A case of multiple organ injury resuscitated by collaboration of damage control surgery and interventional radiology in hybrid emergency room.

Background: Hybrid emergency room systems, namely hybrid ER (HER), enable us to perform computed tomography (CT), surgery, and interventional radiology (IVR) without patient transfer. HER significantly shortened the time to CT after arrival and allowed us to achieve early intervention, resulting in reduced mortality from exsanguination in patients with severe blunt trauma. Case Presentation: We encountered a patient diagnosed with left common iliac artery occlusion and dissection caused by blunt traumatic compressive abdominal injury with transection of the small intestine, kidney, and adrenal and pelvic ring fractures. Although the patient experienced cardiopulmonary arrest (CPA) immediately after CT, we performed damage control surgery (DCS) and IVR after temporary aortic occlusion in the HER and resuscitated the patient. Conclusion: The present case, in which rapid diagnosis and intervention were performed and the patient was successfully resuscitated, supports the efficacy of the HER system for managing severe blunt trauma.

Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders.

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined. METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models. RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. Immunoprofiling showed distinct baseline tumor microenvironments of MOC1 and MOC1esc1, as well as the remodeling of immune compartments on ICB in MOC1esc1 tumors. Single cell sequencing analysis identified several CD8 +TIL subsets including Tcf7 +Pd1- (naïve/memory-like), Tcf7 +Pd1+ (progenitor), and Tcf7-Pd1+ (differentiated effector). Mapping TCR shared fractions identified that successful anti-PD1 or anti-CTLA4 therapy-induced higher post-treatment T cell lineage transitions. CONCLUSIONS: These data highlight critical aspects of CD8 +TIL heterogeneity and differentiation and suggest facilitation of CD8 +TIL differentiation as a strategy to improve HNSCC ICB response.

Trauma induces expansion and activation of a memory-like Treg population.

CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, which suggests that they may react to injury with similar kinetics as memory T cells. Here, we used a mouse burn trauma model to screen for memory-like T cell responses to injury by transferring T cells from sham or burn CD45.1 mice into CD45.2 mice and performing secondary injuries in recipient mice. Among all T cell subsets that were measured, only Tregs expanded in response to secondary injury. The expanded Tregs were a CD44high /CD62Llow subpopulation, markers indicative of memory T cells. CyTOF (cytometry by time-of-flight) mass cytometry was used to demonstrate that injury-expanded Tregs expressed higher levels of CD44, CTLA-4, ICOS, GITR, and Helios than Tregs from noninjured mice. Next, we tested whether a similar population of Tregs might react acutely to burn trauma. We observed that Tregs with a phenotype that matched the injury-expanded Tregs were activated by 6 h after injury. To test if Treg activation by trauma requires functional MHC class II, we measured trauma-induced Treg activation in MHC class II gene deficient (MHCII-/- ) mice or in mice that were given Fab fragment of anti-MHC class II antibody to block TCR activation. Injury-induced Treg activation occurred in normal mice but only partial activation was detected in MHCII-/- mice or in mice that were given Fab anti-MHCII antibody. These findings demonstrate that trauma activates a memory-like Treg subpopulation and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism.

Impact of fecal short-chain fatty acids on prognosis in critically ill patients.

AIM: This study aimed to evaluate the relationship between fecal organic acids and mortality in critically ill patients. METHODS: This retrospective study included 128 patients who fulfilled the criteria of systemic inflammatory response syndrome and had a serum C-reactive protein level of greater than 10 mg/dL. Patients were treated in the intensive care unit for more than 2 days. Patients were divided into two groups: survivors and non-survivors. We measured and compared eight kinds of fecal organic acids between the two groups. We focused on the minimum and maximum value of each fecal organic acid and evaluated prognostic factors by using classification and regression tree (CART) and multivariate logistic regression analyses. RESULTS: We included 90 patients as survivors and 38 as non-survivors. The CART analysis revealed that the dominant factors for mortality were the minimum values of propionate and acetate and the maximum values of lactate and formic acid. In the evaluation of the minimum values of fecal organic acids, propionate was significantly associated with increased mortality (odds ratio, 0.11 [95% confidence interval, 0.024-0.51]; P = 0.005), acetate (0.047 [0.005-0.49]; P = 0.01), and age (1.048 [1.015-1.083]; P = 0.004). In the evaluation of the maximum values, lactate was significantly associated with increased mortality (5.21 [2.024-13.42], P = 0.001) and age (1.050 [1.017-1.084]; P = 0.003). CONCLUSION: An altered balance of fecal organic acids was significantly associated with mortality in critically ill patients.

