Hemorrhagic Shock Research Articles

Abstract B009: Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers

Abstract While the use of ctDNA-based minimal residual disease (MRD) monitoring is gaining popularity in adult cancers, this approach is not yet widely adopted in pediatric cancers (PCs). We developed a robust and sensitive assay to monitor ctDNA in PCs, which overcomes PC-specific challenges including low tumor mutational burden, paucity of hotspot mutations and low blood volume. To address these challenges, our innovations include personalized panel design that targets primary tumor mutations from each patient, a fixed panel targeting hotspot mutations, error suppression from duplex deep sequencing and customized pipeline for tumor burden estimation. We retrospectively analyzed 661 blood or cerebrospinal fluid (CSF) samples from 168 patients. We achieved an average detection limit of 0.005% ctDNA purity leading to MRD detected ranging from 0.001% to 100% with brain tumor consistently showing a low MRD. At disease diagnosis, progression and relapse, our assay identified ctDNA in over 93% of extra- cranial solid tumors, 90% of leukemia, 89% of sarcoma, and 90% of neuroblastoma. For brain tumors, we detected MRD in ∼90% of CSF samples, and in ∼60% of blood samples, a major advance over previous approaches. Importantly, we detected MRD in ∼ 20% of cases with a clinically complete response, predicting relapse up to 6 months before clinical confirmation. Overall, these results demonstrate that our monitoring assay for PCs is an important addition to standard of care for precision-guided treatment. Citation Format: Rob Salomon, Wenhan Chen, Charles Shale, Mojgan Toumari, Aileen Lowe, Wenyan Li, Jingwei Chen, Sajad Razavi-Bazaz, Paulette Barahona, Louise Cui, Chelsea Mayoh, Sam El-Kamand, Vanessa Tyrrell, Marie Wong-Erasmus, Loretta MS Lau, Noemi Fuentes-Bolanos, Edwin Cuppen, Dong-Anh Khoung-Quang, Jordan Staunton, Marion K Mateos, Toby Trahair, Michelle Haber, David S Ziegler, Paul Ekert, Peter Priestley, Mark Cowley. Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B009.

Nonselective beta blockade enhances gut microbiome diversity in a rodent model of trauma, hemorrhage, and chronic stress

BACKGROUND Traumatic injury leads to gut dysbiosis with changes in microbiome diversity and conversion toward a “pathobiome” signature characterized by a selective overabundance of pathogenic bacteria. The use of non-selective beta antagonism in trauma patients has been established as a useful adjunct to reduce systemic inflammation. We sought to investigate whether beta-adrenergic blockade following trauma would prevent the conversion of microbiome to a “pathobiome” phenotype. METHODS Sprague-Dawley rats (n = 6–8/group) were subjected to routine daily handling (naïve), lung contusion with hemorrhagic shock (LCHS), or LCHS with daily chronic stress (LCHS/CS), each with or without administration of intraperitoneal propranolol (BB) (10 mg/kg/day). Fecal microbiome was measured on Days 0, 7, and 14 using high-throughput 16S rRNA sequencing and QIIME2 bioinformatics analyses. Alpha- and beta-diversity and microbiome composition were assessed with significance defined as *p < 0.05. RESULTS Use of propranolol following LCHS or LCHS/CS demonstrated a significant increase in the number of bacterial species (Chao1 index), as well as overall richness and evenness (Shannon index) compared with their untreated counterparts at Day 7. By Day 14, these differences were no longer apparent between BB and untreated groups subjected to LCHS/CS. There was an abundance of commensal bacteria such as Oscillospiraceae and Clostridia in LCHS and LCHS/CS treated with BB after 7 days which persisted at 14 days. CONCLUSION These findings suggest a role for beta-antagonism in altering the diversity of the gut microbiome and the need for further studies to elucidate the cellular and molecular mechanisms underlying this intriguing connection of microbiome with trauma and beta-blockade.

Abstract 4136700: Sodium-Potassium Pump: Newly O-GlcNAc Protein Offering Potential Benefits in Hemorrhagic Shock situation

