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Familial spontaneous pneumothorax (FSP) accounts for 10% of primary spontaneous pneumothoraces. Appropriate investigation of FSP enables early diagnosis of serious monogenic diseases and the practice of precision medicine. Here, we show that a pneumothorax genetics multidisciplinary team (MDT) can efficiently diagnose a range of syndromic causes of FSP. A sizeable group (73.6%) of clinically unclassifiable FSPs remains. Using whole genome sequencing we demonstrate that most of these cases are not known monogenic disorders. Therefore, clinico-radiological assessment by an MDT has high sensitivity for currently known clinically important monogenic causes of FSP, which has relevance for the design of efficient pneumothorax services.
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Pneumotórax , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/genética , Pneumotórax/terapia , Medicina de PrecisãoRESUMO
INTRODUCTION: Pneumothorax and pneumomediastinum have both been noted to complicate cases of coronavirus disease 2019 (COVID-19) requiring hospital admission. We report the largest case series yet described of patients with both these pathologies (including nonventilated patients). METHODS: Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival. RESULTS: 71 patients from 16 centres were included in the study, of whom 60 had pneumothoraces (six with pneumomediastinum in addition) and 11 had pneumomediastinum alone. Two of these patients had two distinct episodes of pneumothorax, occurring bilaterally in sequential fashion, bringing the total number of pneumothoraces included to 62. Clinical scenarios included patients who had presented to hospital with pneumothorax, patients who had developed pneumothorax or pneumomediastinum during their inpatient admission with COVID-19 and patients who developed their complication while intubated and ventilated, either with or without concurrent extracorporeal membrane oxygenation. Survival at 28â days was not significantly different following pneumothorax (63.1±6.5%) or isolated pneumomediastinum (53.0±18.7%; p=0.854). The incidence of pneumothorax was higher in males. 28-day survival was not different between the sexes (males 62.5±7.7% versus females 68.4±10.7%; p=0.619). Patients aged ≥70 years had a significantly lower 28-day survival than younger individuals (≥70â years 41.7±13.5% survival versus <70â years 70.9±6.8% survival; p=0.018 log-rank). CONCLUSION: These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and we encourage continuation of active treatment where clinically possible.
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COVID-19/complicações , Enfisema Mediastínico/epidemiologia , Enfisema Mediastínico/virologia , Pneumotórax/epidemiologia , Pneumotórax/virologia , SARS-CoV-2 , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Oxigenação por Membrana Extracorpórea , Feminino , Hospitalização , Humanos , Incidência , Masculino , Enfisema Mediastínico/terapia , Pessoa de Meia-Idade , Pneumotórax/terapia , Prognóstico , Respiração Artificial , Estudos Retrospectivos , Fatores Sexuais , Taxa de Sobrevida , Reino Unido , Adulto JovemRESUMO
In the original version of this article unfortunately two authors were missing: Dr. Jürgen Weidemann and Dr. Daniel Berthold. The correct list of authors is presented above.
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Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.
