Brain Metastases from Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors

BackgroundThe effectiveness of tyrosine kinase inhibitors (TKI) in preventing brain metastases in patients with renal cell carcinoma is unclear.MethodsPreclinical studies were conducted to determine the steady-state brain and plasma concentrations of sorafenib and sunitinib in mice deficient in the drug efflux transporters; p-glycoprotein, and breast cancer resistance protein. A single-institution retrospective analysis of patients treated from 2008 to 2010 was conducted to assess the incidence of brain metastases before and during TKI treatment.ResultsTransport of sorafenib and sunitinib across the blood-brain barrier was restricted. Retrospective analysis revealed that the median time to develop metastatic brain disease was 28 months (range, 1-108 months) while on TKI therapy and 11.5 months (range, 0-64 months) in patients who did not receive TKI therapy. The incidence of brain metastases per month in patients not treated with TKI therapy was 1.6 higher than the incidence in patients treated with TKI therapy.ConclusionsPenetration of sorafenib or sunitinib through an intact blood-brain barrier to brain tissue is limited; however, the incidence of brain metastases per unit time is decreased in patients on TKI therapy in comparison with the “cytokine” era.     

Non-alcoholic steatohepatitis and the risk of myocardial infarction:A population-based national study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a systemic disease with bidirectional relationships with cardiovascular disease(CVD). Non-alcoholic steatohepatitis(NASH) is a more severe subtype of NAFLD. Patients with NASH exhibit more intra and extrahepatic inflammation, procoagulant imbalances and proatherogenic lipid profiles. Whether NASH increases the risk of ischemic heart disease is currently unclear.AIM To investigate the relationship between acute myocardial infarction(MI) and NASH in a large cohort of subjects in the United States.METHODS We reviewed data from a large commercial database(Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms(SNOMED CT), we identified adult with the diagnosis of NASH from 1999-2019. We included patients with the diagnosis of acute MI from 2018-2019. Comorbidities known to be associated with NASH and MI such as obesity, diabetes mellitus, hyperlipidemia, smoking, male gender, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether NASH is independently associated with the risk of MI.RESULTS Out of 55099280 patients, 43170 were diagnosed with NASH(0.08%) and 107000(0.194%) had a MI within 2018-2019. After adjusting for traditional risk factors, NASH conferred greater odds of MI odds ratio(OR) 1.5 [95% confidence interval(CI): 1.40-1.62]. Hyperlipidemia had the strongest association with MI OR 8.39(95%CI: 8.21-8.58) followed by hypertension OR 3.11(95%CI: 3.05-3.17) and smoking OR 2.83(95%CI: 2.79-2.87). NASH had a similar association with MI as the following traditional risk factors like age above 65 years OR 1.47(95%CI: 1.45-1.49), male gender OR 1.53(95%CI: 1.51-1.55) diabetes mellitus OR 1.89(95%CI: 1.86-1.91).CONCLUSION MI appears to be a prevalent disease in NASH. Patients with NASH may need early identification and aggressive cardiovascular risk modification.