Pilot Investigation of the Association Between Serum Stress Neuropeptide Levels and Lymphocyte Expression of Fas and Fas Ligand in Critical Illness

Introduction: In critical illness, apoptotic loss of immunocytes is associated with immunosuppression. Aim: To explore expression of Fas/Fas ligand (FasL) on B and T cells from critically ill patients without sepsis compared to matched controls and associations with disease severity and neuropeptide Y (NPY), cortisol, adrenocorticotropic hormone (ACTH), and prolactin (PRL) levels. Methods: Repeated-measures correlational design with 36 critically ill patients (14-day follow-up) and 36 controls. Disease severity was assessed using the Multiple Organ Dysfunction Score (MODS) and Multi Organ Failure scale. Fas/FasL values were standardized for viable cell counts. An enzyme-linked immunosorbent assay (NPY) and electrochemiluminescence immunoassay (cortisol, ACTH, and PRL) were employed. Results: Fas and FasL expression on T-helper ( p < .0001–.03) and T-cytotoxic cells ( p < .0001–.002) and Fas expression on B cells ( p < .0001–.03) were higher in patients. MODS severity was associated with FasL expression on cytotoxic T cells ( r = .752–.902, p = .023–.037). There was an inverse association between Day 1 NPY levels and Fas expression on T-helper cells ( r = −.447, p = .019). On the day of maximum severity, we report for the first time an inverse association between NPY levels and FasL expression on helper ( r = −.733, p = .016) and cytotoxic ( r = −.862, p = .003) T cells. Cortisol levels were positively associated with counts of FasL-positive helper ( r = .828) and cytotoxic ( r = .544, p < .05) T cells. Conclusion: Results suggest a potential role for stress neuropeptides in lymphocyte survival and activation in critical illness.

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Critically Ill vs. Non-Critically Ill Patients With COVID-19 Pneumonia: Clinical Features, Laboratory Findings, and Prediction

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.550456 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wandong Hong ◽

Qin Chen ◽

Songzan Qian ◽

Zarrin Basharat ◽

Vincent Zimmer ◽

...

Keyword(s):

Critical Illness ◽

Disease Severity ◽

Critically Ill ◽

Clinical Features ◽

Critically Ill Patients ◽

Interleukin 6 ◽

Discharge Rate ◽

Laboratory Data ◽

Laboratory Findings ◽

Laboratory Parameters

ObjectivesThe objective of this study was to investigate the clinical features and laboratory findings of patients with and without critical COVID-19 pneumonia and identify predictors for the critical form of the disease.MethodsDemographic, clinical, and laboratory data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Laboratory parameters were also collected within 3–5 days, 7–9 days, and 11–14 days of hospitalization. Outcomes were followed up until March 12, 2020.ResultsTwenty-two patients developed critically ill pneumonia; one of them died. Upon admission, older patients with critical illness were more likely to report cough and dyspnoea with higher respiration rates and had a greater possibility of abnormal laboratory parameters than patients without critical illness. When compared with the non-critically ill patients, patients with serious illness had a lower discharge rate and longer hospital stays, with a trend towards higher mortality. The interleukin-6 level in patients upon hospital admission was important in predicting disease severity and was associated with the length of hospitalization.ConclusionsMany differences in clinical features and laboratory findings were observed between patients exhibiting non-critically ill and critically ill COVID-19 pneumonia. Non-critically ill COVID-19 pneumonia also needs aggressive treatments. Interleukin-6 was a superior predictor of disease severity.

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Prognostic Relevance of Altered Lymphocyte Subpopulations in Critical Illness and Sepsis

Journal of Clinical Medicine ◽

10.3390/jcm8030353 ◽

2019 ◽

Vol 8 (3) ◽

pp. 353 ◽

Cited By ~ 9

Author(s):

Philipp Hohlstein ◽

Hendrik Gussen ◽

Matthias Bartneck ◽

Klaudia Theresa Warzecha ◽

Christoph Roderburg ◽

...

