Host immune response in sepsis due to ventilator-associated pneumonia: how is it different?

Current evidence regarding potentially different host response mechanisms in sepsis according to the type of initiating infection is sporadic. It is possible that alterations in cell populations, variations in effector molecules, and the degree of apoptosis differ between sepsis caused by ventilator-associated pneumonia (VAP) and non-VAP sepsis. VAP is one of the most common infections and leading causes of sepsis in the intensive care unit, and mortality remains high. A better understanding of the unique pathophysiologic features of VAP is needed in order to develop interventions that target those specific pathways

The kinetics of T regulatory cells in shock: beyond sepsis

During the past decade, there have been an increasing number of studies investigating the precise role of T regulatory cells in human disease. First recognized for their ability to prevent autoimmunity, T regulatory cells control effector CD4+ and CD8+ T lymphocytes and innate immune cells by several different suppressive mechanisms, like cell to cell contact, secretion of inhibitory cytokines and cytolysis. This suppressive function of T regulatory cells could contribute in a similar way to the profound immune dysfunction seen in critical illness whether the latter is due to sepsis or severe injury

Εφαρμογή πρωτοκόλλου τροποποίησης του τρόπου ζωής σε παιδιά με αυξημένο σωματικό βάρος: συσχετίσεις με βιοδείκτες και παραμέτρους σχετιζόμενες με το στρες και εκτίμηση της κατάστασης υγείας μέσω του ευστασιομέτρου

