Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment.

Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLNKO). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLNKO mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLNWT) or MSLNKO mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLNKO mice compared to MSLNWT mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.

Index Case of COVID-19 Myocarditis Requiring BiV-ICD for Primary Prevention of Sudden Cardiac Death.

INTRODUCTION: The severity of clinical presentation of COVID-19 myocarditis ranges from incidental identification of depressed left ventricular ejection fraction, cardiogenic shock requiring percutaneous mechanical circulatory support, to fatal fulminant myocarditis. In previously reported cases, surviving patients experienced improvement in left ventricular ejection fraction with the use of glucocorticoids and antivirals (+/- intravenous immunoglobulin/ convalescent plasma). We report the first case of COVID-myocarditis in a surviving patient where a persistently depressed left ventricular ejection fraction (less than 35 percent) despite optimal therapy prompted implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden cardiac death. CASE PRESENTATION: A previously healthy 67-year-old man, diagnosed with mild COVID-19 pneumonia five days prior, presented to the emergency department with suspected STEMI (hypoxia, substernal chest pain and known left bundle branch block). Left heart catheterization showed patent coronary arteries. Transthoracic echocardiogram showed severely depressed ejection fraction (15-20 percent). CT showed bilateral infiltrates: treatment was started with dexamethasone, remdesivir and convalescent plasma for acute hypoxic respiratory failure due to COVID-19 pneumonia. After a four-day hospitalization, guideline-directed medical therapy at maximum tolerated doses over three months did not improve left ventricular ejection fraction. CONCLUSION: This is the index case of COVID-19 myocarditis-mediated heart failure with reduced ejection fraction requiring ICD for primary prevention of sudden cardiac death.