Hemorrhagic shock(HS) results from significant blood loss, leading to insufficient oxygen delivery, which causes metabolic changes and multi-organ dysfunction.The HS-related acute kidney injury developed by the patient are mainly due to alteration in Na/K ATPase.In previous O-GlcNAcylomic studies, we identified the Na/K ATPase as potentially O-GlcNAcylated.O-GlcNAcylation, a post-translational modification, plays a role in various cellular processes, such as cell survival and stress response.O-GlcNAcylation may have beneficial effect in shock situations. The objective of this study is to ascertain whether Na/K ATPase is O-GlcNAcylated and to elucidate its potential role during HS. Hemorrhagic shock was induced by an exsanguination of rats.They were then randomly treated or not with an O-GlcNAcase inhibitor, the NButGT(10mg/kg), to increase O-GlcNAc level.Blood pressure and heart rate were monitored throughout the experiment.Blood samples were collected for complete blood analysis, including biochemistry and gas measurements. kidneys were immediately frozen for histological and biochemical studies.To study the O-GlcNAcylation of Na/K ATPase an immunoprecipitation and Wheat Germ Agglutinin(WGA) based lectin affinity gel electrophoresis were used. HEK cells were treated with or without NButGT(100µM,6 hours) and/or ouabain(Na/K ATPase inhibitor) and a colorimetric kit was assessed to study O-GlcNAcylation impact on Na/K ATPase activity. O-GlcNAc levels increased by 2 folds in heart and kidney due to the NButGT treatment(p<0.05).Mean arterial pressure(MAP,p<0.01) and bicarbonate(p<0.01) are restored in treated group as kalemia(Sham:4.2 ± 0.1;HS:4.7±0.1;NButGT:4.3 ±0.1;mmol/L;p<0.05) and natremia(Sham:141.5±0.4;HS:139.8±0.5;NButGT:141.9 ±0.4; mmol/L;p<0.01).The study of the O-GlcNAcylation of the Na/K ATPase validated its O-GlcNAcylation.Histological analysis of the kidney showed that HS decreased Na/K ATPase expression, but treatment restored it(Sham:15.1±1.1;HS:10.3±0.6;NButGT:13.78±1.1;%area;p<0.05). An acute increase in O-GlcNAc levels through NButGT enhances Na/K ATPase activity. Increased O-GlcNAcylation during hemorrhagic shock restored MAP and reduced indicators of metabolic acidosis.Treatment with NButGT restored natremia and kalemia.This effect is linked to an increase in the expression and activity of Na/K ATPase.Our study is the first to confirm that Na/K ATPase is regulated by O-GlcNAcylation, particularly in terms of its localization and stability.

Metabolic Effects of Sodium Thiosulfate During Resuscitation from Trauma and Hemorrhage in Cigarette-Smoke-Exposed Cystathionine-γ-Lyase Knockout Mice

Background: Acute and chronic pre-traumatic cigarette smoke exposure increases morbidity and mortality after trauma and hemorrhage. In mice with a genetic deletion of the H2S-producing enzyme cystathione-γ-lyase (CSE−/−), providing exogenous H2S using sodium thiosulfate (Na2S2O3) improved organ function after chest trauma and hemorrhagic shock. Therefore, we evaluated the effect of Na2S2O3 during resuscitation from blunt chest trauma and hemorrhagic shock on CSE−/− mice with pre-traumatic cigarette smoke (CS) exposure. Since H2S is well established as being able to modify energy metabolism, a specific focus was placed on whole-body metabolic pathways and mitochondrial respiratory activity. Methods: Following CS exposure, the CSE−/− mice underwent anesthesia, surgical instrumentation, blunt chest trauma, hemorrhagic shock for over 1 h (target mean arterial pressure (MAP) ≈ 35 ± 5 mmHg), and resuscitation for up to 8 h comprising lung-protective mechanical ventilation, the re-transfusion of shed blood, fluid resuscitation, and continuous i.v. noradrenaline (NoA) to maintain an MAP ≥ 55 mmHg. At the start of the resuscitation, the mice randomly received either i.v. Na2S2O3 (0.45 mg/gbodyweight; n = 14) or the vehicle (NaCl 0.9%; n = 11). In addition to the hemodynamics, lung mechanics, gas exchange, acid–base status, and organ function, we quantified the parameters of carbohydrate, lipid, and protein metabolism using a primed continuous infusion of stable, non-radioactive, isotope-labeled substrates (gas chromatography/mass spectrometry) and the post-mortem tissue mitochondrial respiratory activity (“high-resolution respirometry”). Results: While the hemodynamics and NoA infusion rates did not differ, Na2S2O3 was associated with a trend towards lower static lung compliance (p = 0.071) and arterial PO2 (p = 0.089) at the end of the experiment. The direct, aerobic glucose oxidation rate was higher (p = 0.041) in the Na2S2O3-treated mice, which resulted in lower glycemia levels (p = 0.050) and a higher whole-body CO2 production rate (p = 0.065). The mitochondrial respiration in the heart, kidney, and liver tissue did not differ. While the kidney function was comparable, the Na2S2O3-treated mice showed a trend towards a shorter survival time (p = 0.068). Conclusions: During resuscitation from blunt chest trauma and hemorrhagic shock in CSE−/− mice with pre-traumatic CS exposure, Na2S2O3 was associated with increased direct, aerobic glucose oxidation, suggesting a switch in energy metabolism towards preferential carbohydrate utilization. Nevertheless, treatment with Na2S2O3 coincided with a trend towards worsened lung mechanics and gas exchange, and, ultimately, shorter survival.

