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BMJ Open ; 10(12): e039560, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-1102180


INTRODUCTION: Ageing-related processes such as cellular senescence are believed to underlie the accumulation of diseases in time, causing (co)morbidity, including cancer, thromboembolism and stroke. Interfering with these processes may delay, stop or reverse morbidity. The aim of this study is to investigate the link between (co)morbidity and ageing by exploring biomarkers and molecular mechanisms of disease-triggered deterioration in patients with pancreatic ductal adenocarcinoma (PDAC) and (thromboembolic) ischaemic stroke (IS). METHODS AND ANALYSIS: We will recruit 50 patients with PDAC, 50 patients with (thromboembolic) IS and 50 controls at Rostock University Medical Center, Germany. We will gather routine blood data, clinical performance measurements and patient-reported outcomes at up to seven points in time, alongside in-depth transcriptomics and proteomics at two of the early time points. Aiming for clinically relevant biomarkers, the primary outcome is a composite of probable sarcopenia, clinical performance (described by ECOG Performance Status for patients with PDAC and the Modified Rankin Scale for patients with stroke) and quality of life. Further outcomes cover other aspects of morbidity such as cognitive decline and of comorbidity such as vascular or cancerous events. The data analysis is comprehensive in that it includes biostatistics and machine learning, both following standard role models and additional explorative approaches. Prognostic and predictive biomarkers for interventions addressing senescence may become available if the biomarkers that we find are specifically related to ageing/cellular senescence. Similarly, diagnostic biomarkers will be explored. Our findings will require validation in independent studies, and our dataset shall be useful to validate the findings of other studies. In some of the explorative analyses, we shall include insights from systems biology modelling as well as insights from preclinical animal models. We anticipate that our detailed study protocol and data analysis plan may also guide other biomarker exploration trials. ETHICS AND DISSEMINATION: The study was approved by the local ethics committee (Ethikkommission an der Medizinischen Fakultät der Universität Rostock, A2019-0174), registered at the German Clinical Trials Register (DRKS00021184), and results will be published following standard guidelines.

Adenocarcinoma , Brain Ischemia , Ischemic Stroke , Pancreatic Neoplasms , Stroke , Adenocarcinoma/epidemiology , Aging , COVID-19 , Cellular Senescence , Cohort Studies , Comorbidity , Female , Germany/epidemiology , Humans , Male , Pancreatic Neoplasms/epidemiology , Prospective Studies , Quality of Life , SARS-CoV-2 , Stroke/epidemiology
Ageing Res Rev ; 62: 101091, 2020 09.
Article in English | MEDLINE | ID: covidwho-343168


Fighting the current COVID-19 pandemic, we must not forget to prepare for the next. Since elderly and frail people are at high risk, we wish to predict their vulnerability, and intervene if possible. For example, it would take little effort to take additional swabs or dried blood spots. Such minimally-invasive sampling, exemplified here during screening for potential COVID-19 infection, can yield the data to discover biomarkers to better handle this and the next respiratory disease pandemic. Longitudinal outcome data can then be combined with other epidemics and old-age health data, to discover the best biomarkers to predict (i) coping with infection & inflammation and thus hospitalization or intensive care, (ii) long-term health challenges, e.g. deterioration of lung function after intensive care, and (iii) treatment & vaccination response. Further, there are universal triggers of old-age morbidity & mortality, and the elimination of senescent cells improved health in pilot studies in idiopathic lung fibrosis & osteoarthritis patients alike. Biomarker studies are needed to test the hypothesis that resilience of the elderly during a pandemic can be improved by countering chronic inflammation and/or removing senescent cells. Our review suggests that more samples should be taken and saved systematically, following minimum standards, and data be made available, to maximize healthspan & minimize frailty, leading to savings in health care, gains in quality of life, and preparing us better for the next pandemic, all at the same time.

Aging/immunology , Biomarkers , Coronavirus Infections , Inflammation/diagnosis , Mass Screening/methods , Pandemics , Pneumonia, Viral , Aged , Betacoronavirus , COVID-19 , Frailty , Humans , Quality of Life , SARS-CoV-2