Drug-induced immune thrombocytopenia (DITP) is a very rare disease, with an estimated annual incidence of 10 cases per million. Oxaliplatin and irinotecan are widely used as chemotherapy for high-risk stage II and III colorectal cancer, and DITP has been reported to occur in patients using those agents. To treat unresectable metastatic colorectal cancer, bevacizumab is used in combination with oxaliplatin or irinotecan, and there have been a few reports of DITP cases in patients receiving that regimen. In this report, we describe a 68-year-old male patient with metastatic colon cancer (KRAS mutant type) to the liver and lung who developed acute immune-mediated thrombocytopenia due to bevacizumab-FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) therapy. During treatment, he showed purpura in his lower extremities on 21st cycle day 2. Lab work revealed a platelet count of less than 2,000/mL, reflecting a decrease from 135,000/mL at the start of the cycle 1 day prior. He did not have any other types of cytopenia or significant changes in laboratory findings. We diagnosed DITP due to bevacizumab-FOLFOX, and the patient did not show isolated thrombocytopenia after switching to Ziv-aflibercept-FOLFIRI (5-fluorouracil, leucovorin, and irinotecan).

The FOLFOX regimen (combination of leucovorin, 5-fluorouracil, and oxaliplatin) is the first-line treatment for high-risk stage 2 and 3 colorectal cancer patients. While hypersensitivity reactions (HSRs) caused by oxaliplatin are commonly reported, HSRs due to leucovorin have been infrequently reported. This report aims to investigate the clinical presentation, diagnosis, and management of leucovorin induced HSRs. A 60-year-old female developed generalized edema, dyspnea, and facial redness during cetuximab plus FOLFOX chemotherapy administered for management of metastatic colorectal cancer. Because HSRs induced by oxaliplatin are commonly reported, we initially presumed an oxaliplatin-induced HSR. However, despite undergoing oxaliplatin desensitization, HSRs persisted, and they were still observed when leucovorin was administered without oxaliplatin. The patient was diagnosed with leucovorin-induced HSR and underwent leucovorin desensitization. However, the reactions recurred within 30 minutes of the initiating the desensitization. Considering unsuccessful leucovorin desensitization, leucovorin was excluded. The patient received cetuximab and oxaliplatin chemotherapy without leucovorin to date without any adverse effects. While leucovorin-induced HSRs are infrequently reported, they should still be regarded as potential adverse effects.

The mosquito-borne pathogen Zika virus may result in neurological disorders such as Guillain–Barré syndrome and microcephaly. The virus is classified as a member of the Flaviviridae family and its wide spread in multiple continents is a significant threat to public health. So has created a need to develop animal models to examine the pathogenesis of the disease and develop vaccines. To examine the clinical profile during Zika virus infection, we infected neonatal and adult wild-type mice (C57BL/6 and Balb/c) and compared the clinical signs of African-lineage strain (MR 766) and Asian-lineage strain (PRVABC59, MEX2-81) of Zika virus. Consistent with previous reports, eight-week-old female Balb/c mice infected with these viral strains showed no changes in body weight, survival rate, and no neurologic signs, but demonstrated increases in the weights of spleens and hearts. However, one-day-old neonates showed significantly lower survival rate and body weight with the African-lineage strain than the Asian-lineage strain. These results confirmed the pathogenic differences between Zika virus strains. We also evaluated the clinical responses in neonatal and adult mice of different strains. Our findings suggest that these are useful mouse models for characterization of Zika virus for vaccine development.

Insulin sensitizers, while effective in glucose-lowering for diabetes control, are linked to an increased risk of heart disease through mechanisms that are not well understood. In this study, we investigated the molecular mechanisms underlying the effects of insulin sensitization on cardiac sinus node dysfunction. We used pharmacologic or genetic approaches to enhance insulin sensitivity, by treating with pioglitazone or rosiglitazone, or through phosphatase and tensin homolog (PTEN) deletion in cardiomyocytes respectively. We employed an angiotensin II (Ang II)-induced hypertensive animal model which causes sinus node dysfunction and accumulation of oxidized calcium/calmodulin-dependent protein kinase II (CaMKII), which also serves as a biomarker for this defect. While neither PTEN deficiency nor insulin sensitizers caused sinus node dysfunction in normotensive mice, both accelerated the onset of sinus node dysfunction and CaMKII oxidation in hypertensive mice.These abnormalities were accompanied by a significant defect in autophagy as revealed by unc-51 like autophagy activating kinase 1 (ULK1) signaling. Indeed, mice deficient in ulk1 in cardiomyocytes and the sinus node also showed early onset of slow atrial impulse conduction with frequent sinus pauses and upregulated CaMKII oxidation following Ang II infusion similar to that seen with PTEN deficiency, or treatment with insulin sensitizers. To further elucidate the role of autophagy in sinus node dysfunction, we treated mice with a peptide D-Tat-beclin1 that enhanced autophagy, which significantly abrogated the frequent sinus pauses and accumulation of oxidized CaMKII induced by insulin sensitizers treatment, or PTEN deficiency in hypertensive animals. Together, these findings provide clear evidence of the detrimental cardiac effects of insulin sensitization that occurs through failure of autophagy-mediated proteolytic clearance.

The mosquito-borne pathogen Zika virus may result in neurological disorders such as Guillain–Barré syndrome and microcephaly. The virus is classified as a member of the Flaviviridae family and its wide spread in multiple continents is a significant threat to public health. So has created a need to develop animal models to examine the pathogenesis of the disease and develop vaccines. To examine the clinical profile during Zika virus infection, we infected neonatal and adult wild-type mice (C57BL/6 and Balb/c) and compared the clinical signs of African-lineage strain (MR 766) and Asian-lineage strain (PRVABC59, MEX2-81) of Zika virus. Consistent with previous reports, eight-week-old female Balb/c mice infected with these viral strains showed no changes in body weight, survival rate, and no neurologic signs, but demonstrated increases in the weights of spleens and hearts. However, one-day-old neonates showed significantly lower survival rate and body weight with the African-lineage strain than the Asian-lineage strain. These results confirmed the pathogenic differences between Zika virus strains. We also evaluated the clinical responses in neonatal and adult mice of different strains. Our findings suggest that these are useful mouse models for characterization of Zika virus for vaccine development.