Abstract 4135095: Outcomes of Atrial Fibrillation Patients with Thrombocytopenia: Insights From a Nationwide Database

Background: While anticoagulation is crucial for atrial fibrillation (AF) patients to prevent ischemic events, those with thrombocytopenia have a potential increased risk of bleeding. This study examines the outcomes of hospitalized AF patients with thrombocytopenia. Methods: The National Inpatient Sample (NIS) from 2016-2020 was analyzed to identify adult patients with AF and thrombocytopenia (using the proper ICD-10 codes). Multivariate logistic and regression analyses were performed after adjusting for multiple patient and hospital confounders to compare outcomes between patients with and without thrombocytopenia. The primary outcome was all-cause inpatient mortality. Secondary outcomes included major bleeding (defined as gastrointestinal, intracranial, pulmonary, or unspecified bleeding), hypovolemic shock, packed red blood cell (pRBC) transfusion, ischemic stroke, length of stay (LOS), and total charges. Results: Among 2,016,244 AF admissions, 75,545 patients (3.75%) had thrombocytopenia. Thrombocytopenia was associated with increased inpatient mortality (adjusted odds ratio [aOR] 2.47, 95% CI 2.21-2.77, p < 0.001). Thrombocytopenia was also associated with increased risk of major bleeding (aOR 1.99, 95% CI 1.8-2.19, p < 0.001), hypovolemic shock (aOR 3.11, 95% CI 2.29-4.24, p < 0.001), pRBC transfusion (aOR 3.07, 95% CI 2.8-3.37, p < 0.001). There was no significant difference in ischemic stroke risk (aOR 0.67, 95% CI 0.37-1.21, p < 0.19) but thrombocytopenia was associated with longer LOS (aMD 1.5 days, 95% CI 1.41-1.59, p < 0.001) and higher total charges (aMD $16,508, 95% CI 14,805-18,211, p < 0.001). Conclusions: Thrombocytopenia in hospitalized AF patients is associated with increased mortality, bleeding risk, and healthcare costs, with no clear impact on ischemic stroke. These findings highlight the need for careful risk-benefit assessment and individualized management strategies for this vulnerable patient population.

Abstract 4136290: Toward Quantitative Assessment of Cerebrovascular Autoregulation in Neonates using Ultrafast Ultrasound Power Doppler

Introduction: Newborns with congenital heart diseases requiring cardiopulmonary bypass are at risk of neurodevelopmental impairment. The impact of deep hypothermia during cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of variable blood pressure is not well understood. Recently, Ultrafast Power Doppler (UPD) showed potential to study CAR in neonates based on the measurement of cerebral blood volume (CBV). However, since CAR relies mainly on the arterial vasoconstriction/vasodilation, the interpretation of brain perfusion based on CBV requires further separation of arterial CBV from total CBV. This study aims to use UPD to monitor CAR during DH-CPB in neonates. Methods: An ultrasonic probe (5.7 MHz) was placed on the anterior fontanel of 6 newborns before, during and after DH-CPB. Using ultrafast sequences generated by a Verasonic Vantage research system, mid-coronal plane images were acquired (PRF of 9 kHz, 5 compounded diverging waves). An adaptive spatiotemporal singular value decomposition was used to separate the blood signal from tissue signal and obtain UPD. CBV was computed in the deep gray matter (DGM). This region was chosen due to its higher susceptibility to hypoxic-ischemic injury. Arterial CBV was isolated from total CBV based on the upward arterial flow obtained using signed-power Doppler (See Fig A). Pearson correlation ® was computed between mean arterial blood pressure (MAP) and arterial CBV to study CAR. Results: Before and after DH-CPB, negative correlations were found between arterial CBV and MAP: -0.30 and -0.43 respectively. This indicates that an increase in MAP is associated with a decrease in cerebral arterial blood volume. This decrease in arterial CBV likely arises from arterial vasoconstriction, suggesting an active CAR response. Conversely, during DH-CPB, no correlation was found (r = -0.02). This means that despite the increase in MAP, arterial CBV remains unchanged. This lack of variation of arterial CBV is likely due to absent arterial vasoconstriction, suggesting an impaired CAR response. Conclusion: Our findings highlight the potential of UPD for continuous monitoring of CAR, paving the way for improving neurovascular management strategies during DH- CPB.

Haemorrhagic shock in a pregnant patient and the unsuspicious subclavian catheter

Introduction: Central venous catheterisation (CVC) is a commonly performed procedure in clinical practice. Although usually safe, complications can arise such inadvertent vascular lesion. This report is of a case of left brachiocephalic vascular lesion due to a subclavian catheter, thus raising awareness about this potential complication, which is not always immediately recognised. Case report: We report the case of a 31-year-old healthy woman, 42 weeks pregnant, who presented with complications during an elective caesarean section. The patient experienced haemorrhagic shock due to the incomplete rupture of the left ovarian pedicle, further complicated by the accidental lesion of the left brachiocephalic vein caused by the tip of a right subclavian catheter, aggravated by the late discovery only after extubation. This case highlights the importance of patient selection, proper technique and the careful monitoring pre- and post-procedure. Conclusion: Brachiocephalic vein lesions arising from CVC insertions are rare but significant complications that require timely recognition and intervention.

