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Biomarcadores , Imunoglobulina G , Doenças Pulmonares Intersticiais , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/sangue , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/sangue , Biomarcadores/sangue , Feminino , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Masculino , Viscosidade Sanguínea/fisiologia , IdosoAssuntos
Empiema , Abscesso Pulmonar , Pneumonia , Teratoma , Humanos , Abscesso Pulmonar/complicações , Abscesso Pulmonar/diagnóstico por imagem , Empiema/complicações , Pneumonia/complicações , Pneumonia/diagnóstico por imagem , Teratoma/complicações , Teratoma/diagnóstico por imagem , Teratoma/cirurgiaRESUMO
BACKGROUND: Haematological malignancy is an important cause of pleural effusion. Pleural effusions secondary to haematological malignancy are usually lymphocyte predominant. However, several other conditions such as carcinoma, tuberculosis, and chronic heart failure also cause lymphocytic effusions. Lymphocyte subset (LS) analysis may be a useful test to identify haematological malignancy in patients with lymphocytic effusions. However, research into their utility in pleural effusion diagnostic algorithms has not yet been published. OBJECTIVES: We aimed to determine the clinical utility of pleural fluid LS analysis and whether it can be applied to a diagnostic algorithm to identify effusions secondary to haematological malignancy. The secondary aim was to evaluate the diagnostic value of pleural fluid differential cell count. METHODS: Consecutive consenting patients presenting to our pleural service between 2008 and 2013 underwent thoracentesis and differential cell count analysis. We proposed an algorithm which selected patients with lymphocytic effusions (>50%) to have further fluid sent for LS analysis. Two independent consultants agreed on the cause of the original effusion after a 12-month follow-up period. RESULTS: A total of 60 patients had samples sent for LS analysis. LS analysis had an 80% sensitivity (8/10) and a 100% specificity for the diagnosis of haematological malignancy. The positive and negative predictive values were 100 and 96.1%, respectively. Overall 344 differential cell counts were analysed; 16% of pleural effusions with a malignant aetiology were neutrophilic or eosinophilic at presentation. A higher neutrophil and eosinophil count was associated with benign diagnoses, whereas a higher lymphocyte count was associated with malignant diagnoses. CONCLUSIONS: LS analysis may identify haematological malignancy in a specific cohort of patients with undiagnosed pleural effusions. A pleural fluid differential cell count provides useful additional information to streamline patient pathway decisions.
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Subpopulações de Linfócitos , Derrame Pleural Maligno/diagnóstico , Algoritmos , Humanos , Contagem de Leucócitos , Derrame Pleural Maligno/citologia , Derrame Pleural Maligno/imunologia , Estudos ProspectivosRESUMO
BACKGROUND: Bacterial pleural infection requires prompt identification to enable appropriate investigation and treatment. In contrast to commonly used biomarkers such as C-reactive protein (CRP) and white cell count (WCC), which can be raised due to non-infective inflammatory processes, procalcitonin (PCT) has been proposed as a specific biomarker of bacterial infection. The utility of PCT in this role is yet to be validated in a large prospective trial. This study aimed to identify whether serum PCT is superior to CRP and WCC in establishing the diagnosis of bacterial pleural infection. METHODS: Consecutive patients presenting to a tertiary pleural service between 2008 and 2013 were recruited to a well-established pleural disease study. Consent was obtained to store pleural fluid and relevant clinical information. Serum CRP, WCC and PCT were measured. A diagnosis was agreed upon by two independent consultants after a minimum of 12 months. The study was performed and reported according to the STARD reporting guidelines. RESULTS: 80/425 patients enrolled in the trial had a unilateral pleural effusion secondary to infection. 10/80 (12.5%) patients had positive pleural fluid microbiology. Investigations for viral causes of effusion were not performed. ROC curve analysis of 425 adult patients with unilateral undiagnosed pleural effusions showed no statistically significant difference in the diagnostic utility of PCT (AUC 0.77), WCC (AUC 0.77) or CRP (AUC 0.85) for the identification of bacterial pleural infection. Serum procalcitonin >0.085 µg/l has a sensitivity, specificity, negative predictive value and positive predictive value of 0.69, 0.80, 0.46 and 0.91 respectively for the identification of pleural infection. The diagnostic utility of procalcitonin was not affected by prior antibiotic use (p = 0.80). CONCLUSIONS: The study presents evidence that serum procalcitonin is not superior to CRP and WCC for the diagnosis of bacterial pleural infection. The study suggests routine procalcitonin testing in all patients with unilateral pleural effusion is not beneficial however further investigation may identify specific patient subsets that may benefit. TRIAL REGISTRATION: The trial was registered with the UK Clinical Research Network ( UKCRN ID 8960 ). The trial was approved by the South West Regional Ethics Committee (Ethical approval number 08/H0102/11).
