Renal arteriovenous malformation treated using glue embolization under inflow and outflow control by balloon occlusion.

A 45-year-old female presented with gross hematuria. Right renal arteriovenous malformation on abdominal contrast-enhanced computed tomography necessitated urgent transcatheter arterial embolization. Right renal digital subtraction angiography revealed a single tortuous and dilated vessel converging to an aneurysmal dilated vein. To selectively embolize the malformation, we closed the arterial side with a microballoon and attempted glue embolization; filling occurred unexpectedly early, and another balloon on the vein side helped control the renal vein blood flow. Glue embolization was performed without adverse events. Glue embolization for high-flow arteriovenous malformation under balloon occlusion-mediated inflow and outflow control can effectively and safely embolize complete target vessels.

Prostaglandin E-major urinary metabolites as a new biomarker for acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is an emergent vascular disease caused by cessation of the blood supply to the small intestine. Despite advances in the diagnosis, intervention, and surgical procedures, AMI remains a life-threatening condition. Prostaglandin E2 major urinary metabolite (PGE-MUM), the urinary metabolite of prostaglandin E2, is known to be stable in urine and has been suggested to be a valuable biomarker for intestinal mucosal inflammation, such as ulcerative colitis. We therefore investigated whether or not PGE-MUM levels reflect the degree of ischemia in an intestinal ischemia-reperfusion model. METHODS: Male rats were used to establish a superior mesenteric artery occlusion (SMAO) group, in which the superior mesenteric artery was clamped, and a sham group. The clamping times in the SMAO group were either 30 minutes or 60 minutes, and reperfusion times were either 3 hours or 6 hours, after which PGE-MUM values were measured. RESULTS: The histological injury score of the SMAO (30-minute ischemia and 6-hour reperfusion group, 1.8 ± 0.4; 60-minute ischemia and 6-hour reperfusion group, 4.7 ± 0.5) and were significantly greater than that of the sham group (0.4 ± 0.7, p < 0.05). The PGE-MUM levels in the SMAO group (30-minutes ischemia and 6-hour reperfusion group, 483 ± 256; 60-minutes ischemia and 6-hour reperfusion group, 889 ± 402 ng/mL) were significantly higher than in the sham group (30-minute and 6-hour observation group, 51 ± 20; 60-minute and 6-hour observation group, 73 ± 32 ng/mL; p < 0.05). Furthermore, the PGE-MUM value was corrected by the concentration of urinary creatinine (Cr). The PGE-MUM/urinary Cr levels in the SMAO group were also significantly higher than in the sham group ( p < 0.05). CONCLUSION: We found that intestinal ischemia-reperfusion increased urinary PGE-MUM levels depending on the ischemic time. This suggests the potential utility of PGE-MUM as a noninvasive marker of intestinal ischemia.

Does frailty impact failure-to-rescue in geriatric trauma patients?

BACKGROUND: Failure-to-rescue (FTR), defined as death following a major complication, is a metric of trauma quality. The impact of patient frailty on FTR has not been fully investigated, especially in geriatric trauma patients. This study hypothesized that frailty increased the risk of FTR in geriatric patients with severe injury. METHODS: A retrospective cohort study was conducted using the TQIP database between 2015 and 2019, including geriatric patients with trauma (age ≥65 years) and an Injury Severity Score (ISS) > 15, who survived ≥48 hours postadmission. Frailty was assessed using the modified 5-item frailty index (mFI). Patients were categorized into frail (mFI ≥ 2) and nonfrail (mFI < 2) groups. Logistic regression analysis and a generalized additive model (GAM) were used to examine the association between FTR and patient frailty after controlling for age, sex, type of injury, trauma center level, ISS, and vital signs on admission. RESULTS: Among 52,312 geriatric trauma patients, 34.6% were frail (mean mFI: frail: 2.3 vs. nonfrail: 0.9, p < 0.001). Frail patients were older (age, 77 vs. 74 years, p < 0.001), had a lower ISS (19 vs. 21, p < 0.001), and had a higher incidence of FTR compared with nonfrail patients (8.7% vs. 8.0%, p = 0.006). Logistic regression analysis revealed that frailty was an independent predictor of FTR (odds ratio, 1.32; confidence interval, 1.23-1.44; p < 0.001). The GAM plots showed a linear increase in FTR incidence with increasing mFI after adjusting for confounders. CONCLUSION: This study demonstrated that frailty independently contributes to an increased risk of FTR in geriatric trauma patients. The impact of patient frailty should be considered when using FTR to measure the quality of trauma care. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Analysis of lipid metabolites derived from gut microbiota in ischemia-reperfusion model.

