Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury.

While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct-with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in a rat model. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expression of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

A new multiple trauma model of the mouse.

BACKGROUND: Blunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls. Two of the most frequent injuries in patients with multiple trauma are chest trauma and extremity fracture. Several trauma mouse models combine chest trauma and head injury, but no trauma mouse model to date includes the combination of long bone fractures and chest trauma. Outcome is essentially determined by the combination of these injuries. In this study, we attempted to establish a reproducible novel multiple trauma model in mice that combines blunt trauma, major injuries and simple practicability. METHODS: Ninety-six male C57BL/6 N mice (n = 8/group) were subjected to trauma for isolated femur fracture and a combination of femur fracture and chest injury. Serum samples of mice were obtained by heart puncture at defined time points of 0 h (hour), 6 h, 12 h, 24 h, 3 d (days), and 7 d. RESULTS: A tendency toward reduced weight and temperature was observed at 24 h after chest trauma and femur fracture. Blood analyses revealed a decrease in hemoglobin during the first 24 h after trauma. Some animals were killed by heart puncture immediately after chest contusion; these animals showed the most severe lung contusion and hemorrhage. The extent of structural lung injury varied in different mice but was evident in all animals. Representative H&E-stained (Haematoxylin and Eosin-stained) paraffin lung sections of mice with multiple trauma revealed hemorrhage and an inflammatory immune response. Plasma samples of mice with chest trauma and femur fracture showed an up-regulation of IL-1ß (Interleukin-1ß), IL-6, IL-10, IL-12p70 and TNF-α (Tumor necrosis factor- α) compared with the control group. Mice with femur fracture and chest trauma showed a significant up-regulation of IL-6 compared to group with isolated femur fracture. CONCLUSIONS: The multiple trauma mouse model comprising chest trauma and femur fracture enables many analogies to clinical cases of multiple trauma in humans and demonstrates associated characteristic clinical and pathophysiological changes. This model is easy to perform, is economical and can be used for further research examining specific immunological questions.

[Possibilities of correction rheological blood svoytv at chipped and cut wounds of the breast ].

The purpose: research objective: to study influence of electromagnetic oscillations of millimetric range on rheological properties of blood at patients with chipped and cut wounds of a breast for the purpose of their correction. Methods. For the solution of a research objective we have carried out studying of changes of rheological properties of blood at the 22nd patient with the getting chipped and cut wounds of a breast without internal injury during the next postoperative period. All patient has executed primary surgical processing and drainage of a pleural cavity. At all patients the volume of blood loss has made 200-500 ml. Criteria of inclusion were: existence of the getting wound of a thorax, existence of a small gemotoraks. Criteria of an exception: blood loss existence more than 500 ml, existence of the combined and multiple damages. The main group is divided into two subgroups, in the first 12 patients with application of electromagnetic oscillations of millimetric range, have entered the second 10 people without application of electromagnetic oscillations of millimetric range. The group of comparison was made by 15 rather healthy donor volunteers of the same age and a floor. To all patients the hemotransfusion wasn't carried out, the volume of infusional therapy was comparable in both groups. Changes of a rheology of blood came to light by means of the accounting of viscosity of blood, change of an index of deformation and aggregation of erythrocytes. Conclusion. As a result of the conducted research it is established that application of electromagnetic oscillation of millimetric range for patients with chipped and cut wounds of a breast prevents development of changes of rheological properties of blood, at the same time patients well transfer this procedure that is shown by lack of side effects.

A new aortic injury score predicts early rupture more accurately than clinical assessment.

