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.

Impact of Fibrosis-4 Index Prior to COVID-19 on Outcomes in Patients at Risk of Non-alcoholic Fatty Liver Disease.

BACKGROUND: Severity of disease and outcomes in patient with COVID-19 has been associated with several risk factors tied to the metabolic syndrome. AIMS: We conducted a study with the objective of describing the association between the baseline Fibrosis-4 (FIB-4) index prior to SARS-CoV-2 infection and the severity of COVID-19 among patients at risk of non-alcoholic fatty liver disease (NAFLD). METHODS: This was a retrospective cohort study of patients with at least two risk factors for metabolic syndrome diagnosed with COVID-19. The main exposure of interest was FIB-4 index prior to infection, categorized into three previously validated age-specific levels. The main outcomes of interest were disease requiring hospitalization and in-hospital mortality. RESULTS: We included 373 patients [median age, 62 years; 194 male (52%); median number of metabolic syndrome risk factors, 3]. The median FIB-4 index was 1.10 (interquartile range 0.78-1.61). In models adjusting for diabetes mellitus and chronic kidney disease, patients with intermediate FIB-4 index had 67% higher odds of hospitalization compared to those in the low category {odds ratio (OR) 1.67 [(95% CI 1.06-2.64); p = 0.03]} and patients with high FIB-4 index had higher odds of mortality compared to intermediate and low category with an OR 2.22 (95% CI 1.20-4.12; p = 0.01). However, when we evaluated components of FIB-4 (age and AST/ALT ratio), we found that age alone was the best predictor of hospitalization and mortality. CONCLUSIONS: Among patients at risk of NAFLD with COVID-19 infection, elevated pre-infection FIB-4 index was associated with worsened clinical outcomes, but age was the strongest predictor.

External versus internal cardioversion for atrial fibrillation: a meta-analysis of randomized controlled trials.

BACKGROUND: Patients with atrial fibrillation (AF) often require rhythm control strategy for amelioration of symptoms. It is unclear if there is any difference between external cardioversion (ECV) and internal cardioversion (ICV) for successful conversion of AF to normal sinus rhythm. METHODS: We performed a meta-analysis of published randomized controlled trials (RCTs) evaluating success of cardioversion using ECV versus ICV. RESULTS: In the pooled analysis of 5 RCTS, there was no difference in success of cardioversion using ECV versus ICV (OR 1.69, 95% CI 0.24-11.83, p = 0.6). In the subgroup analysis, there was no difference between ECV and direct electrode ICV (OR 0.41, 95% CI 0.09-1.83, p = 0.24). However, ECV was significantly better compared with ICV using ICD (OR 11.97, 95% CI 1.87-76.73, p = 0.009). CONCLUSIONS: There was no difference between ECV versus ICV in effectiveness for termination of AF. Larger well-designed randomized controlled trials are needed to confirm our findings.

A Novel Score to Predict Esophageal Varices in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Several criteria have been described to noninvasively predict the presence of high-risk esophageal varices in patients with compensated advanced chronic liver disease (cACLD). However, a recent study showed that treatment with ß blockers could increase decompensation-free survival in patients with clinically significant portal hypertension, thereby making it important to predict the presence of any esophageal varices. We aimed to develop a simple scoring system to predict any esophageal varices. METHODS: We retrospectively reviewed patients who had vibration-controlled transient elastography (VCTE) at Cook County Hospital, Chicago, USA. Patients with cACLD and liver stiffness measurement (LSM) ≥ 10 kPa with esophagogastroduodenoscopy performed within one year of VCTE were analyzed. We generated a novel score to predict esophageal varices, using the beta coefficient of predictive variables. The score was validated in an external cohort at the University of Iowa Hospital, USA. RESULTS: There were 372 patients in the development cohort and 200 patients in the validation cohort. LSM, platelet count, and albumin were identified as predictors of esophageal varices and were included for generating the Cook County score as "platelet count * - 0.0155872 + VCTE score * 0.0387052 + albumin * - 0.8549209." The area under receiver operating curve for our score was 0.86 for any varices and 0.85 for high risk varices and avoided more endoscopies than the expanded Baveno VI criteria while maintaining a very low miss rate (negative predictive value > 99%). CONCLUSION: We propose a new, highly accurate, and easy-to-use scoring system to predict the presence of not only high-risk but any esophageal varices in patients with cACLD.

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.