K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-Ras interacts with Bcl-XL. PKC agonists promote apoptosis of cells transformed with oncogenic K-Ras in a S181-dependent manner. K-Ras with a phosphomimetic residue at position 181 induces apoptosis via a pathway that requires Bcl-XL. The PKC agonist bryostatin-1 inhibited the growth in vitro and in vivo of cells transformed with oncogenic K-Ras in a S181-dependent fashion. These data demonstrate that the location and function of K-Ras are regulated directly by PKC and suggest an approach to therapy of K-Ras-dependent tumors with agents that stimulate phosphorylation of S181.

for the Northwell Health COVID-19 Research Consortium Elevations in troponin levels have been shown to predict mortality in patients with coronavirus disease 2019 (COVID-19). The role of inflammation in myocardial injury remains unclear. We sought to determine the association of elevated troponin with mortality in a large, ethnically diverse population of patients hospitalized with COVID-19, and to determine the association of elevated inflammatory markers with increased troponin levels. We reviewed all patients admitted at our health system with COVID-19 from March 1 to April 27, 2020, who had a troponin assessment within 48 hours of admission. We used logistic regression to calculate odds ratios (ORs) for mortality during hospitalization, controlling for demographics, co-morbidities, and markers of inflammation. Of 11,159 patients hospitalized with COVID-19, 6,247 had a troponin assessment within 48 hours. Of these, 4,426 (71%) patients had normal, 919 (15%) had mildly elevated, and 902 (14%) had severely elevated troponin. Acute phase and inflammatory markers were significantly elevated in patients with mildly and severely elevated troponin compared with normal troponin. Patients with elevated troponin had significantly increased odds of death for mildly elevated compared with normal troponin (adjusted OR, 2.06; 95% confidence interval, 1.68 to 2.53; p < 0.001) and for severely elevated compared with normal troponin (OR, 4.51; 95% confidence interval, 3.66 to 5.54; p < 0.001) independently of elevation in inflammatory markers. In conclusion, patients hospitalized with COVID-19 and elevated troponin had markedly increased mortality compared with patients with normal troponin levels. This risk was independent of cardiovascular co-morbidities and elevated markers of inflammation.

Myocarditis encompasses both primary and secondary processes causing inflammation of the myocardium. Viral infections are a common secondary cause of myocarditis with important clinical relevance. Viral myocarditis has a varied clinical presentation, potentially resulting in significant morbidity and mortality. Acutely, systolic dysfunction and sudden cardiac death may ensue; chronically, myocarditis may result in a dilated cardiomyopathy requiring heart transplantation. Myocarditis is thought to be one of the most common causes of myocardial infarction with nonobstructive coronary arteries (MINOCA), with important consequences for cardiovascular outcomes. Patients with myocarditis are currently underdiagnosed. Cardiac MRI has evolved as the noninvasive test of choice, with cardiac MRI‐specific diagnostic requirements defined in the Lake Louise Criteria (LLC). Detecting the presence of tissue edema, hyperemia, and necrosis in both acute and chronic stages form the foundation of the LLC. Cardiac MR for chronic myocarditis (greater than 8 weeks from symptom onset) has decreased sensitivity for diagnosis. Emerging sequences such as T1 and T2 parametric maps provide tissue characterization regarding inflammation without reliance on reference tissue, overcoming limitations of the LLC. Beyond diagnostic criteria, these imaging techniques have proven useful in further characterizing the diseased tissue, prognostication, and clinical decision‐making. This review describes the utility and evolving use of cardiac MRI in clinical practice. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2018;47:1061–1071.