High resolution optical and acoustic remote sensing datasets of the Puck Lagoon.

The very shallow marine basin of Puck Lagoon in the southern Baltic Sea, on the Northern coast of Poland, hosts valuable benthic habitats and cultural heritage sites. These include, among others, protected Zostera marina meadows, one of the Baltic's major medieval harbours, a ship graveyard, and likely other submerged features that are yet to be discovered. Prior to this project, no comprehensive high-resolution remote sensing data were available for this area. This article describes the first Digital Elevation Models (DEMs) derived from a combination of airborne bathymetric LiDAR, multibeam echosounder, airborne photogrammetry and satellite imagery. These datasets also include multibeam echosounder backscatter and LiDAR intensity, allowing determination of the character and properties of the seafloor. Combined, these datasets are a vital resource for assessing and understanding seafloor morphology, benthic habitats, cultural heritage, and submerged landscapes. Given the significance of Puck Lagoon's hydrographical, ecological, geological, and archaeological environs, the high-resolution bathymetry, acquired by our project, can provide the foundation for sustainable management and informed decision-making for this area of interest.

PET-CT-guided versus CT-guided biopsy in suspected malignant pleural thickening: a randomised trial.

BACKGROUND: Pleural biopsy is the gold standard for diagnosis of pleural malignancy but a significant proportion will have an inconclusive biopsy despite ongoing clinical suspicion of malignancy. We investigated whether positron emission tomography-computed tomography (PET-CT) targeted pleural biopsy is superior to standard CT-guided pleural biopsy following an initial non-diagnostic biopsy. METHODS: The TARGET trial was a multicentre, parallel group randomised trial. Patients with a previous inconclusive pleural biopsy but an ongoing suspicion of pleural malignancy were randomised (1:1) to receive either CT-guided biopsy (standard care) or PET-CT followed by a targeted CT biopsy (intervention). The primary outcome was pleural malignancy correctly identified from the trial biopsy. RESULTS: Between September 2015 and September 2018, 59 participants were randomised from eight UK hospital sites: 29 to CT-only followed by targeted biopsy and 30 to PET-CT followed by targeted biopsy. The proportion of pleural malignancy correctly identified was similar between the groups (risk ratio 1.03 (95% CI 0.83-1.29); p=0.77). The sensitivity of the trial biopsy to identify pleural malignancy was 79% (95% CI 54-94%) in the CT-only group versus 81% (95% CI 54-96%) in the PET-CT group. CONCLUSIONS: The results do not support the practice of PET-CT to guide pleural biopsies in patients with a previous non-diagnostic biopsy. The diagnostic sensitivity in the CT-only group was higher than anticipated and supports the practice of repeating a CT-guided biopsy following an inconclusive result if clinical suspicion of malignancy persists.

Why the geosciences are becoming increasingly vital to the interpretation of the human evolutionary record.

Advanced geoscience techniques are essential to contextualize fossils, artefacts and other archaeologically important material accurately and effectively. Their appropriate use will increase confidence in new interpretations of the fossil and archaeological record, providing important information about the life and depositional history of these materials and so should form an integral component of all human evolutionary studies. Many of the most remarkable recent finds that have transformed the field of human evolution are small and scarce, ranging in size from teeth to strands of DNA, recovered from complex sedimentary environments. Nevertheless, if properly analysed, they hold immense potential to rewrite what we know about the evolution of our species and our closest hominin ancestors.

Impact of SARS-CoV-2 infective exacerbation of chronic obstructive pulmonary disease on clinical outcomes in a prospective cohort study of hospitalised adults.

