Regurgitation under anesthesia in a fasted patient prescribed semaglutide for weight loss: a case report.

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide are a class of medications prescribed to treat type 2 diabetes mellitus, and more recently, as an adjunct for weight loss because of its effects of delaying gastric emptying and suppressing appetite. Semaglutide is a long-acting agent with a half-life of approximately one week, and there are currently no guidelines that address the perioperative management of such agents. CLINICAL FEATURES: We describe an unexpected case of regurgitation of a large volume of gastric contents upon induction of general anesthesia in a nondiabetic, nonobese patient despite a long preoperative fasting period (20 hr for solids and eight hours for clear fluids). This patient had no traditional risk factors for regurgitation or aspiration but was taking the GLP-1 RA semaglutide for weight loss and had last taken the medication two days before their scheduled procedure. CONCLUSIONS: Patients taking long-acting GLP-1 RAs such as semaglutide may be at risk of pulmonary aspiration under anesthesia. We propose strategies to mitigate this risk including holding the medication four weeks prior to a scheduled procedure when feasible and considering full stomach precautions.

RéSUMé: OBJECTIF: Les agonistes des récepteurs du glucagon-like peptide-1 (AR GLP-1) tels que le sémaglutide sont une classe de médicaments prescrits pour traiter le diabète sucré de type 2 et, plus récemment, comme complément à la perte de poids en raison de ses effets de retardement de la vidange gastrique et de suppression de l'appétit. Le sémaglutide est un agent à action prolongée dont la demi-vie est d'environ une semaine, et il n'existe actuellement aucune ligne directrice traitant de la prise en charge périopératoire de ces agents. CARACTéRISTIQUES CLINIQUES: Nous décrivons un cas inattendu de régurgitation d'un important volume de contenu gastrique lors de l'induction de l'anesthésie générale chez une personne non diabétique et non obèse malgré une longue période de jeûne préopératoire (20 heures pour les solides et huit heures pour les liquides clairs). Cette personne ne présentait aucun facteur de risque traditionnel de régurgitation ou d'aspiration, mais prenait du sémaglutide (AR GLP-1) à des fins de perte de poids et avait pris le médicament pour la dernière fois deux jours avant l'intervention prévue. CONCLUSION: Les patient·es prenant des AR GLP-1 à action prolongée tels que le sémaglutide peuvent être à risque d'aspiration pulmonaire sous anesthésie. Nous proposons des stratégies pour atténuer ce risque, y compris d'interrompre la prise du médicament quatre semaines avant une intervention prévue lorsque cela est possible et d'envisager de prendre les précautions requises pour un estomac plein.

pUL21 regulation of pUs3 kinase activity influences the nature of nuclear envelope deformation by the HSV-2 nuclear egress complex.

It is well established that the herpesvirus nuclear egress complex (NEC) has an intrinsic ability to deform membranes. During viral infection, the membrane-deformation activity of the NEC must be precisely regulated to ensure efficient nuclear egress of capsids. One viral protein known to regulate herpes simplex virus type 2 (HSV-2) NEC activity is the tegument protein pUL21. Cells infected with an HSV-2 mutant lacking pUL21 (ΔUL21) produced a slower migrating species of the viral serine/threonine kinase pUs3 that was shown to be a hyperphosphorylated form of the enzyme. Investigation of the pUs3 substrate profile in ΔUL21-infected cells revealed a prominent band with a molecular weight consistent with that of the NEC components pUL31 and pUL34. Phosphatase sensitivity and retarded mobility in phos-tag SDS-PAGE confirmed that both pUL31 and pUL34 were hyperphosphorylated by pUs3 in the absence of pUL21. To gain insight into the consequences of increased phosphorylation of NEC components, the architecture of the nuclear envelope in cells producing the HSV-2 NEC in the presence or absence of pUs3 was examined. In cells with robust NEC production, invaginations of the inner nuclear membrane were observed that contained budded vesicles of uniform size. By contrast, nuclear envelope deformations protruding outwards from the nucleus, were observed when pUs3 was included in transfections with the HSV-2 NEC. Finally, when pUL21 was included in transfections with the HSV-2 NEC and pUs3, decreased phosphorylation of NEC components was observed in comparison to transfections lacking pUL21. These results demonstrate that pUL21 influences the phosphorylation status of pUs3 and the HSV-2 NEC and that this has consequences for the architecture of the nuclear envelope.

The Herpesvirus Nuclear Egress Complex Component, UL31, Can Be Recruited to Sites of DNA Damage Through Poly-ADP Ribose Binding.

The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the herpesvirus nuclear egress complex that not only functions in the egress of DNA containing capsids from the nucleus, but is also required for optimal replication of viral DNA and its packaging into capsids. Here we report that the UL31 protein from HSV-2 can be recruited to sites of DNA damage by sequences found in its N-terminus. The N-terminus of UL31 contains sequences resembling a poly (ADP-ribose) (PAR) binding motif suggesting that PAR interactions might mediate UL31 recruitment to damaged DNA. Whereas PAR polymerase inhibition prevented UL31 recruitment to damaged DNA, inhibition of signaling through the ataxia telangiectasia mutated DNA damage response pathway had no effect. These findings were further supported by experiments demonstrating direct and specific interaction between HSV-2 UL31 and PAR using purified components. This study reveals a previously unrecognized function for UL31 and may suggest that the recognition of PAR by UL31 is coupled to the nuclear egress of herpesvirus capsids, influences viral DNA replication and packaging, or possibly modulates the DNA damage response mounted by virally infected cells.