Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that accounts for 5% of all thoracic neoplasm usually located in the posterior mediastinum and is generally associated with a poor outcome. We present a case of MPNST of the anterior mediastinum presenting in a rare location leading to diagnostic dilemmas and treated primarily by surgical resection.
Background Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter‐cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell‐derived extracellular vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. Methods Immune cell‐derived EV were measured in cirrhosis patients [Child‐Turcotte‐Pugh (Child) score A, n = 15; B n = 16; C n = 43 and Child‐C with sepsis (n = 38)], and healthy controls (HC, n = 11). In vitro and in vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. Results Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (P < .001)and correlated with liver disease severity indices (r2 > 0.3, P < .001), which further increased in Child C sepsis than without sepsis(P < .001); monocyte EV showing the highest association with disease stage [P = .013; Odds ratio‐4.14(1.34‐12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio‐6.2 (2.4‐15.9), AUROC = 0.76, P < .01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (P = .004), reduced basal oxygen consumption rate (P < .001) and induced pro‐inflammatory genes (P < .05). The septic‐EV on adoptive transfer to C57/BL6J mice, induced sepsis‐like condition within 24 h with leukocytopenia (P = .005), intrahepatic inflammation with increased CD11b + cells (P = .03) and bone marrow hyperplasia (P < .01). Conclusion Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients.
Background and Aims Cirrhosis patients exhibit cytopenia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients. Methods Cirrhotic patients ( n =127) and controls ( n =26) with clinically indicated bone marrow (BM) examination were studied. BM assessment was done by qRT-PCR and immunohistochemistry (IHC) for CSF3R . Circulating G-CSF, CSF3R, and carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) were measured. BM hematopoietic precursor cells and their alterations were examined by flow cytometry. The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia. Results The mean age was 48.6±13.4 years, and 80.3% were men. Circulatory CSF3R reduction was noted with the advancement of cirrhosis, and confirmed by qRT-PCR and IHC in BM. CSF3R decline was related to decreased hematopoietic stem cells (HSCs) and downregulation of CSF3R in the remaining HSCs. Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation. Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up. Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia. Conclusions Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circulation, making patients prone to infection and inadequate response to exogenous G-CSF.
Introduction: Cirrhosis patients exhibit cytopenia and variable response to GCSF, with benefits in early cirrhosis. GCSF acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We investigated the possible mechanism for the lack of efficacy of GCSF in advanced cirrhosisMethodsCirrhotic patients (n = 127) and controls (n = 26) who underwent clinically indicated bone marrow (BM) examination were studied. BMs were assessed for RNA sequencing, qRT-PCR, and immunohistochemistry (IHC) for CSF3R and associated genes. Circulating GCSF, CSF3R, and carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) were measured. BM hematopoietic precursor cells and their alterations were examined by flow cytometry. The findings were validated, where the GCSF was administered as for liver regeneration (n = 22) and severe neutropenia (n = 15)ResultsThe mean age was 48.6 ± 13.4 years, 80.3% males. Gene set enrichment analysis showed lowered CSF3R in Child's C compared to A, confirmed by qRT-PCR and IHC. Circulatory CSF3R was also reduced in advanced cirrhosis. CSF3R decline was related to decrease hematopoietic stem cells (HSCs) and downregulation of CSF3R in remaining HSCs. CSF3R inhibitory protein CEACAM1 caused CSF3R downregulation. CEACAM-1, in turn, positively correlated with the increased lysosomal expression in HSCs. Peripheral blood-CSF3R was lesser in those cases who developed an infection Baseline CSF3R was also lower in G-CSF non-responders.ConclusionsCSF3R is downregulated in patients with advanced cirrhosis, and it could be the underlying cause of the inadequate response to GCSF.
Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objective This study aimed to evaluate the antifungal and anti-biofilm activities of silver nanoparticles synthesized using Trillium govanianum, a trans-Himalayan medicinal plant extract, against multidrug-resistant Candida auris. Methods Silver nanoparticles (AgNPs) were synthesized by adopting a green approach. Optimization and characterization of TG-AgNPs were carried out using UV-VIS spectroscopy, TEM, and FTIR. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and antibiofilm activity of the crude extract, as well as TG-nanoparticles, were evaluated. Furthermore, their effect on cell morphology and cell permeability was also analyzed using FESEM. Results Crude extracts of roots of T. govanianum exerted remarkable antifungal activity against multiple strains of Candida auris. The incorporation of silver nanoparticles to plant extract significantly improved the antifungal and antibiofilm activities against the tested strains in a synergistic manner. Conclusion Silver nanoparticles synthesized using Trillium govanianum extract provide eco-friendly, biocompatible nanostructures with antifungal activity and have the potential for use as a therapeutic/nutraceutical agent.
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