Hypoxia-inducible factor (HIF), an important mediator of hypoxia response, is implicated in tumorigenesis in the setting of pseudohypoxia, such as in the inactivation of von Hippel–Lindau tumor suppressor protein (pVHL), leading to development and progression of clear cell renal cell carcinoma (ccRCC). Targeting downstream molecules in HIF pathway, such as vascular endothelial growth factor (VEGF), has led to improvement in clinical outcome for patients with advanced ccRCC, but such therapy thus far has been limited by eventual resistance and treat-ment failure. Following the discovery of HIF-2 alpha playing a key role in ccRCC carcinogenesis, inhibitors targeting HIF-2 alpha have been developed and have demonstrated encouraging efficacy and safety profile in clinical trials. This review discusses HIF-2 alpha as a promising therapeutic target for ccRCC.
Despite androgen dependence in a majority of castration-resistant prostate cancers, some cancer cells are independent of androgen receptor (AR) function, a feature of heterogeneity in prostate cancer. One of the aggressive variants of prostate cancer that are AR independent is neuroendocrine prostate cancer (NEPC). This manuscript will focus on the new finding of human one cut domain family member 2 (ONECUT2) transcription factor and its role in castration resistance, especially in NEPC.
Objectives
To characterize the frequency and association of gastrointestinal (GI) symptoms with outcomes in patients with corona virus disease 2019 (COVID-19) admitted to the hospital.
Methods
Records were retrospectively collected from patients admitted to a tertiary care center in Washington, D.C., with confirmed COVID-19 from March 15, 2020 to July 15, 2020. After adjusting for clinical demographics and comorbidities, multivariate logistic regression analysis was performed.
Results
The most common presenting symptoms of COVID-19 in patients that were admitted to the hospital were cough (38.4%), shortness of breath (37.5%), and fever (34.3%), followed by GI symptoms in 25.9% of patients. The most common GI symptom was diarrhea (12.8%) followed by nausea or vomiting (10.5%), decreased appetite (9.3%), and abdominal pain (3.8%). Patients with diarrhea were more likely to die (odds ratio [OR] 2.750;
p
= 0.006; confidence interval [CI] 1.329–5.688), be admitted to the intensive care unit (ICU) (OR 2.242;
p
= 0.019; CI 1.139–4.413), and be intubated (OR 3.155;
p
= 0.002; CI 1.535–6.487). Additional outcomes analyzed were need for vasopressors, presence of shock, and acute kidney injury. Patients with diarrhea were 2.738 (
p
= 0.007; CI 1.325–5.658), 2.467 (
p
= 0.013; CI 1.209–5.035), and 2.694 (
p
= 0.007; CI 1.305–5.561) times more likely to experience these outcomes, respectively.
Conclusions
Screening questions should be expanded to include common GI symptoms in patients with COVID-19. Health care providers should note whether their patient is presenting with diarrhea due to the potential implications on disease severity and outcomes.
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