COVID-19 Outcomes and Diabetes Mellitus: A Comprehensive Multicenter Prospective Cohort Study.

The link between type 2 diabetes (T2D) and the severe outcomes of COVID-19 has raised concerns about the optimal management of patients with T2D. This study aimed to investigate the clinical characteristics and outcomes of T2D patients hospitalized with COVID-19 and explore the potential associations between chronic T2D treatments and adverse outcomes. This was a multicenter prospective cohort study of T2D patients hospitalized with COVID-19 in Greece during the third wave of the pandemic (February-June 2021). Among the 354 T2D patients included in this study, 63 (18.6%) died during hospitalization, and 16.4% required ICU admission. The use of DPP4 inhibitors for the chronic management of T2D was associated with an increased risk of in-hospital death (adjusted odds ratio (adj. OR) 2.639, 95% confidence interval (CI) 1.148-6.068, p = 0.022), ICU admission (adj. OR = 2.524, 95% CI: 1.217-5.232, p = 0.013), and progression to ARDS (adj. OR = 2.507, 95% CI: 1.278-4.916, p = 0.007). Furthermore, the use of DPP4 inhibitors was significantly associated with an increased risk of thromboembolic events (adjusted OR of 2.249, 95% CI: 1.073-4.713, p = 0.032) during hospitalization. These findings highlight the importance of considering the potential impact of chronic T2D treatment regiments on COVID-19 and the need for further studies to elucidate the underlying mechanisms.

Activin-A impedes the establishment of CD4+ T cell exhaustion and enhances anti-tumor immunity in the lung.

BACKGROUND: Although tumor-infiltrating T cells represent a favorable prognostic marker for cancer patients, the majority of these cells are rendered with an exhausted phenotype. Hence, there is an unmet need to identify factors which can reverse this dysfunctional profile and restore their anti-tumorigenic potential. Activin-A is a pleiotropic cytokine, exerting a broad range of pro- or anti-inflammatory functions in different disease contexts, including allergic and autoimmune disorders and cancer. Given that activin-A exhibits a profound effect on CD4+ T cells in the airways and is elevated in lung cancer patients, we hypothesized that activin-A can effectively regulate anti-tumor immunity in lung cancer. METHODS: To evaluate the effects of activin-A in the context of lung cancer, we utilized the OVA-expressing Lewis Lung Carcinoma mouse model as well as the B16F10 melanoma model of pulmonary metastases. The therapeutic potential of activin-A-treated lung tumor-infiltrating CD4+ T cells was evaluated in adoptive transfer experiments, using CD4-/--tumor bearing mice as recipients. In a reverse approach, we disrupted activin-A signaling on CD4+ T cells using an inducible model of CD4+ T cell-specific knockout of activin-A type I receptor. RNA-Sequencing analysis was performed to assess the transcriptional signature of these cells and the molecular mechanisms which mediate activin-A's function. In a translational approach, we validated activin-A's anti-tumorigenic properties using primary human tumor-infiltrating CD4+ T cells from lung cancer patients. RESULTS: Administration of activin-A in lung tumor-bearing mice attenuated disease progression, an effect associated with heightened ratio of infiltrating effector to regulatory CD4+ T cells. Therapeutic transfer of lung tumor-infiltrating activin-A-treated CD4+ T cells, delayed tumor progression in CD4-/- recipients and enhanced T cell-mediated immunity. CD4+ T cells genetically unresponsive to activin-A, failed to elicit effective anti-tumor properties and displayed an exhausted molecular signature governed by the transcription factors Tox and Tox2. Of translational importance, treatment of activin-A on tumor-infiltrating CD4+ T cells from lung cancer patients augmented their immunostimulatory capacity towards autologous CD4+ and CD8+ T cells. CONCLUSIONS: In this study, we introduce activin-A as a novel immunomodulatory factor in the lung tumor microenvironment, which bestows exhausted CD4+ T cells with effector properties.

ERS International Congress, Madrid, 2019: highlights from the Thoracic Oncology Assembly.

Lung cancer is a devastating disease affecting hundreds of thousands of patients in Europe. Despite recent advances in treatment, its prognosis remains poor. This is mainly attributed to the late stages that diagnoses are usually established at, consequently excluding curative treatment options. During the 2019 European Respiratory Society International Congress in Madrid, Spain, lung cancer experts presented the most recent aspects of lung cancer early detection with low-dose computed tomography.

ESR/ERS statement paper on lung cancer screening.

In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.

ESR/ERS statement paper on lung cancer screening.

In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.Key Points• Pulmonologists and radiologists both have key roles in the set up of multidisciplinary LCS teams with experts from many other fields.• Pulmonologists identify people eligible for LCS, reach out to family doctors, share the decision-making process and promote tobacco cessation.• Radiologists ensure appropriate image quality, minimum dose and a standardised reading/reporting algorithm, together with a clear definition of a "positive screen".• Strict algorithms define the exact management of screen-detected nodules and incidental findings.• For LCS to be (cost-)effective, it has to target a population defined by risk prediction models.

Continuous professional development: elevating thoracic oncology education in Europe.

The @EuroRespSoc launches a new thoracic oncology continuous professional development programme http://bit.ly/31ShuTp.

