Search Results (10)

Background/Objectives: Multi-organ failure (MOF) often complicates advanced heart failure (HF), contributing to a poor prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale incorporates liver and kidney function parameters. This study aims to evaluate the prognostic significance of the MELD-3.0 score in patients with advanced HF who have undergone heart transplantation (HTx). Methods: The MELD-3.0 score was computed using the average values of the international normalized ratio and bilirubin, creatinine, sodium, and albumin levels during a hospital stay following HTx. The average MELD-3.0 scores from the period of 1 month preceding HTx and 1 week after HTx were analyzed. The primary endpoint of the study was the 6-month total mortality, and the secondary endpoint was ICU hospitalization time after HTx. Results: The analysis included 106 patients undergoing HTx, with a median age of 53 years (44–63), 81% of whom were male. Within 6 months post-HTx, 17 patients (16%) died; those patients had a higher 1-week post-HTx MELD-3.0 score of 18.3 (14.5–22.7) in comparison to survivors, whose average score was 13.9 (9.5–16.4), p < 0.01. There was no difference in MELD 3.0 score in the pre-HTx period: 16.6 (11.4–17.8) vs. 12.3 (8.6–17.1), p = 0.36. The post-HTx MELD-3.0 score independently predicted death: RR 1.17 (95% CI 1.05–1.30), p < 0.01. A Receiver Operating Characteristic (ROC) determined the cut-off value of the MELD-3.0 score as 17.3 (AUC = 0.83; sensitivity—67%; specificity—86%). Survivors with scores above this value had a longer ICU hospitalization time: 7 (5.0–11.0) vs. 12 (8–20) days (p = 0.01). Conclusions: The post-HTx MELD-3.0 score serves as an independent predictor of an unfavorable prognosis in patients with advanced HF undergoing HTx. The evaluation of MELD-3.0 scores provides additional prognostic information in this population. Full article

MicroRNAs (miR) are a group of small, non-coding RNAs of 17–25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection—two genotypes (GI.1 and GI.2)—in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection—two genotypes (GI.1 and GI.2)—and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen). Full article

Background: Angiotensin II is a peptide hormone vasopressor that activates angiotensin type 1 (AT1) receptors leading to vasoconstriction, the augmentation of arterial blood pressure (ABP), and organ perfusion. Angiotensin II was found to increase the ABP in catecholamine-refractory vasodilatory shock. Whether this effect improves the chances of survival or not remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of angiotensin II in vasoplegic shock. Objectives: To evaluate the clinical significance of angiotensin II effects in vasoplegic shock concerning the hemodynamic impact, mortality outcomes, and side effects. Methods: Following PRISMA guidelines, we searched PubMed and EMBASE for experimental and observational studies published in English exploring the clinical outcomes of angiotensin II use in vasodilatory shock till 1 July 2024. Two independent authors assessed the quality and risk of bias of the included studies. A random effect model (Mantel–Haenszel) was used to combine data. The primary outcome was in-hospital mortality associated with angiotensin II use in comparison to standard therapy, while the secondary outcomes were mean arterial pressure (MAP) change, multi-organ failure (MOF), and the incidence of atrial fibrillation (AF). The Q test and I² were used to examine heterogeneity, with I² > 50% indicating marked heterogeneity. Results: A total of eight studies (n = 974) comparing angiotensin II to standard therapy in vasoplegic shock were included in the systematic review, with three studies comprising 461 patients included in the final analysis of the primary outcome. Only one study evaluated the use of angiotensin II as a primary vasopressor, while the rest reported angiotensin II use in catecholamine-refractory vasodilatory shock. Overall, angiotensin II use was associated with similar in-hospital mortality compared to standard therapy (risk ratio [RR] = 0.83; 95% CI, 0.68–1.02, I² = 0%). Likewise, there was no difference in MOF and AF (MOF: RR = 1.01; 95% CI, 0.61–1.65, I² = 0%; AF: RR = 1.27; 95% CI, 0.38–4.23, I² = 5%). However, angiotensin II use demonstrated a significant MAP increase (mean difference = −9.60; 95% CI, −9.71, −9.49, I² = 0%). Conclusions: In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy. Nevertheless, it resulted in significant MAP change, which may encourage clinicians to use it in cases of profound hypotension. Full article

