Background Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. Discussion We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. Conclusion Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.
In a series of 602 procedures, over 90% of primary forearm insertions of PTFE grafts between the radial artery and a cubital vein were possible. Thrombosis of the graft, which was invariably due to venous outflow obstruction, was the most common complication encountered. Revision of the venous anastomosis was not necessary in about one-third of the thrombosed grafts if a size 3 coronary dilator could be passed and the augmentation test was satisfactory. For revisions, creation of a new venous anastomosis using a jump graft was preferred over patch angioplasty or venous endarterectomy. Crossing the elbow for this purpose did not adversely affect graft patency. The incidence of aneurysm formation and infection was 16% and 35%, respectively. Infections involving the graft were managed by drainage, antibiotics, and bypass of the infected portion. Immediate bypass and delayed bypass were equally effective. About one-half of the infected grafts were salvaged by these techniques. The most common organism was Staphylococcus aureus. With a combination of the techniques outlined above, the service life of individual PTFE grafts can be extended. Two-year access patency in this series was 77%.
CT scanning of the chest is one of the most important imaging modalities available to a pulmonologist. The advent of high-resolution CT scanning of the chest has led to its increasing use. Although chest radiographs are still useful as an initial test, their utility is limited in the diagnosis of lung diseases that depend on higher resolution images such as interstitial lung diseases and pulmonary vascular diseases. Several metaphoric chest CT scan signs have been described linking abnormal imaging patterns to lung diseases. Some of these are specific to a disease, whereas others help narrow the differential diagnosis. Recognizing these imaging patterns and CT scan signs are thus vitally important. In the present article, we describe a comprehensive list of the commonly encountered metaphoric chest CT scan signs and their clinical relevance.
Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies against checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1). By blocking these receptors and signals, the immune system can be reactivated to fight the tumor. Immunotherapy for advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of treatment options resulting in improved survival and response rates and has a less severe yet unique toxicity profile when compared to chemotherapy. PD-1 inhibitors, nivolumab and pembrolizumab, and PD-L1 inhibitor, atezolizumab, are currently approved by regulatory authorities for the treatment of advanced NSCLC. This article provides a detailed review of these newer agents, their mechanism of action, side-effect profile, therapeutic indications and current evidence supporting their use in the management of NSCLC.
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