Διερευνήσαμε τις σχέσεις μεταξύ πολλαπλών δεικτών στρες, φλεγμονής και μεταβολισμού και παραμέτρων σύστασης σώματος σε 121 (43 αγόρια, 78 κορίτσια) παιδιά και εφήβους , ηλικίας 5 έως 15 ετών. Οι συμμετέχοντες χωρίστηκαν σε 2 ομάδες: συμμετέχοντες με φυσιολογικό σωματικό βάρος (N=40, BMI z-score = -0.1923 ± 0.6), και συμμετέχοντες με υπερβάλλον βάρος και παχυσαρκία (N=81, BMI z-score= 2.1947 ± 1.4). Όλοι οι συμμετέχοντες συμπλήρωσαν το ερωτηματολόγιο εκτίμησης άγχους για παιδιά STAIC και το ερωτηματολόγιο CDI που εκτιμά τα συμπτώματα κατάθλιψης. Παράλληλα, σε όλα τα παιδιά έγινε εκτίμηση του κιρκάδιου ρυθμού έκκρισης κορτιζόλης σιέλου, μέτρηση της κορτιζόλης τρίχας, της κορτιζόλης ορού, της C-αντιδρώσας πρωτεΐνης υψηλής ευαισθησίας (HsCRP), της φερριτίνης, αλλά και δείκτες μεταβολισμού , όπως είναι τα λιπίδια και η ινσουλίνη. Η σύσταση σώματος εκτιμήθηκε με την μέθοδο της εξελιγμένης βιοηλεκτρικής εμπέδησης, ενώ η εκτίμηση της διακύμανσης καρδιακής συχνότητας έγινε με χρήση φωτοπληθυσμογράφου του ευστασιομέτρου. Οι συμμετέχοντες με υπερβάλλον σωματικό βάρος ή παχυσαρκία εμφάνισαν υψηλότερο σκορ στο ερωτηματολόγιο STAIC, υψηλότερο BMI z-score και υψηλότερο ποσοστό σωματικού λίπους συνολικά και ενδοσπλαχνικά. Η διακύμανση καρδιακής συχνότητας δεν διέφερε μεταξύ των ομάδων. Στο σύνολο του δείγματος παρατηρήθηκε σημαντική συσχέτιση των επιπέδων HsCRP, φερριτίνης, δεικτών φλεγμονής και δεικτών ινσουλινοαντίστασης. Παρατηρήθηκε επίσης μια ισχυρή συσχέτιση κορτιζόλης τρίχας και HsCRP, υποδεικνύοντας την σχέση χρόνιου στρες και φλεγμονής, ενώ η συσσώρευση σωματικού λίπους στα παιδιά και τους εφήβους φάνηκε να συσχετίζεται με κλινικούς και εργαστηριακούς δείκτες στρες, φλεγμονής και ινσουλινοαντίστασης. Επιπρόσθετα, μελετήθηκαν ξεχωριστά οι παραπάνω δείκτες σε 50 προεφηβικά κορίτσια, εκ των οποίων τα 24 είχαν φυσιολογικό σωματικό βάρος και τα 26 είχαν διάγνωση παχυσαρκίας. Σε αυτό το μικρότερο δείγμα της μελέτης παρατηρήθηκε ότι τα κορίτσια με παχυσαρκία είχαν υψηλότερα επίπεδα κορτιζόλης τρίχας και κορτιζόλης σιέλου όπως αυτή εκτιμάται με το εμβαδό κάτω από την καμπύλη (Area under the curve with respect to the ground- AUCg) (p < 0.001 and p < 0.002, αντίστοιχα) σε σχέση με τα κορίτσια με φυσιολογικό σωματικό βάρος. Παρατηρήθηκε επίσης θετική συσχέτιση μεταξύ κορτιζόλης τρίχας και BMI Z-score (rho = 0.327, p< 0.025), ενώ αναδείχθηκε μια θετική συσχέτιση κορτιζόλης τρίχας και κορτιζόλης σιέλου (rho=0.3, p<0.048). Συμπερασματικά η κορτιζόλη τρίχας είναι ένας ευαίσθητος δείκτης για την ανίχνευση του χρόνιου στρες, ενώ η παχυσαρκία στα παιδιά φαίνεται να σχετίζεται με την απορρύθμιση της έκκρισης κορτιζόλης. Τέλος, προχωρήσαμε στην ανάλυση του FGF21 σε ένα δείγμα 78 κοριτσιών από το αρχικό δείγμα σε όλα τα στάδια εφηβείας (50 κορίτσια με υπερβάλλον σωματικό βάρος ή παχυσαρκία και 28 κορίτσια με φυσιολογικό σωματικό βάρος). Στα κορίτσια με φυσιολογικό σωματικό βάρος παρατηρήθηκε μια σημαντική συσχέτιση των επιπέδων FGF21 και της κορτιζόλης τρίχας (r=0.54, p<0.006) αλλά και της κορτιζόλης σιέλου (r= 0.463, p< 0.020). Ο FGF21 φαίνεται να επιδρά στον άξονα του στρες και να διαμεσολαβεί την σχέση παχυσαρκίας και στρες.We examined the associations between multiple indices of stress, inflammation and metabolism vs. body composition parameters in 121 (43 boys, 78 girls) children and adolescents, aged 5-15 y. Participants were divided into 2 groups: normal weight (N=40, BMI z-score = -0.1923 ± 0.6), and overweight/obese (N=81, BMI z-score= 2.1947 ± 1.4). All subjects completed the State-Trait Anxiety Inventory for Children (STAIC) and Children’s Depression Inventory (CDI), and had cortisol measured in hair, diurnal series of saliva, and morning serum. Circulating concentrations of high sensitivity C-reactive protein (hsCRP) and other inflammation biomarkers, such as ferritin, and metabolic indices, such as lipids and insulin, were also obtained. Body composition analysis was performed with a clinically validated, advanced bioimpedance apparatus (BIA), while heart rate variability (HRV) was measured as an additional stress biomarker by photoplethysmography (PPG) (eustasiometer). The overweight/obese group had a higher STAIC-state score, BMI-z score, waist-to-hip ratio, skeletal muscle mass, and total and abdominal fat mass, and a lower percent fat-free mass and bone density than the normal weight subjects. HRV did not differ between the two groups. In the entire population, percent fat mass correlated strongly with circulating hsCRP (r=0.397, p=0.001), ferritin, and other inflammatory biomarkers, as well as with indices of insulin resistance. A strong correlation between hair cortisol and serum hsCRP was also observed (r=0.777, p<0.001), suggesting presence of interrelated chronic stress and inflammation. Thus, body fat accumulation in children and adolescents was associated with an elevation in clinical and laboratory biomarkers of stress, inflammation, and insulin resistance. However, unlike adults, neither HRV, nor skeletal muscle mass were influenced negatively by adiposity. -BIA-ACC and PPG can be used as a direct screening and monitoring tool for assessing overweight- and obesity -related health risks in children and adolescents. Moreover, we examined these associations in a smaller group including only 50 girls (tanner stage 1): 25 obese girls and 25 normalweighted, age-matched girls were enrolled. In this smaller part of the study both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p < 0.001 and p < 0.002, respectively). A positive correlation between hair cortisol and BMI Z-score was found (rho = 0.327, p< 0.025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = 0.3, p < 0.048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair. Finally, in a group of 78 girls (50 girls with obesity or overweight and 28 normal-weight girls) from our sample we examined the associations between fibroblast growth factor 21 (FGF21) and the above mentioned stress, inflammation and body composition indices. In normal-weight girls we observed a correlation between hair cortisol concentration and FGF21 levels (r=0.54, p=0.006), as well as a correlation between salivary cortisol concentration and FGF21 levels (r=0.463, p=0.020). FGF 21 possibly plays an important role in the HPA axis activation

