Endothelium and sepsis: functional markers

Introduction. Sepsis is a major cause of morbidity and mortality in ICU area. The endothelium plays a critical role in the pathophysiology of sepsis. Several endothelial biomarkers expressed during sepsis without, however, standardized levels, that would be useful tools for prognosis, diagnosis and outcome of sepsis.Objective. Assessment of microcirculation by near infrared spectroscopy (NIRS) method in combination with Vascular Occlusion Technique (VOT) during sepsis and determination of biomarkers in prognosis of sepsis syndrome.Material–Methods. The study involved 187 non-septic critically ill patients, of whom one hundred twenty two met the inclusion criteria. To estimate the condition of microcirculation we used NIRS technology in combination with vascular occlusion technique in peripheral muscle. Measurements by this method were in four time points: at admission day in ICU, on sepsis day, 24h and 48h after sepsis presence. For the determination of different biomarkers we used ELISA assay, RT-PCR, etc.Results. From one hundrend twenty two non-septic critically ill patients who included in our study, 71 of them, developed sepsis during their stay in ICU while 51 were used as control group (non-septic patients). NIRS measurements of septic patients (N=71) have impaired oxygen consumption rate in sepsis day compared with their baseline. Furthermore, hyperemia recovery time was significantly lower on the sepsis day compared to baseline (137±50sec, vs 169±30sec, p<0.001). This parameter continued to decrease during subsequent time points, at 24hrs and 48hrs after sepsis. Hyperemia recovery area showed significant differences between baseline and sepsis day (19.3±10.6,vs 12.4±8.6,p<0.001), 24hrs (10.7±7.5, p<0.001) and 48hrs (10±4.7,p<0.001). From all biomarkers (sP-selectin , sE-selectin , Ang-1, Ang-2, VE-cadherin, sICAM-1, TNF-α, VEGF, vWf) only sE-selectin and sP- selectin levels were increased at admission day in patients who developed sepsis compared with non-septic patients. By analyzing the results of EPCR we observed increased levels in patients who developed sepsis during their stay in ICU compared with non-septic patients. Multivariate analysis showed that sEPCR is the only factor associated with the development of sepsis with time. Finally, Aqp-1 was increased in polymorphonuclear granulocytes in septic patients , while it increased 3-fold at the onset of septic shock.Conclusions. Our results support the view that the endothelium function is disrupted by appearance of sepsis syndrome. NIRS measurements are associated with microcirculatory alterations in critically ill patients at the early stage of sepsis. Furthermore, sEPCR, sE-selectin and sP-selectin appear to be key factors in the development of sepsis suggesting that they could be used as prognostic biomarkers of sepsis. Finally Aqp-1 induction is associated with increased cell membrane permeability and may therefore be of probable functional significance.Εισαγωγή: Η σήψη αποτελεί την κυριότερη αιτία θνητότητας και θνησιμότητας στο χώρο της ΜΕΘ. Το ενδοθήλιο παίζει έναν κεντρικό ρόλο στην παθοφυσιολογία της σήψης. Αρκετοί είναι οι βιοδείκτες που εκφράζονται κατά την σηπτική διεργασία χωρίς ωστόσο να έχουν σταθμιστεί τα επίπεδα τους ώστε να αποτελούν εργαλείο πρόγνωσης , διάγνωσης και έκβασης της σήψης.