An Observational Study of Patients Presenting in Hypotension and Shock to Emergency Room by Applying RUSH Protocol

Introduction: Care of the patient with shock can be one of the most challenging issues in emergency medicine. The early use of ultrasound at the bedside in such emergency is a very valuable tool to determine the type of shock. Rapid Ultrasound in SHock (RUSH) protocol done by emergency physicians is one such protocol which is being underused. Hence, we conducted this study to assess the effectiveness of the RUSH protocol for patients presenting with undifferentiated hypotension and shock. Materials and methods: This was prospective observational study done on a total of 100 patients presented with hypotension and shock. We performed an early bedside sonographic examination for participants based on RUSH protocol and type of shock was determined. Then the definitive interventions were performed as per the type of shock. The outcome measures were determined either till the survival to discharge from the hospital or till the in-hospital death of the patient. The data was analysed using SPSS version25. Results: In this study, the type of shock most commonly found overall was hypovolemic shock (40%) followed by cardiogenic shock (27%) and distributive shock (17%). Contractility of left ventricle, size of right ventricle, inferior venacava caliber, hemoperitoneum, pneumothorax, hemothorax, pulmonary edema, pleural effusion and lungs consolidation were statistically significant in determining the type of shock except cardiac tamponade, abdominal aortic aneurysm/dissection and deep vein thombosis. Majority of the interventions performed were fluid resuscitation (41%), vasopressors and inotropes (28%) and laparotomy (9%) and were statistically significant (p=0.001). Among all patients, 73% survived and 27% died. The outcome was statistically significant (p=0.002). Conclusion: RUSH protocol used for undifferentiated hypotension and shock is an effective tool at the bedside as an early approach to diagnose the type of shock. It will also help in determining early definitive interventions in shock states and thereby having better patient outcomes.

Effect on Syndecan-1 and Hyaluronan Levels Depending on Multiple Organ Failure, Coagulopathy and Survival: An Observational Study in Major Trauma Patients

Background: Major trauma, as well as traumatic hemorrhagic shock go along with early damage to the endothelial glycocalyx (EG). Shed glycocalyx constituents can activate the innate immune system and aggravate secondary injury. Subsequently, we investigated the relationship between glycocalyx shedding and the occurrence of coagulopathy, multiple organ failure (MOF) and outcome in our cohort after severe trauma. Methods: We included multiple trauma patients, as defined by Injury Severity Score (ISS). Polytraumatized patients must have arrived in our level 1 trauma center within 60 min after trauma. Retrospectively, patients were assigned to predefined clinical conditions, based on injury severity (ISS ≥ 16 points), multiple organ failure (MOF score ≥ 6 points), need for massive transfusion (≥10 RBC units/first 24 h), coagulopathy (prothrombin time < 70% at 0 h) and survival (90-day survival). Syndecan-1 (Sdc-1) and hyaluronan (HA) plasma concentrations were evaluated immediately (0 h), 6 h and 12 h after trauma. Results: 49 patients (mean ISS 35.7 ± 12.1 SD, mean age 45.78 ± 15.6 SD) were included in this study. A total of 37 patients (75.5%) survived, while 12 patients died within the observation period of 90 days after trauma (24.5%). A total of 77% of all patients suffered multiple organ failure (MOF score ≥ 6, n = 30). Initial prothrombin time at 0 h was <70% in 31 patients. Plasma concentrations of circulating both glycocalyx constituents showed a significant increase over the first 12 h after trauma (p = 0.001; p = 0.008). Patients with multiple organ failure showed significantly increased hyaluronan concentrations at all three time points (p = 0.007/0.006/<0.001), and the syndecan-1 levels were significantly elevated 12 h after trauma in the MOF group (p = 0.01). Patients with coagulopathy on admission exhibited significantly higher hyaluronan levels at 12 h (p = 0.042). Non-survivors showed significantly increased syndecan-1 levels at 12 h after trauma (p = 0.024). Conclusions: Glycocalyx shedding occurs immediately after major trauma. Coagulopathy is associated with significantly increased plasma hyaluronan. Further, significant changes in plasma concentrations within the first 12 h help to identify subgroups at risk for developing MOF and death.

