An Atypical Case of Myxedema Coma with Concomitant Nonconvulsive Seizure.

Hypothyroidism is a prevalent condition in the general population that is treatable with appropriately dosed thyroid hormone replacement medication. Infrequently, patients will present with myxedema coma, characterized by hypothermia, hypotension, bradycardia, and altered mental status in the setting of severe hypothyroidism. Myxedema coma has also been known to manifest in a number of unusual and dangerous forms. Here, we present the case of a woman we diagnosed with an uncharacteristic expression of myxedema coma and nonconvulsive seizure complicated by a right middle cerebral artery infarct.

Bosutinib for the Treatment of Philadelphia Chromosome-Positive Leukemias.

INTRODUCTION: Bosutinib is a dual ABL1 and SRC third generation tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with chronic myelogenous leukemia (CML) resistant to or intolerant of other BCR-ABL1 inhibitors. Bosutinib is active against leukemia cells expressing imatinib-resistant BCR-ABL1 mutations. Mechanistically, this agent may also be beneficial for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) because in preclinical animal models, SRC accelerates ALL disease development. AREAS COVERED: Here we review the current scientific and medical literature on the role of bosutinib for the treatment of CML. We address the unique therapeutic advantages of this agent, specifically its ability to inhibit mutant BCR-ABL1 kinases conferring resistance to other TKIs and its unique safety profile consisting of mainly manageable self-limited diarrhea, not cardiovascular, side effects. Long-term toxicities reported with dasatinib, nilotinib and ponatinib have not been described with bosutinib. Lastly, we present preclinical data demonstrating that bosutinib inhibits a broader range of tyrosine kinases than any other TKI, including those implicated in acute leukemia. EXPERT OPINION: We propose that future studies should explore the use of bosutinib in Ph+ ALL due to its multi-kinase inhibitory activity and its relatively long-term safety compared to other second and third generation TKIs.