Σκοπός: Παρακολούθηση της μικροκυκλοφορίας με τη μεθόδο εγγύς του υπερύθρου φασματοσκοπία (Near Infrared Spectroscopy, ΝIRS) και τη τεχνική του αγγειακού αποκλεισμού (Vascular Occlusion Technique, VOT) κατά τη φάση της σήψης και προσδιορισμός των βιοδεικτών στην πρόγνωση του σηπτικού συνδρόμου.Υλικό μέθοδος: Στη μελέτη συμμετείχαν 187 μη σηπτικοί βαρέως πάσχοντες ασθενείς από τους οποίους οι εκατόν είκοσι δυο πληρούσαν τα κριτήρια εισαγωγής. Για την εκτίμηση της μικροκυκλοφορίας χρησιμοποιήθηκε η μέθοδος του ΝΙRS σε συνδυασμό με την αγγειακή απόφραξη άνω άκρου. Οι μετρήσεις με τη μέθοδο αυτή έγιναν σε τέσσερα χρονικά σημεία: κατά την εισαγωγή των ασθενών στη ΜΕΘ, την ημέρα σήψης, 24 και 48 ώρες από την εμφάνιση σήψης. Για των προσδιορισμό των διαφόρων βιοδεικτών χρησιμοποιήθηκαν η δοκιμασία ELISA, η RT-PCR, κ.α .Αποτελέσματα: Από τους εκατόν είκοσι δυο μη σηπτικούς βαρέως πάσχοντες ασθενείς που εντάχθηκαν στη μελέτη μας, 71 παρουσίασαν σήψη κατά την παραμονή τους στη ΜΕΘ, ενώ οι υπόλοιποι χρησιμοποιήθηκαν ως ομάδα ελέγχου (μη σηπτικοί ασθενείς). Οι μετρήσεις με τη μέθοδο NIRS για την εκτίμηση της μικροκυκλοφορίας των σηπτικών ασθενών (Ν=71) παρουσίασαν διαταραχές στον ρυθμό κατανάλωσης οξυγόνου την ημέρα της σήψης συγκριτικά με την ημέρα εισαγωγής τους. Επιπλέον, η μεταβλητή hyperemia recovery time ήταν σημαντικά μειωμένη την ημέρα της σήψης σε σύγκριση με την ημέρα εισαγωγής (137±50sec, vs 169±30sec, p =0,001). Αυτή η παράμετρος συνέχισε να μειώνεται και στις επόμενες χρονικές μετρήσεις, δηλαδή 24h και 48h μετά την εμφάνιση σήψης. Επίσης, η μεταβλητή hyperemia recovery area έδειξε στατιστικά σημαντικές διαφορές μεταξύ ημέρας εισαγωγής και ημέρας σήψης (19,3±10,6 vs 12,4±8,6 p<0,001), μεταξύ 24h (10,7±7,5,p<0,001) και μεταξύ 48h από την εμφάνιση σήψης (10±4,7, p<0,001) αντίστοιχα. Από όλους τους βιοδείκτες (sP-σελεκτίνη, sE-σελεκτίνη, Ang-1, Ang-2,VE-cadherin, sICAM-1, TNF-,VEGF, vWf) μόνο στην sE-σελεκτίνη και στην sP-σελεκτίνη βρέθηκαν αυξημένα επίπεδα την ημέρα εισαγωγής στους ασθενείς που εμφάνισαν σήψη σε σύγκριση με τους μη σηπτικούς ασθενείς. Από την ανάλυση των αποτελεσμάτων του EPCR παρατηρήθηκαν αυξημένα επίπεδα στους ασθενείς που εμφάνισαν σήψη κατά τη διάρκεια παραμονής τους στη ΜΕΘ σε σύγκριση με τους μη σηπτικούς ασθενείς. Από την πολυπαραγοντική ανάλυση πρόεκυψε ότι ο sEPCR αποτελεί τον μοναδικό παράγοντα που σχετίζεται με την ανάπτυξη της σήψης με τον χρόνο. Τέλος, η Aqp-1 βρέθηκε αυξημένη στα πολυμορφοπύρηνα κοκκιοκύτταρα των σηπτικών ασθενών, ενώ αυξήθηκε 3 φορές κατά την εμφάνιση σηπτικής καταπληξίας.Συμπεράσματα. Τα αποτελέσματα μας ενισχύουν την άποψη ότι η λειτουργικότητα του ενδοθηλίου διαταράσσεται κατά την εμφάνιση του σηπτικού συνδρόμου. Οι μετρήσεις NIRS σχετίζονται με μεταβολές της μικροκυκλοφορίας σε βαρέως πάσχοντες ασθενείς τις πρώτες ημέρες της σήψης. Επιπλέον η sE-σελεκτίνη, η sP-σελεκτίνη και o sEPCR, φαίνεται να αποτελούν καθοριστικούς παράγοντες στην ανάπτυξη σήψης γεγονός που δηλώνει ότι θα μπορούσαν να χρησιμοποιηθούν ως προγνωστικοί βιοδείκτες σήψης. Τέλος, η Aqp-1 επαγωγή σχετίζεται με αυξημένη διαπερατότητα κυτταρικής μεμβράνης και μπορεί συνεπώς, να έχει λειτουργική σημασία

