initiated for septic shock. She was noted to have an unstageable sacral decubitus ulcer and CT imaging demonstrated extensive air locules extending from the sacral wound through the soft tissues of the lumbar region, consistent with Fournier’s gangrene. The patient underwent emergent surgical debridement. Despite aggressive therapy over several days, the patient remained unresponsive with persistent vasopressor requirements, and she was ultimately transitioned to comfort care. Discussion: Although this case of Fournier’s gangrene is not proven to have been directly caused by the initiation of an SGLT2i, the association
between this class of medication and necrotizing infections is well documented with more than 50 cases of Fournier’s gangrene in patients taking an SGLT2i. While the incidence of Fournier’s gangrene is increased in all patients with T2DM, the addition of an SGLT2i seems to further increase risk by exacerbating glucosuria and promoting bacterial colonization. It has also been suggested that poor genital hygiene may increase the risk of Fournier’s gangrene. For these reasons, caution should be used when initiating SGLT2i therapy in patients at increased risk for Fournier’s gangrene, specifically those who are obese or have decreased mobility.
SARS-COV-2 DECREASES NEURONAL ACTIVITY IN BRAINSTEM RESPIRATORY CENTERS IN C57BI6/J MICE India Pasley, Ryan Miller, Luke Restivo, Eric Lazartigues, PhD; LSU Health School of Medicine, New Orleans, LA.
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, targets the respiratory system, leading to symptoms such as cough, fever, and difficulty breathing. As the mechanisms behind SARS-CoV-2 infections continue to be studied, understanding of how this virus targets specific tissues becomes more apparent. Angiotensin-converting enzyme-2 (ACE2), the target of SARS-CoV infections and a functional receptor for SARS-CoV-2 invasions is highly expressed in many tissues throughout the body, including the lungs, kidneys, and brain. Notably, our group previously reported that neurons are the main cells within the brain expressing ACE2. Accordingly, we hypothesized that neuronal infection of brainstem respiratory centers by SARS-CoV-2 could contribute to respiratory symptoms associated with COVID-19, specifically respiratory failure. Study: C57BI6/J mice inoculated with different doses of SARS-CoV-2 virus (7.5x103 and 1.5x104 units) or mock-infected intranasally were euthanized 5 days post-infection using CO2 hypoxia. Harvested mice brains received from the BSL-3 facility in Galveston were carefully dissected out and preserved in OTC
before sectioning on a cryostat. Sections containing the retrotrapezoid nucleus (RTN) were selected. Immunohistochemistry for c-Fos, a marker for neuronal activity, was performed, and the sections were incubated overnight with a primary monoclonal antibody (rabbit anti-c-fos, 1:1000) followed with a secondary goat anti-rabbit fluorescent IgG (GFP, 1:200, 1h) antibody. RTN and non-RTN (negative control region) images were taken using a confocal microscope. Activated neurons (c-Fos positive) were counted within a set area overlapping the RTN, by 2 investigators, averaged, and the data were analyzed using a two-way ANOVA followed by Bonferroni multiple comparisons test. Discussion: Our data show that euthanasia by hypoxia led to neuronal activation in RTN of mice, with mock-infected mice showing the highest level of activated neurons. SARS-CoV-2 exposure dose-dependently reduced neuronal activation most likely due to apoptosis. We conclude that SARS-CoV-2 targets neurons in respiratory centers, possibly contributing to impaired respiratory function in infected patients.
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