Liquid Biopsy in Organ Damage: small extracellular vesicle chip-based assessment of polytrauma.

Background: Despite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles (EVs) as potential markers of decision-making in polytrauma. Objective: Our Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma with organ injury from polytrauma without organ injury. We analysed of blood-borne small EVs at the individual level using a combination of immunocapture and high-resolution imaging. Methods: To this end, we isolated, purified, and characterized small EVs according to the latest Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from human blood collected within 24 h post-trauma and validated our results using a porcine polytrauma model. Results: We found that small EVs derived from monocytes CD14+ and CD14+CD61+ were significantly elevated in polytrauma with organ damage. To be precise, our findings revealed that CD9+CD14+ and CD14+CD61+ small EVs exhibited superior performance compared to CD9+CD61+ small EVs in accurately indicating polytrauma with organ damage, reaching a sensitivity and a specificity of 0.81% and 0.97%, respectively. The results in humans were confirmed in an independent porcine model of polytrauma. Conclusion: These findings suggest that these specific types of small EVs may serve as valuable, non-invasive, and objective biomarkers for assessing and monitoring the severity of polytrauma and associated organ damage.

Case report: radiation-induced lumbosacral plexopathy - a very late complication of radiotherapy for cervical cancer.

BACKGROUND: Lumbosacral plexopathy caused by radiotherapy is a rare but severe consequence of cancer treatment. This condition often leads to varying degrees of sensory and motor impairment. Neurological complications, which are typically permanent, manifest a long period after irradiation. CASE PRESENTATION: We describe a case of progressive lower extremity weakness and sensory impairment in a woman who had been effectively treated with radiotherapy for cervical cancer with development 36 years after irradiation. The electrophysiological assessment revealed a subacute bilateral axonal lesion of the lumbosacral plexus. None of the clinical manifestations, serology, cerebrospinal fluid or imaging data discovered an explanation other than radiation-induced lumbosacral plexopathy (RILP). CONCLUSIONS: This case demonstrates that RILP may emerge more than 30 years after the radiotherapy.

Early myocardial damage (EMD) and valvular insufficiency result in impaired cardiac function after multiple trauma in pigs.

One third of multiple trauma patients present abnormal echocardiographic (ECHO) findings. Therefore, ECHO diagnostic after trauma is indicated in case of hemodynamic instability, shock, after chest trauma and after cardiac arrest. 20 male pigs underwent multiple trauma. Blood samples were collected 4 and 6 h after trauma and concentrations of heart-type fatty acid binding protein (HFABP) as a biomarker for EMD were measured. Myocardial damage was evaluated by scoring Hematoxylin-Eosin stained sections. At baseline, 3 and 6 h after trauma, transesophageal ECHO (TOE) was performed, invasive arterial and left ventricular blood pressure were measured to evaluate the cardiac function after multiple trauma. Systemic HFABP concentrations were elevated, furthermore heart injury score in multiple trauma animals was increased determining EMD. A significant decrease of blood pressure in combination with a consecutive rise of heart frequency was observed. Ongoing depression of mean arterial pressure and diastolic blood pressure were accompanied by changes in ECHO-parameters indicating diastolic and systolic dysfunction. Furthermore, a valvular dysfunction was detected. In this study complex myocardial and valvular impairment after multiple trauma in pigs has been observed. Therefore, detection of EMD and progressive valvular dysfunction might be crucial and therapeutically relevant.

Assessment of the interaction effect between injury regions in multiple injuries: A nationwide cohort study in Japan.