The Complex Interplay between Immunonutrition, Mast Cells, and Histamine Signaling in COVID-19

There is an ongoing need for new therapeutic modalities against SARS-CoV-2 infection. Mast cell histamine has been implicated in the pathophysiology of COVID-19 as a regulator of proinflammatory, fibrotic, and thrombogenic processes. Consequently, mast cell histamine and its receptors represent promising pharmacological targets. At the same time, nutritional modulation of immune system function has been proposed and is being investigated for the prevention of COVID-19 or as an adjunctive strategy combined with conventional therapy. Several studies indicate that several immunonutrients can regulate mast cell activity to reduce the de novo synthesis and/or release of histamine and other mediators that are considered to mediate, at least in part, the complex pathophysiology present in COVID-19. This review summarizes the effects on mast cell histamine of common immunonutrients that have been investigated for use in COVID-19

COVID-19 Disease and Outcomes among Critically Ill Patients: The Case of Medical Nutritional Therapy

The recent COVID-19 pandemic, which resulted from SARS CoV-2 coronavirus infection, contributed toa rapid increasein hospital and intensive care unit (ICU) admissions [...

Oxygen therapy practices in the acutely ill medical patients: A social media-based nationwide study of clinicians&apos; preferences and summary of current recommendations

Oxygen is the most commonly used drug in emergency medicine. The aim of this study was to identify healthcare professionals&apos; preferences regarding oxygen therapy in common medical emergencies. An online 9-part-questionnaire was distributed through Facebook to doctors and nurses working in Greek hospitals. The questionnaire included background information of the respondents and addressed individual preferences regarding best oxygenation parameter and oxygen targets in specific acute settings. We received 678 responses and we included 663 in our analysis. We found significant differences between doctors&apos; and nurses&apos; attitudes towards oxygenation targets in ARDS, sepsis, acute coronary syndrome, and post cardiac-arrest patients. Nurses preferred a more conservative oxygen strategy compared to doctors. Furthermore, nurses favor SaO(2) as the best oxygenation parameter, while doctors prefer PaO2. In our survey, the type of hospital and department of the respondents did not affect the preferred oxygen strategy. Social media-based survey research is feasible and effective. In this single country study, doctors showed a tendency to liberally administer oxygen in acutely ill medical patients. On the other hand, Greek nurses preferred a more conservative approach

Prognostic Value of Bone Formation and Resorption Proteins in Heterotopic Ossification in Critically-Ill Patients. A Single-Centre Study

Introduction: A potential complication in critically ill patients is the formation of bone in soft tissues, termed heterotopic ossification. The exact pathogenetic mechanisms are still undetermined. Bone morphogenetic proteins induce bone formation, while signalling through the receptor activator of nuclear factor kappa-B (RANK) and its ligand (RANKL), regulates osteoclast formation, activation, and survival in normal bone modelling and remodelling. Osteoprotegerin protects bone from excessive bone loss by blocking RANKL from binding to RANK. Aim: The study aimed to investigate these molecules as potential prognostic biomarkers of heterotopic ossification development in critically ill patients. Materials and Methods: In this prospective observational study, BMP-2, RANKL, and osteoprotegerin were measured by ELISA in twenty-eight critically-ill, initially non-septic patients, on admission to an ICU, seven days post-admission, and thirty days after ICU discharge. Results: In the critically-ill cohort, nine of the twenty-eight patients developed heterotopic ossification up to the 30-day follow-up time-point. The patients who developed heterotopic ossification exhibited significantly reduced BMP-2 and RANKL levels on ICU admission, compared to patients who did not; Osteoprotegerin readings were similar in both groups. Conclusions: Critically-ill patients who will subsequently develop heterotopic ossification, have significantly lower BMP-2 and RANKL levels at the time of ICU admission, suggesting that these proteins may be useful as prognostic markers for this debilitating condition

The H3 Haplotype of the EPCR Gene Determines High sEPCR Levels in Critically-ill Septic Patients

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b> <a href="https://link.springer.com/article/10.1007/s40121-018-0193-2">https://link.springer.com/article/10.1007/s40121-018-0193-2</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Comparison of the Mortality Prediction Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in COVID-19 and Sepsis

In the last years, biomarkers of infection, such as the soluble urokinase plasminogen activator receptor (suPAR), have been extensively studied as potential diagnostic and prognostic biomarkers in the intensive care unit (ICU). In this study, we investigated whether this biomarker can be used in COVID-19 and non-COVID-19 septic patients for mortality prediction. Serum suPAR levels were measured in 79 non-COVID-19 critically ill patients upon sepsis (within 6 h), and on admission in 95 COVID-19 patients (66 critical and 29 moderate/severe). The non-COVID-19 septic patients were matched for age, sex, and disease severity, while the site of infection was the respiratory system. On admission, COVID-19 patients presented with higher suPAR levels, compared to non-COVID-19 septic patients (p p > 0.05), as opposed to suPAR measured on admission in COVID-19 survivors and non-survivors (p p < 0.0001). suPAR measured early (within 24 h) after hospital admission seems like a specific and sensitive mortality risk predictor in COVID-19 patients. On the contrary, suPAR measured at sepsis diagnosis in non-COVID-19 critically ill patients, does not seem to be a prognostic factor of mortality