Life-threatening Organ Failure Research Articles

The SOFA Score and EWS: Is It Time for an Update?

Background: Intensive care unit (ICU) functions as a structured environment dedicated to providing intensive medical attention to patients in critical condition, monitoring, and organ support to treat life-threatening organ failure. Sepsis occurs when the immune system reacts severely to infection, leading to damage to the body’s tissues and organs. Data from The Global Burden of Disease Sepsis Report estimates 48.9 million sepsis cases annually, with 11 million cases leading to death. Therefore, the early warning score (EWS) and sequential organ failure assessment (SOFA) score systems have the potential to estimate the follow-up of patients treated in the ICU. Evaluation of prognosis based on SOFA and EWS scores is not yet confirmed for the medical state of individuals with sepsis.Objective: To determine the correlation of SOFA score and EWS by the duration of ICU stays for sepsis patients at Rumah Sakit Umum Imelda Pekerja Indonesia Medan.Methods: This study used an analytical observational approach employing cross-sectional design. The method of gathering data relies on medical records and samples are collected through total sampling.Result: On 64 patients diagnosed with sepsis and treated in the ICU of Rumah Sakit Umum Imelda Pekerja Indonesia Medan are obtained employing the Spearman correlation test revealed a significant correlation between EWS length of time sepsis patients spend in the ICU (p=0.001). However, a lack of notable correlation was found between the SOFA score and length of time sepsis patients spend in the ICU (p=0.719).Conclusion: No correlation exists between the SOFA score and the duration of stay among sepsis patients, whereas a correlation exists between EWS and duration of stay among sepsis patients.

Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections.

Gasdermin D drives focal crystalline thrombotic microangiopathy by accelerating immunothrombosis and necroinflammation

AbstractThrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein that serves as the final downstream effector of the pyroptosis/interleukin-1β (IL-1β) pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd deficiency ameliorated immunothrombosis, acute tissue injury, and failure. Gsdmd−/− mice exhibited a decrease in mature IL-1β, as well as in neutrophil maturation, β2-integrin activation, and recruitment to TMA lesions, in which they formed reduced neutrophil extracellular traps in both arteries and interstitial tissue. The GSDMD inhibitor disulfiram dose-dependently suppressed human neutrophil pyroptosis in response to cholesterol crystals. Experiments with GSDMD–deficient, human–induced, pluripotent stem cell–derived neutrophils confirmed the involvement of GSDMD in neutrophil β2-integrin activation, maturation, and pyroptosis. Both prophylactic and therapeutic administration of disulfiram protected the mice from focal TMA, acute tissue injury, and failure. Our data identified GSDMD as a key mediator of focal crystalline TMA and its consequences, including ischemic tissue infarction and organ failure. GSDMD could potentially serve as a therapeutic target for the systemic forms of TMA.

Conventional and unconventional T-cell responses contribute to the prediction of clinical outcome and causative bacterial pathogen in sepsis patients.

Sepsis is characterized by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility of identifying integrative patterns from clinical parameters, plasma biomarkers, and extensive phenotyping of blood immune cells. While no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90-day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90-day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T-cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical, and clinical parameters.

Low-dose Olaparib improves septic cardiac function by reducing ferroptosis via accelerated mitophagy flux

Sepsis is a dysregulated response to infection that can result in life-threatening organ failure, and septic cardiomyopathy is a serious complication involving ferroptosis. Olaparib, a classic targeted drug used in oncology, has demonstrated potential protective effects against sepsis. However, the exact mechanisms underlying its action remain to be elucidated. In our study, we meticulously screened ferroptosis genes associated with sepsis, and conducted comprehensive functional enrichment analyses to delineate the relationship between ferroptosis and mitochondrial damage. Eight sepsis-characterized ferroptosis genes were identified in sepsis patients, including DPP4, LPIN1, PGD, HP, MAPK14, POR, GCLM, and SLC38A1, which were significantly correlated with mitochondrial quality imbalance. Utilizing DrugBank and molecular docking, we demonstrated a robust interaction of Olaparib with these genes. Lipopolysaccharide (LPS)-stimulated HL-1 cells and monocytes were used to establish an in vitro sepsis model. Additionally, an in vivo model was developed using mice subjected to cecal ligation and perforation (CLP). Intriguingly, low-dose Olaparib (5 mg/kg) effectively targeted and mitigated markers associated with ferroptosis, concurrently improving mitochondrial quality. This led to a marked enhancement in cardiac function and a significant increase in survival rates in septic mice (p < 0.05). The mechanism through which Olaparib ameliorates ferroptosis in cardiac and leukocyte cells post-sepsis is attributed to its facilitation of mitophagy, thus favoring mitochondrial integrity. In conclusion, our findings suggest that low-dose Olaparib can improve mitochondrial quality by accelerating mitophagy flux, consequently inhibiting ferroptosis and preserving cardiac function after sepsis.

