Search

Background: The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in the treatment of neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, there are many other vasoactive peptides that could potentially be used for this purpose. Methods: We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the evidence available. Results: We identified 33 vasoactive peptides with potential blood-brain barrier permeability-altering properties. To date, none of these are shown to open the blood-brain barrier in humans. 12 vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 23 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier. Conclusion: Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), first identified in December 2019 in Wuhan, China, has rapidly spread worldwide, is now a public health emergency, and has been declared a pandemic. While SARS-CoV-2 is known to cause significant pulmonary disease, ranging from pneumonia to acute respiratory distress syndrome (ARDS), various extrapulmonary manifestations of COVID-19 have also been reported. Growing evidence suggests that COVID-19 leads to a hypercoagulable state leading to micro and macro-vascular angiopathies. We present a case of an 80-year-old male without a previous history of prothrombotic disorders who developed descending aortic thrombosis, approximately 40% stenosis, at the level of the diaphragmatic hiatus and acute limb ischemia secondary to COVID-19 requiring emergent surgical intervention. After 12 days of persistent ischemic left lower extremity imaging despite thrombectomy, bypass, and therapeutic heparin, the patient's limb was deemed non-salvageable and underwent left above-knee amputation. Transthoracic echocardiogram revealed normal left ventricular function, moderate pulmonary hypertension, and no evidence of atrial septal defect, aortic root abnormalities, or intraventricular thrombi. Evaluation of autoimmune and inflammatory vasculitis was negative. While further study into the prothrombotic nature of this condition still needs to be pursued, the thromboembolic risk of COVID-19 represents an urgent need for appropriate anticoagulation for venous thrombosis. Arterial thrombosis requires other kinds of management to avoid the severe adverse effects of emboli and related ischemia. This current case highlights the need for randomized control trials testing different prophylactic strategies. Further evidence is also required for the role of amputation surgery when initial interventions for revascularization fail to restore blood flow.

Sickle cell hepatopathy is a well-described but uncommonly seen complication of sickle cell disease and is usually caused by multiple overlapping processes. A more acute liver complication is hepatic sequestration which is important to recognize in order to initiate life-saving treatment. A 33-year-old woman with sickle cell disease complicated by painful crises, splenic infarction and significant alcohol abuse presented with gastrointestinal distress, pain crisis, acute-on-chronic anemia, and hyperbilirubinemia in the setting of greater than baseline alcohol consumption. She was found to have hepatomegaly, encephalopathy, severe jaundice, and severe hyperbilirubinemia. She was treated with red cell exchange and supportive care which resulted in an improvement in her symptoms as well as hyperbilirubinemia. She was discharged with plans for monthly red cell exchange, iron chelation therapy, and close monitoring of liver disease was planned upon discharge. This case illustrates that chronic liver disease can occur in sickle cell disease (Hgb SS) especially in the setting of acquired iron overload. More acutely, sequestration is a serious and life-threatening complication of sickle cell disease that can culminate in acute liver failure. Primary treatment for hepatic sequestration is red cell exchange along with management of contributing comorbidities, and symptomatic management of encephalopathy. In end-stage liver disease, transplantation may be considered in the context of the patient’s clinical status.

Bone marrow necrosis (BMN) is a rare pathological diagnosis, with an incidence of 0.3% to 2%. It is most often associated with hematological malignancies and less commonly due to solid tumors, infections, medications, sickle cell disease, chemotherapy, radiotherapy, or idiopathic causes. We reviewed bone marrow biopsies performed in our institution from 2009 to 2019 and found three cases of BMN. Two cases were secondary to neoplastic causes, while the third one was possibly from alcohol abuse.