Association Between Finger Plethysmographic Features and Impedance-Based Thoracic Fluid Content Measurement in a Lower Body Negative Pressure Model of Hemorrhagic Shock

ABSTRACT Introduction Timely identification of the need for lifesaving intervention in battlefield conditions may be improved through automated monitoring of the injured warfighter. Technologies that combine maximal noninvasive insight with minimal equipment footprint give the greatest opportunity for deployment at scale with inexperienced providers in forward areas. Finger photoplethysmography (PPG) signatures are associated with impending hemorrhagic shock but may be insufficient alone. Transthoracic impedance (TTI) monitoring is a complementary modality to PPG and able to identify volume loss and estimate functional cardiovascular parameters. We sought to understand how PPG features correlate with volume loss estimation from TTI during lower body negative pressure (LBNP) challenge. We hypothesized that features of the PPG waveform would correlate with thoracic fluid content (TFC) as measured by TTI. Materials and Methods We obtained physiologic monitoring data from healthy adult subjects in LBNP hemorrhagic shock models after local Institutional Review Board and DoD Human Research Protection Office approval. Subjects were excluded for pregnancy, age >45 years, and conditions prohibitive of LBNP exposure. Subjects were instrumented with noninvasive sensors, including a finger PPG sensor and a TTI monitor. Subjects underwent a stepwise LBNP exposure program of −10 mmHg every 10 minutes and notified laboratory staff at first sign of near syncope, terminating the sequential program. TTI data were continuously streamed to a custom program written in MATLAB and time synchronized. To calculate PPG measures, we downsampled data to 250 Hz, screened, and parsed each beat. We featurized each beat to include a systolic, diastolic, and dicrotic notch peak, beat length and area under the curve (AUC), peak-to-peak systolic/diastolic interval, and leading/trailing slopes, all normalized to instantaneous heart rate. Thoracic fluid content was normalized to subjects’ pre-LBNP baselines. We summarized all PPG features and the TFC using means (SD) generated as a subject average for each step. We used generalized estimating equation models to examine the relationship between TFC and PPG features while controlling for LBNP stage and subject. Results Thirty-two subjects were enrolled; 4 participants were excluded because of sensor malfunction. Twenty-eight subjects had a mean (SD) age of 25.11 (6.66) years. A total of 35.7% of subjects were female. Photoplethysmography analysis demonstrated a decreased systolic-diastolic peak interval, diastolic peak height, and beat AUC with decreased LBNP pressure. End-stage baseline normalized TFC showed an average decrease of 14.68% (±4.98%) (range: 7.54% to 27.69%). The strongest average correlations between stage TFC and PPG occurred in beat length (0.68) and normalized AUC (0.69). In generalized estimating equation models incorporating all stages, beat length, normalized AUC, and the systolic-diastolic interval were all significantly associated with time as a function of LBNP level (P < .001). Thoracic fluid content began decreasing at 12.8 (4.7) minutes, the normalized AUC decreased at 20.7 (7.2) minutes, the beat length decreased at 20.9 (7.0) minutes, and the systolic-diastolic time interval decreased at 30.6 (16.7) minutes. Conclusions While both PPG features and impedance-based TFC trend congruently in the perishock state following LBNP exposure, peripheral pulse wave signals lag redistribution of thoracic fluid volume. Photoplethysmography features of beat length and normalized AUC may serve as a surrogate for TFC when direct thoracic sensing is not available.

In vivo evaluation of an adaptive resuscitation controller using whole blood and crystalloid infusates for hemorrhagic shock

IntroductionHemorrhage remains the leading cause of preventable death on the battlefield. The most effective means to increase survivability is early hemorrhage control and fluid resuscitation. Unfortunately, fluid resuscitation requires constant adjustments to ensure casualty is properly managed, which is often not feasible in the pre-hospital setting. In this study, we showed how an adaptive closed-loop controller for hemorrhage resuscitation can be used to automate hemodynamic management using a swine hemorrhagic shock injury model.MethodsThe adaptive resuscitation controller (ARC) was previously developed to track pressure–volume responsiveness in real time and adjust its infusion rate to reach the target mean arterial pressure (MAP). Swine while maintained under a surgical plane of anesthesia and analgesia underwent a splenectomy, followed by two hemorrhage and resuscitation events. For the first resuscitation event, hemorrhage was induced to reduce the MAP to 35 mmHg until arterial lactate reached 4 mmol/L. The ARC system then infused whole blood (WB) to reach the target MAP and maintained the subject using crystalloids for 120 min. For the second resuscitation event, the subjects were hemorrhaged again but resuscitated using only crystalloid infusion to reach the target MAP and 120-min maintenance.ResultsThe ARC was effective at WB resuscitation, reaching the target MAP in 2.0 ± 1.0 min. The median performance error was 1.1% ± 4.6%, and target overshoot was 14.4% ± 7.0% of the target MAP. The ARC maintained all animals throughout the 120 min maintenance period. For the second crystalloid-based resuscitation, ARC required a longer time to reach the target MAP, at an average rise time of 4.3 ± 4.0 min. However, target overshoot was reduced to 8.4% ± 7.3% of the target MAP. Much higher flow rates were required to maintain the target MAP during the second resuscitation event than during the first resuscitation event.DiscussionThe ARC was able to rapidly reach and maintain the target MAP effectively. However, this sometimes required large volumes of fluid as the ARC’s only goal was to reach the target MAP. Further clinical insight is needed regarding the preferred aggression level to achieve the target MAP. In conclusion, the ARC was successful in its programmed objective of reaching and maintaining the target MAP for extended periods of time in vivo, a critical next step toward improving hemorrhage treatment in the pre-hospital environment.

