Search Results (90)

Background: A major challenge in developing effective immunological damage-control therapies for traumatic hemorrhage (TH) is the lack of animal models that accurately reproduce the immune and pathophysiological responses observed in humans. In this study, we established a clinically relevant rat model that combines blast injury with hemorrhagic shock in a simulated prolonged damage control resuscitation environment. Methods: Male Sprague Dawley rats were anesthetized and subjected to moderate blast overpressure, followed by controlled hemorrhage equivalent to 40% of the estimated total blood volume. Animals then received hypotensive resuscitation with Plasma-Lyte A at twice the shed blood volume. Plasma-Lyte A was used in our study to correct hypovolemia and electrolyte imbalances, thereby helping to standardize the traumatic hemorrhage model. Results: Four of six rats in the blast-plus-hemorrhage (B + H) group survived the 25 h observation period. During resuscitation, mean arterial pressure remained markedly below baseline for at least 4 h. The B + H insult triggered a rapid innate immune response, characterized by elevated circulating HMGB1, terminal complement activation, and increased myeloperoxidase levels. Complement deposition (C4d, C5a, and C5b-9) was evident in lung tissue, accompanied by multi-organ histopathological injury, including pronounced inflammatory cell infiltration, hemorrhage, and cellular degeneration, apoptosis, or necrosis. Metabolic disturbances, including acidosis, hyperkalemia, and dilutional anemia, were also observed. Conclusions: Overall, this model reproduced key features of inflammation-driven multi-organ dysfunction syndrome seen in human polytrauma, supporting its utility for studying TH-related immunopathology and therapeutic interventions during prolonged damage control resuscitation. Full article

One major challenge in optimizing vehicle underbody structures for blast protection is the trade-off between the high cost of physical tests and the limited accuracy of simulations. We introduce a predictive framework that is co-driven by limited physical measurements and systematically augmented simulation datasets. The main problem arises from the complex components of blast impact signals, which makes it difficult to augment the load signals for finite element simulations when only extremely small sample sets are available. Specifically, a small-scale data-augmentation model within the wavelet domain based on a conditional generative adversarial network (CGAN) was designed. Real-time perturbations, governed by cumulative distribution functions, were introduced to expand and diversify the data representations for enhanced dataset enrichment. A predictive model based on Gaussian process regression (GPR) that integrates physical experimental data with augmented data wavelet characteristics is employed to estimate injury indices, using wavelet scale energies reduced via principal component analysis (PCA) as inputs. Cross-validation shows that this hybrid model achieves higher accuracy than using simulations alone. Through the case study, the model demonstrates that increased hull angle and depth can effectively reduce occupant injury. Full article

Repeated exposure to low-level blast overpressure (BOP) during controlled detonations is an emerging occupational health concern for military breachers and Special Operations Forces personnel, given accumulating evidence that chronic exposure may produce subtle, subclinical neurotrauma. This study derived a latent neuroinjury construct integrating three complementary domains of brain health—post-concussive symptoms, working-memory performance, and circulating biomarkers—to determine whether breachers exhibit coherent patterns of neurobiological alteration. Symptom severity was assessed using the Rivermead Post-Concussion Questionnaire (RPQ), and working memory was assessed with the N-Back task and a panel of thirteen neuroproteomic biomarkers was measured reflecting astroglial activation, neuronal and axonal injury, oxidative stress, inflammatory signaling, and neurotrophic regulation. Experienced Canadian Armed Forces breachers with extensive occupational BOP exposure were compared with unexposed controls. Bayesian latent-variable modeling provided probabilistic evidence for a chronic, subclinical neurobiological signal, with the strongest contributions arising from self-reported symptoms and smaller but consistent contributions from the biomarker domain. Working-memory performance did not load substantively on the latent factor. Several RPQ items and circulating biomarkers showed robust loadings, and the latent neuroinjury factor was elevated in breachers relative to controls (97% posterior probability). The pattern is broadly consistent with subclinical neurobiological stress in the absence of measurable cognitive impairment, suggesting early or compensated physiological alterations rather than overt dysfunction. This multidomain, biomarker-informed framework provides a mechanistically grounded and scalable approach for identifying subtle neurobiological strain in military personnel routinely exposed to repetitive low-level blast. It may offer value for risk stratification, operational health surveillance, and the longitudinal monitoring of neurobiological change in high-risk occupations. Full article

