ABSTRACT
Diffuse midline glioma (DMG) with H3K27M mutation is an aggressive and difficult to treat pediatric brain tumor. Recurrent gain of function mutations in H3.3 (H3.3A) and H3.1 (H3C2) at the 27th lysine to methionine (H3K27M) are seen in over 2/3 of DMGs, and are associated with a worse prognosis. Due to the anatomical location of DMG, traditional biopsy carries risk for neurologic injury as it requires penetration of vital midline structures. Further, radiographic (MRI) monitoring of DMG often shows non-specific changes, which makes therapeutic monitoring difficult. This indicates a critical need for more minimally invasive methods, such as liquid biopsy, to understand, diagnose, and monitor H3K27M DMG. Here we review the use of all modalities to date to detect biomarkers of H3K27M in CSF, blood, and urine, and compare their effectiveness in detection, diagnosis, and monitoring treatment response. We provide specific detail of recent efforts to monitor CSF and plasma H3K27M cell-free DNA in patients undergoing therapy with the imipridone ONC201. Lastly, we discuss the future of therapeutic monitoring of H3K27M-DMG, including biomarkers such as mitochondrial DNA, mutant and modified histones, and novel sequencing-based approaches for improved detection methods.
ABSTRACT
Purpose of Review: To highlight the challenges associated with providing sedation and analgesia to critically ill patients with coronavirus disease 2019 (COVID-19) and also understand the pathophysiological alterations induced by the disease process as well as the logistical difficulties encountered by providers caring for these patients. We also discuss the rationale and risks associated with the use of common sedative agents specifically within the context of COVID-19 and provide evidence-based management strategies to help manage sedation and analgesia in such patients. Recent Findings: A significant proportion of patients with COVID-19 require intensive care and mechanical ventilation, thus requiring sedation and analgesia. These patients tend to require higher doses of sedative medications and often for long periods of time. Most of the commonly used sedative and analgesic agents carry unique risks that should be considered within the context of the unique pathophysiology of COVID-19, the logistical issues the disease poses, and the ongoing drug shortages. Summary: With little attention being paid to sedation practices specific to patients with COVID-19 in critical care literature and minimal mention in national guidelines, there is a significant gap in knowledge. We review the existing literature to discuss the unique challenges that providers face while providing sedation and analgesia to critically ill patients with COVID-19 and propose evidence-based management strategies.
ABSTRACT
A 59 year-old woman with liver cirrhosis due to hepatitis C, complicated by refractory hepatic hydrothorax was treated with a TIPS (transjugular intrahepatic portosystemic shunt) procedure. The procedure was complicated by substantial gastrointestinal hemorrhage. EGD (esophagogastroduodenoscopy) was performed and revealed hemobilia. A hepatic angiogram was then performed revealing a fistulous tract between a branch of the hepatic artery and biliary tree. Bleeding was successfully stopped by embolization of the bleeding branch of the right hepatic artery. Hemobilia is a rare cause of upper gastrointestinal bleeding with an increasing incidence due to the widespread use of invasive hepatobiliary procedures. Hemobilia is an especially uncommon complication of TIPS procedures. We recommend that in cases of hemobilia after TIPS placement, a physician should immediately evaluate the bleeding to exclude an arterio-biliary fistula.
