Image Fusion of Real-Time Ultrasonography with Computed Tomography: Factors Affecting the Registration Error and Motion of Focal Hepatic Lesions

Factors affecting the registration error (RE) and motion of focal hepatic lesions (FHLs) in image fusion of real-time ultrasonography (US) with computed tomography (CT) images were prospectively assessed by focusing on respiratory movement and FHL location. Real-time US and pre-acquired CT images at end-inspiration were fused with FHLs for 103 patients. Three-dimensional US data containing FHLs were obtained during end-inspiratory/expiratory phases. Multivariate analysis revealed that diaphragm motion (p < 0.001), chronic liver disease (p = 0.02) and the absolute difference in distance between the FHL and the central portal vein (CPV) during respiration (p = 0.03) were the independent factors that revealed the maximum effect on RE. In contrast, diaphragm motion (p < 0.001) and distance between the FHL and CPV at inspiration (p = 0.036) revealed the maximum effect on FHL motion. In conclusion, RE and FHL motion are affected by the degree of respiratory movement and the location of the FHL. Therefore, image fusion with CT images should be used with caution if the degree of respiratory motion is significant or if the FHL is located at the periphery of the liver.     

Sleep Characteristics in Mothers of Children With Developmental Disabilities

Impaired sleep can contribute to conditions such as cardiometabolic disorders, depression, and decreased immune function. Mothers of children with developmental disabilities (DDs) may be at greater risk for impaired sleep due to the sleep problems of their children. This cross-sectional study described the self-reported sleep characteristics of mothers of children (ages 6-12) with DDs by using a sleep diary and the Pittsburgh Sleep Quality Index (PSQI) as quantitative and qualitative measures of sleep in these mothers. The Consensus Sleep Diary was modified to ascertain how the child's sleep and needs for care during the night impacted the mother's sleep. The results showed that mothers had short sleep duration (nearly 40% slept <7 hours per night), woke up an average of 2.2 times per night (most commonly due to caregiving needs of children), and had poor sleep quality (mean PSQI global score of 7.9 [SD=4.8]). The sleep problems of children with DDs may influence mothers’ sleep.     

Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2

Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a hyperinflammatory state typified by elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID-19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS-CoV-2 binding receptor ACE2. Herein we describe SARS-CoV-2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID-19, demonstrating both heterogeneous ACE2 expression and endothelial damage. In primary endothelial cell cultures, we show that SARS-CoV-2 infection is dependent on the induction of ACE2 protein expression and that this process is facilitated by type 1 interferon-alpha (IFNα) or -beta(β)—two of the main anti-viral cytokines induced in severe SARS-CoV-2 infection—but not significantly by other cytokines (including interleukin 6 and interferon γ/λ). Our findings suggest that the stereotypical anti-viral interferon response may paradoxically facilitate the propagation of COVID-19 from the respiratory epithelium to the vasculature, raising concerns regarding the use of exogenous IFNα/β in the treatment of patients with COVID-19.

     

Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans

Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galβ1-4GalNAcβ), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.     

Comprehensive genetic features of gastric mixed adenoneuroendocrine carcinomas and pure neuroendocrine carcinomas

We aimed to determine the pathogenesis of gastric mixed adenoneuroendocrine carcinoma (MANEC) and pure neuroendocrine carcinoma (NEC), which is largely unknown. Targeted DNA sequencing was performed on 34 tumor samples from 21 patients – 13 adenocarcinoma (ADC)/NEC components from MANECs and eight pure NECs – and 21 matched non‐neoplastic gastric tissues. Mutational profiles of MANECs/NECs were compared with those of other tumors using public databases. The majority (64.1%; 59/92) of mutations in MANEC were shared by both ADC and NEC components. TP53 was the most commonly mutated gene in MANEC (69.2%, 9/13) and pure NEC (87.5%, 8/9). All TP53 mutations in MANEC were pathogenic mutations and were shared by both ADC and NEC components. A subset of TP53^WT MANECs had a microsatellite‐unstable phenotype or amplifications in various oncogenes including ERBB2 and NMYC, and the only TP53^WT pure NEC harbored MYC amplification. Compared to NEC in other organs, NECs arising from the stomach had unique features including less frequent RB1 mutations. Differentially altered genes of MANEC ADC components were significantly associated with receptor tyrosine kinase signaling pathways, while differentially altered genes of MANEC NEC components were significantly associated with the NOTCH signaling pathway. Our data provide evidence suggesting a possible clonal origin of ADC and NEC components of MANEC, and we found that gastric MANECs and pure NECs are distinct entities with unique mutational profiles and underlying protein networks. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.