The complement system is crucial for immune defense, linking innate and adaptive immunity. In the classical and lectin pathways, C4 is split into C4b, triggering opsonization, lysis, and the removal of pathogens and damaged cells. Dysregulated activation of C4 and other components of the classical pathway can lead to tissue damage and heightened inflammation, whereas appropriate regulation of C4b activity serves to mitigate excessive inflammation and prevent injury. ELISA analysis demonstrated C4 activation and cleavage during the co-incubation of PRRSV with fresh porcine serum. Immunoelectron microscopy revealed that porcine red blood cells could immunologically adhere to PRRSV, and C4b was involved in this adhesion process. BLAST (NCBI BLAST+ 2.14.1) analysis revealed that porcine CR1-like CCPs 1-3, CR1-like CCPs 12-14, and CR1-like CCPs 19-21 share high similarity with the CCP 1-3 region of human CR1, which mediates C4b binding. Yeast two-hybrid assays confirmed that all three CR1-like fragments bind C4b. To elucidate the interaction mechanism, homology models of C4b and CR1-like fragments were constructed, followed by molecular docking and dynamics simulations, identifying 18 key amino acids in porcine CR1-like involved in C4b binding. Surface plasmon resonance further validated the binding affinity of CR1-like CCPs 1-3, its mutant 118I, and C4b. These results enhance our understanding of complement regulation and provide a foundation for developing therapeutic strategies targeting complement-related diseases. Full article

Introduction: Allogeneic penetrating limbo-keratoplasty (limbo-PK) is one of the surgical methods for the treatment of limbal stem cell deficiency (LSCD). We report real-life results on different entities. Methods: Patients treated with limbo-PK at the Department of Ophthalmology of the University Medical Center Mainz were evaluated retrospectively. The primary endpoint was the epithelialization of the graft one year postoperatively. In addition, the postoperative best corrected visual acuity (BCVA), ocular concomitant diseases, drug treatment, and the need for further eye surgery postoperatively were examined. Results: We included 14 eyes of 13 patients (4 female) aged 59.8 ± 14.1 years who underwent limbo-PK between 2020 and 2024. Indications for limbo-PK included chemical burns (n = 4), blast injuries (n = 4), thermal burns (n = 2), trauma (n = 1) graft-versus-host disease (n = 1), and ectrodactyly-ectodermal dysplasia (EEC) (n = 1). The mean preoperative BCVA was 2.2 ± 0.6 logMAR (range: light perception to 0.7 logMAR). Four limbo-PK-grafts were HLA-typed. All limbo-PKs were combined with amniotic membrane transplantation; three with cataract surgery and one with tarsorrhaphy. Postoperatively, all patients received local immunosuppression, and 12 (85.7%) received additional systemic immunosuppression. At one-year follow-up mean BCVA increased to 1.0 ± 0.7 logMAR (range: 2.3 to 0.1, p-value = 0.03) and 11 of 14 eyes showed a functional graft with closed epithelium. In the further postoperative course, four patients needed a further Limbo-PK due to graft failure (n = 2), immune graft rejection after stopping local immunosuppressive therapy (n = 1) and perforation of the graft in a severe case of GvHd (n = 1). Conclusions: Limbo-PK is an effective surgical method for the treatment of LSCD. In our study cohort, we observed a significant improvement in mean BCVA one year postoperatively, with a functional, epithelialized graft achieved in 11 of 14 eyes. Full article

