Chest Trauma Research Articles

Case Report: Aspirated Airway Foreign Body Mimicking Endobronchial Mass: A Diagnostic Challenge

Abstract Introduction/Objective Despite advancements in imaging modalities, identifying retained foreign bodies within the lung remains arduous. Detecting small foreign bodies is crucial as they can serve as a focal point for subsequent infections. Initial assessments may mimic malignancy. Herein, we present a case of a retained foreign body masquerading as an endobronchial mass, accompanied by unilateral pleural effusion and persistent hypoxia. Subsequent bronchoscopy showed a pearly white endobronchial mass partially obstructing the segmental bronchus at the posterior basal segment of the right lower lobe of lung with accompanying right pleural effusion and atelectasis. Methods/Case Report This is a 58-year-old male with history of hypertension, deep vein thrombosis, transient ischemic attack, and a recent motor vehicle accident with blunt chest trauma. He had a thoracic spinal cord transection with grade III blunt thoracic aortic injury, developed anasarca, hypoxia, right pleural fluid requiring multiple thoracentesis, and right sided hemothorax requiring massive transfusion protocol. Subsequent evaluations, including bronchoscopic transbronchial forceps biopsies and bronchial wash and pleural fluid cytologic examinations showed no malignant cells. Repeat bronchoscopy was concerning for enlarging mass and obstruction. Bronchoscopy almost 2 months after MVA revealed an endobronchial foreign body (tooth) lodged in the left lower lobe of lung posterior segment. Results (if a Case Study enter NA) N/A Conclusion While aspiration of foreign bodies into the tracheobronchial tree is not uncommon especially in children, foreign bodies, particularly teeth, are rare in adults. Bronchial foreign body aspiration may occur in trauma, with diagnosis typically relying on history and physical examination. Detection remains challenging despite imaging advancements, with implications including infection nidus formation. In our case, delayed diagnosis highlights the importance of considering unusual etiologies in persistent pulmonary pathology. Retrospective imaging analysis and CT findings suggested a foreign body, emphasizing the utility of imaging in suspected cases. Prompt surgical intervention is crucial to prevent complications such as recurrent infections.

Cathepsin L Promotes Pulmonary Hypertension via BMPR2/GSDME-Mediated Pyroptosis.

Pulmonary hypertension (PH) is a fatal progressive disease characterized by pulmonary endothelial injury and occlusive pulmonary vascular remodeling. Lysosomal protease cathepsin L degrades essential molecules to participate in the human pathophysiological process. BMPR2 (bone morphogenetic protein type II receptor) deficiency, an important cause of PH, results from mutational inactivation or excessive lysosomal degradation and induces caspase-3-mediated cell death. Given recent evidence that pyroptosis, as a new form of programmed cell death, is induced by caspase-3-dependent GSDME (gasdermin E) cleavage, we hypothesized that cathepsin L might promote PH through BMPR2/caspase-3/GSDME axis-mediated pyroptosis. Cathepsin L expression was evaluated in the lungs and plasma of patients with pulmonary arterial hypertension. The role of cathepsin L in the progression of PH and vascular remodeling was assessed in vivo. Small interfering RNA, specific inhibitors, and lentiviruses were used to explore the mechanisms of cathepsin L on human pulmonary arterial endothelial cell dysfunction. Cathepsin L expression is elevated in pulmonary artery endothelium from patients with idiopathic pulmonary arterial hypertension and experimental PH models. Genetic ablation of cathepsin L in PH rats relieved right ventricular systolic pressure, pulmonary vascular remodeling, and right ventricular hypertrophy, also restoring endothelial integrity. Mechanistically, cathepsin L promotes caspase-3/GSDME-mediated endothelial cell pyroptosis and represses BMPR2 signaling activity. Cathepsin L degrades BMPR2 via the lysosomal pathway, and restoring BMPR2 signaling prevents the pro-pyroptotic role of cathepsin L in PAECs and experimental PH models. These results show for the first time that cathepsin L promotes the development of PH by degrading BMPR2 to induce caspase-3/GSDME-mediated endothelial pyroptosis.

