COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Hysterectomy and Oophorectomy for Transgender Patients: Preoperative and Intraoperative Considerations.

OBJECTIVE: To review the preoperative and intraoperative considerations for gynecologic surgeons when performing hysterectomy with or without oophorectomy for transgender patients. DESIGN: Stepwise demonstration of techniques with narrated video footage. SETTING: Approximately 0.3% of hysterectomies performed annually in the United States are for transgender men. While some transgender men choose hysterectomy for the same indications as cisgender women, the most prevalent diagnosis for the performed surgeries is gender dysphoria [1]. Hysterectomy with or without oophorectomy can be offered to patients who meet the World Professional Association for Transgender Health criteria [2]. INTERVENTIONS: Important perioperative counseling points for transgender patients include establishing the terminology for the relevant anatomy as well as the patient's name and pronouns; if applicable, discussing options for fertility preservation if the patient desires biological children [3,4] and discussing the use of hormone therapy post oophorectomy to reduce the loss of bone density [5,6]; and reviewing intraoperative and postoperative expectations. When performing an oophorectomy on a transgender patient for gender affirmation, it is especially important to minimize the risk of ovarian remnant syndrome and the need for additional surgery, as, for example, caused by persistent menstruation. A 2-layer vaginal cuff closure should be considered to reduce the risk of vaginal cuff complications and is preferable for patients whose pelvic organs cause gender dysphoria [7,8]. CONCLUSION: Special considerations outlined in this video and the World Professional Association for Transgender Health guidelines should be reviewed by gynecologic surgeons to minimize the transgender patient's experiences of gender dysphoria before, during, and after surgery.