Early Posttraumatic Phase Research Articles

Construction and validation of a functional diagnostic score in anterior cruciate ligament ruptures of the knee in the immediate post-traumatic period. Preliminary results of a multicenter prospective study

IntroductionKnee ligament injuries are frequent and their number is constantly increasing with the development of sports activities. Dynamic knee maneuvers usually make it possible to diagnose anterior cruciate ligament (ACL) injuries but they remain difficult to perform in the early post-traumatic phase. This leads to the almost systematic use of MRI scans, many of which turn out to be superfluous. The aim of this study was to construct a screening score based solely on history-taking, in order to help diagnose ACL injuries, and to define thresholds that could help inform recommendations for MRI usage. The hypothesis was that this score could distinguish a population of patients with a ruptured ACL from a population of patients with other knee injuries. Material and methodsThis prospective multicenter study included 166 patients. Patients were included if they were between 18 and 55 years of age, with knee trauma that had occurred in the last 10 days, and without a bone fracture on standard radiographs. They were excluded if the trauma required immediate surgical management and if they had a history of knee trauma. The screening score was completed by the physician. The score included the following items: assessment of pain, immediate post-traumatic functional impairment, notion of a “pop”, feeling of instability and presence of a swelling. An MRI was systematically performed and the patient consulted a referring physician to compare the initial score with the diagnosis. ResultsEighty-six patients had an injured ACL and 80 had a healthy ACL. Two thresholds could be identified. For a score lower than 4, the risk of an ACL injury was low with a sensitivity of 96% and a negative predictive value of 87%. For a score above 8, the ACL injury was highly probable with a specificity of 88% and a positive predictive value of 83%. Discussion/conclusionThe score was able to distinguish a population of patients with a ruptured ACL from a population of patients with other knee injuries. These preliminary results confirm that the selected items are relevant and that the score can help improve the diagnostic orientation of patients with recent knee trauma. Increasing the sample size in combination with an analysis of influencing factors will determine whether the performance of this score can be refined. Level of evidenceII prospective multicenter study.

Early thromboelastography in acute traumatic coagulopathy: an observational study focusing on pre-hospital trauma care

BackgroundMajor brain injury and uncontrolled blood loss remain the primary causes of early trauma-related mortality. One-quarter to one-third of trauma patients exhibit trauma-induced coagulopathy (TIC). Thromboelastometry (ROTEM) and thrombelastography (TEG) are valuable alternatives to standard coagulation testing, providing a more comprehensive overview of the coagulation process.PurposeEvaluating thromboelastographic profile, the incidence of fibrinolysis (defined as Ly30 > 3%) in severe trauma patients, and factors influencing pathological coagulation pattern.MethodsProspective observational 2 years cohort study on severe trauma patients assisted by Helicopter Emergency Medical System (HEMS) and Level 1 Trauma Center, in a tertiary referral University Hospital.ResultsEighty three patients were enrolled, mean NISS (new injury severity score) 36 (± 13). Mean R value decreased from 7.25 (± 2.6) to 6.19 (± 2.5) min (p < 0.03); 48 (60%) patients had a reduction in R from T0 to T1. In NISS 25–40 and NISS > 40 groups, changes in R value increased their significance (p = 0.04 and p < 0.03, respectively). Pathological TEG was found in 71 (88.8%) patients at T0 and 74 (92.5%) at T1. Hypercoagulation was present in 57 (71.3%) patients at T0, and in 66(82.5%) at T1. 9 (11.3%) patients had hyperfibrinolysis at T0, 7 (8.8%) patients at T1. Prevalence of StO2 < 75% at T0 was greater in patients whose TEG worsened (7 patients, 46.7%) against whose TEG remained stable or improved (8 patients, 17.4%) from T0 to T1 (p = 0.02). 48 (57.8%) patients received < 1000 mL of fluids, while 35 (42.2%) received ≥ 1000 mL. The first group had fewer patients with hypercoagulation (20, 41.6%) than the second (6, 17.6%) at T1 (p < 0.03). No differences were found for same TEG pattern at T0, nor other TEG pattern.ConclusionOur population is representative of a non-hemorrhagic severe injury subgroup. Almost all of our trauma population had coagulation abnormalities immediately after the trauma; pro-coagulant changes were the most represented regardless of the severity of injury. NISS appears to affect only R parameter on TEG. Hyperfibrinolysis has been found in a low percentage of patients. Hypoperfusion parameters do not help to identify patients with ongoing coagulation impairment. Small volume resuscitation and mild hypotermia does not affect coagulation, at least in the early post-traumatic phase.