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Infecções Bacterianas/sangue , Infecções Bacterianas/diagnóstico , Proteína C-Reativa/análise , Calcitonina/sangue , Contagem de Leucócitos/estatística & dados numéricos , Derrame Pleural/sangue , Derrame Pleural/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/mortalidade , Biomarcadores/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Derrame Pleural/mortalidade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Reino Unido/epidemiologiaRESUMO
Pulmonary Fibrosis (PF) describes a group of lung diseases characterised by progressive scarring (fibrosis). Symptoms worsen over time and include breathlessness, tiredness, and cough, giving rise to psychological distress. Significant morbidity accompanies PF, so ensuring patients' care needs are well defined and provided for, represents an important treatment strategy. The purpose of this systematic review was to synthesise what is currently known about the psychosocial morbidity, illness experience and needs of people with pulmonary fibrosis and their informal caregivers. Eight databases (MEDLINE, EMBASE, PUBMED, Cochrane database of Systematic reviews (CDSR), Web of Science Social Sciences Citation Index, PsycINFO, PsycARTICLES and CINAHL) were used to identify studies exploring the supportive needs of adults with PF and/or their caregivers. Methodological quality was assessed using the Mixed Methods Appraisal Tool. 53 studies were included, the majority using qualitative methodology (79 %, 42/53), 6 as part of mixed methodological studies. Supportive care needs were mapped to eight domains using an a priori framework analysis. Findings highlight a lack of psychological support throughout the course of the illness, misconceptions about and barriers to, the provision of palliative care despite its potential positive impacts. Patients and caregivers express a desire for greater disease specific education and information provision throughout the illness. Trials of complex interventions are needed to address the unique set of challenges for patients and carers living with PF.
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Cuidadores , Fibrose Pulmonar , Humanos , Cuidadores/psicologia , Fibrose Pulmonar/psicologia , Fibrose Pulmonar/terapia , Cuidados Paliativos/psicologia , Apoio Social , Adulto , Masculino , Feminino , Qualidade de VidaRESUMO
Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.
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The oxygen-sensing transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a critical role in the regulation of myeloid cell function. The mechanisms of regulation are not well understood, nor are the phenotypic consequences of HIF modulation in the context of neutrophilic inflammation. Species conservation across higher metazoans enables the use of the genetically tractable and transparent zebrafish (Danio rerio) embryo to study in vivo resolution of the inflammatory response. Using both a pharmacologic approach known to lead to stabilization of HIF-1α, and selective genetic manipulation of zebrafish HIF-1α homologs, we sought to determine the roles of HIF-1α in inflammation resolution. Both approaches reveal that activated Hif-1α delays resolution of inflammation after tail transection in zebrafish larvae. This delay can be replicated by neutrophil-specific Hif activation and is a consequence of both reduced neutrophil apoptosis and increased retention of neutrophils at the site of tissue injury. Hif-activated neutrophils continue to patrol the injury site during the resolution phase, when neutrophils would normally migrate away. Site-directed mutagenesis of Hif in vivo reveals that hydroxylation of Hif-1α by prolyl hydroxylases critically regulates the Hif pathway in zebrafish neutrophils. Our data demonstrate that Hif-1α regulates neutrophil function in complex ways during inflammation resolution in vivo.
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Apoptose/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/imunologia , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Movimento Celular/imunologia , Modelos Animais de Doenças , Embrião não Mamífero/imunologia , Feminino , Variação Genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/imunologia , Proteínas de Peixe-Zebra/metabolismoRESUMO
INTRODUCTION: Interstitial lung disease (ILD) is a major cause of disease-related morbidity and one of the leading causes of mortality in patients with systemic sclerosis (SSc). Many patients will be diagnosed with SSc before the emergence of clinically meaningful ILD. Screening and early recognition of SSc-ILD allows prompt intervention and improved clinical outcomes. In recent years, clinical trial data from large well-designed randomized controlled trials have greatly enhanced our understanding of the natural history of SSc-ILD and risk factors for progressive disease. These advances have led to the emergence of treatment paradigms designed to address the management of both established and subclinical disease. AREAS COVERED: The present review shall consider the findings of recent trials and implications for modern pharmacological management of SSc-ILD. Where relevant, knowledge gaps shall be highlighted to outline the potential focus of additional research in this field. EXPERT OPINION: Recent clinical trial data have confirmed beyond doubt the value of immunomodulatory treatment in SSc-ILD, and it is expected this shall translate into improved clinical outcomes in SSc-ILD. We need better methods of cohort enrichment for SSc-ILD clinical trials, and biomarker discovery may establish molecular signatures allowing more personalized approaches to SSc-ILD prevention and management.
