International study of the prevalence and outcomes of infection in intensive care units

Background Coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. Objective We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation. Methods Patients with COVID-19 who were hospitalized from February 29 to April 9, 2020, were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n = 40) followed by a temporally separated validation cohort (n = 49). Results We identified markers of inflammation, lactate dehydrogenase, and creatinine as the variables most predictive of respiratory failure in the evaluation cohort. Maximal IL-6 level before intubation showed the strongest association with the need for mechanical ventilation, followed by maximal CRP level. The respective AUC values for IL-6 and CRP levels in the evaluation cohort were 0.97 and 0.86, and they were similar in the validation cohort (0.90 and 0.83, respectively). The calculated optimal cutoff values during the course of disease from the evaluation cohort (IL-6 level > 80 pg/mL and CRP level > 97 mg/L) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure. Conclusion The maximal level of IL-6, followed by CRP level, was highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP level to guide escalation of treatment in patients with COVID-19–related hyperinflammatory syndrome.

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Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19.

As a greater proportion of patients survive their initial cardiac insult, medical systems worldwide are being faced with an ever-growing need to understand the mechanisms behind the pathogenesis of chronic heart failure (HF). There is a wealth of information about the role of inflammatory cells and pathways during acute injury and the reparative processes that are subsequently activated. We discuss the different causes that lead to chronic HF development and how the sum of initial inflammatory and reparative responses only sets the trajectory for disease progression. Unfortunately, comparatively little is known about the contribution of the immune system once the trajectory has been set, and chronic HF has been established—which clinically represents the majority of patients. It is known that chronic HF is associated with circulating inflammatory cytokines that can predict clinical outcomes, yet the causative role inflammation plays in disease progression is not well defined, and the majority of clinical trials that target aspects of inflammation in patients with chronic HF have largely been negative. This review will present what is currently known about inflammation in chronic HF in both humans and animal models as a means to highlight the gap in our knowledge base that requires further examination.

Chronic Heart Failure and Inflammation: What Do We Really Know?

BACKGROUND Sepsis is a deadly immunological disorder and its pathophysiology is still poorly understood. We aimed to determine if specific pro-inflammatory and anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for sepsis. MATERIALS AND METHODS Recent publications in the MEDLINE database were searched for articles regarding the clinical significance of inflammatory cytokines in sepsis. RESULTS In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis. Importantly, a decrease in IL-6 was associated with a better prognosis and overproduction of IL-10 was found to be the main predictor of severity and fatal outcome. CONCLUSION Both pro-inflammatory and anti-inflammatory cytokines constitute a double-edged sword in sepsis; on one hand they are critical to eliminate the infection while on the other, excessive production can cause tissue and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF-α may have implications in diagnosis and treatment of sepsis.

Role of cytokines as a double-edged sword in sepsis.

Phenotypic plasticity, the capacity of a single genotype to exhibit variable phenotypes in different environments, is common in insects and is often highly adaptive. Virtually any abiotic or biotic factor can serve to induce plasticity, and resulting changes vary from harmful susceptibilities to highly integrated and adaptive alternative phenotypes. Numerous physiological mechanisms accomplish plasticity, including transcription, translation, enzyme, and hormonal regulation, producing local or systemic responses. The timing, specificity, and speed of plastic responses are critical to their adaptive value. Understanding plasticity requires knowing the environment, physiological mechanisms, and fitness outcomes. Plasticity is thought to be evolutionarily favored under specific conditions, yet many theoretical predictions about benefits, costs, and selection on plasticity remain untested. The ecological consequences of plasticity range from simple environmental susceptibilities to mediating interspecific interactions, and extend to structuring of ecological communities, often through indirect effects. Phenotypic plasticity, through its ecological effects, can facilitate evolutionary change and speciation. Plasticity is important because it is an encompassing model to understand life on earth, it can increase fitness, generate novelity, and facilitate evolution, it structures ecological communities, and it has numerous practical applications. As such, all biologists should understand phenotypic plasticity.

