Pathophysiological response in trauma-related acute kidney injury after blunt thoracic trauma and hemorrhagic shock in male mice.

Trauma and shock often severely affect the kidneys. This can lead to trauma-related acute kidney injury (TRAKI), which significantly increases the risk of adverse outcomes. To study the pathophysiology of TRAKI, we established a murine model of combined blunt thoracic trauma and pressure-controlled hemorrhage [trauma and hemorrhagic shock (THS)] that induces mild transient TRAKI.

Damage control orthopaedics is associated with impaired fracture healing and delayed recovery in a rodent model of severe multiple trauma.

Aims: Polytraumatized patients with severe limb injuries often develop complications, which are influenced by the surgical treatment strategy. For the initial fracture stabilization, Early Total Care (ETC) and Damage Control Orthopedics (DCO) are competing concepts, with the treatment choice depending on the patient's condition. Clear guidance factors remain lacking.

Absolute lymphocyte count trajectory predicts clinical outcome in severely injured patients.

Purpose: Lymphopenia is associated with adverse clinical outcome in trauma, but no immunomonitoring method is established to identify patients at risk. Absolute lymphocyte count (ALC) represents a promising biomarker and may support clinical decision-making in the intensive care unit (ICU). This study examined the temporal patterns of ALC in severely injured patients and their correlation with clinical outcomes.

Biomarkers in Aneurysmatic and Spontaneous Subarachnoid Haemorrhage: A Clinical Prospective Multicentre Biomarker Panel Study of S100B, Claudin-5, Interleukin-10, TREM-1, TREM-2 and Neurofilament Light Chain As Well As Immunoglobulin G and M.

Following aneurysmatic subarachnoid haemorrhage (SAH), complex pathophysiological processes take place which result in ischaemia, dysfunction of the blood-brain barrier and the clinical development of vasospasms and delayed cerebral ischaemia (DCI). The aim of this study was to present a biomarker panel that can be used for temporal assignment in the pathophysiological process after haemorrhage, a prediction of vasospasm, DCI or outcome. In a prospective multicentre approach, complex laboratory chemistry tests were used to determine the value of the biomarkers S100B, Claudin-5, Interleukin (IL) -10, Triggering receptor expresses on myeloid cells (TREM)-1 and TREM-2, and neurofilament light chain (NfL) as well as IgG and IgM in plasma and Cerebro-spinal-fluid (CSF) in SAH patients.

TRAUMA AND THE ENTEROCYTE: DISTURBANCE OF COMMUNICATION AND DELINEATION.

The enterocyte as major building stone of the intestinal barrier plays a central role in maintaining cellular homeostasis and mediating host-environment interactions. Trauma, whether direct or remote, disrupts enterocyte function through complex mechanisms including impaired oxygen delivery, disturbed intercellular communication, and compromised nutrient uptake and metabolite clearance. These changes may lead to barrier dysfunction and altered repair mechanisms, facilitating systemic inflammation and remote organ injury.

Dynamic functional assessment of T cells reveals an early suppression correlating with adverse outcome in polytraumatized patients.

Introduction: Most trauma patients require intensive care treatment and are susceptible to developing persistent inflammation and immunosuppression, potentially leading to multi organ dysfunction syndrome (MODS) and dependence on long term care facilities. T cells undergo changes in numbers and function post trauma. T cell dysfunction in polytraumatized patients was characterized using functional immunomonitoring to predict individual clinical outcome.

A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation.

Background: C-reactive protein (CRP) represents a routine diagnostic marker of inflammation. Dissociation of native pentameric CRP (pCRP) into the monomeric structure (mCRP) liberates proinflammatory features, presumably contributing to excessive immune cell activation via unknown molecular mechanisms.

Results: In a multi-translational study of systemic inflammation, we found a time- and inflammation-dependent pCRP dissociation into mCRP.

Modulation of the hepatic RANK-RANKL-OPG axis by combined C5 and CD14 inhibition in a long-term polytrauma model.

Background: Polytrauma and hemorrhagic shock can lead to direct and indirect liver damage involving intricate pathophysiologic mechanisms. While hepatic function has been frequently highlighted, there is minimal research on how the receptor activator of the NF-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system is regulated in the liver following trauma. Furthermore, cross-talking complement and toll-like-receptor (TLR) systems can contribute to the posttraumatic response.

Effect of Unfractionated Heparin Dose on Complement Activation and Selected Extracellular Vesicle Populations during Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation.

Effects of anesthesia with sevoflurane on outcome parameters in murine experimental studies.

Purpose: Multiple murine studies modelling the immuno-pathophysiological consequences of trauma, shock, burn or sepsis were performed during the last decades. Almost every animal model requires anesthesia for practical and ethical reasons. Furthermore, often, corresponding control groups involve untreated animals without or with a limited exposure to anesthetics.

Crepuscular rays - The bright side of complement after tissue injury.

Acute injuries trigger an intense activation of the body's defense mechanisms aiming to limit damage and initiate healing. Among the crucial components of the intravascular immune system, the complement system plays a significant role in traumatic injuries, albeit often negatively. It has been suggested that excessive activation of the complement system, transitioning from a localized and timed response to a systemic one, can lead to a loss of its host-protective characteristics.

Trauma-associated extracellular histones mediate inflammation via a MYD88-IRAK1-ERK signaling axis and induce lytic cell death in human adipocytes.

