Search Results (253)

Endotoxemia is commonly observed in donkeys, secondary to colic, pleuropneumonia, or diarrhea among other disorders. Hematologic ratios are new biomarkers widely used in the diagnosis and prognosis of multiple conditions in human medicine, including sepsis. While the utility of these ratios has been proved in septic foals, no data are available on donkeys. Moreover, reference intervals (RIs) have not been studied in this species. In this study, RIs of the most commonly reported hematologic ratios were determined in 73 healthy adult donkeys. In addition, variations in these ratios in response to LPS infusion were also evaluated in six healthy adult donkeys. Most of the ratios evaluated showed significant variations after induced endotoxemia, with most of them showing values outside of the established RIs. Similarly to septic foals, the neutrophil to lymphocyte ratio was significantly reduced after LPS infusion. No significant changes were observed in the red cell distribution width to platelet ratio, contrary to reports on septic foals. Previously reported cut-off values for both of these ratios should not be extrapolated to donkeys. Future studies evaluating these ratios in natural endotoxemia or other diseases in donkeys, as well as establishing species-specific cut-off values, are necessary. Full article

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article

Background: The identification and clinical implementation of robust biomarkers are essential for improving diagnosis, prognosis, and treatment across a wide range of diseases. Pancreatic stone protein (PSP) has recently emerged as a promising candidate biomarker. Objective: This narrative review aims to provide an updated and comprehensive overview of the clinical applications of PSP in infectious, oncological, metabolic, and surgical contexts. Methods: We conducted a structured literature search using PubMed^®, applying the SANRA framework for narrative reviews. Boolean operators were used to retrieve relevant studies on PSP in a wide range of clinical conditions, including sepsis, gastrointestinal cancers, diabetes, and ventilator-associated pneumonia. Results: PSP has shown strong diagnostic and prognostic potential in sepsis, where it may outperform traditional markers such as CRP and PCT. It has also demonstrated relevance in gastrointestinal cancers, type 1 and type 2 diabetes, and perioperative infections. PSP levels appear to rise earlier than other inflammatory markers and may be less affected by sterile inflammation. Conclusion: PSP represents a versatile and clinically valuable biomarker. Its integration into diagnostic protocols could enhance early detection and risk stratification in critical care and oncology settings. However, widespread adoption is currently limited by the availability of point-of-care assay platforms. Full article

Background: COVID-19-associated coagulopathy (CAC) is a complex condition, with high rates of thrombosis, high levels of inflammation markers and hypercoagulation (increased levels of fibrinogen and D-Dimer), as well as extensive microthrombosis in the lungs and other organs of the deceased. It resembles, without being identical, other coagulation disorders such as sepsis-DIC (SIC/DIC), hemophagocyte syndrome (HPS) and thrombotic microangiopathy (TMA). Platelets (PLTs), key regulators of thrombosis, inflammation and immunity, are considered an important risk mediator in COVID-19 pathogenesis. Platelet index MPV/PLT ratio is reported in the literature as more specific in the prognosis of platelet-related systemic thrombogenicity. Studies of MPV/PLT ratio with regards to the severity of COVID-19 disease are limited, and there are no references regarding this ratio to the outcome of COVID-19 disease at specific time points of hospitalization. The aim of this study is to evaluate the relationship of COVID-19 mortality with the red cell distribution width–coefficient of variation (RDW-CV), platelets and MPV/PLT ratio parameters. Methods: Values of these parameters in 511 COVID-19 hospitalized patients were recorded (a) on admission, (b) as mean values of the 1st and 2nd week of hospitalization, (c) over the total duration of hospitalization, (d) as nadir and zenith values, and (e) at discharge. Results: As for mortality (survivors vs. deceased), statistical analysis with ROC curves showed that regarding the values of the parameters on admission, only the RDW-CV baseline was of prognostic value. Platelet parameters, absolute number and MPV/PLT ratio had predictive potential for the disease outcome only as 2nd week values. On the contrary, with regards to disease severity (mild/moderate versus severe/critical), only the MPV/PLT ratio on admission can be used for prognosis, and to a moderate degree. On multivariable logistic regression analysis, only the RDW-CV mean hospitalization value (RDW-CV mean) was an independent and prognostic variable for mortality. Regarding disease severity, the MPV/PLT ratio on admission and RDW-CV mean were independent and prognostic variables. Conclusions: RDW-CV, platelets and MPV/PLT ratio hematological parameters could be of predictive value for mortality and severity in COVID-19 disease, depending on the hospitalization timeline. Full article

