A Malignant Gastrointestinal Stromal Tumor of the Gallbladder Immunoreactive for PDGFRA and Negative for CD 117 Antigen (c-KIT)

Gastrointestinal stromal tumors (GISTs) compose the largest category of well-recognized nonepithelial neoplasms of the gastrointestinal tract (GI). GISTs of the gallbladder are extremely rare tumors. Only four malignant, two benign and one GIST-like tumor of the gall bladder have ever been described. The four malignant GISTs were all positive for CD 117 antigen (c-kit). We present for the first time a malignant gastrointestinal stromal tumor of the gallbladder, immunoreactive for platelet-derived growth factor receptor alpha (PDGFRA) and negative for CD 117 antigen (c-KIT)

Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Bundle branch reentrant tachycardia treated with cardiac resynchronization therapy in a patient with dilated cardiomyopathy

A 66 years old woman with known dilated cardiomyopathy and severely reduced ejection fraction presented with bundle branch reentrant tachycardia. Bundle branch reentrant tachycardia is an uncommon form of ventricular tachycardia incorporating both bundle branches into the reentry circuit. The diagnosis is based on electrophysiological findings and pacing maneuvres that prove participation of the His- Purkinje system in the tachycardia mechanism. Radiofrequency ablation of right bundle is proposed as the first line therapy. In our patient, the ablation imposed a high risk of complications in view of the existing conduction defects. We decided to proceed with a CRT – D implantation, which improved patient’s symptoms and diminished ventricular tachycardia episodes. As a result, biventricular pacing may serve as an alternative method to ablation treatment

Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study

INTRODUCTION Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications. METHODS Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria. RESULTS One hundred and nineteen patients were recruited. Fifteen (13%) patients required blood transfusion within 24 hours of surgery, 44 (37%) patients developed infections and 3 (2%) patients died prior to discharge. Patients receiving a blood transfusion were more likely to develop postoperative infections (P =0.02) and to have lower tumour necrosis factor alpha (TNFα), interleukin (IL)-12, IL-23 and RAR-related orphan receptor gamma T (RORγt) gene expression in the postoperative period (P <0.05). The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving a blood transfusion over this period. Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult. CONCLUSIONS An association between an immunosuppressive pattern of gene expression and blood transfusion following major elective gastrointestinal surgery is described. This gene expression profile includes a reduction in the activity of innate immunity and T helper cell type 1 (Th1) and T helper cell type 17 (Th17) pathways in those patients receiving a blood transfusion. Blood transfusion was also associated with an excess of infectious complications in this cohort. A mechanistic link is suggested but not proven

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

The effects of modern antiretroviral treatment on markers of cardiovascular morbidity and immune activation in treatment-naïve people living with HIV