The Associated Meniscal Tears and Associated Risk Factors in Concomitant ACL Injuries of the Knee: A Retrospective Analysis

Introduction: The pattern of meniscus tear has significant impact onsubsequent rehabilitation and functional outcome as theyare usually associated with ACL injury.Knowledge about associated meniscus tear helps to identifypatients in the early post-traumatic phase. &#x0D; Objectives: To study meniscus tear patterns and associationbetween different tear patterns of meniscus in ACLinjured subjects and to identify potential demographic andother associated risk factors.&#x0D; Methodology: Routine arthroscopic findings database of 54 patientsoperated for primary ACL reconstruction from January 2017to December 2018 was used to study associated tear of meniscus. Based on arthroscopic evaluation, cases weregrouped into meniscus having no tear, minor tear and majortear. Major tear included complete radial tears, root tearsand unstable longitudinal tears including bucket-handletears.&#x0D; Result: Totalarthroscopycasesinthestudydurationwere124.Ofthose,43% (n=54) underwent ACL reconstruction (ACLR) for tornACL. Among the patients who underwent ACLR, 58% had notear, 26%hadminortears, and16%hadmajortears ofthemeniscus. Therewere significant differencesbetweenthree groups for gender, age groupsandmechanism of injury. Risk factors formajortearsweremalegenderandage&lt;30years.Minorandmajortears were associated with a contact injury.&#x0D; Conclusion: Male, age &lt;30 years and history of contact injury havehigh risks for having an associated meniscus tear. Earlyreferral to magnetic resonance imaging and/or arthroscopyis recommended to allow meniscus repair in a timelymanner.

Therapy with deep oscillations - principle, biological effects, review

The use of electrical energy for therapeutic medical purposes has been known since the 18th century and the first one applied to the patient is described by Johann Gottlob KrA¼ger in 1743. The development in the construction of medical equipment for electrotherapy results in an association of high therapeutic efficacy with mild, non-traumatic effect on biological tissues. The first applications in the clinical practice of an innovative, non-invasive, electromechanical therapeutic method based on electrostatic attraction, characterized by its deep and mild interaction with the tissue in the application area date back to m ore than two decades ago. This allows its use in the early post-traumatic phase, the early postoperative period and acute pain. DEEP OSCILLATION® is a widely used physiotherapeutic concept developed by Physiomed Elektromedizin AG - Germany, which received its first patent in 1988, and in 2002 was approved by the US Food and Drug Administration. The first generator apparatus deep oscillations HIVAMAT - 200 was developed in the early 19 80s at the Department of Physiotherapy at Amber Municipal Hospital of H.Seidel and W. Waldner. Тhe aim of this article is to provide a detailed overview based on a wide range of scientific publications, in chronological order, documented clinical applications and their outcomes, synthesizing the current knowledge of the effect of deep oscillations in a variety of pathological processes, and giving future guidelines in the use of this therapeutic method.

Influence of massive blood transfusion and traumatic brain injury on TIMP‑1 and MMP‑9 serum levels in polytraumatized patients