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infections such as dengue virus. Due to overlapping features with severe dengue and sepsis, diagnosis of HLH in dengue-infected patients remains challenging. Methods: We conducted a narrative review and individual patient data meta-analysis of published cases of dengue-associated HLH. Eligible studies were identified through a search of PubMed and Scopus databases up to 5 March 2025. Clinical, laboratory, microbiological, treatment, and outcome data were extracted and analyzed. Results: A total of 133 patients from 71 studies were included. The median patient age was 18 years, and 56.8% were male. Common clinical features included fever (96.9%), cytopenias, organomegaly, and liver dysfunction. ALT elevation, jaundice, and hypofibrinogenemia were associated with mortality. DENV-1 was the most common serotype (57.4%) and was negatively associated with death. Overall, 19.3% of patients died. Multivariate analysis did not identify independent mortality predictors. Conclusions: Dengue-associated HLH predominantly affects young individuals and carries significant mortality. Key indicators of poor prognosis include hepatic dysfunction and the presence of shock or organ failure. Early recognition and prompt immunomodulatory treatment, particularly corticosteroids, may improve outcomes. Full article

Objective: To evaluate the prognostic utility of the Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score 3 (SAPS 3) in COVID-19 patients and assess whether incorporating C-reactive protein (CRP), procalcitonin, lactate, and lactate dehydrogenase (LDH) enhances their predictive accuracy. Methods: Single-center, observational, cohort study. We analyzed a database of adult ICU patients with severe or critical COVID-19 treated at a large academic center. We used binary logistic regression for all analyses. We assessed the predictive performance of SAPS 3 and SOFA scores within 24 h of admission, individually and in combination with serum lactate, LDH, CRP, and procalcitonin. We examined the independent association of these biomarkers with hospital mortality. We evaluated discrimination using the C-statistic and determined clinical utility with decision curve analysis. Results: We included 1395 patients, 66% of whom required mechanical ventilation, and 59.7% needed vasopressor support. Patients who died (39.7%) were significantly older (61.1 ± 15.9 years vs. 50.1 ± 14.5 years, p < 0.001) and had more comorbidities than survivors. Among the biomarkers, only procalcitonin was independently associated with higher mortality in the multivariable analysis, in a non-linear pattern. The AUROC for predicting hospital mortality was 0.771 (95% CI: 0.746–0.797) for SAPS 3 and 0.781 (95% CI: 0.756–0.805) for the SOFA score. A model incorporating the SOFA score, age, and procalcitonin demonstrated high AUROC of 0.837 (95% CI: 0.816–0.859). These associations with the SOFA score showed greater clinical utility. Conclusions: The SOFA score may aid clinical decision-making, and incorporating procalcitonin and age could further enhance its prognostic utility. Full article

Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration of AM is markedly increased in the novel coronavirus disease COVID-19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research. Full article