Background: Blast-induced spinal cord injuries (bSCI) account for 75% of all combat-related spinal trauma and are associated with long-term functional impairments. However, limited studies have evaluated the neuropathological outcomes in the spinal cord following blast exposure. Objectives In this study, we aimed to determine the acute and sub-acute neuropathological changes in the spinal cord of ferrets after blast exposure. Methods: An advanced blast simulator was used to expose ferrets to tightly coupled repeated blasts. The Catwalk XT system was used to detect gait performances in ferrets at 24 h and 1 month post-blast exposure. After euthanasia, the cervical spinal cord samples were collected at 24 h or 1 month post-blast. A quantitative real-time polymerase chain reaction was performed to evaluate changes in the gene expression of multiple Toll-like Receptors (TLR), Cyclooxygenase (COX-1 and COX-2) enzymes and cytokines. Western blotting was performed to investigate markers of axonal injury (Phosphorylated-Tau, pTau; Phosphorylated Neurofilament Heavy Chain, pNFH; and Neurofilament Light Chain present in degenerating neurons, NFL-degen) and neuroinflammation (Glial Fibrillary Acidic Protein, GFAP; and Ionized Calcium Binding Adaptor Molecule, Iba-1). Results: Blast exposure significantly affected the gait performances in ferrets, especially at 24 h post-blast. Multiple TLRs, COX-2, Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor-α (TNF-α) were significantly upregulated in the spinal cord at 24 h after blast exposure. Although only TLR3 was significantly upregulated at 1 month, non-significant increases in TLR1 and TLR2 were observed in the spinal cord at 1 month post-blast. Phosphorylation of Tau at serine (Ser396 and Ser404) and threonine (Thr205) increased in the spinal cord at 24 h and 1 month post-blast exposure. The increased expression of pNFH and NFL-degen proteins was evident at both time points. The expression of GFAP, but not Iba-1, significantly increased at 24 h and 1 month following blast exposure. Conclusions: Our results indicate that blast exposure causes acute and sub-acute neuroinflammation and associated axonal injury in the cervical spinal cord. These data further suggest that inhibition of TLRs and/or COX-2 enzyme might offer protection against blast-induced injuries to the spinal cord. Full article

Purpose: This case series examines the feasibility and outcomes of using a multi-tissue extracellular matrix (ECM) powder as an adjunct to standard wound care in a conflict zone. Primary objectives were granulation by day 7, wound closure, and minimizing early complications among patients with complex ballistic and blast injuries in Gaza during the 2024 Israeli military offensive. Methods: A retrospective observational study was conducted at the European Gaza Hospital from April to June 2024. Fifteen patients with high-energy soft tissue injuries who received ECM powder (XCellistem™) after surgical debridement were included. Data were extracted from operative reports, wound documentation, and clinical follow-up. Outcomes included granulation by day 7, wound closure method, and complications such as infection or dehiscence. Results: All 15 patients (median age 28; 14 male) sustained severe trauma, with 80% having exposed bone or tendon. ECM was applied directly to wound beds and often co-applied with vancomycin. Granulation tissue was observed in 12 patients by day 7, and 13 achieved wound closure via grafting, flap coverage, or secondary intention. No adverse reactions to ECM were reported. Conclusions: Multi-tissue ECM powder seems feasible and safe under austere conditions and appeared to support wound healing in severely injured patients. Its shelf stability, ease of use, and regenerative potential make it a promising adjunct for surgical care in resource-constrained conflict zones. Full article

Polytrauma is a critical global health concern characterized by immune dysregulation and a high risk of multiple organ dysfunction syndrome (MODS). Early molecular mechanisms linking trauma severity to organ injury are poorly understood. We used two rat blast-polytrauma models: a tourniquet-induced ischemia/reperfusion injury (tIRI) model and a non-ischemia/reperfusion injury (non-IRI) model. Naïve animals served as controls. RT-qPCR of 120 inflammatory genes in the lung, kidney, and liver, combined with STRING protein–protein interaction analysis, revealed distinct yet overlapping inflammatory gene signatures across all the organs. A core set of genes (Il6, Lbp, Nos2, and Lcn2) was consistently upregulated, indicating shared inflammatory pathways. Transcriptomic responses were most pronounced in the tIRI group, with greater magnitude and altered temporal dynamics, uniquely amplifying pro-inflammatory cytokines, immune cell activators, chemokines, and tissue damage markers. Lipocalin-2 (Lcn2/NGAL) emerged as a shared hub gene across all the organs within 24 h post-injury. Its expression significantly correlated with MODS activity and adverse outcomes, independent of the injury model. At 168 h, Lcn2 expression correlated with increased liver damage and NGAL levels correlated with tissue trauma severity. These findings elucidate distinct pro-inflammatory mediators and networks underlying secondary organ dysfunction, highlighting NGAL as a potential universal biomarker of trauma-induced inflammation and MODS activity, suggesting it as a therapeutic target. Full article

Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term neuroendocrine consequences of mild, repetitive brain trauma are poorly understood. In this study, we investigated the temporal dynamics of hypothalamic–pituitary–adrenal (HPA) axis dysregulation following repeated mild concussive head impacts and blast exposures using two clinically relevant rodent models. Male Sprague-Dawley rats were subjected to repeated mild concussive impacts using a modified weight drop model or repeated blast exposures using an advanced blast simulator. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured on days 1 and 30 post-injuries. Our findings revealed that repeated blast exposures induced elevation of plasma ACTH and corticosterone on days 1 and 30 post-blasts. After the repeated mild concussive impacts, increased plasma levels of corticosterone were observed on days 1 and 30, but ACTH levels were increased only on day 30. This study is among the first to directly compare neuroendocrine outcomes of repeated mild concussive impacts and blast exposures within a unified experimental framework. Our findings demonstrate distinct temporal trajectories of HPA axis dysregulation depending on injury type and highlight plasma levels of ACTH and corticosterone as potential biomarkers of subclinical brain trauma. These insights may inform early diagnostic approaches and therapeutic strategies aimed at mitigating long-term stress-related complications following mild traumatic brain injuries. Full article

Blast-induced polytrauma (BIPT) is a common injury among military personnel exposed to explosive blasts. It is increasingly recognized as a complex, multisystem disorder that extends beyond neurological damage to include systemic metabolic and inflammatory dysfunction. Adipokines, particularly leptin and adiponectin, are hormones secreted by adipose tissue and are emerging as key mediators in the pathophysiology of traumatic brain injuries. Yet, their long-term dynamics following blast exposure remain unclear. This study investigated the temporal profiles of plasma leptin and adiponectin in a longitudinal rat model of BIPT. Adult male Sprague Dawley rats were subjected to either a single (B) or repeated (BB) blast exposure (20 psi) or served as sham controls. Plasma samples were collected at 24 h, 1 month, 6 months, and 12 months post-exposure, and adipokine levels were measured using Enzyme-linked Immunosorbent Assay. Adiponectin levels exhibited a biphasic response: both B and BB groups showed significant early decrease at 24 h and 1 month compared to sham animals, followed by robust elevation at 6 and 12 months, particularly in the repeated blast group. In contrast, leptin levels remained unchanged acutely but rose significantly at 6 and 12 months post-blast, with the BB group again showing the highest levels. These patterns indicate sustained, exposure-dependent dysregulation of adipokine signaling after blast trauma. The study provides the first longitudinal profile of systemic adipokine responses to BIPT, revealing their potential as accessible biomarkers and therapeutic targets. These findings support a model of chronic metabolic and inflammatory imbalance in BIPT and warrant further investigation in human cohorts and mechanistic studies. Full article

Ammonia is emerging as a promising zero-carbon marine fuel due to its high hydrogen density, low storage pressure, and long-term stability, making it well-suited for supporting sustainable maritime energy systems. However, its adoption introduces serious safety challenges, as its toxic, flammable, and corrosive properties pose greater risks than many other alternative fuels, necessitating rigorous risk assessment and safety management. This study presents a comprehensive investigation of potential ammonia leakage scenarios that may arise during the fuel gas supply process within confined compartments of marine vessels, such as the fuel preparation room and engine room. The simulations were conducted using FLACS-CFD V22.2, a validated computational fluid dynamics tool specialized for flammable gas dispersion and explosion risk analysis in complex geometries. The model enables detailed assessment of gas concentration evolution, toxic exposure zones, and overpressure development under various leakage conditions, providing valuable insights for emergency planning, ventilation design, and structural safety reinforcement in ammonia-fueled ship systems. Prolonged ammonia exposure is driven by three key factors: leakage occurring opposite the main ventilation flow, equipment layout obstructing airflow and causing gas accumulation, and delayed sensor response due to recirculating flow patterns. Simulation results revealed that within 1.675 s of ammonia leakage and ignition, critical impact zones capable of causing fatal injuries or severe structural damage were largely contained within a 10 m radius of the explosion source. However, lower overpressure zones extended much further, with slight damage reaching up to 14.51 m and minor injury risks encompassing the entire fuel preparation room, highlighting a wider threat to crew safety beyond the immediate blast zone. Overall, the study highlights the importance of targeted emergency planning and structural reinforcement to mitigate explosion risks in ammonia-fueled environments. Full article