OBJECTIVES: To determine whether acute exacerbations of chronic obstructive pulmonary disease (AECOPD) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have worse outcomes than AECOPD caused by other infectious agents or non-infective AECOPD (NI-COPD). DESIGN: A two-hospital prospective cohort study of adults hospitalised with acute respiratory disease. We compared outcomes with AECOPD and a positive test for SARS-CoV-2 (n = 816), AECOPD triggered by other infections (n = 3038) and NI-COPD (n = 994). We used multivariable modelling to adjust for potential confounders and assessed variation by seasons associated with different SARS-CoV-2 variants. SETTING: Bristol UK, August 2020-May 2022. PARTICIPANTS: Adults (≥18 y) hospitalised with AECOPD. MAIN OUTCOME MEASURES: We determined the risk of positive pressure support, longer hospital admission and mortality following hospitalisation with AECOPD due to non-SARS-CoV-2 infection compared with SARS-CoV-2 AECOPD and NI-COPD. RESULTS: Patients with SARS-CoV-2 AECOPD, in comparison to non-SARS-CoV-2 infective AECOPD or NI-COPD, more frequently required positive pressure support (18.5% and 7.5% vs. 11.7%, respectively), longer hospital stays (median [interquartile range, IQR]: 7 [3-15] and 5 [2-10] vs. 4 [2-9] days, respectively) and had higher 30-day mortality (16.9% and 11.1% vs. 5.9%, respectively) (all p < 0.001). In adjusted analyses, SARS-CoV-2 AECOPD was associated with a 55% (95% confidence interval [95% CI]: 24-93), 26% (95% CI: 15-37) and 35% (95% CI: 10-65) increase in the risk of positive pressure support, hospitalisation length and 30-day mortality, respectively, relative to non-SARS-CoV-2 infective AECOPD. The difference in risk remained similar during periods of wild-type, Alpha and Delta SARS-CoV-2 strain dominance, but diminished during Omicron dominance. CONCLUSIONS: SARS-CoV-2-related AECOPD had worse patient outcomes compared with non-SARS-CoV-2 AECOPD or NI-AECOPD, although the difference in risks was less pronounced during Omicron dominance.

Severity of Omicron (B.1.1.529) and Delta (B.1.617.2) SARS-CoV-2 infection among hospitalised adults: A prospective cohort study in Bristol, United Kingdom.

Background: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity. Methods: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection. Findings: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 [Relative Risk (RR) = 0.42 (95%CI: 0.34-0.52), P < 0.001], WHO outcome score >5 [RR = 0.33 (95%CI: 0.21-0.50), P < 0.001], and to have had a LOS > 3 days [RR = 0.84 (95%CI: 0.76-0.92), P < 0.001]. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Interpretation: We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

Incidence of community acquired lower respiratory tract disease in Bristol, UK during the COVID-19 pandemic: A prospective cohort study.

Background: The emergence of COVID-19 and public health measures implemented to reduce SARS-CoV-2 infections have both affected acute lower respiratory tract disease (aLRTD) epidemiology and incidence trends. The severity of COVID-19 and non-SARS-CoV-2 aLRTD during this period have not been compared in detail. Methods: We conducted a prospective cohort study of adults age ≥18 years admitted to either of two acute care hospitals in Bristol, UK, from August 2020 to November 2021. Patients were included if they presented with signs or symptoms of aLRTD (e.g., cough, pleurisy), or a clinical or radiological aLRTD diagnosis. Findings: 12,557 adult aLRTD hospitalisations occurred: 10,087 were associated with infection (pneumonia or non-pneumonic lower respiratory tract infection [NP-LRTI]), 2161 with no infective cause, with 306 providing a minimal surveillance dataset. Confirmed SARS-CoV-2 infection accounted for 32% (3178/10,087) of respiratory infections. Annual incidences of overall, COVID-19, and non- SARS-CoV-2 pneumonia were 714.1, 264.2, and 449.9, and NP-LRTI were 346.2, 43.8, and 302.4 per 100,000 adults, respectively. Weekly incidence trends in COVID-19 aLRTD showed large surges (median 6.5 [IQR 0.7-10.2] admissions per 100,000 adults per week), while other infective aLRTD events were more stable (median 14.3 [IQR 12.8-16.4] admissions per 100,000 adults per week) as were non-infective aLRTD events (median 4.4 [IQR 3.5-5.5] admissions per 100,000 adults per week). Interpretation: While COVID-19 disease was a large component of total aLRTD during this pandemic period, non- SARS-CoV-2 infection still caused the majority of respiratory infection hospitalisations. COVID-19 disease showed significant temporal fluctuations in frequency, which were less apparent in non-SARS-CoV-2 infection. Despite public health interventions to reduce respiratory infection, disease incidence remains high. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

A feasibility randomised trial comparing therapeutic thoracentesis to chest tube insertion for the management of pleural infection: results from the ACTion trial.

