Publications by authors named "Mathew S Lopes"

3 Publications

  • Page 1 of 1

Epidemiology of Acute Heart Failure in Critically Ill Patients With COVID-19: An Analysis From the Critical Care Cardiology Trials Network.

J Card Fail 2022 Apr 17;28(4):675-681. Epub 2022 Jan 17.

Levine Cardiac Intensive Care Unit, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Acute heart failure (HF) is an important complication of coronavirus disease 2019 (COVID-19) and has been hypothesized to relate to inflammatory activation.

Methods: We evaluated consecutive intensive care unit (ICU) admissions for COVID-19 across 6 centers in the Critical Care Cardiology Trials Network, identifying patients with vs without acute HF. Acute HF was subclassified as de novo vs acute-on-chronic, based on the absence or presence of prior HF. Clinical features, biomarker profiles and outcomes were compared.

Results: Of 901 admissions to an ICU due to COVID-19, 80 (8.9%) had acute HF, including 18 (2.0%) with classic cardiogenic shock (CS) and 37 (4.1%) with vasodilatory CS. The majority (n = 45) were de novo HF presentations. Compared to patients without acute HF, those with acute HF had higher cardiac troponin and natriuretic peptide levels and similar inflammatory biomarkers; patients with de novo HF had the highest cardiac troponin levels. Notably, among patients critically ill with COVID-19, illness severity (median Sequential Organ Failure Assessment, 8 [IQR, 5-10] vs 6 [4-9]; P = 0.025) and mortality rates (43.8% vs 32.4%; P = 0.040) were modestly higher in patients with vs those without acute HF.

Conclusions: Among patients critically ill with COVID-19, acute HF is distinguished more by biomarkers of myocardial injury and hemodynamic stress than by biomarkers of inflammation.
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April 2022

Case 30-2019: A 65-Year-Old Woman with Lung Cancer and Chest Pain.

N Engl J Med 2019 Sep;381(13):1268-1277

From the Departments of Medicine (T.E.G., M.J.M., T.G.N.), Radiology (M.K.K.), and Pathology (J.R.S.), Massachusetts General Hospital, the Departments of Medicine (T.E.G., M.S.L., M.J.M., T.G.N.), Radiology (M.K.K.), and Pathology (J.R.S.), Harvard Medical School, and the Department of Medicine, Brigham and Women's Hospital (M.S.L.) - all in Boston.

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September 2019

K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif.

Proc Natl Acad Sci U S A 2015 Jan 5;112(3):779-84. Epub 2015 Jan 5.

New York University Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016;

The two products of the KRAS locus, K-Ras4A and K-Ras4B, are encoded by alternative fourth exons and therefore, possess distinct membrane-targeting sequences. The common activating mutations occur in exons 1 or 2 and therefore, render both splice variants oncogenic. K-Ras4A has been understudied, because it has been considered a minor splice variant. By priming off of the splice junction, we developed a quantitative RT-PCR assay for K-Ras4A and K-Ras4B message capable of measuring absolute amounts of the two transcripts. We found that K-Ras4A was widely expressed in 30 of 30 human cancer cell lines and amounts equal to K-Ras4B in 17 human colorectal tumors. Using splice variant-specific antibodies, we detected K-Ras4A protein in several tumor cell lines at a level equal to or greater than that of K-Ras4B. In addition to the CAAX motif, the C terminus of K-Ras4A contains a site of palmitoylation as well as a bipartite polybasic region. Although both were required for maximal efficiency, each of these could independently deliver K-Ras4A to the plasma membrane. Thus, among four Ras proteins, K-Ras4A is unique in possessing a dual membrane-targeting motif. We also found that, unlike K-Ras4B, K-Ras4A does not bind to the cytosolic chaperone δ-subunit of cGMP phosphodiesterase type 6 (PDE6δ). We conclude that efforts to develop anti-K-Ras drugs that interfere with membrane trafficking will have to take into account the distinct modes of targeting of the two K-Ras splice variants.
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January 2015