Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

BACKGROUND: Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo. OBJECTIVE: Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19. METHOD: We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded. RESULTS: A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively. CONCLUSIONS AND RELEVANCE: This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.

A Double Hit to Ubiquitination Leading to a New Diagnosis of VEXAS Syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly defined illness that bridges hematology, oncology, and rheumatology. Its pathophysiology originates in a mutation in the UBA1 gene that leads to a defect in ubiquitination resulting in a severe systemic inflammatory syndrome. It is associated with significant morbidity and mortality; however, data are scarce due to limited cases described in the literature. Here we describe a case of a male in his 60s who was referred to hematology-oncology due to progressive dyspnea, poor oral intake, and weight loss. He was diagnosed with relapsing polychondritis 2 years prior; however, his symptoms did not improve despite treatment. He was ultimately diagnosed with VEXAS syndrome with a mutation in UBA1 (ubiquitin-like modifier activating enzyme 1) and a concurrent SQSTM1 mutation. In addition, the coexistence of two mutations in the ubiquitination pathway in the same patient has not been reported to date. This patient and the treatment course were compared to pre-existing literature to increase awareness and improve the medical management of VEXAS syndrome.

A Rare and Unusual Cause of Ischemic Stroke to Be Aware of.

Congenital absence of an internal carotid artery (ICA) is an extremely rare vascular anomaly. This case report presents an instance of right ICA agenesis to highlight the importance of early identification of this anomaly and its impact on disease presentation and complications. With transient ischemic attack (TIA), cerebrovascular accident (CVA), and cerebral aneurysms being among the chief presenting scenarios or course of the anomaly, it is important to have a high level of suspicion for these in patients with known ICA agenesis. Understanding the underlying development of this vasculature and its impact on cerebral circulation aids in identifying possible findings on imaging. This case report aims to delineate the pathophysiology of ICA agenesis, recognition of the vasculature that contributes to the anomaly, different presentations of the disease, complications, and obstacles in management.

COVID-19 Infection Presenting With Severe Hydrocephalus and Acute Stroke: A Case Report.

Hydrocephalus is the accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles and is considered an emergency in acute presentation. Hydrocephalus typically presents with symptoms of headache, nausea, vomiting, lethargy, vision changes and seizure; furthermore, narrowing down the underlying etiology of hydrocephalus can aid in treatment and management options. We present a rare case of a patient that presented with a recent diagnosis of COVID-19 and was found to have acute hydrocephalus and stroke. The aim of this case report is to explore the link between COVID-19 and the development of hydrocephalus and stroke by delineating the underlying pathophysiology of COVID-19 as well as the etiologies of hydrocephalus and possible management strategies. We hope to highlight the importance of keeping an open differential for presentations of headaches and also emphasize the potential complications of COVID-19 infection to help better patient outcomes.

The Effects of 1-Hz rTMS on Emotional Behavior and Dendritic Complexity of Mature and Newly Generated Dentate Gyrus Neurons in Male Mice.

Low-frequency repetitive transcranial magnetic stimulation (1-Hz rTMS) is a promising noninvasive tool for the treatment of depression. Hippocampal neuronal plasticity is thought to play a pivotal role in the pathophysiology of depressive disorders and the mechanism of action of antidepressant treatments. We investigated the effect of 1-Hz rTMS treatment on hippocampal dentate gyrus structural plasticity and related emotional behaviors modifications. Experimentally, adult male mice received either five days of 1-Hz rTMS or Sham stimulation. After stimulation, the mice underwent a battery of tests for anxiety-like and depression-like behaviors. We also tested the effect of treatment on mature and newly generated granule cell dendritic complexity. Our data showed that 1-Hz rTMS induced structural plasticity in mature granule cells, as evidenced by increased dendritic length and number of intersections. However, the stimulation did not increase the proliferation of the dentate gyrus progenitor cells. On the contrary, the stimulated mice showed increased dendritic complexity of newly generated neurons. Moreover, 1-Hz rTMS resulted in antidepressant-like effects in the tail suspension test, but it did not affect anxiety-like behaviors. Therefore, our results indicate that 1-Hz rTMS modulates dentate gyrus morphological plasticity in mature and newly generated neurons. Furthermore, our data provide some evidence of an association between the antidepressant-like activity of 1-Hz rTMS and structural plasticity in the hippocampus.