OBJECTIVE: The optimal timing for repair of a high-grade blunt thoracic aortic injury (BTAI) is uncertain. Delayed repair is common and associated with improved outcomes, but some lesions may rupture during observation. To determine optimal patient selection for appropriate management, we developed a pilot clinical risk score to evaluate aortic stability and predict rupture. METHODS: Patients presenting in stable condition with Society for Vascular Surgery grade III or IV BTAI diagnosed on computed tomography (CT) were retrospectively reviewed. To determine clinical and radiographic factors associated with aortic rupture, patients progressing to aortic rupture (defined by contrast extravasation on CT or on operative or autopsy findings) were compared with those who had no intervention ≤48 hours of admission. A model targeting 100% sensitivity for rupture was generated and internally validated by bootstrap analysis. Clinical utility was tested by comparison with clinical assessment by surgeons experienced in BTAI management who were provided with CT images and clinical data but were blinded to outcome. RESULTS: The derivation cohort included 18 patients whose aorta ruptured and 31 with stable BTAI. There was no difference in age, gender, injury mechanism, nonchest injury severity, blood pressure, or Glasgow Coma Scale on admission between patient groups. As dichotomous factors, admission lactate >4 mM, posterior mediastinal hematoma >10 mm, and lesion/normal aortic diameter ratio >1.4 on the admission CT were independently associated with aortic rupture. The model had an area under the receiver operator curve of .97, and in the presence of any two factors, was 100% sensitive and 84% specific for predicting aortic rupture. No aortic lesions ruptured in patients with fewer than two factors. In contrast, clinical assessment had lower accuracy (65% vs 90% total accuracy, P < .01). CONCLUSIONS: This novel risk score can be applied on admission using clinically relevant factors that incorporate patient physiology, size of the aortic lesion, and extent of the mediastinal hematoma. The model reliably identifies and distinguishes patients with high-grade BTAI who are at risk for early rupture from those with stable lesions. Although preliminary, because it is more accurate than clinical assessment alone, the score may improve patient selection for emergency or delayed intervention.

Plasma levels of high mobility group box 1 increase in patients with posttraumatic stress disorder after severe blunt chest trauma: a prospective cohort study.

BACKGROUND: High-mobility group box 1 (HMGB1), a key late mediator of systemic inflammation, is a potentially useful biomarker for predicting outcome in patients with severe blunt chest trauma. The purpose of this study was to define the relationship between plasma levels of HMGB1 and posttraumatic stress disorder (PTSD) in patients with severe blunt chest trauma. METHODS: All patients with severe blunt chest trauma (abbreviated injury score ≥3) who were admitted to traumatic surgery department and ultimately survived to follow-up at 6 mo were eligible for the study. HMGB1 was sampled every other day from day 1-day 7 after admission, and plasma concentrations of HMGB1 were measured by a quantitative enzyme-linked immunosorbent assay test. Multivariate regression analysis was used to define the independent contribution of possible risk factors selected by univariate analysis. RESULTS: PTSD was identified in 43 patients including acute PTSD (n = 21), chronic PTSD (n = 18), and delayed-onset PTSD (n = 4) after 6-mo follow-up, in whom significant higher plasma levels of HMGB1 on days three, five, and seven after blunt chest trauma were noted compared with those seen in patients without PTSD (n = 10). Multivariate logistic analysis showed that transfusion, injury severity score, and HMGB1 levels at day 7 were the valuable risk factors for PTSD. CONCLUSIONS: In blunt chest trauma, plasma HMGB1 levels were significantly higher in patients with PTSD compared with patients with non-PTSD. Our data indicate that patients with high plasma levels of HMGB1 may be more prone to develop PTSD including acute and chronic PTSD.

[The role of oxidative damage of proteins and lipids in pathogenesis of traumatic disease in severe combined thoracic trauma].

The investigation objective was to study the dynamics of indices of the lipids and proteins oxidative damage, as well as search for possible prognostic criteria in the injured persons with severe combined thoracic trauma. Concentration of carbonyl groups of proteins and malonic dialdehyde was determined on 1-2d, 3-4th and 5-6th day after trauma in the blood plasm of 73 patients, ageing 20 -68 yrs old. While in conditions of massive infusion therapy concentration of the indices investigated do not reflect the oxidative processes intensity. Relative concentration in recalculation on concentration of common protein content constitutes a more demonstratable index. On the 5-6th day after trauma a tendency for normalization of the oxidative damage of lipids and proteins indices was observed in the patients, who have recovered, and while lethal outcome--their further enhancement was noted. There was established a one-direction dynamics of a relative indices in both groups up to 3-4-th day after trauma with a step-by-step its enhancement. Concentration of carbonyl groups of proteins more than 15.86 mcmol/g of protein on the 5-6-th day after trauma ought to be considered a trustworthy criterion of unfavorable prognosis.

