Systemic Inflammatory Response Syndrome

The purpose of this clinical trial is to evaluate the safety, tolerability and efficacy of two doses (dose A and dose B) of Standardized Conditioned Medium Obtained by Coculture of M2-macrophages and fat-derived Mesenchymal Stromal Cells (PRS CK STORM) in the modulation of the cytokine storm in participants with acute respiratory infection caused by SARS-Cov-2, influenza A, influenza B and respiratory syncytial virus (RSV) in need for oxygen therapy. The main questions it aims to answer are: * Are both doses of PRS CK STORM (dose A and dose B) safe as an intravenous drug to modulate inflammatory processes, such as the cytokine storm in participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV? * Are both doses of PRS CK STORM (dose A and dose B) effective as an intravenous drug to modulate SIRS-associated cytokine storm caused by SARS-Cov-2, influenza A, influenza B and RSV compared to the control group? * What are the anti-inflammatory and pro-inflammatory cytokine profiles after treatment with two different doses of PRS CK STORM in participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV? Researchers will compare both doses of PRS CK STORM with the control group to test whether the anti-inflammatory action of PRS CK STORM is safe and effective in modulating the cytokine storm for the treatment of SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV. In addition, the anti-inflammatory and pro-inflammatory cytokine profiles after treatment PRS CK STORM compared to placebo group in these participants will be also studied.

The aim of this project is to test the utility of The Gene Z device (as of 2018 Gene Z no longer being used), now using In-Dx and other rapid identification techniques that the investigators have developed in the lab on clinically obtained bodily fluid samples taken from patients with suspected infection or sepsis based on having three of four positive Systemic Inflammatory Response Syndrome markers, or having a known infection for which a specimen is being collected. Specimens will be collected at the University of Michigan Health/Sparrow and McLaren Greater Lansing , processed in our lab and stored for analysis at a later date to determine if the microbial pathogens identified by current methods of culture, as well as pathogen susceptibility to antibiotics by culture results, can be identified by the GeneZ technology (no longer in use) or other developed technology accurately, and more timely. It will not affect current patient care nor impact patient care, which will continue in the standard fashion today for sepsis. Results will be compared to standard culture results and antibiotic sensitivities. A secondary aim is related to the antibiotic resistance of the organism causing the infection in an attempt to determine if there are specific characteristics of the organism that allow it to be resistant to certain antibiotics. This requires analysis of the genetic material of the organism in our laboratory. Because there are also human cells in the specimens collected, with separate permission we will evaluate the human genome of the patient with the infection to determine characteristics and conditions that may predict a complicated versus uncomplicated disease course.

BACKGROUND Controlling vascular leakage, which is independently associated with mortality during Sepsis and cardiogenic shock, may be a promising approach during systemic inflammatory response syndrome (SIRS). During a collaborative work between La Pitié-Salpêtrière intensive care unit (ICU) and the unit INSERM U1050 (National Institute oh Health and medical Research), we identified 38 genes associated with capillary leakage during systemic inflammation response syndrome (SIRS) in humans. The aim of this study is to evaluate their possible implication in vascular hyperpermeability associated with METHODS SIRS-PERM is a prospective multicenter cohort study, testing the correlation between the plasma and broncho-alveolar levels of proteins isolated from our first screening, and the level of vascular leakage during SIRS. All patients admitted in the European Georges-Pompidou or La Pitié-Salpêtrière ICU and presenting a SIRS will be eligible for inclusion. Plasma samples will be collected at day 0, D1, D3 and D7, as well as broncho-alveolar lavage samples if clinically indicated. Concentration of each protein will be determined by ELISA in those samples. A statistical association will be then tested between each protein concentration and, for each time-point, the level of capillary leakage (daily weight and fluid balance, extra-vascular lung water index and pulmonary permeability index measured by transpulmonary thermodilution), and ARDS (acute respiratory distress syndrome) severity (PaO2/FiO2 ratio, Murray score and pulmonary compliance). Its link with hemodynamic status, the level of multiple organ failure, and vital status at day 30, will be also assessed. Basing the calculation of the sample size on the variations of VEGF (Vascular endothelial growth factor) expression in our first screening cohort, we calculated a sample size of 180 patients for this study, for a total duration of the study of 5 years. IMPLICATIONS: SIRS-PERM will assess the determinants of capillary leakage during SIRS. It may thus provide a better understanding of the pathophysiology of this disease, with the goal to isolate new markers of severity, as well as new therapeutic targets to treat it. Modulating specifically capillary leakage is indeed a totally new approach during this pathology.

The goal of this study is to demonstrate the sensitivity and specificity of detecting circulating micro RNA (miRNA) biomarkers in pediatric septic patients. It will also follow expression and modulation of levels in response to therapy in comparison to current biomarkers.

The investigators will be comparing two different filtration methods on cardiopulmonary bypass for pediatric heart surgery patients. Three blood tests will be taken from the patient to compare which filtration method is better at decreasing post-cardiopulmonary bypass inflammation caused by the heart-lung machine.

