Markers Of Organ Failure Research Articles

MR-proADM as Prognostic Factor of Outcome in COVID-19 Patients.

Serum mid-regional proadrenomedullin (MR-proADM) has emerged as a marker of organ failure (mainly lungs and kidneys) and poor prognosis in patients admitted to intensive care (IC); some reports also suggest it and other markers, such as Krebs von den Lungen-6 (KL-6) and interleukin-6 (IL-6), as a prognostic biomarker of COVID-19. The aim of the study was to evaluate the performance MR-proADM in hospitalized COVID-19 patients for predicting in-hospital mortality and need for non-invasive or invasive respiratory support. We enrolled 74 patients hospitalized in the COVID Unit of Siena Hospital from March to May 2020, for whom serum samples were available on admission for assay of MR-proADM, KL-6 and IL-6. Demographic data, comorbidities, medical history and clinical laboratory data on days 1-3 of admission and Simplified Acute Physiology Score and Simplified Organ Failure Assessment scores calculated at day 1 were collected retrospectively, as well as mortality and IC admission data. 12 patients died in hospital (16%) and 14 patients were admitted to IC (19%). Serum concentrations of MR-proADM on admission and on day 1 were higher among non-survivors than among survivors (p = 0.015 and p = 0.045, respectively), while those on day 3 were not significantly different. Patients needing respiratory support had higher MR-proADM concentrations on admission than the others (p = 0.046), and those requiring invasive mechanical ventilation had higher MR-proADM on day 1 (p = 0.017). Serum concentrations of KL-6 and IL-6 were significantly higher in non-survivors (p = 0.03 and p = 0.004, respectively). ROC curve analysis showed that serum MR-proADM on day 1 had the best accuracy in predicting death and/or IC admission (AUC = 0.9583, p = 0.0006); the combination of all three biomarkers further improved the accuracy of prediction of death or IC admission (AUC = 0.9793; p = 0.00004). Our data sustain the potential of serum MR-proADM as a reliable prognostic biomarker of hospitalized COVID-19 patients and confirms the utility of the three markers in the management and risk stratification of hospitalized patients. The markers are collected mini-invasively and are quick to analyze and cost-effective.

Abstract 395: Interferon-induced Transmembrane Protein 3 (ifitm3) Mediates Platelet Functions During Inflammatory Stress

Background: Thrombosis, precipitated by dysregulated platelet responses, contributes to adverse clinical outcomes, including organ failure and death during systemic inflammation (e.g., sepsis). Previously, our lab identified interferon-induced transmembrane protein 3 (IFITM3) as a mediator of anti-viral responses in platelets. However, whether IFITM3 mediates platelet functions and subsequent thrombosis during systemic inflammation is unknown. Methods: Cecal-ligation and Puncture (CLP) model of sepsis and Interferon alpha (IFNα)-induced sterile inflammation model was performed on WT and platelet- and MK-specific IFITM3 knockout strain (IFITM3 fl/fl PF4-Cre +/- ). P-Selectin and CD63 expression, Platelet Factor 4 (PF4) release, platelet-leukocyte aggregates, plasma cytokines (TNF-α, IL-6, CXCL1), as well as survival outcomes, platelet deposition and aggregates within organs (e.g. lungs), plasma aspartate aminotransferase, lactate dehydrogenase, D-Dimer levels were measured by flow cytometry, enzyme-linked immunosorbent assays (ELISAs), and immunohistochemistry. In vivo collagen-epinephrine-induced pulmonary embolism model, and ex vivo thrombus formation under flow using microfluidic devices were performed. Results: CLP sepsis or IFNα-induced sterile inflammation upregulated IFITM3 in platelets which were associated with significantly enhanced secretion of P-Selectin, PF4, and CD63, and increased mortality in a collagen-epinephrine-induced murine pulmonary embolism model. Biochemical assays demonstrated IFITM3 interacts with VAMP-8, the primary v-SNARE that drives platelet secretion. Platelets lacking IFITM3 showed reduced granule secretion and platelet-leukocyte aggregate formation. Sepsis-induced mortality, platelet-leukocyte aggregates, platelet deposition within lungs, and markers of organ failure and thrombosis (e.g., aspartate aminotransferase, lactate dehydrogenase, D-Dimer), and thrombus formation under flow were all significantly reduced in the absence of IFITM3 in CLP sepsis. Conclusions: Collectively, our findings suggest that IFITM3 is a novel regulator of secretion and aggregation in platelets and contributes to thrombotic events during systemic inflammation.

Correlation between Thyroid Responses and Inflammatory Cytokines in Critically Ill COVID-19 Patients.

Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.

