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• To evaluate in SARS-CoV-2 patients the behavior of MR-proADM a peptide derived from adromedullin, that maintains endothelial integrity: the endothelial dysfunction seems to be involved in the spread of the COVID-19 disease and, consequently, the increase in this biomarker concentrations allow to obtain clinically relevant prognostic informations. • To compare the informations provided by MR-proADM with those of some biomarkers routinely measured in patients suffering from multiorgan disease. • To provide additional biochemical informations in patients suffering from SARS-CoV-2 producing an outbreak of pandemic proportions. Endothelial dysfunction, a major complication of SARS-CoV-2 infectionplaying a key-role in multi-organ damage, carries high risk of mortality. To investigate the potential role of Mid-Regional pro-Adrenomedullin (MR-proADM) in detecting endothelial damage with a view to stratifying the risk of adverse events (length of stay, death, admission in Intensive Care Unit) and/or disease resolution. In 135 consecutive patients with SARS-CoV-2 infection, MR-proADM was measured in EDTA-K2 plasma samples using B.R.A.H.M.S. KRYPTOR® COMPACT Plus method (Thermo Fisher Scientific, Hennigsdorf, Germany) Patients were subdivided into three groups based on their MR-proADM value (nmol/L): 1 (n = 20, MR-proADM ≤ 0.55); 2 (n = 82, 0.55 < MR-proADM ≤ 1.50); 3 (n = 33, MR-proADM > 1.50). The higher the MR-proADM value, the greater the patients' age, the more frequent the occurrence of pneumonia, the requiring of more aggressive treatment, the longer the hospitalization and the more frequent a fatal event. Significant differences were found between the three groups for MR-proADM, White-blood cell count, Neutrophil count, D-dimer, C-reactive Protein, Procalcitonin and hs-Troponin I. At logistic regression,it was found that MR-proADM and Log 10 D-dimer were the most significant predictors of adverse events. The findings made in the present study highlight the relevance of MR-proADM values in providing clinically useful information, particularly for stratifying COVID-19 patients according to the risk of a more severe form of disease and to the development of adverse events. [ABSTRACT FROM AUTHOR]

This case demonstrates an unusual presentation of Herpes simplex virus (HSV) ocular infection and the challenges faced during the management of its complications. A thirty year-old lady, a steroid responder with HSV keratouveitis, was referred for non-response to treatment with the prophylactic dose of oral acyclovir and acetazolamide. She presented with large epithelial bullae, anterior chamber reaction, and raised intraocular pressure in her right eye. Initially, she responded to the therapeutic dose of oral acyclovir, but on follow-up visits, she developed high intraocular pressures of up to 45 mmHg on maximum medical therapy. Hence, trabeculectomy with mitomycin-C was performed. One year later, she developed corneal endothelial decompensation, for which a Descemet's stripping automated endothelial keratoplasty (DSAEK) was done. Eight months post-operatively, she had a best corrected visual acuity of 20/20, clear corneal graft, quiet anterior chamber, and well-controlled intraocular pressures. HSV trabeculitis is associated with inflammation of the anterior chamber, endothelitis and raised intra-ocular pressure. A combination of anti-viral, anti-inflammatory, and anti-glaucoma medications helps in the management. However, glaucoma filtration surgery is often needed to the control intra-ocular pressure. Chronic recurrent episodes eventually lead to endothelial failure and demand endothelial keratoplasty (EK). It is prudent to adopt certain measures to perform EK in these phakic eyes without causing any iatrogenic damage to the filtration bleb as well as to the clear crystalline lens. This case highlights the difficulties of treating HSV-related keratouveitis with uncontrolled glaucoma, problems of associated steroid response, and complexities in performing corneal endothelial procedures in young phakic patients especially post-trabeculectomy. • HSV infecting the uveal tract is likely to infect the endothelium and trabecula. • HSV trabeculitis is associated with endothelitis and high intraocular pressure, which is not controlled with maximum medical management. • Glaucoma filtration surgery helps in controlling intraocular pressure. • Chronic cases develop endothelial dysfunction and demand endothelial keratoplasty. • Endothelial keratoplasty in a phakic eye needs a strategical approach intra-operatively. [ABSTRACT FROM AUTHOR]

Background: The incidence of endothelitis in cardiac transplants, and the relationship to clinical symptoms and humoral rejection, is unclear. Recently, the finding of intravascular macrophages has been found to represent antibody-mediated rejection. This study investigated the role of intravascular T lymphocytes in antibody-mediated rejection. Methods: A total of 819 sequential biopsy specimens from 93 cardiac allograft recipients were prospectively studied. Rejection was graded according to International Society for Heart and Lung Transplantation (ISHLT) criteria and inflammatory infiltrates characterized by immunohistochemical staining for CD3, CD4, CD8, CD68, and CD20. Endothelitis was defined as lymphocyte and macrophage infiltrates within arteriolar, capillary, or venular walls, with endothelial swelling, in contrast to perivascular inflammation of cellular rejection. Complement C4d was identified in capillary walls by immunofluorescent staining and immunohistochemical staining on paraffin sections. Results: Endothelitis was identified in 27 specimens (3%) from 14 patients (15%). ISHLT rejection grades were 0 in 6 specimens, 1R in 20 (1A in 8; 1B in 12), and 2R (3A) in 1. In all cases, there were admixtures of macrophages and T lymphocytes. Inflammation was most prominent in venules. C4d was localized in 12 of the 27 specimens (44%). C4d was localized in 31 of 796 specimens without endothelitis (p < 0.001). The endothelial infiltrates were CD3, CD4, CD8, and CD68+. Twelve of 14 patients had > 0 panel reactive antibodies (PRA), 9 were above 10%, and 8 were above 25%; 5 patients were treated for clinical antibody-mediated rejection, and 4 had possible cardiac allograft vasculopathy by ultrasound imaging (mean follow-up, 40 months). Conclusion: Endothelitis is present in more than 10% of heart transplant recipients and is associated with complement deposition on biopsy samples. Approximately 33% of patients have clinical evidence of humoral rejection. The eventual risk for developing graft vascular disease remains undetermined. [Copyright &y& Elsevier]

Abstract: The endothelium is now considered a real endocrine–paracrine organ, important not only as a structural barrier between the circulation and surrounding tissue, but also because it plays an essential role for local hemodynamics, releasing substances that modulate the vascular calibre and blood cell activation. Here, after a brief but detailed analysis of the importance of the endothelium in vascular homeostasis, in the control of coagulation and in the relations with the different blood cells, we will explain the concept of endothelial dysfunction (altered NO release) and activation (amplified adhesion molecule expression) in inflammatory, connective tissue and post-trasplantation diseases. Furthermore, this review will focus on the activity of prostacyclin and synthetic analogs, especially their ability to interact with the vasodilatation system and their role in modulating cell interaction by surface adhesion molecule expression, cytokines and growth factors release as well as gene transcription factors. Finally, we will consider the therapeutic role of prostacyclin analogs in the prevention and treatment of connective tissue diseases. [Copyright &y& Elsevier]