Multiple Injuries Research Articles

Knockdown of BMP7 induced oligodendrocyte apoptosis, demyelination and motor function loss

BackgroundDemyelinating diseases, including multiple sclerosis (MS) and spinal cord injury (SCI), lead to significant neurological deficits primarily due to the loss of oligodendrocytes (OLs). Bone Morphogenetic Protein 7 (BMP7) is expressed abundantly in the central nervous system and previous studies showed its protective effect in reducing OL loss. In this study, we aim to explore BMP7's potential as a biomarker and therapeutic target for demyelinating diseases by investigating its expression and effects on OLs and myelin sheath integrity. MethodWe analyzed multiple Gene Expression Omnibus datasets for BMP7 expression profiles in demyelinating conditions such as MS and SCI. Experimentally, we employed a BMP7 knockdown model in rat spinal cords using adeno-associated virus8 vectors to specifically reduce BMP7 expression. Western blotting, immunofluorescence, and Nissl staining were used to assess the effect on OL and other types of cells. The structure of myelin sheath and locomotor function were evaluated using transmission electron microscopy and BBB scores, and statistical analysis included ROC curves and ANOVA to evaluate BMP7's diagnostic and therapeutic potential. ResultsBMP7 expression consistently decreased across various demyelinating models, and BMP7 knockdown led to increased OL apoptosis through the Smad1/5/9 pathway, with no apparent effect on other cell types. This reduction in OLs was associated with myelin degeneration, axonal damage, and impaired motor function. ConclusionThe study confirms BMP7's significant involvement in the pathophysiology of demyelinating diseases and supports its potential as a therapeutic target or biomarker. Future research should focus on therapeutic strategies to enhance BMP7 function and further investigate the mechanisms by which BMP7 supports myelin integrity.

Postmortem CT and autopsy findings in an elevator-related death: a case report

AbstractElevator-related fatalities and injuries are rarely discussed. Falls have been identified as the first cause of mortality in the majority of these accidents. Evidence suggests that many elevator accidents may be attributed to inadequate equipment maintenance or malfunctions of the devices. This study examines a case involving an elevator maintenance worker found within an elevator shaft, using postmortem computed tomography (PMCT) along with a full autopsy. The autopsy revealed that the cause of death was severe polytrauma resulting from dragging, compression, and crushing mechanisms, which resulted in a dislocated skull and multiple thoraco-abdominal injuries, including exposed organs and viscera. Detailed examination identified a cranio-encephalic crush, leading to a significant alteration in the physiognomy of the facial structures. Additionally, PMCT revealed complex spinal fractures, such as a Jefferson fracture and a complete Chance fracture at the D6 vertebra, accompanied by spinal deviation proximal to the fracture site. Autopsy findings corroborated these PMCT results. A multidisciplinary approach, including PMCT, is proposed as a strategic method for the comprehensive reconstruction of such accidents, facilitating the collection of extensive data.

Heterotopic Ossifications Following Intramedullary Stabilization of Femoral Fractures in Polytraumatized Patients.

Heterotopic ossifications (HOs) are a well-known complication following total hip arthroplasty. Yet only little is known about the development of HOs following a femoral fracture and intramedullary stabilization in polytraumatized patients. Thus, the present study aimed to investigate whether the development of HOs is being observed more frequently in patients suffering polytrauma compared to those with single-extremity trauma. The retrospective outcome study was conducted at our level I trauma center. All patients admitted from 2010 to 2020 were included if they (1) presented with multiple injuries (≥2 body regions), (2) had an Injury Severity Score ≥16, (3) suffered a femoral fracture, and (4) were treated with intramedullary stabilization. Furthermore, a control group was established to match the polytrauma group (sex, age), who were suffering from single-extremity trauma (femoral fracture) which was treated with intramedullary stabilization. Subsequently, X-rays of the hip were performed and evaluated for up to one-year post-trauma. Our study group consisted of 36 patients in total (91.7% male; mean age 39.4 ± 17.4 years, range: 18-82 years). The polytrauma (PT) group included 12 patients (mean age 39.5 years, median ISS 28), whereas the control group (single-extremity-trauma) included 24 patients (mean age 39.3 years). We documented HOs in nine (75%) patients in the PT group vs. five (20.8%) patients in the single-extremity group (p = 0.03). In this study, we were able to demonstrate that heterotopic ossifications are being observed significantly more frequently in patients suffering from polytrauma in comparison to patients with single-extremity trauma following intramedullary stabilization after a femoral fracture.

