Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions.

Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions. Children receiving ECMO and/or CRRT routinely receive 20 or more drugs, and data supporting optimal dosing is lacking for most of these medications. The Pediatric Paracorporeal and Extracorporeal Therapies Summit (PPETS) gathered an international group of experts in the fields of ECMO, CRRT, and other ECLS modalities to discuss the current state of these therapies, disseminate innovative support strategies, share clinical experiences, and foster future collaborations. Here, we summarize the conclusions of PPETS and put forward a pathway to optimize pharmacokinetic (PK) research in this population. We must prioritize specific medications for in-depth study to improve drug use in ECLS and patient outcomes. Based on frequency of use, potential for adverse outcomes if dosed inappropriately, and lack of existing PK data, a list of high priority drugs was compiled for future research. Researchers must additionally reconsider study designs, emphasizing pooling of resources through multi-center studies and the use of innovative PK modeling techniques. Finally, the integration of validated PK models into clinical practice must be streamlined to deliver optimal medication use at the bedside. Focusing on the proposed list of highlighted medications and key methodological considerations will maximize the impact of future research.

The Comparative Impact of Liberal Versus Conservative Oxygenation in Critically Ill COVID-19 Patients: A Retrospective Study.

Objectives Whether a higher or lower partial pressure of oxygen (PaO2) could impact outcomes in patients with coronavirus disease 2019 (COVID-19) remains a matter of debate. So, we planned this retrospective analysis to determine if a higher or lower partial pressure of oxygen in blood had any effect on outcomes in COVID-19 patients. Material and method The records of COVID-19 patients from the beginning of 2020 to the end of 2022 were scanned. Patients were sub-grouped into two groups based on the partial pressure of oxygen (PaO2) values on arterial blood gas (ABG), i.e., high PaO2 group, PaO2 value of 80-100 mm Hg, and low PaO2 group, PaO2 value of 60-80 mm Hg for the first 48 hours after the initiation of oxygenation and/or mechanical ventilation. The two groups were compared in terms of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen (FiO2) concentration (P/F ratio), Sequential Organ Failure Assessment (SOFA) score at presentation and after 48 hours, and clinical outcomes, including mortality, time of mortality, extubation, acute kidney injury (AKI), and change in Glasgow Coma Scale (GCS). Results SOFA score was significantly higher in the low PaO2 group as compared to the high PaO2 group both at baseline (4.59 {1.79} versus 5.51 {1.15}; p-value: 0.005) and at 48 hours (3.06 {1.39} versus 5.11 {2.13}; p-value: 0.007). However, the change in SOFA score over 48 hours did not achieve statistical significance (-1.000 {0.97} versus 0.53 {2.34}; p-value: 0.257). Out of a total of 37 patients, 21 patients died in the high PaO2 group, while 18 patients died in the low PaO2 group. Conclusion Our study highlights that targeting either low or high arterial oxygen content while considering oxygen therapy for COVID-19 patients did not significantly alter the outcomes.

Breaking the chain in organ failure: Role of umbilical cord and bone marrow derived mesenchymal stem cells in treatment of severe acute pancreatitis.

Background: Previous studies showed that MSCs could mitigate damage in the pancreas during acute pancreatitis (AP). However, acute mortality associated with AP was more often a result of persistent failure of remote organs, rather than local damage, especially in severe acute pancreatitis (SAP), and the effect of MSCs may vary depending on their origin. Methods: An SAP model was induced in 8-week C57BL/6 J male mice by retrograde injection of 5 % sodium taurocholate solution through the bile duct. SAP mice were divided into the SAP group, UC-MSCs group, and BMSCs group, which were treated with saline, 1 × 106 UC-MSCs, and 1 × 106 BMSCs respectively, through the tail vein. After treatment, serum markers, inflammation, and morphology were assessed in the pancreas, kidneys, lungs, and hearts. Results: MSCs infusion ameliorated the systemic inflammatory response in SAP mice. In the MSCs-treated SAP mice, local tissue injury and inflammation response in the pancreas were alleviated. But more importantly, the renal and lung injury were all significantly and drastically mitigated, and the levels of pro-inflammatory factors such as IL-6, MCP-1, IL-1ß, and TNF-α in the kidney, lung and heart were sharply decreased. In terms of origin, UC-MSCs exhibited superior efficacy compared with BMSCs. Furthermore, compared to the normal control mice, UC-MSCs showed an earlier appearance, higher distribution densities, and longer duration of presence in the injured tissue. Conclusions: This study provides compelling evidence supporting the therapeutic potential of MSCs in SAP treatment and particularly their ability to mitigate multi-organ failure. Our results also suggested that UC-MSCs may offer greater advantages over BMSCs in SAP therapy.

