Persisting IL-18 levels after COVID-19 correlate with markers of cardiovascular inflammation reflecting potential risk of CVDs development.

COVID-19 manifestation is associated with a strong immune system activation leading to inflammation and subsequently affecting the cardiovascular system. The objective of the study was to reveal possible interconnection between prolongated inflammation and the development or exacerbation of long-term cardiovascular complications after COVID-19. We investigated correlations between humoral and cellular immune system markers together with markers of cardiovascular inflammation/dysfunction during COVID-19 onset and subsequent recovery. We analyzed 22 hospitalized patients with severe COVID-19 within three timepoints (acute, 1 and 6 months after COVID-19) in order to track the impact of COVID-19 on the long-term decline of the cardiovascular system fitness and eventual development of CVDs. Among the cytokines dysregulated during COVID-19 changes, we showed significant correlations of IL-18 as a key driver of several pathophysiological changes with markers of cardiovascular inflammation/dysfunction. Our findings established novel immune-related markers, which can be used for the stratification of patients at high risk of CVDs for further therapy.

Hyperoxemia post thoracic surgery - Does it matter?

Introduction: Post-operative oxygen therapy is used to prevent hypoxemia and surgical site infection. However, with improvements of anesthesia techniques, post-operative hypoxemia incidence is declining and the benefits of oxygen on surgical site infection have been questioned. Moreover, hyperoxemia might have adverse effects on the pulmonary and cardiovascular systems. We hypothesized hyperoxemia post thoracic surgery is associated with post-operative pulmonary and cardiovascular complications. Methods: Consecutive lung resection patients were included in this post-hoc analysis. Post-operative pulmonary and cardiovascular complications were prospectively assessed during the first 30 post-operative days, or hospital stay. Arterial blood gases were analyzed at 1, 6 and 12 h after surgery. Hyperoxemia was defined as arterial partial pressure of oxygen (PaO2)>100 mmHg. Patients with hyperoxemia duration in at least two adjacent time points were considered as hyperoxemic. Student t-test, Mann-Whitney U test and two-tailed Fisher exact test were used for group comparison. P values < 0.05 were considered statistically significant. Results: Three hundred sixty-three consecutive patients were included in this post-hoc analysis. Two hundred five patients (57%), were considered hyperoxemic and included in the hyperoxemia group. Patients in the hyperoxemia group had significantly higher PaO2 at 1, 6 and 12 h after surgery (p < 0.05). Otherwise, there was no significant difference in age, sex, comorbidities, pulmonary function tests parameters, lung surgery procedure, incidence of post-operative pulmonary and cardiovascular complications, intensive care unit and hospital length of stay and 30-day mortality. Conclusion: Hyperoxemia after lung resection surgery is common and not associated with post-operative complications or 30-day mortality.

Prognostic significance of early acute kidney injury in COVID-19 patients requiring mechanical ventilation: a single-center retrospective analysis.

Acute kidney injury (AKI) is associated with impaired outcomes in critically ill COVID-19 patients. However, the prognostic significance of early AKI is poorly described. We aimed to determine whether AKI on admission to the intensive care unit (ICU) and its development within the first 48 h predict the need for renal replacement therapy (RRT) and increased mortality. An analysis of 372 patients with COVID-19 pneumonia requiring mechanical ventilation without advanced chronic kidney disease from 2020 to 2021 was performed. The AKI stages on ICU admission and Day 2 were determined using adapted KDIGO criteria. The early development of renal function was assessed by the change in AKI score and the Day-2/Day-0 creatinine ratio. Data were compared between three consecutive COVID-19 waves and with data before the pandemic. Both ICU and 90-day mortality (79% and 93% vs. 35% and 44%) and the need for RRT increased markedly with advanced AKI stage on ICU admission. Similarly, an early increase in AKI stage and creatinine implied highly increased mortality. RRT was associated with very high ICU and 90-day mortality (72% and 85%), even surpassing that of patients on ECMO. No difference was found between consecutive COVID-19 waves, except for a lower mortality in the patients on RRT in the last omicron wave. Mortality and need for RRT were comparable in the COVID-19 and pre-COVID-19 patients, except that RRT did not increase ICU mortality in the pre-COVID-19 era. In conclusion, we confirmed the prognostic significance of both AKI on ICU admission and its early development in patients with severe COVID-19 pneumonia.