Fracture Mapping in High-Energy Chest Trauma

Background: High-energy chest trauma often results in rib fractures and associated chest injuries. This study explored fracture distribution patterns in high-energy chest trauma, using three-dimensional (3D) fracture mapping technology. Methods: This retrospective study analyzed cases of high-energy chest trauma with rib fractures treated at a Level 1 Trauma Center, from February 2012 to January 2023. Specifically, 3D computed tomography (CT) was used to reconstruct rib fractures and create fracture-frequency heat maps, analyzing the influence of other thoracic fractures on rib fracture distribution. Results: Rib fractures were frequently found in the anterior and posterior thoracic areas. On average, patients sustained 7 ± 3.87 rib fractures, with clavicle fractures in 25.5% and scapular fractures in 19.6% of cases. Scapular fractures led to more posterior rib fractures, while sternal fractures were associated with more anterior rib fractures. Clavicle fractures were linked to fractures of the first to third ribs. Conclusions: Rib fractures in high-energy chest trauma occurred most often in the anterior and posterior regions. Fractures of the scapula and sternum influence the positioning of the fracture lines. Clavicular fractures are associated with a higher incidence of upper rib fractures. These findings can help inform surgical decisions and complication management.

Etiology of nosocomial infections and antibiotic resistance (level of antibiotic resistance) of identified pathogens in patients with traumatic chest injuries

Background. Chest injuries and wounds are common during armed conflicts, with frequent nosocomial infections and mortality up to 35-45% [1-4]. Infectious complications associated with multidrug-resistant microorganisms are an urgent issue in the management of patients with trauma. Aim. To conduct a retrospective review of the main causative agents of infectious complications in patients with traumatic chest injuries and evaluate antibiotic resistance of isolated pathogens. Materials and methods. Samples for microbiological examination were obtained from 160 patients with chest trauma and nosocomial complications. The samples included sputum, pleural fluid, bronchial washings obtained by fiberoptic bronchoscopy, and tracheal secretions. Antibacterial susceptibility tests were performed, and the antibiotic resistance mechanisms in isolated microorganisms were determined. Results. Gram-negative pathogens accounted for 93% of cases. The following organisms prevailed: Klebsiella pneumoniae – 42%, Acinetobacter baumannii – 28%, Pseudomonas aeruginosa – 18%, Escherichia coli – 9%. Of note, 91.4% of K. pneumoniae strains produced extended-spectrum β-lactamases and carbapenemases. The percentage of multidrug-resistant and pandrug-resistant strains was 48.2% and 52%, respectively. Conclusion. The data obtained indicate a wide spread of gram-negative microorganisms and their multiple resistance in patients with traumatic breast injuries complicated by nosocomial infection.

Cardiovascular autonomic function in middle-aged people with long-term cervical and upper thoracic spinal cord injuries

Objectives To examine cardiovascular autonomic function in middle-aged people with long-term cervical and upper thoracic spinal cord injury (SCI) compared with the general population, and explore if the neurological level of injury (NLI) is related to cardiovascular autonomic function. Design Population-based cross-sectional study with matched controls. Setting Outpatient SCI unit in Southern Sweden. Participants Twenty-five individuals (20% women, mean age 58 years and mean time since injury 28 years, NLI C2-T6, American Spinal Injury Association Impairment Scale A-C) from the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA). Matched controls were obtained from the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) at a ratio of 5:1. Interventions Not applicable. Outcome measures 24 h electrocardiography and deep breathing tests. 24 h ambulatory blood pressure (BP) monitoring and orthostatic BP tests. Results In individuals with SCI compared with controls, heart rate variability (24h mean SD of the normal-to-normal interval 112 ms vs 145 ms, P < 0.001) and diastolic orthostatic BP increase (2.0 and 9.4 mmHg, P < 0.001), were significantly lower, whereas BP variability was significantly higher (24h mean systolic SDBP 17.8 mmHg vs 15.7 mmHg, P = 0.029). Circadian patterns of heart rate variability and BP (lack of nocturnal dip) were significantly different among the individuals with SCI than controls. Higher NLI was significantly (P < 0.05) correlated with impairments to various cardiovascular autonomic function variables. Conclusions This exploratory study indicates that cardiovascular autonomic function is impaired in middle-aged people with long-term cervical and upper thoracic SCI compared with the general non-SCI population, and more pronounced with a higher NLI. Future research is needed to understand the pathophysiological mechanisms underlying these impairments, and the prognostic significance for individuals with SCI. Trial registration ClinicalTrials.gov identifier: NCT03515122.

