Firearm Injuries in Young Children: Surgical Resource Utilization and Implications for Prevention.

INTRODUCTION: Pediatric firearm injury prevention research in younger age groups is limited. This study evaluated a large multicenter cohort of younger children with firearm injuries, focusing on injury patterns and surgical resource utilization. METHODS: Children ≤15 y old sustaining firearm injuries between 2016 and 2021 and treated at 10 pediatric trauma centers in Florida were included. Individual cases were reviewed for demographics, shooting details, injury patterns, resource utilization, and outcomes. Patients were grouped by age into preschool (0-5 y), elementary school (6-10 y), middle school (11-13 y), and early high school (14-15 y). Multivariable logistic regression was used to identify predictors of death and critical resource utilization. RESULTS: A total of 489 children (80 preschool, 76 elementary school, 92 middle school, and 241 early high school) met inclusion criteria. Demographics, injury patterns, and resource utilization were similar across age groups. Assault and self-harm increased with age. Self-harm was implicated in 5% of cases but accounted for 18% of deaths. Hand surgery (i.e., below-elbow) procedures were common at 8%. Overall mortality was 10%, but markedly higher for self-harm injuries (47%). On multivariable regression, age and demographics were not predictive of death or critical resource utilization, but self-harm intent was a strong independent risk factor for both. CONCLUSIONS: This study suggests that given the age distribution and disproportionately high impact of self-harm injuries, behavioral health resources should be available to children at the middle school level or earlier. Hand surgery may represent an overlooked but frequently utilized resource to mitigate injury impact and optimize long-term function.

Charting the course for improved outcomes in chronic critical illness: therapeutic strategies for persistent inflammation, immunosuppression, and catabolism syndrome (PICS).

Enhanced critical care delivery has led to improved survival rates in critically ill patients, yet sepsis remains a leading cause of multiorgan failure with variable recovery outcomes. Chronic critical illness, characterised by prolonged ICU stays and persistent end-organ dysfunction, presents a significant challenge in patient management, often requiring multifaceted interventions. Recent research, highlighted in a comprehensive review in the British Journal of Anaesthesia, focuses on addressing the pathophysiological drivers of chronic critical illness, such as persistent inflammation, immunosuppression, and catabolism, through targeted therapeutic strategies including immunomodulation, muscle wasting prevention, nutritional support, and microbiome modulation. Although promising avenues exist, challenges remain in patient heterogeneity, treatment timing, and the need for multimodal approaches.

Golf cart injuries have similar severity to all-terrain vehicle injuries in children: a multicenter comparison over a 5-year period.

Background: Golf carts (GCs) and all-terrain vehicles (ATVs) are popular forms of personal transport. Although ATVs are considered adventurous and dangerous, GCs are perceived to be safer. Anecdotal experience suggests increasing numbers of both GC and ATV injuries, as well as high severity of GC injuries in children. This multicenter study examined GC and ATV injuries and compared their injury patterns, resource utilization, and outcomes. Methods: Pediatric trauma centers in Florida submitted trauma registry patients age <16 years from January 2016 to June 2021. Patients with GC or ATV mechanisms were identified. Temporal trends were evaluated. Injury patterns, resource utilization, and outcomes for GCs and ATVs were compared. Intensive care unit admission and immediate surgery needs were compared using multivariable logistic regression. Results: We identified 179 GC and 496 ATV injuries from 10 trauma centers. GC and ATV injuries both increased during the study period (R2 0.4286, 0.5946, respectively). GC patients were younger (median 11 vs 12 years, p=0.003) and had more intracranial injuries (34% vs 19%, p<0.0001). Overall Injury Severity Score (5 vs 5, p=0.27), intensive care unit (ICU) admission (20% vs 16%, p=0.24), immediate surgery (11% vs 11%, p=0.96), and mortality (1.7% vs 1.4%, p=0.72) were similar for GCs and ATVs, respectively. The risk of ICU admission (OR 1.19, 95% CI 0.74 to 1.93, p=0.47) and immediate surgery (OR 1.04, 95% CI 0.58 to 1.84, p=0.90) remained similar on multivariable logistic regression. Conclusions: During the study period, GC and ATV injuries increased. Despite their innocuous perception, GCs had a similar injury burden to ATVs. Heightened safety measures for GCs should be considered. Level of evidence: III, prognostic/epidemiological.

