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Critical Care Explorations Jul 2024To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with...
High Levels of Triggering Receptor Expressed in Myeloid Cells-Like Transcript-1 Positive, but Not Glycoprotein 1b+, Microparticles Are Associated With Poor Outcomes in Acute Respiratory Distress Syndrome.
OBJECTIVES
To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with clinical outcomes and/or disease severity in acute respiratory distress syndrome (ARDS).
DESIGN
Retrospective cohort study.
SETTING
ARDS Network clinical trials.
PATIENTS
A total of 564 patients were diagnosed with ARDS.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Using flow cytometry, we demonstrated the presence of TLT-1+ platelet-derived microparticles (PMP) that bind fibrinogen in plasma samples from fresh donors. We retrospectively quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive microparticles in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA (Studies 01 and 03 lower versus higher tidal volume, ketoconazole treatment, and lisofylline treatment Clincial Trials) ARDS Network clinical trials and evaluated the relationship between these measures and clinical outcomes. No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa+ and TLT-1+ MPs (χ2p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT+ PMP in the 75th percentile. In all three cohorts, patients whose TLT+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors.
CONCLUSIONS
Although both αIIbβIIIa+ and TLT+ microparticles (αIIbβIIIa, TLT-1) were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with Acute Physiology and Chronic Health Evaluation III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression.
Topics: Humans; Respiratory Distress Syndrome; Male; Female; Retrospective Studies; Middle Aged; Cell-Derived Microparticles; Adult; Membrane Glycoproteins; Aged; Cohort Studies; Platelet Glycoprotein GPIb-IX Complex; Flow Cytometry; Receptors, Immunologic
PubMed: 38935146
DOI: 10.1097/CCE.0000000000001108 -
Medicina (Kaunas, Lithuania) Jun 2024: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits... (Observational Study)
Observational Study
: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits collagen synthesis, which leads to organ and systems failure, including hepato- and splenomegaly, immune disorders, chronic ulcerative wounds, respiratory infections, and pulmonary fibrosis. The complexity of the problems associated with this disease necessitates a comprehensive approach and the involvement of an interdisciplinary team. The objective was to present the treatment and care plan, as well as complications of PD, in a young woman following admission to an intensive care unit (ICU). : A retrospective observational single-case study. : A 26-year-old woman with PD was hospitalized in the ICU for acute respiratory failure. The presence of difficult-to-heal extensive leg ulcers and the patient's immunocompromised condition resulted in the development of sepsis with multiple organ failure (respiratory and circulatory, liver and kidney failure). Complex specialized treatment consisting of wound preparation, limb amputation, the minimization of neuropathic pain, mechanical ventilation, renal replacement therapy, circulatory stabilization, and the prevention of complications of the disease and of therapy were applied. On the 83rd day of hospitalization, the patient expired. : Despite the use of complex treatment and care, due to the advanced nature of the disease and the lack of therapies with proven efficacy, treatment was unsuccessful. There is a need for evidence-based research to develop effective treatment guidelines for PD.
Topics: Humans; Female; Adult; Multiple Organ Failure; Intensive Care Units; Sepsis; Prolidase Deficiency; Retrospective Studies; Fatal Outcome
PubMed: 38929623
DOI: 10.3390/medicina60061006 -
Medicina (Kaunas, Lithuania) May 2024SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury... (Observational Study)
Observational Study
SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19-100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19-100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11-4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26-8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19-100 ng/L was 2.58 (95% CI 1.83-3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01-4.39) compared to patients with normal cTnI levels. Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients.
Topics: Humans; COVID-19; Troponin I; Male; Female; Retrospective Studies; Middle Aged; Hospital Mortality; Aged; Prognosis; Hospitalization; Biomarkers; SARS-CoV-2; Adult; Aged, 80 and over; Risk Factors
PubMed: 38929459
DOI: 10.3390/medicina60060842 -
Children (Basel, Switzerland) Jun 2024The suppression of tumorigenicity 2 (ST2) is a receptor member belonging to the interleukin-1 (IL-1) family. The ligand and soluble versions are its two isoforms. The...
INTRODUCTION
The suppression of tumorigenicity 2 (ST2) is a receptor member belonging to the interleukin-1 (IL-1) family. The ligand and soluble versions are its two isoforms. The IL-33-ST2L ligand complex's development provides protection against heart fibrosis and hypertrophy. Investigations on heart failure in adults have demonstrated that it does not change by age, body mass index (BMI), creatinine, hemoglobin, and albumin levels, in contrast to NT pro BNP. In adult heart failure patients, it has been demonstrated to be an independent predictor of mortality and cardiovascular events. The most recent guideline recommends using it as class 2b in the diagnosis of adult heart failure. Studies on ST2 in children are rare. The purpose of this study is to assess the prognostic value of ST2 for cardiovascular events in young individuals suffering from heart failure.
