Organ Injury Research Articles

Intramyocardial immunomodulation with human CD16+ monocytes to treat myocardial infarction in pig: a blind randomized preclinical trial.

Human CD16+ monocytes (hCD16+ Ms) have proangiogenic properties. We assessed the feasibility, safety and efficacy of hCD16+ Ms in a porcine model of myocardial infarction (MI). A total of 27 female Large White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR). Five days later, animals received intramyocardial injections of hCD16+ Ms in saline (n = 13) or saline only (n = 14). hCD16+ Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87%, respectively. No feasibility/safety concerns were associated with the use of hCD16+ Ms. The LV scar dropped by 14.5gr (from 25.45 ± 8.24 to 10.8 ± 3.4 gr; -55%) and 6.4gr (from 18.83 ± 5.06 to 12.4 ± 3.9gr; -30%) in the hCD16+ Ms and control groups, respectively (p = 0.015). The 30-day LVEF did not differ between groups, but a prespecified sub-analysis within the hCD16+ Ms group showed that LVEF was 2.8% higher and LV scar 1.9gr lower in the subgroup receiving a higher cell dose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6 and lower levels of TGF-β were observed in the hCD16+ Ms group. The use of hCD16+ Ms in acute MI is feasible, safe and associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts and IL-6 and reduced pro-fibrotic TGF-β at 30-day post-injections. A higher cell dose might increase the LVEF effect while reducing scar size, but this warrants validation in future studies.

Study of Pattern and Management of Abdominal Trauma Patients at a University Hospital of Nepal

Background: Injury related death is a leading cause of death globally. Abdominal injuries may occur in up to one third of patients with trauma. Road traffic accidents have become the commonest mechanism of trauma. Materials and Methods: This was a hospital based retrospective descriptive study conducted at Dhulikhel Hospital-Kathmandu University Hospital. Patients admitted with abdominal trauma from July 2021 to December 2023 were included in this study. Results: This study included 60 patients with abdominal trauma. Mean age of patients was 35.60 ± 15.81 (10-76) years. Majority of patients belonged to age group 21-40 years (n=32, 53.3%) with male predominance (Male:female ratio=3.6:1). Blunt abdominal trauma (n=58, 96.7%) was more common than penetrating abdominal trauma (n=2, 3.3%). Road traffic accident (n=31, 51.7%), fall from height (n=22, 36.7%) and physical assaults (n=7, 11.7%) were the mechanisms of injury. In our study, commonly injured organs were spleen(n=19, 30.64%), liver(n=15, 24.19%) and small bowel(n=14, 22.58%). Among the patients with penetrating abdominal trauma, one patient had rectal injury and next patient had stab injury with protruding omentum through the wound. Thirty four patients (56.7%) were managed conservatively and 26 patients (43.3%) underwent operative management. The mortality rate was 8.33% (n=5) of which 4 (80%) had undergone operative management and 1 (20%) was being managed conservatively. Conclusion: Majority of patients with solid organ injury can be managed conservatively while hollow viscus injury undergoes operative treatment. Physically active male population is the most affected group. Road traffic accidents are the leading cause of abdominal trauma followed by fall from height and physical assaults.

Poly I: C Alleviated Duck Intestinal Injury Infected with Duck Viral Enteritis by Inhibiting Apoptosis.

Duck enteritis virus (DEV) may lead to vascular injury, gastrointestinal mucosal erosion, lymphoid organ injury, and Polyinosinic-polycytidylic acid (Poly I:C) has an antiviral effectby inducing low levels of interferon. The purpose of this study was to explore the pathogenesis of DEV-induced intestinal injury in ducks and to verify the therapeutic effects of different concentrations of Poly I:C. In this study, duck enteritis model was established by infecting healthy Pekin ducks with DEV. Duck intestinal tissues were extracted from normal control group, model group, and treatment group with different doses of Poly I:C. In vivo, HE and TUNEL staining were used to observe the morphological changes and apoptosis. In vitro, the proliferation and apoptosis of duck intestinal epithelial cells were evaluated by MTT assay, TUNEL staining, and flow cytometry. The results showed that Poly I:C protected ducks from DEV toxicity by improving intestinal morphology and inhibiting apoptosis. In addition, the antiviral effect of Poly I:C on DEV was found in a dose-dependent manner, with a more relatively obvious effect at a high dose of Poly I:C. All in all, these results demonstrated that Poly I:C played a vital role in the apoptosis induced by DEV in ducks and modest dose of Poly I:C treatment worked well and may provide important reference for the development of new antiviral drugs in the future.