The morbidity and mortality of polytrauma patients are substantially influenced by the extent of the posttraumatic inflammatory reaction. Studies have shown that TIMP‑1 and MMP‑9 play amajor role in posttraumatic immune disorder in genome-wide mRNA microarray analyses. Furthermore, both showed differential gene expression profiles depending on the clinical parameters massive blood transfusion and traumatic brain injury. The aim of this study was to evaluate TIMP‑1 and MMP‑9 serum concentrations in polytraumatized patients depending on the clinical parameters massive blood transfusion and traumatic brain injury in the early posttraumatic phase. Polytrauma patients (≥18years) with an "Injury Severity Score" (ISS) ≥ 16points were enrolled in this prospective study. Serum levels of TIMP‑1 and MMP‑9 were quantified (at 0 h, 6 h, 12 h, 24 h, 48 h and 72 h) using an enzyme-linked immunosorbent assay (ELISA). Groups were divided according to the clinical parameter massive blood transfusion (≥10 red blood cell units [RBC units] in the first 24-hour posttrauma) and traumatic brain injury (CCT postive [cranial computed tomography]). Following massive blood transfusion (n = 21; 50 ± 15.7 years; ISS 39 ± 12.8 points) patients showed overall significantly increased TIMP‑1 levels (p = 0.003) and significantly higher TIMP‑1 values after 12-72 h. Traumatic brain injury patients (n = 28; 44 ± 19years; ISS 42 ± 10points) showed significantly higher MMP‑9 levels (p = 0.049) in the posttraumatic period. Polytraumatized patients who received massive blood transfusions following major trauma showed significantly higher TIMP‑1 levels than patients who did not receive massive transfusions. This seems to be an expression of a massively excessive inflammatory reaction and therefore represents a substantial factor in the pathogenesis of severe posttraumatic immune dysfunction in this collective. Furthermore, the significant increase in MMP‑9 with accompanying traumatic brain injury reflects the pivotal role of matrix metalloproteinases in the pathophysiology of traumatic brain injury.

Polymorphonuclear (PMN) elastase in patients after severe traumatic brain injury

BackgroundData on PNM elastase levels in cerebrospinal fluid following traumatic brain injury (TBI) in humans are not available in the literature. Therefore, the aim of this prospective study was to evaluate the dynamics of PMN elastase in the cerebrospinal fluid (CSF) of patients after TBI.MethodsPatients suffering from isolated, closed TBI, presenting with an initial Glasgow coma score ≤ 8 and with intracerebral hemorrhage on the initial cranial computed tomography scan (performed within 90 min after TBI) were enrolled. CSF and blood samples were obtained immediately, 12 h, 24 h, 48 h, and 72 h after admission. ELISA testing was used to quantify the PMN elastase levels in CSF. In addition, the ratio of CSF albumin to serum albumin was calculated to evaluate the role of the blood–cerebrospinal fluid barrier (BCSFB). As controls, CSF samples were taken from patients receiving spinal anesthesia for elective orthopedic surgery of the lower extremity.ResultsTwenty-three patients meeting the inclusion criteria and ten control patients were enrolled. The PMN elastase showed a significant elevation at 48 and 72 h after TBI. When comparing the PMN elastase levels of patients with intact BCSFB to patients with defective BCSFB, there was no significant difference for the respective observation points.ConclusionsThis is the first study to demonstrate that the PMN elastase levels in CSF significantly increased in the early posttraumatic phase (48 h and 72 h after TBI) in patients. The function of the BCSFB showed no significant influence on the PMN levels.

Evaluation of serum bone specific alkaline phosphatase levels in isolated closed diaphyseal fractures of long bones in relation to fracture healing

Introduction: In day-to-day practice, progression of bone healing is assessed mainly by clinico-radiological parameters. Furthermore, clinicians are unable to identify the delayed and non-unions early, and even advanced imaging techniques may not be helpful in these cases. To date, the methods used to monitor the bone healing process have been based on the patients’ assessment and the radiographic findings. In view of the fact that patient opinion is highly subjective, that the radiographic findings depend on the radiologist’s experience and that the monitoring of bone healing is a long-lasting process, measurements of biochemical parameters appear to be the only objective evidence of the changes occurring during bone regeneration. The aim of this study was to examine whether the assessment of Serum bone specific ALP (BsALP) as a biochemical parameter in the early posttraumatic phase may indicate the course of fracture healing. Methods: Changes in BsALP levels were observed at definitive intervals in 30 adult patients (enrolled as per inclusion/exclusion criterion) with closed fresh (within 1 week) traumatic diaphyseal fractures of long bone. All the patients had been surgically treated. Regular follow up of these patients was done till 6 months. The changes in serum BsALP levels were recorded and correlated with the clinico-radiological progression of fracture healing in these patients. Result: The mean BsALP increased significantly from baseline to 6 and 12 weeks and then decreased significantly at 16 to 24 weeks. Conclusion: BsALP levels were increased in all cases of closed isolated long bone diaphyseal fractures with maximum increase at 12 weeks and never reached to baseline levels till 24 weeks. The increase in BsAlp levels was more in surgical fixation done with nailing as compared to plating. No relationship was observed between BsALP levels and fracture healing outcome.

Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model.

In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.

Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma.

In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients.

Associated tears of the lateral meniscus in anterior cruciate ligament injuries: risk factors for different tear patterns.

BackgroundThe pattern of lateral meniscus tears observed in anterior cruciate ligament (ACL)-injured subjects varies greatly and determines subsequent management. Certain tear patterns with major biomechanical consequences should be repaired in a timely manner. Knowledge about risk factors for such tears may help to identify patients in the early posttraumatic phase and subsequently may improve clinical results.MethodsA database of 268 patients undergoing primary ACL reconstruction was used to identify all patients with isolated ACL tears and patients with an associated tear of the lateral meniscus. Patients who underwent surgery >6 months after the injury were excluded. Based on the arthroscopic appearance of the lateral meniscus, patients were assorted to one of three groups: ‘no tear,’ ‘minor tear,’ and ‘major tear.’ Tear patterns defined as major included root tears, complete radial tears, and unstable longitudinal tears including bucket-handle tears. Univariate analysis was performed by comparing the three groups with regard to gender, age, height, weight, BMI, type of injury (high-impact sport, low-impact sport, and not sports related), and mechanism of injury (non-contact vs. contact). Multivariate logistic regression was carried out to identify independent risk factors for minor and major meniscal tears and to calculate odds ratios (OR).ResultsTwo hundred fifteen patients met the inclusion and exclusion criteria. Of those, 56% had isolated ACL tears, 27% had associated minor tears, and 17% had associated major tears of the lateral meniscus. Univariate analysis revealed significant differences between the three groups for gender (p = 0.002), age groups (p = 0.026), and mechanism of injury (p < 0.001). A contact injury mechanism was a risk factor for minor tears (OR: 4.28) and major tears (OR: 18.49). Additional risk factors for major tears were male gender (OR: 7.38) and age <30 years (OR: 5.85).ConclusionMale patients, patients <30 years, and particularly patients who sustained a contact injury have a high risk for an associated major lateral meniscus tear. Special attention is therefore necessary in those patients and early referral to magnetic resonance imaging and/or arthroscopy is recommended to allow meniscus repair in a timely manner.

Epidemiology and risk factors of multiple-organ failure after multiple trauma

In the severely injured who survive the early posttraumatic phase, multiple-organ failure (MOF) is the main cause of morbidity and mortality. An enhanced prediction of MOF might influence individual monitoring and therapy of severely injured patients. We performed a retrospective analysis of a nationwide prospective database, the TraumaRegister DGU of the German Trauma Society. Patients with complete data sets (2002-2011) and a relevant trauma load (Injury Severity Score [ISS] ≥ 16), who were admitted to an intensive care unit, were included. Of a total of 31,154 patients enclosed in this study, 10,201 (32.7%) developed an MOF according to the Sequential Organ Failure Assessment score. During the study period, mortality of all patients decreased from 18.1% in 2002 to 15.3% in 2011 (p < 0.001). Meanwhile, MOF occurred significantly more often (24.6% in 2002 vs. 31.5% in 2011, p < 0.001), but mortality of MOF patients decreased (42.6% vs. 33.3%, p < 0.001). MOF patients who died survived 2 days less (11 days in 2002 vs. 8.9 days in 2011, p < 0.001). Independent risk factors for the development of MOF following severe trauma were age, ISS, head Abbreviated Injury Scale (AIS) score of 3 or higher, thoracic AIS score of 3 or higher, male sex, Glasgow Coma Scale (GCS) score of 8 or less, mass transfusion, base excess of less than -3, systolic blood pressure less than 90 mm Hg at admission, and coagulopathy. Over one decade, we observed an ongoing decrease of mortality after multiple trauma, accompanied by decreasing mortality in the subgroup with MOF. However, incidence of MOF in the severely injured increased significantly. Thus, MOF after multiple trauma remains a challenge in intensive care. The risk factors from multivariate analysis could be instrumental in anticipating the early development of MOF. Furthermore, a reliable prediction model might be supportive for patient enrolment in trauma studies, in which MOF marks the primary end point. Epidemiologic study, level III.