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven^® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven^® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven^® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation. Full article

High-density lipoprotein cholesterol (HDL-C) is reported as a biomarker of systemic inflammation and multi-organ failure (MOF), which has been rarely investigated in acute pancreatitis (AP), a frequent condition in the emergency department (ED). The objective was to study the predictive capacity of the decrease in HDL-C to the progression of MOF in AP in the ED; analyzing 114 patients with AP for one year in a longitudinal and prospective study, AP severity was obtained by the Atlanta classification, in relation to modified Marshall and Bedside Index for Severity in Acute Pancreatitis (BISAP) scores, and clinical and laboratory parameters in a 48 h hospital stay. The area under the receiver operating characteristic (ROC) curve was used to estimate the validity of the predictor and define optimal cut-off points. It was found that AP was classified as severe in 24.5%, mainly for biliary etiology (78.9%) and female sex (73.6%). As a biomarker, HDL-C decreased from 31.6 to 29.5 mg/dL in a 48 h stay (p < 0.001), correlating negatively with the increase in severity index > 2 and the modified Marshall (p < 0.032) and BISAP (p < 0.009) scores, finding an area under the ROC curve with a predictive capacity of 0.756 (95% CI, 0.614–0.898; p < 0.004) and a cut-off point of 28.5 mg/dL (sensitivity: 79%, specificity: 78%), demonstrating that the decrease in HDL-C levels serves as a useful indicator with a predictive capacity for MOF in mild to severe AP, during a 48 h hospital stay in the ED. Full article

According to “Sepsis-3” consensus, sepsis is a life-threatening clinical syndrome caused by a dysregulated inflammatory host response to infection. A rapid identification of sepsis is mandatory, as the extent of the organ damage triggered by both the pathogen itself and the host’s immune response could abruptly evolve to multiple organ failure and ultimately lead to the death of the patient. The most commonly used therapeutic strategy is to provide hemodynamic and global support to the patient and to rapidly initiate broad-spectrum empiric antibiotic therapy. To date, there is no gold standard diagnostic test that can ascertain the diagnosis of sepsis. Therefore, once sepsis is suspected, the presence of organ dysfunction can be assessed using the Sepsis-related Organ Failure Assessment (SOFA) score, although the diagnosis continues to depend primarily on clinical judgment. Clinicians can now rely on several serum biomarkers for the diagnosis of sepsis (e.g., procalcitonin), and promising new biomarkers have been evaluated, e.g., presepsin and adrenomedullin, although their clinical relevance in the hospital setting is still under discussion. Non-codingRNA, including long non-codingRNAs (lncRNAs), circularRNAs (circRNAs) and microRNAs (miRNAs), take part in a complex chain of events playing a pivotal role in several important regulatory processes in humans. In this narrative review we summarize and then analyze the function of circRNAs-miRNA-mRNA networks as putative novel biomarkers and therapeutic targets for sepsis, focusing only on data collected in clinical settings in humans. Full article

Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species (ROS) are main contributors to organ dysfunction in AKI, but they are not alone. The precise mechanisms behind multi-organ dysfunction are not yet fully accounted for. The building up of uremic toxins specific to AKI might be a plausible explanation for these disturbances. However, controversies have arisen around their effects in organs other than the kidney, because animal models usually depict AKI as a kidney-specific injury. Meanwhile, humans present AKI frequently in association with multi-organ failure (MOF). Until now, medium-molecular-weight molecules, such as inflammatory cytokines, have been proven to play a role in endothelial and epithelial injury, leading to increased permeability and capillary leakage, mainly in pulmonary and intestinal tissues. Full article

Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group Box 1 (HMGB1) systemic release. We investigated this issue in an animal model of MOF induced by aortic cross-clamping. Anesthetized rabbits were submitted to supra-coeliac aortic cross-clamping for 30 min, followed by 300 min of reperfusion. They were randomly divided into three groups (n = 7/group). The Control group inhaled nitrogen (70%) and oxygen (30%). The Argon group was exposed to a mixture of argon (70%) and oxygen (30%). The last group inhaled nitrogen/oxygen (70/30%) with an administration of the HMGB1 inhibitor glycyrrhizin (4 mg/kg i.v.) 5 min before aortic unclamping. At the end of follow-up, cardiac output was significantly higher in Argon and Glycyrrhizin vs. Control (60 ± 4 and 49 ± 4 vs. 33 ± 8 mL/kg/min, respectively). Metabolic acidosis was attenuated in Argon and Glycyrrhizin vs. Control, along with reduced amount of norepinephrine to reverse arterial hypotension. This was associated with reduced interleukin-6 and HMGB1 plasma concentration in Argon and Glycyrrhizin vs. Control. End-organ damages were also attenuated in the liver and kidney in Argon and Glycyrrhizin vs. Control, respectively. Argon inhalation reduced HMGB1 blood level after experimental aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition. Full article

Sepsis is a widespread life-threatening disease, with a high mortality rate due to inflammation-induced multiorgan failure (MOF). Thus, new effective modulators of the immune response are urgently needed to ameliorate the outcome of septic patients. As growth arrest-specific gene 6 (Gas6)/Tyro3, Axl, MerTK (TAM) receptors signaling has shown immunomodulatory activity in sepsis, here we sought to determine whether Gas6 protein injection could mitigate MOF in a cecal slurry mouse model of sepsis. Mice, divided into different groups according to treatment—i.e., placebo (B), ampicillin (BA), Gas6 alone (BG), and ampicillin plus Gas6 (BAG)—were assessed for vitality, histopathology and cytokine expression profile as well as inducible nitric oxide synthase (iNOS), ALT and LDH levels. BAG-treated mice displayed milder kidney and lung damage and reduced levels of cytokine expression and iNOS in the lungs compared to BA-treated mice. Notably, BAG-treated mice showed lower LDH levels compared to controls. Lastly, BAG-treated cells of dendritic, endothelial or monocytic origin displayed reduced ROS formation and increased cell viability, with a marked upregulation of mitochondrial activity. Altogether, our findings indicate that combined treatment with Gas6 and antibiotics ameliorates sepsis-induced organ damage and reduces systemic LDH levels in mice, suggesting that Gas6 intravenous injection may be a viable therapeutic option in sepsis. Full article

Purpose: The purpose of this study was to evaluate epidemiological and clinically relevant sex-related differences in polytraumatized patients at a Level 1 Trauma Center. Methods: 646 adult patients (210 females and 436 males) who were classified as polytraumatized (at the point of admission) and treated at our Level I Trauma Center were reviewed and included in this study. Demographic data as well as mechanism of injury, injury severity, injury pattern, frequency of preclinical intubation, hemodynamic variables on admission, time of mechanical ventilation and of intensive care unit (ICU) treatment, as well as the incidence of acute respiratory distress syndrome (ARDS), multi organ failure (MOF), and mortality were extracted and analyzed. Results: A total of 210 female and 436 male patients formed the basis of this report. Females showed a higher mean age (44.6 vs. 38.3 years; p < 0.0001) than their male counterparts. Women were more likely to be injured as passengers or by suicidal falls whereas men were more likely to suffer trauma as motorcyclists. Following ICU treatment, female patients resided significantly longer at the casualty ward than men (27.1 days vs. 20.4 days, p = 0.013) although there was no significant difference regarding injury severity, hemodynamic variables on admission, and incidence of MOF, ARDS, and mortality. Conclusion: The positive correlation of higher age and longer in-hospital stay in female trauma victims seems to show women at risk for a prolonged in-hospital rehabilitation time. A better understanding of the impact of major trauma in women (but also men) will be an important component of efforts to improve trauma care and long-term outcome. Full article