Acute Multiple Organ Dysfunction Research Articles

Cardiac steroid ouabain transcriptionally increases human leukocyte antigen DR expression on monocytes

Sepsis is a life-threatening disease characterized by acute multiple organ dysfunction and immunosuppression that is also called as immunoparalysis. Increasing evidence suggests that immunoparalysis largely contributes to the high mortality of sepsis, but the effective remedies are lacking. As an important antigen presentation molecule, human leukocyte antigen DR (HLA-DR) is remarkably down-regulated in sepsis-induced immunoparalysis, therefore, re-stimulation of HLA-DR expression is expected to be useful in reversing immunoparalysis. We previously described that ouabain, as a Na+, K+-ATPase ligand, is able to counteract immunoparalysis by regulating TH1 cytokines expression. Here, we expanded the finding that ouabain not only prevents LPS-induced down-regulation of HLA-DR on monocytes, but also transcriptionally activates HLA-DR α/β expression mediated by CIITA4, IRF1, c-Src, and Stat1 phosphorylation. Since ouabain can improve sepsis-induced immunoparalysis by multiple mechanisms, we propose that ouabain may be a promising agent in septic therapy that deserves further investigation.

Association between early serum cholinesterase activity and 30-day mortality in sepsis-3 patients: A retrospective cohort study.

Low serum cholinesterase (SCHE) activity has been associated with poor prognoses in a variety of conditions, including sepsis. However, such an association has not been well characterized since the Third International Consensus Definitions Task Force modified the definition of sepsis to “life-threatening organ dysfunction due to a dysregulated host response to infection” (known as sepsis-3) in 2016. In the current retrospective cohort study, we examined whether 30-day mortality in sepsis-3 patients is associated with SCHE activity. A total of 166 sepsis-3 patients receiving treatment at an emergency intensive care unit (EICU) were included. The 30-day death rate was 33.1% (55/166). SCHE activity upon EICU admission was lower in nonsurvivors (3.3 vs. 4.5 KU/L in survivors, p = 0.0002). Subjects with low SCHE activity (defined as <4 KU/L) had higher 30-day mortality rates than subjects with normal SCHE activity (45.5%, 40/88 vs. 19.2%, 15/78; p<0.001). A multivariate logistic regression analysis revealed an association between 30-day mortality and lower SCHE activity after adjustments for relevant factors, such as acute multiple organ dysfunction. The odds ratio (OR) for every unit decrease in SCHE activity was 2.11 (95% confidence interval (CI), 1.37–3.27; p = 0.0008). The area under the curve (AUC) of SCHE activity for predicting 30-day mortality was 0.67 (95% CI 0.59–0.74), and the AUC of lactate for predicting 30-day mortality was 0.64 (95% CI 0.57–0.70). Using a combination of SCHE and lactate, the AUC was 0.74 (95% CI 0.69–0.83). These data suggest that lower SCHE activity is an independent risk factor for 30-day mortality in sepsis-3 patients.

Leptospirosis renal disease: Understanding the initiation by Toll-like receptors

Leptospirosis is a prevalent infectious disease affecting both humans and animals worldwide. This infection is associated with occupational or recreational exposure to animals as well as contact with leptospires, particularly in flood-prone areas. Multiple organ dysfunctions may be associated with acute severe leptospirosis. A triad presentation of fever, jaundice, and acute renal failure in patients with acute multiple organ dysfunction should alert physicians to possible leptospirosis. Penicillin is effective and can rescue multiple organ failure if administered early. Renal involvement is common in leptospirosis characterized by tubulo-interstitial nephritis, and tubular dysfunction. Leptospira outer membrane proteins (OMPs) may elicit tubular injury and inflammation through Toll-like receptors (TLRs)-dependent pathway followed by activation of nuclear transcription factor kappa B and mitogen-activated protein kinases and a differential induction of chemokines and cytokines relevant to tubular inflammation. Leptospira OMP may also induce activation of the transforming growth factor-beta/Smad-associated fibrosis pathway leading to accumulation of extracellular matrix. Thus, leptospirosis renal disease is a model for understanding the pathogenesis and initiation of pathogen-induced tubulo-interstitial nephritis and fibrosis. In particular, TLRs may be important mediators.