patología , Recurrencia Local de NeoplasiaRESUMEN
OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: ⢠Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. ⢠Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. ⢠Agreement for serial CXR change is moderate, limiting utility in guiding management.
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COVID-19 , Humanos , Radiografía Torácica/métodos , Reproducibilidad de los Resultados , Radiografía , Radiólogos , Estudios RetrospectivosRESUMEN
OBJECTIVES: Successful lung cancer screening delivery requires sensitive, timely reporting of low-dose computed tomography (LDCT) scans, placing a demand on radiology resources. Trained non-radiologist readers and computer-assisted detection (CADe) software may offer strategies to optimise the use of radiology resources without loss of sensitivity. This report examines the accuracy of trained reporting radiographers using CADe support to report LDCT scans performed as part of the Lung Screen Uptake Trial (LSUT). METHODS: In this observational cohort study, two radiographers independently read all LDCT performed within LSUT and reported on the presence of clinically significant nodules and common incidental findings (IFs), including recommendations for management. Reports were compared against a 'reference standard' (RS) derived from nodules identified by study radiologists without CADe, plus consensus radiologist review of any additional nodules identified by the radiographers. RESULTS: A total of 716 scans were included, 158 of which had one or more clinically significant pulmonary nodules as per our RS. Radiographer sensitivity against the RS was 68-73.7%, with specificity of 92.1-92.7%. Sensitivity for detection of proven cancers diagnosed from the baseline scan was 83.3-100%. The spectrum of IFs exceeded what could reasonably be covered in radiographer training. CONCLUSION: Our findings highlight the complexity of LDCT reporting requirements, including the limitations of CADe and the breadth of IFs. We are unable to recommend CADe-supported radiographers as a sole reader of LDCT scans, but propose potential avenues for further research including initial triage of abnormal LDCT or reporting of follow-up surveillance scans. KEY POINTS: ⢠Successful roll-out of mass screening programmes for lung cancer depends on timely, accurate CT scan reporting, placing a demand on existing radiology resources. ⢠This observational cohort study examines the accuracy of trained radiographers using computer-assisted detection (CADe) software to report lung cancer screening CT scans, as a potential means of supporting reporting workflows in LCS programmes. ⢠CADe-supported radiographers were less sensitive than radiologists at identifying clinically significant pulmonary nodules, but had a low false-positive rate and good sensitivity for detection of confirmed cancers.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Computadores , Detección Precoz del Cáncer/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based 'real-world' LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a 'lung health check'. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment.
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Carcinoma/diagnóstico , Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico , Aceptación de la Atención de Salud , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dosis de Radiación , Factores Socioeconómicos , Reino UnidoRESUMEN
Rationale: Individuals eligible for lung cancer screening (LCS) by low-dose computed tomography (LDCT) are also at risk of chronic obstructive pulmonary disease (COPD) due to age and smoking exposure. Whether the LCS episode is useful for early detection of COPD is not well established.Objectives: To explore associations between symptoms, comorbidities, spirometry, and emphysema in participants enrolled in the Lung Screen Uptake Trial.Methods: This cross-sectional study was a prespecified analysis nested within Lung Screen Uptake Trial, which was a randomized study testing the impact of differing invitation materials on attendance of 60- to 75-year-old smokers and ex-smokers to a "lung health check" between November 2015 and July 2017. Participants with a smoking history ≥30 pack-years and who quit ≤15 years ago, or meeting a lung cancer risk of ≥1.51% via the Prostate Lung Colorectal Ovarian model or ≥2.5% via the Liverpool Lung Project model, were offered LDCT. COPD was defined and classified according to the GOLD (Global Initiative for Obstructive Lung Disease) criteria using prebronchodilator spirometry. Analyses included the use of descriptive statistics, chi-square tests to examine group differences, and univariable and multivariable logistic regression to explore associations between symptom prevalence, airflow limitation, and visually graded emphysema.Results: A total of 560 of 986 individuals included in the analysis (57%) had prebronchodilator spirometry consistent with COPD; 67% did not have a prior history of COPD and were termed "undiagnosed." Emphysema prevalence in those with known and "undiagnosed" COPD was 73% and 68%, respectively. A total of 32% of those with "undiagnosed COPD" had no emphysema on LDCT. Inhaler use and symptoms were more common in the "known" than the "undiagnosed" COPD group (63% vs. 33% with persistent cough [P < 0.001]; 73% vs. 33% with dyspnea [P < 0.001]). Comorbidities were common in all groups. Adjusted odds ratio (aOR) of respiratory symptoms were more significant for airflow obstruction (aOR GOLD 1 and 2, 1.57; confidence interval [CI], 1.14-2.17; aOR GOLD 3 and 4, 4.6; CI, 2.17-9.77) than emphysema (aOR mild, 1.12; CI, 0.81-1.55; aOR moderate, 1.33; CI, 0.85-2.09; aOR severe, 4.00; CI, 1.57-10.2).Conclusions: There is high burden of "undiagnosed COPD" and emphysema in LCS participants. Adding spirometry findings to the LDCT enhances identification of individuals with COPD.Clinical trial registered with www.clinicaltrials.gov (NCT02558101).