Sepsis is a dysregulated host response to an infection characterized by the presence of coagulopathy and endothelial dysfunction. Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils that bind invasive pathogens. These extracellular traps are involved in the activation and dysfunction of several pathways during the process of sepsis syndrome, including the immune response to injury, inflammation, and coagulation. Those formations consist of many molecules that have been studied as biomarkers for multiple sepsis pathophysiological pathways that reflect various complications. The best-studied segments of such formations, circulating free DNA, citrullinated histone 3 and myeloperoxidase, are considered to contribute to upscaling specificity. Plenty of NET end-products have been recently studied as indirect biomarkers for NET-related sepsis complications. Several studies have examined the relationship between NET end-products and established sepsis severity scores, such as Acute Physiology and Chronic Health Evaluation II (APACHE 2) and Multiple Organ Dysfunction Score (MODS). These studies also explore how these end-products contribute to the prognosis of acute respiratory distress syndrome (ARDS), mortality, and their efficacy in evaluating disseminating intravascular coagulation (DIC). This is a short review of the current literature regarding the evaluation of neutrophil extracellular trap levels in the prognosis of sepsis patients. Full article

Neutrophils are essential components of innate immunity, executing a range of effector functions including phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). A key hallmark of NET formation is the presence of citrullinated histone H3 (CitH3), produced by peptidylarginine deiminases (PAD2 and PAD4) to facilitate chromatin decondensation. While NETs play critical antimicrobial roles, excessive or dysregulated NET formation, termed NETosis, can drive tissue injury, chronic inflammation, and organ dysfunction across a wide spectrum of diseases. Beyond its structural role within NETs, CitH3 acts as a damage-associated molecular pattern (DAMP), amplifying immune activation and pathological inflammation. Elevated CitH3 levels have been identified as biomarkers in sepsis, viral infections, ischemia–reperfusion injury, organ transplantation, diabetic wounds, autoimmune diseases, and cancer. Despite increasing recognition of CitH3’s pathogenic contributions, its therapeutic potential remains largely untapped. This review summarizes recent advances in understanding the role of CitH3 in NETosis and immune dysfunction, highlights emerging strategies targeting CitH3 therapeutically, and identifies critical knowledge gaps. Collectively, these insights position CitH3 as a promising druggable biomarker for the diagnosis, prognosis, and treatment of acute and chronic inflammatory diseases. Full article

Background: Pleural empyema (PE) is a major cause of morbidity and mortality worldwide. This study aimed to analyze the epidemiological characteristics of patients hospitalized for PE in Spain between 2016 and 2022. Methods: This retrospective observational study of PE cases was based on the hospital discharge records from the National Health System between 2016 and 2022. The variables analyzed were sex, age, comorbidities, discharge diagnoses and procedures, overall severity, whether empyema was a primary or secondary diagnosis, admission to the intensive care unit (ICU), length of stay (LOS), in-hospital mortality, and healthcare costs. Results: Between 2016 and 2022, 19864 PE cases were diagnosed in Spain, revealing an overall rate of 0.64 per 1000 hospitalizations, with the exception of a slight decline in 2021. The mean age of the patients with PE was 61 years, and 73.85% were men. Most patients had low comorbidities, with a median Charlson comorbidity index (CCI) of 1.7. Most cases (63%) involved secondary diagnoses (pneumonia, pneumococcal pneumonia, sepsis, COVID, or lung cancer). The in-hospital mortality rate was higher in the secondary diagnosis group than in the primary diagnosis group (13.4% vs. 6.2%, respectively, p < 0.001). The factors associated with increased mortality included older age (≥66 years), higher CCI scores, ICU admission, and shorter LOS (<10 days). Conversely, pleural drainage and pneumonia as secondary diagnoses were protective factors. Conclusions: PE is an increasingly common pathology in clinical practice, especially in older and frail patients. It is associated with high morbidity and mortality, and its prognosis worsens with age and comorbidities. Therefore, early and appropriate diagnosis and standardized management strategies are required to mitigate the mortality and healthcare costs. Full article

