Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

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 pro-inflammatory, 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Selection of the appropriate control group is essential in evaluating the cytokine storm in COVID-19

Background/Aim: Lately, studies have reported contradicting results on the cytokine storm seen in critically-ill COVID-19 patients. Depending on the control group used, cytokines have been found to be higher, similar or even lower in COVID-19 compared to critical illnesses associated with elevated cytokine concentrations. However, most of these studies do not take into account critical illness severity. Hence, we decided to compare cytokine levels in critically-ill COVID-19 patients and critically-ill patients of a general intensive care unit (ICU), who did not have sepsis or septic shock, but had an equal disease severity. Patients and Methods: Interleukin (IL)-6, IL-8, IL-10 and tumour necrosis factor-α (TNF-α) were measured on ICU admission in mechanically ventilated, COVID-19 (N=36) and non-COVID-19 (N=30) patients, who had not received dexamethasone, and had equal critical illness severity. Non-COVID-19 patients did not have sepsis or septic shock. Results: In our case control study, circulating IL-6 and IL-10 were lower, while TNF-α and IL-8 levels were higher in critically-ill COVID-19 patients, compared to critically-ill non-COVID-19 patients. Conclusion: It is difficult to infer whether the cytokine storm seen in COVID-19 differs from other critical conditions. It is important to recognize that the conclusions of related studies may depend on control group selection. © 2021 International Institute of Anticancer Research. All rights reserved

Serum admission 25-hydroxyvitamin d levels and outcomes in initially non-septic critically ill patients

Introduction: To examine whether very low levels of 25-hydroxyVitamin D {25(OH)D} upon admission to the intensive care unit (ICU) are associated with worse outcomes. Methods: Retrospective observational cohort study of critically ill patients treated in a multidisciplinary ICU. Two hundred twenty seven initially non-septic, critically ill patients, in whom 25-hydroxyVitamin D was measured at ICU admission. An additional group of 192 healthy subjects was also used. Patients were categorized according to their Vitamin D levels at admission; the two patient groups were those with severely low 25-hydroxyVitamin D levels (<7 ng/mL, N=101) and those with Vitamin D levels <7 ng/mL, N=126. Results: ICU admission 25-hydroxyVitamin D levels of critically ill patients were much lower than those of healthy subjects (P<0.0001). The median time to sepsis for the two patient groups did not differ, nor did the length of ICU stay (days). Both groups exhibited similar hospital mortality rates. However, among the fraction of patients who eventually became septic (N=145), the odds ratio (OR) for developing respiratory infections in patients with admission vitamin levels<7 ng/mL compared with patients with admission Vitamin D levels <7 ng/mL was 5.25 {95% confidence interval (CI) 1.5-18.32, P=0.009}. Conclusions: Initially non-septic critically ill patients appear to have very low ICU admission 25-hydroxyVitamin D levels. Among critically ill patients, severely low Vitamin D levels (<7 ng/mL) at ICU admission do not predict sepsis development, increased risk of in-hospital mortality, or longer stay in the ICU. However, these severely low admission Vitamin D levels in patients who will eventually develop sepsis are associated with development of respiratory tract infections. © 2018 Lippincott Williams and Wilkins. All rights reserved

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

Introduction: A soluble (s) form of the endothelial protein C receptor (EPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in the septic process is under investigation. This study determined the frequencies of EPCR haplotypes H1 and H3 to investigate possible associations with plasma admission levels of sEPCR in an intensive care unit (ICU) cohort of septic patients. Methods: Three polymorphisms in the EPCR gene were genotyped in 239 Caucasian critically ill patients, and their plasma sEPCR levels were also measured at the time of admission to the ICU. Multivariate logistic regression analysis controlling for sepsis severity, age, acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores, lactate level, sex, diagnostic category, length of ICU stay and hospital mortality was performed to determine the effect of EPCR haplotypes H1 and H3 on the levels of sEPCR. Results: Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (p < 0.001). No differences were found in the distribution of the H3 allele in the patient groups categorized using the pre-existing and current sepsis-3 definitions. Conclusion: Using the preceding and current sepsis definitions, sEPCR levels and the H3 haplotype were not associated with sepsis severity and the risk of poor outcomes in septic patients; however, the EPCR H3 allele contributed to higher levels of sEPCR. © 2018, The Author(s)

Celiac Artery Avulsion Secondary to Blunt Trauma: A Case Report

Celiac artery (CA) injuries are very rare and are often associated with high mortality. These injuries are associated more often with penetrating trauma rather than blunt trauma injury. Our case highlights a blunt trauma injury of CA in a hemodynamically stable patient without any symptoms that was treated conservatively. © 2017 Elsevier Inc