Self-Cascade Redox Modulator Trilogically Renovates Intestinal Microenvironment for Mitigating Endotoxemia.

Endotoxemia is a life-threatening multiple organ failure disease caused by bacterial endotoxin infection. Unfortunately, current single-target therapy strategies have failed to prevent the progression of endotoxemia. Here, we reported that alanine fullerene redox modulator (AFRM) remodeled the intestinal microenvironment for multiple targets endotoxemia mitigation by suppressing inflammatory macrophages, inhibiting macrophage pyroptosis, and repairing epithelial cell barrier integrity. Specifically, AFRM exhibited broad-spectrum and self-cascade redox regulation properties with superoxide dismutase (SOD)-like enzyme, peroxidase (POD)-like enzyme activity, and hydroxyl radical (•OH) scavenging ability. Guided by proteomics, we demonstrated that AFRM regulated macrophage redox homeostasis and down-regulated LPS/TLR4/NF-κB and MAPK/ERK signaling pathways to suppress inflammatory hyperactivation. Of note, AFRM could attenuate inflammation-induced macrophage pyroptosis via inhibiting the activation of gasdermin D (GSDMD). In addition, our results revealed that AFRM could restore extracellular matrix and cell-tight junction proteins and protect the epithelial cell barrier integrity by regulating extracellular redox homeostasis. Consequently, AFRM inhibited systemic inflammation and potentiated intestinal epithelial barrier damage repair during endotoxemia in mice. Together, our work suggested that fullerene based self-cascade redox modulator has the potential in the management of endotoxemia through synergistically remodeling the inflammation and epithelial barriers in the intestinal microenvironment.

The synergism of cytosolic acidosis and reduced NAD+/NADH ratio is responsible for lactic acidosis-induced vascular smooth muscle cell impairment in sepsis

BackgroundDuring sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in vasoplegia, hypotension and hypoperfusion. In addition, septic patients have an altered cell metabolism that leads to lactic acidosis. Septic patients suffering from lactic acidosis have a high risk of mortality. In addition, septic survivors are at risk of secondary vascular disease. The underlying mechanisms of whether and how lactic acidosis leads to the changes in VSMCs is not well understood. The aim of this study was to comprehensively investigate the effect of lactic acidosis on VSMCs and additionally compare the effects with those induced by pure acidosis and sodium lactate.MethodsPrimary human aortic smooth muscle cells (HAoSMCs) were treated for 48 h with lactic acidosis (LA_pH 6.8), hydrochloric acid (HCl_pH 6.8), sodium lactate (Na+-lactate_pH 7.4) and the respective controls (ctrl._pH 7.4; hyperosmolarity control: mannitol_pH 7.4) and comparatively analyzed for changes in (i) transcriptome, (ii) energy metabolism, and (iii) phenotype.ResultsBoth types of acidosis led to comparable and sustained intracellular acidification without affecting cell viability. RNA sequencing and detailed transcriptome analysis revealed more significant changes for lactic acidosis than for hydrochloric acidosis, with lactate being almost ineffective, suggesting qualitative and quantitative synergism of acidosis and lactate. Bioinformatic predictions in energy metabolism and phenotype were confirmed experimentally. Lactic acidosis resulted in strong inhibition of glycolysis, glutaminolysis, and altered mitochondrial respiration which reduced cellular ATP content, likely due to increased TXNIP expression and altered NAD+/NADH ratio. Hydrochloric acidosis induced significantly smaller effects without changing the NAD+/NADH ratio, with the ATP content remaining constant. These metabolic changes led to osteo-/chondrogenic/senescent transdifferentiation of VSMCs, with the effect being more pronounced in lactic acidosis than in pure acidosis.ConclusionsOverall, lactic acidosis exerted a much stronger effect on energy metabolism than pure acidosis, whereas lactate had almost no effect, reflecting the qualitative and quantitative synergism of acidosis and lactate. As a consequence, lactic acidosis may lead to acute functional impairments of VSMC, sustained perturbations of the transcriptome and cellular dedifferentiation. Moreover, these effects may contribute to the acute and prolonged vascular pathomechanisms in septic patients.

