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Genetic analysis is emerging for interstitial lung diseases (ILDs); however, ILD practices are not yet standardized. We surveyed patients', relatives' and pulmonologists' experiences and needs on genetic testing in ILD to evaluate the current situation and identify future needs. A clinical epidemiologist (MT) together with members of the ERS taskforce and representatives of the European Idiopathic Pulmonary Fibrosis and related disorders Federation (EU-IPFF) patient organisation developed a survey for patients, relatives and pulmonologists. Online surveys consisted of questions on five main topics: awareness of hereditary ILD, the provision of information, genetic testing, screening of asymptomatic relatives and clinical impact of genetic analysis in ILD. Survey respondents consisted of 458 patients with ILD, 181 patients' relatives and 352 pulmonologists. Most respondents think genetic testing can be useful, particularly for explaining the cause of disease, predicting its course, determining risk for developing disease and the need to test relatives. Informing patients and relatives on genetic analysis is primarily performed by the pulmonologist, but 88% (218) of pulmonologists identify a need for more information and 96% (240) ask for guidelines on genetic testing in ILD. A third of the pulmonologists who would offer genetic testing currently do not offer a genetic test, primarily because they have limited access to genetic tests. Following genetic testing, 72% (171) of pulmonologists may change the diagnostic work-up and 57% (137) may change the therapeutic approach. This survey shows that there is wide support for implementation of genetic testing in ILD and a high need for information, guidelines and access to testing among patients, their relatives and pulmonologists.

Obesity is one of the leading preventable causes of cancer; however, little is known about the effects of obesity on anti-tumor immunity. Here, we investigated the effects of obesity on CD8 T cells in mouse models and patients with endometrial cancer. Our findings revealed that CD8 T cell infiltration is suppressed in obesity, which was associated with a decrease in chemokine production. Tumor-resident CD8 T cells were also functionally suppressed in obese mice, which was associated with a suppression of amino acid metabolism. Similarly, we found that a high BMI negatively correlated with CD8 infiltration in human endometrial cancer and that weight loss was associated with a complete pathological response in six of nine patients. Moreover, immunotherapy using anti-PD-1 led to tumor rejection in lean and obese mice and partially restored CD8 metabolism and anti-tumor immunity. These findings highlight the suppressive effects of obesity on CD8 T cell anti-tumor immunity, which can partially be reversed by weight loss and/or immunotherapy.

Objectives This study aimed to present a new approach of thorough preclinical testing of a novel left atrial appendage (LAA) occluder device. Background The development of a safe and effective LAA occluder has been shown to be challenging. Methods The novel OMEGATM LAA occluder (Eclipse Medical, Ireland) was tested in a porcine model and three-dimensional (3D) human LAA models – this as a prelude to its first-in-human use. Results In a first series of in-vivo experiments, the OMEGATM LAA occluder was shown to have a satisfactory device biocompatibility in a porcine model. The design of the OMEGATM device was further refined and optimized following three more series of in-vivo experiments. The second generation OMEGATM device was designed with thinner wires, leading to a profile reduction. Based on in-vitro testing of different OMEGATM device sizes implanted at different depths in human three-dimensional (3D) LAA models, it could be determined that (1) the landing zone should be measured at a median depth of 12 mm from the LAA ostium; (2) the distal self-retaining inverted cup should have 10%-25% compression to minimize device embolization risk; and (3) the disc should be slightly inverted, i.e. pulled into the LAA, to promote complete LAA occlusion. The combined in-vivo and in-vitro testing resulted in an optimized pre-procedural planning of the first-in-human case treated with the OMEGATM device. Conclusions This series of carefully planned in-vivo and in-vitro experiments allowed demonstration of the safety and efficacy of the OMEGATM LAA occluder. This approach of thorough preclinical testing of medical devices may reduce the risk of complications in first-in-human cases and may become the standard approach for device development and preclinical testing in the future.

Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective. The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numbers of animals employed, thereby enhancing the ethical standards and translational capacity of experimental research. The task force statement addresses general issues of experimental research (ethics, species, sex, age, ex vivo and in vitro models, gene editing). The statement also includes research recommendations on modelling asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung infections, acute lung injury and pulmonary hypertension. The task force stressed the importance of using multiple models to strengthen validity of results, the need to increase the availability of human tissues and the importance of standard operating procedures and data quality.

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropr