Introduction: Pneumomediastinum (PM) is characterized by the presence of air within the mediastinum. The association between PM and coronavirus 2019 (COVID-19) has not been well established in the current literature. We sought to summarize the limited body of literature regarding PM in patients with COVID-19 and characterize the presentation and clinical outcomes of PM in patients with severe acute respiratory syndrome (SARS)-COV-2 pneumonia at our institution to better define the incidence, prognosis, and available treatment for this condition. Materials and Methods: All patients with a proven diagnosis of COVID-19 and PM between March 18, 2020 and May 5, 2020 were identified through hospital records. Retrospective analysis of radiology records and chart review were conducted. Clinical characteristics and outcomes were collected and descriptive statistics was analyzed. Results: Thirty-six patients met inclusion criteria. Out of the 346 intubated COVID-19 patients, 34 (10%) had PM. The incidence of PM increased for the first 4 weeks of the pandemic, and then began to decrease by week 5. At the endpoint of the study, 12 (33.33%) patients were alive and 24 patients (66.67%) had died. Conclusion: PM, although a rare phenomenon, was more prevalent in COVID-19 patients compared with historical patients with adult respiratory distress syndrome. The etiology of this condition may be attributed to higher susceptibility of patients infected with SARS-CoV-2 to a combination of barotrauma and airway injury.
Background: Pneumomediastinum and pneumothorax are complications which may be associated with barotrauma in mechanically ventilated patients. The current literature demonstrates unclear outcomes regarding barotrauma in critically ill patients with severe COVID-19. The purpose of this study was to examine the incidence of barotrauma in patients with severe COVID-19 pneumonia and its influence on survival. Study Design and Methods: A retrospective cohort study was performed from March 18, 2020 to May 5, 2020, with follow-up through June 18, 2020, encompassing critically ill intubated patients admitted for COVID-19 pneumonia at an academic tertiary care hospital in Brooklyn, New York. Critically ill patients with pneumomediastinum, pneumothorax, or both (n = 75) were compared to those without evidence of barotrauma (n = 206). Clinical characteristics and short-term patient outcomes were analyzed. Results: Barotrauma occurred in 75/281 (26.7%) of included patients. On multivariable analysis, factors associated with increased 30-day mortality were elevated age (HR 1.015 [95% CI 1.004-1.027], P = 0.006), barotrauma (1.417 [1.040-1.931], P = 0.027), and renal dysfunction (1.602 [1.055-2.432], P = 0.027). Protective factors were administration of remdesivir (0.479 [0.321-0.714], P < 0.001) and receipt of steroids (0.488 [0.370-0.643], P < 0.001). Conclusion: Barotrauma occurred at high rates in intubated critically ill patients with COVID-19 pneumonia and was found to be an independent risk factor for 30-day mortality.
Background Mast cells are indispensible for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate septic responses. ITK and BTK regulate mast cell responses to allergen, but their roles in mast cell responses in LPS-induced sepsis are unclear. Objectives We sought to investigate the roles of ITK and BTK in mast cell responses during LPS-induced septic inflammation. Methods Mice (genetically modified or BMMC-reconstituted Sash) were given LPS to induce septic hypothermia, in the presence or absence of indicated inhibitors. Flow cytometry was used to determine LPS-induced cell influx and TNF-α production in peritoneal cells. Microarray was used for genome-wide gene expression analysis on BMMCs. Quantitative PCR and multiplex were used to determine transcribed and secreted pro-inflammatory cytokines. Microscopy and western blotting were used to determine activation of signal transduction pathways. Results The absence of ITK and BTK leads to exacerbation of LPS-induced septic hypothermia and neutrophil influx. Itk−/−Btk−/− mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, and lead to more severe LPS-induced septic hypothermia when reconstituted into mast cell deficient Sash mice. LPS-induced NF-κB, Akt and p38 activation is enhanced in Itk−/−Btk−/− mast cells, and blockage of PI3K, Akt or p38 downstream MNK1 activation significantly suppresses TNF-α hyper-production and attenuates septic hypothermia. Conclusions ITK and BTK regulate thermal homeostasis during septic response through mast cell function in mice. They share regulatory function downstream of TLR4/LPS in mast cells, through regulating the activation of canonical NF-κB, PI3K/Akt and p38 signaling pathways.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid and hematological malignancies. ICIs are not only able to produce long and durable responses, but also very well tolerated by patients. There are several approved indications of use of ICIs in treatment of metastatic gastrointestinal malignancies including gastric, esophageal, colorectal and hepatocellular carcinoma. In addition, ICIs can be used in microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB) tumors in chemotherapy-resistant setting. Despite having good efficacy and superior safety profile, ICIs are clinically active in small subset of patients, therefore, there is a huge unmet need to enhance their efficacy and discover new predictive biomarkers. There are several ongoing clinical trials that are exploring the role of ICIs in various gastrointestinal cancers either as single agent or in combination with chemotherapy, radiation therapy, targeted agents or other immunotherapeutic agents. In this review, we discuss the published and ongoing trials for ICIs in gastrointestinal malignancies, including esophageal, gastric cancer, pancreatic, hepatocellular, biliary tract, colorectal and anal cancers. Specifically, we focus on the use of ICIs in each line of therapy and discuss the future directions of these agents in each type of gastrointestinal cancer.
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