Single impact cartilage trauma and TNF-α: Interactive effects do not increase early cell death and indicate the need for bi-/multidirectional therapeutic approaches

Blunt trauma of articular cartilage, often resulting from accidents or sports injuries, is associated with local inflammatory reactions and represents a major risk factor for development of post-traumatic osteoarthritis. TNF-α is increased in synovial fluid early after trauma, potentiates injury-induced proteoglycan degradation and may act proapoptotic under permissive conditions. We asked whether TNF-α also influences chondrocyte death, gene expression of catabolic and anabolic markers and the release of proinflammatory mediators in the early post-traumatic phase. Interactive effects of a defined single impact trauma (0.59 J) and TNF-α (100 ng/ml) on human early-stage osteoarthritic cartilage were investigated in vitro over 24 h. Exposure of traumatized cartilage to TNF-α did not increase chondrocyte death. IL-6-synthesis was augmented by trauma, TNF-α and combined treatment. The impact increased the release of PGE2 and PGD2 in the presence and absence of TNF-α to a similar extent while TNF-α alone showed no effect. In contrast, NOS2A-expression and nitric oxide (NO)-release were not affected by trauma but significantly increased by TNF-α. Expression of OPG and RANKL was not affected by TNF-α but modulated by trauma. TNF-α with and without trauma significantly induced MMP1 gene expression. These results indicate that TNF-α does not potentiate early cell death in early-stage osteoarthritic cartilage after blunt injury. However, trauma and TNF-α showed independent and interactive effects concerning prostaglandin and NO release. TNF-α probably contributes to cartilage degradation after trauma by an early induction of MMP1 gene expression. Our study confirms that an anti-TNF-α therapy may have inhibitory effects on catabolic and, partly, on inflammatory processes after a single impact trauma. As TNF-α does not contribute to the loss of chondrocytes in the initial post-traumatic phase, a combination with pharmaco-therapeutic strategies reducing early cell death could be reasonable.

CT and MR imaging of primary cerebrovascular complications in pediatric head trauma

The incidence of severe traumatic head injury in children has constantly increased over the last years. Diagnostic imaging has become an unrenounceable tool for the documentation and follow-up of intracranial lesions. The use of magnetic resonance imaging (MRI) in the early posttraumatic phase has led to a more thorough understanding of intracranial injuries. We retrospectively analyzed the cranial computed tomography (CCT) and magnetic resonance (MR)-studies of patients with traumatic head injuries for primary cerebrovascular complications. In 64 children (45 male, 19 female) with traumatic head injuries, CCT and MR examinations were available for analysis. The children's age ranged from 3 months to 15 years with a median age of 7 years. All patients had initial CCT on admission to the hospital with follow-up examinations depending on clinical state and initial imaging findings. All patients had at least one MR examination between 0 to 120 days after the trauma with a median time interval of 17 days. In five of 64 (7.8%) patients, cerebrovascular complications were found on imaging studies. Initial imaging within the first 24 h after the trauma detected a complete middle cerebral artery infarction in one patient and extensive sinus thrombosis after a complex skull fracture in another. In two patients, thrombosis of the transverse sinus appeared on MRI 4 to 6 days after the trauma. In another patient with open-skull injury, a posttraumatic aneurysm of the pericallosal artery was diagnosed on MRI 30 days after the trauma. Our study shows that, although primary cerebrovascular lesions after traumatic head injuries in children are rare, the radiologist should be aware of the characteristic injury patterns and the time appearance of imaging findings on CT and MRI.

