Background: Our simulations previously predicted focal areas of gaseous pollutant dose delivered to the airway mucosa of a patient with idiopathic pulmonary fibrosis (IPF). We hypothesize a relation between these dose predictions and clinically meaningful endpoints in IPF which link toxicant-driven epithelial injury and disrepair to IPF etiology and pathogenesis. Objective: To determine associations between patient-specific modeling of tracheal geometry, computer simulations of toxicant dose, and lung histopathology in patients with IPF. Methods: The first three conducting airway generations of ten patients diagnosed with IPF were reconstructed from their high-resolution CT chest scans. We quantified geometric abnormalities of the reconstructed tracheas based on their curvature and eccentricity (cross-sectional flattening), and performed three-dimensional computer simulations to predict the average and upper values (i.e. hotspots) of reactive toxicant dose to the underlying mucosa. Distal biopsy tissue samples were characterized by epithelial cell phenotype, extent of fibrosis, and histopathologic severity scores. Non-parametric correlation analysis examined associations between these descriptors. Results: Computed values for curvature and eccentricity of IPF-deformed trachea varied widely among patients and correlated with more subjective rankings of tracheal deformation, and with predicted toxicant dose. Overall histopathologic severity was positively correlated with tracheal deformation and upper decile toxicant uptake. Tracheal curvature was significantly correlated with fibroblastic foci. Conclusions: These results demonstrate an association of tracheal curvature with predicted toxicant dose and with histopathologic indicators in distal tissue. This suggests that these measures may be predictors of risk for acute IPF exacerbations, subsequent clinical deterioration, and disease progression. © 2024

OBJECTIVE: The diagnostic criteria of lymphatic vascular invasion have not been standardized. Our investigation assesses the factors associated with lymphatic vascular invasion positive tumors and the impact of lymphatic vascular invasion on overall survival for patients with non-small cell lung cancer undergoing (bi)lobectomy with an adequate node dissection. METHODS: The National Cancer Database was queried from the years 2010 to 2015 to find surgical patients who underwent lobectomy with at least 10 lymph nodes examined (adequate node dissection) and with known lymphatic vascular invasion status. Paired t tests were used to distinguish differences between the patients with and without lymphatic vascular invasion in their specimen. Multivariable analysis was used to determine factors associated with overall survival. Propensity score matching adjusting for overall survival factors was used to determine the lymphatic vascular invasion's overall survival impact by grade, histology, p-T/N/overall stage, and tumor size. RESULTS: Lymphatic vascular invasion status was reported in 91.6% and positive in 23.4% of 28,842 eligible patients. Academic medical centers, institutions with populations more than 1,000,000, and the mid-Atlantic region reported higher rates of lymphatic vascular invasion positive tumors as well as overall survival compared with other cancer centers. Lymphatic vascular invasion was independently associated with a significant decrement in overall survival as per multivariable analysis and propensity score matching. Propensity score matching demonstrated that lymphatic vascular invasion was associated with a significant decrement in overall survival for all histologies, tumor grades, tumor sizes, and stages, except for more advanced pathologic stages T3/III/N2 and larger tumors greater than 4 cm for which overall survival was trending worse with lymphatic vascular invasion positive. CONCLUSIONS: Lymphatic vascular invasion positive varies based on hospital location/type and population, but it was associated with a decrement in overall survival that was independent of pathologic T/N/overall stage, histology, and tumor grade. Lymphatic vascular invasion must be standardized and considered as a staging variable and should be considered as a sole determinant for prognosis, especially for those with earlier-stage and smaller tumors.

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.