The MangLE score: A novel simple tool to identify patients who are unlikely to require amputation following severe lower extremity injury.

There are no validated and sensitive models that can guide the decision regarding amputation in patients with mangled lower extremities. We sought to describe a simple scoring model, the Mangled Lower Extremity (MangLE) score, which can predict those who are highly unlikely to need an amputation as a means to direct resources to this cohort. This is a retrospective study using the 2013-2021 American College of Surgeons Trauma Quality Improvement Program data set. Adult patients with a mangled lower extremity, defined as a crush injury or a fracture of the femur or tibia combined with severe soft tissue injury, arterial injury, or nerve injury, were included. Patients who suffered a traumatic lower extremity amputation, underwent amputation within 24 hours of admission, or who died within 24 hours of admission were excluded. Patients were divided into those who did/did not undergo amputation during their hospital stay. Demographics, injury mechanism, Injury Severity Score, and Abbreviated Injury Scale score, initial vital signs, and comorbid conditions were abstracted. A logistic regression model was constructed and the top five most important variables were used to create the score. The study includes 107,620 patients, of whom 2,711 (2.5%) underwent amputation. The five variables with the highest predictive value for amputation were arterial injury, lower-extremity Abbreviated Injury Scale score of ≥3, crush injury, blunt mechanism, and shock index. The lowest possible MangLE score was 0, and the highest was 15. The model demonstrated an excellent predictive ability for lower extremity amputation in both the development and validation data set with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval, 0.80-0.82) and 0.82 (95% confidence interval, 0.81-0.84), respectively. The negative predictive value for a score of <8 is 99%. The MangLE score is able to identify patients who are unlikely to require amputation. Resources for limb salvage can be directed to this cohort. Prospective and Epidemiologic; Level IV.

Neonatal Presentation of Severe Hemophilia A: An Original Case Report and a Literature Review

Introduction: We report the case of a neonate diagnosed with severe hemophilia A (HA) and conduct a literature review of cases of severe HA presenting at the neonatal age to help define the clinical diagnostic findings and existing differences between the sporadic and familial onset of this condition. Report of a Case: A 6-day-old newborn presented with worsening pallor, inappetence, and hyporeactivity for 48 h. The diagnosis was severe hemophilia A (HA), leading to an unfavorable outcome. A literature review focusing on case reports and series focusing on the clinical expression of HA in neonates was conducted, documenting clinical presentation, family history, and outcomes. Literature review: Forty patients were included. HA was observed in five cases (12.5%) of very preterm births (≤32 weeks) and in four cases (10%) of moderately or late preterm births. Seventeen patients (43%) had a family history, with inheritance being sporadic (21 newborns, 53%) or acquired (2 cases, 4%). Clinical onset typically occurred within the first week of life (approximately 8 out of 10 cases), while only three cases (7.5%) had onset after the first month. Inherited cases presented with hemorrhagic states (nine cases), hypovolemic shock (five cases), or intracranial hypertension (two cases). Sporadic cases showed localized bleeding (11 cases), hypovolemic shock (5 cases), or neurological symptoms like seizures and anisocoria (5 cases). Acquired cases included severe intracranial hemorrhage in one case. Conclusions: Neonatal HA can manifest with severe symptoms and rapid progression, making early diagnosis crucial. Non-specific signs and the absence of coagulophaty disorders in family history can delay diagnosis. Symptoms like prolonged bleeding, cutaneous hematomas, or intracranial bleeding necessitate ruling out major coagulopathy, and neurological signs require immediate imaging to exclude intracranial bleeding.

Muscle Tissue Response to Vipera berus berus and Vipera berus nikolskii Venoms: A Study on Matrix Metalloproteinases and Cytokine Modulation