Abstract We070: The role of neutrophil YAP in cardiac inflammation and injury

Background: There is a growing appreciation that neutrophils demonstrate plasticity, not unlike the macrophage, and can modulate both inflammation and repair following organ injury. Neutrophils are rapidly recruited to the heart after acute myocardial infarction (MI) and participate in cardiac inflammation and remodeling. Nevertheless, mechanisms regulating neutrophil function during heart injury remain largely unknown. Research Question/Aim: Previous work demonstrated that Yes-Associated Protein (YAP) regulates macrophage function during heart injury. However, whether YAP regulates neutrophil function in any context, including reperfused MI (I/R), remains unexplored. Approach: We generated neutrophil-specific YAP KO mice (MRP8 Cre ) and subjected them to I/R to elicit inflammation and injury. Cell-based experiments were performed using primary isolated mouse neutrophils. We utilized flow cytometry, single-cell RNAseq, and histological and biochemical assays to investigate underlying mechanisms. Results: Neutrophils isolated from the blood and heart of WT mice subjected to I/R revealed increased YAP expression. Compared to control mice, neutrophil YAP KO hearts had decreased infarct size after 24 hours reperfusion, and better cardiac function after 2 weeks. Single-cell RNAseq of heart leukocytes indicated suppression of inflammatory, migratory, and superoxide production pathways in YAP KO neutrophils. Characterization of neutrophils by flow cytometry indicated a shift toward reparative polarization in YAP KO mice during early reperfusion. Bone marrow-derived neutrophils (BMDNs) from KO mice had attenuated inflammatory gene expression and ROS production compared to control cells. Pharmacological inhibition of YAP using verteporfin produced comparable results. Ongoing experiments are investigating how YAP modulates neutrophil inflammatory function, and will determine the therapeutic potential of targeted YAP inhibition for I/R injury. Conclusion: These results suggest that YAP regulates neutrophil function during I/R injury in the heart and that suppression of neutrophil YAP affords cardioprotection.

Effect of Alcohol on Clock Synchrony and Tissue Circadian Homeostasis in Mice.

Alcohol use disorder accounts for a growing worldwide health system concern. Alcohol causes damages to various organs, including intestine and liver, primarily involved in its absorption and metabolism. However, alcohol-related organ damage risk varies significantly among individuals, even when they report consuming comparable dosages of alcohol. Factor(s) that may modulate the risk of organ injuries from alcohol consumption could be responsible for inter-individual variations in susceptibility to alcohol-related organ damages. Accumulating evidence suggests disruptions in circadian rhythm can exacerbate alcohol-related organ damages. Here we investigated the interplay between alcohol, circadian rhythm, and key tissue cellular processes at baseline, after a regular and a shift in the light/dark cycle (LCD) in mice. Central/peripheral clock expression of core clock genes (CoClGs) was analyzed. We also studied circadian homeostasis of tissue cellular processes that are involved in damages from alcohol. These experiments reveal that alcohol affects the expression of CoClGs causing a central-peripheral dyssynchrony, amplified by shift in LCD. The observed circadian clock dyssynchrony was linked to circadian disorganization of key processes involved in the alcohol-related damages, particularly when alcohol was combined with LCD. These results offer insights into the mechanisms by which alcohol interacts with circadian rhythm disruption to promote organ injury.

Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial

Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. XVIVO Perfusion.

Adrenal gland injury in trauma patients and its impact on clinical outcomes.

