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
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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.
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Serum chemotactic activity is important in regulating neutrophil migration. The ability of neutrophils to migrate to infectious site is crucial for host effective pathogen control, but unregulated neutrophil activation can also cause tissue damage. During bacterial sepsis, the complement alternative pathway (AP) is massively activated in blood and tissues and reportedly contributes to sepsis pathogenesis. ⋯ To delineate the contribution of these downstream effectors, we incubated AP-active sera (AP activated by zymosan/CVF) or sera from sham and septic mice with anti-C5a or mAb1379 (anti-Ba) neutralizing antibody. We found that anti-C5a, but not mAb1379, markedly attenuated the neutrophil chemotactic effect of the AP-activated sera and that of septic sera. Taking together, these data suggest that the complement AP activation during bacterial sepsis plays a pivotal role in promoting blood chemotactic activity through a C5a-dependent mechanism.
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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.
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Autophagy plays an important role in cell survival, sequestering, and degrading a wide variety of substrates. Although an increase of autophagosomes in liver has been reported in sepsis patients as well as in septic mice, the influence of autophagy on liver injury, the interaction between autophagy, and other types of cell death in sepsis remain unclear. The aim of this study was to elucidate the contribution of liver autophagy to the pathophysiology of sepsis. ⋯ Serum aspartate transaminase levels (P = 0.005) and serum interleukin-6 levels (P = 0.020) were significantly increased in the KO mice compared with controls. Deficiency of autophagy in liver significantly decreased survival in the murine sepsis model (P = 0.025). In conclusion, blocking liver autophagy accelerates time to mortality in the murine sepsis model, suggesting that liver autophagy plays a protective role for organ failure through degradation of damaged mitochondria, as well as prevention of apoptosis.