Sepsis is not only a significant cause of mortality worldwide, but has particularly devastating effects on the Central Nervous System of survivors. It is therefore crucial to understand the molecular structure, physiology, and events involved in the pathogenesis of Sepsis Associated Encephalopathy (SAE), so that potential therapeutic advances can be achieved. A key determinant to the development of this type of encephalopathy is morphological and functional modification of the blood brain barrier, whose function is to protect the CNS from pathogens and toxic threats. Key mediators of pathologic sequelae of sepsis in the brain include cytokines, including TNF-ɑ, and sphingolipids which are biologically active components of cellular membranes which possess diverse functions. Emerging data demonstrated an essential role for sphingolipids in the pulmonary vascular endothelium. This raises the question of whether endothelial stability in other organs systems such as the CNS may also be mediated by sphingolipids and their receptors. In the present review, we will model the structure and vulnerability of the blood brain barrier, and hypothesize mechanisms for therapeutic stabilization and repair following a confrontation with sepsis-induced inflammation.

Coronavirus disease (COVID-19), the clinical syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global health pandemic with substantial morbidity and mortality. COVID-19 has cast a shadow on nearly every aspect of society, straining health systems and economies across the world. Although it is widely accepted that a close relationship exists between obesity, cardiovascular disease, and metabolic disorders on infection, we are only beginning to understand ways in which the immunological sequelae of obesity functions as a predisposing factor related to poor clinical outcomes in COVID-19. As both the innate and adaptive immune systems are each primed by obesity, the alteration of key pathways results in both an immunosuppressed and hyperinflammatory state. The present review will discuss the cellular and molecular immunology of obesity in the context of its role as a risk factor for severe COVID-19, discuss the role of cytokine storm, and draw parallels to prior viral epidemics such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and 2009 H1N1.

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and fibrotic transformation of the lung parenchyma, resulting in the progressive loss of respiratory function and, often, death. Current treatments that target profibrotic factors can slow the rate of progression but are unable to ultimately stop it. In the past decade, many studies have shown that increased vascular permeability may be both a predictive and perpetuating factor in fibrogenesis. Consequently, there is a search for therapeutic targets to try and modulate vascular permeability in fibrotic lungs. One such class of targets that show great promise is sphingolipids. Sphingolipids are common in cell membranes and are increasingly recognized as critical to many cell signaling pathways, including those that affect the integrity of the vascular endothelial barrier. In this focused review we look at sphingolipids, particularly the sphingosine-1-phosphate (S1P) axis and its effects on vascular permeability, and how those effects may affect the pathogenesis of IPF. We further examine existing S1P modulators and their potential efficacy as therapeutics for IPF.

Mounier-Kuhn syndrome (MKS) or tracheobronchomegaly is an uncommon disease of the central airways. It is characterized by pathological dilatation of the trachea and main bronchi and inevitably leads to recurrent respiratory infections, bronchiectasis, hospitalizations, and results in considerable morbidity and mortality. Despite numerous case reports, there is a shortage of evidence on clinical outcomes and limited data on interventions, thus presenting a significant gap in the literature. Fortunately, new strategies and increasing clinical experience have improved the clinical approach, diagnostic workup, classification, and management of MKS. Articles in English, Spanish, and French were searched from databases, including Pubmed, Google Scholar, Medline, and SCOPUS, using the terms "Mounier-Kuhn syndrome," "Tracheomegaly," "Tracheobronchomegaly," and "Bronchomegaly," without date restrictions. A total of 360 articles with the aforementioned syntax were indexed on Pubmed. This state-of-the-art review attempts to fill a void in the current literature by summarizing the current scientific knowledge and highlighting novel interventional strategies in the management of Mounier Kuhn Syndrome.

Objectives: The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose computed tomography (CT) for lung cancer screening (LCS). The NLST found the greatest benefit to LCS for patients who underwent annual screening for a full 3-year follow-up period. The adherence to serial imaging in the NLST was 95%. Methods: We conducted a prospective study of 268...

This prospective investigation derived a prediction model for identifying risk of incident lung cancer among patients with visible lung nodules identified on computed tomography (CT). Among 2,924 eligible patients referred for evaluation of a pulmonary nodule to the Stony Brook Lung Cancer Evaluation Center between January 1, 2002 and December 31, 2015, 171 developed incident lung cancer during the observation period. Cox proportional hazard models were used to model time until disease onset. The sample was randomly divided into discovery (n = 1,469) and replication (n = 1,455) samples. In the replication sample, concordance was computed to indicate predictive accuracy and risk scores were calculated using the linear predictions. Youden index was used to identify high-risk versus low-risk patients and cumulative lung cancer incidence was examined for high-risk and low-risk groups. Multivariable analyses identified a combination of clinical and radiologic predictors for incident lung cancer including ln-age, ln-pack-years smoking, a history of cancer, chronic obstructive pulmonary disease, and several radiologic markers including spiculation, ground glass opacity, and nodule size. The final model reliably detected patients who developed lung cancer in the replication sample (C = 0.86, sensitivity/specificity = 0.73/0.81). Cumulative incidence of lung cancer was elevated in high-risk versus low-risk groups [HR = 14.34; 95% confidence interval (CI), 8.17–25.18]. Quantification of reliable risk scores has high clinical utility, enabling physicians to better stratify treatment protocols to manage patient care. The final model is among the first tools developed to predict incident lung cancer in patients presenting with a concerning pulmonary nodule.