Identifying Mechanism of RSV for the Treatment of COVID-19 and Idiopathic Pulmonary Fibrosis via Suppressing Inflammation Response Through IL-17 Signaling Pathway from the Perspectives of in silico Study.

Both coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) could cause severe pulmonary injury and have extremely dismal prognoses with a high risk of mortality. Resveratrol (RSV), a natural polyphenol, has promising potential in the treatment of viral infection and pulmonary fibrosis. The purpose of this research was to investigate the unclear mechanism of RSV as an anti-COVID-19 and IPF therapy. Utilizing relevant databases, the intersection of genes related to IPF, COVID-19, and possible RSV targets was discovered. Then the obtained targets were investigated using GO and KEGG analysis, TP and PPI network analysis. Furthermore, the binding affinities between core targets and RSV were calculated using molecular docking. The 1101 COVID-19 targets, 2166 IPF targets, and 341 RSV targets intersected with 21 overlapping targets. PPI network reveals the interactions among targets and TP network reveals interactions between targets and pathways. Five targets including JUN, CCL2, CXCL8, IL6, and SERPINE1 were identified as the core targets through two network analyses. GO analysis demonstrated chemotaxis, inflammatory response and angiogenesis were the significant pathophysiological processes. Combing TP network analysis and KEGG analysis, IL-17 signaling pathway was considered as the significant pathway. Except for JUN, molecular docking showed the binding energies of other four targets were lower than -5 kcal/mol indicating intimate interactions between RSV and other targets. Our research elucidate the targets, pathways and pathophysiological processes of RSV involved in effects of anti-COVID-19 and IPF, suggesting RSV could be a therapeutic candidate for reducing infection and fibrosis.

Veno-arterial extracorporeal membrane oxygenation uses in trauma: a retrospective analysis of the Japanese nationwide trauma registry.

Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and vital organ oxygenation and is potentially useful as a bridge therapy in some trauma cases. We aimed to demonstrate the characteristics and outcomes of patients with trauma treated with veno-arterial ECMO (V-A ECMO) using data from a Japanese nationwide trauma registry. This retrospective descriptive study analyzed data from the Japan Trauma Data Bank between January 2019 and December 2021. Patients with severe trauma (injury severity score [ISS] ≥ 9) and treated using V-A ECMO were assessed. Among the 72,439 patients with severe trauma, 51 received V-A ECMO. Sixteen patients (31.3%) survived until hospital discharge. On hospital arrival, six (37.5%) survivors and 15 (42.9%) non-survivors experienced cardiac arrest. The median ISS for the survivor and non-survivor group was 25 (range, 25-39) and 25 (range, 17-33), respectively. Thoracic trauma was the most common type of trauma in both groups. In the non-survivor group, open-chest cardiopulmonary resuscitation, aortic cross-clamping, and resuscitative endovascular balloon occlusion of the aorta were performed in 10 (28.6%), 5 (14.3%), and 4 (11.4%) patients, respectively. However, these procedures were not performed in the survivor group. Peripheral oxygen saturation tended to be lower in the survivor group both before and upon arrival at the hospital. The results of this study suggest the potential benefit of V-A ECMO in some challenging trauma cases. Further studies are warranted to assess the indications for V-A ECMO in patients with trauma.

Damage control thoracic surgery: What you need to know.

Damage control surgery in trauma prioritizes patient stabilization through an initial temporizing surgical approach to rapidly control hemorrhage and contamination, minimizing intraoperative time to allow for resuscitation and the correction of hypothermia, coagulopathy, and acidosis in the intensive care unit. This is followed by definitive repair of injuries once physiological parameters have improved. While damage control techniques for traumatic intra-abdominal and extremity injuries are well established and frequently utilized, the same cannot be said for damage control thoracic surgery. The complexity of thoracic injuries, the intricate decision making process, the level of surgical expertise required, and potential complications make damage control thoracic surgery particularly challenging. However, advances in surgical techniques, improvements in perioperative care, and the emergence of adjuncts such as extracorporeal membrane oxygenation have significantly enhanced decision making and underscored the importance of timely and decisive intervention in damage control thoracic surgery to optimize patient outcomes. This review aims to provide a comprehensive overview of damage control thoracic surgery, detailing the principles, indications, operative techniques, perioperative management, and the integration of advanced therapies to improve outcomes in patients with severe thoracic injuries.