What is phenotypic plasticity and why is it important

Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

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Cytokine profile in severe gram-positive and gram-negative abdominal sepsis

This study investigates the effects of exertional heat stress and acclimation status on physiological and cognitive performance. Forty male soldiers performed an exertional heat stress test (EHST) either in a cool (20°C, 16°C wet bulb globe temperature), or in a hot environment (40°C, 29°C wet bulb globe temperature), unacclimatized, or after 10 days of passive or active acclimation. Mean skin and tympanic (Tty) temperatures and heart rates (HR) measured physiological strain. A cognitive test (the computerized Cambridge Neuropsychological Test Automated Batteries attention battery) is administered before and immediately after EHST. EHST in hot conditions induced physiological heat stress (increase in Tty and HR), which caused mild deficits in attention in U group (decreased number of correct responses, and prolonged movement time). Acclimated (passive and active) soldiers suffered no detrimental effects of exertional heat stress, despite almost the same degree of heat strain, measured by Tty and HR.

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Effects of acclimation on cognitive performance in soldiers during exertional heat stress

Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients.

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Immunoinflammatory Response in Critically Ill Patients: Severe Sepsis and/or Trauma

GOAL AND BACKGROUND One of the most important cytokines in pathogenesis of acute pancreatitis is tumor necrosis factor (TNF)-α. The aim of our study was to determine whether the plasma levels of TNF-α in patients with severe acute pancreatitis (SAP) on admission correlate with severity and outcome of SAP. STUDY Blood samples were obtained from 100 patients with SAP. Patients were divided into 2 groups according to severity: SAP group (n=69) and SAP-induced multiple organ dysfunction syndrome (MODS) group (n=31). Survivors were patients who were alive 90 days after taking the blood sample for cytokine measurement (53/100). Blood sample for cytokine measurement was drawn immediately after admission. TNF-α was measured by commercial ELISA test in plasma. RESULTS When comparing SAP group with SAP-induced MODS group, we found that mean values of TNF-α on admission were 191.5-fold lower in group with SAP-induced MODS (P<0.01). When comparing nonsurvivors with survivors, we found that mean values of TNF-α on admission were 63-fold higher in survivors (P<0.01). At cut-off level of 7.95 pg/mL sensitivity was 83.9% and specificity was 72.5%. Patients with TNF-α level lower than 7.95 pg/mL had 3.2-fold higher probability to develop SAP with MODS. At cut-off level of 10.5 pg/mL sensitivity was 83% and specificity was 77.4%. Patients with TNF-α level higher than 10.5 pg/mL had 4.8-fold higher probability to survive. CONCLUSIONS TNF-α is good predictor of severity and outcome. Low TNF-α concentration in patients with SAP predicts development of MODS and fatal outcome.

Tumor necrosis factor-α levels early in severe acute pancreatitis: is there predictive value regarding severity and outcome?

The aim of this study was to assess the prognostic value of tumor necrosis factor (TNF) α, interleukin (IL)-8, IL-4, and IL-10 in combat casualties. Fifty-six casualties with severe trauma (blast and explosive) who developed sepsis and 20 casualties with the same severity of trauma without sepsis were enrolled in this study. Fifty-five casualties developed multiple organ dysfunction syndrome; 36 died. Blood was drawn on the first day of trauma. Concentrations of IL-8, TNF-α, IL-4, and IL-10 were determined in plasma using enzyme-linked immunosorbent assays. Mean values of IL-8 were 230-fold, IL-10 were 42-fold, and TNF-α were 17-fold higher in trauma and sepsis group (p < 0.01). Mean values of IL-8 were 60-fold, TNF-α were 43.5-fold, and IL-10 were 70-fold higher in the multiple organ dysfunction syndrome group (p < 0.01). Mean values of IL-8 were 2.3-fold and IL-10 were 1.4-fold higher in nonsurvivors and TNF-α were 2.2-fold higher in survivors (p < 0.01). IL-4 had no significance as a predictor...

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Sonja Radakovic

Papers

Cytokine profile in severe gram-positive and gram-negative abdominal sepsis

Effects of acclimation on cognitive performance in soldiers during exertional heat stress

Immunoinflammatory Response in Critically Ill Patients: Severe Sepsis and/or Trauma

Tumor necrosis factor-α levels early in severe acute pancreatitis: is there predictive value regarding severity and outcome?

Immune cytokine response in combat casualties: blast or explosive trauma with or without secondary sepsis.