Retroperitoneal leiomyomas with intratumoral bleeding: Presentation with multiple-organ dysfunction syndrome - A case report.

Background: Retroperitoneal leiomyomas are rare benign smooth muscle tumours. Diagnosing these tumours is often challenging due to their unique growth site and nonspecific clinical manifestations. There are a few reports of leiomyomas with intratumoral bleeding. Case presentation: A patient with a giant retroperitoneal leiomyoma presented with multiple-organ dysfunction syndrome accompanied by a progressive decrease in haemoglobin. Computed tomography (CT) revealed two cystic tumours in the abdominal cavity. The patient was underwent transabdominal retroperitoneal tumour resection. During surgery, we found two retroperitoneal tumours-one contained approximately 9000 mL of dark red fluid and the other contained 1000 mL of light brown fluid. She has recovered well without any complications. Conclusions: There have been only a few reports of retroperitoneal leiomyomas with intratumoral bleeding. This case highlights the importance of recognizing intratumoral haemorrhage in patients with large leiomyomas and a progressive decrease in haemoglobin after ruling out external haemorrhage. If necessary, dynamic monitoring via CT may help clarify the diagnosis.

Epidemiology of postinjury multiple organ failure: a prospective multicenter observational study.

PURPOSE: Postinjury multiple organ failure (MOF) is the sequela to the disease of polytrauma. We aimed to describe the contemporary population-based epidemiology of MOF within a mature trauma system, to analyse the time taken for MOF to develop, and to evaluate the temporal patterns and contributions of the individual constituent organ failures. METHODS: Prospective observational study conducted across five Level-1 trauma centers in New South Wales, Australia. Trauma patients at-risk of MOF (Denver > 3 from 48 h post-admission), aged > 16 years, ISS > 15, and who stayed in ICU for ≥ 48 h were eligible for inclusion. RESULTS: From May 2018-February 2021, 600 at-risk polytrauma patients were prospectively enrolled (mean(SD)age = 49(21)years, males = 453/600(76%),median(IQR)ISS = 26(20,34)). MOF incidence was 136/600(23%) among at-risk patients, 142/6248(2%) among major trauma patients (ISS > 12 per Australian definition), and 0.8/100,000 in the general population. The mortality rate was 55/600(11%) in the overall study population, and 34/136(25%) in MOF patients. 82/136(60%) of MOF patients developed MOF on day-3. No patients developed MOF after day-13. Among MOF patients, 60/136(44%) had cardiac failures (mortality = 37%), 39/136(29%) had respiratory failures (mortality = 23%), 24/136(18%) had renal failures (mortality = 63%), and 12/136(9%) had hepatic failures (mortality = 50%). CONCLUSION: Although a rare syndrome in the general population, MOF occurred in 23% of the most severely injured polytrauma patients. When compared to previous risk-matched cohorts, MOF become more common, but not more lethal, despite a decade older cohort. The heart has superseded the lungs as the most common organ to fail. Cardiac and respiratory failures occurred earlier and were associated with lower mortality than renal and hepatic failures.

Comparison of pSOFA with PRISM III and PIM 2 as Predictors of Outcome in a Tertiary Care Pediatric ICU: A Prospective Cross-sectional Study.