Monocytic Phagocytes in the Immunopathogenesis of Cytokine Storm Syndromes.

Cytokine storm syndromes (CSSs) are caused by a dysregulated host immune response to an inciting systemic inflammatory trigger. This maladaptive and harmful immune response culminates in collateral damage to host tissues resulting in life-threatening multisystem organ failure. Knowledge of the various immune cells that contribute to CSS pathogenesis has improved dramatically in the past decade. Monocytes, dendritic cells, and macrophages, collective known as monocytic phagocytes, are well-positioned within the immune system hierarchy to make key contributions to the initiation, propagation, and amplification of the hyperinflammatory response in CSS. The plasticity of monocytic phagocytes also makes them prime candidates for mediating immunoregulatory and tissue-healing functions in patients who recover from cytokine storm-mediated immunopathology. Therefore, approaches to manipulate the myriad functions of monocytic phagocytes may improve the clinical outcome of CSS.

Tissue Injury Protection: The Other Face of Anticoagulant Treatments in the Context of Ischemia and Reperfusion Injury with a Focus on Transplantation.

Organ transplantation has enhanced the length and quality of life of patients suffering from life-threatening organ failure. Donors deceased after brain death (DBDDs) have been a primary source of organs for transplantation for a long time, but the need to find new strategies to face organ shortages has led to the broadening of the criteria for selecting DBDDs and advancing utilization of donors deceased after circulatory death. These new sources of organs come with an elevated risk of procuring organs of suboptimal quality. Whatever the source of organs for transplant, one constant issue is the occurrence of ischemia-reperfusion (IR) injury. The latter results from the variation of oxygen supply during the sequence of ischemia and reperfusion, from organ procurement to the restoration of blood circulation, triggering many deleterious interdependent processes involving biochemical, immune, vascular and coagulation systems. In this review, we focus on the roles of thrombo-inflammation and coagulation as part of IR injury, and we give an overview of the state of the art and perspectives on anticoagulant therapies in the field of transplantation, discussing benefits and risks and proposing a strategic guide to their use during transplantation procedures.

NLRP3 inflammasome-produced pro-inflammatory cytokines IL-1b and IL-18 are critical exacerbating factors of septic cardiomyopathy

