Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is characterized by hypercytokinemia leading to overwhelming inflammation. We describe the use of a hemadsorption device as part of the supportive treatment for cytokine storm.

Introduction: A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). Identifying patients with a dysregulated inflammatory response and at high risk for severe respiratory failure, organ dysfunction, and death is clinically relevant, as they could benefit from the specific therapies, such as cytokine removal by hemoadsorption. This study aimed to evaluate cytokine hemoadsorption as rescue therapy in critically ill patients with SARS-CoV-2 pneumonia, severe respiratory failure refractory to prone positioning, and hypercytokinemia.Methods: In this single center, observational and retrospective study, critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure, and hypercytokinemia were analyzed. All the patients underwent cytokine hemoadsorption using CytoSorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate clinical response to the prone position, and hypercytokinemia.Results: Among a total of 343 patients who were admitted to the intensive care unit (ICU) due to SARS-CoV-2 infection between March 3, 2020 and June 22, 2020, six patients received rescue therapy with cytokine hemoadsorption. All the patients needed invasive mechanical ventilation and prone positioning. A significant difference was found in the pre- and post-treatment D-dimer (17,868 mcg/ml [4,196–45,287] vs. 4,488 mcg/ml [3,166–17,076], p = 0.046), C-reactive protein (12.9 mg/dl [10.6] vs. 3.5 mg/dl [2.8], p = 0.028), ferritin (1,539 mcg/L [764–27,414] vs. 1,197 ng/ml [524–3,857], p = 0.04) and interleukin-6 (17,367 pg/ml [4,539–22,532] vs. 2,403 pg/ml [917–3,724], p = 0.043) levels. No significant differences in the pre- and post-treatment interleukin-10 levels (22.3 pg/ml [19.2–191] vs. 5.6 pg/ml [5.2–36.6], p = 0.068) were observed. Improvements in oxygenation (prehemoadsorption PaO2/FIO2 ratio 103 [18.4] vs. posthemoadsorption PaO2/FIO2 ratio 222 [20.9], p = 0.029) and in the organ dysfunction (prehemoadsorption SOFA score 9 [4.75] vs. posthemoadsorption SOFA score 7.7 [5.4], p = 0.046) were observed. ICU and in-hospital mortality was 33.7%.Conclusions: In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and SOFA score were also observed.

The mortality of septic shock remains high [Ann Intensive Care. 2017;7:19], so apart from usual therapy based on source control and antibiotics, some patients may need rescue therapies. Blood purification systems may play a role by facilitating the nonspecific removal of inflammatory mediators and microbiological toxins. There are different hemoadsorption systems, we describe in this case report the sequential use of Polymyxin B (PMX) endotoxin-adsorbing column (Toraymixin PMX-20R; Toray, Tokyo, Japan) and Cytosorb® (Cytosorbents Corp., New Jersey, USA).

Introduction The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Methods Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. Results 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. Conclusion In sepsis there are proteomic patterns associated with organ dysfunction and mortality.

Background : A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). There is a subgroup of patients who develop a hyperinflammatory response with severe respiratory failure and organ dysfunction with high mortality. Identifying these patients is outstanding as they could benefit from specific therapies, such as cytokine removal by hemoadsorption. Methods: Single-center, observational and prospective study of critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure and hypercytokinemia. All patients received cytokine hemoadsorption using Cytosorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate prone response, and hypercytokinemia. Results : A total of 343 patients were admitted to the ICU due to SARS-Cov-2 infection between March 3, 2020, to June 22, 2020. Of these, six patients [5 (83.3%) men; mean age 57 (10.5) years; SOFA 5 (1.4); mean Acute Physiology And Chronic Health Evaluation (APACHE) II score 19.5 (6)] underwent hemoadsorption with Cytosorb®. All patients fulfilled the Berlin criteria for severe acute respiratory distress syndrome (ARDS), underwent prone positioning, and were on mechanical ventilation for 15.2 (7.2) days. One session of 16 (9.0) hours duration was performed. IL-6 levels were significantly reduced [(pre- hemoadsorption levels 17.367 (4.539– 22.532) pg/ml; post-hemoadsorption levels 2.403 (917 – 3.724) pg/ml, p = 0.043], and improvements in oxygenation were observed [pre-hemoadsorption PaO 2 /FiO 2 ratio was 103 (18.4), post- hemoadsorption PaO2/FiO2 ratio was 222 (20.9), p = 0.029]. We documented the clinical improvement and rapid reversal of organ dysfunction [pre-hemoadsorption Sequential Organ Failure Assessment (SOFA) score 9 (4.7); post- hemoadsorption SOFA score 7.7 (5.4), p = 0.046]. Inflammatory markers (C-reactive protein, D-dimer, and ferritin) also improved significantly. Mean ICU stay was 17.2 (8.0) days. ICU and in-hospital mortality was 33.7%. Conclusions : In our cohort, patients with SARS-CoV-2 pneumonia and severe acute respiratory failure and hypercytokinemia who received cytokine hemoadsorption, an important reduction in IL-6 levels and improvements in oxygenation and SOFA score were observed.

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Extracorporeal Membrane Oxygenation (ECMO) is commonly associated with a high blood transfusion requirement. Jehovah’s Witness patients present a particular challenge. The impossibility of transfusing blood cells and starting anticoagulation treatment are common contraindications for this supportive measure. Here we report the case of a Jehovah’s Witness patient with refractory hypoxemia due to influenza A H1N1 pneumonia who required venovenous ECMO for 11 days. We describe the use of a bloodless approach to reduce the waste of blood, avoiding anticoagulation, and improving red blood cell production. We then summarize the current literature on the use of ECMO in Jehovah’s Witness patients and, finally, we propose some recommendations for their management.