Empagliflozin-associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis.

BACKGROUND: Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors is a rare, relatively new and potentially fatal clinical entity, characterized by metabolic acidosis with normal or only moderately elevated glycemia. The mechanisms are not fully understood but involve increased ketogenesis and complex renal metabolic dysfunction, resulting in both ketoacidosis and hyperchloremic acidosis. We report a rare case of fatal empagliflozin-associated acidosis with profound hyperchloremia and review its pathogenesis. CASE PRESENTATION: A patient with type 2 diabetes mellitus treated with empagliflozin underwent an elective hip replacement surgery. Since day 4 after surgery, he felt generally unwell, leading to cardiac arrest on the day 5. Empagliflozin-associated euglycemic diabetic ketoacidosis with severe hyperchloremic acidosis was identified as the cause of the cardiac arrest. CONCLUSIONS: This unique case documents the possibility of severe SGLT2 inhibitor-associated mixed metabolic acidosis with a predominant hyperchloremic component. Awareness of this possibility and a high index of suspicion are crucial for correct and early diagnosis.

Use of fondaparinux in patients with heparin-induced thrombocytopenia on veno-venous extracorporeal membrane oxygenation: A three-patient case series report.

Heparin-induced thrombocytopenia is a life-threatening immune-mediated complication of unfractionated heparin therapy. Fondaparinux is a therapeutic alternative, but it has limited evidence for its use in patients on extracorporeal membrane oxygenation (ECMO). We present a series of three adult patients with COVID-19 on ECMO who were diagnosed with heparin-induced thrombocytopenia after 7-12 days of unfractionated heparin treatment and were switched to fondaparinux. Fondaparinux was initiated with an intravenous loading dose of 5 mg, followed by a dose of 2.5 mg subcutaneously every 8-12 h. Dosage was adjusted according to daily measured anti-Xa concentration with a target range of 0.4-0.7 mg/L. The total duration of treatment with fondaparinux and ECMO ranged from 13 to 26 days. One major bleeding episode unrelated to fondaparinux therapy was observed, and the transfusions requirement was also low in all patients. The ECMO circuit was changed once in each patient. This series provides a deep insight into the use of fondaparinux over an extended period of time in patients on ECMO. Based on the presented data, fondaparinux can be considered a reasonable and affordable anticoagulant in patients without a high risk of bleeding.

The risk of post-operative pulmonary complications in lung resection candidates with normal forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide: a prospective multicentre study.

Introduction: According to the guidelines for preoperative assessment of lung resection candidates, patients with normal forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (D LCO) are at low risk for post-operative pulmonary complications (PPC). However, PPC affect hospital length of stay and related healthcare costs. We aimed to assess risk of PPC for lung resection candidates with normal FEV1 and D LCO (>80% predicted) and identify factors associated with PPC. Methods: 398 patients were prospectively studied at two centres between 2017 and 2021. PPC were recorded from the first 30 post-operative days. Subgroups of patients with and without PPC were compared and factors with significant difference were analysed by uni- and multivariate logistic regression. Results: 188 subjects had normal FEV1 and D LCO. Of these, 17 patients (9%) developed PPC. Patients with PPC had significantly lower pressure of end-tidal carbon dioxide (P ETCO2 ) at rest (27.7 versus 29.9; p=0.033) and higher ventilatory efficiency (V'E/V'CO2 ) slope (31.1 versus 28; p=0.016) compared to those without PPC. Multivariate models showed association between resting P ETCO2 (OR 0.872; p=0.035) and V'E/V'CO2 slope (OR 1.116; p=0.03) and PPC. In both models, thoracotomy was strongly associated with PPC (OR 6.419; p=0.005 and OR 5.884; p=0.007, respectively). Peak oxygen consumption failed to predict PPC (p=0.917). Conclusions: Resting P ETCO2 adds incremental information for risk prediction of PPC in patients with normal FEV1 and D LCO. We propose resting P ETCO2 be an additional parameter to FEV1 and D LCO for preoperative risk stratification.

Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation.

Introduction: Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity. Cohorts: To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses - in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other. Results: We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation - in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03. Discussion: Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.

Prediction of Postoperative Complications: Ventilatory Efficiency and Rest End-tidal Carbon Dioxide.