Abstract Background Sepsis is life-threatening multiple organ failure due to systemic infection, and frequently causes septic cardiomyopathy (SCM). Recent evidence has established that cytokine storm, an aberrant increase in various cytokines leading to severe inflammation and tissue damage, plays a crucial role in SCM. However, it is unknown which cytokines are the most critical initiators and exacerbating factors of SCM. Purpose To investigate how IL-1β and IL-18 driven by NLRP3 inflammasome contribute to the pathophysiology of SCM, and to study whether blockage of these cytokines can ameliorate cardiac dysfunction in a murine model of lipopolysaccharide (LPS)-induced SCM. Methods Wild-type, Nlrp3-/-, Casp1/11-/-, and Il1b-/- mice were injected intraperitoneally with 6 mg/kg of LPS to induce SCM. To suppress IL-18, the adeno-associated virus (AAV) vectors encoding IL-18 binding protein (IL-18BP) were injected intramuscularly 14 days before LPS. Bone marrow transplantation (5 Gy x2) was performed 6 weeks prior to LPS. Results While 40% of wild-type mice died 48 h after LPS injection in our SCM model, none of Nlrp3-/- mice died. Cardiac function, as determined by echocardiography and BNP, was significantly decreased 6 h after LPS injection in WT mice but not in Nlrp3-/- or Casp1/11-/- mice. Serum CK-MB increase was also ameliorated in Nlrp3-/- or Casp1/11-/- mice. Serum levels of various pro-inflammatory cytokines including TNFα, IL-1β, IL-6, IL-18, and IFNγ were suppressed in Nlrp3-/- mice. These findings collectively indicated a critical role of NLRP3 inflammasome in LPS-induced SCM. However, unexpectedly, genetic deletion of IL-1β, the canonical effector molecule of NLRP3 inflammasome, in Il1b-/- mice failed to alleviate cardiac dysfunction and damage caused by LPS. In addition, IL-18 suppression by AAV-mediated overexpression of IL-18BP, a high-affinity IL-18 decoy receptor, only partially prevented LPS-induced SCM. On the other hand, intriguingly, dual inhibition of IL-1β and IL-18 successfully protected mice from LPS-induced SCM, demonstrating that concomitant blockage of two NLRP3 inflammasome products, IL-1β and IL-18, was necessary and sufficient to prevent SCM. Finally, while bone marrow transplantation experiments showed that cardiac dysfunction after LPS injection was suppressed in recipient Nlrp3-/- mice transplanted with wild-type bone marrow cells, cardiomyocyte-specific deletion of NLRP3 in αMHC-Cre;Nlrp3-/- mice did not prevent LPS-induced SCM. These data suggest that NLRP3 inflammasome in resident cells other than bone marrow-derived cells and cardiomyocytes is important in the pathophysiology of SCM. Conclusion The present study indicates that concomitant blockage of IL-1β and IL-18 driven by NLRP3 inflammasome is necessary and sufficient to prevent SCM. Our data provide fundamental evidence that combination therapy targeting both IL-1β and IL-18 could serve as a new approach to the treatment of SCM.

The laboratory parameters and scoring systems used to predict clinical outcomes in geriatric patients with acute pancreatitis.

Acute pancreatitis (AP) is the leading cause of hospital admissions among gastrointestinal system disorders, and it can resolve independently or lead to life-threatening multiple organ failure. Acute pancreatitis can have a more severe clinical presentation in geriatric patients as compared to younger patients. In this study, we aimed to elucidate the clinical and laboratory characteristics of patients aged 65 and older who presented to the emergency department with a diagnosis of AP and assessed their impact on hospital stay, in-hospital mortality, and cost. We reviewed the records of patients aged 65 and older who presented to the emergency department and had lipase levels measured as exceeding three times the upper limit of the reference range during the evaluation. We recorded these patients' vital signs, medical histories, laboratory values, and etiologies. Using these data, we calculated the patients' clinical scores. We recorded data on 218 patients who met the inclusion criteria. The median age of the patients was 76 (65-113). Of these, 70.6% were females, 54.6% had gallstones, 90.4% (n = 197) were admitted to the general ward from the emergency department, and 7.3% (n = 16) were admitted to the intensive care unit (ICU). In-hospital mortality was 5.63% (n = 12). The Ranson, Glasgow Severity Score (GSS), and Bedside Index for Severity in Acute Pancreatitis (BISAP) scores, as well as lactate, procalcitonin, and the lymphocyte-albumin ratio, were independent predictors of ICU admission and mortality. The early diagnosis of AP is essential. When a severe disease course is likely, initiating treatment promptly becomes crucial, especially in patients aged 65 and older. This approach can lead to significant reductions in both complication rates and treatment costs.

Quizartinib inhibits necroptosis by targeting receptor-interacting serine/threonine protein kinase 1.

Systemic inflammatory response syndrome (SIRS), at least in part driven by necroptosis, is characterized by life-threatening multiple organ failure. Blocking the progression of SIRS and consequent multiple organ dysfunction is challenging. Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is an important cell death and inflammatory mediator, making it a potential treatment target in several diseases. Here, using a drug repurposing approach, we show that inhibiting RIPK1 is also an effective treatment for SIRS. We performed cell-based high-throughput drug screening of an US Food and Drug Administration (FDA)-approved drug library that contains 1953 drugs to identify effective inhibitors of necroptotic cell death by SYTOX green staining. Dose-response validation of the top candidate, quizartinib, was conducted in two cell lines of HT-22 and MEFs. The effect of quizartinib on necroptosis-related proteins was evaluated using western blotting, immunoprecipitation, and an in vitro RIPK1 kinase assay. The in vivo effects of quizartinib were assessed in a murine tumor necrosis factor α (TNFα)-induced SIRS model. High-throughput screening identified quizartinib as the top "hit" in the compound library that rescued cells from necroptosis in vitro. Quizartinib inhibited necroptosis by directly inhibiting RIPK1 kinase activity and blocking downstream complex IIb formation. Furthermore, quizartinib protected mice against TNFα-induced SIRS. Quizartinib, as an FDA-approved drug with proven safety and efficacy, was repurposed for targeted inhibition of RIPK1. This work provides essential preclinical data for transferring quizartinib to the treatment of RIPK1-dependent necroptosis-induced inflammatory diseases, including SIRS.