Vipera berus, also known as the common adder, is a snake species widely distributed in Europe and parts of Asia. Its venom is a mix of enzymatic and non-enzymatic components causing both local and systemic effects including edema, hemorrhage, myonecrosis, gastrointestinal disorders, and rarely – rhabdomyolysis, coagulopathy and hypovolemic shock. Matrix metalloproteinases (MMPs) and cytokines, being inflammatory mediators, participate both in the development of these reactions and in tissue regeneration after acute damage. The current study was aimed at analyzing the concentrations of important mediators of tissue damage, inflammation and regeneration, namely, MMP-1, -2, -3, -8, -10, TIMP-1 (a tissue inhibitor of MMPs), and pro- and anti-inflammatory cytokines, in rat muscle after intraperitoneal injection of venoms from two subspecies of adders – V. berus berus and V. berus nikolskii — to clarify their role in the local response of skeletal muscle to the studied venoms. Changes in muscle tissue were revealed, namely, significant increase in almost all MMPs including MMP-2, as well as TIMP-1, IFN-γ and anti-inflammatory IL-4 and IL-10 content. Moreover, a tendency for some pro-inflammatory cytokines levels to decline 24 h after venom administration was observed, which may be a sign of inflammation suppression and the beginning of reparative processes associated with extracellular matrix remodeling and formation of an optimal environment for muscle regeneration. However, to establish the exact mechanisms of the changes we found, further studies are needed. The ability of V. berus nikolskii venom to induce more pronounced changes was also shown. Our results may be useful for the development of differentiated and more effective treatment strategies for the consequences of bites by these snakes, which include myonecrosis

Using shock index, pediatric age adjusted (SIPA) to predict prolonged length of stay in perforated appendicitis: a retrospective review.

Hospital length of stay (LOS) following admission for appendicitis is difficult to predict. Shock index, pediatric age adjusted (SIPA) accurately identifies severely injured trauma patients and predicts mortality among children admitted to the ICU. Our aim was to determine if elevated SIPA at presentation, and time to normalization of SIPA, can identify children with perforated appendicitis and predict hospital LOS. This was a retrospective cohort study of children 1-17years admitted to a quaternary care referral center with appendicitis after appendectomy in 2021. The primary outcomes were presence of perforated appendicitis and hospital LOS. Generalized linear regressions were performed. Covariates included in all models were age, sex, fecalith, initial temperature, and time from diagnosis to OR. We included 169 patients; 53 (31.4%) had perforated appendicitis. After adjustment, elevated SIPA was associated with presence of perforated appendicitis (p = 0.0002) and longer LOS (p < 0.0001). A patient presenting with appendicitis and elevated SIPA had 5.447 times higher odds of having perforated appendicitis (95% CI: 2.262, 13.826), a mean hospital LOS 2.047 times longer (95% CI: 1.564, 2.683), a mean time to toleration of regular diet 4.995 times longer (95% CI: 2.914, 8.918), and a mean duration of antibiotics that is 1.761 times longer (95% CI: 1.383, 2.243) than a patient with normal SIPA. In children with appendicitis, elevated SIPA at presentation is associated with higher risk of perforation. These findings support the incorporation of SIPA during triage of patients with appendicitis and counseling families after surgery. Level 3.

Comparing the Push–Pull Technique to Pressure Bag for Administration of Blood Products: A Prospective Nonblinded Observation Simulation-based Study (CoPP toP Study)

Abstract Introduction: Shock is defined as inadequate delivery of oxygen to meet the tissue’s demands. There are four main types of shock: cardiogenic, obstructive, distributive, and hypovolemic. Hypovolemic shock causes include hemorrhage, dehydration, and burns. Blood loss results in inadequate oxygen delivery to the cells resulting in tissue death if not reversed. Rapid infusers allow for the rapid administration of blood and crystalloid products to patients in shock; however, many community emergency departments do not have these devices. The aim of our study is to determine the fastest way to administer blood when the viscosity of the fluid is taken into consideration in a simulated setting. Methods: Volunteers were assigned to one of two arms: either the push–pull technique or pressure bag technique. The push–pull technique involved using a 50 cc syringe connected to a 3-way stop-cock to withdraw and infuse the fluid. The pressure bag technique involved pumping a pressure bag up to the maximum to infuse the fluids. The speed of infusing 250 mL of intravenous fluids was recorded. The time for the subjects to collect the materials throughout the emergency department was also recorded. Results: A total of three trials were conducted. On average, the push–pull technique took 228 s and the pressure bag technique took 340 s. The push–pull technique took an average of 112 s less than the pressure bag technique. Subjects took 62 s to find the materials for the pressure bag technique. It took 133 s to find the material for the push–pull technique. Conclusion: This prospective nonblinded observation simulation-based study demonstrated that the push–pull technique was significantly faster than the pressure bag technique.

Pregnancy and trauma: What you need to know.

Nearly 4% of pregnant patients have an injury-related visit to the emergency department during their pregnancy. There are important physiologic changes that occur during pregnancy that make managing pregnant trauma patients different from the standard management of a nonpregnant patient. This review discusses these changes and the initial assessment, laboratory, and imaging workups for the pregnant trauma patient. In addition, management of specific injuries in pregnancy including pelvic fractures, hemorrhagic shock, and postpartum hemorrhage are reviewed as well as key points regarding resuscitative hysterotomy and fetal support that trauma surgeons should be aware of. Original Research Article; Level II.