Keyword(s):

T Cells ◽

Intensive Care ◽

T Cell ◽

Critical Illness ◽

Healthy Volunteers ◽

Critically Ill ◽

Critically Ill Patients ◽

Peripheral Blood ◽

Icu Patients ◽

T Cell Depletion

Lymphopenia and functional defects in lymphocytes may impact the prognosis in patients with critical illness or sepsis. Therefore, we prospectively analyzed peripheral blood leukocytes from 63 healthy volunteers, 50 non-critically ill standard care (SC) patients with infections, and 105 intensive care unit (ICU) patients (52 with sepsis, 53 without sepsis) using flow cytometry. Compared to healthy volunteers, SC and ICU patients showed significant leukocytosis, especially in sepsis, while lymphocyte numbers were significantly decreased. All major lymphocyte populations (B, T, and natural killer (NK) cells) decreased in ICU patients. However, we observed a relative reduction of T cells, alongside decreased CD8+ T cells, in critically ill patients, independent of sepsis. High absolute T cell counts (>0.36/nL) at ICU admission were associated with a significantly reduced mortality, independent of patient’s age. Moreover, patients that survived ICU treatment showed dynamic changes within 48 h towards restoration of lymphopenia and T cell depletion, while non-surviving patients failed to restore lymphocyte counts. In conclusion, the flow-cytometric analysis of peripheral blood revealed striking changes in circulating lymphocyte subsets in critically ill patients, independent of sepsis. Lymphopenia and T cell depletion at ICU admission were associated with increased mortality, supporting their relevance as predictive biomarkers and potential therapeutic targets in intensive care medicine.

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Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity*

Critical Care Medicine ◽

10.1097/ccm.0000000000001633 ◽

2016 ◽

Vol 44 (6) ◽

pp. 1034-1041 ◽

Cited By ~ 18

Author(s):

Jeremy Cohen ◽

Carel J. Pretorius ◽

Jacobus P. J. Ungerer ◽

John Cardinal ◽

Antje Blumenthal ◽

...

Keyword(s):

Septic Shock ◽

Disease Severity ◽

Critically Ill ◽

Critically Ill Patients ◽

Glucocorticoid Sensitivity

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Critical Illness Outcomes Study: An Observational Cohort Of Critically Ill Patients

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6788 ◽

2012 ◽

Author(s):

Jonathan E. Sevransky ◽

William Checkley ◽

Timothy D. Girard ◽

Steven M. Pastores ◽

Sajid Shahul ◽

...

Keyword(s):

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Observational Cohort ◽

Outcomes Study ◽

Illness Outcomes

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Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia

Journal of Clinical Medicine ◽

10.3390/jcm10132935 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2935

Author(s):

Jose Bordon ◽

Ozan Akca ◽

Stephen Furmanek ◽

Rodrigo Silva Cavallazzi ◽

Sally Suliman ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Critical Illness ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Critically Ill ◽

Critically Ill Patients ◽

Distress Syndrome ◽

Invasive Mechanical Ventilation ◽

Overall Mortality

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic’s death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.

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Regulation and Prognostic Relevance of Symmetric Dimethylarginine Serum Concentrations in Critical Illness and Sepsis

Mediators of Inflammation ◽

10.1155/2013/413826 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Alexander Koch ◽

Ralf Weiskirchen ◽

Jan Bruensing ◽

Hanna Dückers ◽

Lukas Buendgens ◽

...

Keyword(s):

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Multiorgan Failure ◽

Microvascular Dysfunction ◽

Serum Levels ◽

Serum Concentrations ◽

Symmetric Dimethylarginine ◽

Term Survival ◽

Severity Scores

In systemic inflammation and sepsis, endothelial activation and microvascular dysfunction are characteristic features that promote multiorgan failure. As symmetric dimethylarginine (SDMA) impacts vascular tension and integrity via modulating nitric oxide (NO) pathways, we investigated circulating SDMA in critical illness and sepsis. 247 critically ill patients (160 with sepsis, 87 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 84 healthy controls. SDMA serum levels were significantly elevated in critically ill patients at admission to ICU compared to controls and remained stably elevated during the first week of ICU treatment. The highest SDMA levels were found in patients with sepsis. SDMA levels closely correlated with disease severity scores, biomarkers of inflammation, and organ failure (renal, hepatic, and circulatory). We identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival. Thus, the significant increase of circulating SDMA in critically ill patients indicates a potential pathogenic involvement in endothelial dysfunction during sepsis and may be useful for mortality risk stratification at the ICU.

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T helper cell polarisation as a measure of the maturation of the immune response

Mediators of Inflammation ◽

10.1080/0929350310001619744 ◽

2003 ◽

Vol 12 (5) ◽

pp. 285-292 ◽

Cited By ~ 4

Author(s):

Scott B. Cameron ◽

Ellen H. Stolte ◽

Anthony W. Chow ◽

Huub F. J. Savelkoul

Keyword(s):

Immune Response ◽

T Cells ◽

Intracellular Cytokine Staining ◽

T Helper Cell ◽

Helper Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Intracellular Cytokine ◽