Adrenal gland injury (AGI) associated with trauma is an uncommon and often overlooked condition. This study aimed to evaluate the frequency of AGI in individuals with severe trauma injuries and investigate the outcomes of patients with AGI. All patients admitted to a tertiary trauma referral center under the trauma protocol who had a computed tomography (CT) scan between January 2012 and January 2023 were analyzed retrospectively. Patients who were dead on arrival and patients with incomplete data were excluded. They were classified into two main groups, adult and pediatric, and further subcategorized by the presence or absence of radiologically evident AGI. Demographic data, mechanism of injury, injury severity scores (ISS), presence of concurrent abdominal injury, and 30-day mortality rates were compared. A separate analysis was performed for factors affecting mortality rates. A total of 1,253 patients were included: 950 adults and 303 pediatric patients. In the adult group, AGI was detected in 45 (4.7%) patients and was more commonly associated with the following mechanisms of injury: motor vehicle accidents (26.7% vs. 14.3%) and pedestrian accidents (37.8% vs. 15.5%). Injury to the right side was more common (55.6%). Patients with AGI had higher rates of concurrent liver (17.8% vs. 3.9%), spleen (11.1% vs. 3.6%), and kidney injuries (15.6% vs. 1.3%). In the pediatric population, AGI was detected in 30 patients (14.8%), a significantly higher rate compared to the adult group. Similar to the adult group, AGI was more commonly associated with concurrent abdominal injuries and had a right-sided dominance (60%), but the rate of concurrent abdominal injuries was higher in the pediatric group (80% vs. 46%). The 30-day mortality was significantly higher in both adult and pediatric AGI groups compared to patients without AGI (adult: 15.6% vs. 2.9%, pediatric: 10% vs. 1.8%). In patients with AGI, major head and neck injuries and chest injuries were associated with mortality. Adrenal gland injuries due to trauma are not uncommon. They are usually associated with blunt trauma and other concurrent abdominal organ injuries. The major contributors to mortality in patients with AGI were major head and neck injuries and chest injuries.

Targeting miR-29 mitigates skeletal senescence and bolsters therapeutic potential of mesenchymal stromal cells

Mesenchymal stromal cell (MSC) senescence is a key factor in skeletal aging, affecting the potential of MSC applications. Identifying targets to prevent MSC and skeletal senescence is crucial. Here, we report increased miR-29 expression in bone tissues of aged mice, osteoporotic patients, and senescent MSCs. Genetic overexpression of miR-29 in Prx1-positive MSCs significantly accelerates skeletal senescence, reducing cortical bone thickness and trabecular bone mass, while increasing femur cross-sectional area, bone marrow adiposity, p53, and senescence-associated secretory phenotype (SASP) levels. Mechanistically, miR-29 promotes senescence by upregulating p53 via targeting Kindlin-2 mRNA. miR-29 knockdown in BMSCs impedes skeletal senescence, enhances bone mass, and accelerates calvarial defect regeneration, also reducing lipopolysaccharide (LPS)-induced organ injuries and mortality. Thus, our findings underscore miR-29 as a promising therapeutic target for senescence-related skeletal diseases and acute inflammation-induced organ damage.

Gynaecological cancer-related deaths in a tertiary hospital: A four-year retrospective review.

The aim of this study is to describe the profile, causes of death, and associated complications among women who died with a diagnosis of gynecological cancer during a four-year period in a gynae oncology unit in a tertiary hospital. The study is based on a retrospective review of clinical records of patients. There were 368 gynecological cancer admissions during the study period and 51 gynecological cancer-related deaths (13.8%); however, only 48 (13%) of the 51 files were available for analysis. The mean age of the women who died was 52.7 years (SD ±16.92). Most of the women who died were South African citizens (41, 85%), black (44, 91.7%) and unemployed (37, 77.1%). The most common comorbidities were hypertension and HIV which occurred at similar frequencies (20, 41.7%), followed by diabetes mellitus (7, 14,6%). The three most common cancers were cervical (18, 37.5%), ovarian (13, 27.1%), and endometrial (12, 25,0%). All women who died (48, 100%) had some form of cancer-related complications on admission to the hospital. The most common complication at presentation was obstructive uropathy (16, 31.3%) followed by ascites (11, 21.6%) and pleural effusion (8, 15.8%). Just less than half of the patients (22, 45.8%) received palliative treatment due to advanced-stage disease, and the remainder, (20, 41.6%) and (5, 10.4%) surgical and radiation therapy, respectively. The surgical procedure performed was staging laparotomy for ovarian and endometrial cancer (19, 95%) and radical hysterectomy and lymph node dissection for operatable cervical cancer (01, 5%). Forty-nine complications were recorded among the 20 women who underwent surgical treatment. The most common complications were sepsis and hemorrhage followed by organ injury.