BACKGROUND: There have been no clinical studies to sufficiently reveal the interaction effect generated by combinations of injury regions of multiple injuries. We hypothesized that certain combinations of trauma regions might lead to increased risk of traumatic death and aimed to verify this hypothesis using a nationwide trauma registry in Japan. MATERIALS AND METHODS: This was a retrospective study of trauma patients registered in the Japan Trauma Data Bank between 2004 and 2017. We included patients who suffered blunt trauma with an Injury Severity Score of 16 or more. The trauma was classified into four regions (head, chest, abdomen, and extremities), and a multivariable logistic regression analysis was performed that included interaction terms derived from the combination of two regions as covariates. RESULTS: We included 78,280 trauma patients in this study. Among them, 16,100 (20.6%) patients were discharged to death. Multivariable logistic regression showed the odds ratio (OR) of in-hospital death compared with patients without injury of an Abbreviated Injury Scale score of 3 or more in each injured region as follows: head score, 2.31 (95% confidence interval [CI], 2.13-2.51); chest score, 2.28 (95% CI, 2.17-2.39); abdomen score, 1.68 (95% CI, 1.56-1.82); and extremities score, 1.84 (95% CI, 1.76-1.93), respectively. In addition, the ORs of the statistically significant interaction terms were as follows: head-chest 1.29 (95% CI, 1.13-1.48), chest-abdomen 0.77 (95% CI, 0.67-0.88), chest-extremities 1.95 (95% CI, 1.77-2.14), and abdomen-extremities 0.70 (95% CI, 0.62-0.79), respectively. CONCLUSION: In this population, among patients with multiple injuries, a combination of head-chest trauma and chest-extremities trauma was shown to increase the risk of traumatic death. LEVEL OF EVIDENCE: Prognostic, Level III.

Correlation Between Traumatic Skin and Subcutaneous Injuries and the Severity of Polytrauma Injury.

PURPOSE: To examine the relationship between superficial lesions (such as bruises, hematomas, deep abrasions, and soft tissue emphysema) and internal post-traumatic injuries, assessed using whole-body computed tomography (WBCT), and to determine if these are valid markers for internal injuries. METHODS AND MATERIALS: 250 patients who underwent WBCT emergency scans for suspected polytrauma were retrospectively analyzed after institutional review board approval of the study. The scans were carried out on patients who met the criteria for standard operating procedures for WBCT emergency scans. WBCT covering the entire head, neck, chest, and abdomen (including pelvis and proximal lower extremities) and at least one phase with intravenous contrast agent were included in the study. Initial analyses of immediate WBCT scans was carried out by a consultant radiologist and a radiological resident. The first reading focused on internal damage that needed immediate therapy. The second reading focused on a detailed analysis of the skin and subcutaneous tissue and their relation to internal injuries without the time pressure of an emergency setting, carried out by another experienced radiologist. All skin lesions and the degree of penetration and a comparison between the two readings were reported in tables. RESULTS: Superficial lesion of the chest was detected in 19 patients, 17 of them had an internal injury of the thorax while only two patients, with hematoma of the chest wall, had no internal injuries. Skin and subcutaneous lesions of the chest had the strongest association with an internal injury. Skin lesions of the abdominal wall were observed in 30 patients. In only 11 cases, these lesions were correlated with internal injuries, such as fractures or active bleeding. 52 skin and subgaleal lesions of the scalp were observed. In 20 of these patients, an intracranial or internal injury was detected. In 3 patients, skin abrasions of the neck were present and in only one of them, this finding was associated with an internal injury. CONCLUSION: Trauma patients whose history and clinical presentation meet the standard operating procedures for WBCT emergency scans and who present with a cutaneous lesion, especially at the neurocranium or chest wall, should be observed for internal injuries by WBCT. KEY POINTS: · Presence or lack of a superficial injury of the abdominal wall is not a reliable predictive indication of any internal abdominal injury.. · Superficial lesions of the chest and the neurocranium require a CT scan.. · Superficial injuries of the chest wall had the strongest association with internal injuries.. CITATION FORMAT: · Klempka A, Fischer C, Kauczor H et al. Correlation Between Traumatic Skin and Subcutaneous Injuries and the Severity of Trauma. Fortschr Röntgenstr 2021; 193: 177 - 185.

Polytrauma from a North American Black Bear Attack.

Bear attacks, although rare, can inflict life-threatening injuries. We present the case of a 50-y-old woman from rural Pennsylvania who was attacked by a North American black bear, Ursus americanus. She sustained multiple complex injuries including near-complete scalp avulsion, bilateral ear avulsions, and fractures of the face, ribs, and pelvis. These injuries are similar to those sustained in other bear maulings reported in the literature and required both acute intervention and a multidisciplinary approach to recovery.

Characterization of the cortisol response to traumatic hemorrhage and intra-abdominal contamination models in Cynomologus Macaques.