Blast-induced mild traumatic brain injury (mTBI) occurs when shock waves travel through blood vessels and cerebrospinal fluid, leading to cerebral demyelination, which results in cognitive impairments and neuropsychiatric issues that impact quality of life. This study aims to evaluate myelin changes in white matter in mice with mTBI induced by an open-field low-intensity blast (LIB) using a newly implemented 3D adiabatic T1ρ prepared fast spin echo (Adiab-T1ρ-FSE) sequence for quantitative T1ρ MRI mapping. Thirty male C57BL/6 mice, including 15 mTBI and 15 sham controls, were scanned on a 3T Bruker MRI scanner. Luxol fast blue (LFB) staining was performed to assess myelin content differences between the mTBI and sham control groups. A significantly higher T1ρ value in the medial corpus callosum (MCC) was found in mTBI mice compared to controls (126.8 ± 2.5 ms vs. 129.8 ± 2.5 ms; p < 0.001), consistent with the reduced myelin observed in LFB staining (0.80 ± 0.14 vs. 1.02 ± 0.06; p = 0.004). Moreover, a significant negative correlation between T1ρ and histological myelin content measurements was observed (r = −0.57, p = 0.02). Our findings demonstrate that T1ρ is a promising biomarker for detecting mTBI-associated demyelination in the brain. Full article

The management of penetrating rectal trauma has evolved from a historic 4-D algorithm (Divert, Drain, Direct repair, and Distal washout) to a more selective approach. This case report describes a patient with multiple wounds, including a high-grade extraperitoneal rectal injury resulting from a pelvic explosive injury. The patient was successfully treated with intraluminal vacuum therapy (ILVT). This case highlights ILVT as a novel method for managing complicated blast-related rectal injuries. While there are limited publications on combat-related penetrating rectal injuries that provide evidence-based guidelines, we suggest an aggressive surgical approach combined with negative pressure wound therapy for optimal patient outcomes. Full article

Firework-related injuries remain a serious public health issue in Germany, especially during New Year’s Eve. While many injuries are minor, the misuse of illegal or homemade fireworks can cause severe trauma resembling military combat injuries and can heavily burden emergency services. Notably, injury rates declined during the COVID-19 firework bans, underscoring the impact of preventive measures. We report two cases of young males with severe injuries from illicit fireworks. The first is a case of a 16-year-old that detonated an illegal Polish firework ball bomb, sustaining 9% total body surface area (TBSA) burns (second- to third-degree), hand fractures, compartment syndrome of the hand, and soft-tissue trauma. He underwent multiple surgeries, including fasciotomy, osteosynthesis, and skin grafting. The other case presented is a 19-year-old man who was injured by a homemade device made of bundled firecrackers, suffering deep facial and bilateral hand burns. He required prolonged ventilation, surgical debridement, and treatment with Kerecis^® fish skin and Epicite^® dressings. Both required intensive ICU care, interdisciplinary management, and lengthy rehabilitation. Total hospital costs amounted to €58,459.52 and €94,230.23, respectively, as calculated according to the standardized German DRG. These cases illustrate the devastating impact of illegal fireworks. The devastating consequences of explosive trauma are often difficult to treat and may lead to long-term functional and psychological impairments. Prevention through public education, stricter regulations, and preparedness is essential. Pandemic-era injury reductions support sustained policy efforts. Full article

It is increasingly recognized that early perturbation of energy metabolism might have important implications in management and ultimately the neurological outcome in patients with traumatic brain injury (TBI). At the same time, treatments and screening tools successfully developed in preclinical TBI models have failed to translate to the clinic. As ferrets possess primate-like gyrencephalic brains that may better replicate the human response to neurologic injury, the goal of this study was to noninvasively measure brain energy metabolism after injury in a ferret model of TBI. To this end, metabolic imaging of hyperpolarized (HP) [1-¹³C]pyruvate (Pyr) and its conversion to lactate (Lac) and bicarbonate (Bic) was performed in ferrets before and after combined under-vehicle blast and controlled cortical impact injury. Reduced Bic/Pyr, reflecting reduced pyruvate dehydrogenase activity, was detected 8–10 days post-injury whereas no difference in Lac/Pyr was observed. These results demonstrate the feasibility of using metabolic imaging of HP [1-¹³C]Pyr to measure perturbations in brain energy metabolism in a novel highly translatable animal model of TBI. The method may contribute to both improved understanding of injury mechanisms and more effective drug development. Full article