EXPERT-EPIDEMIOLOGICAL FEATURES OF NON-LETHAL MOTORCYCLE-RELATED TRAUMA

The forensic examination of victims of motorcycle trauma is a current issue in forensic practice. However, the forensic characteristics of contemporary nonfatal motorcycle injuries have not been adequately investigated. Aim of the work. To investigate the epidemiology of nonfatal motorcycle injuries and to determine the forensic characteristics of injuries typical of victims of motorcycle traffic accidents. Materials and methods. The study material consisted of 40 forensic medical reports on individuals affected by motorcycle injuries, performed at the Ternopil Regional Forensic Medical Bureau between 2016 and 2023. The data extraction was performed in a formalised card for each case, containing details about the injured person, circumstances, location and conditions of the injury. The types of injuries, their location and distribution by body part (head, trunk, limbs) were meticulously recorded. The data obtained were processed using variational statistical methods. Results. Research shows that the majority of nonfatal injuries to motorcyclists occur on the roads during the summer and early autumn, with peaks in June and September, typically as a result of collisions with other vehicles (usually cars). The victims are predominantly male (35 (87.5%)), young (19 (47.5%)) and mature (13 (32.5%)). Of these, 31 (77.5%) were motorcyclists, 6 (15.0%) were passengers and only 3 (7.5%) were pedestrians (p≤0.01). Different lower limb injuries were identified in 35 victims (87.5%, p≤0.01), upper limb injuries in 22 (55%) of the injured and head injuries in 20 (50%). Combined injuries involving two or more different anatomical parts of the body (head, torso and limbs) were found in 35 (87.5%) victims. Head injuries presented as abrasions, bruises or contusions, mainly to the face, often to several facial areas at the same time, typically accompanied by concussion or cerebral contusion. All victims with torso trauma were diagnosed with various soft tissue injuries, of which 18 (90%) were located on the anterior surface of the chest, in the pelvic or abdominal area (often in combination), with spinal injuries occurring in only 2 (10%) victims. Upper limb trauma was associated with various soft tissue injuries, as well as fractures and ligamentous damage in more than half of the victims with upper limb injuries. Victims with lower limb trauma had both superficial soft tissue injuries (abrasions, bruises, haematomas, contusions) and deeper injuries (lacerations or crush injuries), together with open or closed fractures of the femur, tibia and fibula, or multiple fractures. Isolated injuries involving only the trunk or upper extremities, or only the head and trunk, or only the trunk and lower extremities in nonfatal motorcycle trauma were found only in isolated cases. Conclusions. Non-fatal motorcycle trauma usually occurs on the road, in warm weather conditions, as a result of the motorcycle colliding with another vehicle. The majority of victims are motorcyclists, young and middle-aged males. Characteristic features of non-lethal motorcycle trauma are: a significant number of superficial soft tissue injuries and their predominance over fractures or internal organ injuries; the combination of head, trunk and limb injuries with a predominance of lower limb injuries; the predominant location of injuries on the frontal surface of the victims' bodies.

EVALUATION AND MANAGEMENT STRATEGIES FOR PATIENTS WITH BLUNT ABDOMINAL TRAUMA: A HOSPITAL-BASED STUDY

Introduction:Blunt trauma to the abdomen occurs due to forces that induce shearing, compression, or deceleration injuries, particularly affecting anatomical structures that are relatively immobile. The evaluation of abdominal injuries is challenging and often results in missed diagnoses due to the complexity of symptoms and the difficulty in identifying subtle signs of internal injury. Aims & Objectives:To study the clinical presentation, evaluation, diagnostic investigations, and management strategies for various intra-abdominal organ injuries resulting from blunt trauma to the abdomen. Methods: - Following initial resuscitation and attainment of hemodynamic stability, all blunt abdominal trauma patients underwent meticulous clinical history-taking and comprehensive physical examination. Subsequent management decisions, whether operative or non-operative, were determined based on the integrated findings of clinical assessments and radiological evaluations. Results:Between August 2022 and August 2023, fifty (50) patients with blunt trauma to the abdomen were admitted to Basaveshwara Teaching and General Hospital, Kalaburagi. In this study, males predominated in the 21 to 30-year age group, which represented the most frequent demographic for abdominal blunt trauma. Traffic collisions were identified as the leading cause of abdominal blunt trauma. The spleen emerged as the organ most frequently affected. Of the patients, 28 underwent conservative management, while 22 required surgical intervention. Conclusion:In cases of blunt trauma to the abdomen, the early hours following injury are critically significant and represent a crucial window, often referred to as the golden period of trauma, associated with higher survival rates. Timely intervention andappropriate management during this phase have been shown to significantly decrease morbidity and mortality rates associated with blunt trauma abdomenandappropriate management during this phase have been shown to significantly decrease morbidity and mortality rates associated with blunt trauma abdomen.