Organ function biomarker abnormalities, associated factors and disease outcome among hospitalized patients with COVID-19.

Background: The aim of this study was to determine the magnitude of abnormal organ function tests and biomarkers in hospitalized patients with confirmed COVID-19 and to define the association among markers of organ failure, disease severity and its outcome in hospitalized COVID-19 patients in Ethiopia. Methods: A prospective cohort study was conducted among COVID-19 patients admitted to Millennium COVID-19 Treatment Center from December 2020 to June 2021. Results: The median age of the 440 study participants was 60.3 ± 1.3 years, and from these 71.3% of patients were male. Disease severity: p-value: 0.032; adjusted odds ratio (AOR) (95% CI): 4.4 (0.022–0.085); and the presence of any co-morbidity; p-value: 0.012; AOR (95% CI): 0.80 (0.47–0.83) was significantly associated with mortality. Aspartate transaminase, alanine transaminase and alkaline phosphatase parameter values of patients overall, were elevated – mainly among critical patients (56.9 ± 57.7, 58.5 ± 63 and 114.6 ± 60, respectively).

Absolute lymphocyte count is a prognostic marker in Covid-19: A retrospective cohort review.

IntroductionPrognostic factors are needed to aid clinicians in managing Covid‐19, a respiratory illness. Lymphocytopenia has emerged as a simply obtained laboratory value that may correlate with prognosis.MethodsIn this article, we perform a retrospective cohort review study on patients admitted to one academic hospital for Covid‐19 illness. We analyzed basic demographic, clinical, and laboratory data to understand the relationship between lymphocytopenia at the time of hospital admission and clinical outcomes.ResultsWe discovered that lymphocyte count is lower (P = .01) and lymphocytopenia more frequent by an odds ratio of 3.40 (95% CI: 1.06‐10.96; P = .04) in patients admitted to the Intensive Care Unit (ICU), a marker of disease severity, relative to those who were not. We additionally find that patients with lymphocytopenia were more likely to develop an acute kidney injury (AKI), a marker of organ failure, during admission by an odds ratio of 4.29 (95% CI: 1.35‐13.57; P = .01).ConclusionThis evidence supports the hypothesis that lymphocytopenia can be an early, useful, and easily obtained, prognostic factor in determining the clinical course and disease severity of a patient admitted to the hospital for Covid‐19.

Reversal of Severe Multiorgan Failure Associated With Sickle Cell Crisis Using Plasma Exchange: A Case Series.

Red blood cell exchange (RBCE) is the standard of care for patients with sickle cell disease (SCD) who present with severe vaso-occlusive crisis (VOC). However, subsets of these critically ill patients have progressive multiorgan failure (MOF) despite RBCE therapy. The purpose of this case series is to describe the use of plasma exchange (PLEX) for the treatment of SCD-related MOF that is refractory to RBCE. A retrospective case review of patients with severe MOF from sickle cell crisis unresponsive to RBCE who underwent PLEX in a 14-bed adult medical intensive care unit (ICU) at a tertiary care university hospital over a 4-year time period. Key laboratory data including complete blood count, indices of hemolysis, and markers of organ failure were recorded before and after both RBCE and PLEX. Our primary objective is to evaluate the effectiveness of PLEX, in addition to RBCE, on organ dysfunction, laboratory indices, and mortality. Of the 7 patients, 6 survived. Of the patients who survived, all remained hemodynamically stable during PLEX sessions and showed both clinical and laboratory evidences of improvement in hemolysis and organ function. Average time from completion of first PLEX treatment to initial laboratory signs of organ failure reversal for patients who survived was 15.6 hours, the average length of stay in the ICU was 5.6 days, and the average total length of stay in the hospital was 14 days. Plasma exchange, in addition to RBCE, may be a novel synergistic treatment option to decrease risk of mortality in patients with refractory VOC and MOF.

Persistently elevated osteopontin serum levels predict mortality in critically ill patients.

IntroductionInflammatory, autoimmune and metabolic disorders have been associated with alterations in osteopontin (OPN) serum levels. Furthermore, elevated serum levels of OPN were reported from a small cohort of patients with sepsis. We therefore analyzed OPN serum concentrations in a large cohort of critically ill medical patients.MethodsA total of 159 patients (114 with sepsis, 45 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) as well as after 3 days of ICU treatment and compared to 50 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately 1 year.ResultsWe found significantly elevated serum levels of OPN at admission to the ICU and after 3 days of treatment in critically ill patients compared to healthy controls. OPN concentrations were related to disease severity and significantly correlated with established prognosis scores and classical as well as experimental markers of inflammation and multi-organ failure. In the total cohort, OPN levels decreased from admission to day 3 of ICU treatment. However, persistently elevated OPN levels at day 3 of ICU treatment were a strong independent predictor for an unfavorable prognosis, with similar or better diagnostic accuracy than routinely used markers of organ failure or prognostic scoring systems such as SAPS2 or APACHE II score.ConclusionsPersistently elevated OPN serum concentrations are associated with an unfavourable outcome in patients with critical illness, independent of the presence of sepsis. Besides a possible pathogenic role of OPN in critical illness, our study indicates a potential value for OPN as a prognostic biomarker in critically ill patients during the early course of ICU treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0988-4) contains supplementary material, which is available to authorized users.

