Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy.

The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood. The intervillous spaces and villi were infiltrated with maternal macrophages and T cells. Transcriptome analysis showed an increased expression of chemokines and pathways associated with viral infection and inflammation. Infection of placental cultures with live SARS-CoV-2 and spike protein-pseudotyped lentivirus showed infection of syncytiotrophoblast and, in rare cases, endothelial cells mediated by ACE2 and Neuropilin-1. Viruses with Alpha, Beta, and Delta variant spikes infected the placental cultures at significantly greater levels.

SARS-CoV-2 Infects Syncytiotrophoblast and Activates Inflammatory Responses in the Placenta.

SARS-CoV-2 infection during pregnancy leads to an increased risk of adverse pregnancy outcomes. Although the placenta itself can be a target of virus infection, most neonates are virus free and are born healthy or recover quickly. Here, we investigated the impact of SARS-CoV-2 infection on the placenta from a cohort of women who were infected late during pregnancy and had tested nasal swab positive for SARS-CoV-2 by qRT-PCR at delivery. SARS-CoV-2 genomic and subgenomic RNA was detected in 23 out of 54 placentas. Two placentas with high virus content were obtained from mothers who presented with severe COVID-19 and whose pregnancies resulted in adverse outcomes for the fetuses, including intrauterine fetal demise and a preterm delivered baby still in newborn intensive care. Examination of the placental samples with high virus content showed efficient SARS-CoV-2 infection, using RNA in situ hybridization to detect genomic and replicating viral RNA, and immunohistochemistry to detect SARS-CoV-2 nucleocapsid protein. Infection was restricted to syncytiotrophoblast cells that envelope the fetal chorionic villi and are in direct contact with maternal blood. The infected placentas displayed massive infiltration of maternal immune cells including macrophages into intervillous spaces, potentially contributing to inflammation of the tissue. Ex vivo infection of placental cultures with SARS-CoV-2 or with SARS-CoV-2 spike (S) protein pseudotyped lentivirus targeted mostly syncytiotrophoblast and in rare events endothelial cells. Infection was reduced by using blocking antibodies against ACE2 and against Neuropilin 1, suggesting that SARS-CoV-2 may utilize alternative receptors for entry into placental cells.

Trends in hearing rehabilitation use among vestibular schwannoma patients.

OBJECTIVE: Most patients with vestibular schwannoma (VS) have significant hearing loss in the affected ear as a result of either their tumor or treatment. There is a paucity of data on which hearing rehabilitation options, if any, are preferred by patients with VS. Our study analyzed the use of hearing rehabilitation devices among VS patients. METHODS: Patients with unilateral VS treated at our institution from January 2008 to August 2018 were identified. Those with bilateral VS, profound hearing loss in the contralateral ear, neurofibromatosis type 2, or inadequate follow-up were excluded. Patients who met inclusion criteria were given two online questionnaires: an 8-item instrument that assesses use of hearing rehabilitation devices and the Abbreviated Profile of Hearing Aid Benefit. RESULTS: Of 212 eligible patients, 61 completed both surveys. The majority (88%) were able to hear "poorly" or "not at all" in the affected ear, but less than one-third had ever used a hearing rehabilitation device. Most had used conventional hearing aids (30%) or contralateral routing of signal/bilateral contralateral routing of signal (30%), whereas only a handful had used bone-anchored hearing devices or cochlear implant. Patients who did not pursue hearing rehabilitation were either not bothered by their deficit or were unaware of their options. Most had good functionality despite their deficit. CONCLUSION: Whereas 88% of patients treated for VS had a significant hearing loss, the majority did not pursue hearing rehabilitation but maintained good functional performance. Many did not remember being counseled about hearing rehabilitation options, indicating that regular and repeated counseling may be needed to increase patient utilization of hearing rehabilitation after VS treatment. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1558-1564, 2020.

The PreOp Program: Intensive Preclinical Surgical Exposure is Associated With Increased Medical Student Surgical Interest and Competency.

OBJECTIVE: As medical students' interest in surgical fields wanes, we investigated the impact of a preclinical surgical exposure program on students' attitudes toward pursuing surgical careers. DESIGN: This is a prospective longitudinal study of PreOp, a preclinical rotation-based surgical exposure program for first-year medical students, from 2013 to 2017. Surveys assessed PreOp rotation quality, students' surgical interest, and students' self-reported preparedness for the surgical clerkship. Surgery clerkship grades were obtained as a measure of surgical competency and compared to class-wide peers. Match data was collected and compared to class-wide peers as well as historical norms. SETTING: NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY; tertiary care center. PARTICIPANTS: Fifty-four PreOp students from 2013 to 2017. RESULTS: Fifty-four PreOp participants were recruited. After completing the PreOp program, 66.7% of PreOp students reported being very likely to apply into a surgical field compared to 29.4% when they started medical school. Ultimately, 71.4% of PreOp students versus 21.7% of non-PreOp class-wide peers matched into surgical fields (p < 0.001). From the preceding 5 match years before PreOp implementation, 21.4% of all students matched into surgical fields compared to 25.6% of all students after PreOp was started (p = 0.26). In terms of preparedness, 75% of PreOp students reported feeling more prepared for the third-year surgery clerkship than their non-PreOp peers after the second year of medical school. PreOp students were significantly more likely than non-PreOp class-wide peers to receive honors in the surgery clerkship when controlling for cumulative clerkship GPA (p = 0.012, adjusted odds ratio = 5.5 [95% confidence interval 1.5-22.1]). CONCLUSIONS: Hands-on preclinical surgical exposure was associated with student-reported increased surgical interest that was maintained longitudinally and reflected in significantly increased surgical matches relative to non-PreOp class-wide peers. This study uniquely demonstrates that participation in PreOp was also associated with increased self-reported surgical preparedness and significantly higher surgery clerkship grades relative to overall academic performance.