Jillian S. Caldwell

The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (-/-) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (-/-) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (-/-) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (-/-) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy.

ABSTRACT: Although the number of deaths due to coronavirus disease 2019 (COVID-19) is higher in men than women, prior studies have provided limited sex-stratified clinical data.We evaluated sex-related differences in clinical outcomes among critically ill adults with COVID-19.Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate 28-day in-hospital mortality, severe acute kidney injury (AKI requiring kidney replacement therapy), and respiratory failure occurring within 14 days of intensive care unit admission.A total of 4407 patients were included (median age, 62 years; 2793 [63.4%] men; 1159 [26.3%] non-Hispanic White; 1220 [27.7%] non-Hispanic Black; 994 [22.6%] Hispanic). Compared with women, men were younger (median age, 61 vs 64 years, less likely to be non-Hispanic Black (684 [24.5%] vs 536 [33.2%]), and more likely to smoke (877 [31.4%] vs 422 [26.2%]). During median follow-up of 14 days, 1072 men (38.4%) and 553 women (34.3%) died. Severe AKI occurred in 590 men (21.8%), and 239 women (15.5%), while respiratory failure occurred in 2255 men (80.7%) and 1234 women (76.5%). After adjusting for age, race/ethnicity and clinical variables, compared with women, men had a higher risk of death (OR, 1.50, 95% CI, 1.26-1.77), severe AKI (OR, 1.92; 95% CI 1.57-2.36), and respiratory failure (OR, 1.42; 95% CI, 1.11-1.80).In this multicenter cohort of critically ill adults with COVID-19, men were more likely to have adverse outcomes compared with women.

Aim: NGAL, IL-18, KIM-1 as well as urinary TIMP2 and IGFBP7 and their mathematical product (TIMP2*IGFBP7) were evaluated for detecting pediatric aminoglycoside acute kidney injury (AG-AKI). Methods: In a prospective study, noncritically ill children received aminoglycosides (AG) ≥3 days. The area under the curve (AUC) for biomarkers to detect AKI was calculated by a) days before AKI onset; b) treatment days. Results: There were 113 AG episodes (68% febrile neutropenia). The AKI group had a higher proportion with febrile neutropenia. The AKI group had significantly lower NGAL 3 days before AKI, as patients with febrile neutropenia had a lower NGAL during AG treatment (p < 0.05). NGAL, IL-18 and TIMP2*IGFBP7 had AUC ≥0.73 at 3, 2 and 2 days before AKI onset. Conclusion: NGAL, IL-18 and TIMP2*IGFBP7 were modest early biomarkers of AG-AKI. Febrile neutropenia was associated with lower NGAL.