Meningococcal meningitis, a life-threatening disease with a dangerous skin rash: two case reports

Meningococcal meningitis (MM) is a medical emergency that progresses rapidly to cause life-threatening organ failure, and a high level of suspicion is required for early diagnosis and intervention with antibiotics and fluid resuscitation. Herein, we present two cases of meningococcal meningitis in an adolescent boy and a young female child who presented with fever and rash; the purpose is to alert the emergency physicians about this life-threatening condition as early disease recognition and management is highly important for the patient’s survival.

Fluid Resuscitation in Septic Patients.

Sepsis is a life-threatening organ failure caused by a dysregulated response to infection. Fluid resuscitation and vasopressors are used to maintain systolic blood pressure and organ perfusion. Fluid resuscitation can be done with liberal or restricted fluids as well as colloids or crystalloid fluids. This review analyses the evidence for the use of liberal or restrictive fluids and colloids or crystalloids for the management of sepsis. A methodical search was conducted across PubMed, Cochrane Library, and ScienceDirect, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines were followed for this study. Randomized controlled trials and retrospective observational studies were included in this study. Liberal and restrictive fluid strategies were found to be comparable in efficacy, but restrictive fluid regimens had the added benefit of a lower incidence of fluid overload. Balanced crystalloidswere safer and more effective when compared to normal saline. Albumin replacement was found to be safe and showed efficacy in reducing mortality in patients with sepsis and septic shock.

Diagnosis and treatment of sepsis-induced cardiomyopathy using hemosorption therapy: a case report

Introduction. Sepsis is a life-threatening organ failure caused by the body’s dysregulated response to infection. The prevalence of sepsis-induced cardiomyopathy (SICM) in patients with sepsis ranges from 10 to 70%, while there are no special sections on SICM in the known resuscitation manuals. There is also a lack of large clinical trials evaluating the effectiveness of SICM treatment.Case. A 59-year-old patient was urgently hospitalized in the intensive care unit with shock of unknown origin. Emergency coronary angiography revealed no coronary obstruction. Two hours after admission, asystole was recorded with effective cardiopulmonary resuscitation, mechanical ventilation, infusion of inotropic and vasopressor drugs. The patient was diagnosed with leukocytosis up to 19*109/l, procalcitonin &gt;0,5 ng/ml. Subsequently, stage 2 acute kidney injury, pneumonia, acute respiratory distress syndrome, sepsis, SICM, combined shock (cardiogenic, septic) were diagnosed. Antibiotic and hemosorption therapy using a CytoSorb column were started. On the 6th day, there was a improvement of hemodynamic parameters, a decrease in the rate of vasopressor infusion, and normalization of the left ventricular ejection fraction. The condition has stabilized with further favorable changes.Discussion. Despite the wide prevalence and high mortality in SICM, this condition is not well described in the literature, and there are no clear diagnostic criteria and treatment algorithms. This case demonstrates the effective treatment of SICM at the stage when the prognosis of patients becomes extremely unfavorable, reaching 90% mortality.Conclusion. This case demonstrates the effective treatment of SICM as an element of multiple organ failure, in the outcome of sepsis, using efferent methods, when the prognosis becomes extremely unfavorable. Personalized approach and management of these patients is critical to improve disease outcomes.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

The impact of caring on caregivers of patients with life-threatening organ failure.