The post-septic peripheral myeloid compartment reveals unexpected diversity in myeloid-derived suppressor cells.

Introduction: Sepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness. Methods: Cellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering. Results: We identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome. Discussion: The origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.

TRANSCRIPTOMIC DIFFERENCES IN PERIPHERAL MONOCYTE POPULATIONS IN SEPTIC PATIENTS BASED ON OUTCOME.

ABSTRACT: Postsepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. As classical and nonclassical monocytes are key leukocytes in both the innate and adaptive immune systems, we sought to delineate the transcriptomic response of these cell types. Using single-cell RNA sequencing and pathway analyses, we identified gene expression patterns between these two groups that are consistent with differences in TNF-α production based on clinical outcome. This may provide therapeutic targets for those at risk for chronic critical illness in order to improve their phenotype/endotype, morbidity, and long-term mortality.

Disparities in insurance status negatively affect patients with infantile hypertrophic pyloric stenosis.

PURPOSE: Infantile hypertrophic pyloric stenosis (IHPS) is suspected to have worse outcomes when length of illness prior to presentation is prolonged. Our objective was to evaluate how social determinants of health influence medical care and outcomes for babies with IHPS. METHODS: A retrospective review was performed over 10 years. Census data were used as proxy for socioeconomic status via Geo-Identification codes and correlated with food access and social vulnerability variables. The cohort was subdivided to understand the impact of Medicaid Managed Care (MMC). RESULTS: The cohort (279 cases) was divided into two groups; early group from 2011 to 2015 and late from 2016 to 2021. Cases in the late group were older at the time of presentation (41.5 vs. 36.5 days; p = 0.022) and presented later in the disease course (12.8 vs. 8.9 days; p = 0.021). There was no difference in race (p = 0.282), gender (p = 0.874), or length of stay. CONCLUSIONS: Patients who presented with IHPS after implementation of phased MMC were older, had a longer symptomatic course, and shorter pylorus measurements. Patients with public insurance after the implementation of MMC were more likely to follow-up with an outpatient pediatrician within a month of hospitalization. These results suggest that MMC may have improved access to care for infants with IHPS.

The unnecessary workups and admissions of adolescents and young adults with spontaneous pneumomediastinum.

Spontaneous pneumomediastinum (SPM) is a rare condition in children and young adults that raises concern for esophageal perforation or extension of an air leak, resulting in admissions with multiple interventions performed. To assess our outcomes, and to evaluate our resource utilization, we reviewed our experience with SPM. We conducted a retrospective review of SPM cases in patients aged 5-25 years old occurring between 2011 and 2021 at a single academic tertiary care center. Clinical, demographic, and outcome variables were collected and analyzed, and cohorts were compared using Fischer's Exact Test and Welch's T Test. 166 SPM cases were identified-all of which were Emergency Department (ED) presentations. 84% of the cases were admitted. 70% had Computerized Tomography (CT) scans, with no defined criteria for imaging. Comparison of floor admissions with discharges from the ED showed no significant difference in presenting symptoms, demographics, or outcomes between the two groups. Recurrence was noted in 4 patients with a range of 5.9 months-4.9 years from the initial episode. In the largest SPM study in the pediatric and young adult population, we noted no significant difference in management or outcomes in admitted or ED discharge patients nor those with CT imaging. Our results suggest that a large number of SPM can be managed safely with discharge from the ED.

Social determinants of health in pediatric trauma: Associations with injury mechanisms and outcomes in the context of the COVID-19 pandemic.

BACKGROUND: Relationships between social determinants of health and pediatric trauma mechanisms and outcomes are unclear in context of COVID-19. METHODS: Children <16 years old injured between 2016 and 2021 from ten pediatric trauma centers in Florida were included. Patients were stratified by high vs. low Social Vulnerability Index (SVI). Injury mechanisms studied were child abuse, ATV/golf carts, and firearms. Mechanism incidence trends and mortality were evaluated by interrupted time series and multivariable logistic regression. RESULTS: Of 19,319 children, 68% and 32% had high and low SVI, respectively. Child abuse increased across SVI strata and did not change with COVID. ATV/golf cart injuries increased after COVID among children with low SVI. Firearm injuries increased after COVID among children with high SVI. Mortality was predicted by injury mechanism, but was not independently associated with SVI, race, or COVID. CONCLUSION: Social vulnerability influences pediatric trauma mechanisms and COVID effects. Child abuse and firearm injuries should be targeted for prevention.

