No abstract

Background Previous reports have shown various cardiac complications to be associated with COVID-19 including: myocardial infarction, microembolic complications, myocardial injury, arrythmia, heart failure, coronary vasospasm, non-ischemic cardiomyopathy, stress (Takotsubo) cardiomyopathy, pericarditis and myocarditis. These COVID-19 cardiac complications were associated with respiratory symptoms. However, our case illustrates that COVID-19 myopericarditis with cardiac tamponade can present without respiratory symptoms. Case presentation A 58-year-old Caucasian British woman was admitted with fever, diarrhoea and vomiting. She developed cardiogenic shock and Transthoracic echocardiogram (TTE) found a pericardial effusion with evidence of cardiac tamponade. A nasopharyngeal swab showed a COVID-19 positive result, despite no respiratory symptoms on presentation. A pericardial drain was inserted and vasopressor support required on intensive treatment unit (ITU). The drain was removed as she improved, an antibiotic course was given and she was discharged on day 12. Conclusions Our case demonstrates that patients without respiratory symptoms could have COVID-19 and develop cardiac complications. These findings can aid timely diagnosis of potentially life-threatening COVID-19 myopericarditis with cardiac tamponade.

BackgroundThe current TNM staging system for oesophageal adenocarcinoma (OAC) has limited ability to stratify patients and inform clinical management following neo-adjuvant chemotherapy and surgery.ResultsFunctional genomic analysis of the gene expression data using Gene Set Enrichment Analysis (GSEA) identified GLUT1 as putative prognostic marker in OAC.In the discovery cohort GLUT1 positivity was observed in 114 patients (80.9%) and was associated with poor overall survival (HR 2.08, 95% CI 1.1-3.94; p=0.024) following multivariate analysis. A prognostic model incorporating GLUT1, CRM and nodal status stratified patients into good, intermediate and poor prognosis groups (p< 0.001) with a median overall survival of 16.6 months in the poorest group.In the validation set 182 patients (69.5%) were GLUT1 positive and the prognostic model separated patients treated with neo-adjuvant chemotherapy and surgery (p<0.001) and surgery alone (p<0.001) into three prognostic groups.Patients and MethodsTranscriptional profiling of 60 formalin fixed paraffin-embedded (FFPE) biopsies was performed. GLUT1 immunohistochemical staining was assessed in a discovery cohort of 141 FFPE OAC samples treated with neo-adjuvant chemotherapy and surgery at the Northern Ireland Cancer Centre from 2004-2012. Validation was performed in 262 oesophageal adenocarcinomas collected at four OCCAMS consortium centres. The relationship between GLUT1 staining, T stage, N stage, lymphovascular invasion and circumferential resection margin (CRM) status was assessed and a prognostic model developed using Cox Proportional Hazards.ConclusionsGLUT1 staining combined with CRM and nodal status identifies a poor prognosis sub-group of OAC patients and is a novel prognostic marker following potentially curative surgical resection.

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.