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Brônquios/patologia , Síndromes de Imunodeficiência/patologia , Parede Torácica/patologia , Adolescente , Adulto , Idoso , Bronquiectasia/patologia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/patologia , Feminino , Humanos , Lactente , Masculino , Espirometria/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
RATIONALE: There is a need to develop imaging protocols which assess neutrophilic inflammation in the lung. AIM: To quantify whole lung neutrophil accumulation in (1) healthy volunteers (HV) following inhaled lipopolysaccharide (LPS) or saline and (2) patients with COPD using radiolabelled autologous neutrophils and single-photon emission computed tomography/CT (SPECT/CT). METHODS: 20 patients with COPD (Global initiative for chronic obstructive lung disease (GOLD) stages 2-3) and 18 HVs were studied. HVs received inhaled saline (n=6) or LPS (50 µg, n=12) prior to the injection of radiolabelled cells. Neutrophils were isolated using dextran sedimentation and Percoll plasma gradients and labelled with 99mTechnetium (Tc)-hexamethylpropyleneamine oxime. SPECT was performed over the thorax/upper abdomen at 45 min, 2 hours, 4 hours and 6 hours. Circulating biomarkers were measured prechallenge and post challenge. Blood neutrophil clearance in the lung was determined using Patlak-Rutland graphical analysis. RESULTS: There was increased accumulation of 99mTc-neutrophils in the lungs of patients with COPD and LPS-challenged subjects compared with saline-challenged subjects (saline: 0.0006±0.0003 mL/min/mL lung blood distribution volume [mean ±1 SD]; COPD: 0.0022±0.0010 mL/min/mL [p<0.001]; LPS: 0.0025±0.0008 mL/min/mL [p<0.001]). The accumulation of labelled neutrophils in 10 patients with COPD who underwent repeat radiolabelling/imaging 7-10 days later was highly reproducible (0.0022±0.0010 mL/min/mL vs 0.0023±0.0009 mL/min/mL). Baseline interleukin (IL)-6 levels in patients with COPD were elevated compared with HVs (1.5±1.06 pg/mL [mean ±1 SD] vs 0.4±0.24 pg/mL). LPS challenge increased the circulating IL-6 levels (7.5±2.72 pg/mL) 9 hours post challenge. CONCLUSIONS: This study shows the ability to quantify 'whole lung' neutrophil accumulation in HVs following LPS inhalation and in subjects with COPD using autologous radiolabelled neutrophils and SPECT/CT imaging. Moreover, the reproducibility observed supports the feasibility of using this approach to determine the efficacy of therapeutic agents aimed at altering neutrophil migration to the lungs.
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Pulmão/diagnóstico por imagem , Neutrófilos/fisiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Idoso , Biomarcadores/sangue , Feminino , Humanos , Interleucina-6/sangue , Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Reprodutibilidade dos Testes , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , TecnécioRESUMO
BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. RESULTS: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. CONCLUSION: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.
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Classe I de Fosfatidilinositol 3-Quinases/genética , Síndromes de Imunodeficiência/genética , Transtornos Linfoproliferativos/genética , Mutação/genética , Infecções Respiratórias/genética , Adolescente , Adulto , Animais , Antibioticoprofilaxia , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Estudos de Coortes , Inibidores Enzimáticos/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/mortalidade , Infecções por Herpesviridae/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/terapia , Lactente , Cooperação Internacional , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva , Infecções Respiratórias/mortalidade , Infecções Respiratórias/terapia , Inquéritos e Questionários , Análise de Sobrevida , Adulto JovemRESUMO
The reported incidence of ARDS is highly variable (2.5%-19% of intensive care unit (ICU) patients) and varies depending on study patient population used. We undertook a 6-month, prospective study to determine the incidence and outcome of ARDS in a UK adult University Hospital ICU. 344 patients were admitted during the study period, of these 43 (12.5%) were determined to have ARDS. Patients with ARDS had increased mortality at 28 days and 2 years post-diagnosis, and there was under-recognition of ARDS in both medical records and death certificattion. Our findings have implications for critical care resource planning.
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Unidades de Terapia Intensiva , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/epidemiologia , Diagnóstico Diferencial , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório/mortalidade , Taxa de SobrevidaRESUMO
The National COVID-19 Chest Imaging Database (NCCID) is a centralized UK database of thoracic imaging and corresponding clinical data. It is made available by the National Health Service Artificial Intelligence (NHS AI) Lab to support the development of machine learning tools focused on Coronavirus Disease 2019 (COVID-19). A bespoke cleaning pipeline for NCCID, developed by the NHSx, was introduced in 2021. We present an extension to the original cleaning pipeline for the clinical data of the database. It has been adjusted to correct additional systematic inconsistencies in the raw data such as patient sex, oxygen levels and date values. The most important changes will be discussed in this paper, whilst the code and further explanations are made publicly available on GitLab. The suggested cleaning will allow global users to work with more consistent data for the development of machine learning tools without being an expert. In addition, it highlights some of the challenges when working with clinical multi-center data and includes recommendations for similar future initiatives.