Pityriasis Rosea Induced by COVID-19 Vaccination

It is increasingly recognized that SARS-CoV-2 infection and COVID-19 vaccines have been associated with skin disorders, including pityriasis rosea. It has been reported that pityriasis rosea has been triggered by several vaccines, as a rare side-effect. We present two cases of COVID-19 vaccine-induced pityriasis rosea. Skin lesions appeared in a 49-year-old female 8 days after the first dose of the BNT162b2 mRNA vaccine and in a 53-year-old male 7 days after the second dose of the same vaccine. The exanthem was self-limited in both patients over a period of a month

Influenza Virus—Host Co-evolution. A Predator-Prey Relationship?

Influenza virus continues to cause yearly seasonal epidemics worldwide and periodically pandemics. Although influenza virus infection and its epidemiology have been extensively studied, a new pandemic is likely. One of the reasons influenza virus causes epidemics is its ability to constantly antigenically transform through genetic diversification. However, host immune defense mechanisms also have the potential to evolve during short or longer periods of evolutionary time. In this mini-review, we describe the evolutionary procedures related with influenza viruses and their hosts, under the prism of a predator-prey relationship

Severity of RSV infection in Southern European elderly patients during two consecutive winter seasons (2017–2018)

In Europe, the respiratory syncytial virus (RSV) surveillance system is very heterogeneous and there is growing evidence of the importance of RSV infections resulting in hospitalization of elderly patients. The aim of this study was to assess the severity of RSV infection in the elderly living in the aged Southern European countries. We conducted a retrospective study of elderly patients (≥65-year old) admitted for laboratory-confirmed RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons (2017–2018). Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on radiologically confirmed pneumonia, use of noninvasive ventilation (NIV), and in-hospital death (IHD). A total of 166 elderly patients were included. Pneumonia was evident in 29.5%. NIV was implemented in 16.3%, length of stay was 11.8 ± 12.2 days, and IHD occurred in 12.1%. Multivariable analyses revealed that the risk of pneumonia was higher in patients with chronic kidney disease (CKD) (odds ratio [OR]: 2.57; 95% confidence interval [CI]: 1.12–5.91); the use of NIV was higher in patients with obstructive sleep apnea or obesity hypoventilation syndrome (OSA or OHS) (OR: 5.38; 95% CI: 1.67–17.35) and CKD (OR: 2.52; 95% CI: 1.01–6.23); the risk of IHD was higher in males (OR: 3.30; 95% CI: 1.07–10.10) and in patients with solid neoplasm (OR: 9.06; 95% CI: 2.44–33.54) and OSA or OHS (OR: 8.39; 95% CI: 2.14–32.89). Knowledge of factors associated with RSV infection severity may aid clinicians to set priorities and reduce disease burden. Development of effective antiviral treatment and vaccine against RSV is highly desirable.publishersversionpublishe

insights from a 2-year multi-centre cohort study (2017–2018)