METHOD
This study included pediatric patients (0-18 years old) with congenital heart disease or cardiomyopathy who needed medical care, as well as surgical or interventional treatment. Height, weight, gender, saturation, heart failure classification (Ross or NYHA), medications, the electrocardiogram, echocardiography, pro BNP, and sST2 values of the patients, as well as any hospitalization, lower respiratory tract infection, organ dysfunction, or need for angiography or surgery during follow-up data on arrhythmia and death were gathered during a 1-year follow-up. The SPSS software version 25 application was used to carry out the statistical analysis.
RESULTS
This study included 59 patients, of whom 27 (46.6%) were male. The average age of the patients was 55.5 months (1-228 months) and the average body weight was 16 kg (2.6-90 kg). Major cardiovascular events occurred in 45 of 59 patients (76.3%). Twenty-four patients experienced one MACE, while twenty-one patients experienced multiple MACEs. Pro BNP and sST2 levels were similar in the groups that developed MACE compared to those that did not. Pro BNP was discovered to be significantly higher in patients with hospitalization, growth retardation, lower respiratory tract infection, and organ failure, however, when assessing each situation ( = 0.001, = 0.011, = 0.001, = 0.007, respectively). Soluble ST2 was found to be higher in patients with growth retardation than in those without ( = 0.037). Although the soluble ST2 level failed to demonstrate a correlation with pro BNP, it did show a positive correlation (r = 0.437) with the Ross score. When compared to other groups, it was discovered to be higher in patients with valvular insufficiency type heart disease.
CONCLUSIONS
In this study, higher sST2 levels were discovered, particularly in the group with valve insufficiency and children with growth retardation. It was associated with the Ross score, but not with the pro BNP level. Although it increases in correlation with clinical heart failure, its predictive value for MACE is low. Similarly, pro BNP is not proven to be predictive; nonetheless, its high levels in patients with hospitalization, growth retardation, lower respiratory tract infection, and organ failure demonstrate that pro BNP may increase for a variety of causes. Long-term studies with more patients are needed for ST2 to be suitable for clinical use in pediatric patients.
PubMed: 38929297
DOI: 10.3390/children11060718 -
Cancers Jun 2024The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better... (Review)
Review
The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment. Moreover, he must deal not only with organ issues related to MM such as bone disease, renal failure or neurological disease but also with adverse events, often very serious, related to novel therapies, particularly new generation immunotherapies such as CAR T cell therapy and bispecific antibodies. In this review, we provide an overview on the newer MM diagnostic and monitoring strategies and on the main side effects of MM therapies, focusing on adverse events occurring during treatment with CAR T cells and bispecific antibodies.
PubMed: 38927968
DOI: 10.3390/cancers16122263 -
Biomedicines May 2024Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to...
Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction.
PubMed: 38927377
DOI: 10.3390/biomedicines12061170 -
Frontiers in Veterinary Science 2024Infectious bursal disease (IBD) is one of the dangerous diseases of poultry that affects the bursa of Fabricius, which is an important organ of the bird's immune system.... (Review)
Review
Infectious bursal disease (IBD) is one of the dangerous diseases of poultry that affects the bursa of Fabricius, which is an important organ of the bird's immune system. IBD virus is resistant to many drugs, making its control difficult. Vaccination of IBD is in practice for a long time worldwide to control IBD, but secondary issues like vaccine failure and lower efficacy lead to their reduced use in the field. Multiple medicines are currently used, but the phytochemicals have emerged as promising agents for controlling IBD. The drugs to be developed should possess direct antiviral properties by targeting viral entry mechanisms, enhancing the host immune response, and inhibiting viral protein synthesis. Phytochemicals have potential to contribute to food security by minimizing the possibility of disease outbreaks and ensuring that consumers worldwide obtain healthy poultry products. It has been now claimed that direct and indirect activities of phytochemicals can be effective in the control of IBDV. Although available evidence suggest that the phytochemicals can contribute in controlling occurrence IBDV, there is a definite need of focused studies to gain more insight and develop rational strategies for their practical use. This review highlights the disease caused by IBDV, inhibition of viral replication, boosting the immune system, disruption of viral membrane, and important phytochemicals showing antiviral activities against IBDV.
PubMed: 38919155
DOI: 10.3389/fvets.2024.1421668 -
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