Shenfu injection ameliorates endotoxemia-associated endothelial dysfunction and organ injury via inhibiting PI3K/Akt-mediated glycolysis

Ethnopharmacological relevanceMicrocirculatory dysfunction is one of the main characteristics of sepsis. Shenfu Injection (SFI) as a traditional Chinese medicine is widely applied in clinical severe conditions. Recent studies have shown that SFI has the ability to ameliorate sepsis-induced inflammation and to improve microcirculation perfusion. Aim of the studyThis study aims to investigate the underlying mechanism of SFI for ameliorating sepsis-associated endothelial dysfunction and organ injury. Materials and methodsSide-stream dark-field (SDF) imaging was used to monitor the sublingual microcirculation of septic patients treated with or without SFI. Septic mouse model was used to evaluate the effects of SFI in vivo. Metabolomics and transcriptomics were performed on endothelial cells to identify the underlying mechanism for SFI-related protective effect on endothelial cells. ResultsSFI effectively abolished the disturbance and loss of sublingual microcirculation in septic patients. Twenty septic shock patients with or without SFI administration were enrolled and the data showed that SFI significantly improved the levels of total vessel density (TVD), perfused vessel density (PVD), microvascular flow index (MFI), and the proportion of perfused vessels (PPV). The administration of SFI significantly decreased the elevated plasma levels of Angiopoietin-2 (Ang2) and Syndecan-1, which are biomarkers indicative of endothelial damage in sepsis patients. In the mouse septic model in vivo, SFI inhibited the upregulation of endothelial adhesion molecules and Ly6G + neutrophil infiltration while restored the expression of VE-Cadherin in the vasculature of the lung, kidney, and liver tissue. Additionally, SFI reduced the plasma levels of Ang2, Monocyte Chemoattractant Protein-1(MCP1), and Interleukin-6 (IL6), and alleviated liver and kidney injury in septic mice. Moreover, SFI significantly inhibited the inflammatory activation and increased permeability of endothelial cells induced by endotoxins in vitro. By performing metabolomics and transcriptomics, we identified the activation of PI3K/Akt-mediated glycolysis as the underlying mechanism for SFI-related protective effect on endothelial cells. ConclusionsOur findings revealed that SFI may improve microcirculation perfusion and endothelial function in sepsis via inhibiting PI3K/Akt-mediated glycolysis, providing theoretical evidence for the clinical application of SFI.

Predictive parameters for early detection of clinically relevant abdominal trauma in multiple-injury or polytraumatised patients: a retrospective analysis

Diagnosis of relevant organ injury after blunt abdominal injury (AI) in multiple-injury/polytraumatised patients is challenging. AI can be distinguished between injuries of parenchymatous organs (POI) of the upper abdomen (liver, spleen) and bowel and mesenteric injuries (BMI). Still, such injuries may be associated with delays in diagnosis and treatment. The present study aimed to verify laboratory parameters, imaging diagnostics, physical examination and related injuries to predict intraabdominal injuries. This retrospective, single-centre study includes data from multiple-injury/polytraumatised patients between 2005 and 2017. Two main groups were defined with relevant abdominal injury (AI+) and without abdominal injury (AI−). The AI+ group was divided into three subgroups: BMI+, BMI+/POI+, and POI+. Groups were compared in a univariate analysis for significant differences. Logistic regression analysis was used to determine predictors for AI+, BMI+ and POI+. 26.3% (271 of 1032) of the included patients had an abdominal injury. Subgroups were composed of 4.7% (49 of 1032) BMI+, 4.7% (48 of 1032) BMI+/POI+ and 16.8% (174 of 1032) POI+. Pathological abdominal signs had a sensitivity of 48.7% and a specificity of 92.4% for AI+. Transaminases were significantly higher in cases of AI+. Pathological computed tomography (CT) (free fluid, parenchymal damage, Bowel Injury Prediction Score (BIPS), CT Grade > 4) was summarised and had a sensitivity of 94.8%, a specificity of 98%, positive predictive value (PPV) of 94.5% and, negative predictive value (NPV) of 98.2% for AI+. The detected predictors for AI+ were pathological abdominal findings (odds ratio (OR) 3.93), pathological multi-slice computed tomography (MSCT) (OR 668.9), alanine (ALAT) ≥ 1.23 µmol/ls (OR 2.35) and associated long bone fractures (OR 3.82). Pathological abdominal signs, pathological MSCT and lactate (LAC) levels ≥ 1.94 mmol/l could be calculated as significant risk factors for BMI+. For POI+ pathological abdominal MSCT, ASAT ≥ 1.73 µmol/ls and concomitant thoracic injuries had significant relevance. The study presents reliable risk factors for abdominal injury and its sub-entities. The predictors can be explained by the anatomy of the trunk and existing studies. Elevated transaminases predicted abdominal injury (AI+) and, specifically, the POI+. The pathological MSCT was the most reliable predictive parameter. However, it was essential to include further relevant parameters.

