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The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival. In this multicohort study, we used five separate and independent datasets from randomised controlled trials to investigate potential biomarkers of survival and pleurodesis. Mass spectrometry-based discovery was used to investigate pleural fluid samples for differential protein expression in patients from the discovery group with different survival and pleurodesis outcomes. Clinical, radiological, and biological variables were entered into least absolute shrinkage and selection operator regression to build a model that predicts 3-month mortality. We evaluated the model using internal and external validation. 17 biomarker candidates of survival and seven of pleurodesis were identified in the discovery dataset. Three independent datasets (n=502) were used for biomarker validation. All pleurodesis biomarkers failed, and gelsolin, macrophage migration inhibitory factor, versican, and tissue inhibitor of metalloproteinases 1 (TIMP1) emerged as accurate predictors of survival. Eight variables (haemoglobin, C-reactive protein, white blood cell count, Eastern Cooperative Oncology Group performance status, cancer type, pleural fluid TIMP1 concentrations, and previous chemotherapy or radiotherapy) were validated and used to develop a survival score. Internal validation with bootstrap resampling and external validation with 162 patients from two independent datasets showed good discrimination (C statistic values of 0·78 [95% CI 0·72–0·83] for internal validation and 0·89 [0·84–0·93] for external validation of the clinical PROMISE score). To our knowledge, the PROMISE score is the first prospectively validated prognostic model for malignant pleural effusion that combines biological and clinical parameters to accurately estimate 3-month mortality. It is a robust, clinically relevant prognostic score that can be applied immediately, provide important information on patient prognosis, and guide the selection of appropriate management strategies. European Respiratory Society, Medical Research Funding-University of Oxford, Slater & Gordon Research Fund, and Oxfordshire Health Services Research Committee Research Grants.

Introduction and Aims. The first COVID-19 case in Malta was confirmed on the 7th of March 2020. This study is aimed at investigating a significant difference between the number of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) admissions and their inpatient outcome at Mater Dei Hospital during the COVID-19 pandemic when compared to the same period in 2019. Furthermore, we aim to determine predictors of mortality in AECOPD inpatients. Method. Data was collected retrospectively from electronic hospital records during the periods 1st March until 10th May in 2019 and 2020. Results. There was a marked decrease in AECOPD admissions in 2020, with a 54.2% drop in admissions (n=119 in 2020 vs. n=259 in 2019). There was no significant difference in patient demographics or medical comorbidities. In 2020, there was a significantly lower number of patients with AECOPD who received nebulised medications during admission (60.4% in 2020 vs. 84.9% in 2019; p≤0.001). There were also significantly lower numbers of AECOPD patients admitted in 2020 who received controlled oxygen via venturi masks (69.0% in 2020 vs. 84.5% in 2019; p=0.006). There was a significant increase in inpatient mortality in 2020 (19.3% [n=23] and 8.4% [n=22] for 2020 and 2019, respectively, p=0.003). Year was found to be the best predictor of mortality outcome (p=0.001). The lack of use of SABA pre-admission treatment (p=0.002), active malignancy (p=0.003), and increased length of hospital stay (p=0.046) were also found to be predictors of mortality for AECOPD patients; however, these parameters were unchanged between 2019 and 2020 and therefore could not account for the increase in mortality. Conclusions. There was a decrease in the number of admissions with AECOPD in 2020 during the COVID-19 pandemic, when compared to 2019. The year 2020 proved to be a significant predictor for inpatient mortality, with a significant increase in mortality in 2020. The decrease in nebuliser and controlled oxygen treatment noted in the study period did not prove to be a significant predictor of mortality when corrected for other variables. Therefore, the difference in mortality cannot be explained with certainty in this retrospective cohort study.

Background Correct inhaler technique is recommended by guidelines for optimum asthma care. The objective of the study is to determine real life predictors of correct pressurized metered dose inhaler (pMDI) technique in Asthma and COPD patients. Methods Two hundred eight adult patients aged 18+ from respiratory outpatients (69.2%) and the community on regular pMDI for a diagnosis of Asthma (78.9%) or COPD, were recruited. A questionnaire containing 31 possible predictors was administered and pMDI technique with or without spacer was observed by trained researchers on 12 point steps, of which 4 were considered critical. Results 23.1% of patients had no errors in inhaler technique and 32.2% had no critical errors. Patients had a median of 10 correct steps (IQR9-11), and 3(IQR2-4) correct critical steps. Using binary logistic regression the predictors of 10 correct steps were, other healthcare professional (pharmacist, nurse, physiotherapist) explained OR 3.73(1.63–8.54, p = 0.001), male gender 2.70(1.35–5.39, p = 0.004), self-score 1–10 1.21(1.05–1.39, p = 0.007), spacer use 0.38(0.19–0.79, p = 0.007), inhaled steroid 3.71(1.34–10.25, p = 0.01), heart disease 0.31(0.13–0.77, p = 0.01), pneumococcal vaccine 2.48(1.0–6.15, p = 0.043), education level 1–4 1.44(1.00–2.06, p = 0.05) and respiratory physician explained 0–7 times, 1.11(0.99–1.26, p = 0.08). Using ordinal logistic regression, predictors for correct critical steps 0–4, were: technique self-score 1–10 1.2(1.05–1.42, p = 0.006), inhaled corticosteroid use 2.78(1.1–7.31, p = 0.03) and education level 1–4 1.41(1.02–1.95, p = 0.03 Times respiratory physician explained inhaler technique 0–7 1.1(0.98–1.24, p = 0.1), married status 1.55(0.85–2.82, p = 0.15), hypercholesterolaemia 0.52(0.25–1.01, p = 0.054) and male gender 1.76(0.97–3.18, p = 0.06). Conclusions Known predictors of correct pMDI use, such as gender and education level were confirmed, while age and concomitant use of dry powder inhaler were not. Pneumococcal vaccination and awareness of steroid side effects were possible novel positive predictors, while the use of a spacer and co-morbidity with heart disease were found to be negative predictors. Patients’ self-assessment correlated well with actual performance. This information may be useful in defining approaches to optimize inhaler techniques which are so susceptible to human error.