Analytical Validation and Assessment of Baseline Fecal Glucocorticoid Metabolites in Northern Sea Otters (Enhydra lutris kenyoni) in Human Care.

Fecal glucocorticoid metabolites (FGMs) have been used as a non-invasive and indirect measurement of the complex stress response in a variety of species. Animals in facilities under managed care allow for the longitudinal study of FGMs in a controlled environment. Animal histories often include environmental, husbandry, and medical notes that can be matched to FGM concentrations to aid in the physiological validation of adrenal stimulation and response. The goal of this study was to demonstrate analytical validations using two enzyme-linked immunosorbent assays (EIA) to measure FGMs from northern sea otters (Enhydra lutris kenyoni) under human care (Seattle Aquarium, Seattle, WA, USA) and to determine baseline and stress response spike levels for individual sea otters. Individual variation was found among the four subjects in the study with fecal baseline levels ranging from 20.2 to 83.7 ng/g for cortisol-immunoreactive metabolites and 52.3 to 102 ng/g for corticosterone-immunoreactive metabolites. As a retrospective study, 39 percent of hormone peaks were associated with notes and most FGM spikes were associated with veterinary procedures or days in which enrichment items were provided and produced an excitatory response. Monitoring baseline FGMs levels and events associated with hormone peak values may provide insight into effective husbandry management to improve the overall welfare of sea otters and other marine mammals.

Monocyte anisocytosis corresponds with increasing severity of COVID-19 in children.

Introduction: Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children. Methods: We performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children. Results: Monocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters. Conclusion: Monocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.

VARIABLES INFLUENCING THE DIFFERENTIAL HOST RESPONSE TO BURNS IN PEDIATRIC AND ADULT PATIENTS.

ABSTRACT: Burn injury is a significant source of morbidity and mortality in the pediatric population. Although 40,000 pediatric patients in the United States are admitted to the hospital with burn wounds annually, significant differences exist in the management and treatment of these patients, even among highly specialized burn centers. Some aspects of pediatric burn research, such as metabolic changes and nutritional support after burn injury, have been studied extensively; however, in many aspects of burn care, pediatric research lags behind the study of adult populations. This review compares and contrasts a wide array of physiologic and immune responses between children and adults after burn injury. Such a review elucidates where robust research has been conducted, where adult research is applicable to pediatric patients, and where additional pediatric burn research needs to be conducted.

TRAINED IMMUNITY: A POTENTIAL APPROACH FOR IMPROVING HOST IMMUNITY IN NEONATAL SEPSIS.

ABSTRACT: Sepsis, a dysregulated host immune response to infection, is one of the leading causes of neonatal mortality worldwide. Improved understanding of the perinatal immune system is critical to improve therapies to both term and preterm neonates at increased risk of sepsis. Our narrative outlines the known and unknown aspects of the human immune system through both the immune tolerant in utero period and the rapidly changing antigen-rich period after birth. We will highlight the key differences in innate and adaptive immunity noted through these developmental stages and how the unique immune phenotype in early life contributes to the elevated risk of overwhelming infection and dysregulated immune responses to infection upon exposure to external antigens shortly after birth. Given an initial dependence on neonatal innate immune host responses, we will discuss the concept of innate immune memory, or "trained immunity," and describe several potential immune modulators, which show promise in altering the dysregulated immune response in newborns and improving resilience to sepsis.

Structural evaluation of child physical abuse in trauma: Social determinants of health at the population level.

