Daily Sepsis Research Analysis

INTRODUCTION: The choice of optimal resuscitation fluid for patients with septic shock remains a controversial topic. The 2021 Sepsis Surviving Campaign Guidelines strongly recommend using crystalloids as the first-line resuscitation fluid for adults with sepsis or septic shock, with balanced crystalloids as a weak recommendation. However, two large-scale network meta-analyses in 2020 concluded that balanced crystalloids are most advantageous. This study reevaluates the efficacy and safety of different resuscitation fluids in septic shock through a network meta-analysis (NMA. METHODS: Databases including PubMed, EMBASE, and WOS were searched, and reference lists of relevant literature up to September 2024 were reviewed. Studies involving adult patients with sepsis requiring fluid resuscitation were selected. The fluids covered include balanced crystalloid (BC), saline, iso-oncotic albumin (Iso-Alb), hyper-oncotic albumin (Hyper-Alb), low molecular weight hydroxyethyl starch (L-HES), high molecular weight hydroxyethyl starch (HES), and gelatin. A network meta-analysis was conducted to assess the effects of different fluid types. RESULTS: A total of 32 RCTs were included in the analysis. The NMA probability ranking results show that balanced crystalloid (BC) had the lowest all-cause mortality rate, with the highest SUCRA value (83.1%). Gelatin was shown to confer the greatest advantage in terms of kidney injury, with the highest SUCRA value (80.7%). Hyper-oncotic albumin had the lowest occurrence of renal replacement therapy events, showing the highest SUCRA value (94.1%). Patients treated with balanced crystalloids had the shortest ICU stays and hospital lengths of stay. CONCLUSION: Balanced solutions (BS) are the preferred resuscitation fluids for septic shock. High molecular weight hydroxyethyl starch (H-HES) is associated with increased risks of mortality, acute kidney injury (AKI), and renal replacement therapy (RRT), as well as prolonged hospital stays, and its use is advised against. Gelatin is associated with poorer outcomes in terms of mortality, continuous renal replacement therapy (CRRT), and length of hospital stay. SYSTEMATIC REVIEW REGISTRATION: Registration ID: INPLASY2024100049 https://doi.org/10.37766/inplasy2024.10.0049.

BACKGROUND: The overall benefits and potential risks of corticosteroids, frequently administered to critically ill patients remain uncertain. This systematic review and meta-analysis evaluated the efficacy and safety of corticosteroid therapy in critically ill patients with severe community-acquired pneumonia, sepsis or septic shock, or acute respiratory distress syndrome. We hypothesized that corticosteroids reduce short-term mortality in critically ill patients. METHODS: We performed a search of Medline, Embase, and the Cochrane Central Register of Controlled Trials from database inception up to November 30, 2024. The search was limited to randomized controlled trials in human populations published in English. Dichotomous outcomes are reported as relative risk (RRs) and continuous outcomes as mean differences (MDs), both with 95% confidence intervals (CIs). The primary outcome was short-term mortality (28-day or nearest reported). Secondary outcomes included ICU/hospital length of stay, mechanical ventilation duration, ventilator-free days at 28 days, oxygenation index, reversed shock in sepsis or septic shock, and adverse events. We evaluated heterogeneity using I RESULTS: Forty-three randomized controlled trials (n = 10853) were included. Corticosteroids reduced short-term mortality in critically ill patients compared to placebo (RR, 0.85; 95% CI, 0.77-0.94). Corticosteroid treatment for critically ill patients reduced intensive care unit (MD, - 2.02 days; 95% CI, - 3.14 - -0.90) and hospital (MD, - 2.66 days; 95% CI, - 4.58 - -0.74) lengths of stay, and duration of mechanical ventilation (MD, - 4.24 days; 95% CI, - 6.38 - -2.10); it increased ventilator-free days at 28 days (MD, 2.83 days; 95% CI, 1.20-4.47), improved oxygenation index (PaO CONCLUSIONS: Subgroup analysis indicated that early initiation (≤ 72 h), low-dose (e.g., < 400 mg/day hydrocortisone equivalent), and prolonged (≥ 7 days) corticosteroid therapy was associated with reduced short-term mortality in critically ill patients with severe community-acquired pneumonia or acute respiratory distress syndrome. For septic shock, combination therapy (hydrocortisone plus fludrocortisone) may enhance efficacy. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42024517843.

Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis, yet the underlying mechanisms remain elusive. The current study, using a Lipopolysaccharide (LPS)-induced septic rat model, revealed the hyperphosphorylation of tau and cognitive impairments, accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats. Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10) as a central regulator of neuroinflammation. LPS triggered CXCL10 secretion in astrocytes, and astrocyte-conditioned medium from LPS-treated astrocytes induced tau hyperphosphorylation and synaptic deficits. Recombinant CXCL10 recapitulated these effects in vitro and in vivo. Blocking CXCL10-CXCR3 interaction reversed tau phosphorylation, synaptic impairment, and cognitive decline. Mechanistically, CXCL10-CXCR3 interaction activated CaMKII, driving tau hyperphosphorylation, while CaMKII inhibition restored synaptic protein levels. These findings establish CXCL10 as a key driver of tau pathology in SAE and suggest CXCL10-CXCR3 as a therapeutic target for sepsis-induced cognitive impairments.