Aims and background: Severity scores are used to predict the outcome of children admitted to the intensive care unit. A descriptive score such as the pediatric sequential organ failure assessment (pSOFA) may be useful for prediction of outcome. This study was planned to compare the pSOFA score with these well-studied scores for prediction of mortality. Materials and methods: This prospective cross-sectional study was conducted at the pediatric intensive care units (PICU) of a tertiary care hospital. Children aged from 1 month to 12 years were enrolled sequentially. The pediatric index of mortality (PIM 2) score was calculated within 1 hour, and pediatric risk of mortality (PRISM) III and pSOFA scores were calculated within 24 hours of PICU admission. The pediatric sequential organ failure assessment score was recalculated after 72 hours. The primary outcome variable was hospital mortality, and secondary outcome variables were duration of PICU stay, need for mechanical ventilation, and occurrence of acute kidney injury (AKI). Appropriate statistical tests were used. Results: About 151 children with median (IQR) age of 36 (6, 84) months were enrolled. Mechanical ventilation was required in 87 (57.6%) children. Mortality was 21.2% at 28 days. The median (IQR) predicted mortality using PRISM III and PIM 2 score were 3.4 (1.5%, 11%) and 8.2 (3.1%, 16.6%) respectively. Area under ROC for prediction of mortality was highest for pSOFA 72 with a cut-off of 6.5 having sensitivity of 83.3% and specificity of 76.9%. Conclusion: The pSOFA score calculated at admission and at 72 hours had a better predictive ability for the PICU mortality compared to PRISM III and PIM 2 score. How to cite this article: Agrwal S, Saxena R, Jha M, Jhamb U, Pallavi. Comparison of pSOFA with PRISM III and PIM 2 as Predictors of Outcome in a Tertiary Care Pediatric ICU: A Prospective Cross-sectional Study. Indian J Crit Care Med 2024;28(8):796-801.

Intensive care unit cardiac arrest among very elderly critically ill patients - is cardiopulmonary resuscitation justified?

INTRODUCTION: The proportion of very elderly patients in the intensive care unit (ICU) is expected to rise. Furthermore, patients are likely more prone to suffer a cardiac arrest (CA) event within the ICU. The occurrence of intensive care unit cardiac arrest (ICU-CA) is associated with high mortality. To date, the incidence of ICU-CA and its clinical impact on outcome in the very old (≥ 90 years) patients treated is unknown. METHODS: Retrospective analysis of all consecutive critically ill patients ≥ 90 years admitted to the ICU of a tertiary care university hospital in Hamburg (Germany). All patients suffering ICU-CA were included and CA characteristics and functional outcome was assessed. Clinical course and outcome were assessed and compared between the subgroups of patients with and without ICU-CA. RESULTS: 1,108 critically ill patients aged ≥ 90 years were admitted during the study period. The median age was 92.3 (91.0-94.2) years and 67% (n = 747) were female. 2% (n = 25) of this cohort suffered ICU-CA after a median duration 0.5 (0.2-3.2) days of ICU admission. The presumed cause of ICU-CA was cardiac in 64% (n = 16). The median resuscitation time was 10 (2-15) minutes and the initial rhythm was shockable in 20% (n = 5). Return of spontaneous circulation (ROSC) could be achieved in 68% (n = 17). The cause of ICU admission was primarily medical in the total cohort (ICU-CA: 48% vs. No ICU-CA: 34%, p = 0.13), surgical - planned (ICU-CA: 32% vs. No ICU-CA: 37%, p = 0.61) and surgical - unplanned/emergency (ICU-CA: 43% vs. No ICU-CA: 28%, p = 0.34). The median Charlson Comorbidity Index (CCI) was 2 (1-3) points for patients with ICU-CA and 1 (0-2) for patients without ICU-CA (p = 0.54). Patients with ICU-CA had a higher disease severity according to SAPS II (ICU-CA: 54 vs. No ICU-CA: 36 points, p < 0.001). Patients with ICU-CA had a higher rate of mechanically ventilation (ICU-CA: 64% vs. No ICU-CA: 34%, p < 0.01) and required vasopressor therapy more often (ICU-CA: 88% vs. No ICU-CA: 41%, p < 0.001). The ICU and in-hospital mortality was 88% (n = 22) and 100% (n = 25) in patients with ICU-CA compared to 17% (n = 179) and 28% (n = 306) in patients without ICU-CA. The mortality rate for patients with ICU-CA was observed to be 88% (n = 22) in the ICU and 100% (n = 25) in-hospital. In contrast, patients without ICU-CA had an in-ICU mortality rate of 17% (n = 179) and an in-hospital mortality rate of 28% (n = 306) (both p < 0.001). CONCLUSION: The occurrence of ICU-CA in very elderly patients is rare but associated with high mortality. Providing CPR in this cohort did not lead to long-term survival at our centre. Very elderly patients admitted to the ICU likely benefit from supportive care only and should probably not be resuscitated due to poor chance of survival and ethical considerations. Providing personalized assurances that care will remain appropriate and in accordance with the patient's and family's wishes can optimise compassionate care while avoiding futile life-sustaining interventions.