Thyroxin regulates BDNF expression to promote survival of injured neurons

A growing amount of evidence indicates that neuronal trauma can induce a recapitulation of developmental-like mechanisms for neuronal survival and regeneration. Concurringly, ontogenic dependency of central neurons for brain-derived neurotrophic factor (BDNF) is lost during maturation but is re-acquired after injury. Here we show in organotypic hippocampal slices that thyroxin, the thyroid hormone essential for normal CNS development, induces up-regulation of BDNF upon injury. This change in the effect of thyroxin is crucial to promote survival and regeneration of damaged central neurons. In addition, the effect of thyroxin on the expression of the K-Cl cotransporter (KCC2), a marker of neuronal maturation, is changed from down to up-regulation. Notably, previous results in humans have shown that during the first few days after traumatic brain injury or spinal cord injury, thyroid hormone levels are often diminished. Our data suggest that maintaining normal levels of thyroxin during the early post-traumatic phase of CNS injury could have a therapeutically positive effect.

Apoptosis differs in dendritic cell subsets early after severe trauma

Dendritic cells (DC) represent an integral part of the immune system. However it is unclear how apoptosis in myeloid DC (MDC) and plasmacytoid DC (PDC) is affected and whether pro- or antiapoptotic properties dominate during the early post-traumatic phase. Blood samples were obtained on day 1 and day 4 after hospital admission from 10 severely traumatized patients and 10 healthy volunteers. Mononucleated cells were isolated and incubated with LPS. Apoptosis of MDC and PDC was assessed by annexin-V staining using flow cytometry. Expression of genes involved in apoptosis (Caspase-8, Flice inhibitory protein [FLIP], Bcl-2, Bax, Gadd45) in DC was measured by reverse transcriptase polymerase chain reaction. For statistical evaluation, the Kruskal-Wallis test was used ( p < 0.05). Severe trauma increased apoptotic MDC compared with those in healthy controls ( p < 0.05), whereas apoptosis of PDC was not influenced by the trauma impact. LPS stimulation decreased MDC apoptosis until day 4 after trauma; by contrast, for PDCs this effect was present only on day 1 after trauma. The Bcl-2/Bax ratio in DCs increased significantly. We conclude that peripheral MDCs are more susceptible to undergo apoptosis after trauma compared with PDCs. However, the overall response of DCs early after trauma is characterized by an increased activation of antiapoptotic mediators that might indicate a compensatory life-prolonging reaction.

Early down-regulation of the pro-inflammatory potential of monocytes is correlated to organ dysfunction in patients after severe multiple injury: a cohort study

IntroductionSevere tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. However, there is little known about the functional alterations of monocytes in the early posttraumatic phase, characterized by the battle of the individual with the initial trauma.MethodsThirteen patients with severe multiple injury; injury severity score (ISS) >16 points (17 to 57) were included. The cytokine synthesis profiles of monocytes were characterized on admission, and followed up 6, 12, 24, 48, and 72 hours after severe multiple injury using flow cytometry. Whole blood was challenged with lipopolysaccharide (LPS) and subsequently analyzed for intracellular monocyte-related TNF-α, IL-1β, IL-6, and IL-8. The degree of organ dysfunction was assessed using the multiple organ dysfunction syndrome (MODS)-score of Marshall on admission, 24 hours and 72 hours after injury.ResultsOur data clearly show that the capacity of circulating monocytes to produce these mediators de novo was significantly diminished very early reaching a nadir 24 hours after severe injury followed by a rapid and nearly complete recovery another 48 hours later compared with admission and controls, respectively. In contrast to the initial injury severity, there was a significant correlation detectable between the clinical signs of multiple organ dysfunction and the ex vivo cytokine response.ConclusionsAs our data derived from very narrow intervals of measurements, they might contribute to a more detailed understanding of the early immune alterations recognized after severe trauma. It can be concluded that indeed as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function. Moreover, our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is not only an in vitro phenomenon but also undistinguishable associated with the onset of organ dysfunction in the clinical scenario.

Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients

BackgroundMultiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro-and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24 h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period.Patients and methods58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters.ResultsInterleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35).ConclusionThe current study presents an image of the serum Il-6, 8 and 10 releases in multiple trauma patients in the very early post-trauma period. We could thereby demonstrate that interleukin levels can clearly differentiate the presence of hemorrhagic shock and subsequent massive blood product substitution, the development of multiple organ failure and clinical outcome. No significant connection to age, gender and brain injury could be detected. Most importantly, changes in interleukin levels can be observed in the very early posttraumatic phase, at the earliest 90 minutes after trauma.

