The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the severity and mortality in COVID-19 patients with underlying kidney and liver diseases. We retrieved data on the clinical features and primary composite end point of COVID-19 patients from Medline and Embase which had been released from inception by the April 16, 2020. The data on two comorbidities, liver diseases and chronic kidney disease, were pooled and statistically analysed to explain the associated severity and mortality rate. One hundred and forty-two abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and chronic kidney disease (CKD) were 3% (95% CI; 2–3%) and 1% (95% CI; 1–2%), respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) of cases were severe, with 17.65% mortality, while in CKD patients, 83.93% (47/56) of cases were severe and 53.33% (8/15) mortality was reported. This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases or CKD. This will lead to better clinical management and inform the process of implementing more stringent preventative measures for this group of patients.
Pancreatic neuroendocrine tumours (pNETs) are a heterogeneous group of epithelial tumours with neuroendocrine differentiation. Although rare (incidence of <1 in 100,000), they are the second most common group of pancreatic neoplasms after pancreatic ductal adenocarcinoma (PDAC). pNET incidence is however on the rise and patient outcomes, although variable, have been linked with 5-year survival rates as low as 40%. Improvement of diagnostic and treatment modalities strongly relies on disease models that reconstruct the disease ex vivo. A key constraint in pNET research, however, is the absence of human pNET models that accurately capture the original tumour phenotype. In attempts to more closely mimic the disease in its native environment, three-dimensional culture models as well as in vivo models, such as genetically engineered mouse models (GEMMs), have been developed. Despite adding significant contributions to our understanding of more complex biological processes associated with the development and progression of pNETs, factors such as ethical considerations and low rates of clinical translatability limit their use. Furthermore, a role for the site-specific extracellular matrix (ECM) in disease development and progression has become clear. Advances in tissue engineering have enabled the use of tissue constructs that are designed to establish disease ex vivo within a close to native ECM that can recapitulate tumour-associated tissue remodelling. Yet, such advanced models for studying pNETs remain underdeveloped. This review summarises the most clinically relevant disease models of pNETs currently used, as well as future directions for improved modelling of the disease.