BACKGROUND: Disruption of intestinal barrier caused by intestinal ischemia due to hemorrhagic shock is associated with the pathogenesis of multiple organ dysfunction (MOD) after severe trauma. Mesenteric lymph (ML) plays an important role as a route for transporting inflammatory mediators, including lipids. Postbiotics, such as 10-hydroxy-cis-12-octadecenoic acid (HYA), have received much attention as a treatment option. However, the relationship between postbiotics and MOD has yet to be clarified. The aim of the present study was to analyze lipid metabolites derived from gut microbiota in the intestinal ischemia-reperfusion (IR) rat model. METHODS: Male Sprague-Dawley rats underwent laparotomy, and their ML duct and superior mesenteric artery were exposed. The superior mesenteric artery was clamped for 60 minutes, followed by 120 minutes of reperfusion. The ML and the plasma were collected before and after intestinal IR. Lipids were extracted from plasma and ML, and liquid chromatography-tandem mass spectrometry was performed. RESULTS: The concentration of linoleic acid in plasma samples was not different before and after IR; however, the linoleic acid concentration in the ML samples increased after intestinal IR. Eicosapentaenoic acids and docosahexaenoic related to linoleic acids showed similar changes with IR-induced increase in the ML. The concentration of HYA, a linoleic acid-derived bioactive metabolite produced by gut bacteria, was high in ML samples, while that in plasma samples was low. The relative increase rate of HYA in ML samples after IR was higher than that of the plasma samples (the ML samples: relative increase, 3.23 ± 1.36; the plasma samples: relative increase, 0.95 ± 0.35; n = 3, p = 0.048). CONCLUSION: The present study demonstrated increased linoleic acids and high concentrations of HYA, lipid metabolites derived from gut bacteria in the ML after intestinal IR. These findings may contribute to clarifying the relation between gut microbiota and MOD after severe trauma.

A case of blindness caused by Lemierre's syndrome.

Key Clinical Message: We describe a patient who lost her vision because of Lemierre's syndrome. Ophthalmologic complications of Lemierre's syndrome are rare, and very few cases have been reported. Clinicians need to recognize that it is a serious condition that can lead to blindness in some cases. Abstract: Lemierre's syndrome is a systemic septic embolism resulting from thrombophlebitis of the internal jugular vein. We report a case of blindness caused by Lemierre's syndrome, despite prompt diagnosis and early treatment. A 36-year-old woman was transported to our hospital. She presented with fever, facial swelling, and right visual acuity deterioration. Contrast-enhanced computed tomography revealed a retropharyngeal abscess and right internal jugular vein thrombosis. Blood culture revealed Fusobacterium necrophorum, suggesting Lemierre's syndrome. The patient had septic shock and disseminated intravascular coagulation. We diagnosed her visual impairment as orbital-apex syndrome due to spread of inflammation. After 6 weeks of antimicrobial drug treatments, her general condition had improved, and the retropharyngeal abscess had disappeared. On Day 49 of her illness, she was transferred to a rehabilitation hospital, but her visual acuity was not restored. Clinicians should be aware that Lemierre's syndrome can, although rarely, cause blindness.

Association between body mass index and clinical outcomes in patients with out-of-hospital cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation: A multicenter observational study.

