A rare case report of Erdheim-Chester disease with pericardial effusion, conduction abnormalities, and atrial infiltration.

Background: Erdheim-Chester disease (ECD) is a rare multisystem disorder that primarily affects adults. It is characterized by the excessive production and accumulation of histiocytes, a type of white blood cell, within multiple tissues and organs, including the cardiovascular system. The infiltration of histiocytes can cause a range of cardiovascular symptoms, including pericardial effusion, myocardial infiltration, and heart failure, among others. Despite the potential severity of these cardiovascular manifestations, ECD is often misdiagnosed or underdiagnosed, leading to delays in appropriate treatment and poor outcomes for patients. As such, there is a pressing need for increased awareness and understanding of ECD's cardiovascular manifestations among clinicians and researchers. This article aims to highlight the importance of considering ECD as a potential underlying cause of cardiovascular complaints and to encourage further investigation into this uncommon but potentially life-threatening condition. Case summary: A 63-year-old man presented as outpatient complaining of dyspnoea on exertion during the last 3 weeks (New York Heart Association functional class III). He had also experienced a left shoulder and bilateral knee pain over the last 6 months. The patient was found to have a massive pericardial effusion associated with ECD. While pericardial effusions can have various causes, including infection, cancer, and autoimmune disorders, ECD is one potential cause of this condition. Therefore, it is important for clinicians to consider ECD in the differential diagnosis of patients presenting with unexplained pericardial effusions, particularly in the context of other systemic symptoms suggestive of ECD. We discuss about this specific aetiology and the clinical management of this uncommon condition. Discussion: Erdheim-Chester disease, a non-Langerhans cell histiocytosis, is a rare multisystem disorder. Diagnosis is challenging and should be suspected in the presence of a pericardial effusion with conduction abnormalities with indicators of a multisystem disease.

Retrograde CTO-PCI Using an Internal Thoracic Bypass Graft Segment in a Patient with Acute Inferior ST-Elevation Myocardial Infarction and Cardiogenic Shock.

Background: Percutaneous coronary intervention (PCI) of the "culprit" artery is the recommended mechanical reperfusion strategy in the setting of ST-segment elevation myocardial infarction (STEMI). As PCI of bypass grafts may be associated with higher risks and lower procedural success rates, in patients with a history of previous coronary artery surgery, PCI directed at revascularization of the native vessels should be considered, but this may be difficult in the setting of a chronically occluded artery. Case Presentation: A patient with a history of multivessel coronary artery disease and a chronic total occlusion (CTO) of the right coronary artery (RCA) requiring arterial bypass surgery, presented with an acute inferior STEMI and cardiogenic shock. It was felt that shock was caused by the acute thrombotic occlusion of a right internal thoracic artery (RITA) bypass graft that had been sequentially anastomosed to the left circumflex (LCx) and right coronary arteries. Despite initiation of extracorporeal membrane oxygenation (ECMO), the patient remained in refractory shock and acute revascularization of the right coronary artery was performed through the RITA bypass segment using antegrade access to the graft through the LCx and then a retrograde approach to open a CTO of the RCA. After successful revascularization, the patient was successfully weaned from ECMO. Over 12 months of follow-up, the patient did well and was documented to have improved left ventricular systolic function. Conclusion: This report is the first to document the successful use of a retrograde approach through an arterial graft segment to revascularize a chronic total occlusion in the setting of acute STEMI and cardiogenic shock.

Effects of GIT-27NO, a NO-donating compound, on hepatic ischemia/reperfusion injury.

Hepatic ischemia/reperfusion injury (IRI) is a clinical condition that may lead to cellular injury and organ dysfunction that can be observed in different conditions, such as trauma, shock, liver resection, and transplantation. Moderate levels of nitric oxide (NO) produced by the endothelial isoform of the NO synthase protect against liver IRI. GIT-27NO is a NO-derivative of the toll-like receptor 4 antagonist VGX-1027 that has been shown to possess both antineoplastic and immunomodulatory properties in vitro and in vivo. In this study, we have investigated the effects of this compound in vitro, in a model of oxidative stress induced in HepG2 cells by hydrogen peroxide (H2O2), and in vivo, in a rat model of IRI of the liver. GIT-27NO significantly counteracted the toxic effects induced by the H2O2 on the HepG2 cells and in vivo, GIT-27NO reduced the transaminase levels and the histological liver injury by reducing necrotic areas with preservation of viable tissue. These effects were almost similar to that of the positive control drug dimethyl fumarate. These data suggest that the beneficial effect of GIT-27NO in the hepatic IRI can be secondary to anti-oxidative effects and hepatocyte necrosis reduction probably mediated by NO release.

The H2S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.

GYY4137 is a hydrogen sulfide (H2S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 µM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H2S donor, Na2S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.

Overexpression of macrophage migration inhibitory factor and functionally-related genes, D-DT, CD74, CD44, CXCR2 and CXCR4, in glioblastoma.

The macrophage migration inhibition factor (MIF) is a cytokine with multiple biological functions, including the cancer-associated processes, cell cycle deregulation, angiogenesis and metastatization. The present study investigated the expression of MIF and its functionally associated genes (D-DT, CD74, CD44, CXCR2 and CXCR4) in glioblastoma multiforme (GBM). The data were obtained from The Cancer Genome Atlas databank, through the cBioportal web-based utility (cbioportal.org/). A significant increase was observed in the majority of these genes in GBM samples compared with lower grade gliomas, however no significant correlation among the selected genes and the overall survival of the patients was identified. In contrast, the expression of MIF exhibited a trend toward an increase in overall survival and a significant increase of MIF expression was observed in samples of patients who underwent neoadjuvant treatment. In conclusion these data indicate that MIF and its receptors are involved in GBM progression and maintenance. Deciphering the precise biological significance in GBM would favor the adoption of tailored approaches to modulate the function of MIF and its associated genes for the treatment of the disease.