Hyperechogenicity of the pyloroduodenal junction in small dogs: Population prevalence in 175 dogs and histological correlation in 14 specimens.

At the pyloroduodenal junction (PDJ), an increase in wall echogenicity is frequently observed. A prospective study was performed to assess the PDJ sonographically in 175 adults and small dogs (>1 year old, <11.4 kg (25 lb)) over 12 months to evaluate the prevalence of this finding. Additionally, changes in echogenicity were correlated with histology in 14 postmortem specimens. A scoring system of echogenicity change centered on the mucosa and submucosa of the PDJ was implemented; 0: no change, 1: mild, 2: moderate to marked. Other included parameters were age, sex, breed, gastric distention, gastric contents, and reported vomiting at the time of presentation. Hyperechogenicity of the PDJ was highly prevalent (scores 1 and 2: 85.7%). No statistical association between hyperechogenicity of the PDJ and age, sex, gastric distention, gastric contents, or vomiting was identified. Hyperechogenicity of the PDJ is thought to represent an anatomical transition zone, and based on histology, hyperechogenicity of the PDJ may represent a variation in distribution and amount of fibrous connective tissue, glandular number, and glandular dilation within the submucosa and mucosa.

PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.