Translation, extension, and evaluation of usability, usefulness, and safety of a fall prevention and management program for people living with spinal cord injury and multiple sclerosis who use wheelchairs or scooters full time.

Falls are prevalent among people living with Multiple Sclerosis (PwMS) and Spinal Cord Injury (PwSCI) who use wheelchairs or scooters (WC/S) full time, however, there is a scarcity of evidence-based fall prevention and management programs. To describe the systematic translation of an in-person fall prevention and management program (Individualized Reduction Of FaLLs - iROLL) for PwMS to an online platform, extending its scope to include PwSCI, and to evaluate the preliminary useability, usefulness, and safety of the intervention. iROLL was systematically translated to an online platform (iROLL-O). PwMS and PwSCI who use a WC/S full time, experienced at least one fall within the past 36 months, and could transfer independently or with minimal to moderate assistance, enrolled in iROLL-O. Usability, usefulness, and safety were evaluated through 1:1 semi-structured interviews, gathering feedback on: perceived impact of the intervention on falls and functional mobility, program experiences, adverse events, and recommendations for improvement. Five participants successfully completed the iROLL-O program. No safety concerns were raised by participants. Themes emerging from the semi-structured interviews included: (1) barriers and facilitators to program access, (2) motivation for participation, (3) program outcomes, and (4) program content and structure. Participants reported reduced concerns about falling, enhanced functional mobility skills, and highlighted the supportive nature of synchronous group meetings for learning. No adverse events occurred during the implementation of iROLL-O and participants found the program to be useable and useful. Further testing is needed to examine efficacy among a large and diverse population.

Lifetime history of head injury is associated with reduced perivascular space number in acute mild traumatic brain injury.

Traumatic brain injury impairs function of the glymphatic system, a perivascular network involved in waste clearance. Enlarged perivascular spaces visible on MRI are an emerging biomarker of glymphatic function. This study characterized enlarged perivascular spaces in acute head injury with 7 T MRI. Healthy controls (n = 8) and patients (n = 11) with mild traumatic brain injury underwent MRI within 7 days of injury and were evaluated for lifetime history of head injury, neurobehavioral symptoms and sleep disturbances. MRI-visible perivascular spaces were quantified and assessed according to published criteria. The number of enlarged perivascular spaces was significantly higher in traumatic brain injury patients than controls (P = 0.015). Among healthy controls, 6/8 scored 'none' or 'mild' on the perivascular space rating scale, while 10/11 patients scored 'moderate', 'frequent' or 'severe'. There was an inverse relationship between perivascular space number and number of lifetime head injuries. Patients with more prior head injuries exhibited fewer enlarged perivascular spaces (P = 0.014). These results indicate that mild head injury results in acute alterations in perivascular space number, and this effect is mediated by previous head injury history. Enlarged perivascular spaces may reflect a glymphatic response that is diminished after multiple head injuries, although this will require further study.

Roles of HMGB1 on life-threatening traumatic brain injury and sequential peripheral organ damage

Traumatic brain injury (TBI) has been found to be associated with certain peripheral organ injuries; however, a few studies have explored the chronological influences of TBI on multiple organs and the systemic effects of therapeutic interventions. Particularly, high-mobility group box 1 (HMGB1) is a potential therapeutic target for TBI; however, its effects on peripheral organs remain unclear. Therefore, this study aimed to determine whether severe TBI can lead to multiple organ injury and how HMGB1 inhibition affects peripheral organs. This study used a weight drop-induced TBI mouse model and found that severe TBI can trigger short-lived systemic inflammation, in the lungs and liver, but not in the kidneys, regardless of the severity of the injury. TBI led to an increase in circulating HMGB1 and enhanced gene expressions of its receptors in every organ. Anti-HMGB1 antibody treatment reduced neuroinflammation but increased inflammation in peripheral organs. This study also found that HMGB1 inhibition appears to have a beneficial role in early neuroinflammation but could lead to detrimental effects on peripheral organs through decreased peripheral immune suppression. This study provides novel insights into the chronological changes in multiple organs due to TBI and the unique roles of HMGB1 between the brain and other organs.

SIRT1 in acute lung injury: unraveling its pleiotropic functions and therapeutic development prospects.

Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, often associated with severe complications and even death. In ALI, macrophages, alveolar epithelial cells and vascular endothelial cells in the lung are damaged to varying degrees and their function is impaired. Research in recent years has focused on the use of SIRT1 for the treatment of ALI. In this paper, we reviewed the role of SIRT1 in ALI in terms of its cellular and molecular mechanism, targeting of SIRT1 by non-coding RNAs and drug components, as well as pointing out the value of SIRT1 for clinical diagnosis and prognosis. Based on the current literature, SIRT1 exhibits diverse functionalities and possesses significant therapeutic potential. Targeting SIRT1 may provide new therapeutic ideas for the treatment of ALI.

Aortic Dissection in a Neonate Receiving Extracorporeal Life Support Therapy: A Case Report.

Extracorporeal life support (ECLS) therapy is increasingly being used to support children with refractory cardiorespiratory failure, but its use is occasionally associated with complications.1 Neonatal aortic dissection in association with ECLS is rare and the clinical sequelae of aortic dissection in neonates are poorly understood. We report a case of extensive type B aortic dissection in a neonate receiving ECLS therapy for refractory cardiogenic shock secondary to tachycardia-induced cardiomyopathy and Wolf Parkinson White (WPW) syndrome. The patient was noted to have aortic dissection along with multiple abdominal organ ischemic injury a day after ECLS arterial cannula position adjustment. The patient was rapidly decannulated from ECLS and the aortic dissection was managed conservatively with good outcome. We discuss our approach and rationale behind conservative management of this rarely reported complication associated with ECLS therapy and discuss available literature.

Combined analysis of cecal microbiota and metabolomics reveals the intervention mechanism of Dayuan Yin in acute lung injury.

The ancient Chinese medicinal formula, Dayuan Yin (DYY), has a long history of use in treating respiratory ailments and is shown to be effective in treating acute infectious diseases. This study aims to explore how DYY may impact intestinal flora and metabolites induced by acute lung injury (ALI). ALI rats were induced with lipopolysaccharide (LPS) to serve as models for assessing the anti-ALI efficacy of DYY through multiple lung injury indices. Changes in intestinal microflora were assessed via 16SrRNA gene sequencing, while cecum contents were analyzed using non-targeted metabonomics. Differential metabolites were identified through data analysis, and correlations between metabolites, microbiota, and inflammatory markers were examined using Pearson's correlation analysis. DYY demonstrated a significant improvement in LPS-induced lung injury and altered the composition of intestinal microorganisms, and especially reduced the potential harmful bacteria and enriched the beneficial bacteria. At the gate level, DYY exhibited a significant impact on the abundance of Bacteroidota and Firmicutes in ALI rats, as well as on the regulation of genera such as Ruminococcus, Lactobacillus, and Romboutsia. Additionally, cecal metabonomics analysis revealed that DYY effectively modulated the abnormal expression of 12 key metabolic biomarkers in ALI rats, thereby promoting intestinal homeostasis through pathways such as purine metabolism. Furthermore, Pearson's analysis indicated a strong correlation between the dysregulation of intestinal microbiota, differential metabolites, and inflammation. These findings preliminarily confirm that ALI is closely related to cecal microbial and metabolic disorders, and DYY can play a protective role by regulating this imbalance, which provides a new understanding of the multi-system linkage mechanism of DYY improving ALI.

Chronic UVB exposure induces hepatic injury in mice: Mechanistic insights from integrated multi-omics

Chronic UVB exposure poses a significant threat to both skin and visceral health. In recent years, the adverse role of chronic UVB exposure in liver health has been suggested but not fully elucidated. This study aims to comprehensively investigate the effects of chronic UVB exposure on liver health in male SKH-1 hairless mice and clarify potential mechanisms through multi-omics approaches. The findings suggested that 10-week chronic skin exposure to UVB not only triggers hepatic inflammation and oxidative stress but also, more importantly, results in lipid metabolism abnormalities in the liver. Hepatic transcriptomic analysis revealed significant alterations in various signaling pathways and physiological processes associated with inflammation, oxidative stress, and lipid metabolism. Further lipidomic analysis illustrated significant changes in the metabolism of glycerolipids, sphingolipids, and glycerophospholipids in the liver following chronic UVB exposure. The 16S rRNA sequencing analysis indicated that chronic UVB exposure disrupts the structure and function of the microbiota. In search of potential mechanisms used by the microbiome to regulate the hepatic disease morphology, we filtered mouse fecal supernatants and cultured the supernatants with HepG2 cells. Fecal supernatant from UVB-exposed mice induced increased secretion of the inflammatory cytokine IL-8, accumulation of MDA, reduced SOD activity, and decreased lipid content in normal hepatic cells. In summary, skin chronic exposure to UVB induces multiple liver injuries and gut microbiota dysbiosis in mice and gut microbiota metabolites may be one of the contributing factors to hepatic injury caused by chronic UVB exposure. These discoveries deepen the comprehension of the health risks associated with chronic UVB exposure.

