Incidence and recognition of acute respiratory distress syndrome in a UK intensive care unit.

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.This is the final version of the article. It first appeared from BMJ Thorax via ://dx.doi.org/10.1136/thoraxjnl-2016-20840

Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

This is the final version of the article. It first appeared from the BMJ Group via http://dx.doi.org/10.1136/thoraxjnl-2015-207156The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.The authors thank all the staff at the Department of Nuclear Medicine at Addenbrooke’s Hospital and the Wellcome Trust Clinical Research Facility, Cambridge; Cambridge Biomedical Research Centre Core Biochemistry Assay Laboratory; and the National Institute for Health Research, through the Comprehensive Clinical Research Network. This work was supported by Asthma-UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], and Cambridge NIHR Biomedical Research Centre. Written informed consent was obtained in accordance with the Declaration of Helsinki. The study was approved by Cambridgeshire Research Ethics Committee (09/H0308/119) and the Administration of Radioactive Substances Advisory Committee of the United Kingdom (83/3130/25000)

Unmet supportive care needs of breast, colorectal and testicular cancer survivors in the first 8 months post primary treatment:A prospective longitudinal survey

Objectives To explore the supportive care needs of cancer survivors, the characteristics of patients with high levels of unmet need, changes in unmet need after treatment ends and differences in unmet needs of breast, colorectal and testicular survivors. Methods The method used was a prospective longitudinal mailed survey. Unmet needs, measured by 25-item modified Cancer Survivors Unmet Needs survey at baseline (immediately post-treatment) and 8 months later, were analysed descriptively. Results Of 434 breast, 186 colorectal and 75 testicular patients responding at baseline, 56.2%, 65.6% and 50.7%, respectively, had no unmet needs, the top decile having >= 10 (breast) or seven (colorectal and testicular) different needs and seven different unmet needs. The most frequently reported unmet need (all groups) was fear of cancer recurrence. Unmet needs fell significantly at 8 months for breast patients. Some patients reported new needs. Needs were lowest amongst colorectal survivors and differed between the three groups. Higher levels of unmet needs (breast and colorectal) were associated with having had chemotherapy. Conclusion Most survivors reported few unmet needs, but a small proportion have persisting or emerging needs. Routine or regular monitoring of unmet needs is required so that healthcare professionals can deliver personalised care based on individual needs, preferences and circumstances

UPBEAT-UK::a programme of research into the relationship between coronary heart disease and depression in primary care patients

Many people with coronary heart disease (CHD) are depressed and research on people who have had a heart attack found that depression increases the chance of further heart attacks. The UPBEAT-UK team conducted research with people on general practitioner CHD registers in 33 south London practices to: examine any link between CHD, depression and worse future heart disease; and develop case\ud management by practice nurses for people with CHD and depression. We followed 803 people with CHD for up to 3 years, assessing them for depression, chest pain and\ud worsening of heart disease, and also measured care costs. We asked patients, GPs and nurses how people with CHD and depression should be treated. From this, we developed care designed for each person called ‘personalised care’ (PC). We tested it in 41 people (while 40 people received their usual care from GPs)\ud with chest pain and depression, to assess how acceptable it is, whether or not it helps and what the costs would be. PC was acceptable to people, and those who received it reported less chest pain 6 and 12 months later. Costs were lower following PC but the difference was not statistically significant. Just under half of those with CHD had chest pain. Depression was frequent, but anxiety was more\ud common and increased the chances of both heart attacks and death. We conclude that further research is needed to understand the links between anxiety, chest pain and heart\ud disease, and to further develop our promising findings that PC can be helpful in reducing chest pain in\ud general practice

In vivo imaging reveals increased eosinophil uptake in the lungs of obese asthmatic patients.