Lactate dehydrogenase can be used for differential diagnosis to identify patients with severe polytrauma with or without chest injury-A retrospective study.

BACKGROUND: Chest injury is an important factor regarding the prognosis of patients with polytrauma (PT), and the rapid diagnosis of chest injury is of utmost importance. Therefore, the current study focused on patients' physiology and laboratory findings to quickly identify PT patients with chest injury. METHOD: Data on 64 PT patients treated at a trauma center level I between June 2020 and August 2021 were retrospectively collected. The patients were divided into a PT group without chest injury (Group A) and a PT group including chest injury (Group B). The relationship between chest injury and the patients' baseline characteristics and biochemical markers was analyzed. RESULTS: Heart rate, respiration rate, Sequential Organ Failure Assessment (SOFA) score, glutamate oxaloacetate aminotransferase (GOT), glutamate pyruvate transaminase (GPT), creatine kinase MB (CK-MB), leucocytes, hemoglobin (Hb), platelets, urine output, lactate, and lactate dehydrogenase (LDH) in groups A and B exhibited statistically significant differences at certain time points. Multifactorial analysis showed that blood LDH levels at admission were associated with chest injury (P = 0.039, CI 95% 1.001, 1.022). CONCLUSION: LDH may be a promising indicator for screening for the presence of chest injury in patients with severe polytrauma.

Prognostic indicators in patients with isolated thoracic trauma: A retrospective cross-sectional study.

BACKGROUND: Thoracic trauma is a significant cause of mortality, especially among those arriving at hospitals. This study explores the associations between mortality, the shock index (SI), and specific metabolic and biochemical markers in patients with isolated thoracic trauma. METHODS: This retrospective cross-sectional study included all consecutive adult patients presenting with isolated thoracic trauma to a high-volume emergency department from January 2019 to December 2023. The predictive capability of SI levels and selected biomarkers upon admission for estimating mortality was assessed by determining the areas under the receiver operating characteristic curves (AUCs). Optimal cutoff values were determined using the Youden index method. RESULTS: The study involved 352 patients, with 285 (81%) being males and an average age of 50.0±17.7 years. The mortality rate was 9.6%. Mortality was significantly associated with higher shock index (odds ratio [OR]: 14.02, [95% confidence interval [CI] 0.847-0.916], AUC=0.885, p=0.001), glucose/potassium ratio (OR: 1.24 [95% CI 1.14-1.35], AUC=0.869, p<0.001), and lactate levels (OR: 4.30 [95% CI 2.29-8.07], AUC=0.832, p<0.001). The optimal cutoff values determined for the shock index, glucose/potassium ratio, ionized calcium, and lactate were 1.02 (sensitivity, 94.1%; specificity 69.5%; positive predictive value [PPV], 24.8; negative predictive value [NPV], 99.1), 36.85 (sensitivity, 76.5%; specificity, 87.7%; PPV, 40.0; NPV, 97.2), 1.23 (sensitivity, 94.1%; specificity, 56.0%; PPV, 18.6; NPV, 98.9), and 1.98 (sensitivity, 70.6%; specificity, 80.5%; PPV, 27.9; NPV, 96.2), respectively. CONCLUSION: This study demonstrates that higher shock index, glucose/potassium ratio, and lactate levels are significantly associated with increased mortality in patients with isolated thoracic trauma. These findings suggest that these markers can be effective prognostic indicators, potentially guiding clinical decision-making and improving patient outcomes.

Plasma proteomics profile-based comparison of torso versus brain injury: A prospective cohort study.

