Timely adherence to follow-up after high-risk lung cancer screenings.

OBJECTIVE: To achieve the lung cancer screening (LCS) mortality benefit in clinical trials, timely, real-world follow-up of abnormal test results is necessary. Presently, annual LCS rates are lower than in trials, and adherence to follow-up after suspicious findings has not been well studied. This study examined timely adherence to follow-up recommendations after positive low-dose computed tomography (LDCT) screenings. METHODS: This retrospective study included individuals from two academic primary care practices in New York City who met United States Preventative Services Task Force LCS eligibility and had a positive LDCT scan between 2013 and 2020. They were recommended for shorter interval follow-up repeat computed tomography (CT), CT biopsy, or positron emission tomography/CT. Adherence was completion of the prescribed imaging by 15 days after the recommended 7-, 30-, and 90-day follow-up and by 30 days after the 180-day recommended follow-up. RESULTS: Among 106 individuals with a positive LDCT scan, 64 (60%) were adherent to follow-up recommendations. Adherence was 72%, 63%, and 42% for recommended follow-ups of 30, 90, and 180 days, respectively. Being male was a predictor of a lower adherence rate. Among 23 individuals newly diagnosed with lung cancer after a positive LDCT scan, 83% were adherent to follow-up testing and 82% of cancers were Stage 1A or limited stage. CONCLUSIONS: There was variable adherence to the LCS follow-up recommendations despite positive screening CT, suggesting that even in a well-established screening program there may not be an efficient, systematic approach for follow-up. The delays in repeat testing potentially undermine the benefits of early detection.

A review of hepatic fibrosis-associated histopathology in aged cadavers.

This article reviews hepatic fibrosis-associated histopathology of aged cadavers (mean age 82 years). A study of 68 livers identified steatosis in 35.5%, central vein fibrosis in 49.2%, perisinusoidal fibrosis in 63.2%, portal tract fibrosis in 47.7%, septa formation in 44.1%, bridging fibrosis in 30.8%, and cirrhosis in 4.4% of the samples as well as one hepatocellular carcinoma and six metastatic tumors. Other studies have revealed that collagens I, III, IV, V, and VI and fibronectin constitute the matrices of fibrous central veins, perisinusoidal space, portal tracts, and septa. Elastin is rich in portal tracts and fibrous septa but absent from the perisinusoidal space. Hepatic stellate cells are ubiquitous in the liver parenchyma while myofibroblasts localize in fibrotic foci. Factor VIII-related antigen expression signals sinusoidal to systemic vascular endothelium transformation while collagen IV and laminin codistribution indicates formation of perisinusoidal membranes. Their coincidence reflects focalized capillarization of sinusoids in the aged liver. In response to fibrogenesis, hepatic progenitor cells residing in the canal of Hering in the periportal parenchyma undergo expansion and migration deep into the lobule. Concomitantly, intermediate hepatocyte-like cells increase in advanced fibrosis stages, which is possibly related to hepatic regeneration. Metabolic zonation of glutamine synthetase expands from the perivenous to non-perivenous parenchyma in fibrosis progression but its expression is lost in cirrhosis, while cytochrome P-4502E1 expression is maintained in centrilobular and midlobular zones in fibrosis progression and expressed in cirrhosis. Hence, cadaveric livers provide a platform for further investigation of hepatic histopathologies associated with the aging liver.

Patient impressions of the impact of comorbidities on lung cancer screening benefits and harms: A qualitative analysis.

OBJECTIVE: To learn about the beliefs and preferences of lung cancer screening (LCS) among patients undergoing LCS decision making. Specifically, we investigated how their comorbidity influences their interest in screening. The goal was to inform shared-decision making discussions around the role of comorbidities and LCS. METHODS: We recruited English-speaking LCS-eligible individuals with comorbidities from general medicine outpatient clinics at an academic medical center in New York City. The interviewers followed a semi-structured interview guide and all interviews were professionally transcribed. Study investigators independently conducted thematic analysis of de-identified transcripts; after coding, investigators discussed and agreed upon identified themes (Jacobs et al., 1999 [3]). This study was IRB-approved. RESULTS: We achieved thematic saturation after 15 interviews. We identified the following themes: 1) Comorbidities were perceived as unrelated to LCS decision-making, 2) Lung cancer knowledge is valuable and worth any risks, 3) No matter what the guidelines or my providers say, the LCS decision is up to me. CONCLUSION/PRACTICE IMPLICATIONS: Implications of these findings are that conversations where providers recommend against LCS may likely require time, patient education, and appreciation of the patient perspective.

Notch activation is required for downregulation of HoxA3-dependent endothelial cell phenotype during blood formation.

Hemogenic endothelium (HE) undergoes endothelial-to-hematopoietic transition (EHT) to generate blood, a process that requires progressive down-regulation of endothelial genes and induction of hematopoietic ones. Previously, we have shown that the transcription factor HoxA3 prevents blood formation by inhibiting Runx1 expression, maintaining endothelial gene expression and thus blocking EHT. In the present study, we show that HoxA3 also prevents blood formation by inhibiting Notch pathway. HoxA3 induced upregulation of Jag1 ligand in endothelial cells, which led to cis-inhibition of the Notch pathway, rendering the HE nonresponsive to Notch signals. While Notch activation alone was insufficient to promote blood formation in the presence of HoxA3, activation of Notch or downregulation of Jag1 resulted in a loss of the endothelial phenotype which is a prerequisite for EHT. Taken together, these results demonstrate that Notch pathway activation is necessary to downregulate endothelial markers during EHT.