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COVID-19 , Tórax , Humanos , Inteligência Artificial , Aprendizado de Máquina , Medicina Estatal , Radiografia Torácica , Tórax/diagnóstico por imagemRESUMO
Neutrophils are the most abundant circulating white cell in humans and play a crucial role in the innate immune response. Accumulation and activation of neutrophils, together with delayed clearance, have been shown to be a key event in the pathogenesis of acute lung injury. Previously, it has been proposed that there is substantial pooling of neutrophils within the pulmonary vasculature, even under physiological conditions, making the lung especially vulnerable to neutrophil-mediated tissue injury. However, more recent evidence suggests that only primed neutrophils accumulate in the pulmonary vasculature. This article examines the evidence for these two opposing views and proposes a new two-step model for the recruitment of neutrophils into the lung. Firstly, neutrophils that become primed, by exposure to a range of inflammatory mediators or physicochemical perturbations, become shape changed and stiff because of alterations in their cytoskeleton, and as a result, accumulate within the pulmonary circulation. In the absence of further stimuli, the healthy pulmonary vasculature is able to selectively retained these primed cells, allow them to 'de-prime' and be released back into the circulation in a quiescent, state. If this pulmonary 'de-priming' mechanism fails, or a second insult occurs, such as ventilator-associated barotrauma, which causes loss of alveolar integrity, primed neutrophils migrate from the pulmonary vasculature into the interstitial space with resultant lung injury. This canonical 'two step' model highlights the importance of neutrophil priming in the genesis of lung injury and the importance of adopting strategies to minimise alveolar injury.
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Lesão Pulmonar Aguda/etiologia , Ativação de Neutrófilo/fisiologia , Neutrófilos/fisiologia , Circulação Pulmonar/fisiologia , Lesão Pulmonar Aguda/imunologia , Animais , Humanos , Modelos Animais , Modelos Biológicos , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Circulação Pulmonar/imunologiaRESUMO
OBJECTIVE: We evaluated the reliability of various multidetector computed tomography (MDCT) parameters for diagnosis and severity assessment of pulmonary hypertension (PH) with consideration of World Health Organization (WHO) classification. METHODS: A total of 172 patients were included in this retrospective study. One hundred fourteen patients had a diagnosis of PH (mean pulmonary artery pressure ≥25 mm Hg), and 58 patients without PH (mean pulmonary artery pressure <20 mm Hg) served as control subjects. The patients with PH were grouped according to the WHO classification based on PH etiology. RESULTS: The patients with PH had significantly greater main, left, and right pulmonary artery diameters than the control subjects (P < 0.001). No significant differences within the PH subgroups were found. Receiver operating characteristic analysis showed reasonable sensitivity and specificity for selected MDCT parameters. The severity of PH did not correlate with MDCT parameters. CONCLUSIONS: Easy-to-determine MDCT parameters allow detection of PH independent of the WHO group. In patients with dilated aorta, the vertebra can be an alternative internal standard. Severity of PH cannot be estimated by MDCT parameters.
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Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Cateterismo Cardíaco , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Organização Mundial da SaúdeRESUMO
BACKGROUND: CT pulmonary angiography (CTPA) is an increasingly popular imaging test for assessing patients with acute chest pain. PURPOSE: To evaluate the number of CTPA performed in 2009 compared with 2006 and assess the frequency of pulmonary embolus (PE) versus alternative diagnoses. MATERIAL AND METHODS: Numbers of CTPA and V/Q scans performed in a six-month period of 2006 and 2009 were established by review of the hospital radiology information system. CTPAs were evaluated by two radiologists in consensus and the incidence of pulmonary embolism and alternative diagnoses in 2006 and 2009 were recorded. RESULTS: The final study groups were 99 patients who underwent CTPA in 2006 and 149 patients in 2009. There was a significant fall in the incidence of PE identified on CTPA in 2009 compared to 2006 (11% versus 21%, P = 0.04). There was a non-significant rise in the incidence of alternative diagnoses in 2009 compared to 2006 (45% versus 40%, P = 0.48). Nine types of alternative radiological diagnoses were made on CTPA, the most common of which was pneumonia in both time periods (17% and 12%). Eighty-seven V/Q scans were performed in the study period in 2006, compared to 109 in 2009. The incidence of PE identified on V/Q scanning remained stable (8% in 2009 versus 12% in 2006, P = 0.44). CONCLUSION: The numbers of CTPAs being performed has increased in three years. The incidence of PE identified has fallen and there has been a modest increase in the number of alternative diagnoses.