Background: We examined the association between body mass index (BMI) and outcomes in patients with out-of-hospital cardiac arrest (OHCA) undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: We retrospectively analyzed the database of an observational multicenter cohort in Japan. Adult patients with OHCA of cardiac etiology who received ECPR between 2013 and 2018 were categorized as follows: underweight, BMI < 18.5; normal weight, BMI = 18.5-24.9; overweight, BMI = 25-29.9; and obese, BMI ≥ 30 kg/m2. The primary outcome was in-hospital mortality; secondary outcomes were unfavorable neurological outcomes at discharge (cerebral performance category ≥ 3) and ECPR-related complications. BMI's association with outcomes was assessed using a logistic regression model adjusted for age, sex, comorbidities, witness/bystander CPR, initial rhythm, prehospital return of spontaneous circulation, and low-flow time. Results: In total, 1,044 patients were analyzed. Their median age was 61 (IQR, 49-69) years; the median BMI was 24.2 (21.5-26.9) kg/m2. The overall rates of in-hospital mortality, unfavorable neurological outcome, and ECPR-related complications were 62.2%, 79.9%, and 31.7%, respectively. In multivariate analysis, the overweight and obese groups had higher in-hospital mortality odds than the normal BMI group (odds ratio [95%CI], 1.37 [1.02-1.85], p = 0.035; and 2.09 [1.31-3.39], p < 0.001, respectively). The odds ratio for unfavorable neurological outcomes increased more in the obese than in the normal BMI group (3.17 [1.69-6.49], p < 0.001). ECPR-related complications were not significantly different among groups. Conclusions: In OHCA patients undergoing ECPR, a BMI ≥ 25 kg/m2 was associated with increased in-hospital mortality, and a BMI ≥ 30 kg/m2 was also associated with a worse neurological outcome.

Profiles of lipid, protein and microRNA expression in exosomes derived from intestinal epithelial cells after ischemia-reperfusion injury in a cellular hypoxia model.

Intestinal ischemia-reperfusion injury leads to proinflammatory responses via gut-derived mediators, and accumulating evidence suggests that exosomes secreted by intestinal epithelial cells are involved in the development of systemic inflammation. Studies have reported changes in protein, lipid, and microRNA (miRNA) expression; however, considering the different experimental conditions, information on the relationships among these biomolecules remains insufficient. The aim of this study was to elucidate the multiple changes that simultaneously occur in exosomes after ischemic stimulation. Here, differentiated human intestinal Caco-2 cells were exposed to 95% air (normoxia group) or 5% O2 (hypoxia group) for 6 h. Cells in each group were subsequently incubated for 24 h in an atmosphere of 5% CO2 plus 95% air. The conditioned medium of each group was collected for isolating intestinal epithelial cell-derived exosomes. Together with proteome analyses, lipid analyses, and miRNA quantification, biological functional assays were performed using monocytic NF-κB reporter cells. Lipid metabolism-related protein expression was upregulated, miRNA levels were slightly altered, and unsaturated fatty acid-containing lysophosphatidylcholine concentration increased after hypoxia and reoxygenation injury; this suggested that the changes in exosomal components associated with ischemia-reperfusion injury activates inflammation, including the NF-κB pathway. This study elucidated the multiple changes that co-occur in exosomes after ischemic stimulation and partially clarified the mechanism underlying exosome-mediated inflammation after intestinal ischemic recanalization.

Case volume and rate are associated with outcomes in geriatric trauma: A case for geriatric trauma centers?

BACKGROUND: Increased morbidity and mortality in geriatric trauma patients are usually due to decreased physiologic reserve and increased comorbidities. It is unclear whether geriatric trauma case volume and rates correlate with survival. We hypothesized that geriatric patients would have increased survival when treated in high-case volume and rate trauma centers. METHODS: A retrospective cohort study was conducted using the Trauma Quality Improvement Program database between 2015 and 2019. Geriatric trauma patients (≥65 years) with severe injury (Injury Severity Score ≥16) were included. Geriatric case volume (GCV) was defined as the mean annual number of treated geriatric trauma patients, while geriatric case rate (GCR) was the mean annual number of elderly trauma patients divided by all trauma patients in each center. Trauma centers were classified into low-, medium-, and high-volume and rate facilities based on GCV and GCR. The association of GCV and GCR with in-hospital mortality and complication rates was assessed using the generalized additive model (GAM) and multivariate generalized linear mixed model adjusted for patient characteristics (age, sex, Injury Severity Score, Revised Trauma Score, and Modified Frailty Index) as fixed-effect variables and hospital characteristics as random effect variables. RESULTS: A total of 164,818 geriatric trauma patients from 812 hospitals were included in the analysis. The GAM plots showed that the adjusted odds of in-hospital mortality decreased as GCV and the GCR increased. The generalized linear mixed model revealed that both high GCV and high GCR hospitals had lower mortality rates than low GCV and GCR hospitals (adjusted odds ratio [95% confidence interval], high GCV and high GCR centers; 0.82 [0.72-0.92] and 0.81 [0.73-0.90], respectively). CONCLUSION: Both high geriatric trauma volume and rates were associated with decreased mortality of geriatric trauma patients. Consolidation of care for elderly patients with severe injury in specialized high-volume centers may be considered. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 µg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Clinical Benefits of Early Concurrent Use of Cryoprecipitate and Plasma Compared With Plasma Only in Bleeding Trauma Patients.