BACKGROUND: Pleural infection is a complex condition with a considerable healthcare burden. The average hospital stay for pleural infection is 14 days. Current standard of care defaults to chest tube insertion and intravenous antibiotics. There have been no randomised trials on the use of therapeutic thoracentesis (TT) for pleural fluid drainage in pleural infection. AIMS AND OBJECTIVES: To assess the feasibility of a full-scale trial of chest tube vs TT for pleural infection in a single UK centre. The primary outcome was defined as the acceptability of randomisation to patients. METHODS: Adult patients admitted with a pleural effusion felt to be related to infection and meeting criteria for drainage (based on international guidelines) were eligible for randomisation. Participants were randomised (1:1) to chest tube insertion or TT with daily review assessing need for further drainages or other therapies. Neither participant nor clinician were blinded to treatment allocation. Patients were followed up at 90 days post-randomisation. RESULTS: From September 2019 to June 2021, 51 patients were diagnosed with pleural infection (complex parapneumonic effusion/empyema). Eleven patients met the inclusion criteria for trial and 10 patients were randomised (91%). The COVID-19 pandemic had a substantial impact on recruitment. Data completeness was high in both groups with no protocol deviations. Patients randomised to TT had a significantly shorter overall mean hospital stay (5.4 days, SD 5.1) compared to the chest tube control group (13 days, SD 6.0), p = 0.04. Total number of pleural procedures required per patient were similar, 1.2 in chest tube group and 1.4 in TT group. No patient required a surgical referral. Adverse events were similar between the groups with no readmissions related to pleural infection. CONCLUSIONS: The ACTion trial met its pre-specified feasibility criteria for patient acceptability but other issues around feasibility of a full-scale trial remain. From the results available the hypothesis that TT can reduce length of stay in pleural infection should be explored further. TRIAL REGISTRATION: ISRCTN: 84674413.

Lymphocyte predominance in blood, pleural fluid, and tumour stroma; a prognostic marker in pleural mesothelioma.

BACKGROUND: As promising novel treatments develop for malignant pleural mesothelioma (MPM), early prognostication has become increasingly important. Circulating and local inflammatory cells are known to play a significant role in other tumour types. We assessed the proportion of lymphocyte populations within blood, pleural fluid and tumour stroma to prognosticate patients with MPM at diagnosis. METHODS: Consecutive patients diagnosed with biopsy-proven MPM were prospectively recruited to an observational cohort study and followed up for a minimum of 7.5 years. Blood and pleural fluid results at presentation were extracted from the medical records. Biopsy specimens were independently reviewed by 2 pathologists who scored the degree of lymphocytic and neutrophilic infiltration. RESULTS: Baseline results were available for 184 patients. The predominant pleural fluid cell type was calculable for 84 patients and 118 patients had biopsy specimens available for review. A low blood neutrophil/lymphocyte ratio (NLR < 4) inferred a better prognosis with a median survival of 420 days versus 301 days (p < 0.01). Survival was better for patients with a lymphocyte-predominant pleural effusion (430 vs 306 days, p < 0.01). Lymphocyte infiltration of tumour stroma was also associated with improved survival (n = 92, survival 430 days) compared with neutrophilic or acellular samples (n = 26, survival 342 days p < 0.01). In multivariable modelling lymphocyte predominance in blood, pleural fluid and tumour stroma were all associated with a better prognosis. CONCLUSIONS: Lymphocyte predominance within tumour stroma, pleural fluid or blood infers a better prognosis in patients with MPM.

The priorities of people with mesothelioma and their carers: A qualitative interview study of trial participation and treatment decisions.

PURPOSE: Treatment options for mesothelioma are increasing, as are the number of clinical trials available to patients. However, little is known about patients' and relatives' priorities when making decisions about treatment and trial participation. The aim of this study was to provide insight into people's experiences of participating in clinical research and explore the factors influencing decision-making. METHODS: Face to face, semi-structured interviews were undertaken with mesothelioma patients who were participating in the TILT trial (a randomised trial of intra-pleural immunotherapy) and their relatives. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: Twelve people were interviewed, comprising five mesothelioma patients and seven relatives. Four themes were identified relating to the experience of mesothelioma: physicality, quality of life, uncertainty and risk, and planning for an unpredictable future. A further theme related to attitudes to research participation. PARTICIPANTS: valued physical strength and were careful not to jeopardise this with potential side effects of medication. Quality of life was important and was often prioritised over survival. Participants found ambiguity challenging and sought certainty, potentially in response to the uncertainty surrounding their future. The desire for certainty impacted on risk perception; an important factor in decision-making. Relatives often advocated on behalf of patients and were more reluctant about research participation due to concern about potential risks. CONCLUSION: The study confirmed previous qualitative findings around physicality, stoicism and uncertainty, building on these themes to highlight their influence on decision-making. Important findings for practice include the challenges associated with risk communication and the differing care needs and attitudes to research of relatives.