BACKGROUND: Trauma-related deaths and posttraumatic sequelae are a global health concern, necessitating a deeper understanding of the pathophysiology to advance trauma therapy. Proteomics offers insights into identifying and analyzing plasma proteins associated with trauma and inflammatory conditions; however, current proteomic methods have limitations in accurately measuring low-abundance plasma proteins. This study compared plasma proteomics profiles of patients from different acute trauma subgroups to identify new therapeutic targets and devise better strategies for personalized medicine. METHODS: This prospective observational single-center cohort study was conducted between August 2020 and September 2021 in the intensive care unit of Osaka University Hospital in Japan. Enrolling 59 consecutive patients with blunt trauma, we meticulously analyzed plasma proteomics profiles in participants with torso or head trauma, comparing them with those of controls (mild trauma). Using the Olink Explore 3072 instrument (Olink Proteomics AB, Uppsala, Sweden), we identified five endotypes (α-ε) via unsupervised hierarchical clustering. RESULTS: The median time from injury to blood collection was 47 minutes [interquartile range, 36-64 minutes]. The torso trauma subgroup exhibited 26 unique proteins with significantly altered expression, while the head trauma subgroup showed 68 unique proteins with no overlap between the two. The identified endotypes included α (torso trauma, n = 8), ß (young patients with brain injury, n = 5), γ (severe brain injury postsurgery, n = 8), δ (torso or brain trauma with mild hyperfibrinolysis, n = 18), and ε (minor trauma, n = 20). Patients with torso trauma showed changes in blood pressure, smooth muscle adaptation, hypermetabolism, and hypoxemia. Patients with traumatic brain injury had dysregulated blood coagulation and altered nerves regeneration and differentiation. CONCLUSION: This study identified unique plasma protein expression patterns in patients with torso trauma and traumatic brain injury, helping categorize five distinct endotypes. Our findings may offer new insights for clinicians, highlighting potential strategies for personalized medicine and improved trauma-related care. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

[Treatment of post-traumatical coagulated hemothorax. Videothoracoscopy or open surgery].

Comparative estimation of videothoracic and open surgery efficacy in the treatment of post-traumatic coagulated hemothorax have been shown in 612 patients. According to the achieved results, effectiveness of videothoracoscopy (92.4%) is better than open surgeries. Apart from that, reduction in the hospitalization days (9.6 days compared to 11.5 days in open surgeries), frequency of complications (4.5% and 13.8%), traumatic intervention and rehabilitation time. All the patients alive. Best results are achieved using videothoracoscopical operations at the earliest in posttraumatic coagulated hemothorax.

Elevated cardiac troponin I level in cases of thoracic nonaccidental trauma.

BACKGROUND: Injury patterns in nonaccidental trauma (NAT) often include injury to the chest. However, signs and symptoms of cardiac insult are often nonspecific and may be missed. Evaluation with serum cardiac troponin I (CTnI), a specific indicator of myocardial injury, could improve the comprehensive evaluation of patients with suspected NAT. OBJECTIVE: The objective of this study was to describe the patient characteristics and results of CTnI testing in children with thoracic NAT. METHODS: Children presenting to the emergency department were included if CTnI was obtained and they had at least one of the following: history of blunt trauma to the chest, bruising or abrasions to the chest, or fractures of the ribs, sternum, or clavicles. A serum CTnI level above 0.04 ng/mL was considered elevated. RESULTS: Ten patients (6 males) with an age range from 2 months to 4 years (mean [SD], 20 [20] months) were identified during the 17-month study period. All patients were evaluated with NAT. Cardiac troponin I level was elevated in 7 (70%) of 10 patients with levels between 2 and 50 times the upper limit of normal. CONCLUSIONS: This report is the first to document elevation of CTnI levels in cases of thoracic NAT. The elevation of the level of this specific biomarker may be indicative of sufficient chest trauma to result in the heart being injured, independent of the presence of cardiac decompensation or shock from other causes. Prospective evaluation of the forensic and clinical use of CTnI in this population is warranted.