Histological Changes in the Blood Vessels of Ruptured Human Anterior Cruciate Ligaments.

Anterior cruciate ligament (ACL) rupture is a commonly encountered sports injury worldwide.ACL rupture is known to have poor healing capacity, hypothesized to be due to low vascularity. ACL reconstruction surgery with ligament removal and tendon graft became essential for the higher grades of ACL tears. However, ACL-reconstructed patients faced post-traumatic osteoarthritis 10-15 years after surgery. In the recent past, the tibial remnant of ACL was shown to have intrinsic healing potential. Blood vessel density and the location of blood vessels of ACL remnants have critical implications in the newly upcoming remnant-preservation ACL reconstruction surgeries that showed better healing response. This study was performed to characterize the histological features of ruptured ACL remnants in terms of blood vessels to assess the healing potential and their utility in novel surgical techniques. This was a descriptive cross-sectional study in which the tibial remnant of 24 ruptured ACL samples was evaluated for blood vessel density (per sq. mm), luminal area (sq. µm), and location of blood vessels using hematoxylin and eosin (H&E) staining with ImageJ software (U. S. National Institutes of Health, Bethesda, Maryland, USA). The blood vessel density and location of blood vessels were compared among various groups based on the duration of injury and number of injuries. Twenty-three male and one female adult patients with a mean duration of injury of 7.54 ± 5.63 months (range: 2-24 months) were included in the study. They were divided into three groups based on duration of injury: group I (2-5 months; n = 10), group II (6-8 months; n = 8), and group III (9-24 months; n = 6). The median blood vessel density (blood vessels per sq. mm) was 5.50 (3.30, 10.23) per sq. mm. There was no correlation of blood vessel density observed with duration of injury. All groups showed similar results statistically.More patients in earlier duration of injury showed very high range (10.1-40 per sq. mm) of blood vessels compared to the patients of later duration. Immature and intermediary blood vessels were identified denoting angiogenesis. Location of blood vessels varied in the groups based on duration of injury. There was no significant difference in blood vessel density and location of blood vessels between patients with single injury and those with multiple injuries. The present study demonstrates the presence of healing potential of ruptured anterior cruciate ligaments in terms of blood vessel density, luminal area, and location of blood vessels. Future studies looking into the functional outcome would enhance the understanding of utility of novel remnant-preservation surgeries in place of standard graft reconstruction surgeries.

Parental Perception of Vulnerability, Child’s Temperament, and Health Locus of Control: Who Made You Boo-Boo?

Background: In Pakistan, where unintentional injuries among toddlers pose a significant public health challenge, understanding the factors that contribute to elevated injury risks is crucial. A two-dimensional approach including parental factors (internal/external health locus of control and perceived vulnerability) and child factors (the child’s temperament) is explored as contributing to the unintentional injury behaviors of toddlers. Method: The study involved 241 parents of toddlers aged 18–36 months from daycare centers in three major Pakistani cities who had observed multiple recent injuries in their children. The comprehensive online assessment, lasting 15–20 minutes, incorporated the child vulnerability scale, injury behavior checklist, parent health locus of control questionnaire, and early childhood behavior questionnaire. Demographic details included child and parent age distributions, with a focus on educational backgrounds. The participants comprised both fathers and mothers, and the data analysis employed Smart-PLS software for structural equation modeling. Result: The results suggested there is no direct relationship between parental health locus of control (internal/external) and injury behaviors in children. However, an indirect and significant path was observed from the parental health locus of control (internal/external) to perceived child vulnerability and injury behaviors through moderation of temperamental characteristics. Conclusion: Our research underscores the indirect link between parental factors, child temperament, and toddler injuries in Pakistan. Culturally sensitive interventions targeting parental awareness can play a pivotal role in safeguarding the well-being of the youngest members of society.

Return to Work One Year after Moderate to Severe Traumatic Injury in a Working Age Population.

