RESUMEN
BACKGROUND: Since many COVID-19 publications lack consensus reviews or controls, interpretive accuracy is unclear; abdominal processes unique or infrequent during the pandemic remain unknown. The incidence and nature of CT findings accounting for abdominal complaints in COVID patients, reader agreement and overcalling will be determined. METHODS: A retrospective study was performed on COVID patients with abdominal complaints from 3/15/2020-5/31/2020 and 11/1/2020-4/15/2021 including matched controls. Reviewers blinded to initial reads interpreted abdominopelvic CT exams, with discordant cases resolved in consensus. Reader agreement was measured by Cohen's Kappa, differences between cohorts by permutation tests and factors affecting false positive/negative rates by Fisher's Exact Test and logistic regression. RESULTS: 116 first wave (average age 65 years [±15.3], 63 [54%] women) and 194 second wave COVID cases (average age 64 years [±16.3], 103 [53%] women) including 116 wave 1 and 194 wave 2 prepandemic controls were included. Concordance was lower among COVID cases than controls (Cohen's Kappa of 0.58 vs. 0.82 [p ≤ 0.001]) and among wave 1 than wave 2 cases (Cohen's Kappa of 0.45 vs. 0.66 [p = 0.052]). With true positives defined as consensus between the initial reader and study reader, false positive rates were higher among COVID cases than controls (OR = 0.42, p = 0.003) and for initial than study reader (OR = 0.36, p ≤ 0.001), but lower in wave 2 than 1 (OR = 0.5, p = 0.028). CONCLUSION: Greater reader disagreement occurred during COVID than prepandemic with no reader bias as both initial and study readers called more false positives among COVID cases than controls. More overcalling occurred during COVID with colitis and cystitis most common.
Asunto(s)
COVID-19 , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Consenso , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Anciano de 80 o más AñosRESUMEN
The transcription factor CREB (cyclic AMP response element (CRE)-binding protein) is implicated in the pathophysiology and treatment of depression. Structural and functional studies in both animals and humans suggest that abnormalities of the hippocampus may play a role in depression. CREB regulates thousands of genes, yet to date, only a handful that mediate depression or antidepressant response have been identified as relevant CREB targets. In order to comprehensively identify genes regulated by CREB in the hippocampus, we employed translating ribosome affinity purification (TRAP) to detect actively translating mRNAs in wild type and CREB-deficient mice. Using CrebloxP/loxP; RosaLSL-GFP-L10a mice, we conducted whole genome sequencing to identify transcripts only in cells that lack CREB, as introduction of Cre-recombinase simultaneously deleted CREB and expressed GFP-tagged L10a ribosomes that enabled TRAP. We identified over 200 downregulated genes predominantly associated with inflammation and the immune system, including toll-like receptor 1 (TLR1). To determine if baseline disruption in gene expression in the hippocampus of CREB-deficient mice can modulate behavior, we used unpredictable chronic mild stress (UCMS) to produce a set of behavioral alterations with strong validity for depression. We found that CREB-deficient mice demonstrated resilience to the physiological effects of UCMS and also showed changes in affective behaviors specifically in the presence of stress. TLR1 expression was increased following UCMS in control but not in CREB-deficient mice. The results suggest that CREB-mediated regulation of immune system and inflammatory factors may provide additional targets for the treatment of depression.