[Pulmonary alveolar hemorrhage--a rare complication of isolated thoracic injury]. / Pl'úcna alveolárna hemorágia--zriedkavá komplikácia izolovaného poranenia hrudníka.

Occurrence of Diffuse Alveolar Hemorrhage Syndrome (DAH) after blunt thoracic trauma is rare. It is more common to occure in a immuno deficient patient or in drug dependent people. We present a case of DAH, which occured in young man after blunt thoracic injury. Clinically it was presented by hemoptysis. No respiratory insufficiency was recorded and DAH was treated without need of mechanical pulmonal ventilation.

P-selectin antibody treatment after blunt thoracic trauma prevents early pulmonary arterial thrombosis without changes in viscoelastic measurements of coagulation.

INTRODUCTION: Previously, in a murine model of blunt thoracic trauma, we provided evidence of primary pulmonary thrombosis associated with increased expression of the cell adhesion molecule, P-selectin. In this study, mice are treated with P-selectin blocking antibody after injury to investigate the clinical viability of this antibody for the prevention of pulmonary thrombosis. In addition, viscoelastic testing is performed to investigate if P-selectin inhibition has a detrimental impact on normal hemostasis. METHODS: A murine model of thoracic trauma was used. Mice were divided into sham control and experimental injury groups. Thirty minutes after trauma, mice were treated with the following: P-selectin blocking antibody, isotype control antibody, low-dose heparin, high-dose heparin, or normal saline. At 90 minutes, whole blood was collected for characterization of coagulation by viscoelastic coagulation monitor (VCM Vet; Entegrion, Durham, NC). Mean clotting time, clot formation time, clot kinetics (α angle), and maximum clot firmness were compared between each treatment group. RESULTS: Mice that received P-selectin antibody 30 minutes after blunt thoracic trauma had four- to fivefold less (p < 0.001) arterial fibrin accumulation than those that received the isotype control. In both sham and trauma groups, compared with vehicle (normal saline) alone, no statistical difference was noted in any coagulation parameters after injection with P-selectin antibody, isotype control, or low-dose heparin. In addition, blinded histopathological evaluation yielded no difference in hemorrhage scores between injured mice treated with P-selectin blocking antibody and those treated with isotype antibody control. CONCLUSION: This study supports the clinical use of P-selectin blocking antibody for the prevention of pulmonary thrombosis by confirming its efficacy when given after a blunt thoracic trauma. In addition, we demonstrated that the administration of P-selectin antibody does not adversely affect systemic coagulation as measured by viscoelastic testing, suggesting that P-selectin antibody can be safely given during the acute posttraumatic period.

Serial white blood cell counts in trauma: do they predict a hollow viscus injury?

BACKGROUND: The significance of serial white blood cell (WBC) counts in trauma patients with a suspected hollow viscus injury (HVI) is unknown. The purpose of this study was to examine the role of serial WBC counts in the diagnosis of a HVI. METHODS: After institutional review board approval, all injured patients admitted to a Level I trauma center from January 2003 to December 2007 with at least one WBC measurement were included in a retrospective analysis. The WBC profiles for patients with a HVI were compared against those without HVI. All WBC counts are reported as [x10(3)/microL]. RESULTS: The mean WBC count of the overall study population (n = 5,950) on admission was 11.6 +/- 5.3. Overall, 59.2% had an elevated WBC count on admission. A significant relationship between increasing Injury Severity Score and increasing WBC count on admission was found by linear regression. When comparing patients with HVI (n = 267) with patients without HVI (n = 5,683), no significant difference was found for admission WBC count. The highest WBC count within the first 24 hours for patients with HVI was 16.7 +/- 4.7. This was significantly higher than that for the 4,520 patients without any intraabdominal injury (13.0 +/- 5.2, adjusted p < 0.001). Penetrating injury, a concomitant severe thoracic trauma (chest Abbreviated Injury Scale value >or=3), and highest WBC count >or=20.0 in the first 24 hours were independent risk factors for HVI. A maximal WBC count or=20.0 are independently associated with a HVI, whereas counts

The role of elevated high-sensitivity cardiac troponin on outcomes following severe blunt chest trauma.