Management of Busulfan-Induced Lung Injury in Pediatric Patients with High-Risk Neuroblastoma

Background/Objectives: Integrating the cytotoxic drug busulfan into a high-dose chemotherapy regimen prior to autologous hematopoietic stem cell rescue in patients with high-risk neuroblastoma has improved the survival of children battling this deadly disease. Busulfan-induced toxicities can, however, be severe. Here, we describe the diagnosis and successful treatment of acute pulmonary injury by total-body-weight-adjusted busulfan therapy in two children with high-risk neuroblastoma. Case series: Patient 1 developed life-threatening biphasic acute respiratory failure on days +60 and +100 after busulfan therapy, requiring intubation and invasive mechanical ventilation. Despite intensive anti-inflammatory and immunomodulatory therapy, including systemic corticosteroids, topical inhalation regimens, azithromycin, nintedanib and extracorporal photopheresis, patient 1 required extended intensive care measures and non-invasive respiratory support for a total of 20 months. High-resolution computed tomography showed diffuse intra-alveolar and interstitial patterns. Patient 2 developed partial respiratory failure with insufficient oxygen saturation and dyspnea on day +52 after busulfan therapy. Symptoms were resolved after 6 months of systemic corticosteroids, topical inhalation regimens and azithromycin. High-resolution computed tomography showed atypical pneumonic changes with ground-glass opacities. While both patients fully recovered without evidence of pulmonary fibrosis, cancer therapy had to be paused and then modified until full recovery from busulfan-induced lung injury. Conclusions: Busulfan-induced lung injury requires prompt diagnosis and intervention. Symptoms and signs are nonspecific and difficult to differentiate from other causes. Therapeutic busulfan drug level monitoring and the identification of patients at risk for drug overdosing through promoter polymorphisms in the glutathione S-transferase alpha 1 gene encoding the main enzyme in busulfan metabolism are expected to reduce the risk of busulfan-induced toxicities.

Features of diagnosis and treatment of a polytrauma victim with predominant closed chest trauma with lung and diaphragm rupture. Clinical case

The article describes a clinical case and presents clinical signs of traumatic rupture of the diaphragm and lung on the background of a wave‑like course of the postoperative period. Open diaphragmatic injuries are more common than closed ones. In this case, the closed chest and abdominal trauma was sustained as a result of a road traffic accident. The injury was combined and severe, with signs of traumatic shock. The location of the diaphragmatic injury was on the right side, which is less common. The severe condition of the patient with respiratory failure (respiratory rate over 30 per minute) was an indication for artificial lung ventilation, which made it impossible to take complaints and anamnesis. The individual spatial topography of the diaphragm depends on the size and location of the abdominal organs, body structure, and depends on the line of examination. The movement of internal organs into the pleural cavity indicates a diaphragmatic rupture, but in this case, the extrahepatic location of the diaphragmatic defect was covered by the liver, the lower lobe of the right lung, and adhesions, which led to the cover­up of the diaphragmatic defect. Increased abdominal size due to polytrauma and mechanical ventilation in case of closed chest and abdominal trauma; increased air discharge through pleural drainage during video laparoscopy or increased abdominal size during video thoracoscopy; clamping of the pleural drainage with a spiral computed tomography of the chest and abdominal organs allows detecting pneumoperitoneum and pneumothorax, which indicates the presence of a defect in the diaphragm and lung. The use of video thoracoscopy, video laparoscopy, and spiral computed tomography does not always provide complete information about the existing damage to the diaphragm, so dynamic observation with control radiological examinations is preferred.

Air under pressure: a case report on tension pneumomediastinum arising from traumatic injury

Abstract Background Tension pneumomediastinum (TPM) is a rare but critical condition characterized by the accumulation of air in the mediastinum, leading to increased intrathoracic pressure and cardiovascular compromise. This case report is novel due to the rarity of TPM arising from blunt chest trauma and the necessity for emergent surgical intervention after initial conservative management failed. Case presentation A 63-year-old male presented with severe chest pain and dyspnea following a high-impact motor vehicle collision. Initial assessment revealed tachypnea, tachycardia, and hypotension, along with extensive subcutaneous emphysema over the chest and neck. Imaging confirmed pneumomediastinum and bilateral pneumothoraxes, consistent with TPM. Despite initial management with high-flow oxygen and bilateral chest tube insertion, the patient’s condition deteriorated, necessitating emergent mediastinal decompression via an anterior subxiphoid incision. This intervention resulted in immediate hemodynamic improvement. Conclusions This case underscores the importance of recognizing TPM in patients with chest trauma and highlights the need for prompt surgical intervention in cases of hemodynamic instability. Early and accurate diagnosis and timely surgical management are crucial for improving patient outcomes in TPM.