The regulatory toll-like receptor 4 genetic polymorphism rs11536889 is associated with renal, coagulation and hepatic organ failure in sepsis patients.

BackgroundToll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3’-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype.MethodsAdult Caucasian patients with sepsis from the intensive care unit of a university medical center were followed up for 90 days, and organ failure was recorded as the primary outcome variable. Blood samples were collected at enrollment for TLR4 rs11536889 genotyping. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure.ResultsA total of 210 critically ill patients with sepsis were enrolled into this study. Wild-type GG was compared to GC/CC. During their stay in the intensive care unit, GG patients presented significantly higher SOFA scores than did C allele carriers (7.9 ± 4.5 and 6.8 ± 4.2, respectively; p = 0.0005). Analysis of organ-specific SOFA sub-scores revealed significant differences in three organ systems: renal, coagulation and hepatic (p = 0.0005, p = 0.0245 and p < 0.0001, respectively). Additionally, the rs11536889 polymorphism was associated with a higher incidence of gram-negative infections.ConclusionsThese results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.

Pancreatic Stone Protein: A Marker of Organ Failure and Outcome in Ventilator-Associated Pneumonia

Pancreatic Stone Protein: A Marker of Organ Failure and Outcome in Ventilator-Associated Pneumonia

Pancreatic Stone Protein: A Marker of Organ Failure and Outcome in Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired, life-threatening infection. Poor outcome and health-care costs of nosocomial pneumonia remain a global burden. Currently, physicians rely on their experience to discriminate patients with good and poor outcome. However, standardized prognostic measures might guide medical decisions in the future. Pancreatic stone protein (PSP)/regenerating protein (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill patients is unknown. The aim of this pilot study was to evaluate PSP/reg in VAP. One hundred one patients with clinically diagnosed VAP were assessed. PSP/reg was retrospectively analyzed using deep-frozen serum samples from VAP onset up to day 7. The main end point was death within 28 days after VAP onset. Serum PSP/reg was associated with the sequential organ failure assessment score from VAP onset (Spearman rank correlation coefficient 0.49 P < .001) up to day 7. PSP/reg levels at VAP onset were elevated in nonsurvivors (n = 20) as compared with survivors (117.0 ng/mL [36.1-295.3] vs 36.3 ng/mL [21.0-124.0] P = .011). The areas under the receiver operating characteristic curves of PSP/reg to predict mortality/survival were 0.69 at VAP onset and 0.76 at day 7. Two PSP/reg cutoffs potentially allow for identification of individuals with a particularly good and poor outcome. Whereas PSP/reg levels below 24 ng/mL at VAP onset were associated with a good chance of survival, levels above 177 ng/mL at day 7 were present in patients with a very poor outcome. Serum PSP/reg is a biomarker related to organ failure and outcome in patients with VAP. ISRCTN.org; No.: ISRCTN61015974; URL: www.isrctn.org.

Delirium and use of sedation agents in intensive care

The aim of the review was to consider the relationship between delirium and aspects of sedative and analgesic drug use in mechanically ventilated intensive care patients. The basis for routine delirium screening and the implications for nurses are discussed along with a brief outline of the treatment of delirium. Delirium is common in intensive care patients and like other markers of organ failure is associated with worse outcomes. The risk of developing delirium is dependent on the patients' individual vulnerability and on the burden of precipitating factors they are exposed to. Detection of delirium in intensive care patients is often difficult and requires the regular use of a validated screening tool. Intensive care patients are exposed to multiple delirium risk factors, and sedative and analgesic agents present an important subgroup, which we can attempt to control. Sedative and analgesic drug choice, their mode of administration, monitoring and titration have consequences for delirium development. Literature review. Sedative and analgesic drugs have an important role in the prevention and treatment of delirium in intensive care patients. Routine delirium screening should be included as part of sedation monitoring practice. When detected, treatment is focused on the prompt correction of precipitating factors, non-pharmacological interventions and appropriate drug therapy for symptom control.