INTRODUCTION: Trauma, hemorrhage, and peritonitis have widely varying impacts on endocrine response in the injured patient. We sought to examine cortisol response in established non-human primate models of traumatic hemorrhage and intra-abdominal contamination. METHODS: Cynomologus Macaques were separated into two experimental groups, the polytrauma and hemorrhage model, involving a laparoscopic liver resection with uncontrolled hemorrhage, cecal perforation, and soft tissue excision; and the traumatic hemorrhage model, involving only liver resection and uncontrolled hemorrhage. Cortisol levels were measured pre-operatively, at the time of injury, and at regular intervals until post-operative day 1. RESULTS: Cortisol levels increased 600% from the pre-operative value in the polytrauma and hemorrhage model, with minimal changes (20%) in the hemorrhage only model. CONCLUSION: Cortisol levels increase dramatically in response to polytrauma and intra-abdominal contamination as compared to hemorrhage only. The lack of response in the hemorrhage only group may be due to relative adrenal insufficiency caused by the shock state or lack of enticing stimuli from fecal peritonitis.

Altered cell surface receptor dynamics and circulatory occurrence of neutrophils in a small animal fracture model.

INTRODUCTION: Excessive activation of the immune response after femoral fractures and fracture fixation is potentially associated with the development of systemic and local complications, particularly in multiple trauma patients. A dysregulated function of neutrophils, the most prevailing immune cells in circulation, has been discussed as a central pathophysiological background for these unfavourable post-traumatic courses. Our aim was to investigate alterations in activity and functionality as expressed by the cell surface receptor dynamics of circulatory neutrophils after femoral fracture and intramedullary stabilization. MATERIAL AND METHODS: After intramedullary stabilization, an isolated femur fracture was induced in 18 Sprague-Dawley rats. Animals were terminated at different time points, i.e. after 3 (n = 5, group 3d), 7 (n = 5, group 7d) and 14 (n = 5, Group 14d) days and grouped accordingly. Additionally, baseline measurements were performed in one control animal per study group (n = 3) after anaesthesia induction and termination, without prior intramedullary nailing and fracture induction. The numbers and cell surface expression of CD11b, CD11a, CD62 L, and CD49d of circulating neutrophils were compared between groups. RESULTS: Neutrophil numbers were significantly reduced at 3 days compared with baseline measurements (1.2 × 105 vs. 6.3 × 105 cells/mL, p < 0.01). By day 7, neutrophil counts significantly increased back to homeostatic levels (p < 0.05). At day 3, CD11b-expression was significantly reduced, whereas CD11a-expression was increased compared with the baseline measurements (p < 0.05). At day 7, the circulatory neutrophil pool exhibited a unique CD11bhigh/CD11ahigh-neutrophil subset showing a significantly increased co-expression of CD49d. The expression of CD62 L did not change significantly throughout the experiment compared with baseline measurements. CONCLUSIONS: This descriptive small animal fracture study is the first to show that an intramedullary stabilized femur fracture is associated with a temporary reduction in circulatory neutrophil count and concurrent changes in circulatory neutrophil function. Moreover, we demonstrated that the restoration to homeostatic neutrophil activation status occurs concomitantly with the appearance of a novel neutrophil subtype (CD11bhigh/CD11ahigh) in circulation. Our fundamental new findings of the changes in circulatory neutrophil count and functionality after trauma form an excellent basis for future studies to further elucidate the role of neutrophils as activators and regulators of different post-traumatic processes, potentially resulting in local (e.g., fracture healing disturbances) or systemic (e.g., MODS) complications. This might result in the development of specific therapies to reduce adverse outcomes after trauma.

Death scene investigation and autopsy proceedings in identifying the victims of the terror attack on the Breitscheidplatz in Berlin 19th December 2016.

We describe and discuss the forensic mission after the terrorist attack on the Breitscheidplatz in Berlin on 19th December 2016, focusing on co-operation with police authorities, and the injury patterns of the deceased. Even after massive blunt trauma, severe injury patterns are often unrecognizable by visual inspection of the body ("Casper's sign"), which could instill false security among rescuers or, as happened on the Breitscheidplatz, may lead to distress or even trauma in rescue personnel when obviously primarily uninjured patients die suddenly.

A type VI acromioclavicular joint injury: subcoracoid dislocation in a patient with polytrauma.