OBJECTIVES: The effectiveness of cryoprecipitate (Cryo) in trauma has not been well established; the benefits of Cryo might have been overestimated in previous studies since the difference in the total amount of administered clotting factors was not considered. We aimed to evaluate the benefits of the concurrent use of Cryo in combination with fresh frozen plasma (FFP) for bleeding trauma patients. DESIGN: Retrospective cohort study. SETTING: The American College of Surgeons Trauma Quality Improvement Program database between 2015 and 2019. PATIENTS: Patients who received greater than or equal to 5 units of packed RBCs and at least 1 unit of FFP within the first 4 hours after arrival to a hospital were included and dichotomized according to whether Cryo was used within the first 4 hours of hospital arrival. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The outcomes of patients treated with Cryo and FFP were compared with those treated with FFP only using propensity score-matching analysis. The dose of administered clotting factors in each group was balanced. The primary outcome was inhospital mortality, and the secondary outcome was the occurrence rate of adverse events. A total of 24,002 patients (Cryo+FFP group: 6,018; FFP only group: 17,984) were eligible for analysis, of whom 4,852 propensity score-matched pairs were generated. Significantly lower inhospital mortality (1,959 patients [40.4%] in the Cryo+FFP group vs 2,142 patients [44.1%] in the FFP only group; odds ratio [OR], 0.86; 95% CI, 0.79-0.93) was observed in the Cryo+FFP group; no significant difference was observed in the occurrence rate of adverse events (1,857 [38.3%] vs 1,875 [38.6%]; OR, 1.02; 95% CI, 0.94-1.10). Several sensitivity analyses showed similar results. CONCLUSIONS: Cryo use combined with FFP was significantly associated with reduced mortality in bleeding trauma patients. Future randomized controlled trials are warranted to confirm these results.

Life-saving case of cardiopulmonary arrest by secondary aortoenteric fistula formed in the anastomotic site between the inferior mesenteric artery and aortic graft.

Background: Secondary aortoenteric fistula is a fatal cause of gastrointestinal bleeding after aortic reconstructive surgery with a prosthesis. In most cases, the proximal suture line is involved. We herein report a rare case in which the fistula formed between the suture line of inferior mesenteric artery reimplantation and the jejunum. Case Presentation: An 82-year-old man was transferred to our hospital due to hematemesis with severe hypovolemic shock. Although he fell into cardiopulmonary arrest, immediate resuscitation achieved return of spontaneous circulation. As his surgical history of aortic reconstruction and computed tomography findings suggested potential secondary aortoenteric fistula, emergency surgery was carried out. The anastomosis between the inferior mesenteric artery and aortic graft was communicating with the jejunum. Partial jejunal resection was undertaken, and the aortic graft was replaced. Conclusion: The anastomosis between the inferior mesenteric artery and aortic graft in the previous aortic replacement can become the site of secondary aortoenteric fistula.

Association between the plasma-to-red blood cell ratio and survival in geriatric and non-geriatric trauma patients undergoing massive transfusion: a retrospective cohort study.