PURPOSE: Child physical abuse (CPA) is closely linked to social factors like insurance status with limited evaluation at a structural population-level. This study evaluates the role of social determinants of health within the built environment on CPA. METHODS: A single-institution retrospective review of pediatric trauma patients was conducted between January 2016 and December 2020. Patient address was geocoded to the census-tract level. Socioeconomic metrics, including poverty rate, supermarket access and Social Vulnerability Index (SVI) were estimated from the Food Access Research Atlas. Univariate and multivariable regression analyses were conducted to compare demographics and outcomes. RESULTS: Of 3,540 patients, 317 (9.0%) had concern for physical abuse reported in the registry. CPA patients were younger (7.5 vs 9.6 years, p<0.0001) and more often Black (37.0%, N = 117 vs 23.5%, N = 753; p<0.0001). CPA had higher injury severity scores (ISS) (7.9 vs 5.8, p<0.0001) and longer length of stay (5.3 vs 2.9 days, p<0.0001). CPA had higher Medicaid (73.0%, N = 232 vs 53.8%, N = 1748, p<0.0001) and SVI (0.65 vs 0.59, p<0.0001) with lower median income ($52,100 vs $56,100, p<0.0001) and more low-food access tracts (59.6% vs 53.6%, p = 0.06). Combined low-income and low-food access populations showed widened disparities (40.0% vs 28.9%, p = 0.0002). On multivariate analysis, CPA was associated with poverty (OR 2.3, 95% CI [0.979, 3.60], p = 0.0006), low-access Black share (OR 3.3, 95% CI [1.18, 5.47], p = 0.002) and urban designation (OR 1.5, 95% CI [1.13, 1.87], p = 0.004). CONCLUSION: The built-environment and population-level social determinants of health are related to child physical abuse and should influence advocacy and prevention. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective.

Exploring Limited English Proficiency in the Clinical Outcomes of Pediatric Burn Patients.

INTRODUCTION: Limited English proficiency (LEP) is linked to lower health care access and worse clinical outcomes. This study aims to explore the potential role of LEP on clinical outcomes of pediatric burn patients. METHODS: We conducted a single-institution retrospective study of burn patients presenting at a tertiary pediatric burn referral program between January 2016 and December 2020. Patient demographics, burn mechanism, severity, interventions, and primary patient language were abstracted from the electronic health record. Clinical outcomes (length of stay [LOS], clinic follow-up, and 30-day readmission) of patients with LEP were compared to patients with English as primary language (EPL). RESULTS: Thirty-five (4.2%) patients with LEP were identified of 840 total patients. On univariate analysis, there was no difference in mean total body surface area (6.5% versus 6.1%), report of physical abuse (2.9% versus 8.9%), or need for grafting (14.3% versus 15.0%) comparing patients with LEP to those with EPL. Patients with LEP were more likely to have a scald burn (68.6% versus 48.9%, P = 0.025) and less likely to have a flame/fire burn (20.0% versus 37.6%, P = 0.047). On multivariate analysis, there was no difference between patients with LEP compared to patients with EPL for LOS (2.9 versus 3.5 d), 30-day readmissions (5.6% versus 5.7%), or clinic follow-up (80.6% versus 75.0%). In patients with >10% total body surface area, patients with LEP had a longer emergency department LOS (277 min versus 145 min, P = 0.06) but no difference in outcome measures. CONCLUSIONS: Pediatric patients with LEP were not found to have worse burn outcomes compared to EPL patients in our patient sample. However, a true association is difficult to determine given the small sample size of LEP patients and the potential underestimation of language discordancy as recorded in the electronic medical record. Further research is needed to better explore the role of primary language and health communication as a social determinant of health in pediatric burn patients.

Effects of vessel traffic and ocean noise on gray whale stress hormones.

Human use of marinescapes is rapidly increasing, especially in populated nearshore regions where recreational vessel traffic can be dense. Marine animals can have a physiological response to such elevated human activity that can impact individual health and population dynamics. To understand the physiological impacts of vessel traffic on baleen whales, we investigated the adrenal stress response of gray whales (Eschrichtius robustus) to variable vessel traffic levels through an assessment of fecal glucocorticoid metabolite (fGC) concentrations. This analysis was conducted at the individual level, at multiple temporal scales (1-7 days), and accounted for factors that may confound fGC: sex, age, nutritional status, and reproductive state. Data were collected in Oregon, USA, from June to October of 2016-2018. Results indicate significant correlations between fGC, month, and vessel counts from the day prior to fecal sample collection. Furthermore, we show a significant positive correlation between vessel traffic and underwater ambient noise levels, which indicates that noise produced by vessel traffic may be a causal factor for the increased fGC. This study increases knowledge of gray whale physiological response to vessel traffic and may inform management decisions regarding regulations of vessel traffic activities and thresholds near critical whale habitats.

Social determinants of health in pediatric scald burns: Is food access an issue?