BACKGROUND: Blunt cardiac injuries (BCI) result in poor outcomes following chest trauma. Admission ECG and troponin levels are frequently obtained in patients with suspected BCI, nevertheless, the prognostic value of cardiac troponins remains controversial. The purpose of the current study was to review the prognostic value of elevated high-sensitivity cardiac troponin T (hs-cTnT) in patients with severe blunt chest injuries. We hypothesized that elevated hs-cTnT result in poor outcomes in this subgroup of severe trauma patients. METHODS: After IRB approval, all consecutive patients with Injury Severity Score (ISS) > 15 and chest Abbreviated Injury Scale (AIS) score ≥3 admitted to the major trauma centers between 1/2015 and 6/2017 were retrospectively reviewed. Primary outcomes were in-hospital and one-year mortality. Secondary outcomes included ventilator days and Glasgow Outcome Scale (GOS) score at hospital discharge. RESULTS: Overall, 147 patients were included. Mean age was 49.0 (19.1) years and 75% were male. Serum troponin levels on admission were accrued in 82 (56%) patients with elevated and normal hs-cTnT levels found in 54 (66%) and in 28 (34%) patients, respectively. Elevated hs-cTnT group had significantly higher ISS and lactate level, and lower systolic blood pressure on admission. In-hospital mortality was significantly higher in patients with elevated hs-cTnT levels compared to patients with normal hs-cTnT levels (26% vs. 4%, p = 0.02). Hs-cTnT level > 14 ng/L was significantly associated with extended ventilator days and lower GOS score at hospital discharge. CONCLUSION: Blunt chest trauma victims with elevated hs-cTnT levels experience significantly poorer adjusted outcomes compared to patients with normal levels. Compliance with EAST practice management guidelines following severe blunt chest trauma was not fully complied in our study cohort that warrants prospective performance improvement measures.

Increased S-100 B levels are associated with fractures and soft tissue injury in multiple trauma patients.

BACKGROUND: S-100 B protein was identified as a biomarker for traumatic brain injury, but studies suggest that extracranial injuries may also lead to increased S-100 B serum levels. In this study, we aim to quantify the impact of injury patterns on S-100 B levels in patients with suspected multiple trauma. METHODS: Patients with suspected multiple trauma treated at a Level 1 Trauma centre in Switzerland were included in this retrospective patient chart review. Extent of injuries and severity was assessed and S-100 B levels on admission measured. Potential predictors of increased S-100 B levels (>0.2 µg/L) were identified through uni- and multivariable analyses. RESULTS: In total, 1,338 patients with suspected multiple trauma were included. Multivariable logistic regression showed a significant association with increased S-100 B levels in long bone fracture (OR 2.3, 95% CI: 1.3-4.1, p = 0.004), non-long bone fracture (OR 3.0, 95% CI: 2.2-4.3, p<0.001), thoracic injury (OR 2.6, 95% CI: 1.6-4.2, p<0.001), and deep tissue injury/wounds (OR 1.9, 95% CI: 1.4-2.6, p<0.001). Head trauma with intracerebral bleeding was only weakly associated (OR 2.0, 95% CI 1.2-3.5, p = 0.01) and head trauma without intracranial bleeding was not associated with an increased S-100 B protein level (p = 0.71). Trauma severity was also related to increased S-100 B levels (OR per ISS: 1.1, 95% CI 1.0-1.1, p<0.001). S-100 B levels <0.57 µg/L had a high diagnostic value to rule out in-hospital mortality (negative predictive value: 1.0, 95% CI: 0.98-1.00). CONCLUSION: Fractures and thoracic injuries appeared as main factors associated with increased S-100 B levels. Head injury may only play a minor role in S-100 B protein elevation in multiple trauma patients. A normal S-100 B has a good negative predictive value for in-hospital mortality. S100-B levels were associated with trauma severity and might thus be of use as a prognostic marker in trauma patients.

Early local neutralization of CC16 in sepsis­induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival.

