Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes and possibly The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and DNA damage-mediated cellular stresses. This seems to be the first report that p53 activates a viral oncogene; therefore, the discovery would be interesting to a broad readership from the fields of oncology to virology.

Objective The effect of body habitus for patients who require extracorporeal membrane oxygenation (ECMO) support has not been well‐studied and may provide insight into patient survival and outcomes. We sought to determine if there is a correlation of body mass index (BMI) with ECMO outcomes. Methods A retrospective chart review was performed for patients who required any form of ECMO support at our institution between 2012 and 2016. Time variables (overall hospital length of stay, intensive care, and ventilator days), and outcomes variables (ability to wean from ECMO, extubation status, hospital survival, 30‐day survival) were studied. Patients were divided into cohorts based on BMI. Descriptive statistics were used to summarize data. Spearman correlation, Fisher's exact test, and independent t‐test were used to assess associations. Results A total of 231 patients required ECMO with a mean BMI of 29 (±6.47; BMI range, 17.6‐57.9). The mean BMI did not differ based on type of support provided (veno‐veno ECMO [VV] vs veno‐arterial [VA]). There was no difference between BMI cohorts for length of stay, time in the intensive care unit (ICU), ability to wean from ECMO, hospital survival or 30‐day survival. Raw BMI did not predict if or when patients were extubated. Conclusions Neither obesity classification nor BMI as a continuous variable affected any of the outcome variables. Respiratory outcomes including the ability to extubate and to remain ventilator‐free were also independent of patient BMI. These data suggest that extremes of body habitus alone should not be used as an exclusion criteria for consideration of ECMO support.

Outcomes for repeat ECMO patients compare favorably to the overall ECMO population and suggest a need to explore and broaden the clinical indications for repeat ECMO.

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This is a response to the Letter to Editor received regarding the article "The effect of patient obesity on extracorporeal membrane oxygenator outcomes and ventilator dependency." We aim to address the authors' comments regarding the relationship between BMI and survival after venoarterial extracorporeal membrane oxygenation (VA-ECMO).