BACKGROUND: Cardiopulmonary exercise testing parameters including ventilatory efficiency (VE/VCO2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. VE/VCO2 slope is closely related to the partial pressure of end-tidal carbon dioxide (PETCO2). We hypothesized PETCO2 at rest predicts postoperative pulmonary complications. METHODS: Consecutive lung resection candidates were included in this prospective multicenter study. Postoperative respiratory complications were assessed from the first 30 postoperative days or from the hospital stay. Student t test or Mann-Whitney U test was used for comparison. Multivariate stepwise logistic regression analysis was used to analyze association with the development of postoperative pulmonary complications. The De Long test was used to compare area under the curve (AUC). Data are summarized as median (interquartile range). RESULTS: Three hundred fifty-three patients were analyzed, of which 59 (17%) developed postoperative pulmonary complications. PETCO2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and VE/VCO2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest PETCO2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and VE/VCO2 slope with odds ratio 1.10 (95% CI 1.05-1.16); P < .01 were independently associated with postoperative pulmonary complications by multivariate stepwise logistic regression analysis. There was no significant difference between AUC of both models (rest PETCO2: AUC = 0.79 (95% CI 0.74-0.85); VE/VCO2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48). CONCLUSIONS: PETCO2 at rest has similar prognostic utility as VE/VCO2 slope, suggesting rest PETCO2 may be used for postoperative pulmonary complications prediction in lung resection candidates.

Prognostic value of soluble endoglin in patients with septic shock and severe COVID-19.

Sepsis is a clinical syndrome characterized by a dysregulated response to infection. It represents a leading cause of mortality in ICU patients worldwide. Although sepsis is in the point of interest of research for several decades, its clinical management and patient survival are improving slowly. Monitoring of the biomarkers and their combinations could help in early diagnosis, estimation of prognosis and patient's stratification and response to the treatment. Circulating soluble endoglin (sEng) is the cleaved extracellular part of transmembrane glycoprotein endoglin. As a biomarker, sEng has been tested in several pathologic conditions where its elevation was associated with endothelial dysfunction. In this study we have tested the ability of sEng to predict mortality and its correlation with other clinical characteristics in the cohort of septic shock patients (n = 37) and patients with severe COVID-19 (n = 40). In patients with COVID-19 sEng did not predict mortality or correlate with markers of organ dysfunction. In contrast, in septic shock the level of sEng was significantly higher in patients with early mortality (p = 0.019; AUC = 0.801). Moreover, sEng levels correlated with signs of circulatory failure (required dose of noradrenalin and lactate levels; p = 0.002 and 0.016, respectively). The predominant clinical problem in patients with COVID-19 was ARDS, and although they often showed signs of other organ dysfunction, circulatory failure was exceptional. This potentially explains the difference between sEng levels in COVID-19 and septic shock. In conclusion, we have confirmed that sEng may reflect the extent of the circulatory failure in septic shock patients and thus could be potentially used for the early identification of patients with the highest degree of endothelial dysfunction who would benefit from endothelium-targeted individualized therapy.

Ventilatory efficiency is superior to peak oxygen uptake for prediction of lung resection cardiovascular complications.

INTRODUCTION: Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection. METHODS: Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR). RESULTS: Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications. CONCLUSION: VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates.

High CD4-to-CD8 ratio identifies an at-risk population susceptible to lethal COVID-19.

Around half of people with severe COVID-19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS-CoV-2 differs between ICU patients that recover and those that do not. We conducted whole-blood immunophenotyping of COVID-19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID-19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4-to-CD8 T cell and neutrophil-to-CD8 T cell ratios. ROC and Kaplan-Meier analyses demonstrated that both CD4-to-CD8 and neutrophil-to-CD8 ratios at admission were strong predictors of in-ICU mortality. Therefore, we propose the use of the CD4-to-CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro-active intervention in ICU.

Polymorphonuclear Cells Show Features of Dysfunctional Activation During Fatal Sepsis.