Dynamics of changes in proteins of the acute phase of inflammation in the postoperative period in patients with disseminated peritonitis.

OBJECTIVE: Aim: To determine the effect of the developed complex treatment of patients with peritonitis on the dynamics of humoral factors of nonspecific reactivity in the course of the disease. PATIENTS AND METHODS: Materials and Methods: The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups. Group I (main) included 39 patients whose complex treatment included cytochrome C. Group II (main) included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride. The comparison group comprised 44 patients who did not receive the specified drugs. The patients underwent determination of the levels of fibronectin, ceruloplasmin, and procalcitonin in the serum during the course of the disease. RESULTS: Results: In patients of the I and II main groups, the use of the proposed treatment contributed to the optimization of the production of acute phase proteins: a decrease in procalcitonin production during the study, optimization of ceruloplasmin and fibronectin production, especially in the II main group. In patients of the comparison group, decompensation in the production of humoral inflammatory factors was determined, associated with a significant increase in fibronectin production, a decrease in ceruloplasmin content, and an increase in procalcitonin throughout the entire period. CONCLUSION: Conclusions: The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize the production of acute phase proteins, which leads to a decrease in inflammation and the preservation of factors of nonspecific humoral activity at a subcompensated level.

Organ crosstalk and dysfunction in sepsis.

Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Sepsis-associated organ dysfunction involves multiple inflammatory mechanisms and complex metabolic reprogramming of cellular function. These mechanisms cooperate through multiple organs and systems according to a complex set of long-distance communications mediated by cellular pathways, solutes, and neurohormonal actions. In sepsis, the concept of organ crosstalk involves the dysregulation of one system, which triggers compensatory mechanisms in other systems that can induce further damage. Despite the abundance of studies published on ​​organ crosstalk in the last decade, there is a need to formulate a more comprehensive framework involving all organs to create a more detailed picture of sepsis. In this paper, we review the literature published on organ crosstalk in the last 10 years and explore how these relationships affect the progression of organ failure in patients with septic shock. We explored these relationships in terms of the heart-kidney-lung, gut-microbiome-liver-brain, and adipose tissue-muscle-bone crosstalk in sepsis patients. A deep connection exists among these organs based on crosstalk. We also review how multiple therapeutic interventions administered in intensive care units, such as mechanical ventilation, antibiotics, anesthesia, nutrition, and proton pump inhibitors, affect these systems and must be carefully considered when managing septic patients. The progression to multiple organ dysfunction syndrome in sepsis patients is still one of the most frequent causes of death in critically ill patients. A better understanding and monitoring of the mechanics of organ crosstalk will enable the anticipation of organ damage and the development of individualized therapeutic strategies.

Tools for Screening, Predicting, and Evaluating Sepsis and Septic Shock: A Comprehensive Review.

Sepsis is characterized by life-threatening organ dysfunction due to dysregulated host response to infection. It can progress to cause circulatory and cellular/metabolic abnormalities, resulting in septic shock that may significantly increase mortality. The pathophysiology of sepsis involves a complex interplay of invading pathogens and the body's immune defense, causing alteration in normal homeostasis, eventually leading to derangements in the cellular, humoral, circulatory, and metabolic functions. Several scoring systems have been developed to rapidly predict or suspect sepsis, such as Sequential Organ Failure Assessment (SOFA), modified SOFA (mSOFA), quick SOFA (qSOFA), shock index (SI), and modified SI (mSI). Each of these scores has been utilized for triaging patients with sepsis, and as per medical advancements these scoring systems have been modified to include or exclude certain criteria to improve their clinical utility. This review aims to compare the individual scores and their usage for sepsis that may be used for laying the foundation for early recognition and prediction of sepsis and for formulating more precise definitions in the future.

[Functional hemodynamic monitoring]. / Funktionelles hämodynamisches Monitoring.