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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Escleroderma Sistêmico/complicações , Fatores de Risco , Pulmão , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
A 46-year-old woman presented with sudden onset of shortness of breath and pleuritic chest pain. A CT pulmonary angiogram identified a 5 cm cement pulmonary embolus within the right main pulmonary artery with a surrounding thrombus. She had undergone an L4 vertebroplasty 3 years prior to presentation for a benign lytic lesion. Cement embolus is a known complication of cement vertebroplasty with incidence rates of approximately 0.9%. Management is usually conservative and associated morbidity and mortality rates are low. It is not known whether a previous cement embolus could provide a nidus for thrombus formation.
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Embolia Pulmonar , Vertebroplastia , Cimentos Ósseos/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/etiologia , Vertebroplastia/efeitos adversosRESUMO
Introduction: Internationally it is estimated that six million people participate in self-contained underwater breathing apparatus (SCUBA) diving each year. Registries suggest a significant proportion of divers have a current or historical diagnosis of asthma. Previously individuals with asthma were prohibited from diving, however, several contemporary guidelines suggest a select population of patients with asthma may be able to dive with an acceptable degree of risk. Areas covered: Divers with asthma may be at an increased risk of a variety of diving-related medical injuries including; pulmonary barotrauma (PBT), pneumothorax, pneumomediastinum, arterial gas embolism (AGE), reduction in pulmonary function, bronchospasm and decompression sickness (DCS). This article will discuss the latest evidence on the incidence of adverse events in diving with a focus on those caused by asthma. Expert opinion: Physicians can be faced with the difficult task of counseling patients with asthma who wish to dive. This review article will aim to explore the current guidelines which can assist a physician in providing a comprehensive dive safety assessment.
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Asma/complicações , Mergulho/efeitos adversos , Espasmo Brônquico/etiologia , Doença da Descompressão/etiologia , Humanos , Lesão Pulmonar/etiologia , Pneumotórax/etiologiaRESUMO
Undiagnosed pleural effusions present an increasing diagnostic burden upon healthcare providers internationally. The investigation of pleural effusions often requires the acquisition of tissue for histological analysis and diagnosis. Historically there were two options for tissue biopsy: a 'gold standard' surgical biopsy or a "blind" closed pleural biopsy. Over the last decade however, image-guided Tru-cut biopsies and local anaesthetic thoracoscopic (local anaesthetic thoracoscopy) biopsies have become more widespread. Image-guided techniques acquire samples under ultrasound (US) or computed tomography (CT) guidance whereas LAT involves the direct visualisation and biopsy of the pleura with pleuroscopy. Both techniques have been shown to be superior to 'blind' closed pleural biopsy for the diagnosis of pleural or metastatic malignancy. However, closed biopsy remains a viable method of investigation in areas of high incidence of tuberculosis (TB). Beyond this, each investigative technique has its own advantages and disadvantages. Image-guided biopsy is less invasive, usually carried out as an outpatient procedure, and enables tissue biopsy in frail patients and those with pleural thickening but no pleural fluid. Local anaesthetic thoracoscopy (LAT) provides diagnostic and therapeutic capabilities in one procedure. Large volume thoracentesis, multiple pleural biopsies and talc poudrage can be carried out in a single procedure. The overall diagnostic yield is similar for both techniques, although there are no large-scale direct comparisons. Both techniques share low complication rates.
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Oxygen is one of the most commonly administered drugs in UK hospitals. Our quality improvement project aimed to increase the safety of oxygen therapy at University Hospitals Bristol NHS Foundation Trust. We aimed to increase the rate of oxygen prescribing and increase the percentage of nurses signing appropriately for oxygen titration and administration. We hypothesised this would result in a higher percentage of patients achieving their appropriate oxygen saturations. Our project ran on several acute medical and surgical wards. We tested several interventions with a plan, do, study, act method of continuous data collection. We firstly focussed on the education of junior doctors and then the wider multi-disciplinary team with a trust-wide "safety focus". We utilised patient safety systems already in place in the hospital, such as the clinical risk register and incident reporting system. We also trialled an intervention that was successfully implemented by another group in a different trust in the UK. Oxygen prescription increased from 44.4% to 76.9% over the duration of the project. Appropriate nursing signatures increased from 26.6% to 60%. The number of patients achieving appropriate target saturations rose from 61.8% to 76.7%. The most successful interventions were the trust safety briefing and oxygen safety hangers. Our project has showed the importance of integrating new projects within safety schemes already available. Persistence and careful intervention are key to changing strongly engrained cultures in large organisations. Interventions that have proved to be successful in other trusts can be implemented to enact change.