A comparison between precedex versus solumedrol as anti-inflammatory stress response inhibitors in patients undergoing on-pump CABG using different inflammatroy response parameters and the outcome of the drugs on the cognitive and cardiac status post extubation

Worldwide, the use of Extracorporeal Blood Purification (EBP) in everyday clinical practice is becoming increasingly common, particularly in critical care settings. The efficacy of most of these treatments on removal of inflammatory mediators is the main rationale behind the use of EBP in critically ill patients with multiorgan dysfunction. Nonetheless, there are still some doubts as to the clinical efficacy of bacterial toxins and cytokines removal and many clinical trials aiming at exploring the effect of EBP on long-term outcomes of septic patients have failed to demonstrate consistent results regarding 28 day- or hospital-mortality rates. The primary aim of this observational prospective web-based registry is to define the possible clusters of critically ill patients - treated with extracorporeal blood purification therapies worldwide - who are homogeneous regarding both clinical and treatment characteristics and seem to benefit the most from EBP.

The use of extracorporeal blood purification therapies (EBPT) is becoming increasingly widespread worldwide in everyday clinical practice, particularly in the critical care setting. Nonetheless, most of the clinical trials aimed at exploring the effect of EBPT on patients' long-term outcomes have failed to demonstrate consistent results regarding 28 day- or hospital- mortality rates. The aim of this observational prospective registry is to evaluate if there is a cluster of critically ill patients that mostly benefits from extracorporeal blood purification therapies with different EBPTs.

The investigators developed a GMP protocol to isolate Treg cells from thymic tissue (thyTreg). The thyTreg cells are being evaluated in a Phase I/II clinical trial to evaluate the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children (NCT04924491), with preliminary results indicating the feasibility and safety of the therapy. In addition, thyTreg cells have shown low immunogenicity in the pre-clinical setting, indicating that allogeneic use of these thyTreg cells (allo-thyTreg) would have a low risk of adverse effects. These thyTreg cells could inhibit an excessive inflammation in SARS-CoV-2 infection, or ameliorate the immunological affection underlying Acute respiratory distress syndrome, improving life-threatening manifestations, restoring immune balance, and protecting affected tissues. This clinical trial is an open-label Sequential Parallel Group Phase I/II study to evaluate the safety and efficacy of allogeneic thymus derived Tregs (thyTreg) (thyTreg) in controlling the immune dysregulation associated with SARS-CoV-2 infection and/or Acute Respiratory Distress Syndrome.

Septic shock is associated with substantial burden in terms of both mortality and morbidity for survivors of this illness. Pre-clinical sepsis studies suggest that mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance pathogen clearance and tissue repair and reduce death. Our team has completed a Phase I dose escalation and safety clinical trial that evaluated MSCs in patients with septic shock. The Cellular Immunotherapy for Septic Shock Phase I (CISS) trial established that MSCs appear safe and that a randomized controlled trial (RCT) is feasible. Based on these data, the investigators have planned a phase II RCT (UC-CISS II) at several Canadian academic centres which will evaluate intermediate measures of clinical efficacy (primary outcome), as well as biomarkers, safety, clinical outcome measures, and a health economic analysis (secondary outcomes).

Systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are the major causes of death in patients with cardiovascular diseases. Therefore, the prevention of SIRS and MODS is of great clinical value, and immunomodulatory therapy with sivelestat may be beneficial. This study was designed to test the hypothesis that the administration of sivelestat during the acute phase of cardiovascular diseases will result in a reduced incidence of SIRS and MODS.

The goal of our research project is to measure and compare oxidative stress markers, and systemic inflammatory response in patients undergoing open heart surgery with either conventional or minimally invasive extracorporeal circulation as well as develop pharmacokinetic profiles of different oxidative stress markers for further research on inflammatory response after open heart surgery. The main questions our study aims to answer are : * Does the type of extracorporeal circulation affect the levels of different oxidative stress markers? * Can preoperative and postoperative oxidative stress marker levels be of prognostic values? * Do preoperative and postoperative oxidative stress markers correlate with the clinical outcomes in patients? Researchers will compare the effect of conventional and minimally invasive extracorporeal circulation on clinical outcomes, oxidative stress marker levels, and systemic inflammatory response. Participants will be randomised into two groups (one undergoing arrested-heart surgery with the use of conventional extracorporeal circulation, and the second group undergoing arrested-heart surgery with the use of minimally invasive extracorporeal circulation) and laboratory data, oxidative stress markers, and clinical data will be collected until discharge.

Lobectomy is a major, high-risk surgical procedure that in addition to one-lung ventilation (OLV) exerts a potent surgical stress response. An overwhelming immune cell recruitment may lead to excessive tissue damage, peripheral organ injury and immunoparesis. The effect of anesthesia on the immune system is modest, compared to the effects induced by major surgery. However, to an immunocompromised patient, due to cancer and/or other comorbidities, the immunosuppressive effects of anesthesia may increase the incidence of post-operative infections, morbidity, and mortality. Exogenous opioids have been correlated with immunosuppression, opioid-induced hyperalgesia, and respiratory depression, with deleterious outcomes. An Opioid-Free Anaesthesia-Analgesia (OFA-A) strategy is based on the administration of a variety of anaesthetic/analgesic and other pharmacological agents with different mechanisms of action, including immunomodulating and anti-inflammatory effects. Our basic hypothesis is that the implementation of a perioperative multimodal OFA-A strategy, will lead to an attenuated surgical stress response and attenuated immunosuppression, compared to a conventional Opioid-Based Anaesthesia-Analgesia (OBA-A) strategy. The aforementioned effects, are presumed to be associated with equal or improved analgesia and decreased incidence of postoperative infections compared to a perioperative OBA-A technique.