Early recognition and timely treatment of sepsis and septic shock is vital. Despite appropriate management, mortality and morbidity rates remain high. In recent years, many of the research efforts have been directed towards finding novel biomarkers that would rapidly identify, classify and risk-stratify the severity of sepsis in order to achieve prompt and targeted treatment of patients with sepsis and septic shock. Among these biomarkers, adrenomedullin (ADM) in the form of the biologically active fragment (bio-ADM) and dipeptidyl peptidase 3 (DPP3) have recently been in the spotlight. The aim of this narrative review is to summarize current evidence on these two novel biomarkers regarding their clinical utility in diagnosis, prognosis, treatment monitoring and therapy guidance of sepsis and septic shock in the emergency department (ED) and in the intensive care unit (ICU) setting. Bio-ADM seems to be a promising biomarker with respect to the overall management of sepsis (diagnosis, severity prediction, prognosis and treatment monitoring and guidance). On the other hand, DPP3 appears to be useful mainly for sepsis prognosis and for predicting sepsis-induced acute kidney injury. Given their potential clinical utility in sepsis management, the use of these two novel biomarkers, in conjunction with established biomarkers and clinical scores, could lead to the application of refined integrated protocols in the ED and the ICU, which could promptly and effectively inform clinical decision-making in patients presenting with sepsis or septic shock. Full article

Generalized secondary peritonitis is a life-threatening intra-abdominal infection requiring urgent surgical intervention. Despite advances in surgical and antimicrobial therapy, morbidity and mortality remain high. Identifying key prognostic factors is crucial for improving patient outcomes. This review examines significant prognostic indicators and explores the potential role of scoring systems and artificial intelligence in risk stratification. A review was conducted using PubMed, Web of Science, Scopus, and Medline databases. Studies published from 2000 to 2024 focusing on prognostic factors in secondary peritonitis were included. A total of 145 studies were identified, with 40 selected based on relevance and methodological quality. Data extraction included patient demographics, comorbidities, severity scores, microbiological profiles, and artificial intelligence applications in peritonitis management. Poor prognosis was associated with advanced age, severe sepsis, organ failure, chronic kidney disease, cardiovascular comorbidities, and diabetes mellitus. The Mannheim Peritonitis Index (MPI) remains a widely validated prognostic tool, while APACHE II and SOFA scores also provide valuable risk estimates. Increasing multidrug-resistant infections further complicate management and impact outcomes. Emerging evidence suggests that machine learning algorithms may improve early risk stratification and individualized outcome prediction when integrated with conventional scoring systems. Identifying prognostic factors remains essential for optimizing outcomes in secondary peritonitis, and future research should prioritize the clinical validation and integration of AI-based models into perioperative management protocols. Full article

Background/Objectives: Phytochemicals are increasingly recognized for their therapeutic potential in treating various diseases, including vascular disorders. High mobility group box 1 (HMGB1), a key mediator of late-stage sepsis, triggers the release of proinflammatory cytokines, leading to inflammation and systemic complications. Elevated plasma levels of HMGB1 impair diagnosis and prognosis while worsening outcomes in inflammatory conditions. 3-deoxysappanchalcone (3-DSC), a compound derived from Biancaea sappan (L.) Tod., has demonstrated anti-influenza and anti-allergic effects, though its role in HMGB1-mediated severe vascular inflammation remains unclear. This study hypothesized that 3-DSC could modulate lipopolysaccharide-induced HMGB1 activity and its downstream inflammatory pathways in human umbilical vein endothelial cells (HUVECs). Methods: In vitro and in vivo permeability; cell viability, adhesion, and excavation of leukocytes; the development of cell adhesion molecules; and lastly, the production of proinflammatory substances were investigated on human endothelial cells and mouse disease models to investigate the efficacy of 3-DSC in inflammatory conditions. Results: Experiments revealed that 3-DSC inhibited HMGB1 translocation from HUVECs, reduced neutrophil adhesion and extravasation, suppressed HMGB1 receptor formation, and blocked nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) synthesis. Conclusions: These findings suggest that 3-DSC effectively mitigates HMGB1-driven inflammation, offering promise as a therapeutic candidate for inflammatory diseases. Full article

