Patient reported upper gastro-intestinal symptoms associated with fractionated image-guided conformal radiotherapy for metastatic spinal cord compression

Background and purpose Palliative radiotherapy is given to sustain or improve quality of life for patients with advanced cancer. Radiotherapy may however result in symptomatic side effects, which may affect the patient negatively. This prospective longitudinal study of 30 patients aimed at investigating the incidence and severity of early toxicity, particularly focusing on dysphagia, esophagitis and mucositis, following fractionated radiotherapy for cervical and thoracic metastatic spinal cord compression (MSCC), as well as determining the relationship between esophageal dose and early upper gastro-intestinal symptoms. Materials and methods Thirty patients receiving radiotherapy of 3Gyx10 for MSCC were included in the study. Patients were assessed for a total of 7 weeks from onset of radiotherapy using the Edmonton Symptom Assessment System (ESAS) questionnaire. Upper gastro-intestinal symptoms and severity were assessed from the tenth and eleventh question section of the ESAS questionnaire of “other problems” and how much this affected them. The relationships between the mean and maximum esophageal doses and incidence of dysphagia, esophagitis or mucositis were estimated and dose response curves determined. Results Eleven patients reported esophageal symptoms (average duration eleven days, range 1–18 days). Incidence of esophageal toxicity in patients treated at Th8 or above was 79 percent, while no patients treated below Th8 reported any symptoms (p < 0.001). Furthermore, 2 out of 3 patients irradiated at the cervical region reported substantial changes in taste sensation. Risk of symptoms correlated with both mean and maximum esophageal dose and may be a useful tool in planning radiotherapy for MSCC, potentially reducing early upper gastro-intestinal toxicity

Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population

COPD exacerbation; Coagulation; Cross-linked fibrin degradationExacerbación de la EPOC; Coagulación; Degradación de fibrina reticuladaExacerbació de la MPOC; Coagulació; Degradació de fibrina reticuladaCardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.This study was funded by the Danish Regions Medical Fund (grant no. 5894/16), the Danish Council for Independent Research (grant no. 6110-00268B), and the Novo Nordisk foundation (grant no. NNF20OC0060657). Author D.D.M. received personal funding from the Danish National Research Foundation (DNRF126)

Management of hospitalised adults with coronavirus disease 2019 (COVID-19):A European Respiratory Society living guideline

INTRODUCTION Hospitalised patients with coronavirus disease 19 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require non-invasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS Based on the available evidence at the time of guideline development (February 20th, 2021) the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for IL-6 receptor antagonist monoclonal antibody treatment and high flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine and azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available

Update March 2022:management of hospitalised adults with coronavirus disease-19 (COVID-19): a european respiratory society living guideline

The ERS COVID-19 guidelines make recommendations for corticosteroids, anti-IL-6 monoclonal antibodies, baricitinib, anticoagulation and non-invasive respiratory support for hospitalised patients with COVID-19 https://bit.ly/3QgHH7

The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma

[Background] Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC.[Methods] Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score.[Findings] We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum.[Interpretation] NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients.We thank all funding sources: The laboratory of JBA is supported by the Novo Nordisk Foundation (14040, 0058419), Danish Cancer Society (R98-A6446, R167-A10784, R278-A16638), and the Danish Medical Research Council (4183-00118A, 1030-00070B). Data used for validation in this study provided by JMB was funded by the Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud Carlos III’ grants (PI18/01075, Miguel Servet Programme CON14/00129 and CPII19/00008) co-financed by ’Fondo Europeo de Desarrollo Regional’ (FEDER); CIBERehd, Spain; IKERBASQUE, Basque foundation for Science, Spain; BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD); Department of Health of the Basque Country (2017111010), Euskadi RIS3 (2019222054, 2020333010); Department of Industry of the Basque Country (Elkartek: KK-2020/00008), AECC Scientific Foundation and European Commission Horizon 2020 program (ESCALON project no.: 825510). Similarly, MAJ was funded by grants from the Fondo Nacional De Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and the Comisión Nacional de Investigación, Ciencia y Tecnología (CONICYT, AFB170005, CARE Chile UC).Peer reviewe

Adherence to inhaled corticosteroids and long-acting β2-agonists in asthma:A MASK-air study

Introduction Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting β2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. Materials and methods We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. Results In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). Conclusions In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2LEN consensus

Background: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p&nbsp;&lt;.001). Conclusions: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire