BACKGROUND Patients with myasthenia gravis (MG) are at a higher risk of developing Takotsubo cardiomyopathy (TTC), particularly during a myasthenic crisis. Myasthenic crisis-associated TTC occurs predominantly in women. In this case report, we present a man with metastasized prostate carcinoma who developed TTC after new-onset MG. CASE SUMMARY An 81-year-old man with non-insulin dependent diabetes mellitus and metastasized prostate carcinoma presented with dyspnea. During primary assessment examination at the emergency department, there was evident blepharoptosis of his right eye. His electrocardiograms were suggestive of an acute anterior wall myocardial infarction, for which he underwent emergency coronary angiography. No obstructive coronary artery disease was found. During the coronary angiography, the patient developed respiratory failure and was admitted to the Intensive Care Unit for non-invasive respiratory support. The following day, diagnostic neostigmine test revealed a myasthenic crisis. Bedside echocardiography revealed left ventricular apical ballooning with a typical appearance of TTC. Despite the potentially reversible character of both MG and TTC, the patient and family requested an end of support in the Intensive Care Unit due to age and chronic malignancy with reduced quality of life in recent months after non-chemo-responding prostate carcinoma. The patient died soon after treatment withdrawal. CONCLUSION Elderly men should be carefully evaluated for TTC when new-onset MG is diagnosed.

<p>Supplementary method and supplementary figures</p>

<div>Abstract<p>The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors, such as glioblastomas (GBM). Microglia/macrophages comprising approximately 40% of a GBM tumor may limit virotherapeutic efficacy. Here, we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis. Internalized virus remained capable of expressing reporter genes while viral replication was blocked. Macrophage/microglia formed a nonpermissive OV barrier, preventing dissemination of oHSV-1 in the glioma mass. The deficiency in viral replication in microglial cells was associated with silencing of particular viral genes. Phosphorylation of STAT1/3 was determined to be responsible for suppressing oHSV-1 replication in macrophages/microglia. Treatment with the oxindole/imidazole derivative C16 rescued oHSV-1 replication in microglia/macrophages by inhibiting STAT1/3 activity. In the U87 xenograft model of GBM, C16 treatment overcame the microglia/macrophage barrier, thereby facilitating tumor regression without causing a spread of the virus to normal organs. Collectively, our results suggest a strategy to relieve a STAT1/3-dependent therapeutic barrier and enhance oHSV-1 oncolytic activity in GBM.</p><p><b>Significance:</b> These findings suggest a strategy to enhance the therapeutic efficacy of oncolytic virotherapy in glioblastoma. <i>Cancer Res; 78(3); 718–30. ©2017 AACR</i>.</p></div>

<p>Supplementary method and supplementary figures</p>

<div>Abstract<p>The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors, such as glioblastomas (GBM). Microglia/macrophages comprising approximately 40% of a GBM tumor may limit virotherapeutic efficacy. Here, we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis. Internalized virus remained capable of expressing reporter genes while viral replication was blocked. Macrophage/microglia formed a nonpermissive OV barrier, preventing dissemination of oHSV-1 in the glioma mass. The deficiency in viral replication in microglial cells was associated with silencing of particular viral genes. Phosphorylation of STAT1/3 was determined to be responsible for suppressing oHSV-1 replication in macrophages/microglia. Treatment with the oxindole/imidazole derivative C16 rescued oHSV-1 replication in microglia/macrophages by inhibiting STAT1/3 activity. In the U87 xenograft model of GBM, C16 treatment overcame the microglia/macrophage barrier, thereby facilitating tumor regression without causing a spread of the virus to normal organs. Collectively, our results suggest a strategy to relieve a STAT1/3-dependent therapeutic barrier and enhance oHSV-1 oncolytic activity in GBM.</p><p><b>Significance:</b> These findings suggest a strategy to enhance the therapeutic efficacy of oncolytic virotherapy in glioblastoma. <i>Cancer Res; 78(3); 718–30. ©2017 AACR</i>.</p></div>