ACLF is a severe stage of liver cirrhosis, characterized by multiple organ failure, systemic inflammation, and high short-term mortality. The intestinal microbiota (IM) influences its pathophysiology; however, there are currently no studies in Latin American populations. Therefore, we analyzed IM and its relationships with sepsis, organ failure, and mortality. In parallel, we quantified serum lipopolysaccharides as a marker of bacterial translocation. Fecal samples from 33 patients and 20 healthy controls (HCs) were obtained. The IMs were characterized by 16S-rRNA amplicon sequencing, the metagenomic functional predictive profiles were analyzed by PICRUSt2, and LPS quantification was performed by ELISA. Patients with ACLF showed significant alterations in alpha and beta diversity compared to the HCs. A strong dominance index accurately predicted 28-day and 90-day mortalities. The IMs showed a polarization toward Proteobacteria associated with increased LPS. The LPS correlated with clinical severity, organ dysfunction, and higher pathogenic taxa. The Klebsiella/Faecalibacterium ratio showed good performance in identifying sepsis (AUROC = 0.83). Furthermore, Morganella, Proteus, and Klebsiella were enriched in patients with multiorgan failure. Lactobacillus, Escherichia/Shigella, Veillonella, and Ruminococcus gnavus exhibited potential in predicting 28- and 90-day mortalities. The IM alterations in ACLF may be useful as clinical biomarkers of poor prognosis, primarily for mortality and sepsis. These findings are representative of western Mexico. Full article

Introduction: Critically ill patients in intensive care units (ICUs) are at high risk of malnutrition, which can result in muscle atrophy, polyneuropathy, increased mortality, or prolonged hospitalizations with complications and higher costs during the recovery period. They often develop ICU-acquired weakness, exacerbated by sepsis, immobilization, and drug treatments, leading to rapid muscle mass loss and long-term complications. Studies indicate that adequate protein and calorie intake can decrease mortality and improve prognosis and recovery. However, optimal implementation remains a critical challenge. Objectives: This narrative review aims to summarize recent advances in nutritional strategies for critically ill patients. It highlights the benefits and limitations of current approaches including enteral (EN) and parenteral nutrition (PN) and examines their impact on clinical outcomes and overall mortality. Additionally, the review explores the emerging role of precision nutrition in critical care using technologies such as metabolomics and artificial intelligence (AI) to provide valuable insights into optimizing nutritional care in critically ill patients. Methods: A comprehensive literature search was conducted to identify recent studies, clinical guidelines, and expert consensus papers on nutritional support for ICU patients. The investigation focused on critical aspects such as the optimal timing for intervention, the route of administration, specific protein and energy targets, and technological innovations to support personalized nutrition, ensuring that each patient receives tailored support based on their unique needs. Results: Guidelines recommend initiating EN or PN nutrition within the first 48 h of admission, using indirect calorimetry (IC) to estimate energy needs, and supplementing protein up to 1.2 g/kg/day after stabilization. IC has gained importance in assessing energy needs but is still underused in the ICU. EN is preferred because it maintains intestinal integrity, reduces the risk of infections, and is recommended within the first 48 h of ICU admission. PN is used when EN is infeasible, but it increases the risk of infection. By integrating metabolomics with transcriptomic and genomic data, we can gain a deeper understanding of the effect of nutrition on cellular homeostasis, facilitating personalized treatments and enhancing the recovery of critically ill patients. Conclusions: AI is becoming increasingly important in monitoring and evaluating artificial nutrition, providing a more accurate and efficient alternative to traditional methods. AI can assist in identifying and managing malnutrition and is effective for estimating caloric and nutrient intake. AI minimizes human error, enables continuous monitoring, and integrates various data sources. The nutritional care of critically ill patients requires collaboration among specialists from diverse fields, including physicians, nutritionists, pharmacists, radiologists, IT experts, and policymakers. Full article