Improved Discriminability of Severe Lung Injury and Atelectasis in Thoracic Trauma at Low keV Virtual Monoenergetic Images from Photon-Counting Detector CT

Objectives: To evaluate the value of virtual monoenergetic images (VMI) from photon-counting detector CT (PCD-CT) for discriminability of severe lung injury and atelectasis in polytraumatized patients. Materials &amp; Methods: Contrast-enhanced PCD-CT examinations of 20 polytraumatized patients with severe thoracic trauma were included in this retrospective study. Spectral PCD-CT data were reconstructed using a noise-optimized virtual monoenergetic imaging (VMI) algorithm with calculated VMIs ranging from 40 to 120 keV at 10 keV increments. Injury-to-atelectasis contrast-to-noise ratio (CNR) was calculated and compared at each energy level based on CT number measurements in severely injured as well as atelectatic lung areas. Three radiologists assessed subjective discriminability, noise perception, and overall image quality. Results: CT values for atelectasis decreased as photon energy increased from 40 keV to 120 keV (mean Hounsfield units (HU): 69 at 40 keV; 342 at 120 keV), whereas CT values for severe lung injury remained near-constant from 40 keV to 120 keV (mean HU: 42 at 40 keV; 44 at 120 keV) with significant differences at each keV level (p &lt; 0.001). The optimal injury-to-atelectasis CNR was observed at 40 keV in comparison with the remaining energy levels (p &lt; 0.001) except for 50 keV (p &gt; 0.05). In line with this, VMIs at 40 keV were rated best regarding subjective discriminability. VMIs at 60–70 keV, however, provided the highest subjective observer parameters regarding subjective image noise as well as image quality. Conclusions: Discriminability between severely injured and atelectatic lung areas after thoracic trauma can be substantially improved by virtual monoenergetic imaging from PCD-CT with superior contrast and visual discriminability at 40–50 keV.

Fibroblast growth factor 21 attenuates pulmonary ischemia/reperfusion injury via inhibiting endoplasmic reticulum stress-induced ferroptosis though FGFR1/PPARδ signaling pathway

BackgroundAcute lung injury is a critical life-threatening complication of pulmonary and cardiac surgery with a high rate of morbidity and mortality. Fibroblast growth factor 21 (FGF21) has been reported to play an important role in protecting vital organs from damage. This study aims to investigate the potential protective role and mechanism of FGF21 in pulmonary ischemia/reperfusion (I/R)-induced acute lung injury. MethodsA pulmonary epithelial cell line was treated with hypoxia/regeneration (H/R) in vitro and a mouse model of acute lung injury was induced with pulmonary I/R in vivo. Lung injury after pulmonary I/R was compared between FGF21-konckout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. ResultsCirculating levels of FGF21 in mice with pulmonary I/R injury were significantly higher than in those without pulmonary I/R injury. Lung injury was aggravated in FGF21-KO mice compared with WT mice and the administration of FGF21 alleviated lung injury in mouse treated with I/R and pulmonary epithelial cell injury treated with H/R. FGF21 treatment decreased endoplasmic reticulum (ER) stress, Fe2+ and lipid reactive oxygen species (ROS) contents and GPX4 expression and increased PTGS2 levels. Mechanistically, FGF21 upregulated the expression of FGFR1 and PPARδ, ameliorated ER stress and ER stress induced-ferroptosis. Furthermore, FGF21 increased the expression level of PPARδ in pulmonary epithelial cell exposed to H/R, which was inhibited by FGFR1 inhibitor (PD173074). The protective effects of FGF21 were abolished by co-treatment with PPARδ inhibitor (GSK0660), indicating FGF21 attenuated ER stress-induced ferroptosis by dependent on FGFR1/PPARδ signaling pathway. ConclusionOur study reveals that FGF21 protects against pulmonary I/R injury via inhibiting ER stress-induced ferroptosis though FGFR1/PPARδ signaling pathway. Boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for pulmonary IRI.

