Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Several reviews of resuscitative thoracotomy (RT) use over the last five decades have been conducted, most recently the evidence-based practice management guideline (PMG) of the Eastern Association for the Surgery of Trauma (EAST). The present study was designed to examine contemporary RT utilization and outcomes compared with historical data (n = 10,238) from the EAST PMG review from published series 1974 to 2013. ⋯ Comparison of historical RT controls to more contemporary patients from the AORTA registry suggests that practices and outcomes following RT have not changed. Despite a wealth of accumulated data over several decades, RT continues to be performed for patients after blunt mechanisms of injury who present W/O SOL despite lack of demonstrated hope for survival benefit.
-
Fluid overload is associated with increased morbidity and mortality in critically ill patients. However, researches rarely study the precise start or end point of fluid removal and no protocol was developed to control the fluid removal process. We hypothesized that individualized fluid removal with ultrasound-guided protocol could improve the efficacy and safety of fluid removal in post-resuscitated critically ill patients. ⋯ The time of lung B-lines to reduce to zero was shorter and B-line at the end point was less (49.5 ± 36.6 h vs. 75.6 ± 58.8 h, 0[1] vs. 0[0], P < 0.05) in Ultrasound group. The length of intensive care unit stay in shock subgroup had a tendency to shorten (96.1 ± 61.5 h vs. 174.6 ± 132.0 h, P > 0.05) in Ultrasound group. We concluded that fluid removal with individualized ultrasound-guided protocol improves the efficacy and safety of dehydration in critically ill patients.
-
Hemodynamic collapse and myocardial dysfunction are among the major causes of death in severe sepsis. The purpose of this study was to assess the role played by toll-like receptor 4 and by the NLRP3 inflammasome in the cardiac dysfunction that occurs after high-grade polymicrobial sepsis. We performed the colon ascendens stent peritonitis (CASP) surgery in Tlr4, Nlrp3, and caspase-1 mice. ⋯ Similar heart response was found when Nlrp3 mice were submitted to high-grade cecal ligation and puncture. Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3 mice had reduced circulating levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. Our results demonstrate that the genetic ablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite preventing the increase in pro-inflammatory cytokines, indicating that these are not feasible targets to therapy in high-grade sepsis.
-
We recently reported that CD4CD25 regulatory T cells (Tregs) contributed to the recovery of patients with acute lung injury (ALI) by upregulating T cell immunoglobulin and mucin-domain containing-3 (Tim-3). However, the molecular mechanism by which Tim-3 regulates Tregs' function in the resolution and fibroproliferation after ALI remains unknown. In this study, we adoptively transferred Tim-3Tregs or Tim-3Tregs into lipopolysaccharide -induced ALI mice model. ⋯ In vitro experiments further demonstrated that cell-contact cocultures with Tregs lacking Tim-3 presented decreased polarization of M2-like macrophages partially mediated by a decreased expression and function of STAT-3. Therefore, these data demonstrate a previously unrecognized function of Tim-3 on Tregs in their ability to repress the fibroproliferation of ALI by inducing alternative macrophages polarization. Moreover, the data highlight that Tim-3Tregs-mediated induction of M2-like macrophages may be a novel treatment modality with transitional potential.
-
N-Formyl-Met-Leu-Phe (fMLP), a mimic of N-formyl oligopeptides that are released from bacteria, is a potent leukocyte chemotactic factor. It induces intracellular calcium ([Ca]i) transient that is important for various neutrophil biological functions, e.g., adhesion, ROS, and cytokine productions. Toll-like receptors (TLRs), an essential part of host innate immunity, regulate neutrophil activities, but their role in [Ca]i signaling is less clear. ⋯ Surprisingly, deletion of TLR2 or MyD88 in neutrophils had no impact on the Pam3Cys4's effect, suggesting a TLR2-MyD88-independent mechanism. Finally, using the pan PKC activator and inhibitor, we demonstrated that PKC negatively regulated fMLP-induced [Ca]i transients and that inhibition of PKC did not prohibit Pam3Cys4's synergistic effect on the fMLP-induced calcium influx. In conclusion, the present study identified a novel synergistic effect of Pam3Cys4 on fMLP-induced [Ca]i transients, a process important for many neutrophil biological functions.