Sepsis and septic shock remain leading causes of morbidity and mortality for patients in the intensive care unit. During the early phase, immune cells produce various cytokines leading to prompt activation of the immune system. Polymorphonuclear leukocytes (PMNs) respond to different signals producing inflammatory factors and executing their antimicrobial mechanisms, resulting in the engulfment and elimination of invading pathogens. However, excessive activation caused by various inflammatory signals produced during sepsis progression can lead to the alteration of PMN signaling and subsequent defects in their functionality. Here, we analyzed samples from 34 patients in septic shock, focusing on PMNs gene expression and proteome changes associated with septic shock. We revealed that, compared to those patients who survived longer than five days, PMNs from patients who had fulminant sepsis were characterized by a dysfunctional hyper-activation, show altered metabolism, and recent exit from the cell cycle and signs of cellular lifespan. We believe that this multi-omics approach, although limited, pinpoints the alterations in PMNs' functionality, which may be rescued by targeted treatments.

Extracorporeal Membrane Oxygenation Use in Thoracic Surgery.

This narrative review is focused on the application of extracorporeal membrane oxygenation (ECMO) in thoracic surgery, exclusive of lung transplantation. Although the use of ECMO in this indication is still rare, it allows surgery to be performed in patients where conventional ventilation is not feasible-especially in single lung patients, sleeve lobectomy or pneumonectomy and tracheal or carinal reconstructions. Comparisons with other techniques, various ECMO configurations, the management of anticoagulation, anesthesia, hypoxemia during surgery and the use of ECMO in case of postoperative respiratory failure are reviewed and supported by two cases of perioperative ECMO use, and an overview of published case series.

A phase I, open-label study evaluating the safety and pharmacokinetics of trifluridine/tipiracil in patients with advanced solid tumors and varying degrees of renal impairment.

PURPOSE: Trifluridine/tipiracil (FTD/TPI) is approved for advanced colorectal and gastric/gastroesophageal cancer; however, data in patients with renal impairment (RI) are limited. This phase I study evaluated FTD/TPI in patients with advanced solid tumors and varying degrees of RI to develop dosing guidance. METHODS: Patients were enrolled into normal renal function (CrCl ≥ 90 mL/min), mild RI (CrCl 60-89 mL/min), or moderate RI (CrCl 30-59 mL/min) cohorts and administered the recommended FTD/TPI dose (35 mg/m2 twice daily, days 1-5 and 8-12; 28-day cycle). Based on interim pharmacokinetics/safety data, patients with severe RI (CrCl 15-29 mL/min) were enrolled and received FTD/TPI 20 mg/m2 twice daily. RESULTS: Forty-three patients (normal renal function [n = 12]; mild RI [n = 12]; moderate RI [n = 11]; severe RI [n = 8]) were enrolled and treated. At steady state, compared to values in patients with normal renal function, FTD area under the curve (AUC) was not significantly different in patients with RI, but TPI AUC was significantly higher and increased with RI severity. FTD/TPI safety profile was consistent with prior experience, but grade ≥ 3 adverse events (AEs) were more frequent in the RI cohorts (83.3% [mild], 90.9% [moderate], 75.0% [severe], and normal [50.0%]). Hematologic AEs (anemia and neutropenia) were more frequent with RI. Overall, seven patients discontinued because of unrelated, nonhematologic AEs. CONCLUSION: FTD/TPI is safe and tolerable at the recommended 35 mg/m2 dose in patients with mild/moderate RI and at the reduced 20 mg/m2 dose in patients with severe RI. TRIAL REGISTRATION: NCT02301117, registration date: November 21, 2014.

Human myeloid-derived suppressor cell expansion during sepsis is revealed by unsupervised clustering of flow cytometric data.

Myeloid-derived suppressor cells (MDSCs) are important regulators of immune processes during sepsis in mice. However, confirming these observations in humans has been challenging due to the lack of defined preparation protocols and phenotyping schemes for MDSC subsets. Thus, it remains unclear how MDSCs are involved in acute sepsis and whether they have a role in the long-term complications seen in survivors. Here, we combined comprehensive flow cytometry phenotyping with unsupervised clustering using self-organizing maps to identify the three recently defined human MDSC subsets in blood from severe sepsis patients, long-term sepsis survivors, and age-matched controls. We demonstrated the expansion of monocytic M-MDSCs and polymorphonuclear PMN-MDSCs, but not early-stage (e)-MDSCs during acute sepsis. High levels of PMN-MDSCs were also present in long-term survivors many months after discharge, suggesting a possible role in sepsis-related complications. Altogether, by employing unsupervised clustering of flow cytometric data we have confirmed the likely involvement of human MDSC subsets in acute sepsis, and revealed their expansion in sepsis survivors at late time points. The application of this strategy in future studies and in the clinical/diagnostic context would enable rapid progress toward a full understanding of the roles of MDSC in sepsis and other inflammatory conditions.