BACKGROUND: The benefits of a high plasma-to-red blood cell (RBC) ratio on the survival of injured patients who receive massive transfusions remain unclear, especially in older patients. We aimed to investigate the interaction of age with the plasma-to-RBC ratio and clinical outcomes of trauma patients. METHODS: In this retrospective study conducted from 2013 to 2016, trauma patients who received massive transfusions were included. Using a generalized additive model (GAM),we assessed how the plasma-to-RBC ratio and age affected the in-hospital mortality rates. The association of the plasma-to-RBC ratio [low (< 0.5), medium (0.5-1.0), and high (≥ 1.0)] with in-hospital mortality and the incidence of adverse events were assessed for the overall cohort and for patients stratified into non-geriatric (16-64 years) and geriatric (≥ 65 years) groups using logistic regression analyses. RESULTS: In total, 13,894 patients were included. The GAM plot of the plasma-to-RBC ratio for in-hospital mortality demonstrated a downward convex unimodal curve for the entire cohort. The low-transfusion ratio group was associated with increased odds of in-hospital mortality in the non-geriatric cohort [odds ratio 1.38, 95% confidence interval (CI) 1.22-1.56]; no association was observed in the geriatric group (odds ratio 0.84, 95% CI 0.62-1.12). An increase in the transfusion ratio was associated with a higher incidence of adverse events in the non-geriatric and geriatric groups. CONCLUSION: The association of the non-geriatric age category and plasma-to-RBC ratio for in-hospital mortality was clearly demonstrated. However, the relationship between the plasma-to-RBC ratio with mortality among geriatric patients remains inconclusive.

Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury.

BACKGROUND: Inflammatory lipid mediators in mesenteric lymph (ML), including arachidonic acid (AA), are considered to play an important role in the pathogenesis of multiple-organ dysfunction after hemorrhagic shock. A previous study suggested that vagus nerve stimulation (VNS) could relieve shock-induced gut injury and abrogate ML toxicity, resulting in the prevention of multiple-organ dysfunction. However, the detailed mechanism of VNS in lymph toxicity remains unclear. The study aimed to investigate the relationship between VNS and inflammatory lipid mediators in ML. METHODS: Male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery obstruction (SMAO) for 60 minutes to induce intestinal ischemia followed by reperfusion and observation. The ML duct was cannulated, and ML samples were obtained both before and after SMAO. The distal ileum was removed at the end of the observation period. In one group of animals, VNS was performed from 10 minutes before 10 minutes after SMAO (5 V, 0.5 Hz). Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of AA was performed for each ML sample. The biological activity of ML was examined using a monocyte nuclear factor κ-light-chain-enhancer of activated B cells activation assay. Western blotting of phospholipase A2 group IIA (PLA2-IIA) was also performed for ML and ileum samples. RESULTS: Vagus nerve stimulation relieved the SMAO-induced histological gut injury. The concentration of AA and level of nuclear factor κ-light-chain-enhancer of activated B cells activation in ML increased significantly after SMAO, whereas VNS prevented these responses. Western blotting showed PLA2-IIA expression in the ML and ileum after SMAO; however, the appearance of PLA2-IIA band was remarkably decreased in the samples from VNS-treated animals. CONCLUSION: The results suggested that VNS could relieve gut injury induced by SMAO and decrease the production of AA in ML by altering PLA2-IIA expression in the gut and ML.

Physician-led prehospital management is associated with reduced mortality in severe blunt trauma patients: a retrospective analysis of the Japanese nationwide trauma registry.