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Pneumopatias/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Encaminhamento e Consulta/estatística & dados numéricos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Pneumonia/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Sistemas de Informação em Radiologia , Adulto JovemRESUMO
Tuberculosis remains a major global health issue affecting all countries and age groups. Radiology plays a crucial role in the diagnosis and management of pulmonary tuberculosis (PTB). This review aims to improve understanding and diagnostic value of imaging in PTB. We present the old, well-established findings ranging from primary TB to the common appearances of post-primary TB, including dissemination with tree-in-bud nodularity, haematogenous dissemination with miliary nodules and lymphatic dissemination. We discuss new concepts in active PTB with special focus on imaging findings in immunocompromised individuals. We illustrate PTB appearances borrowed from other diseases in which the signs were initially described: the reversed halo sign, the galaxy sign and the cluster sign. There are several radiological signs that have been shown to correlate with positive or negative sputum smears, and radiologists should be aware of these signs as they play an important role in guiding the need for isolation and empirical anti-tuberculous therapy.
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Hypothesis/Gap Statement. The impacts of increased biomarker testing on antifungal prescribing have not yet been fully examined in a real-life setting.Objectives. Biomarkers for invasive fungal disease (IFD) have been shown to reduce antifungal prescriptions in neutropaenic haemato-oncology patients. Our study aimed to assess the real-life impacts of introducing a novel biomarker-based pathway, incorporating serum galactomannan and Aspergillus PCR, for pyrexial haemato-oncology admissions.Methods. Patients with neutropaenic fever were identified prospectively after introduction of the new pathway from 2013-2015. A historical group of neutropaenic patients who had blood cultures taken from 2009-2012 was generated for comparison. Clinical details, including demographics, underlying diagnosis, investigations, radiology and antimicrobial treatment were obtained.Results. Prospective data from 308 patients were compared to retrospective data from 302 patients. The proportion of patients prescribed an antifungal medication was unchanged by the pathway (P=0.79), but the pattern was different, with more patients receiving targeted antifungals (P=0.04). A negative serum galactomannan test was not sufficient evidence to withhold therapy, with 17.2% of these episodes felt to have possible or probable IFD using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. There was no difference in 30-day mortality (P=0.21) or 1-year mortality (P=0.57) following introduction of the pathway.Conclusions. Biomarkers can be used safely as part of a multidisciplinary approach to the diagnosis of IFD in neutropaenic haemato-oncology patients. Whilst they do not necessarily result in antifungal therapy being withheld, they can allow more confident diagnosis of IFD and more specific antifungal therapy in selected cases.
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Infecções Fúngicas Invasivas , Micoses , Neoplasias , Antifúngicos/uso terapêutico , Biomarcadores/análise , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Micoses/diagnóstico , Neoplasias/complicações , Estudos Prospectivos , Estudos RetrospectivosRESUMO
INTRODUCTION: Without universal access to point-of-care SARS-CoV-2 testing, many hospitals rely on clinical judgement alone for identifying cases of COVID-19 early. METHODS: Cambridge University Hospitals NHS Foundation Trust introduced a 'traffic light' clinical judgement aid to the COVID-19 admissions unit in mid-March 2020. Ability to accurately predict COVID-19 was audited retrospectively across different stages of the epidemic. RESULTS: One SARS-CoV-2 PCR positive patient (1/41, 2%) was misallocated to a 'green' (non-COVID-19) area during the first period of observation, and no patients (0/32, 0%) were mislabelled 'green' during the second period. 33 of 62 (53%) labelled 'red' (high risk) tested SARS-CoV-2 PCR positive during the first period, while 5 of 22 (23%) 'red' patients were PCR positive in the second. CONCLUSION: COVID-19 clinical risk stratification on initial assessment effectively identifies non-COVID-19 patients. However, diagnosing COVID-19 is challenging and risk of overcalling COVID-19 should be recognised, especially when background prevalence is low.