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Neoplasias Pulmonares/diagnóstico por imagen , Tamizaje Masivo/métodos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Fumar/efectos adversos , Anciano , Tos/etiología , Estudios Transversales , Detección Precoz del Cáncer , Enfisema/diagnóstico por imagen , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Espirometría , Tomografía Computarizada por Rayos X , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5â years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Pequeñas/patología , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/patología , Esputo/citología , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Broncoscopía , Carcinoma de Células Grandes/complicaciones , Carcinoma de Células Grandes/diagnóstico por imagen , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Células Pequeñas/complicaciones , Carcinoma de Células Pequeñas/diagnóstico por imagen , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Técnicas Citológicas , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Imagen Óptica , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Medición de Riesgo , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Reino UnidoRESUMEN
INTRODUCTION: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) offers an opportunity to impact both lung cancer and coronary heart disease mortality through detection of coronary artery calcification (CAC). Here, we explore the value of CAC and cardiovascular disease (CVD) risk assessment in LCS participants in the Lung Screen Uptake Trial (LSUT). METHODS: In this cross-sectional study, current and ex-smokers aged 60-75 were invited to a 'lung health check'. Data collection included a CVD risk assessment enabling estimation of 10 year CVD risk using the QRISK2 score. Participants meeting the required lung cancer risk underwent an ungated, non-contrast LDCT. Descriptive data, bivariate associations and a multivariate analysis of predictors of statin use are presented. RESULTS: Of 1005 individuals enrolled, 680 were included in the final analysis. 421 (61.9%) had CAC present and in 49 (7.2%), this was heavy. 668 (98%) of participants had a QRISK2≥10% and QRISK2 was positively associated with increasing CAC grade (OR 4.29 (CI 0.93 to 19.88) for QRISK2=10%-20% and 12.29 (CI 2.68 to 56.1) for QRISK2≥20% respectively). Of those who qualified for statin primary prevention (QRISK2≥10%), 56.8% did not report a history of statin use. In the multivariate analysis statin use was associated with age, body mass index and history of hypertension and diabetes. CONCLUSIONS: LCS offers an important opportunity for instituting CVD risk assessment in all LCS participants irrespective of the presence of LDCT-detected CAC. Further studies are needed to determine whether CAC could enhance uptake and adherence to primary preventative strategies.
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Enfermedades Cardiovasculares/prevención & control , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Anciano , Enfermedades Cardiovasculares/complicaciones , Estudios de Cohortes , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/diagnóstico por imagen , Estudios Transversales , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias Pulmonares/complicaciones , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Prevención Primaria/métodos , Estudios Prospectivos , Dosis de Radiación , Medición de Riesgo/métodos , Tomografía Computarizada por Rayos X/métodos , Calcificación Vascular/complicaciones , Calcificación Vascular/diagnóstico por imagenRESUMEN
This corrects the article DOI: 10.1038/nature22364.
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BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. METHODS: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. RESULTS: We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10-4), which remained significant in multivariate analysis. CONCLUSIONS: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Inestabilidad Cromosómica , Heterogeneidad Genética , Neoplasias Pulmonares/genética , Mutación , Recurrencia Local de Neoplasia/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Variaciones en el Número de Copia de ADN , Supervivencia sin Enfermedad , Evolución Molecular , Exoma , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Filogenia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Análisis de Secuencia de ADN/métodosRESUMEN
The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Linaje de la Célula/genética , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Evolución Molecular , Neoplasias Pulmonares/genética , Metástasis de la Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Biopsia/métodos , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Rastreo Celular , Células Clonales/metabolismo , Células Clonales/patología , Análisis Mutacional de ADN , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Detección Precoz del Cáncer/métodos , Humanos , Límite de Detección , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Reacción en Cadena de la Polimerasa Multiplex , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Cuidados Posoperatorios/métodos , Reproducibilidad de los Resultados , Carga TumoralRESUMEN
We present five cases of cytomegalovirus (CMV) pneumonitis occurring in patients after recent T cell deplete allogeneic stem cell transplantation (AlloHSCT). These cases were complicated by an organising pneumonia (during the recovery period) with a predominantly central peribronchial pattern. All patients presented with evidence of active CMV pneumonitis which was treated successfully with anti-viral therapy but was followed by persistent severe dyspnoea, cough and hypoxia. High resolution computed tomography (HRCT) imaging showed widespread central peribronchial consolidation with traction bronchiectasis. There was a marked clinical and physiological improvement after treatment with systemic corticosteroids. However, in all patients the lung function remained abnormal and in some cases imaging revealed a fibrosing lung disease. These cases represent a previously undescribed central peribronchial pattern of organising pneumonia complicating CMV pneumonitis that can result in chronic lung damage.