Background/Objectives: Physical trauma may cause long-term disabilities. The importance of place of residence in the return to work after injuries is little researched. The primary aims of this study were to describe return to work or school (RTW) at 6 and 12 months after moderate to severe traumatic injury and to investigate demographic and injury-related predictors for RTW with an initial focus on geographic centrality of residency. The secondary aim was to investigate the association between RTW and functioning. Methods: A prospective cohort study conducted at two Norwegian trauma centres. Inclusion criteria: age 18 to 70 years, at least a two-day hospital stay and a New Injury Severity Score > 9. Information about centrality, demographics, injuries, and return to work were collected. Associations between possible predictors and RTW were assessed using binary logistic regression. Results: Of the 223 participants, 68% had returned to work after 6 months and 77% after 12 months. Twelve-month RTW was 89% after thorax/abdomen injuries, 78% after extremity/spine injuries and 73% after head injuries. More central residency was a significant predictor for RTW in univariable but only within the extremity/spine injury subgroup in multivariable analysis. Negative factors were age, having a blue-collar job, number of injuries and rehabilitation complexity. Function 12 months post-injury was associated with RTW in the multivariable model. Conclusions: RTW after one year was high in all major trauma groups. Demographic and injury-related factors were more important predictors of RTW than centrality of residency. Blue-collar workers and patients with multiple injuries and high rehabilitation complexity should be given special attention to support RTW.

Talar head fractures: An observational study of 33 talar head fractures derived from the Swedish Fracture Register

BackgroundReports in the literature on talar head fractures are rare and limited to case reports and small case series. Questions/PurposesThis study aimed to describe a national cohort of talar head fractures for fracture characteristics, associated injuries, treatment, and reoperations. MethodsWe reviewed all radiographs of patients enrolled in the SFR between 2011 and 2021 showing talar head fractures (AO/OTA 81-A3). We excluded those with talar head avulsion fractures, misclassified, multiple registrations, or with a privacy notice in their medical records. The cohort was reviewed using medical records and radiographs at a minimum 2-year follow-up. ResultsThe study included 32 patients (33 fractures) ≥18 years of age. The median age was 32 (range 18–65) years, 84 % were men, and the main trauma mechanisms were motor vehicle accidents (28 %) and falls from heights (28 %) and graded as high-energy injuries in 50 % of the cases. 18 (55 %) were displaced and 15 (45 %) had comminuted fractures. 14 talar head fractures (42 %) had multiple injuries to the same foot. 21 patients (66 %) underwent surgical treatment, most commonly with screw fixation. Surgery was performed in 15 of 18 patients with displaced fractures. Four patients were reoperated, one with arthrodesis of the talonavicular joint and three for implant removal. No cases of avascular necrosis were identified. ConclusionsTalar head fractures are rare and occur mainly in men. They are associated with other foot injuries. Most talar head fractures are treated operatively. In this case series, we did not identify any case of avascular necrosis. Levels of EvidenceIV, retrospective observational cohort study

Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 μM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

Watershed regions are more susceptible to tissue microstructural injury in multiple sclerosis.

Histopathologic studies report higher concentrations of multiple sclerosis white matter lesions in watershed areas of the brain, suggesting that areas with relatively lower oxygen levels may be more vulnerable to disease. However, it is unknown at what point in the disease course lesion predilection for watershed territories begins. Accordingly, we studied a cohort of people with newly diagnosed disease and asked whether (1) white matter lesions disproportionally localize to watershed-regions and (2) the degree of microstructural injury in watershed-lesions is more severe. Fifty-four participants, i.e. 38 newly diagnosed people with multiple sclerosis, clinically isolated syndrome or radiologically isolated syndrome, and 16 age- and sex-matched healthy controls underwent brain magnetic resonance imaging. T1-weighted and T2-weighted fluid-attenuated inversion recovery sequences, selective inversion recovery quantitative magnetisation transfer images, and the multi-compartment diffusion imaging with the spherical mean technique were acquired. We computed the macromolecular-to-free pool size ratio, and the apparent axonal volume fraction maps to indirectly estimate myelin and axonal integrity, respectively. We produced a flow territory atlas in each subject's native T2-weighted fluid-attenuated inversion recovery images using a T1-weighted magnetic resonance imaging template in the Montreal Neurological Institute 152 space. Lesion location relative to the watershed, non-watershed and mixed brain vascular territories was annotated. The same process was performed on the T2-weighted fluid-attenuated inversion recovery images of the healthy controls using 294 regions of interest. Generalized linear mixed models for continuous outcomes were used to assess differences in size, pool size ratio and axonal volume fraction between lesions/regions of interests (in healthy controls) situated in different vascular territories. In patients, we assessed 758 T2-lesions and 356 chronic black holes (cBHs). The watershed-territories had higher relative and absolute concentrations of T2-lesions (P≤0.041) and cBHs (P≤0.036) compared to either non-watershed- or mixed-zones. T2-lesions in watershed-areas also had lower pool size ratio relative to T2-lesions in either non-watershed- or mixed-zones (P = 0.039). These results retained significance in the sub-cohort of people without vascular comorbidities and when accounting for periventricular lesions. In healthy controls, axonal volume fraction was higher only in mixed-areas regions of interest compared to non-watershed-ones (P = 0.008). No differences in pool size ratio were seen. We provide in vivo evidence that there is an association between arterial vascularisation of the brain and multiple sclerosis-induced tissue injury as early as the time of disease diagnosis. Our findings underline the importance of oxygen delivery and healthy arterial vascularisation to prevent lesion formation and foster a better outcome in multiple sclerosis.