BACKGROUND: Critically ill patients in the intensive care unit require intensified monitoring to control the treatment with volume and/or vasoactive substances. RESEARCH QUESTION: What role does functional hemodynamic monitoring play in controlling treatment and what techniques are used to manage this? MATERIAL AND METHODS: Review of the current literature. RESULTS AND DISCUSSION: Precise knowledge of the physiology of the cardiovascular system as well as the pathophysiology of individual clinical pictures and the possibilities of invasive and noninvasive monitoring are the prerequisites for the indications, implementation and interpretation of functional hemodynamic monitoring. An understanding of the heart-lung interaction and the influence of invasive ventilation on the volumetric target parameters, such as stroke volume variation, systolic pressure variation and pulse pressure variation as well as sonography of the inferior vena cava are indispensable prerequisites for the question of volume responsiveness. Other maneuvers, such as the passive leg raising test, can be very helpful when deciding on volume administration in everyday clinical practice. Static parameters such as central venous pressure generally play no role and if any only a subordinate one.

Characteristics of the Cerebrospinal Fluid in Septic Patients with Critical Illness Polyneuropathy - A Retrospective Cohort Study.

Background: Critical illness polyneuropathy (CIP) is a complex disease commonly occurring in septic patients which indicates a worse prognosis. Herein, we investigated the characteristics of cerebrospinal fluid (CSF) in septic patients with CIP. Methods: This retrospective study was conducted between Match 1, 2018, and July 1, 2022. Patients with sepsis who underwent a CSF examination and nerve electrophysiology were included. The levels of protein, glucose, lipopolysaccharide, white blood cell (WBC), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF) α in CSF were measured. The fungi and bacteria in CSF were also assessed. Results: Among the 175 septic patients, 116 (66.3%) patients were diagnosed with CIP. 28-day Mortality in CIP patients was higher than that in non-CIP patients (25.0% vs. 10.2%, P = 0.02) which was confirmed by survival analysis. The results of propensity score matching analysis (PSMA) indicated a significant difference in the level of protein, WBC, IL-1, IL-6, IL-8, and TNFα present in the CSF between CIP patients and non-CIP patients. The results of the receiver operating characteristic (ROC) analysis showed that IL-1, WBC, TNFα, and their combined indicator had a good diagnostic value with an AUC > 0.8. Conclusion: The increase in the levels of WBC, IL-1, and TNFα in CSF might be an indicator of CIP in septic patients.

Clinical Features of Cytokine Storm Syndrome.

Cytokine storm syndrome (CSS) is a severe life-threatening condition characterized by a clinical phenotype of overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multiple organ failure (MOF), and, if untreated, it can potentially lead to death. The hallmark of CSS is an uncontrolled and dysfunctional immune response involving the continual activation and expansion of lymphocytes and macrophages, which secrete large amounts of cytokines, causing a cytokine storm. Many clinical features of CSS can be explained by the effects of pro-inflammatory cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and IL-18 [1-7]. These cytokines are elevated in most patients with CSS as well as in animal models of CSS [8, 9]. A constellation of symptoms, signs, and laboratory abnormalities occurs that depends on the severity of the syndrome, the underlying predisposing conditions, and the triggering agent.

Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Two cases of complex traumatic aortic dissection combined with multiple organ injuries.

Traumatic aortic injury (TAI) is an acute, critical, and severe disease, and then combined with multiple organ damage, it is even more dangerous. TAI progresses very rapidly, with a pre-hospital mortality rate of 57% - 80%, and even when arriving at the hospital, more than one-third of the patients die within 4 h, and it is the 2nd leading cause of death in individuals aged 4 - 34 years. In addition, the incidence of TAI combined with injury was 81.4%. Therefore, early diagnosis, expeditious surgery, and timely and effective multidisciplinary cooperation are essential for successful rescue. The authors report 2 patients with acute traumatic aortic dissection combined with multiple organ injuries and treated with emergency endovascular surgery to discuss their clinical characteristics and treatment experience, and to provide experience in the diagnosis and treatment of such patients.

[Ethical aspects regarding the management of patients with liver disease in the intensive care unit]. / Ethische Aspekte beim Management von Patienten mit Lebererkrankung auf der Intensivstation.