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Patients with an unexplained pleural effusion often require urgent investigation. Clinical practice varies due to uncertainty as to whether an effusion should be drained completely before diagnostic imaging. We performed a retrospective study of patients undergoing medical thoracoscopy for an unexplained effusion. In 110 patients with paired (pre- and post-drainage) chest X-rays and 32 patients with paired computed tomography scans, post-drainage imaging did not provide additional information that would have influenced the clinical decision-making process.
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Drenaje , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Toracoscopía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Definitive diagnosis of pleural disease (particularly malignancy) depends upon histologic proof obtained via pleural biopsy or positive pleural fluid cytology. Image-guided sampling is now standard practice. Local anesthetic thoracoscopy has a high diagnostic yield for malignant and nonmalignant disease, but is not always possible in frail patients, if pleural fluid is heavily loculated, or where the lung is adherent to the chest wall. Such cases can be converted during the same procedure as attempted thoracoscopy to cutting-needle biopsy. This study aimed to determine the diagnostic yield of a physician-led service in both planned biopsies and cases of failed thoracoscopy. METHODS: This study was a retrospective review of all ultrasound-guided, cutting-needle biopsies performed at the Oxford Centre for Respiratory Medicine between January 2010 and July 2013. Histologic results were assessed for the yield of pleural tissue, final diagnosis, and clinical follow-up in nonmalignant cases. RESULTS: Fifty ultrasound-guided biopsies were undertaken. Overall, 47 (94.0%) successfully obtained sufficient tissue for histologic diagnosis. Of the 50 biopsy procedures, 13 were conducted after failed thoracoscopy (5.2% of 252 attempted thoracoscopies over the same time period); of these 13, 11 (84.6%) obtained sufficient tissue. Thirteen of 50 biopsy specimens (26.0%) demonstrated pleural malignancy on histology (despite previous negative pleural fluid cytology), while 34 specimens (68.0%) were diagnosed as benign. Of the benign cases, 10 were pleural TB, two were sarcoidosis, and 22 were benign pleural thickening. There was one "false negative" of mesothelioma (median follow-up, 16 months). CONCLUSIONS: Within this population, physician-based, ultrasound-guided, cutting-needle pleural biopsy obtained pleural tissue successfully in a high proportion of cases, including those of failed thoracoscopy.
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Biopsia con Aguja/métodos , Biopsia Guiada por Imagen/métodos , Pleura/patología , Enfermedades Pleurales/diagnóstico , Toracoscopía/métodos , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Médicos , Enfermedades Pleurales/patología , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To assess the repeatability in human volunteers of software-quantified small bowel motility captured with magnetic resonance (MR) imaging and to test the ability to detect changes in motility induced by pharmacologic agents. MATERIALS AND METHODS: The study was approved by the Royal Free Research Ethics Committee, and all subjects gave full written informed consent. Twenty-one healthy volunteers (14 men, seven women; mean age, 28 years) underwent cine MR imaging with a three-dimensional balanced turbo field-echo sequence to capture small bowel motility. Volume blocks (15 cm thick) were acquired every second during a 20-second breath hold. A randomized, blinded, placebo-controlled crossover study of either 0.5 mg neostigmine or saline (n = 11) or 20 mg intravenous butylscopolamine or saline (n = 10) was performed with motility MR imaging at baseline and repeated at a mean of 4 weeks (range, 2-7 weeks). Two readers independently drew regions of interest around the small bowel, and motility was quantified by using a registration algorithm that provided a global motility metric in arbitrary units. Repeatability of the motility measurements at baseline was assessed by using Bland-Altman and within-subject coefficient of variation measures. Changes in mean motility measurements after drug administration were compared with those after placebo administration by using paired t testing. RESULTS: The repeatability between baseline measurements of motility was high; the Bland-Altman mean difference was -0.0025 (range, 0.28-0.4), the 95% limit of agreement was ±0.044 arbitrary units (au), and the within-subject coefficient of variation was 4.9%. Measured motility with neostigmine (mean, 0.39 au) was significantly higher than that with placebo (mean, 0.34 au; P < .001), whereas that with butylscopolamine (mean, 0.13 au) was significantly lower than that with placebo (mean, 0.30 au; P < .001). CONCLUSION: Quantification of small bowel motility with use of MR imaging in healthy volunteers is repeatable and sensitive to changes induced by means of pharmacologic manipulation. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130151/-/DC1.