This study aimed at characterizing 3 populations of family/friend caregivers of patients with different life-threatening organ failure regarding health-related quality of life, caregiver burden, and dyadic coping. Three cross-sectional (population) studies were conducted at a tertiary hospital in Denmark (2019-2020). Patients with renal failure (RF), cystic fibrosis (CF), and intestinal failure (IF) were asked to designate the closest person with ≥18years old involved in the care (caregiver) to participate in this study. Number of caregivers included were RF=78, CF=104, and IF=73. Electronic questionnaires were filled in by caregivers to assess health-related quality of life and caregiver burden and by caregivers and respective patients to assess dyadic coping. The 3 caregiver groups had self-perception of poor health and energy; however, caregivers of CF patients perceived their physical role functioning better than those caregiving for RF and IF patients (p=0.002). The level of caregiver burden was reported as not high, but caregivers used in average 13hours/day for caring. Moreover, cleaning tasks (p=0.005) and personal care (p=0.009) were more demanding in RF and IF patients. Caregivers also did not differ regarding dyadic coping. When comparing patients and caregivers, stress communication by oneself and the partner differed (p<0.001). Caregivers spent many hours in the care role, they reported poor health, and dyadic coping may be improved. Interventions in caregivers of patients with life-threatening organ failure could help to improve care management at home, caregiver's health, and dyadic coping between caregiver and patient and consequently reduce caregiver burden.

Epidemiology and clinical characteristics of pediatric sepsis in PICUs of China: A national cross-sectional study.

Epidemiology and clinical characteristics of pediatric sepsis in PICUs of China: A national cross-sectional study.

Sepsis et immunodépression acquise en réanimation

AbstractSepsis is defined as the dysregulation of the host’s inflammatory response to an infection, leading to life-threatening organ failure. In 2017, sepsis was declared a major public health problem by the World Health Organization. It has recently been demonstrated that sepsis induces profound immunosuppression. Most importantly, this phase of immunosuppression is significantly associated with dormant virus reactivation, increased nosocomial infections, increased length of stay in intensive care and increased mortality. Understanding the mechanisms sustaining this immunosuppression has enabled the development of biomarkers (monocyte HLA-DR, % immature neutrophils, lymphocyte count, and PD-1 lymphocyte expression) that identify the patients most at risk. For the latter, a therapeutic alternative is currently being evaluated. This is based on individualized immunostimulation (IFN-γ, IL-7, anti-PD-1) which aims to accelerate the return of immune functions to normal ranges. Phase III trials are underway. This review provides an inventory of sepsis-induced immunosuppression and more generally introduces the notion of acquired immunodeficiency in intensive care.

Acute respiratory distress syndrome and acute lung injury in a trauma population with and without long bone fractures

Introduction: Trauma is the leading cause of death in persons under the age of 45. Recovery in patients who survive initial trauma are frequently complicated by sequelae of injury that increases susceptibility to infection and inflammation. Uncontrolled inflammation can advance into life-threatening organ failure, including acute respiratory distress syndrome (ARDS). Similarities exist between biomarkers established in the etiology of acute respiratory distress syndrome and those identified in the acute inflammatory and healing phase of bone fractures. This study investigates the impact of long bone fractures on the development of acute respiratory distress syndrome where it is hypothesized that patients with long bone fractures would have different biomarker profiles and increased development of lung injury compared to patients without long bone fractures.Methods: This is a retrospective data analysis of patients from an observational data repository from three trauma centers. Trauma patients with and without long bone fractures were matched and analyzed for the presence of known biomarkers of acute respiratory distress syndrome and for the development of acute respiratory distress syndrome.Results: There were no differences in overall acute respiratory distress syndrome development or hospital outcomes, however long bone fracture patients had a 2.35-fold higher hazard ratio of acute respiratory distress syndrome in the first 10 hospital days. There was a statistically significant increase in the levels of IL-6 in patients with long bone fractures (p = .0007). Structural equations modeling demonstrated that IL-6 was positively influenced by long bone fractures and IL-8.Conclusion: The presence of long bone fractures did not result in differences in the overall development of acute respiratory distress syndrome or hospital outcomes, though was found to have an increased hazard ratio for acute respiratory distress syndrome development in the first 10 days. Further research is needed to better characterize the relationship between varying cytokine profiles and the development of acute respiratory distress syndrome in a trauma population.