RNA Virus Gene Signatures Detected in Patients With Cardiomyopathy After Chemotherapy; A Pilot Study.

Background: Viral infections are pervasive and leading causes of myocarditis. Immune-suppression after chemotherapy increases opportunistic infections, but the incidence of virus-induced myocarditis is unknown. Objective: An unbiased, blinded screening for RNA viruses was performed after chemotherapy with correlation to cardiac function. Methods: High-throughput sequencing of RNA isolated from blood samples was analyzed following chemotherapy for hematological malignancies (N = 28) and compared with left ventricular ejection fraction (LVEF). Results: On initial rigorous analysis, low levels of influenza orthomyxovirus and avian paramyxovirus sequences were detectable, but without significant correlation to LVEF (r = 0.208). A secondary broad data mining analysis for virus sequences, without filtering human sequences, detected significant correlations for paramyxovirus with LVEF after chemotherapy (r = 0.592, P < 0.0096). Correlations were similar for LVEF pre- and post- chemotherapy for orthomyxovirus (R = 0.483, P < 0.0421). Retrovirus detection also correlated with LVEF post (r = 0.453, p < 0.0591), but not pre-chemotherapy, but is suspect due to potential host contamination. Detectable phage and anellovirus had no correlation. Combined sequence reads (all viruses) demonstrated significant correlation (r = 0.621, P < 0.0078). Reduced LVEF was not associated with chemotherapy (P = NS). Conclusions: This is the first report of RNA virus screening in circulating blood and association with changes in cardiac function among patients post chemotherapy, using unbiased, blinded, high-throughput sequencing. Influenza orthomyxovirus, avian paramyxovirus and retrovirus sequences were detectable in patients with reduced LVEF. Further analysis for RNA virus infections in patients with cardiomyopathy after chemotherapy is warranted.

Deriving Immune Modulating Drugs from Viruses-A New Class of Biologics.

Viruses are widely used as a platform for the production of therapeutics. Vaccines containing live, dead and components of viruses, gene therapy vectors and oncolytic viruses are key examples of clinically-approved therapeutic uses for viruses. Despite this, the use of virus-derived proteins as natural sources for immune modulators remains in the early stages of development. Viruses have evolved complex, highly effective approaches for immune evasion. Originally developed for protection against host immune responses, viral immune-modulating proteins are extraordinarily potent, often functioning at picomolar concentrations. These complex viral intracellular parasites have "performed the R&D", developing highly effective immune evasive strategies over millions of years. These proteins provide a new and natural source for immune-modulating therapeutics, similar in many ways to penicillin being developed from mold or streptokinase from bacteria. Virus-derived serine proteinase inhibitors (serpins), chemokine modulating proteins, complement control, inflammasome inhibition, growth factors (e.g., viral vascular endothelial growth factor) and cytokine mimics (e.g., viral interleukin 10) and/or inhibitors (e.g., tumor necrosis factor) have now been identified that target central immunological response pathways. We review here current development of virus-derived immune-modulating biologics with efficacy demonstrated in pre-clinical or clinical studies, focusing on pox and herpesviruses-derived immune-modulating therapeutics.

Chronological Impact of Earthquakes on Blood Pressure: A Literature Review and Retrospective Study of Hypertension in Haiti Before and After the 2010 Earthquake.

Objective: We review prior studies on the incidence of hypertension (HTN) after earthquakes and present a retrospective analysis of HTN after the 2010 earthquake in Haiti. Methods: Prior reports on HTN incidence were reviewed and a retrospective chart review for diagnosis of HTN in 4,308 patient charts was performed over a 7 year period (five clinics). A retrospective cohort study (RCS) was then performed on 11 patients with linear follow-up. Results: The Literature review revealed a significant increase in acute and subacute HTN following earthquakes. However, the chronic effects of earthquakes varied. Our chart review uncovered no significant difference in diagnosed HTN in a Fort-Liberté clinic 128 kilometers (km) distant and 4 weeks post-event. A secondary linear RCS for 11 individuals, prior to and after the earthquake, also did not detect a significant change in HTN prevalence. Conclusion: Prior studies demonstrate acute and subacute, increases in HTN after earthquakes, but late changes have varied. Retrospective studies in the Fort-Liberté clinic, 128 km distant and 4 weeks post-event, revealed no significant change in HTN, confirming prior findings that changes in HTN after earthquakes are early and local events. Further work examining HTN after earthquakes is needed to improve early health care after natural disasters.