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Critical Care Explorations Jul 2024While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these... (Observational Study)
Observational Study
OBJECTIVES
While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.
DESIGN
In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).
SETTING
Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.
PATIENTS
Ninety-six adult septic and critically ill nonseptic patients were enrolled.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.
CONCLUSIONS
Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.
Topics: Humans; Prospective Studies; Critical Illness; Sepsis; Male; Female; Middle Aged; Multiple Organ Failure; Aged; Organ Dysfunction Scores; Adult; Cytokines; Cohort Studies; Predictive Value of Tests; Lipopolysaccharides
PubMed: 38916619
DOI: 10.1097/CCE.0000000000001106 -
Scientific Reports Jun 2024Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of...
Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.
Topics: Humans; Shock, Septic; Thromboplastin; Male; Female; Lipoproteins; Middle Aged; Aged; Multiple Organ Failure; Disseminated Intravascular Coagulation; Case-Control Studies; Adult; Biomarkers
PubMed: 38914630
DOI: 10.1038/s41598-024-65262-3 -
Heliyon Jun 2024A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have...
A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.
PubMed: 38912444
DOI: 10.1016/j.heliyon.2024.e32647 -
Heliyon Jun 2024Hyperammonemia syndrome has a high mortality rate in the immunosuppressed population due to its association with mental status changes. Recently studies have shown that...
Hyperammonemia syndrome has a high mortality rate in the immunosuppressed population due to its association with mental status changes. Recently studies have shown that organisms' infection can lead to hyperammonemia in post-transplant patients. Symptoms typically occur within 30 days postoperatively. However, the late-onset hyperammonemia caused by infection after kidney transplantation has never been reported. In this case study, a 64-year-old Chinese male presented with symptoms such as nausea, vomiting, trouble sleeping, and deteriorating mental status 81 days after kidney transplantation. His plasma ammonia level was significantly elevated, and there was no evidence of liver synthetic dysfunction. Although common methods for ammonia clearance, such as haemodialysis and oral lactulose were initiated, his serum ammonia levels remained high. Metagenomic sequencing of serum determined infection. Levofloxacin and minocycline were administered respectively, which resulted in a decrease in ammonia levels, but normalization was not achieved. The computed tomographic scan revealed the presence of cerebral edema. Unfortunately, the patient eventually became brain dead with multiple organ failure. This case highlights that can cause late-onset hyperammonemia in kidney transplant patients. Once the mental status changes are identified, immediate empiric treatments should be initiated without waiting for a confirmed diagnosis of spp. infection.
PubMed: 38912440
DOI: 10.1016/j.heliyon.2024.e32134 -
International Journal of Applied &... 2024Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which...
BACKGROUND AND OBJECTIVES
Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU).
METHODOLOGY
30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily.
RESULTS
D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases ( = 0.04). D-dimer in ICU patients was significantly elevated ( = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate ( = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure.
CONCLUSION
Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.
PubMed: 38912365
DOI: 10.4103/ijabmr.ijabmr_483_23 -
World Journal of Clinical Cases Jun 2024Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and...
Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and potentially fatal outcomes. Reports suggest that the mortality of DQ poisoning can be as high as 50%. DQ poisoning can be categorized as mild, moderate to severe or fulminant. In cases of fulminant poisoning, victims often succumb to multiple organ failure within 48 h. This presents a significant challenge in the clinical management. Scholars have discovered that oxidative stress, inflammatory injury, and cell apoptosis play crucial roles in the DQ poisoning. However, the underlying connection of the extensive organ damage remains unknown. The abnormal function and activity of endothelial cells (EC) should play a crucial role in tissue damage caused by DQ due to rich microcirculation and high sensitivity to perfusion in the vulnerable organs. However, reports on DQ-induced EC injury is rare. We made a preliminary discovery-the presence of severe vascular endothelial damage in the kidneys and lungs affected by DQ. Therefore, we hypothesize that DQ poisoning may be attributed to EC damage, ultimately resulting in multiple organ failure.
PubMed: 38898842
DOI: 10.12998/wjcc.v12.i17.2917 -
International Journal of Molecular... May 2024The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1...
The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, < 0.001) and thrombocytopenia (<150/nL, = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.
Topics: Humans; Hepatitis A Virus Cellular Receptor 1; Sepsis; Male; Female; Middle Aged; Critical Illness; Aged; Acute Kidney Injury; Biomarkers; Severity of Illness Index; Multiple Organ Failure; Intensive Care Units; Adult
PubMed: 38892009
DOI: 10.3390/ijms25115819 -
Communications Medicine Jun 2024Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity...
BACKGROUND
Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups.
METHODS
Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N = 494).
RESULTS
We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality immunocompetent group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The immunosuppressed group members show signs of a dysfunctional immune response, the acute-inflammation group is set apart by molecular features of the innate immune response, while the immunometabolic group is characterized by metabolic pathways such as heme biosynthesis.
CONCLUSIONS
Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.
PubMed: 38890515
DOI: 10.1038/s43856-024-00542-7 -
BMC Pulmonary Medicine Jun 2024This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute... (Comparative Study)
Comparative Study
OBJECTIVE
This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS).
METHODS
A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded.
RESULTS
The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P < 0.05). The mechanical ventilation time, intensive care unit (ICU) hospitalization time, and duration of antimicrobial medication in the observation group were shorter and multiple organ dysfunction syndrome incidence was lower than those in the control group (P < 0.05). The mortality rate of patients in the observation group (35.71%) was lower than that in the control group (52.38%), but there was no statistically significant difference between the two groups (P > 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P < 0.05). After treatment, respiratory function, inflammation, and oxidative stress were improved in the observation group (P < 0.05). Adverse reactions were not significantly different between the two groups (P > 0.05).
CONCLUSION
The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS.
Topics: Humans; Male; Sepsis; Respiratory Distress Syndrome; Female; Middle Aged; Glycoproteins; Aged; Drug Therapy, Combination; Glycine; Sulfonamides; Treatment Outcome; Respiration, Artificial; APACHE; Adult; Multiple Organ Failure; Oxidative Stress; Organ Dysfunction Scores; Intensive Care Units; Trypsin Inhibitors
PubMed: 38886709
DOI: 10.1186/s12890-024-03083-w -
Aging Jun 2024Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes...
Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes is still needed. Rosuvastatin, a typical β-hydroxy β-methylglutaryl-CoA reductase inhibitor licensed for reducing the levels of low-density lipoprotein cholesterol in patients with hyperlipidemia, has displayed anti-inflammatory capacity in different types of organs and tissues. However, its effects on the development of sepsis are less reported. Here, we found that the administration of Rosuvastatin reduced the mortality of sepsis mice and prevented body temperature loss. Additionally, it inhibited the production of inflammatory cytokines such as tumor necrosis factor (TNF-α), Interleukin-6 (IL-6), interleukin-1β (IL-1β), and migration inhibitory factor (MIF) in peritoneal lavage supernatants of animals. The increased number of mononuclear cells in the peritoneum of sepsis mice was reduced by Rosuvastatin. Interestingly, it ameliorated lung inflammation and improved the hepatic and renal function in the sepsis animals. Further experiments show that Rosuvastatin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory cytokines in RAW 264.7 macrophages by preventing the activation of nuclear factor kappa-B (NF-κB). Our findings demonstrate that the administration of Rosuvastatin hampered organ dysfunction and mitigated inflammation in a relevant model of sepsis.
PubMed: 38885061
DOI: 10.18632/aging.205937