Immune cell response to strenuous resistive breathing: comparison with whole body exercise and the effects of antioxidants

Andreas Asimakos,1,2,* Dimitrios Toumpanakis,1,2,* Maria-Helena Karatza,3 Spyridoula Vasileiou,3 Paraskevi Katsaounou,1,2 Zafeiria Mastora,1,2 Theodoros Vassilakopoulos1,2,4 1GP Livanos and M Simou Laboratories, Thorax Foundation, 2Critical Care Department and Pulmonary Unit, Evangelismos Hospital, Medical School, National and Kapodistrian University of Athens, 3Flow Cytometry Unit, Hematology Clinic Evangelismos Hospital, 43rd Department of Critical Care Medicine, Evgenideion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece *These authors contributed equally to this work Background/hypothesis: Whole body exercise (WBE) changes lymphocyte subset percentages in peripheral blood. Resistive breathing, a hallmark of diseases of airway obstruction, is a form of exercise for the inspiratory muscles. Strenuous muscle contractions induce oxidative stress that may mediate immune alterations following exercise. We hypothesized that inspiratory resistive breathing (IRB) alters peripheral blood lymphocyte subsets and that oxidative stress mediates lymphocyte subpopulation alterations following both WBE and IRB.Patients and methods: Six healthy nonathletes performed two WBE and two IRB sessions for 45 minutes at 70% of VO2 maximum and 70% of maximum inspiratory pressure (Pimax), respectively, before and after the administration of antioxidants (vitamins E, A, and C for 75 days, allopurinol for 30 days, and N-acetylcysteine for 3 days). Blood was drawn at baseline, at the end of each session, and 2 hours into recovery. Lymphocyte subsets were determined by flow cytometry.Results: Before antioxidant supplementation at both WBE end and IRB end, the natural killer cell percentage increased, the T helper cell (CD3+ CD4+) percentage was reduced, and the CD4/CD8 ratio was depressed, a response which was abolished by antioxidants only after IRB. Furthermore, at IRB end, antioxidants promoted CD8+ CD38+ and blunted cytotoxic T-cell percentage increase. CD8+ CD45RA+ cell percentage changes were blunted after antioxidant supplementation in both WBE and IRB.Conclusion: We conclude that IRB produces (as WBE) changes in peripheral blood lymphocyte subsets and that oxidative stress is a major stimulus predominantly for IRB-induced lymphocyte subset alterations. Keywords: resistive breathing, exercise, antioxidants, lymphocyt

Contribution of pain to inspiratory muscle dysfunction after upper abdominal surgery - A randomized controlled trial

Upper abdominal surgery causes respiratory muscle dysfunction. Multiple factors have been implicated in the occurrence of such dysfunction; however, the role of pain remains unclear. To elucidate the role of pain, we studied 50 patients undergoing elective upper abdominal surgery in a randomized, controlled investigation. Inspiratory and expiratory muscle function were assessed through sniff mouth pressure (Psniff) and maximal expiratory pressure (MEP), respectively. Pain during the pressure maneuvers was assessed with a visual analog scale (VAS), Measurements were made before surgery (Session 1), 24 h after surgery (Session 2), and 1 h later, after intramuscular administration of pethidine (analgesia group) or placebo (placebo group) (Session 3). To evaluate the effect of pain, we used a mixed-effects model with random intercept, having either Psniff or MEP as the dependent variable and both surgical operation and the level of pain as fixed effects. Upper abdominal surgery decreased Psniff in both the analgesia and placebo groups (from 70 +/- 15 to 42 +/- 11 cm H2O [p < 0.05] in the analgesia group, and from 69 +/- 15 to 42 +/- 10 cm H2O [p < 0.05] in the placebo group). Intramuscular pethidine caused an increase in Psniff to 56 +/- 14 cm H2O (p < 0.05), whereas placebo had no effect. Pain increased comparably after upper abdominal surgery in both groups (from 0.3 +/- 0.6 to 4.4 +/- 1.5) [p < 0.05] in the analgesia group and from 0.4 +/- 0.5 to 4.3 +/- 1.5 [p < 0.05] in the placebo group). Intramuscular pethidine decreased pain as measured by VAS score to 2.1 +/- 1.0 (p < 0.05) in the analgesia group, whereas placebo had no effect. Psniff had a statistically significant relationship to pain (p < 0.001). Adjusting for the occurrence of surgical operation did not affect this result. MEP showed the same tendency as Psniff, but the observed changes did not reach statistical significance. We conclude that pain contributes to inspiratory muscle dysfunction after upper abdominal surgery