Selecting the Most Relevant Mouse Strains for Evaluating Radiation-Induced Multiple Tissue Injury after Leg-Shielded Partial-Body Gamma Irradiation.

Animal studies are needed that best simulate a large-scale, inhomogeneous body exposure after a radiological or nuclear incident and that provides a platform for future development of medical countermeasures. A partial-body irradiation (PBI) model using 137Cs gamma rays with hind limb (tibia) shielding was developed and assessed for the sequalae of radiation injuries to gastrointestinal tract, bone marrow (BM) and lung and among different genetic mouse strains (C57BL/6J, C57L/J, CBA/J and FVB/NJ). In this case, a marginal level of BM shielding (∼2%) provided adequate protection against lethality from infection and hemorrhage and enabled escalation of radiation doses with evaluation of both acute and delayed radiation syndromes. A steep radiation dose-dependent body weight loss was observed over the first 5 days attributed to enteritis with C57BL/6J mice appearing to be the most sensitive strain. Peripheral blood cell analysis revealed significant depression and recovery of leukocytes and platelets over the first month after PBI and were comparable among the four different mouse strains. Latent pulmonary injury was observed on micro-CT imaging at 4 months in C57L/J mice and confirmed histologically as severe pneumonitis that was lethal at 12 Gy. The lethality and radiological densitometry (HUs) dose responses were comparable to previous studies on C57L/J mice after total-body irradiation (TBI) and BM transplant rescue as well as after localized whole-thorax irradiation (WTI). Indeed, the lethal radiation doses and latency appeared similar for pneumonitis appearing in rhesus macaques after WTI or PBI as well as predicted for patients given systemic radiotherapy. In contrast, PBI treatment of C57BL/6 mice at a higher dose of 14 Gy had far longer survival times and developed extreme and debilitating pIeural effusions; an anomaly as similarly reported in previous thorax irradiation studies on this mouse strain. In summary, a radiation exposure model that delivers PBI to unanesthetized mice in a device that provides consistent shielding of the hind limb BM was developed for 137Cs gamma rays with physical characteristics and relevance to relatively high photon energies expected from the detonation of a nuclear device or accidental release of ionizing radiation. Standard strains such as C57BL/6J mice may be used reliably for early GI or hematological radiation syndromes while the C57L/J mouse strain stands out as the most appropriate for evaluating the delayed pulmonary effects of acute radiation exposure and recapitulating this disease in humans.

External Fixators as a Tool for Damage Control Orthopedics in Severely Injured or Polytrauma Patients.

The purpose of this study is to explore the use of damage control techniques in the emergency surgical management of polytrauma patients - those with traumatic injuries affecting at least two anatomical regions - at a District General Hospital in Greece. We conducted a retrospective review of medical records from patients who visited the orthopedic emergency department between 2021 and 2024. From approximately 10,000 injured patients treated annually in our emergency department, we selected a sample of 29 polytrauma patients who required surgical intervention. We utilized the Injury Severity Score (ISS) to evaluate these patients. For 16 patients, the initial surgical intervention was also the definitive treatment, utilizing intramedullary nailing or internal osteosynthesis techniques. In the remaining 13 patients, damage control techniques, including external osteosynthesis (ExFix), were employed. The ISS was the primary criterion for deciding between definitive management and damage control procedures. Data on the 13 patients managed with damage control techniques were further analyzed and are presented in this study. External osteosynthesis was used to stabilize fractures and control bleeding, particularly in patients with multiple orthopedic injuries such as femoral or diaphyseal tibial fractures. This approach facilitated resuscitation and recovery. Our findings suggest that stabilizing long bone fractures with external fixation in patients with an ISS greater than 9 is both safe and likely contributes to overall recovery. This study demonstrates that a damage control approach for polytrauma patients with significant orthopedic trauma is effective for fracture stabilization and bleeding control. Additionally, in three cases, this approach also served as the definitive treatment.