The Rockwood type VI acromioclavicular joint injury describes subcoracoid dislocation of the distal end of the clavicle. This injury pattern is exceedingly rare, with only 12 cases described in the literature. Diagnosis can be challenging; it is often the result of a high-energy mechanism and patients frequently have other severe distracting injuries. We report the case of a 23-year-old man who presented to our department after falling from a fifth-floor balcony. Alongside multiple intra-abdominal and musculoskeletal injuries, the patient sustained a type VI acromioclavicular joint dislocation. This injury was not picked up on the initial clinical assessment or described in the initial radiology report, with the diagnosis only made upon subsequent repeat review of the imaging by the admitting team. Fortunately, this delay did not increase the time to the patient receiving appropriate treatment. Despite its rarity, awareness of this injury pattern and its association with polytrauma is essential to reduce the risk of the diagnosis being overlooked in the acute setting.

Forensic Pathological Considerations of a Unique Case of "Complicated Suicide"*,†.

In the forensic literature, peculiar and uncommon cases of suicides defined as "complicated" are reported. In these circumstances, the suicide method chosen by the victim fails, and death occurs due to a subsequent unforeseen accidental event defined as secondary trauma. Through retrospective examination of 25,512 autopsies in 27 years (1993-2019) at the Bureau of Legal Medicine of Milan, a unique case of complicated suicide was identified from a total of 4497 suicides. It concerns an elderly man who, after killing his wife by inflicting incised wounds to her neck, tried to hang himself by tying a rope to a heater and jumping from the window located over the heater itself. However, the rope suddenly snapped and the man fells to the ground causing fatal traumatic injuries. Death occurred because of an accidental event caused by the failure of the hanging mechanism. Therefore, a peculiar yet characteristic case of complicated suicide is described.

miR-142-3p Expression Is Predictive for Severe Traumatic Brain Injury (TBI) in Trauma Patients.

BACKGROUND: Predictive biomarkers in biofluids are the most commonly used diagnostic method, but established markers in trauma diagnostics lack accuracy. This study investigates promising microRNAs (miRNA) released from affected tissue after severe trauma that have predictive values for the effects of the injury. METHODS: A retrospective analysis of prospectively collected data and blood samples of n = 33 trauma patients (ISS ≥ 16) is provided. Levels of miR-9-5p, -124-3p, -142-3p, -219a-5p, -338-3p and -423-3p in severely injured patients (PT) without traumatic brain injury (TBI) or with severe TBI (PT + TBI) and patients with isolated TBI (isTBI) were measured within 6 h after trauma. RESULTS: The highest miR-423-3p expression was detected in patients with severe isTBI, followed by patients with PT + TBI, and lowest levels were found in PT patients without TBI (2-∆∆Ct, p = 0.009). A positive correlation between miR-423-3p level and increasing AIShead (p = 0.001) and risk of mortality (RISC II, p = 0.062) in trauma patients (n = 33) was found. ROC analysis of miR-423-3p levels revealed them as statistically significant to predict the severity of brain injury in trauma patients (p = 0.006). miR-124-3p was only found in patients with severe TBI, miR-338-3p was shown in all trauma groups. miR-9-5p, miR-142-3p and miR-219a-5p could not be detected in any of the four groups. CONCLUSION: miR-423-3p expression is significantly elevated after isolated traumatic brain injury and predictable for severe TBI in the first hours after trauma. miR-423-3p could represent a promising new biomarker to identify severe isolated TBI.

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing.

BACKGROUND: Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied. EXPERIMENTAL APPROACH: 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. RESULTS: After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP. DISCUSSION: Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences.

Postmortem Computed Tomography in Firearm Homicides: A Retrospective Case Series.

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and analyzed with McNemar's test. We included 60 males and 20 females (median age 31 years, range 3-73). Based on PMCT, 56 (79.1%) cases had injuries relevant to the cause of death in a single body region (24 head-neck region, 32 thoracoabdominal region). Out of these 56 cases, 9 had a missed major diagnosis by PMCT outside that region, including 6 extremity injuries visible during standard external examination. Yet all had evident lethal firearm injury. We showed that PMCT identifies major firearm injuries in homicide victims and excludes injuries related to the cause of death in other regions when a single body region is injured. Although PMCT has a known limited sensitivity for soft tissue and vascular pathology, it can be combined with external examination to potentially reduce or focus dissections in some of these cases depending on the circumstances and medicolegal needs.