Reduced microRNA-744 expression in mast cell-derived exosomes triggers epithelial cell ferroptosis in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a critical disorder characterized by immune-related damage to epithelial cells; however, its underlying mechanism remains elusive. This study investigated the effects of alterations in microRNA (miRNA) expression in mast cell-derived exosomes on human bronchial epithelial (HBE) cells and ARDS development in cellular and mouse models challenged with lipopolysaccharide. Lipopolysaccharide-treated mast cell-derived exosomes reduced glutathione peroxidase 4 (GPX4) expression and increased long-chain acyl-CoA synthetase 4 (ACSL4), 15-lipoxygenase (ALOX15), and inflammatory mediator levels in HBE cells. miRNA sequencing revealed a reduction in mast cell-derived exosomal miR-744 levels, which was associated with the regulation of ACSL4, ALOX15, and GPX4 expression. This downregulation of exosomal miR-744 expression reduced miR-744 levels and promoted ferroptosis in HBE cells, whereas the experimental upregulation of miR-744 reversed these adverse effects. Down-regulation of miR-744 induced the expression of markers for ferroptosis and inflammation in HBE cells and promoted pulmonary ferroptosis, inflammation, and injury in LPS-stimulated mice. In vivo, treatment with ACSL4, ALOX15, and GPX4 inhibitors mitigated these effects, and experimental miR-744 expression rescued the lipopolysaccharide-induced changes in HBE cells and mouse lungs. Notably, miR-744 levels were reduced in the plasma and exosomes of patients with ARDS. We concluded that decreased mast cell-derived exosomal miR-744 levels trigger epithelial cell ferroptosis, promoting lung inflammation and damage in ARDS. This study provides new mechanistic insights into the development and sustained pulmonary damage associated with ARDS and highlights potential therapeutic strategies.

A-239 Cxcl10 induced gut dysbiosis exacerbates acute lung injury and secondary infection in influenza by inhibiting il22

Abstract Background Secondary infections are the most cause of severe pulmonary injury and death in influenza. CXCL10, known as interferon γ-induced protein 10(IP-10), is highly upregulated in response to IFN-γstimulation during influenza. Previous studies show that CXCL10 contributes to bacteria co-infections and worse finales in influenza. However, the underlying mechanisms by which CXCL10 facilitate secondary infections remains unclear. Emerging evidences show that influenza virus infections disturb the composition and function of gut microbiota, which in turn influences the infection process. Herein, we aimed to explore whether CXCL10 could affect the progress of influenza infection and secondary infection in a gut microbiota dependent manner. Methods CXCL10 knockout mice were used to determine the role of CXCL10 in staphylococcus aureus co-infection after influenza A virus (IAV) infection. Lung tissues from CXCL10 knockout mice were collected for Transcriptomics sequencing. Feces from mice and clinicals including IAV patients and healthy individuals were collected for Metagenomic sequencing. Paired serum samples were collected for Metabolomic sequencing. QRT-PCR was performed to determine the expression of inflammatory factors in lung tissues from CXCL10 knockout mice. Elisa assays were used to measure the serum expression levels of CXCL10 and IL22. Flow cytometry was applied to detect the proportion of IL22+ cells. Fecal microbiota transplantation (FMT) was applied to confirm that CXCL10 plays an adverse role in acute lung injury and staphylococcus aureus co-infection after IAV infection by disrupting intestinal microbiome homeostasis. Results CXCL10 aggravated acute lung injury and promoted staphylococcus aureus coinfection after IAV infection. Transcriptomics sequencing results suggests improved cell membrane integrity and regeneration of epithelial cells after IAV infection in CXCL10 knockout mice with an upregulation of integrity proteins. CXCL10 knockout significantly increased the expression levels of IL22 without influencing virus duplication. rh-IL22 protects lung epithelial cell from staphylococcus aureus co-infection in influenza and increased the expression of tight junction proteins. The gut microbiome shows different structures between wild type mice and knockout mice, as well as clinical samples according to serum CXCL10 expression levels. We found some genera were markedly increased in knockout mice and patients with low serum CXCL10 expression levels including Lactobacillus, Lachnospiraceae, Oscillibacter, Odoribacter, Eubacterium. FMT from patients with low serum CXCL10 levels and healthy individuals ameliorating lung pathological damage. Conclusions This study interpreted that CXCL10 exacerbates acute lung injury and secondary infection in influenza by inducing gut dysbiosis, suggesting that balancing the gut flora could be assistant treatments to protect from acute lung injury and secondary infections in influenza. And IL22 may be a potential mediating factor between gut-lung axis to improve epithelial integrity.