Despite advances in the treatment and care of severe physical injuries, trauma remains one of the main reasons for disability-adjusted life years worldwide. Trauma patients often suffer from disturbances in energy utilization and metabolic dysfunction, including hyperglycemia and increased insulin resistance. White adipose tissue plays an essential role in the regulation of energy homeostasis and is frequently implicated in traumatic injury due to its ubiquitous body distribution but remains poorly studied.

X-Ray-Based 3D Histopathology of the Kidney Using Cryogenic Contrast-Enhanced MicroCT.

The kidney's microstructure, which comprises a highly convoluted tubular and vascular network, can only be partially revealed using classical 2D histology. Considering that the kidney's microstructure is closely related to its function and is often affected by pathologies, there is a need for powerful and high-resolution 3D imaging techniques to visualize the microstructure. Here, we present how cryogenic contrast-enhanced microCT (cryo-CECT) allowed 3D visualization of glomeruli, tubuli, and vasculature.

Glomerular injury after trauma, burn, and sepsis.

Acute kidney injury development after trauma, burn, or sepsis occurs frequently but remains a scientific and clinical challenge. Whereas the pathophysiological focus has mainly been on hemodynamics and the downstream renal tubular system, little is known about alterations upstream within the glomerulus post trauma or during sepsis. Particularly for the glomerular endothelial cells, mesangial cells, basal membrane, and podocytes, all of which form the glomerular filter, there are numerous in vitro studies on the molecular and functional consequences upon exposure of single cell types to specific damage- or microbial-associated molecular patterns.

Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance?

The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.

Neurochemical Monitoring of Traumatic Brain Injury by the Combined Analysis of Plasma Beta-Synuclein, NfL, and GFAP in Polytraumatized Patients.

Traumatic brain injury (TBI) represents a major determining factor of outcome in severely injured patients. However, reliable brain-damage-monitoring markers are still missing. We therefore assessed brain-specific beta-synuclein as a novel blood biomarker of synaptic damage and measured the benchmarks neurofilament light chain (NfL), as a neuroaxonal injury marker, and glial fibrillary acidic protein (GFAP), as an astroglial injury marker, in patients after polytrauma with and without TBI.

Adipose tissue: a neglected organ in the response to severe trauma?

Despite the manifold recent efforts to improve patient outcomes, trauma still is a clinical and socioeconomical issue of major relevance especially in younger people. The systemic immune reaction after severe injury is characterized by a strong pro- and anti-inflammatory response. Besides its functions as energy storage depot and organ-protective cushion, adipose tissue regulates vital processes via its secretion products.

Trauma-related acute kidney injury during inpatient care of femoral fractures increases the risk of mortality: A claims data analysis.

Although femoral fractures can hit anyone, they carry an especially high burden in the elderly and are multifaceted in their injury pattern, related complications, and subsequent therapeutic strategies. An often underestimated posttraumatic risk is the development of trauma-related acute kidney injury (TRAKI). However, for TRAKI, no outcome study with a large data approach exists addressing fractures.

Temporal-spatial organ response after blast-induced experimental blunt abdominal trauma.

Abdominal trauma (AT) is of major global importance, particularly with the increased potential for civil, terroristic, and military trauma. The injury pattern and systemic consequences of blunt abdominal injuries are highly variable and frequently underestimated or even missed, and the pathomechanisms remain still poorly understood. Therefore, we investigated the temporal-spatial organ and immune response after a standardized blast-induced blunt AT.

Small Extracellular Vesicles Propagate the Inflammatory Response After Trauma.

Trauma is the leading cause of death in individuals under 44 years of age. Thorax trauma (TxT) is strongly associated with trauma-related death, an unbalanced innate immune response, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction. It is shown that different in vivo traumata, such as TxT or an in vitro polytrauma cytokine cocktail trigger secretion of small extracellular nanovesicles (sEVs) from endothelial cells with pro-inflammatory cargo.

New Insights into Xenotransplantation for Cartilage Repair: Porcine Multi-Genetically Modified Chondrocytes as a Promising Cell Source.

Transplantation of xenogenic porcine chondrocytes could represent a future strategy for the treatment of human articular cartilage defects. Major obstacles are humoral and cellular rejection processes triggered by xenogenic epitopes like α-1,3-Gal and Neu5Gc. Besides knockout (KO) of genes responsible for the biosynthesis of respective epitopes (GGTA1 and CMAH), transgenic expression of human complement inhibitors and anti-apoptotic as well as anti-inflammatory factors (CD46, CD55, CD59, TNFAIP3 and HMOX1) could synergistically prevent hyperacute xenograft rejection.

Evaluation of the gut microbiome in association with biological signatures of inflammation in murine polytrauma and shock.

Severe injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage.

Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury.

The immune response following trauma represents a major driving force of organ dysfunction and poor outcome. Therefore, we investigated the influence of an additional hemorrhagic shock (HS) on the early posttraumatic immune dysbalance in the whole population of blood leukocytes. A well-established murine polytrauma (PT) model with or without an additional pressure-controlled HS (mean arterial pressure of 30 mmHg (±5 mmHg) for 60 mins, afterwards fluid resuscitation with balanced electrolyte solution four times the volume of blood drawn) was used.

Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity.

Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a "C3 bypass" activation of C5.

Thirty-Eight-Negative Kinase 1 Is a Mediator of Acute Kidney Injury in Experimental and Clinical Traumatic Hemorrhagic Shock.

Trauma represents a major socioeconomic burden worldwide. After a severe injury, hemorrhagic shock (HS) as a frequent concomitant aspect is a central driver of systemic inflammation and organ damage. The kidney is often strongly affected by traumatic-HS, and acute kidney injury (AKI) poses the patient at great risk for adverse outcome.