Immunomonitoring of Monocyte and Neutrophil Function in Critically Ill Patients: From Sepsis and/or Trauma to COVID-19.

Immune cells and mediators play a crucial role in the critical care setting but are understudied. This review explores the concept of sepsis and/or injury-induced immunosuppression and immuno-inflammatory response in COVID-19 and reiterates the need for more accurate functional immunomonitoring of monocyte and neutrophil function in these critically ill patients. in addition, the feasibility of circulating and cell-surface immune biomarkers as predictors of infection and/or outcome in critically ill patients is explored. It is clear that, for critically ill, one size does not fit all and that immune phenotyping of critically ill patients may allow the development of a more personalized approach with tailored immunotherapy for the specific patient. In addition, at this point in time, caution is advised regarding the quality of evidence of some COVID-19 studies in the literature

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing strategies for the use of immunomodulators in COVID-19. Immunomodulating therapy is very challenging; there are still underpowered or, in other ways, insufficient studies with inconclusive or conflicting results regarding a rationale for adding a second immunomodulatory drug to dexamethasone. Bearing in mind that a "cytokine storm" is not present in the majority of COVID-19 patients, it is to be expected that the path to the adequate choice of a second immunomodulatory drug is paved with uncertainty. Anakinra, a recombinant human IL-1 receptor antagonist, is a good choice in this setting. Yet, the latest update of the COVID-19 Treatment Guidelines Panel (31 May 2022) claims that there is insufficient evidence to recommend either for or against the use of anakinra for the treatment of COVID-19. EMA's human medicines committee recommended extending the indication of anakinra to include treatment of COVID-19 in adult patients only recently (17 December 2021). It is obvious that this is still a work in progress, with few ongoing clinical trials. With over 6 million deaths from COVID-19, this is the right time to speed up this process. Our conclusion is that, during the course of COVID-19, the immune response is changing from the early phase to the late phase in individual patients, so immunomodulating therapy should be guided by individual responses at different time points

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

Background. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. Methods. A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. Results. NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. Conclusions. NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential

Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial

Background: Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. Methods: PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. Discussion: PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. Trial registration: The trial was registered in clinicaltrials.gov (NCT02963025) on 15 November 2016