To The Editor: Eosinophils play an important pathogenic role in pulmonary and systemic conditions including eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.1,2 While progress has been made in understanding the mechanisms responsible for the activation of these cells, existing biomarkers of eosinophilic inflammation are indirect and/or invasive and do not always correlate with tissue eosinophilia. Hence, there is a need to develop non-invasive biomarkers of tissue eosinophilia. We have previously demonstrated the capacity of SPECT (single photon emission computed tomography) to quantify neutrophil uptake into the lungs of COPD patients.3 We sought to determine whether this methodology could be used to quantify eosinophil kinetics and pulmonary uptake, which may differ amongst diseases characterized by eosinophilic inflammation. In particular, the role of the eosinophil in asthma with obesity, a distinct asthma endotype associated with increased severity,4 is controversial. We hypothesized that injection of radiolabeled eosinophils, coupled with SPECT/CT, would reveal changes in eosinophil kinetics in patients compared to healthy volunteers.This work was supported by Asthma UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], Cambridge NIHR Biomedical Research Centre, Wellcome Trust Senior Fellowship (to CEB) [grant number WT082265], AirPROM 7th EU Framework grant and Leicester NIHR Biomedical Research Centre

The effectiveness of ablative and non-surgical therapies for early hepatocellular carcinoma: systematic review and network meta-analysis of randomised controlled trials

Background & Aims Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. Methods Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non-surgical therapy versus any comparator in patients with HCC ≤ 3cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. Results Thirty-seven eligible RCTs were included (including over 3700 patients). Most were from China (n=17) or Japan (n=7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16-1.82), progression-free survival (HR: 1.36, 95% CrI: 1.11-1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02-1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19-2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. Conclusions It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake. Funding: National Institute for Health and Care Research (UK). Registration: PROSPERO CRD42020221357

Evidence of a recent decline in UK emissions of hydrofluorocarbons determined by the InTEM inverse model and atmospheric measurements

National greenhouse gas inventories (GHGIs) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGIs. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emission Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high global warming potentials (GWPs), and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication, its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions from 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009-2012 shows a drop of 35ĝ€¯%, indicating progress toward the target of a 79ĝ€¯% decrease in sales by 2030. The total InTEM HFC emission estimates (2008-2018) are on average 73 (62-83)ĝ€¯% of, or 4.3 (2.7-5.9)ĝ€¯Tgĝ€¯CO2-eqĝ€¯yr-1 lower than, the total HFC emission estimates from the UK GHGI. There are also significant discrepancies between the two estimates for the individual HFCs.</p

Neutrophil GM-CSF receptor dynamics in acute lung injury.

GM-CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM-CSF receptor (GM-CSFRα) complex, a process essential for signaling. Whereas GM-CSF controls many aspects of neutrophil biology, regulation of GM-CSFRα expression is poorly understood, particularly the role of GM-CSFRα in ligand clearance and whether signaling is sustained despite major down-regulation of GM-CSFRα surface expression. We established a quantitative assay of GM-CSFRα surface expression and used this, together with selective anti-GM-CSFR antibodies, to define GM-CSFRα kinetics in human neutrophils, and in murine blood and alveolar neutrophils in a lung injury model. Despite rapid sustained ligand-induced GM-CSFRα loss from the neutrophil surface, which persisted even following ligand removal, pro-survival effects of GM-CSF required ongoing ligand-receptor interaction. Neutrophils recruited to the lungs following LPS challenge showed initially high mGM-CSFRα expression, which along with mGM-CSFRβ declined over 24 hr; this was associated with a transient increase in bronchoalveolar lavage fluid (BALF) mGM-CSF concentration. Treating mice in an LPS challenge model with CAM-3003, an anti-mGM-CSFRα mAb, inhibited inflammatory cell influx into the lung and maintained the level of BALF mGM-CSF. Consistent with neutrophil consumption of GM-CSF, human neutrophils depleted exogenous GM-CSF, independent of protease activity. These data show that loss of membrane GM-CSFRα following GM-CSF exposure does not preclude sustained GM-CSF/GM-CSFRα signaling and that this receptor plays a key role in ligand clearance. Hence neutrophilic activation via GM-CSFR may play an important role in neutrophilic lung inflammation even in the absence of high GM-CSF levels or GM-CSFRα expression