Daily Sepsis Research Analysis

BACKGROUND: Sepsis-induced acute kidney injury (AKI) is a severe condition characterized by dysregulation of pro- and anti-inflammatory responses. Targeting macrophage polarization between pro-inflammatory M1 and anti-inflammatory M2 cells offers a potential therapeutic approach for AKI. Trametinib (TRAM), an inhibitor of the MEK1/2 signaling pathway, was evaluated for its impact on M1/M2 polarization in AKI. METHODS: Wild-type (WT) mice were subjected to lipopolysaccharide (LPS)-induced AKI and intraperitoneally treated with dimethyl sulfoxide (DMSO) or TRAM (10 mg/kg) for three days. Renal function was assessed by measuring creatinine levels. While histopathological changes, RNA sequencing data, and serum cytokine levels were analyzed. Macrophage M1/M2 polarization in kidney tissues was examined using flow cytometry and immunohistochemistry. Murine bone marrow-derived macrophages (BMDMs) were polarized to the M1 or M2 phenotype in vivo and treated with or without TRAM (10 μM). M1/M2 polarization was analyzed via flow cytometry, and PI3K/Akt signaling was evaluated by western blotting. RESULTS: TRAM significantly improved renal function, as demonstrated by reduced serum creatinine levels (p < 0.01) and ameliorated histopathological damage (p < 0.01). Flow cytometry and immunohistochemistry revealed that TRAM markedly inhibited pro-inflammatory M1 macrophage polarization (p < 0.001). Additionally, TRAM reduced serum level of IFN-γ (p < 0.01) and IL-17 (p < 0.001). In vitro, TRAM suppressed M1 polarization (p < 0.05) by inhibiting the PI3K/Akt signaling pathway. CONCLUSION: TRAM mitigated LPS-induced AKI by suppressing M1 macrophage polarization via the PI3K/Akt pathway, highlighting its therapeutic potential for AKI and other inflammatory kidney diseases.

BACKGROUND: Pancreatic Stone Protein (PSP) seems to have higher accuracy for sepsis detection compared to other biomarkers. As PSP has never been studied in patients with liver failure (LF), our purpose was to assess its accuracy for diagnosis of infection and prognosis in this population. METHODS: We conducted a prospective pilot cohort study on patients with LF consecutively admitted to the Intensive Care Unit of a liver transplant center in 2021-2023. Ongoing overt infection was an exclusion criterion. Daily measurements of biomarkers were performed until discharge, death, or for 21 days. Analysis was performed by adjusting the baseline for the first infection episode (median on D3), which was the reference for those non-infected. RESULTS: Sixteen patients were included, 7 with acute and 9 with acute-on-chronic LF. Median age was 54 (interquartile range 42-64) years, half were female, with admission SOFA score of 10 (IQR 8-12). Hospital mortality was 43.8% (n = 7). An infection was observed in 8 patients, who presented non-significantly higher levels of PSP than non-infected ones during follow-up. Levels were higher in non-survivors than survivors (p < 0.05 from D4 on and since the day of infection considering only infected patients). Similarly, patients under renal replacement therapy had higher PSP levels than others (p < 0.05, D2 to D7 after admission). CONCLUSION: This pilot study provides early insights into PSP kinetics, suggesting a potential role for prognosis in patients with LF. PSP rises in both ALF and ACLF to levels sustainably higher than those expected for healthy adults. Further research is needed to reassess its diagnostic accuracy for infection and redefine cut-offs in this population.

Septic shock is associated with significant morbidity and mortality, but a subset of patients with sepsis will experience transient myocardial depression, termed sepsis-associated cardiomyopathy, which markedly increases observed mortality. Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) can provide temporary mechanical circulatory support in medically refractory sepsis, survival in patients with VA-ECMO for sepsis has been historically poor. Concerns regarding numerous potential harms associated with VA-ECMO, including further seeding of infection, exacerbation of inflammation and vasoplegia, bleeding, thrombosis, and distal limb ischemia have further tempered enthusiasm in the setting of sepsis. However, there may be a subset of patients with profound sepsis refractory to medical therapy that could potentially derive some benefit from VA-ECMO. This review provides an overview of the pathophysiology, diagnosis, and treatment of sepsis-associated cardiomyopathy and then focuses on the utility of VA-ECMO in this patient population. A summary of the scant published outcomes of VA-ECMO in sepsis-associated cardiomyopathy is provided, followed by a discussion of important management considerations to optimize outcomes in these extremely sick patients, and finally the pros and cons of VA-ECMO in the setting of sepsis are presented. Using available published data and current state-of-the-art practice, we conclude that VA-ECMO may be a reasonable consideration in highly selected patients with low ejection fraction sepsis-associated cardiomyopathy and refractory hypoperfusion in appropriately equipped health care systems, but more supportive data are required before VA-ECMO can be generally recommended in patients with septic shock.