Blunt thoracic trauma (TxT) is a common injury pattern in polytraumatized patients. When combined with a secondary trigger, TxT often results in acute lung injury (ALI), which negatively affects outcomes. Recent findings suggest that ALI is caused by both local and systemic inflammatory reactions. Club cell protein (CC)16 is an anti­inflammatory peptide associated with lung injury following TxT. Recently, the anti­inflammatory properties of endogenous CC16 in a murine model of TxT with subsequent cecal­ligation and puncture (CLP) as the secondary hit were demonstrated by our group. The present study aimed to determine whether CC16 neutralization improves survival following 'double­hit'­induced ALI. For this purpose, a total of 120 C57BL/6N mice were subjected to TxT, followed by CLP after 24 h. Sham­operated animals underwent anesthesia without the induction of TxT + CLP. CC16 neutralization was performed by providing a CC16 antibody intratracheally following TxT (early) or following CLP (late). Survival was assessed in 48 animals for 6 days after CLP. Sacrifice was performed 6 or 24 h post­CLP to evaluate the anti­inflammatory effect of CC16. The results revealed that CC16 neutralization enhanced pro­inflammatory CXCL1 levels, thereby confirming the anti­inflammatory characteristics of CC16 in this model. Early CC16 neutralization immediately following TxT significantly prolonged survival within 60 h; however, the survival rate did not change until 6 days post­trauma. Late CC16 neutralization did not provide any survival benefits. On the whole, the present study demonstrated that neutralizing CC16 confirmed its anti­inflammatory potential in this double­hit ALI model. Early CC16 neutralization prolonged survival within 60 h; however, no survival benefits were observed after 6 days post­CLP in any group.

Association between computed tomographic thoracic injury scores and blood gas and acid-base balance in dogs with blunt thoracic trauma.

OBJECTIVE: To determine the association between thoracic injuries evaluated by computed tomography (CT) and arterial blood gas and acid-base status in dogs with blunt thoracic trauma caused by motor vehicle accidents. DESIGN: Prospective observational clinical study. SETTING: University teaching hospital. ANIMALS: Thirty-one client owned traumatized dogs and 15 healthy dogs. PROCEDURES: All trauma group dogs underwent a CT scan and simultaneous arterial blood gas analysis within 24 hours, but not before 4 hours, after the traumatic incident within a 45-month enrollment period. MEASUREMENTS AND MAIN RESULTS: Thorax injuries were classified as pulmonary, pleural space, or rib cage and each of these components was scored for severity using a CT composite pulmonary, pleural, and rib score. The trauma group arterial blood gas and acid-base status were evaluated for statistical difference from the control group. The pulmonary-arterial oxygen pressure was significantly lower in the trauma group compared to the control group that was supported by significant differences in the calculated variables of arterial blood oxygenation as well. There was also a significant correlation between the composite lung score and pleural score and the variables of arterial oxygen status. The pulmonary-arterial carbon dioxide pressure was not significantly different to any of the thoracic injury variables indicating normal alveolar ventilation. Acid-base imbalances were generally mild, insignificant, and variable. CONCLUSIONS AND CLINICAL RELEVANCE: Blunt thoracic trauma causes significant pulmonary and pleural injury and the blood oxygen economy is significantly affected by this. The functional measures of arterial blood oxygenation were well correlated with thoracic CT pathology. Alveolar ventilation was mostly spared but a clinically significant ventilation perfusion mismatch was present.

IL-33 and its increased serum levels as an alarmin for imminent pulmonary complications in polytraumatized patients.