BACKGROUND: Although the results of previous studies suggested the effectiveness of physician-led prehospital trauma management, it has been uncertain because of the limited number of high-quality studies. Furthermore, the advantage of physician-led prehospital management might have been overestimated due to the shortened prehospital time by helicopter transportation in some studies. The present study aimed to evaluate the effect of physician-led prehospital management independent of prehospital time. Also, subgroup analysis was performed to explore the subpopulation that especially benefit from physician-led prehospital management. METHODS: This retrospective cohort study analyzed the data of Japan's nationwide trauma registry. Severe blunt trauma patients, defined by Injury Severity Score (ISS) ≥16, who were transported directly to a hospital between April 2009 and March 2019 were evaluated. In-hospital mortality was compared between groups dichotomized by the occupation of primary prehospital healthcare provider (i.e., physician or paramedic), using 1:4 propensity score-matched analysis. The propensity score was calculated using potential confounders including patient demographics, mechanism of injury, vital signs at the scene of injury, ISS, and total time from injury to hospital arrival. Subpopulations that especially benefit from physician-led prehospital management were explored by assessing interaction effects between physician-led prehospital management and patient characteristics. RESULTS: A total of 30,551 patients (physician-led: 2976, paramedic-led: 27,575) were eligible for analysis, of whom 2690 propensity score-matched pairs (physician-led: 2690, paramedic-led: 10,760) were generated and compared. Physician-led group showed significantly decreased in-hospital mortality than paramedic-led group (in-hospital mortality: 387 [14.4%] and 1718 [16.0%]; odds ratio [95% confidence interval] = 0.88 [0.78-1.00], p = 0.044). Patients with age < 65 years, ISS ≥25, Abbreviated Injury Scale in pelvis and lower extremities ≥3, and total prehospital time < 60 min were likely to benefit from physician-led prehospital management. CONCLUSIONS: Physician-led prehospital trauma management was significantly associated with reduced in-hospital mortality independent of prehospital time. The findings of exploratory subgroup analysis would be useful for the future research to establish efficient dispatch system of physician team.

Open-chest versus closed-chest cardiopulmonary resuscitation in trauma patients with signs of life upon hospital arrival: a retrospective multicenter study.

BACKGROUND: The effectiveness and indications of open-chest cardiopulmonary resuscitation (OCCPR) have been still debatable. Although current guidelines state that the presence of signs of life (SOL) is an indication for OCCPR, scientific evidence corroborating this recommendation has been scarce. This study aimed to compare the effectiveness of OCCPR to closed-chest cardiopulmonary resuscitation (CCCPR) in severe trauma patients with SOL upon arrival at the emergency department (ED). METHODS: A retrospective cohort study analyzing data from the Trauma Quality Improvement Program (TQIP) database, a nationwide trauma registry in the USA, between 2010 and 2016 was conducted. Severe trauma patients who had SOL upon arrival at the hospital and received cardiopulmonary resuscitation within the first 6 h of ED admission were identified. Survival to hospital discharge was evaluated using logistic regression analysis, instrumental variable analysis, and propensity score matching analysis adjusting for potential confounders. RESULTS: A total of 2682 patients (OCCPR 1032; CCCPR 1650) were evaluated; of those 157 patients (15.2%) in the OCCPR group and 193 patients (11.7%) in the CCCPR group survived. OCCPR was significantly associated with higher survival to hospital discharge in both the logistic regression analysis (adjusted odds ratio [95% confidence interval] = 1.99 [1.42-2.79], p <  0.001) and the instrumental variable analysis (adjusted odds ratio [95% confidence interval] = 1.16 [1.02-1.31], p = 0.021). In the propensity score matching analysis, 531 matched pairs were generated, and the OCCPR group still showed significantly higher survival at hospital discharge (89 patients [16.8%] in the OCCPR group vs 58 patients [10.9%] in the CCCPR group; odds ratio [95% confidence interval] = 1.66 [1.13-2.42], p = 0.009). CONCLUSIONS: Compared to CCCPR, OCCPR was associated with significantly higher survival at hospital discharge in severe trauma patients with SOL upon ED arrival. Further studies to confirm these results and to assess long-term neurologic outcomes are needed.

The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation.

BACKGROUND: Intestinal ischemia caused by hemorrhagic shock is known to induce systemic inflammatory responses. Previous studies have shown that mesenteric lymph (ML) plays a crucial role in gut-mediated inflammation. Lipid mediators, such as lysophosphatidylcholines (LPCs), which contain polyunsaturated fatty acids (PUFAs), are present in the postshock ML. Exosomes are also present in the ML and act as transcellular carriers of lipids; however, their role in postshock systemic inflammation has not been revealed. Here, we aimed to identify changes in lipid mediators in ML exosomes after intestinal ischemia. METHODS: Male Sprague-Dawley rats underwent laparotomy, followed by ML duct cannulation. Animals were subjected to 60 minutes of intestinal ischemia by superior mesenteric artery clamping, followed by 120 minutes of reperfusion. Mesenteric lymph was obtained before and after intestinal ischemia, and exosomes were isolated from ML by ultracentrifugation. The biological activity of ML exosomes was determined using the monocyte nuclear factor κB (NF-κB) activation assay. Lipids of ML exosomes were extracted and quantified by liquid chromatography/electrospray ionization mass spectrometry. RESULTS: Mesenteric lymph exosome-induced NF-κB activation significantly increased after intestinal ischemia, and lipid analysis revealed a significant increase in the concentration of PUFA-containing LPCs. In addition, PUFA-containing LPCs also induced NF-κB activation. CONCLUSION: Our results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia.