Altered monocyte and NK cell phenotypes correlate with posttrauma infection.

BACKGROUND: Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection. METHODS: Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons. RESULTS: The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection. CONCLUSION: This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients. LEVEL OF EVIDENCE: Prognostic study, level II.

Rapid and Sustained Long-Term Decrease of Fecal Short-Chain Fatty Acids in Critically Ill Patients With Systemic Inflammatory Response Syndrome.

BACKGROUND: The gut is an important target organ for injury after severe insult. Short-chain fatty acids (SCFAs) are end-products of fermentation of dietary fibers by anaerobic microbiota. They are related to intestinal energy, motility, and transport and to protective effects against infection and inflammation. However, there are few clinical data on SCFAs in critically ill patients. We evaluated serial change in fecal SCFAs in patients with severe systemic inflammatory response syndrome (SIRS). PATIENTS AND METHODS: This study included 140 intensive care unit (ICU) patients who fulfilled the criteria of SIRS and had a serum C-reactive protein level of >10 mg/dL. A fecal sample was used for quantitative measurement of fecal SCFA (butyrate, propionate, and acetate) concentrations by high-performance liquid chromatography. Fecal SCFAs were evaluated weekly for 6 weeks after admission. Data obtained from patients were compared with corresponding data from healthy volunteers. RESULTS: SIRS resulted from infection in 78 patients, trauma in 30, burns in 12, and other causes in 20. Fecal concentrations of butyrate, propionate, and acetate in these patients decreased significantly compared with those in healthy volunteers and remained low throughout the 6 weeks of the patients' ICU stay. Fecal concentrations of SCFAs in the patients with gastrointestinal complications, including enteritis and dysmotility, were lower than those in the patients without gastrointestinal complications. CONCLUSIONS: Concentrations of fecal SCFAs in patients with severe SIRS were significantly lower than those in healthy volunteers over a 6-week period. Maintenance of SCFAs may have therapeutic potential to prevent gastrointestinal complications in critically ill patients.

Patterns of Gram-stained fecal flora as a quick diagnostic marker in patients with severe SIRS.

BACKGROUND: The gut is an important target organ of injury during critically ill conditions. Although Gram staining is a common and quick method for identifying bacteria, its clinical application has not been fully evaluated in critically ill conditions. AIMS: This study's aims were to identify patterns of Gram-stained fecal flora and compare them to cultured bacterial counts and to investigate the association between the patterns and septic complications in patients with severe systemic inflammatory response syndrome (SIRS). METHODS: Fifty-two patients with SIRS were included whose Gram-stained fecal flora was classified into three patterns. In a diverse pattern, large numbers of multiple kinds of bacteria completely covered the field. In a single pattern, one specific kind of bacteria or fungi predominantly covered the field. In a depleted pattern, most bacteria were diminished in the field. RESULTS: In the analysis of fecal flora, the numbers of total obligate anaerobes in the depleted pattern was significantly lower than those in the diverse pattern and single pattern (p < 0.05). The concentrations of total organic acids, acetic acid, and propionic acid in the depleted pattern were significantly lower than those in diverse pattern and single pattern (p < 0.05). Mortality due to multiple organ dysfunction syndrome for the single pattern (52%) and the depleted pattern (64%) was significantly higher than that for the diverse pattern (6%) (p < 0.05). CONCLUSIONS: Gram-stained fecal flora can be classified into three patterns and are associated with both cultured bacterial counts and clinical information. Gram-stained fecal bacteria can be used as a quick bedside diagnostic marker for severe SIRS patients.