IntroductionCurrent guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a ‘real world’ population.MethodsA retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration.ResultsA diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ2 1df=26.27, p<0.001) and insufficient samples (χ2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures.ConclusionsAn initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered.

SLC34A2 mutations lead to widespread intra-alveolar deposition of phosphates, and this likely leads to the spherical sand-like calcispherites in PAM. 1 Calcium and phosphate metabolism is usually normal, and extrapulmonary calcifications are rare, although there are reported cases of associated cardiac valve calcification, cholelithiasis and nephrocalcinosis. 2 Most known PAM cases are European, 3 and usually an incidental finding, as in this case, because of a striking lack of symptoms despite extensive characteristic radiographic changes, which are almost pathognomonic.

An 18-year-old man presented to the local hospital in Malta, with dyspnoea, cough, mild haemoptysis, chest pain and night sweats. CT revealed a right hilar mass. Pleural tap, bronchoscopy and open lung biopsy were inconclusive. Biopsies obtained at repeat bronchoscopy and endobronchial ultrasound (EBUS) revealed a likely diagnosis of inflammatory myofibroblastic tumour (IMT). The patient subsequently underwent right pneumonectomy, and histology revealed the presence of two further nodules apart from the main tumour. Follow-up with positron emission tomography (PET)/CT showed the development of a right basal paracardial lesion due to recurrence and the presence of lymph node, pleural and skeletal disease. Despite radiotherapy to the recurrent nodule and chemotherapy, there was skeletal disease progression. Treatment with an anaplastic lymphoma kinase inhibitor, ceritinib, resulted in very good metabolic response. This case report highlights the importance of keeping IMT in mind when the diagnosis of lung tumours is difficult, as delayed diagnosis may lead to worsened prognosis.

Pacemaker lead-associated thrombosis is a possible complication of any cardiac implantable electronic device. We present a case of a middle-aged woman with a history of ischaemic left ventricular failure, who presented with fever and other non-specific symptoms 4 months after cardiac resynchronisation therapy. A transoesophageal echocardiogram confirmed a vegetation-like structure originating from the pacemaker lead in the right atrium. The patient was treated with intravenous antibiotics followed by open heart surgery in order to remove this mass as well as the pacing device, including all three pacing leads. Histology and culture of the retrieved mass confirmed a sterile thrombus with no features to suggest an infected mass (vegetation). The patient made an uncomplicated recovery and there were no long-term sequelae on follow-up during the 2 years after the event.

BackgroundPleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway. We designed a study to determine the time frame of drained PF volume induction on intrapleural delivery of t-PA±DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway.MethodsData and samples from the MIST2 study were used (210 PI patients randomised to receive for 3 days either: t-PA and DNase, t-PA and placebo, DNase and placebo or double placebo). PF MCP-1 levels were measured by ELISA. One-way and two-way analysis of variance (ANOVA) with Tukey’s post hoc tests were used to estimate statistical significance. Pearson’s correlation coefficient was used to assess linear correlation.ResultsIntrapleural administration of t-PA±DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1–3). No significant difference was detected between any groups during the post-treatment period (days 5–7). Intrapleural administration of t-PA increased MCP-1 PF levels during treatment; however, no statistically significant difference was detected between patients who received t-PA and those who did not. PF MCP-1 expression was not correlated to the drug given nor the volume of drained PF.ConclusionsWe conclude that the PF volume drainage increment seen with the administration of t-PA does not appear to act solely via activation of the MCP-1 pathway.

IntroductionRespiratory trainees in the UK face challenges in meeting current Royal College of Radiologists (RCR) Level 1 training requirements for thoracic ultrasound (TUS) competence, specified as attending ‘at least one session per week over a period of no less than 3 months, with approximately five scans per session performed by the trainee (under supervision of an experienced practitioner)’. We aimed to clarify where TUS training opportunities currently exist for respiratory registrars.MethodsData were collected (over a 4-week period) to clarify the number of scans (and therefore volume of training opportunities) within radiology departments and respiratory services in hospitals in the South West, North West deaneries and Oxford.Results14 hospitals (including three tertiary pleural centres) provided data. Of 964 scans, 793 (82.3%) were conducted by respiratory teams who performed a mean of 17.7 scans per week, versus 3.1 TUS/week in radiology departments. There was no radiology session in any hospital with ≥5 TUS performed, whereas 8/14 (86%) of respiratory departments conducted such sessions. Almost half (6/14) of radiology departments conducted no TUS scans in the period surveyed.ConclusionsThe currently recommended exposure of regularly attending a list or session to undertake five TUS is not achievable in radiology departments. The greatest volume of training opportunities exists within respiratory departments in a variety of scheduled and unscheduled settings. Revision of the competency framework in TUS, and where this is delivered, is required.