GPX4 allosteric activators inhibit ferroptosis and exert myocardial protection in doxorubicin-induced myocardial injury mouse model

Ferroptosis is a unique type of non-apoptotic form of cell death characterized by increased lipid hydroperoxide levels. It has relevance for a number of pathological conditions including multiple organ injuries and degenerative diseases. GPX4 plays an important role in ferroptosis by repairing lipid hydroperoxides. Based on the reported allosteric sites, we obtained the GPX4 allosteric activator hit compound A9 through virtual screening. A9 can bind to GPX4 and prevent RSL3-induced lipid peroxidation production in HT-1080 cells. In addition, A9 can specifically rescue erastin-induced cell death. Further chemical modification and structure-activity relationship studies afforded the optimized compound C3. C3 showed the activity of alleviating myocardial injury in the doxorubicin-induced myocardial injury mouse model. This study demonstrated that inhibiting ferroptosis by activating GPX4 is expected to be a potential solution to treat myocardial injury.

Transmural gastric mesh migration after hiatal hernia repair: Case report and literature review

IntroductionMesh reinforcement of the hiatus has been shown to reduce the hernia recurrence rate. But serious related complications have been reported including bleeding, erosion or migration, infection, stricture, and adhesions. Complete transmural gastric migrations of the mesh have been rarely cited in the literature. CaseWe herein report a case of a 62-year-old woman who presented for dysphagia and weight loss, 2 years after hiatal hernia repair with mesh cruroplasty. On endoscopy, complete transmural mesh migration into the stomach was identified, but it was difficult to remove. The mesh was then removed surgically. DiscussionThe possible mechanism of mesh erosion can be related to the anatomy of the distal esophagus, fixation, position, and distance of the mesh to the esophagus when placed at surgery. Endoscopic mesh retrieval is the first line of treatment when safe and feasible. Other surgical treatments in case of failure of endoscopic removal are case by case depending on the position of the mesh and the extent of organ injury. Surgery can be done laparoscopically or via laparotomy. ConclusionIn conclusion, dysphagia may manifest during the early postoperative period after mesh repair antireflux surgery, but such dysphagia usually resolves; if it doesn’t or if it worsens, mesh migration must be excluded

THE RELATIONSHIP BETWEEN BODY MASS INDEX AND ABDOMINAL CIRCUMFERENCE WITH INTRAABDOMINAL ORGAN INJURY IN HIGH ENERGY BLUNT TRAUMA PATIENTS

ABSTRACT Objective: The aim of this study was to determine the impact of body mass index (BMI) and abdominal circumference on intra-abdominal organ injury in high energy blunt trauma patients presenting to the emergency department. Materials and Methods: This prospective, cross-sectional, and analytical study included patients who presented to the Ankara Bilkent City Hospital Emergency Medicine Clinic between June 15, 2022, and December 31, 2022, due to high-energy blunt trauma and underwent contrast-enhanced abdominal computed tomography (CT). Patient demographics, vital signs, height, weight, BMI, mechanism of injury, abdominal injuries, injuries to other systems, abdominal circumference measurements, emergency department outcomes, and laboratory results were recorded in the data collection form. CT images were evaluated by a single radiology specialist, and abdominal circumference and subcutaneous fat tissue thickness were measured. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 20.0. Statistical significance was assessed using the p-value, and a significance level of p

Imaging-guided companion diagnostics in radiotherapy by monitoring APE1 activity with afterglow and MRI imaging

Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations in target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion diagnostics tool for dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy in vivo. We employ ultrabright afterglow nanoparticles and ultrasmall FeMnOx nanoparticles as dual contrast agents, significantly broadening signal change range and enhancing the sensitivity of APE1 imaging (limit of detection: 0.0092 U/mL in afterglow imaging and 0.16 U/mL in MRI). We devise longitudinally and transversely subtraction-enhanced imaging (L&T-SEI) strategy to markedly enhance MRI contrast and signal-to-noise ratio between tumor and normal tissue of living female mice. The combined afterglow and MRI facilitate both anatomical and functional imaging of APE1 activity. This probe enables correlation of afterglow and MRI signals with APE1 expression, radiation dosage, intratumor ROS, and DNA damage, enabling early prediction of radiotherapy outcomes (as early as 3 h), significantly preceding tumor size reduction (6 days). By monitoring APE1 levels, this probe allows for early and sensitive detection of liver organ injury, outperforming histopathological analysis. Furthermore, MRI evaluates APE1 expression in radiation-induced abscopal effects provides insights into underlying mechanisms, and supports the development of treatment protocols.

Icariin alleviates cisplatin-induced premature ovarian failure by inhibiting ferroptosis through activation of the Nrf2/ARE pathway

Cisplatin is a widely used chemotherapeutic drug that can induce ovarian damage. Icariin (ICA), a natural antioxidant derived from Epimedium brevicornum Maxim., has been found to protect against organ injury. The aim of the present study was to investigate whether ICA can exert an ovarian-protective effect on cisplatin induced premature ovarian failure (POF) and the underlying mechanism involved. The preventive effect of ICA was evaluated using body weight, the oestrous cycle, ovarian histological analysis, and follicle counting. ICA treatment increased body weight, ovarian weight, and the number of follicles and improved the oestrous cycle in POF mice. ICA reduced cisplatin-induced oxidative damage and upregulated the protein expression levels of Nrf2, GPX4 and HO-1. Moreover, ICA reduced the expression levels of Bax and γH2AX and inhibited ovarian apoptosis. In addition, ICA activated the Nrf2 pathway in vitro and reversed changes in the viability of cisplatin-induced KGN cells, reactive oxygen species (ROS) levels, lipid peroxidation, and apoptosis, and these effects were abrogated when Nrf2 was knocked down or inhibited. Molecular docking confirmed that ICA promotes the release of Nrf2 by competing with Nrf2 for binding to Keap1. The inhibitory effects of ICA on cisplatin-induced oxidative stress, ferroptosis, and apoptosis may be mediated by its modulatory effects on the Nrf2 pathway, providing a novel perspective on the potential mechanisms by which ICA prevents POF.

R406 reduces lipopolysaccharide-induced neutrophil activation

Modulating SYK has been demonstrated to have impacts on pathogenic neutrophil responses in COVID-19. During sepsis, neutrophils are vital in early bacterial clearance but also contribute to the dysregulated immune response and organ injury when hyperactivated. Here, we evaluated the impact of R406, the active metabolite of fostamatinib, on neutrophils stimulated by LPS. We demonstrate that R406 was able to effectively inhibit NETosis, degranulation, ROS generation, neutrophil adhesion, and the formation of CD16low neutrophils that have been linked to detrimental outcomes in severe sepsis. Further, the neutrophils remain metabolically active, capable of releasing cytokines, perform phagocytosis, and migrate in response to IL-8. Taken together, this data provides evidence of the potential efficacy of utilizing fostamatinib in bacterial sepsis.

Physiological Roles of Eumelanin- and Melanogenesis-Associated Diseases: A Look at the Potentialities of Engineered and Microbial Eumelanin in Clinical Practice.

This paper aims to highlight the physiological actions exerted by eumelanin present in several organs/tissues of the human body and to rationalise the often conflicting functional roles played by this biopolymer on the basis of its peculiar properties. Besides pigmentary disorders, a growing number of organ injuries and degenerative pathologies are presently ascribed to the modification of physiological eumelanin levels in terms of alterations in its chemical/structural features, and of a partial loss or uneven distribution of the pigment. The present review analyses the more recent research dedicated to the physiological and pathological actions of eumelanin and provides an insight into some melanogenesis-associated diseases of the skin, eye, ear, and brain, including the most significant neurodegenerative disorders. Also described are the potentialities of therapies based on the localised supply of exogeneous EU and the opportunities that EU produced via synthetic biology offers in order to redesign therapeutical and diagnostic applications.