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Background: Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity which complicates the delivery of personalized therapies. Our goals were to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could 1)improve sepsis prognostication based on clinical variables and 2)guide the stratification of septic patients in subgroups with shared characteristics of immune response or survival outcomes., Methods: We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis., Results: IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94 [1.17-3.20]) and 30-day mortality (1.61 [1.14-2.28]). HRs of IRAK-M and Galectin-1 for predicting 1-year mortality were 1.52 (1.20-1.92) and 1.64 (1.13-2.36), respectively. A prognostic model including IRAK-M, Galectin-1, and clinical variables (Charlson Comorbidty Index, multiple source of sepsis, and SOFA score) had high discrimination for death at 7 days and 30 days (area under the curve 0.90 [0.82-0.99]) and 0.86 [0.79-0.94], respectively). Patients with elevated serum levels of IRAK-M and Galectin-1 had clinical traits of immune suppression and low survival rates. None of the 12 biomarkers were independent predictors of 2-year mortality., Conclusions: Two inhibitory immune checkpoint biomarkers (IRAK-M and Galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in targeted therapeutic trials., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies., Methods: A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method., Results: The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions., Conclusions: Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice., (© 2024. The Author(s).)

Critically ill septic patients present variable clinical trajectories, with some succumbing to hyperinflammatory responses while others develop a chronic critical illness, characterized by a prolonged low-grade inflammation, muscle atrophy, and mechanical ventilation dependency and often develop secondary infections often caused by from low-virulence microorganisms or reactivated latent viruses. The Seraph-100 ® hemoperfusion cartridge takes advantage from heparin-coated ultra-high molecular weight polyethylene microbeads mimicking pathogen-binding cell receptors and can adsorb both pathogens and damage-associated molecular patterns released by injured tissues. We describe two chronic critically ill patients who developed secondary viral bloodstream infections successfully treated with this device., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Polyclonal Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis and septic shock because the current guidelines recommend against their use despite many investigations that have demonstrated their beneficial effects in different subsets of patients. The biology, mechanisms of action, and clinical experience related to the administration of IvIg are reviewed, which aim to give a more in-depth understanding of their properties in order to clarify their possible indications in sepsis and septic shock patients.

The Waterhouse-Friderichsen syndrome represents a critical condition characterized by a septic shock associated with a disseminated intravascular coagulation causing the plugging of the microvascular network virtually all organs and systems, including the skin, the kidneys, the liver, and adrenal glands; the mortality rate is elevated, and survivors often must undergo multiple limb amputations. Here, we describe the uncommon case of an asplenic patient who developed this syndrome after a superficial wound caused by a dog bite causing an initial infection due to Capnocytophaga canimorsus that is part of the normal oral microbiome of pets. The clinical and pathological findings and the current and future therapeutic options are reviewed and discussed., (© 2023. The Author(s).)

Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as blood purification techniques. Their main categories include blood- and plasma processing procedures, which can run in a stand-alone mode or, more commonly, in association with a renal replacement treatment. The different techniques and principles of function, the clinical evidence derived from multiple clinical investigations, and the possible side effects are reviewed and discussed along with the persisting uncertainties about their precise role in the therapeutic armamentarium of these syndromes.

Introduction: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb ® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb ® interval and its intensity on the outcome., Methods: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA., Results: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59-76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb ® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS., Conclusions: In this group of septic shock patients, the earlier initiation of Cytosorb ® , its longer duration and the higher volume of blood processed were associated with a better survival.

The extracorporeal elimination of a pathogen or damage-associated molecular pattern via blood purification techniques is increasingly being used in patients with septic shock and other clinical conditions characterized by a life-threatening inflammatory response. The removal of these substances can be accomoplished by means of ultrafiltration or hemoadsorption. Independently from the blood putification technique used, they could also affect the clearance of antibacterial and antifungal agents with a potentially significant clinical impact. In our review, we describe the basic principles of ultrafiltration and hemoadsorption, the available devices for this latter and the existing experimental and clinical studies; the final paragraph is dedicated to practical considerations that can help clinicians to consider the clearance of antibiotics and antifungals attributable to these techniques to minimize the risk of a iatrogenic underdosage.

Objective: To assess the variations of Interleukin-6 (IL-6) in patients with SARS-CoV-2 infection treated with Tocilizumab (TCZ) alone or in association with hemoadsorption (HA)., Design: Retrospective., Setting: An Intensive Care Unit (ICU) admitting mechanically ventilated patients with SARS-CoV-2 pneumonia., Patients: Four adult patients., Interventions: We compared the blood values of IL-6, C-reactive protein (CRP) and of other biochemical variables including the PaO 2 /FiO 2 in two patients who received TCZ alone and in other 2 in whom it was associated with the HA (TCZ-HA) due to the presence of impending or established organ failures other than the lung. All variables were measured before, during and after the treatment., Main Results: In all patients, the IL-6 increased during the treatment; after its termination, its values sharply decreased only in those treated also with HA; conversely, the CRP decreased in all patients; the PaO 2 /FiO 2 increased in three patients and remained stable in the remaining one. Both the TCZ and the HA were well tolerated; all patients were weaned from the mechanical ventilation and discharged from the hospital., Limitations: Although the limited number of patients does not allow to draw firm conclusions, the increase of the IL-6 of can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ-HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with the SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators.

Background: Dexamethasone is commonly used for the prevention of postoperative nausea and vomiting (PONV), and recent reviews suggest a role for dexamethasone in postoperative analgesia. The aim of this study is to evaluate the efficacy of dexamethasone as an analgesic adjuvant in minimally invasive thoracic surgery. Primary outcome was morphine consumption 24 h after surgery; secondary outcomes were pain control, measured as numeric rating scale (NRS), glycemic changes, PONV, and surgical wound infection., Results: We performed a retrospective cohort study considering 70 patients who underwent elective lobectomy, segmentectomy, or wedge resection surgery with a mini-thoracotomy approach or video-assisted thoracoscopic surgery (VATS). All patients received the same locoregional techniques and short-acting opioids during surgery; 46 patients received dexamethasone at induction. There were no significant differences in morphine consumption at 24 h (p = 0.09) and in postoperative pain scores. Nevertheless, a higher frequency of rescue therapy (p = 0.01) and a tendency for a higher attempted-PCA pushes count were observed in patients who did not receive dexamethasone. No cases of surgical wound infections were detected, and the incidence of PONV was similar in the two groups. Postoperative glycemia was transiently higher in the dexamethasone group (p = 0.004), but the need of hypoglycemic therapy was not significantly different., Conclusions: Preoperative administration of dexamethasone did not cause a significant reduction in morphine consumption, but appears to be safe and plays a role in a multimodal anesthesia approach for patients undergoing elective minimally invasive thoracic surgery., (© 2021. The Author(s).)