Unusual presentation of lepidic adenocarcinoma in a healthy female.

BACKGROUND: Lepidic adenocarcinoma represents a histologic pattern of non-small cell lung cancer that characteristically arises in the lung periphery with tracking alongside pre-existing alveolar walls. Noninvasive and invasive variants of lepidic adenocarcinoma are dependent on parenchymal destruction, vascular, or pleural invasion. The lepidic-predominant lung malignancies are collectively recognized as slow growing with rare metastasis and excellent prognosis. The World Health Organization classification of lung malignancies depends on molecular and histopathological findings. CT findings most commonly include ground-glass characteristics, commonly mistaken for inflammatory or infectious etiology. These tumors are generally surgically resectable and associated with better survival given infrequent nodal and extrathoracic involvement. Rarely these tumors present with diffuse pneumonic-type involvement associated with worse outcomes despite lack of nodal and distant metastases. CASE PRESENTATION: A 63-year-old Caucasian athletic immunocompetent female presented with 2 months of progressive shortness of breath, fatigue, loss of appetite and 15 pound weight loss. History was only notable for well controlled essential hypertension and hypothyroidism. Contrast computed tomography angiogram and positron emission tomography revealed diffuse hypermetabolic interstitial and airspace abnormalities of the lungs without lymphadenopathy (or distant involvement) in addition to right hydropneumothorax and left pleural effusion. Baseline laboratory testing was unremarkable, and extensive bacterial and fungal testing returned negative. Bronchoscopy and video-assisted thoracoscopic surgery was subsequently performed with pleural fluid cytology, lung and pleural biopsies returning positive for lepidic adenocarcinoma with 2% programmed death ligand 1 expression and genomic testing positive for PTEN gene deletion. Prior to treatment, the patient perished on day 15 of admission. CONCLUSION: We present a rare case of lepidic predominant adenocarcinoma with extensive bilateral aerogenous spread in the context of no lymphovascular invasion in a healthy, low risk patient. This case presentation may add to the body of knowledge regarding the different behavior patterns of lepidic predominant adenocarcinomas.

Genome-wide DNA methylation investigation of glucocorticoid exposure within buccal samples.

AIM: Glucocorticoids play a major role in regulating the stress response, and an imbalance of glucocorticoids has been implicated in stress-related disorders. Within mouse models, CpGs across the genome have been shown to be differentially methylated in response to glucocorticoid treatment, and using the Infinium 27K array, it was shown that humans given synthetic glucocorticoids had DNA methylation (DNAm) changes in blood. However, further investigation of the extent to which glucocorticoids affect DNAm across a larger proportion of the genome is needed. METHODS: Buccal samples were collected before and after synthetic glucocorticoid treatment in the context of a dental procedure. This included 30 tooth extraction surgery patients who received 10 mg of dexamethasone. Genome-wide DNAm was assessed with the Infinium HumanMethylationEPIC array. RESULTS: Five CpGs showed genome-wide significant DNAm changes that were >10%. These differentially methylated CpGs were in or nearest the following genes: ZNF438, KLHDC10, miR-544 or CRABP1, DPH5, and WDFY2. Using previously published datasets of human blood gene expression changes following dexamethasone exposure, a significant proportion of genes with false-discovery-rate-adjusted significant CpGs were also differentially expressed. A pathway analysis of the genes with false-discovery-rate-adjusted significant CpGs revealed significant enrichment of olfactory transduction, pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and steroid hormone biosynthesis pathways. CONCLUSION: High-dose synthetic glucocorticoid administration in the setting of a dental procedure was significantly associated with DNAm changes within buccal samples. These findings are consistent with prior findings of an influence of glucocorticoids on DNAm in humans.

GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.

BACKGROUND: Large sample GWAS is needed to identify genetic factors associated with depression. This study used genome-wide genotypic and phenotypic data from the COPDGene study to identify genetic risk factors for depression. METHODS: Data were from 9716 COPDGene subjects with ≥10 pack-year history. Depression was defined as antidepressant use and/or a HADS depression subscale score ≥8. Non-Hispanic White (6576) and African-American (3140) subsets were analyzed. A GWAS pipeline identified SNPs associated with depression in each group. Network analysis software analyzed gene interactions through common biological pathways, genetic interactions, and tissue-specific gene expression. RESULTS: The mean age was 59.4 years (SD 9.0) with 46.5% female subjects. Depression was in 24.7% of the NHW group (1622) and 12.5% of the AA group (391). No SNPs had genome-wide significance. One of the top SNPs, rs12036147 (p = 1.28 × 10-6), is near CHRM3. Another SNP was near MDGA2 (rs17118176, p = 3.52 × 10-6). Top genes formed networks for synaptic transmission with a statistically significant level of more co-expression in brain than other tissues, particularly in the basal ganglia (p = 1.00 × 10-4). LIMITATIONS: Limitations included a depression definition based on antidepressant use and a limited HADS score subgroup, which could increase false negatives in depressed patients not on antidepressants. Antidepressants used for smoking cessation in non-depressed patients could lead to false positives. CONCLUSIONS: Systems biology analysis identified statistically significant pathways whereby multiple genes influence depression. The gene set pathway analysis and COPDGene data can help investigate depression in future studies.

Delirium detection by a novel bispectral electroencephalography device in general hospital.

AIM: Delirium is common and dangerous among elderly inpatients; yet, it is underdiagnosed and thus undertreated. This study aimed to test the diagnostic characteristics of a noninvasive point-of-care device with two-channel (bispectral) electroencephalography (EEG) for the screening of delirium in the hospital. METHODS: Patients admitted to the University of Iowa Hospitals and Clinics were assessed for the presence of delirium with a clinical assessment, the Confusion Assessment Method for Intensive Care Unit and Delirium Rating Scale. Subsequently, we obtained a 10-min bispectral EEG (BSEEG) recording from a hand-held electroencephalogram device during hospitalization. We performed power spectral density analysis to differentiate between those patients with and without delirium. RESULTS: Initially 45 subjects were used as a test dataset to establish a cut-off. The BSEEG index was determined to be a significant indicator of delirium, with sensitivity 80% and specificity 87.7%. An additional independent validation dataset with 24 patients confirmed the validity of the approach, with a sensitivity of 83.3% and specificity of 83.3%. CONCLUSION: In this pilot study, the BSEEG method was able to distinguish delirious patients from non-delirious patients. Our data showed the feasibility of this technology for mass screening of delirium in the hospital.