Electrical stimulation of the vagus nerve improves intestinal blood flow after trauma and hemorrhagic shock.

BACKGROUND: Gut damage after trauma/hemorrhagic shock contributes to multiple organ dysfunction syndrome. Electrical vagal nerve stimulation is known to prevent gut damage in animal models of trauma/hemorrhagic shock by altering the gut inflammatory response; however, the effect of vagal nerve stimulation on intestinal blood flow, which is an essential function of the vagus nerve, is unknown. This study aimed to determine whether vagal nerve stimulation influences the abdominal vagus nerve activity, intestinal blood flow, gut injury, and the levels of autonomic neuropeptides. METHODS: Male Sprague Dawley rats were anesthetized, and the cervical and abdominal vagus nerves were exposed. One pair of bipolar electrodes was attached to the cervical vagus nerve to stimulate it; another pair of bipolar electrodes were attached to the abdominal vagus nerve to measure action potentials. The rats underwent trauma/hemorrhagic shock (with maintenance of mean arterial pressure of 25 mmHg for 30 min) without fluid resuscitation and received cervical vagal nerve stimulation post-injury. A separate cohort of animals were subjected to transection of the abdominal vagus nerve (vagotomy) just before the start of cervical vagal nerve stimulation. Intestinal blood flow was measured by laser Doppler flowmetry. Gut injury and noradrenaline level in the portal venous plasma were also assessed. RESULTS: Vagal nerve stimulation evoked action potentials in the abdominal vagus nerve and caused a 2-fold increase in intestinal blood flow compared to the shock phase (P < .05). Abdominal vagotomy eliminated the effect of vagal nerve stimulation on intestinal blood flow (P < .05). Vagal nerve stimulation protected against trauma/hemorrhagic shock -induced gut injury (P < .05), and circulating noradrenaline levels were decreased after vagal nerve stimulation (P < .05). CONCLUSION: Cervical vagal nerve stimulation evoked abdominal vagal nerve activity and relieved the trauma/hemorrhagic shock-induced impairment in intestinal blood flow by modulating the vasoconstriction effect of noradrenaline, which provides new insight into the protective effect of vagal nerve stimulation.

Comparison of diagnostic accuracy for nonocclusive mesenteric ischemia in models with biomarkers including intestinal fatty acid-binding protein in addition to clinical findings.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is an acute and life-threatening gastrointestinal disorder, requiring rapid therapeutic intervention for ischemic bowel. However, its rapid detection remains challenging. This retrospective, observational study was aimed at comparing the diagnostic accuracy for NOMI in models of biomarkers, including intestinal fatty acid-binding protein (I-FABP), and clinical findings. METHODS: All consecutive patients who presented to the emergency department of the study hospital with suspected NOMI were prospectively enrolled. Receiver operating characteristic analysis compared the diagnostic accuracy of I-FABP with traditional biomarkers (white blood cell count, C-reactive protein, lactate, creatine kinase, and D-dimer) alone and in combination with the baseline model established from clinical findings. RESULTS: Of 96 patients with suspected NOMI, 25 (26.0%) were clinically diagnosed with NOMI. In-hospital mortality was higher in patients with NOMI than those with other conditions (56.0% vs. 4.2%, p < 0.001). Receiver operating characteristic analyses revealed that the I-FABP model had the highest area under the curve (0.805) in the diagnosis of NOMI, compared with other biomarkers. The diagnostic model of clinical findings including age, cardiovascular disease history, undergoing hemodialysis, hypotension, and consciousness disturbance in combination with I-FABP showed the best discrimination (area under the curve, 0.883), compared with other biomarkers. The bootstrap optimism estimate showed the lowest discrimination among the other models with other biomarkers (0.006). CONCLUSION: The usefulness of I-FABP for final diagnosis of NOMI in patients with clinically suspected NOMI at the emergency department was internally validated. Further external validation study is warranted. LEVEL OF EVIDENCE: Diagnostic test, level III.