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Teste para COVID-19 , COVID-19 , Medição de Risco , Humanos , Estudos Retrospectivos , SARS-CoV-2Assuntos
Embolia Gordurosa/complicações , Hemorragia Retiniana/complicações , Fraturas da Tíbia/complicações , Lesão Pulmonar Aguda/diagnóstico por imagem , Lesão Pulmonar Aguda/etiologia , Adulto , Dispneia/etiologia , Embolia Gordurosa/etiologia , Humanos , Masculino , Hemorragia Retiniana/diagnóstico , Síndrome , Tomografia Computadorizada por Raios X , Transtornos da Visão/etiologiaRESUMO
We describe two cases of patients with emphysema who, in the lead up to hyperinflation intervention, developed pneumonia with significant physiological, anatomical, functional and quality of life improvement observed following. This directly goes against the natural history of both disease processes, demonstrating the benefit resulting from infective autobullectomy.
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Objectives: To estimate the prevalence of non-calcified coronary artery disease (CAD) in patients with suspected stable angina and a zero coronary artery calcification (CAC) score, and to assess the prognostic significance of a zero CAC in these symptomatic patients. Methods: In this prospective cohort study, consecutive patients with stable chest pain underwent CAC scoring ± CT coronary angiography (CTCA) as part of routine clinical care at a single tertiary centre over 7 years. Major adverse cardiac event (MACE) was defined as cardiac death, non-fatal myocardial infarction and/or non-elective revascularisation. Results: A total of 915 of 1753 (52.2%) patients (mean age 56.8 ± 12.0 years; 46.2% male) had a zero CAC score. Of the 751 (82.1%) patients with a zero CAC in whom CTCA was performed, 674 (89.7%) had normal coronary arteries, 63 (8.4%) had non-calcified CAD with < 50% stenosis and 14 (1.9%) had ≥ 50% stenosis in at least one coronary artery. The negative predictive value of a zero CAC for excluding a ≥ 50% CTCA stenosis was 98.1%. Over a median follow-up period of 2.2 years (range 1.0-7.0 years), the absolute annualised rates of MACE were as follows: zero CAC 1.9 per 1000 person-years and non-zero CAC 7.4 per 1000 person-years (HR 3.8, p = 0.009). However, after adjusting for age, gender and cardiovascular risk factors using a multivariable Cox proportional hazards model, there was no statistically significant difference in the risk of MACE between the two patient cohorts (p = 0.19). After adjusting for age, gender and cardiovascular risk factors, the HR for all-cause mortality among the zero CAC cohort vers non-zero CAC was 2.1 (p = 0.27). Conclusion: A zero CAC score in patients undergoing CT scanning for suspected stable angina has a high negative predictive value for the exclusion of obstructive CAD and is associated with a good medium-term prognosis.
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BACKGROUND: The lymphocyte-depleting antibody alemtuzumab is a highly effective treatment of relapsing-remitting multiple sclerosis (RRMS); however 50% of patients develop novel autoimmunity post-treatment. Most at risk are individuals who reconstitute their T-cell pool by proliferating residual cells, rather than producing new T-cells in the thymus; raising the possibility that autoimmunity might be prevented by increasing thymopoiesis. Keratinocyte growth factor (palifermin) promotes thymopoiesis in non-human primates. METHODS: Following a dose-tolerability sub-study, individuals with RRMS (duration ≤10 years; expanded disability status scale ≤5·0; with ≥2 relapses in the previous 2 years) were randomised to placebo or 180mcg/kg/day palifermin, given for 3 days immediately prior to and after each cycle of alemtuzumab, with repeat doses at M1 and M3. The interim primary endpoint was naïve CD4+ T-cell count at M6. Exploratory endpoints included: number of recent thymic-emigrants (RTEs) and signal-joint T-cell receptor excision circles (sjTRECs)/mL of blood. The trial primary endpoint was incidence of autoimmunity at M30. FINDINGS: At M6, individuals receiving palifermin had fewer naïve CD4+T-cells (2.229x107/L vs. 7.733x107/L; p=0.007), RTEs (16% vs. 34%) and sjTRECs/mL (1100 vs. 3396), leading to protocol-defined termination of recruitment. No difference was observed in the rate of autoimmunity between the two groupsConclusion: In contrast to animal studies, palifermin reduced thymopoiesis in our patients. These results offer a note of caution to those using palifermin to promote thymopoiesis in other settings, particularly in the oncology/haematology setting where alemtuzumab is often used as part of the conditioning regime. TRIAL REGISTRATION: ClinicalTrials.gov NCT01712945Funding: MRC and Moulton Charitable Foundation.