DDAH1 deficiency exacerbates cerebral vascular endothelial dysfunction by aggravating BBB disruption and oxidative stress in thoracic blast-induced brain injury

As terrorist incidents and underground explosion events have become more frequent around the world, brain injury caused by thoracic blast exposure has been more highlighted due to its injured organ, subsequent social and economic burden. It has been reported dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays important roles in regulating vascular endothelial injury repair and angiogenesis, but its role in thoracic blast-induced brain injury remains to be explained. This study seeks to investigate the mechanism of DDAH1 on thoracic blast-induced brain injury. 40 C57BL/6 wild type mice and 40 DDAH1 knockout mice were randomly and equally divided into control group and blast group, respectively. The integrity of blood-brain barrier (BBB) was detected by Evans blue test. The serum inflammatory factors, nitric oxide (NO) contents, and asymmetric dimethylarginine (ADMA) levels were determined through ELISA. HE staining and reactive oxygen species (ROS) detection were performed for histopathological changes. Western blot was used to detect the proteins related to oxidative stress, tight junction, focal adhesion, vascular endothelial injury, and the DDAH1/ADMA/eNOS signaling pathway. DDAH1 deficiency aggravated thoracic blast-induced BBB leakage, inflammatory response, and the increased levels of inflammatory-related factors. Additionally, DDAH1 deficiency also increased ROS generation, MDA and IRE-α expression. Regarding cerebral vascular endothelial dysfunction, DDAH1 deficiency increased the expression of MCAM, FN1, LIMK1, VEGF, MMP9, Vimentin and N-cadherin, while lowering the expression of FMR1, Occludin, claudin-3, claudin-5, Lyn, LIMA1, Glrb, Sez6, Dystrophin, and phosphorylation of VASP. Also, DDAH1 deficiency exacerbated explosion-induced increase of ADMA and decrease of eNOS activity and NO contents. Thus, we conclude that DDAH1 could prevent cerebral vascular endothelial dysfunction and related injury by inhibiting ADMA signaling and increasing eNOS activity in thoracic blast induced brain injury.

Pulmonary Artery Injury Following Endocardial Left Atrial Appendage Occlusion: The Known and Unknown.

Left atrial appendage closure (LAAC) is frequent alternative for stroke prophylaxis in patients for whom oral anticoagulation is contraindicated. Pulmonary artery injury (PAI) is a feared yet rare complication of endocardial LAAC, but its surrounding literature is scarce. The aim of the current study was to review prior PAI published reports and the U.S. Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database to understand evidence and mechanisms of PAI after LAAC. A systematic review was conducted of the literature and MAUDE database for previously reported cases of PAI, and cases were reviewed for patient characteristics and outcomes. In addition, we identify risks and review our strategies to avoid this injury. Thirty-six cases (16 case reports and 20 MAUDE reports) of PAI were found. These patients had a mean age of 73.6 ± 8.2 years with a median CHA2DS2VASC score of 5 (quartile 1-quartile 3: 3-6). Most commonly, LAAC associated with PAI involved a dual-seal (75%) followed by lobular occlusive devices (19.4%); the device was unspecified in 2.8% of cases. PAI commonly presented postprocedurally, either within the first 24 hours (50%) or beyond (38.9%), with cardiac tamponade (61.1%) or cardiac arrest (19.4%). Overall, 52.8% required surgery with or without antecedent pericardiocentesis, and 16.7% were managed with pericardiocentesis. PAI was associated with a high mortality rate (ie,33.3%). Unfortunately, no specific cardiac imaging or procedural details to predict PAI were noted in the reports. Presentation of PAI after LAAC can occur immediately following the procedure or be delayed. Thus, the threshold for suspicion, especially with rapid and hemodynamically significant pericardial effusion, after LAAC should be low.