Interpretive discrepancies caused by target values inter-batch variations in chemiluminescence immunoassay for SARS-CoV-2 IgM/IgG by MAGLUMI.

Plasma specimens from coronavirus disease 2019 patients were double-tested for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies by two different batches of MAGLUMI 2019-nCov immunoglobulin M/immunoglobulin G (IgM/IgG) assays to evaluate IgM/IgG levels, qualitative interpretation, antibody kinetics, and linearity of diluted specimen. Here we show that (i) high-level IgM specimens need to be diluted with negative human plasma but not kit diluents and (ii) measured anti-SARS-CoV-2 IgM/IgG concentrations are substantially higher with later marketed immunoassay batch leading to (iii) the change of qualitative interpretation (positive vs. negative) in 12.3% of specimens measured for IgM, (iv) the informative time-course pattern of antibody production only when data from different immunoassay batches are not combined.

Ischaemic Stroke Caused by a Gunshot Wound to the Chest.

INTRODUCTION: Pneumatic weapons rarely cause severe trauma. However, pellet embolisation can cause severe and unexpected injuries. REPORT: This is the case study of a 32 year old man, who was shot in the chest with a pneumatic rifle. Initially, urgent damage control surgery was performed to resolve pneumothorax and pericardial tamponade, but no projectile was found. Subsequent atypical symptomatology led to more extensive imaging that found a pellet embolised into the right carotid artery, thrombosis of the middle cerebral artery, and development of a large right hemispheric ischaemic area. After an unsuccessful endovascular intervention, the projectile was removed during an open surgical procedure. The right hemisphere oedema required decompressive hemicraniectomy, but long term intensive care and physiotherapy resulted in a satisfactory recovery with moderate neurological sequelae. CONCLUSION: An unusual clinical presentation in combination with an absent exit wound might be symptomatic of projectile embolisation and should lead to a search for it. When the projectile position is convenient, surgical removal is the treatment of choice while an endovascular approach should be reserved for inaccessible locations or asymptomatic cases.

Differences in monocyte subsets are associated with short-term survival in patients with septic shock.

Sepsis is characterized by dynamic changes of the immune system resulting in deregulated inflammation and failure of homoeostasis and can escalate to septic shock. Circulating monocytes and other innate immune cells are among the first ones to recognize and clear pathogens. Monocytes have an important role in sepsis and septic shock and have been studied as potential diagnostic markers. In total, forty-two patients with septic shock were recruited and blood samples obtained within first 12 hours of ICU admission. We showed that frequency of classical and intermediate monocytes assessed at the time of admission to the intensive care unit are significantly distinct in patients with septic shock who survived longer that five days from those who died. These parameters correlate significantly with differences in serum levels of inflammatory cytokines MCP-1, IL-6, IL-8, IL-10, and IL-18, and with the proportion of helper and cytotoxic T cells. The described changes in frequency of monocyte subsets and their activation status may predict short-term septic shock survival and help with fast identification of the group of vulnerable patients, who may profit from tailored therapy.

Phagocytosis-Inflammation Crosstalk in Sepsis: New Avenues for Therapeutic Intervention.

Phagocytosis is a complex process by which cells within most organ systems remove pathogens and cell debris. Phagocytosis is usually followed by inflammatory pathway activation, which promotes pathogen elimination and inhibits pathogen growth. Delayed pathogen elimination is the first step in sepsis development and a key factor in sepsis resolution. Phagocytosis thus has an important role during sepsis and likely contributes to all of its clinical stages. However, only a few studies have specifically explored and characterized phagocytic activity during sepsis. Here, we describe the phagocytic processes that occur as part of the immune response preceding sepsis onset and identify the elements of phagocytosis that might constitute a predictive marker of sepsis outcomes. First, we detail the key features of phagocytosis, including the main receptors and signaling hallmarks associated with different phagocytic processes. We then discuss how the initial events of phagosome formation and cytoskeletal remodeling might be associated with known sepsis features, such as a cytokine-driven hyperinflammatory response and immunosuppression. Finally, we highlight the unresolved mechanisms of sepsis development and progression and the need for cross-disciplinary approaches to link the clinical complexity of the disease with basic cellular and molecular mechanisms.