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Cell migration is a vital process in living organisms. In particular we are interested in the way that white blood cells such as neutrophils migrate during episodes of inflammation which are important events in the working of the innate immune system. Migration of populations of many kinds can be modelled using drift-diffusion models by drawing analogies between the individual agents and the molecules in a fluid. It is challenging to arrive at a data-driven estimate of the parameters of this kind of process, particularly so if the individual agents have time varying properties that are not uniform over the population. In this paper, we offer a novel framework to estimate migration dynamics in this context. It makes use of the Approximate Bayesian Computation approach for parameter estimation and model selection. The Framework is applied to zebrafish neutrophil dynamics but is applicable for general migration scenarios.
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Neutrófilos/citologia , Algoritmos , Animais , Teorema de Bayes , Movimento Celular , Modelos Biológicos , Método de Monte Carlo , Peixe-ZebraRESUMO
Neutrophil function is thought to be regulated, in large part, by limitation of lifespan by apoptosis. A number of studies suggest that circulating neutrophils have a half-life of approximately 6 hours, although contradictory evidence exists. Measuring tissue neutrophil lifespan, however, is more problematic. It is thought that tissue neutrophils survive longer, perhaps with a half-life in the order of 3-5 days, but this has never been directly measured. Zebrafish are an emerging model organism, with several advantages for the study of vertebrate immunity. In zebrafish, neutrophils constitutively assume tissue locations allowing their direct study in vivo. Using a transgenic approach, neutrophils were labelled with a photoconvertible pigment, Kaede. Photoconversion parameters were optimised and the stability of the Kaede confirmed. Individual neutrophils were photoconverted by scanning a confocal 405 nm laser specifically over each cell and their survival monitored for 48 hours, revealing an in vivo half-life for zebrafish tissue neutrophils of around 120 hours (117.7 hrs, 95% CI 95.67-157.8). Laser energy did not extend neutrophil lifespan, and we conclude that this represents a lower bound for the lifespan of a resting tissue neutrophil in the developing zebrafish larva. This is the first direct measurement of the lifespan of an in vivo tissue neutrophil.
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Following neutralization of infectious threats, neutrophils must be removed from inflammatory sites for normal tissue function to be restored. Recently, a new paradigm has emerged, in which viable neutrophils migrate away from inflammatory sites by a process best described as reverse migration. It has generally been assumed that this process is the mirror image of chemotaxis, where neutrophils are drawn into the areas of infection or tissue damage by gradients of chemotactic cues. Indeed, efforts are underway to identify cues that drive neutrophils away by the reverse process, fugetaxis. By using photoconvertible pigments expressed in neutrophils in transparent zebrafish larvae, we were able to image the position of each neutrophil during inflammation resolution in vivo. These neutrophil coordinates were analysed within a dynamic modelling framework, using different forms of the drift-diffusion equation with model selection and parameter estimation based on approximate Bayesian computation. This analysis revealed the experimental data were best fitted by a model incorporating a diffusion term but no drift term-where the presence of drift would indicate fugetaxis. This result, for the first time, provides rigorous data-driven evidence that reverse migration of neutrophils in vivo is not a form of fugetaxis, but rather a stochastic redistribution.
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Movimento Celular , Modelos Biológicos , Neutrófilos/fisiologia , Cicatrização , Peixe-Zebra/imunologia , Animais , Teorema de Bayes , Inflamação/imunologia , Processos EstocásticosRESUMO
Neutrophils must be removed from inflammatory sites for inflammation to resolve. Recent work in zebrafish has shown neutrophils can migrate away from inflammatory sites, as well as die in situ. The signals regulating the process of reverse migration are of considerable interest, but remain unknown. We wished to study the behaviour of neutrophils during reverse migration, to see whether they moved away from inflamed sites in a directed fashion in the same way as they are recruited or whether the inherent random component of their migration was enough to account for this behaviour. Using neutrophil-driven photoconvertible Kaede protein in transgenic zebrafish larvae, we were able to specifically label neutrophils at an inflammatory site generated by tailfin transection. The locations of these neutrophils over time were observed and fitted using regression methods with two separate models: pure-diffusion and drift-diffusion equations. While a model hypothesis test (the F-test) suggested that the datapoints could be fitted by the drift-diffusion model, implying a fugetaxis process, dynamic simulation of the models suggested that migration of neutrophils away from a wound is better described by a zero-drift, "diffusion" process. This has implications for understanding the mechanisms of reverse migration and, by extension, neutrophil retention at inflammatory sites.