Hepatic stellate cell single cell atlas reveals a highly similar activation process across liver disease aetiologies

Background & AimsThe progression of chronic liver disease (CLD) is characterized by excessive extracellular matrix deposition, disrupting hepatic architecture and function. Upon liver injury, hepatic stellate cells (HSCs) differentiate towards myofibroblasts and become inflammatory, proliferative and fibrogenic. To date it is still unclear whether HSC activation is driven by similar mechanisms in different aetiologies. MethodsHSCs from multiple publicly available single-cell RNA-sequencing datasets were annotated and merged into a single-cell HSC activation atlas. Spheroid co-cultures of primary mouse hepatocytes/HSCs (n=5) and ELISAs on patient plasma samples (n=80) were performed to validate the mechanistic insight obtained from the HSC atlas. ResultsWe established an HSC activation atlas in which HSCs are clearly divided into 3 distinct transcriptomic profiles: quiescent HSCs, initiatory HSCs and myofibroblasts. These transcriptomic profiles are present in each of the investigated mouse liver injury models as well as in human chronic liver diseases, indicating that HSC activation is a conserved process. This activation process is driven by a core set of transcription factors independent of liver injury or species. Furthermore, we reveal novel ligands associated with activation of HSCs in multiple liver injury models and validate the profibrotic effect of parathyroid hormone. Finally, we identify COLEC10 as a conserved marker for quiescent HSCs and a biomarker of liver fibrosis in patients with different CLDs (p<0.0001). ConclusionsWe reveal unexpected similarities in the regulatory mechanisms of HSCs across diverse liver injury settings and species. The HSC activation atlas has the potential to provide novel insights into liver fibrosis and steer novel treatment options. Impact and implicationsThis study establishes a single-cell atlas of hepatic stellate cells across various liver injuries, highlighting a conserved activation process between different injuries and across species. The discovery of novel activating ligands and the biomarker COLEC10 in human plasma enhances diagnostic and therapeutic strategies. Additionally, the conserved activation process supports the use of any mouse model for mechanistic studies and testing of new anti-fibrotic compounds, streamlining preclinical research efforts.

Systematic analysis of the occurrence characteristics and impact on hospitalization costs of trauma complications

BackgroundTrauma complications increase the burden of disease and hospitalization costs for patients. More research evidence is needed on how to more effectively prevent these complications and reduce hospitalization costs based on the characteristics of trauma patients. Therefore, this study will systematically analyze the characteristics of trauma complications and their specific impact on hospitalization costs. MethodsThis is a multi-center retrospective study of trauma hospitalizations from 2018 to 2023. Associations between population characteristics, trauma features, and each complication occurrence were investigated using multiple correspondence analysis. Logistic regression analysis assessed factors influencing trauma complications. Additionally, a generalized linear model analyzed the relative increase in hospital costs for each complication. ResultsA total of 48,032 trauma patients were included, with 22.0% experiencing at least one complication. Thrombosis is more prevalent among elderly women (aged ≥65) with pelvic and extremity trauma. In men aged 18–44 years, respiratory insufficiency and post-traumatic anemia primarily occurred in cases of head injuries and multiple injuries. Chest and multiple injuries predispose people aged 45–64 to pneumonia and electrolyte disorders. Body surface injuries are prone to surgical site infections. Complications resulted in an average relative increase in overall hospitalization costs of 1.32-fold, with thrombosis (1.58-fold), respiratory insufficiency (1.11-fold), post-traumatic anemia (0.58-fold), surgical site infection (0.48-fold), pneumonia (0.53-fold), electrolyte disorders (0.47-fold). ConclusionsThis study systematically analyzed the occurrence characteristics of trauma complications and the burden trends of hospitalization costs due to complications, providing a reference for the formulation of trauma classification and management strategies.