Background: According to recently published findings, we hypothesized that serum interleukin-33 (IL-33) may qualify for predicting pulmonary complications in polytraumatized patients. Methods: One hundred and thirty patients (age ≥ 18 years, ISS ≥ 16) were included in our prospective analysis after primary admission to our level I trauma center during the first post-traumatic hour. Serum samples immediately after admission and on day 2 after trauma were obtained and analyzed. Results: Median initial IL-33 levels (in picograms per milliliter) were higher in polytrauma victims (1) with concomitant thoracic trauma [5.08 vs. 3.52; p = 0.036], (2) sustaining parenchymal lung injury (PLI) [5.37 vs. 3.71; p = 0.027], and (3) developing acute respiratory distress syndrome (ARDS) [6.19 vs. 4.48; p = 0.003], compared to the respective rest of the study group. The median initial IL-33 levels were higher in patients experiencing both PLI and ARDS compared to those sustaining PLI and not developing ARDS [6.99 vs. 4.69; p = 0.029]. ROC statistics provided an AUC of 0.666 (p = 0.003) and a cut-off value of 4.77 (sensitivity, 71.8%; specificity, 75.7%) for predicting ARDS. Moreover, a higher initial median IL-33 level was revealed in the deceased compared to the survivors [12.25 vs. 4.72; p = 0.021]. ROC statistics identified the initial level of IL-33 as a predictor of death with 11.19 as cut-off value (sensitivity, 80.0%; specificity, 80.0%; AUC = 0.805; p = 0.021). Conclusions: Following tissue damage, IL-33 is abundantly released in the serum of polytraumatized patients immediately after their injuries occurred. As initial IL-33 levels were particularly high in individuals experiencing both PLI and ARDS, IL-33 release after trauma seems to be involved in the promotion of ARDS and might serve already at admission as a solid indicator of impending death in polytraumatized patients.

Higher Mortality Rate in Moderate-to-Severe Thoracoabdominal Injury Patients with Admission Hyperglycemia Than Nondiabetic Normoglycemic Patients.

BACKGROUND: Hyperglycemia at admission is associated with an increase in worse outcomes in trauma patients. However, admission hyperglycemia is not only due to diabetic hyperglycemia (DH), but also stress-induced hyperglycemia (SIH). This study was designed to evaluate the mortality rates between adult moderate-to-severe thoracoabdominal injury patients with admission hyperglycemia as DH or SIH and in patients with nondiabetic normoglycemia (NDN) at a level 1 trauma center. METHODS: Patients with a glucose level ≥200 mg/dL upon arrival at the hospital emergency department were diagnosed with admission hyperglycemia. Diabetes mellitus (DM) was diagnosed when patients had an admission glycohemoglobin A1c ≥6.5% or had a past history of DM. Admission hyperglycemia related to DH and SIH was diagnosed in patients with and without DM. Patients who had a thoracoabdominal Abbreviated Injury Scale score <3, a polytrauma, a burn injury and were below 20 years of age were excluded. A total of 52 patients with SIH, 79 patients with DH, and 621 patients with NDN were included from the registered trauma database between 1 January 2009, and 31 December 2018. To reduce the confounding effects of sex, age, comorbidities, and injury severity of patients in assessing the mortality rate, different 1:1 propensity score-matched patient populations were established to assess the impact of admission hyperglycemia (SIH or DH) vs. NDN, as well as SIH vs. DH, on the outcomes. RESULTS: DH was significantly more frequent in older patients (61.4 ± 13.7 vs. 49.8 ± 17.2 years, p < 0.001) and in patients with higher incidences of preexisting hypertension (2.5% vs. 0.3%, p < 0.001) and congestive heart failure (3.8% vs. 1.9%, p = 0.014) than NDN. On the contrary, SIH had a higher injury severity score (median [Q1-Q3], 20 [15-22] vs. 13 [10-18], p < 0.001) than DH. In matched patient populations, patients with either SIH or DH had a significantly higher mortality rate than NDN patients (10.6% vs. 0.0%, p = 0.022, and 5.3% vs. 0.0%, p = 0.043, respectively). However, the mortality rate was insignificantly different between SIH and DH (11.4% vs. 8.6%, odds ratio, 1.4; 95% confidence interval, 0.29-6.66; p = 0.690). CONCLUSION: This study revealed that admission hyperglycemia in the patients with thoracoabdominal injuries had a higher mortality rate than NDN patients with or without adjusting the differences in patient's age, sex, comorbidities, and injury severity.