Age-Related Characteristics and Outcomes for Patients With Severe Trauma: Analysis of Japan's Nationwide Trauma Registry.

STUDY OBJECTIVE: Although geriatric trauma patients are becoming more common, few large-scale analyses have comprehensively evaluated geriatric-specific characteristics in trauma. This study aims to clarify the age-specific characteristics, outcomes, and predictive accuracy of current trauma scoring systems among geriatric trauma patients. METHODS: Patients with severe trauma, with an Abbreviated Injury Scale score greater than or equal to 3, and registered in the Japan Trauma Data Bank during 2004 to 2015 were retrospectively reviewed. Age-related differences were assessed for injury mechanism, injured region, anatomic and physiologic severity, and inhospital mortality. The mortality risk was evaluated with multivariate mixed-effect models adjusted for Injury Severity Score, Revised Trauma Score, year of injury, and treating facility. Age-related differences in the accuracy of the Injury Severity Score and Revised Trauma Score for predicting inhospital mortality were evaluated with an area under the receiver operating characteristic curve. RESULTS: We identified 127,303 patients, including 67,316 geriatric patients (52.9%) who were aged 60 years or older. The percentage of geriatric patients increased from 31.9% to 59.7% during the study period. The most frequent injury mechanism was ground-level falls (55.2%) and the most frequently injured region was the pelvis and lower extremities (43.7%). Severity-adjusted mixed-effects models revealed a marked age-dependent increase in mortality. Although the Injury Severity Score had similar predictive accuracy among all generations, the accuracy of the Revised Trauma Score decreased with increasing age. CONCLUSION: The characteristics of trauma patients varied widely according to age, and mortality risk increased steadily with increasing age, despite a decrease in anatomic injury severity. The Revised Trauma Score had decreasing predictive accuracy at older ages, suggesting that an alternative measure is needed.

Gut epithelial cell-derived exosomes trigger posttrauma immune dysfunction.

BACKGROUND: Exosomes are extracellular vesicles that act as endogenous mediators of the immune response. We have previously shown that exosomes released into mesenteric lymph (ML) following trauma (T)/hemorrhagic shock (HS) induce proinflammatory cytokine production in macrophages and are involved in the pathogenesis of postshock acute lung injury. However, the cellular origin of ML exosomes and their role in the posttrauma immune response remains unclear. We hypothesized that exosomes released from damaged-intestinal epithelial cells contribute to posttrauma immune dysfunction by altering the function of dendritic cells (DCs), key regulators of the adaptive immunity. METHODS: Male rats underwent cannulation of the femoral artery, jugular vein and ML duct. T/HS was induced by laparotomy and 60 minutes of hemorrhagic shock followed by resuscitation. The ML was collected before (preshock) and after T/HS (post-T/HS) for isolation of exosomes. Surface epitopes of exosomes isolated from ML were assessed by flow cytometry to determine their cellular origin and phenotypic changes. The immunomodulatory effects of ML exosomes on DCs were assessed by Annexin V apoptosis assay, expression of costimulatory molecules, and antigen-presenting capacity to lymphocytes. RESULTS: Exosomes isolated from ML highly expressed CD63 (exosome marker) and epithelial cell-specific marker, suggesting their derivation from intestinal epithelial cells. The expression of immunomodulatory molecules, such as major histocompatibility complex class II and Fas ligand on ML exosomes, was significantly increased after T/HS. Coincubation of DCs with exosomes isolated from ML after T/HS increased DC apoptosis twofold compared with preshock ML exosomes. Furthermore, post-T/HS ML exosomes significantly suppressed lipopolysaccharide-mediated expression of CD80 and CD86 on DCs as well as decreased their antigen-presenting capacity to induce lymphocytes proliferation. CONCLUSION: Gut epithelial cells release immunomodulatory exosomes into the ML after T/HS and resuscitation. Mesenteric lymph exosomes may be critical mediators of posttraumatic immunosuppression causing depletion and dysfunction of DCs.