Spontaneous Oropharyngeal Hemorrhage Complicated by Cirrhosis, Resulting in Hemorrhagic Shock.

BACKGROUND Spontaneous oropharyngeal hemorrhage is rare and is often associated with other predisposing factors. This can result in hemodynamic instability in the presence of other bleeding sources. It is oftentimes difficult to diagnose due to its limitations to visual inspection of the oropharyngeal structures. It is commonly mistaken for hemoptysis or hematemesis upon initial evaluation. Trauma, infection, pulmonary pathologies (ie, lung cancer or tuberculosis), gastrointestinal pathologies (ie, esophageal/gastric varices, Mallory-Weiss tears, esophagitis), coagulopathies, medications, and prolonged intubation have been shown to increase the risk of oropharyngeal hemorrhage. CASE REPORT A 54-year-old man with a medical history of alcohol use disorder, liver cirrhosis, portal hypertension, and gastric varices presented with altered mental status. He was subsequently intubated for airway protection. Bleeding from the oropharynx was later found. Esophagogastroduodenoscopy (EGD) and bronchoscopy were unrevealing. Computed tomography angiography (CTA) of the head and neck revealed active bleeding of the right posterior pharyngeal artery, which was emergently embolized. Over the next few days, he continued to bleed from the oropharynx and became hemodynamically unstable. CTA abdomen showed bleeding from gastric varices and large-volume hemoperitoneum with multiple sources of active bleeding from the liver, duodenum, and jejunum. CONCLUSIONS We present a rare case of spontaneous oropharyngeal hemorrhage and gastric variceal bleeding resulting in hemorrhagic shock in a cirrhotic patient with multiple predisposing factors. If a patient presents with spontaneous oropharyngeal hemorrhage, clinicians should consider bleeding from the oropharynx if EGD and bronchoscopy are unrevealing. Thus, an emergent CTA of the head and neck should be strongly considered to further evaluate a potential source of active bleeding, as delayed diagnosis can be life-threatening.

A synergetic screening approach with companion effector for combination therapy: application to retinoblastoma.

For many cancers, the lack of potency and the toxicity of current drugs limits the dose achievable in patients and the efficacy of treatment. Among them, retinoblastoma is a rare cancer of the eye for which better chemotherapeutic options are needed. Combination therapy is a compelling approach to enhance the efficacy of current treatment, however clinical trials to test rationally designed combinations of approved drugs are slow and expensive, and limited by our lack of in-depth knowledge of drug specificity. Since many patients already turn to nutraceuticals in hopes of improving their condition, we hypothesized that certain approved drugs could potentially synergize with widely consumed supplements. Following this hypothesis, we devised an alternative screening strategy aimed at taking advantage of a bait compound such as a nutraceutical with potential therapeutic benefits but low potency, by screening chemical libraries for approved drugs that synergize with this companion effector. As a proof of concept, we sought to identify approved drugs with synergetic therapeutic effects toward retinoblastoma cells in combination with the antioxidant resveratrol, popular as a supplement. We systematically tested FDA-approved drugs and known bioactives seeking to identify such pairs, which led to uncovering only a few additive combinations; but to our surprise, we identified a class of anticancer drugs widely used in the clinic whose therapeutic effect is antagonized with resveratrol. Our observations could explain in part why some patients do not respond well to treatment. Our results validate this alternative approach, and we expect that our companion effector strategy could significantly impact both drug discovery and the nutraceutical industry.