Publisher Copyright: © 2021 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.Background: Viral community-acquired pneumonia (CAP) is a potentially serious illness, particularly in adult patients with underlying chronic conditions. In addition to the most recent SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) are considered the most relevant causes of viral CAP. Aims: To describe the clinical features of hospitalised adults admitted for influenza-A/B and RSV pneumonia and analyse, according to aetiology, factors associated with non-invasive ventilation (NIV) failure and in-hospital death (IHD). Methods: This was a retrospective and multi-centre study of all adults who were admitted for laboratory-confirmed influenza-A/B or RSV pneumonia, during two consecutive winter seasons (October–April 2017–2018 and 2018–2019) in three tertiary hospitals in Portugal, Italy and Cyprus. Results: A total of 356 adults were included in the study. Influenza-A, influenza-B and RSV were deemed to cause pneumonia in 197 (55.3%), 85 (23.9%) and 74 (20.8%) patients, respectively. Patients with both obstructive sleep apnoea or obesity hypoventilation syndrome and influenza-A virus pneumonia showed a higher risk for NIV failure (odds ratio (OR) 4.66; 95% confidence interval (CI) 1.42–15.30). Patients submitted to NIV showed a higher risk for IHD, regardless of comorbidities (influenza-A OR 3.00; 95% CI 1.35–6.65, influenza-B OR 4.52; 95% CI 1.13–18.01, RSV OR 5.61; 95% CI 1.26–24.93). Conclusion: The increased knowledge of influenza-A/B and RSV pneumonia burden may contribute to a better management of patients with viral CAP.publishersversionpublishe

Multicentre Surveillance of Candida Species from Blood Cultures during the SARS-CoV-2 Pandemic in Southern Europe (CANCoVEU Project)

Introduction: Surveillance of Candida species isolates from blood cultures (BCs) in Europe is considered fragmented, unable to allow the definition of targets of antifungal stewardship recommendations especially during the SARS-CoV-2 pandemic. Methods: We performed a multicentric retrospective study including all consecutive BC Candida isolates from six Southern European tertiary hospitals (1st January 2020 to 31st December 2021). Etiology, antifungal susceptibility patterns, and clinical setting were analyzed and compared. Results: C. albicans was the dominant species (45.1%), while C. auris was undetected. Candida species positive BC events increased significantly in COVID-19 ICUs in 2021 but decreased in other ICUs. Resistance to azole increased significantly and remained very high in C. albicans (fluconazole from 0.7% to 4.5%, p = 0.03) and C. parapsilosis complex (fluconazole up to 24.5% and voriconazole up to 8.9%), respectively. Resistance to caspofungin was remarkable in C. tropicalis (10%) and C. krusei (20%), while resistance to at least one echinocandin increased in 2021, especially in C. parapsilosis complex (from 0.8% to 5.1%, p = 0.05). Although no significant differences were observed over the study period, fluconazole and echinocandin resistance increased in COVID-19 ICUs by up to 14% and 5.8%, respectively, but remained undetected in non-intensive COVID-19 wards. Conclusions: Antifungal stewardship activities aimed at monitoring resistance to echinocandin in C. tropicalis and C. krusei, and against the spread of fluconazole resistant C. parapsilosis complex isolates are highly desirable. In COVID-19 patients, antifungal resistance was mostly present when the illness had a critical course.publishersversionpublishe