Verletzungen von Becken und Azetabulum

Unstable and dislocated fractures of the pelvis and acetabulum represent rare lesions with a serious prognosis and are often found in multiply injured or polytraumatized patients. The specific risk potential and complication rates are high. A variety of potential errors and pitfalls in diagnosis and therapy can adversely affect the final outcome and correspond to limited individual experience with these fracture entities. Consequently, patients with unstable and/or dislocated pelvic or acetabular fractures should be transferred to institutions in which these fracture patterns are frequently treated. Although evidence-based recommendations are widely lacking, it appears advisable to follow the diagnostic and therapeutic algorithms based on expert opinion and adapt them to the individual fracture pattern to develop a treatment concept with minimized risks. A selection of typical errors of the early posttraumatic phase and their potential solutions is the basis of the present review and underlines a strategy of error prevention. Quality control options may be a useful component.

Outcomes for Conservative Management of Traumatic Conductive Hearing Loss

To evaluate the natural history of traumatic conductive hearing loss. Retrospective chart review. Otologic and audiometric evaluations of patients in the early posttraumatic phase were compared with evaluations at follow-up. Assessment included etiologies of trauma, classification of hearing loss, factors causing conductive loss, and analyses of changes in air-bone gaps, pure-tone averages and hearing loss class. There were 45 patients, representing 47 ears, with sufficient initial and follow-up documentation to analyze the natural history of traumatic conductive hearing loss. Overall, 77% of ears showed an improvement in pure-tone averages without surgical intervention. Air-bone gaps closed from an average of 24.8 +/- 12.1 to 13.2 +/- 11.1 dB. Only 11% of ears demonstrated a decrease in pure-tone averages, and 12% showed no change in thresholds. All forms of injury contributing to the conductive hearing loss had good outcomes. Specifically, tympanic membrane perforations showed final air-bone gaps of 14.9 +/- 11.2 dB; cases of hemotympanum had final air-bone gaps of 10.0 +/- 8.1 dB; and suspected ossicular chain disruptions had final air-bone gaps of 13.9 +/- 12.3 dB. Only 5 of 47 ears ultimately required surgical intervention for persistent pathology. Patients with all forms of traumatic conductive hearing loss can be initially managed conservatively. Even suspected ossicular chain disruptions have a high rate of spontaneous reparation. Surgical intervention for perforation or conductive hearing loss should be undertaken in the rare cases when these conditions persist greater than 6 months.

Molecular Profiling of Experimental Blunt Chest Trauma

Trauma to the chest still causes approximately a quarter of all trauma-related deaths and pulmonary contusion itself has an age-dependent mortality up to 42%. Here we explore the diverse transcriptional programs activated after blunt thoracic trauma, which is still poorly understood. Bilateral lung injury was induced in rats by a single blast wave, followed by RNA-isolation and microarray analysis at various time points after trauma (0–24h post-trauma). To determine the protective effects of a systemic C5a-blockade in the 3h post trauma window, either pre-immune IgG or anti-C5a IgG was applied intravenously. During the early post-traumatic phase, proteins of the intracellular PIP3-kinase pathway were significantly downregulated, while various cytokines and their receptors were upregulated. Proteins encoding for the coagulation system were massively upregulated. Whereas the expression of the complement split product C4a was consistently reduced, C3 was upregulated 12h post injury. In the late post-traumatic phase, MAP-kinase and ion-channels were also affected and down-regulated. While various important complement players, MAP-kinase and the bradykinin-receptor were down-regulated 3h post injury in IgG-treated animals, systemic C5a blockade after trauma led to a more transcriptional balance program similar to the sham treated group. These data might lead to a better understanding of the molecular signature after severe trauma and reveal new therapeutic targets to prevent the severe consequences of blunt chest trauma. This work was supported by NIH Grants No. GM-61656, GM-29507 and HL-31963.