Fatal mauling by tigers.

Lethal injuries due to large animal attack are uncommon in routine forensic practice in Europe. Specifically, few incidents are reported concerning tiger/lion attacks that usually involve captive circus or zoo animals. We present the case of a 61-year old animal tamer who was mauled to death by four tigers while he was training them for a circus performance. Careful investigation of the circumstances surrounding the fatality revealed that the tamer had most likely been struck with a tiger paw and then mauled by additional tigers resulting in serious and fatal injuries. Although a full medico-legal autopsy was not authorized, total body CT scan coupled with post-mortem external examination allowed a reconstruction of events.

Fatal gyroplane crash.

Gyroplanes are mainly used for sports aviation. Experience is required when flying these special aircraft because in 40% of gyroplane crashes, the passengers do not survive. Herein, a fatal gyroplane crash of a tandem-seat gyroplane with two occupants is reported. The occupants, both 49-year-old males, fell from a height of approximately 20 m to 30 m. In both cases, the cause of death was polytrauma with typical findings of deceleration trauma. The pilot, who probably lost his helmet in the crash, had a ring fracture at the base of his skull. As there is not much literature on autopsy findings in the case of light aircraft crashes, these autopsy findings are presented and discussed.

Deadly injuries through recoilless anti-tank weapons while military shooting practice-two case studies from Germany and Switzerland.

In this casuistry, two accidents from Germany and Switzerland are presented that happened during the shot of recoilless anti-tank weapons. In both cases, the injuries led to the death of two soldiers: A 22-year-old soldier in Germany was struck by the counter mass of a so-called Davis gun which had been fired by a comrade during a firing exercise; he died from his severe injuries, especially in the abdominal part of the body. As a peculiarity of the wound morphology, it was found to be a thick-layered, metallic, gray material in the wound cavity, which corresponded to the material of the counter mass that was ejected opposite to the shooting direction. The other case took place in Switzerland, where a 24-year-old soldier was seriously injured during an exercise with portable anti-tank rockets. At the time the shot was fired, he stood behind the launcher and was hit by the propulsion jet of the rocket motor. He died as well from his severe injuries, which were located at the chest done by the gas jet and by the very high pressure. In both cases, two different causes of death were present: massive blunt violence in the first case versus a jet of hot gases of very high speed and temperature in the second case.

A Case of Multiple Self-Inflicted Stab Wounds of the Neck Captured on Surveillance Video.

Multiple sharp force injuries in a victim make it difficult to distinguish between homicide and suicide. Forensic pathologists also may be unable to determine the total survival time and the survival time with physical activity due to lack of evidence. The authors report here on a case of nineteen stab wounds of the neck, which led to an initial suspicion of homicide. The scene was however captured on surveillance video, which provided a precise description of the wound mechanism and led to the injuries being reclassified as suicidal. No other description of a suicide with such a high number of severe stab wounds has been documented in the literature. The video footage provided additional information concerning survival time. Physical activity was well documented during at least 4 min after the last stab wound and the total survival period was at least 6 min, despite the perforation of both jugular veins and the trachea. Vein injuries are less rapidly lethal than artery injuries. Injuries of the major airways are not immediately lethal and do not lead to immediate incapacitation. The benefit of the video evidence is to highlight wound features that may suggest a suicidal manner and inform forensic pathologists about survival intervals after severe stab wounds to the neck.

Beyond the Brain: Peripheral Interactions after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability, and there are currently no pharmacological treatments known to improve patient outcomes. Unquestionably, contributing toward a lack of effective treatments is the highly complex and heterogenous nature of TBI. In this review, we highlight the recent surge of research that has demonstrated various central interactions with the periphery as a potential major contributor toward this heterogeneity and, in particular, the breadth of research from Australia. We describe the growing evidence of how extracranial factors, such as polytrauma and infection, can significantly alter TBI neuropathology. In addition, we highlight how dysregulation of the autonomic nervous system and the systemic inflammatory response induced by TBI can have profound pathophysiological effects on peripheral organs, such as the heart, lung, gastrointestinal tract, liver, kidney, spleen, and bone. Collectively, this review firmly establishes TBI as a systemic condition. Further, the central and peripheral interactions that can occur after TBI must be further explored and accounted for in the ongoing search for effective treatments.