Aerosol emission from the respiratory tract: an analysis of aerosol generation from oxygen delivery systems.

INTRODUCTION: continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) provide enhanced oxygen delivery and respiratory support for patients with severe COVID-19. CPAP and HFNO are currently designated as aerosol-generating procedures despite limited high-quality experimental data. We aimed to characterise aerosol emission from HFNO and CPAP and compare with breathing, speaking and coughing. MATERIALS AND METHODS: Healthy volunteers were recruited to breathe, speak and cough in ultra-clean, laminar flow theatres followed by using CPAP and HFNO. Aerosol emission was measured using two discrete methodologies, simultaneously. Hospitalised patients with COVID-19 had cough recorded using the same methodology on the infectious diseases ward. RESULTS: In healthy volunteers (n=25 subjects; 531 measures), CPAP (with exhalation port filter) produced less aerosol than breathing, speaking and coughing (even with large >50 L/min face mask leaks). Coughing was associated with the highest aerosol emissions of any recorded activity. HFNO was associated with aerosol emission, however, this was from the machine. Generated particles were small (<1 µm), passing from the machine through the patient and to the detector without coalescence with respiratory aerosol, thereby unlikely to carry viral particles. More aerosol was generated in cough from patients with COVID-19 (n=8) than volunteers. CONCLUSIONS: In healthy volunteers, standard non-humidified CPAP is associated with less aerosol emission than breathing, speaking or coughing. Aerosol emission from the respiratory tract does not appear to be increased by HFNO. Although direct comparisons are complex, cough appears to be the main aerosol-generating risk out of all measured activities.

Predicting outcomes of COVID-19 from admission biomarkers: a prospective UK cohort study.

INTRODUCTION: COVID-19 has an unpredictable clinical course, so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. METHODS: Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were consented. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (interleukin-6 (IL-6), soluble urokinase plasminogen activator receptor (suPAR), Krebs von den Lungen 6, troponin, ferritin, lactate dehydrogenase, B-type natriuretic peptide, procalcitonin) were performed in addition to routinely performed markers (C reactive protein (CRP), neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, National Early Warning Score (NEWS2), CURB-65 and radiographic severity score on initial chest radiograph were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission or death, with area under the curve (AUC) (figures calculated). RESULTS: 187 patients had 28-day outcomes at the time of analysis. CRP (AUC: 0.69, 95% CI: 0.59 to 0.78), lymphocyte count (AUC: 0.62, 95% CI: 0.53 to 0.72) and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.77, 0.65 to 0.88) and suPAR (AUC: 0.81, 0.72 to 0.88) showed some promise, but simple clinical features alone such as NEWS2 score (AUC: 0.70, 0.60 to 0.79) or age (AUC: 0.70, 0.62 to 0.77) performed nearly as well. DISCUSSION: Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS2 score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should focus on the additive value of these biomarkers to routine care.

Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks.

INTRODUCTION: Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up. METHODS: Prospective single centre observational study. RESULTS: Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml). CONCLUSIONS: The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.

Epidemiology of pleural empyema in English hospitals and the impact of influenza.

Pleural empyema represents a significant healthcare burden due to extended hospital admissions and potential requirement for surgical intervention. This study aimed to assess changes in incidence and management of pleural empyema in England over the past 10 years and the potential impact of influenza on rates.Hospital Episode Statistics data were used to identify patients admitted to English hospitals with pleural empyema between 2008 and 2018. Linear regression was used to analyse the relationship between empyema rates and influenza incidence recorded by Public Health England. The relationship between influenza and empyema was further explored using serological data from a prospective cohort study of patients presenting with pleural empyema.Between April 2008 and March 2018 there were 55 530 patients admitted with pleural empyema. There was male predominance (67% versus 33%), which increased with age. Cases have increased significantly from 4447 in 2008 to 7268 in 2017. Peaks of incidence correlated moderately with rates of laboratory-confirmed influenza in children and young adults (r=0.30). For nine of the 10 years studied, the highest annual point incidence of influenza coincided with the highest admission rate for empyema (with a 2-week lag). In a cohort study of patients presenting to a single UK hospital with pleural empyema/infection, 24% (17 out of 72) had serological evidence of recent influenza infection, compared to 7% in seasonally matched controls with simple parapneumonic or cardiogenic effusions (p<0.001).Rates of empyema admissions in England have increased steadily with a seasonal variation that is temporally related to influenza incidence. Patient-level serological data from a prospective study support the hypothesis that influenza may play a pathogenic role in empyema development.

Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort.

The longer-term consequences of SARS-CoV-2 infection are uncertain. Consecutive patients hospitalised with COVID-19 were prospectively recruited to this observational study (n=163). At 8-12 weeks postadmission, survivors were invited to a systematic clinical follow-up. Of 131 participants, 110 attended the follow-up clinic. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) and limitations in reported physical ability. However, clinically significant abnormalities in chest radiograph, exercise tests, blood tests and spirometry were less frequent (35%), especially in patients not requiring supplementary oxygen during their acute infection (7%). Results suggest that a holistic approach focusing on rehabilitation and general well-being is paramount.

Using creative co-design to develop a decision support tool for people with malignant pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a common, serious problem predominantly seen in metastatic lung and breast cancer and malignant pleural mesothelioma. Recurrence of malignant pleural effusion is common, and symptoms significantly impair people's daily lives. Numerous treatment options exist, yet choosing the most suitable depends on many factors and making decisions can be challenging in pressured, time-sensitive clinical environments. Clinicians identified a need to develop a decision support tool. This paper reports the process of co-producing an initial prototype tool. METHODS: Creative co-design methods were used. Three pleural teams from three disparate clinical sites in the UK were involved. To overcome the geographical distance between sites and the ill-health of service users, novel distributed methods of creative co-design were used. Local workshops were designed and structured, including video clips of activities. These were run on each site with clinicians, patients and carers. A joint national workshop was then conducted with representatives from all stakeholder groups to consider the findings and outputs from local meetings. The design team worked with participants to develop outputs, including patient timelines and personas. These were used as the basis to develop and test prototype ideas. RESULTS: Key messages from the workshops informed prototype development. These messages were as follows. Understanding and managing the pleural effusion was the priority for patients, not their overall cancer journey. Preferred methods for receiving information were varied but visual and graphic approaches were favoured. The main influences on people's decisions about their MPE treatment were personal aspects of their lives, for example, how active they are, what support they have at home. The findings informed the development of a first prototype/service visualisation (a video representing a web-based support tool) to help people identify personal priorities and to guide shared treatment decisions. CONCLUSION: The creative design methods and distributed model used in this project overcame many of the barriers to traditional co-production methods such as power, language and time. They allowed specialist pleural teams and service users to work together to create a patient-facing decision support tool owned by those who will use it and ready for implementation and evaluation.

The Prevalence and Clinical Relevance of Nonexpandable Lung in Malignant Pleural Mesothelioma. A Prospective, Single-Center Cohort Study of 229 Patients.

Rationale: Nonexpandable lung is a recognized phenomenon that can create management challenges in patients with mesothelioma. Its prevalence and clinical importance are unknown.Objectives: The aim of this study was to describe the prevalence of nonexpandable lung and to evaluate whether there was any association between nonexpandable lung and survival in a clinical cohort of patients with mesothelioma.Methods: This was a prospective, observational cohort study of patients with mesothelioma who were seen in a single center between March 1, 2008, and August 3, 2017. Baseline characteristics were collected at diagnosis. Serial chest radiographs were assessed for the presence of pleural effusions and nonexpandable lung (defined as a lack of lung expansion after pleural aspiration or drainage). Patients were followed until they died or were censored on March 14, 2019.Results: Of 229 patients, 192 (82.7%) had a pleural effusion at presentation, and nonexpandable lung was observed in 64 of these 192 patients (33.3%). Breathlessness and cough were more frequent in patients with pleural effusions, especially in those with underlying nonexpandable lung, whereas chest pain was more prevalent in patients without effusions. Patients with pleural effusions, both with and without underlying nonexpandable lung, were more likely to have epithelioid or early-stage disease and to receive chemotherapy than patients with no pleural effusion. Nonexpandable lung was an independent risk factor for short survival, with a hazard ratio for mortality of 1.80 (95% confidence interval, 1.16-2.80) compared with patients without nonexpandable lung. The presence of a pleural effusion did not appear to be associated with a worse prognosis compared with patients with an effusion (adjusted hazard ratio, 1.86; 95% confidence interval, 0.93-3.72).Conclusions: This is the first study to describe the prevalence and clinical implications of nonexpandable lung in mesothelioma. It demonstrates that nonexpandable lung is a relatively common phenomenon that is associated with significant symptomatology and shorter survival.Keywords: mesothelioma; nonexpandable lung; pleural effusion.

Investigating unilateral pleural effusions: the role of cytology.

The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.