General Anesthesia Alters the Diversity and Composition of the Intestinal Microbiota in Mice.

Dysbiosis of the intestinal microbiota has been shown to result in altered immune responses and increased susceptibility to infection; as such, the state of the intestinal microbiome may have profound implications in the perioperative setting. In this first-in-class study, we used 16s ribosomal RNA sequencing and analysis in a mouse model of general anesthesia to investigate the effects of volatile anesthetics on the diversity and composition of the intestinal microbiome. After 4-hour exposure to isoflurane, we observed a decrease in bacterial diversity. Taxonomic alterations included depletion of several commensal bacteria including Clostridiales. These data identify volatile anesthetics as potential contributors to microbial dysbiosis in the postoperative patient.

Blood utilization and mortality in victims of gun violence.

BACKGROUND: Blood transfusion can be lifesaving for patients with hemorrhage; however, transfusion requirements for victims of gun violence are poorly understood. STUDY DESIGN AND METHODS: In an urban, Level 1 trauma center, 23,422 trauma patients were analyzed in a retrospective cohort study. Patients with gunshot wounds (GSWs) (n = 2,672; 11.4% of trauma patients) were compared to those with non-GSW traumatic injuries from 2005 to 2017, to assess blood utilization. RESULTS: The GSW cohort was approximately five times more likely to require transfusion (538 of 2672 [20.1%] vs. 798 of 20,750 [3.9%]; p < 0.0001), and the number of blood component units transfused per patient was approximately 10 times greater (3.3 ± 13.5 vs. 0.31 ± 3.8 units/patient; p < 0.0001), compared to the non-GSW cohort. The risk-adjusted likelihood of requiring high-dose transfusion was greater in the GSW cohort (odds ratio, 2.38; 95% confidence interval, 1.14-5.80), and requirements were increased for all four blood components (red blood cells, platelets, plasma, and cryoprecipitate). Patients with GSWs had approximately 14 times greater overall mortality (653 of 2672 [24.4%] vs. 352 of 20,750 [1.7%]; p < 0.0001]. Compared to non-GSW penetrating injuries (e.g., stab wounds), those with GSWs had approximately four times higher transfusion requirements (3.3 ± 13.5 vs. 0.80 ± 3.8 units/patient; p < 0.0001), and approximately eight times greater overall mortality (653 of 2672 [24.4%] vs. 28 of 956 [2.9%]; p < 0.0001). CONCLUSIONS: Compared to other traumatic injuries, GSW injuries are associated with substantially greater blood utilization and mortality. Trauma centers treating GSW injuries should have ready access to all blood components and ability to implement massive transfusions.

Impact of Intensive Care Unit Nutrition on the Microbiome and Patient Outcomes.

The bipartite relationship between nutrition and the intestinal microbiome represents an exciting frontier in critical care medicine. In this review, the authors first address these topics independently, leading with a summary of recent clinical studies assessing intensive care unit nutritional strategies, followed by an exploration of the microbiome in the context of perioperative and intensive care, including recent clinical data implicating microbial dysbiosis as a key driver of clinical outcomes. Finally, the authors address the intersection of nutrition and the microbiome, exploring the use of supplemental pre-, pro-, and synbiotics to influence microbial composition and improve outcomes in critically ill and postsurgical patients.

Role of Resident Microbial Communities in Biofilm-Related Implant Infections: Recent Insights and Implications.

The use of medical implants continues to grow as the population ages. Biofilm-related implant infection is the leading cause of medical implant failure and remains difficult to diagnose and treat. Recent technologies have enhanced our understanding of the composition and complex functions of microbiota occupying various body site niches. In this review, we leverage data from molecular sequencing technologies to explore how silent changes in microbial communities from various sites can influence the development of biofilm-related infections. Specifically, we address biofilm formation and recent insights of the organisms involved in biofilm-related implant infections; how composition of microbiomes from skin, nasopharyngeal, and nearby tissue can impact biofilm-formation, and infection; the role of the gut microbiome in implant-related biofilm formation; and therapeutic strategies to mitigate implant colonization.

The Epiaortic Ultrasound Diagnosis of Iatrogenic Subadventitial Hematoma.

Iatrogenic aortic injury is a rare but potentially lethal complication of cardiac surgery. While sometimes resulting in aortic dissection or intramural hematoma, injury more frequently results in subadventitial hematoma, a more benign pathology. Here, we describe a case where intraoperative transesophageal echocardiography (TEE) identified such a hematoma but was unable to rule out dissection. Epiaortic ultrasound was subsequently performed, which definitively demonstrated the absence of a dissection flap or extraluminal flow. Per our review, this is the first report documenting the successful use of epiaortic imaging to identify subadventitial hematoma in the setting of inconclusive TEE findings.

Attrition of memory CD8 T cells during sepsis requires LFA-1.

CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69+CD25intCD62LHI) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis.

Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.