Prevalence, Distribution, and Risk Factor Correlates of High Thoracic Periaortic Fat in the Framingham Heart Study

Background: Thoracic periaortic adipose tissue (TAT) is associated with atherosclerosis and cardiovascular disease (CVD) risk factors and may play a role in obesity‐mediated vascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high TAT. Methods and Results: Participants from the Framingham Heart Study (n=3246, 48% women, mean age 51.1 years) underwent multidetector computed tomography; high TAT and visceral adipose tissue (VAT) were defined on the basis of sex‐specific 90th percentiles in a healthy referent sample. The prevalence of high TAT was 38.1% in women and 35.7% in men. Among individuals without high VAT, 10.1% had high TAT. After adjustment for age and VAT, both women and men with high TAT in the absence of high VAT were older and had a higher prevalence of CVD (P<0.0001) compared with those without high TAT. In addition, men in this group were more likely to be smokers (P=0.02), whereas women were more likely to have low high‐density lipoprotein cholesterol (P=0.005). Conclusions: Individuals in our community‐based sample with high TAT in the absence of high VAT were characterized by an adverse cardiometabolic profile. This adipose tissue phenotype may identify a subset of individuals with distinct metabolic characteristics

Thoracic Periaortic and Visceral Adipose Tissue and Their Cross-sectional Associations with Measures of Vascular Function

Objective: Perivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) are associated with vascular function. Design and Methods TAT and VAT were quantified in Framingham Heart Study participants using multidetector computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone and arterial tonometry (n= 2735, 48% women, mean age 50 years, mean BMI 27.7 kg/m2). Using multiple linear regression, we examined relations between TAT, VAT, and vascular measures while adjusting for cardiovascular risk factors. Results: Mean TAT and VAT volumes were 13.2 and 1763 cm3. TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (p0.06). Conclusion: Thoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function

Left destroyed lung caused by a pen cap in the left lower lobe bronchus swallowed 25 years ago

A delayed diagnosis of tracheobronchial foreign body aspiration (FBA) may result in severe respiratory complications such as pneumonia, bronchiectasis, and atelectasis. Here, we present a rare case of a left lung destruction caused by a pen cap that remained in the left lower lobe bronchus for 25 years and was previously misdiagnosed as cavitary tuberculosis. The foreign body was not detected in bronchoscopic examination prior to surgery due to severe stenosis of the left main bronchus. The foreign body was found incidentally while the patient was undergoing left pneumonectomy. To the best of our knowledge, this the second longest delay to diagnosis of FBA reported. This case also exemplifies the grave consequences of misdiagnosis of FBA

Neutrophil expansion defines an immunoinhibitory peripheral and intratumoral inflammatory milieu in resected non-small cell lung cancer: a descriptive analysis of a prospectively immunoprofiled cohort

Background The biological underpinnings of the prognostic and predictive significance of a relative neutrophilia in patients with non-small lung cancer (NSCLC) are undefined. We sought to comprehensively examine the relationships between circulating and intratumoral neutrophil populations and features of the immune contexture in patients undergoing NSCLC resection.Methods Preoperative soluble cytokine and angiogenic factors; tumor multiplex immunofluorescence; RNA, whole exome, and T-cell receptor sequencing; and flow cytometry were analyzed for relationships with populations of circulating (from complete blood counts) and intratumoral neutrophils (transcriptional signatures) in a prospectively enrolled resected NSCLC cohort (n=66). In a historical cohort (n=1524), preoperative circulating neutrophil and lymphocyte counts were analyzed for associations with overall survival (OS).Results Circulating neutrophil populations were positively correlated with increased tumor burden, and surgical tumor resection was followed by a subsequent reduction in peripheral neutrophil counts. Expansion of the circulating neutrophil compartment was associated with increased levels of pro-granulopoietic (IL-1β, IL-17A, TNFα, IL-6) and TH2-associated (IL-5, IL-13) cytokines. Tumors with high intratumoral neutrophil burden were marked by a blunted T-cell response characterized by reduced expression of cytotoxic T-cell genes (CD8A, CD8B, GZMA, GZMB), decreased CD3+CD8+ cell infiltration, and diminished expression of IFNγ-related genes. The associations between increased intratumoral neutrophil burden and reduced CD3+CD8+ infiltration persisted after adjustment for tumor size, histology, mutational burden, and PD-L1 expression. In 1524 patients, elevated preoperative circulating neutrophil count was independently associated with worse OS (main effect HR 1.82, 95% CI 1.24 to 2.68, p=0.002).Conclusions Our findings demonstrate that neutrophil expansion reflects protumorigenic and immunosuppressive processes that manifest as worse OS in patients undergoing NSCLC resection. These results justify further investigation of therapeutic strategies targeting neutrophil-associated immune evasion