SARS-CoV-2 Infection during Pregnancy in a Rural Midwest All-delivery Cohort and Associated Maternal and Neonatal Outcomes.

OBJECTIVE: This study aimed to estimate the prevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) among pregnant patients at the time of delivery in a rural Midwest tertiary care hospital and to examine demographics, clinical factors, and maternal and neonatal outcomes associated with SARS-CoV-2 infection during pregnancy. STUDY DESIGN: This prospective cohort study included all delivering patients between May 1 and September 22, 2020 at the University of Iowa Hospitals and Clinics. Plasma SARS-CoV-2 antibody testing was performed. SARS-CoV-2 viral reverse-transcription polymerase chain reaction (RT-PCR) results and maternal and neonatal outcomes were collected from the electronic medical record. Data were analyzed using univariate statistical methods with clustering for multiple births. RESULTS: In total, 1,000 patients delivered between May 1 and September 22, 2020. Fifty-eight (5.8%) were SARS-CoV-2 antibody positive. Twenty-three also tested viral positive during pregnancy. Three of 1,000 (0.3%) were viral positive on admission but antibody negative. The median age was 30 years (interquartile range [IQR]: 26-33 years) and body mass index was 31.75 kg/m2 (IQR 27.7-37.5 kg/m2). The cesarean delivery rate was 34.0%. The study population was primarily white (71.6%); however, 41.0% of SARS-CoV-2 infected patients identified as Black, 18.0% as Hispanic/Latino, 3.3% as Native Hawaiian/Pacific Islander, and only 27.9% as White (p < 0.0001). SARS-CoV-2 infection was more likely in patients without private insurance (p = 0.0243). Adverse maternal and/or neonatal outcomes were not more likely in patients with evidence of infection during pregnancy. Two SARS-CoV-2 infected patients were admitted to the intensive care unit. There were no maternal deaths during the study period. CONCLUSION: In this largely rural Midwest population, 6.1% of delivering patients had evidence of past or current SARS-CoV-2 infection. Rates of SARS-CoV-2 during pregnancy were higher among racial and ethnic minorities and patients without private insurance. The SARS-CoV-2 infected patients and their neonates were not found to be at increased risk for adverse outcomes. KEY POINTS: · SARS-CoV-2 seroprevalence rate in pregnant population in Iowa is 5.8%.. · Infections are higher among minorities, non-English speakers, and patients without private insurance.. · No increased adverse maternal/neonatal outcomes observed for SARS-CoV-2 infected mothers..

Local cortical overexpression of human wild-type alpha-synuclein leads to increased dendritic spine density in mouse.

Lewy body dementias are characterized by deposition of alpha-synuclein (α-syn) protein aggregates known as Lewy bodies and Lewy neurites in cortical regions, in addition to brainstem. These aggregates are thought to cause the death of dopaminergic neurons in the substantia nigra and other vulnerable cell types in patients, leading to parkinsonism. There is evidence from mice that localized overexpression of wild-type α-syn leads to dopaminergic cell death in the substantia nigra. However, it is not known how cortical neurons are affected by α-syn. In this study, we used viral overexpression of α-syn to investigate whether localized overexpression within the cortex affects the density, length, and morphology of dendritic spines, which serve as a measure of synaptic connectivity. An AAV2/6 viral vector coding for wild-type human α-syn was used to target overexpression bilaterally to the medial prefrontal cortex within adult mice. After ten weeks the brain was stained using the Golgi-Cox method. Density of dendritic spines in the injected region was increased in layer V pyramidal neurons compared with animals injected with control virus. Immunohistochemistry in separate animals showed human α-syn expression throughout the region of interest, especially in presynaptic terminals. However, phosphorylated α-syn was seen in a discrete number of cells at the region of highest overexpression, localized mainly to the soma and nucleus. These findings demonstrate that at early timepoints, α-syn overexpression may alter connectivity in the cortex, which may be relevant to early stages of the disease. In addition, these findings contribute to the understanding of α-syn, which when overexpressed in the wildtype, non-aggregated state may promote spine formation. Loss of spines secondary to α-syn in cortex may require higher expression, longer incubation, cellular damage, concomitant dopaminergic dysfunction or other two-hit factors to lead to synaptic degeneration.

Temporal bone carcinoma: Treatment patterns and survival.