Human immunodeficiency virus (HIV) infection represents a major cardiovascular risk factor and the cardiovascular disease (CVD) burden among ageing people living with HIV (PLWH) constitutes a leading cause of morbidity and mortality. Therefore, it is necessary to evaluate and properly stratify the cardiovascular risk assessment in PLWH with appropriate screening tools. This approach will optimize the stratification of patients who are at higher risk for CVD and will benefit most from prevention measures and timely management. Endothelial glycocalyx may represent such a potential assessment tool as its derangement has been associated with CVD. However, studies on endothelial integrity among PLWH, are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received tenofovir alafenamide fumarate / emtricitabine (TAF/FTC), combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed endothelial glycocalyx at baseline, at 24 (±4) and at 48 (±4) weeks, by measuring the Perfused Boundary Region (PBR), the area that is permeable by erythrocytes, and thus it is inversely proportional to EG thickness, in sublingual microvessels. In total, 66 consecutive PLWH [60 (90.9%) males] with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40 (60.6%) received an INSTI-based regimen. The mean (standard deviation, SD) PBR decreased significantly from 2.17 (0.29) μm at baseline to 2.04 (0.26) μm (p = 0.019), and then to 1.93 (0.3) μm (p <0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. However, PLWH on INSTIs had a sytatistically significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low viremia level experienced the greatest PBR reduction. This study is the first reporting the benefit of antiretroviral treatment on glycocalyx improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.Η λοίμωξη από τον ιό της ανθρώπινης ανοσοανεπάρκειας (Human Immunodeficiency Virus, HIV) αποτελεί σημαντικό παράγοντα καρδιαγγειακού κινδύνου και η καρδιαγγειακή νόσος (Cardiovascular Disease, CVD) μεταξύ των ατόμων που ζουν με τον HIV (People Living with HIV, PLWH) αποτελεί πλέον μια από τις σημαντικότερες αιτίες νοσηρότητας και θνησιμότητας. Ως εκ τούτου, είναι απαραίτητη η σωστή αξιολόγηση του καρδιαγγειακού κινδύνου στους PLWH με εργαλεία προσυμπτωματικού ελέγχου κατάλληλα για αυτόν τον πληθυσμό. Αυτή η προσέγγιση θα βελτιστοποιήσει τη αναγνώριση των PLWH εκείνων που διατρέχουν τον υψηλότερο καρδιαγγειακό κίνδυνο και θα ωφεληθούν περισσότερο από την εφαρμογή προληπτικών μέτρων. Ο ενδοθηλιακός γλυκοκάλυκας μπορεί να αντιπροσωπεύει ένα τέτοιο εργαλείο αξιολόγησης καθώς η διαταραχή του έχει συσχετιστεί με την CVD. Ωστόσο, μέχρι σήμερα δεν υπάρχουν μελέτες που να εξετάζουν την ακεραιότητα του ενδοθηλιακού γλυκοκάλυκα σε PLWH στα πλαίσια διερεύνησης της CVD. Διεξάγαμε μια προοπτική μελέτη παρατήρησης με PLWH που δεν είχαν λάβει αντιρετροϊκή θεραπεία στο παρελθόν και έλαβαν εμτρισιταμπίνη/τενοφοβίρη αλαφεναμίδη, σε συνδυασμό είτε με έναν αναστολέα ιντεγκράσης (Integrase Strand Transfer Inhibitor, INSTI: ντολουτεγκραβίρη, ραλτεγκραβίρη ή ελβιτεγκραβίρη/κομπισιστάτη) είτε με τον αναστολέα πρωτεάσης (Protease Inhibitors, PI) δαρουναβίρη/κομπισιστάτη. Εκτιμήσαμε το πάχος του ενδοθηλιακού γλυκοκάλυκα πριν, στις 24 (±4) και στις 48 (±4) εβδομάδες από την έναρξη της θεραπείας, εκτιμώντας το Perfused Boundary Region (PBR) - δηλαδή την περιοχή που είναι διαπερατή από τα ερυθροκύτταρα και επομένως είναι αντιστρόφως ανάλογη με το πάχος του γλυκοκάλυκα - στα υπογλώσσια αγγεία. Στη μελέτη εντάχθηκαν συνολικά 66 PLWH [60 (90,9%) άνδρες] με διάμεση ηλικία (ενδοτεταρτημοριακό εύρος, Interquartile Range, IQR) 37 (12) έτη, εκ των οποίων οι 40 (60,6%) έλαβαν αντιρετροϊκό σχήμα με έναν INSTI. Το μέσο (τυπική απόκλιση, SD) PBR μειώθηκε στατιστικά σημαντικά από 2,17 (0,29) μm πριν την έναρξη αγωγής, σε 2,04 (0,26) μm (p = 0,019) και στη συνέχεια σε 1,93 (0,3) μm (p <0,0001) στις 24 (±4) και 48 (±4) εβδομάδες, αντίστοιχα, γεγονός που υποδεικνύει τη σαφή βελτίωση του πάχους του γλυκοκάλυκα εντός του πρώτου έτους έναρξης της αντιρετροϊκής αγωγής. Αν και το PBR δεν διέφερε μεταξύ των ομάδων θεραπείας, οι PLWH που έλαβαν INSTI είχαν στατιστικά σημαντική μείωση του PBR στις 48 (±4) εβδομάδες. Επιπλέον, οι καπνιστές και οι PLWH με χαμηλό αρχικό ιικό φορτίο παρουσίασαν τη μεγαλύτερη μείωση PBR. Πρόκειται για την πρώτη μελέτη που αναφέρει το όφελος της αντιρετροϊκής θεραπείας στη βελτίωση του ενδοθηλιακού γλυκοκάλυκα σε PLWH που δεν είχαν λάβει ποτέ θεραπεία στο παρελθόν, υποδεικνύοντας έτσι έναν πιθανό βιοδείκτη και ενδεχόμενο θεραπευτικό στόχο για την CVD στους PLWH

Serious complications of COVID-19 vaccines: A mini-review.

Τhe most promising approach of fighting COVID-19 and restraining the course of this pandemic is indisputably the universal vaccination of the population with safe and effective vaccines. However, besides the common and usually mild side effects of the authorized vaccines, some rare, major adverse reactions are increasingly being reported worldwide during the post marketing surveillance phase of vaccines&apos; circulation, such as anaphylaxis, vaccine-induced thrombotic thrombocytopenia, myopericarditis and Guillain-Barré syndrome. Despite rare cases with complications from COVID-19 vaccines, the net benefit-risk ratio shows a clearly favorable balance towards COVID-19 vaccination for all age and sex groups. Vaccine adverse events should be identified early and monitored closely. As many aspects of these adverse effects remain still obscure for the medical community and the relevant stakeholders, it is also highly important to be promptly reported. Nonetheless, these complications should not constitute a reason to change the vaccine policy and further studies are needed to alleviate concerns and reluctance to COVID-19 vaccinations

Future Perspectives in the Diagnosis and Treatment of Sepsis and Septic Shock

Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, represents the primary cause of death due to infection [...

Editorial for special issue “multidrug-resistant pathogens”

The era of injudicious use of antibiotics in both humans and animals has led to the selection of multidrug-resistant (MDR) pathogens, which in turn has left the medical community with limited therapeutic options [...]