From Hemorrhagic Shock to Postoperative Complications: Anesthesia, Intensive Care, and Surgical Management of a Young Male With Pulmonary Aspergillosis

From Hemorrhagic Shock to Postoperative Complications: Anesthesia, Intensive Care, and Surgical Management of a Young Male With Pulmonary Aspergillosis

Point of care lactate for differentiating septic shock from hypovolemic shock in non-ICU settings: a prospective observational study

BackgroundSeptic shock and hypovolemic shock are life-threatening illnesses that necessitate immediate recognition and intervention, as they can result in deadly consequences. While the underlying processes may vary, both entities can exhibit hypotension and organ dysfunction. No studies have been conducted on bedside testing to differentiate between these illnesses. Lactate measurement has been established as a viable option for early detection of septic shock. However, its role in diagnosing hypovolemic shock has yet to be evaluated. The aim of the study was to investigate alterations in lactate levels among diarrheal patients with septic shock and hypovolemic shock following the administration of first fluid resuscitation. MethodsWe conducted a prospective observational study in critically ill diarrheal adults aged ≥18 years in the emergency ward in Dhaka Hospital of icddr,b from 21st October 2021 to 31st May 2023 (total 19 months). The enrollment process was operational between 8:30 AM and 5:00 PM. Diarrheal adults with a diagnosis of sepsis with shock featured with poor peripheral perfusion (characterized by cold periphery and weak or absent pulse and capillary refill time >3 sec) or hypotension (characterized by mean arterial pressure <65 mm-Hg) were enrolled as cases and consecutive diarrheal patients without any obvious features of sepsis with hypovolemic shock (due to severe dehydration) comprised the comparison group.POC lactate test was done at hours 0, 1st and 6th by StatStrip Lactate meters (Nova Biomedical, US) to all enrolled patients. For comparison of POC lactate levels, we used paired t-test for comparing the lactate samples drawn at hour 0, hour 1 and 6 with the septic shock and hypovolemic shock group. Odds ratio (OR) and their 95% confidence intervals (CIs) were used to demonstrate the strength of association. The study was registered at Clinicaltrials.gov (NCT05108467) and received institutional ethical approval (PR-21097). FindingsOf 435 patients, 135 had septic shock and 141 had hypovolemic shock, rest 41 patient responded with fluid bolus. 25% (34/135) of the people in the septic shock group died whereas there is no mortality in the hypovolemic shock group. The number of patients visiting from outside Dhaka city had more septic shock than from inside were higher in comparison with (55% vs. 28%; p <0.001). Statistically significant difference was observed between septic shock and hypovolemic shock group for a median POC lactate in 0, 1st and 6th hours with an OR of 1.07 (95% CI: 0.99, 1.17; p=0.039); 1.48, (95% CI: 1.28, 1.70; p<0.001) and 2.36 (95% CI: 1.85, 3.00; p<0.001), respectively. The gradient of 1st to 2nd sample between septic shock and hypovolemic shock was found to be significantly different (OR:0.74, 95% CI: 0.64, 0.85; p<0.001). InterpretationPOC lactate test can detect septic shock by differentiating hypovolemic shock in diarrheal patients. By providing quick, reliable and accurate result this test can help clinicians quickly diagnose and treat time-sensitive condition, like septic shock. FundingThe study was funded by Global Affairs of Canada (GR-01726). The donors had no role in the design, implementation, analysis, data interpretation or writing manuscript, or decision to publish. The corresponding author had access to all data and takes responsibility for the final approval and submission of the manuscript.

A spontaneous rupture of a simple renal cyst complicated by hemorrhagic shock: a case report

Introduction and importance: The spontaneous and non-traumatic rupture of renal cysts is a rare clinical condition, which can lead to hemorrhagic shock. In this paper, the authors report a case of spontaneous rupture of a renal cyst and discuss the main features of this condition. Case report: A 21-year-old patient presented urgently with hemorrhagic shock with no history or evidence of trauma. Physical examination revealed a swollen left lumbar fossa on palpation. Abdominal CT revealed an abundant retroperitoneal hematoma. Resuscitation measures were urgently initiated to ensure hemodynamic stabilization, followed by a hemostasis nephrectomy. The patient was stabilized, and subsequent postoperative recovery proceeded without complications. He was sent home on the seventh day following his admission. Discussion: Spontaneous retroperitoneal hemorrhages may stem from various pathologies, including simple renal cysts, and frequently manifest with Lenk’s triad. Wunderlich syndrome, an infrequent manifestation of such hemorrhages, necessitates prompt recognition and hemodynamic stabilization, with potential treatment including embolization or surgical intervention. Conclusion: Although simple renal cysts are generally asymptomatic, they can lead to serious complications such as hemorrhage that could be life-threatening without appropriate medical intervention. The treatment involves performing an emergency nephrectomy for hemostasis, along with implementing resuscitation measures.