OBJECTIVES/HYPOTHESIS: Carcinomas of the temporal bone are rare, and appropriate treatment, staging, and survival data are limited. This study evaluates clinical characteristics and survival rates for patients with temporal bone carcinoma treated with resection at a single tertiary-care institution, with a focus on the outcomes of patients with locally advanced disease including skull base and/or dural invasion. STUDY DESIGN: Retrospective chart review. METHODS: Demographic, tumor-specific, and survival data were collected for patients with primary carcinomas of the external auditory canal with involvement of the temporal bone from 2003 to 2015. All patients were staged according to the modified Pittsburgh system. Kaplan-Meier and logistic regression analysis were used to calculate factor-specific survival outcomes. RESULTS: Sixty-seven patients met inclusion criteria; 85% were male. There were 43 squamous cell carcinomas (64%) and 24 basal cell carcinomas (BCCs) (36%). Tumor stage was 24 (36%) T2, 12 (18%) T3, and 31 (46%) T4 tumors; 53% had recurrent disease. Surgical management included 49 lateral temporal bone resections and 18 subtotal temporal bone resections. Kaplan-Meier analyses revealed more favorable 5-year survival rates associated with BCC histology (P = .01), lateral temporal bone resection compared to subtotal temporal bone resection (P < .01), lack of immunocompromise (P = .04), and absence of perineural/lymphovascular invasion (P = .01). Multivariate regression analysis did not yield statistically significant results. CONCLUSIONS: Factors predictive of more favorable survival include lack of immunocompromise, BCC histology, absence of perineural/lymphovascular invasion, and disease extent amenable to lateral temporal bone resection. Dural invasion is not an absolute contraindication to surgery, with a subset of patients surviving >5 years. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:E11-E20, 2020.

Urinary tract infection and drug-resistant urinary tract infection after intradetrusor onabotulinumtoxinA injection versus sacral neuromodulation.

INTRODUCTION AND HYPOTHESIS: Intradetrusor onabotulinumtoxinA (BTX) and sacral neuromodulation (SNM) are effective treatments for refractory urgency urinary incontinence/overactive bladder (UUI/OAB). BTX carries a risk of urinary tract infection (UTI), which is concerning for the development of multidrug resistant (MDR) UTI. We hypothesized that BTX might carry a higher risk of UTI and MDR UTI compared with SNM and that UTI and MDR UTI risk might increase after repeat BTX injection. METHODS: This retrospective cohort study included women undergoing BTX or SNM for refractory UUI/OAB in 2012-2016. UTI and MDR UTI were assessed up to 1 year post-treatment or until repeat treatment and compared between initial BTX and SNM and between repeat BTX injections. Univariate analyses included Chi-squared and Fisher's exact tests and generalized linear models (GLM) with logit link function. Multivariate analyses used GLM to assess the best predictor variables for any UTI. RESULTS: One hundred and one patients were included (28 BTX, 73 SNM). Rates of UTI (39.3% [95% CI 21.5, 59.4] BTX vs 37.0% [95% CI 26.0, 49.1] SNM) were similar in the two groups at all time intervals. One MDR UTI occurred after SNM. Risk of UTI did not increase with repeat BTX (11 out of 28 [39.3%], 6 out of 17 [35.3%], and 4 out of 7 [57.1%] after 1, 2, and ≥ 3 treatments respectively; p = 0.62). Multivariate analysis found that history of recurrent UTI (OR 2.5, 95%CI 0.98-6.39) and prolapse repair (OR 4.6, 95%CI 1.23-17.07) had increased odds of UTI. CONCLUSIONS: Rates of UTI were similar in patients undergoing BTX and SNM. MDR UTI was rare. Patients with prior prolapse repair or recurrent UTI may be at a higher risk of UTI after either procedure.

Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection.

Pathogenic human coronaviruses (CoVs), such as the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome-CoV, cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent Middle East respiratory syndrome outbreak indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared with age-matched females. The degree of sex bias to SARS-CoV infection increased with advancing age, such that middle-aged mice showed much more pronounced differences compared with young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage, and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages and neutrophils in the lungs of male mice, and depletion of inflammatory monocyte macrophages partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality, indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in the susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.

Altered Treg and cytokine responses in RSV-infected infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in children under 1 y of age in the USA. The host immune response is believed to contribute to RSV-induced disease. We hypothesize that severe RSV infection in infants is mediated by insufficient regulation of the host immune response of regulatory T cells (Tregs) resulting in immunopathology. METHODS: Blood and nasal aspirates from 23 RSV-infected and 17 control infants under 1 y of age were collected. Treg frequencies were determined by flow cytometry from peripheral blood mononuclear cells. Analysis of 24 cytokines was measured by multiplex assay on nasal aspirates. RESULTS: We demonstrate that the frequency of activated Tregs is significantly reduced in the peripheral blood of RSV-infected infants compared with age-matched controls. Surprisingly, T helper (Th)17 related cytokines including interleukin (IL)-1ß, IL-17A, and IL-23 were associated with a reduction in clinical symptoms of respiratory distress. In addition, the amount of IL-33 protein in nasal washes, a cytokine important in maintaining Treg homeostasis in mucosal tissues, was decreased in RSV-infected children. CONCLUSION: These results suggest that decreased Treg numbers and an inability to properly control the host inflammatory response results in severe RSV infection.