BACKGROUND: Burn injury risk, severity, and outcomes have been associated with socioeconomic status. Limited data exist to evaluate health access-related influences at a structural population level. This study evaluated factors at the Census-tract level, specifically evaluating food access and social vulnerability in pediatric scald burns. METHODS: A single-institution retrospective review using the trauma registry and electronic medical record was conducted of pediatric burns between 2016 and 2020. Home address was coded to the Census-tract level and bulk analyzed. Socioeconomic metrics of the home environment were evaluated from publicly available databases, the United States Food and Drug Administration Food Access Research Atlas, and the Centers for Disease Control's Social Vulnerability Index. RESULTS: There were 840 patients that met inclusion criteria (49.8% scald, N = 418). The mean total body surface area for scalds was 6.6% with an age of 10.2 years; 76% (n = 317) of scalds had Medicaid, and 15% (n = 63) were due to hot noodles. Scalds occurred more in females (45.7%, N = 191 vs 28.0%, N = 118; P < .0001), non-White race (62.7%, N = 262 vs 29.1%, N = 123; P < .0001), and low-income and low-food access populations (39.8%, N = 147 vs 30.4%, N = 116; P = .007). Low-food access Black populations showed increased scald injury (18% [interquartile range 6-35] vs 10% [interquartile range 4-25]), whereas all other populations showed no association. The patients with scalds had a higher overall social vulnerability index (0.67 vs 0.62, P = .008). CONCLUSION: Often related to poverty, health access, and health equity, population-level social determinants of health like social vulnerability and food access have significant impact on health care and should influence health outreach and systems improvement.

Heterogeneity in the evaluation of suspected MIS-C: a cross-sectional vignette-based survey.

BACKGROUND AND OBJECTIVES: Multisystem Inflammatory Syndrome in Children (MIS-C) is an emerging complication of COVID-19 which lacks a definitive diagnostic test and evidence-based guidelines for workup. We sought to assess practitioners' preferences when initiating a workup for pediatric patients presenting with symptoms concerning for MIS-C. METHODS: In a cross-sectional vignette-based survey, providers were presented with clinical vignettes of a patient presenting with 24 h of fever from a community with high rates of COVID-19. Respondents were asked about their general practices in pursuing a workup for potential MIS-C including testing obtained, criteria for diagnosis, and timing to confirm or rule out the diagnosis. RESULTS: Most of the 174 respondents were physicians from the United States at academic medical centers. The majority of providers would not initiate MIS-C workup for fever and non-specific symptoms unless the fever lasted more than 72 h. Skin rash, abdominal pain, and shortness of breath were symptoms that raised greatest concern for MIS-C. Most providers would obtain COVID-19 PCR or antigen testing, plus blood work, in the initial workup. The list of laboratory studies providers would obtain is extensive. Providers primarily rely on cardiac involvement to confirm a MIS-C diagnosis, and establishing a diagnosis takes 24-48 h. CONCLUSIONS: Significant heterogeneity exists amongst providers as to when to initiate the MIS-C workup, the order and content of the workup, and how to definitively diagnose MIS-C. A diagnostic test with high sensitivity and specificity for MIS-C and refined evidence-based guidelines are needed to expedite diagnosis and treatment.

Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. METHODS: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. RESULTS: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78-100%) and 80% specificity (95% CI 69-88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80-100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. CONCLUSIONS: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.

T-Cell Activation and LPS: A Dangerous Duo for Organ Dysfunction.

Lipopolysaccharide (LPS), one of the main components of cell membranes in gram-negative bacteria, is commonly used to promote inflammation-induced organ dysfunction. In the TLR4/LPS pathway, LPS binding protein and CD14 enable lipid A of LPS to be recognized by the TLR4-MD2 receptor complex. The intracellular domain of the TLR4/LPS complex stimulates MyD88-dependent/independent and TRIF-dependent pathways, which in turn activate NF-B and IRF3, leading to subsequent production of pro-inflammatory mediators. LPS has been demonstrated to induce microcirculatory disturbances via promotion of leukocyte adhesion to the vascular endothelium and the release of reactive oxygen species (ROS), damaging the vessels and causing vascular dysfunction. Thus, LPS is frequently used as a systemic model of inflammation as LPS administration increases circulating pro-inflammatory mediators, which triggers leukocyte adhesion and leads to multi-organ failure and death.