Clinical Risk Factors Associated with the Need for Tracheostomy in Traumatic Cervical and High Thoracic Spinal Cord Injury

BackgroundOur objective was to assess the association of completeness and level of spinal cord injury (SCI) with the need for tracheostomy and identify additional risk factors predictive of tracheostomy. MethodsThis was a retrospective review of patients with SCI between January 2017 and December 2022. ResultsPatients with complete SCI were roughly thirty-three times more likely to have a tracheostomy when compared to incomplete injury (82% vs 12%, p<0.001, OR = 32.9). The rate of tracheostomy did not differ between spinal cord levels for complete (p=0.68) or incomplete (p=0.08) injuries. Penetrating injury, low GCS, high ISS, and polytrauma were associated with tracheostomy need in incomplete SCI. ConclusionComplete injury was statistically significantly associated with the need for tracheostomy while level of injury failed to reach significance. Patients with incomplete SCI that have certain clinical risk factors should be considered for early tracheostomy.

Machine Learning Differentiates Extracorporeal Membrane Oxygenation Mortality Risk Profiles Among Trauma Patients.

Extracorporeal membrane oxygenation (ECMO) is resource intensive with high mortality. Identifying trauma patients most likely to derive a survival benefit remains elusive despite current ECMO guidelines. Our objective was to identify unique patient risk profiles using the largest database of trauma patients available. ECMO patients ≥16years were identified using Trauma Quality Improvement Program data (2010-2019). Machine learning K-median clustering (ML) utilized 101 variables including injury severity, demographics, comorbidities, and hospital stay information to generate unique patient risk profiles. Mortality and patient and center characteristics were evaluated across profiles. A total of 1037 patients were included with 33% overall mortality, mean age 32years, and median ISS = 26. The ML identified 3 unique patient risk profile groups. Although mortality rates were equivalent across the 3 groups, groups were distinguished by (Group 1) young (median 25years), severely injured (ISS = 34) patients with thoracic and head injuries (99%) via blunt mechanism (93%), and a high prevalence of ARDS (77%); (Group 2) relatively young (median 30years) and moderately injured (ISS = 22) patients with exposure-related injuries (11%); and (Group 3) older (median 46years) patients with a high proportion of comorbidities (69%) and extremity injuries (100%). There were no differences based on center ECMO volume, teaching status, or ACS-Level across all 3 groups. Machine learning compliments traditional analyses by identifying unique mortality risk profiles for trauma patients receiving ECMO. These details can further inform treatment guidelines, clinical decision making, and institutional criteria for ECMO usage.

CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME.

Introduction: Sepsis-induced degradation of endothelial glycocalyx heparan sulfate (HS) contributes to the pulmonary microvascular endothelial injury characteristic of acute respiratory distress syndrome (ARDS) pathogenesis. Our objectives were to (1) examine relationships between plasma indices of HS degradation and protein biomarkers of endothelial injury and (2) identify patient subgroups characterized by distinct profiles of HS degradation in children with ARDS. Methods: We analyzed prospectively collected plasma (2018-2020) from a cohort of invasively mechanically ventilated children (aged >1 month to <18 years) with ARDS. Mass spectrometry characterized and quantified patterns of HS disaccharide sulfation. Protein biomarkers reflective of endothelial injury (e.g., angiopoietin-2, vascular cell adhesion molecule-1, soluble thrombomodulin) were measured with a multiplex immunoassay. Pearson correlation coefficients were used to construct a biomarker correlation network. Centrality metrics detected influential biomarkers (i.e., network hubs). K-means clustering identified unique patient subgroups based on HS disaccharide profiles. Results: We evaluated 36 patients with pediatric ARDS. HS disaccharide sulfation patterns, 6S, NS, and NS2S, positively correlated with all biomarkers of endothelial injury (all P < 0.05) and were classified as network hubs. We identified three patient subgroups, with cluster 3 (n = 5) demonstrating elevated levels of 6S and N-sulfated HS disaccharides. In cluster 3, 60% of children were female and nonpulmonary sepsis accounted for 60% of cases. Relative to cluster 1 (n = 12), cluster 3 was associated with higher oxygen saturation index (P = 0.029) and fewer 28-day ventilator-free days (P = 0.016). Conclusions: Circulating highly sulfated HS fragments may represent emerging mechanistic biomarkers of endothelial injury and disease severity in pediatric ARDS.