Highlights of thoracic oncology from the 2018 ERS International Congress.

Lung cancer is a substantial global burden for patients, healthcare professionals and healthcare systems. Multiple scientific international and national initiatives are tackling the various problems associated with this disease, which is currently the leading cause of cancer-related mortality worldwide. During the European Respiratory Society International Congress 2018 in Paris, France, lung cancer experts gathered to present the most recent aspects of lung cancer care, and discuss the need for joint initiatives and an international lung cancer alliance, aiming to provide high quality, accessible health care. The US experience and American Lung Association/American Thoracic Society implementation guide on lung cancer screening programmes, the key features of optimising and implementing such programmes, the challenges of treatment in the subset of patients where lung cancer is combined with interstitial lung disease, and novel lung cancer biomarkers and immunotherapy were among the most anticipated issues covered during the congress.

Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer.

VAM(LA) has adequate sensitivity to be considered as the approach of choice for preoperative mediastinal staging in the subgroup of early-stage operable NSCLC patients http://ow.ly/42Wn30m78Zw.

Assembly 11: thoracic oncology.

Meet @ERStalk Assembly 11: thoracic oncology http://ow.ly/6Fhb30js5LE.

Novel therapies for severe asthma in children and adults.

The heterogeneous nature of asthma requires personalised treatments. Monoclonal antibody treatments showed good efficacy, and should be considered when symptoms are poorly controlled despite good inhaler technique, compliance and controlled comorbidities. http://ow.ly/UWpg30hImQh.

Early Career Members at the ERS LSC 2017: mechanistic overlap between chronic lung injury and cancer.

.@EarlyCareerERS looks back on #LSC2017 http://ow.ly/I3M730fkn5X.

Asbestos and the lung: highlights of a detrimental relationship.

Novel aspects of the pathogenesis of asbestos-related diseases are still coming to light http://ow.ly/EPDa30e8JqK.

Early Career Members at the ERS International Congress 2017: highlights from the Assemblies.

.@EarlyCareerERS reflect on the highlights from the #ERSCongress 2017 http://ow.ly/klLS30gAN49.

Clinical asthma phenotypes in the real world: opportunities and challenges.

Asthma is a common, chronic and heterogeneous syndrome, affecting people of all ages, all races and both sexes. It may range from mild disease with barely noticeable symptoms, to very severe disease with constant symptoms that greatly hinder the life of the patient. Guidelines issued by various medical societies provide guidance on how to diagnose and manage asthmatic patients. It is now increasingly recognised that asthma management must be individualised, tailored not only to the severity of the disease but to the phenotypic characteristics of each patient. The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation. Asthma control can be easily assessed clinically through simple screening tools such as the use of validated questionnaires and spirometry. The use of inflammatory biomarkers can be an alternative approach that, however, requires more time and resources. Asthma treatment involves the use of controllers, mainly inhaled corticosteroids and long-acting ß2-agonists, and relievers, mainly rapid-acting ß2-agonists. Controller medications reduce airway inflammation, lead to better symptom control and reduce the risk of future exacerbations. Reliever (rescue) medications alleviate symptoms and prevent exercise-induced bronchoconstriction. Treatment must be based on a "stepwise approach" in order to achieve good control of symptoms and to minimise future risks of exacerbations. That is, less treatment for mild disease, more treatment for severe, uncontrolled disease. Once good asthma control has been achieved and maintained, treatment should be stepped down. In severe asthmatics, phenotypic characterisation becomes more clinically useful and add-on treatment such as anti-immunoglobulin E monoclonal antibodies may be required. Despite our better understanding of asthma, there are still patients who will not respond to treatment and remain symptomatic. Dissemination of guidelines and national plans allowing early diagnosis of asthma as well as access to specialised primary and secondary care for asthmatic patients, personalised treatment and continuity of care may lead to excellence in care and controlled asthma for the majority of patients. Education of the patient in asthma is also very important, as in every chronic disease, as the patients live with the disease every day while they visit a healthcare professional a few times a year. Future planning for new treatments should focus on the needs of such severe asthma patients.

Mediastinal widening and miliary chest radiograph pattern in a middle aged man: could it be sarcoidosis?

A diagnosis of sarcoidosis is based on suggestive radiographic pattern, presence of non-caseating granulomas and negative fungal and acid-fast bacilli (AFB) cultures. Sarcoidosis usually presents with hilar and/or mediastinal lymphadenopathy and distinct parenchymal radiographic patterns, such as fine nodular, reticulonodular or acinar opacities and rarely focal nodules or masses. A diffuse miliary pattern occurs in less than 1% of cases and can be identical to patterns seen in tuberculosis, fungal infections, histiocytosis and miliary metastases. Here the authors report the case of a 48-year-old man who presented with mediastinal widening and miliary pattern on chest radiograph, initially erroneously treated for tuberculosis. Transbronchial biopsies, bronchoalveolar lavage (BAL) and serological tests were compatible with sarcoidosis, while BAL cultures were negative for fungi and AFB growth. The patient finally demonstrated clinical and radiological remission under corticosteroids. Clinicians should consider sarcoidosis in the differential diagnosis when bilateral miliary-type lesions are revealed on chest X-ray.