BACKGROUND: Especially in terms of alcohol-related liver cirrhosis, discussions quickly arise in times of scarce resources about the justification for carrying out (prolonged) intensive care measures. AIMS, MATERIALS, AND METHODS: The following review aims to address ethical aspects specifically in patients with liver cirrhosis in the intensive care unit. A possible structured approach is presented. CONCLUSION: A general recommendation is not possible. Ultimately, decisions remain on a case-by-case basis and have to take a wide variety of perspectives into account.

The Combination of Systemic Immune-Inflammation Index and Serum Procalcitonin has High Auxiliary Predictive Value for Short-Term Adverse Prognosis in Septic Shock Patients.

BACKGROUND: Septic shock is the most serious complication of sepsis, with more secure and efficient biomarkers urgently needed. Systemic immune-inflammation index (SII) and serum procalcitonin (PCT) show involvement in predicting septic shock prognosis. OBJECTIVE: Herein, we explored the clinical value of the SII-PCT combination in the short-term prognosis of septic shock patients. METHODS: Totally 200 septic shock patients were analyzed retrospectively and allocated into the survival and death groups upon 28-day in-hospital outcomes. Correlations of SII, PCT, acute physiology and chronic health evaluation II (APACHE II)/sepsis-related organ failure assessment (SOFA) scores, C-reactive protein (CRP), and serum creatinine (Scr) were analyzed using Spearman. The influencing factors of SII and serum PCT for short-term poor prognosis were analyzed using logistic multivariate regression model. The auxiliary predictive value of SII, PCT, and their combination for short-term adverse septic shock prognosis was evaluated by the receiver operating characteristic curve. Differences in the area under the curve (AUC) were compared using MedCalc. RESULTS: The death group had higher APACHE II/SOFA scores, LYM, CRP, Scr, SII, and PCT levels than the survival group. SII and PCT were positively correlated with APACHE II and SOFA scores, LYM, CRP, and Scr, and were independent risk factors influencing the adverse septic shock prognosis. The AUC of the SII-PCT combination in predicting short-term adverse septic shock prognosis was 0.893 (0.841-0.932), with 76.12% sensitivity and 87.97% specificity, with the combination showing a higher AUC than SII/PCT alone. CONCLUSIONS: The SII-PCT combination helps predict the adverse prognosis of septic shock patients.

Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome.

BACKGROUND: Multiple organ failure/dysfunction syndrome (MOF/MODS) is a major cause of mortality and morbidity among severe trauma patients. Current clinical practices entail monitoring physiological measurements and applying clinical score systems to diagnose its onset. Instead, we aimed to develop an early prediction model for MOF outcome evaluated soon after traumatic injury by performing machine learning analysis of genome-wide transcriptome data from blood samples drawn within 24 h of traumatic injury. We then compared its performance to baseline injury severity scores and detection of infections. METHODS: Buffy coat transcriptome and linked clinical datasets from blunt trauma patients from the Inflammation and the Host Response to Injury Study ("Glue Grant") multi-center cohort were used. According to the inclusion/exclusion criteria, 141 adult (age ≥ 16 years old) blunt trauma patients (excluding penetrating) with early buffy coat (≤ 24 h since trauma injury) samples were analyzed, with 58 MOF-cases and 83 non-cases. We applied the Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) algorithms to select features and develop models for MOF early outcome prediction. RESULTS: The LASSO model included 18 transcripts (AUROC [95% CI]: 0.938 [0.890-0.987] (training) and 0.833 [0.699-0.967] (test)), and the XGBoost model included 41 transcripts (0.999 [0.997-1.000] (training) and 0.907 [0.816-0.998] (test)). There were 16 overlapping transcripts comparing the two panels (0.935 [0.884-0.985] (training) and 0.836 [0.703-0.968] (test)). The biomarker models notably outperformed models based on injury severity scores and sex, which we found to be significantly associated with MOF (APACHEII + sex-0.649 [0.537-0.762] (training) and 0.493 [0.301-0.685] (test); ISS + sex-0.630 [0.516-0.744] (training) and 0.482 [0.293-0.670] (test); NISS + sex-0.651 [0.540-0.763] (training) and 0.525 [0.335-0.714] (test)). CONCLUSIONS: The accurate assessment of MOF from blood samples immediately after trauma is expected to aid in improving clinical decision-making and may contribute to reduced morbidity, mortality and healthcare costs. Moreover, understanding the molecular mechanisms involving the transcripts identified as important for MOF prediction may eventually aid in developing novel interventions.