T Helper

Background:T helper cell polarisation is important under chronic immune stimulatory conditions and drives the type of the evolving immune response. Mice treated with superantigensin vivodisplay strong effects on Thsubset differentiation. The aim of the study was to detect the intrinsic capacity of T cells to polarise under variousex vivoconditions.Methods:Purified CD4+T cells obtained from superantigen-treated mice were cultured under Thpolarising conditionsin vitro. By combining intracellular cytokine staining and subsequent flow cytometric analysis with quantitative cytokine measurements in culture supernatants by enzyme-linked immunosorbent assay (ELISA), the differential Thpolarising capacity of the treatment can be detected in a qualitative and quantitative manner.Results and conclusions:BALB/c mice were shown to be biased to develop strong Th2 polarised immune responses using Th0 stimulation of purified CD4+T cells from phosphate-buffered saline-treated mice. Nevertheless, our analysis methodology convincingly showed that even in these mice, Toxic Shock Syndrome Toxin-1 treatmentin vivoresulted in a significantly stronger Th1 polarising effect than control treatment. Our results indicate that populations of Thcells can be assessed individually for their differential Th1 or Th2 maturation capacityin vivoby analysing robustin vitropolarisation cultures combined with intracellular cytokine staining and ELISA.

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Low albumin levels are associated with poorer outcomes in a case series of COVID-19 patients in Spain: a retrospective cohort study

10.1101/2020.05.07.20094987 ◽

2020 ◽

Cited By ~ 2

Author(s):

Roberto de la Rica ◽

Marcio Borges ◽

María Aranda ◽

Alberto del Castillo ◽

Antonia Socias ◽

...

Keyword(s):

Disease Severity ◽

Critically Ill ◽

Critically Ill Patients ◽

Case Series ◽

Hospitalized Patients ◽

University Hospital ◽

Limited Information ◽

Icu Patients ◽

Epidemiological Features ◽

Initial Symptoms

ABSTRACTOBJECTIVETo describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior hospitalization, in one of the main hospitals in The Balearic Islands health care system.DESIGNRetrospective observational studySETTINGSon Llatzer University Hospital in Palma de Mallorca (Spain)PARTICIPANTSAmong a cohort of 52 hospitalized patients as of 31 March 2020, 48 with complete demographic information and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test, were analyzed. Data were collected between March 15th, 2020, and March 31th 2020, inclusive of these dates.MAIN OUTCOMESClinical, vital signs and routine laboratory outcomes at the time of hospitalization, including symptoms reported prior to hospitalization. Demographics and baseline comorbidities were also collected. Mortality was reported at the end of the study.RESULTS48 patients (27 non-ICU and 21 ICU) resident in Mallorca, Spain (mean age, 66 years, [range, 33-88 years]; 67% males) with positive SARS-CoV-2 infection were analyzed. There were no differences in age or sex among groups (p >.05). Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). The majority of patients in this case series were hospitalized because of low SpO2 (SpO2 below 90%) and presentation of bilateral pneumonia (94%) at triage. ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs 61%, p = .022). Acute respiratory syndrome (ARDS) was presented in 100% of the ICU-patients. All the patients included in the study required oxygen therapy. ICU-patients had lymphopenia as well as hypoalbuminemia. Inflammatory markers such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < .001).Lower albumin levels were associated with poor prognosis measured as longer hospital length (r= −0.472, p <.001) and mortality (r= −0.424, p=.003). Interestingly we also found, that MCV was lower among of those patients who died (p=.0002). As of April 28, 2020, 10 patients (8 ICU and 2 non-ICU) had died (21% mortality) and while 100% of the non-ICU patients had been discharged, 33% of ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward).CONCLUSIONCritically ill patients with COVID-19 present lymphopenia, hypoalbuminemia as well high levels of inflammation. Lower levels of albumin were associated with poorer outcomes in COVID-19 patients. Albumin might be of importance because of its association with disease severity in patients infected with SARS-CoV-2.WHAT IS ALREADY KNOWN IN THIS TOPICSpain has been hit particularly hard by the pandemic. By the time that this manuscript was written more than 25.000 deaths related to COVID-19 have been confirmed. There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for COVID-19. Also, it is important to know the characteristics of the hospitalized patients who become critically illWHAT THIS STUDY ADDSThis small case series provides the first steps towards a comprehensive clinical characterization of severe and critical COVID-19 adult patients in Spain. The overall mortality in our patients was 21%. To our knowledge this is the first report with reporting these features in Spain. At triage the majority of patients had lower SpO2 (<90%) and bilateral pneumonia. The most common comorbidities were hypertension (70%), dyslipidemia (62%) and cardiovascular disease (30%). Critically ill patients present hypoalbuminemia and lymphopenia, as well as higher levels of inflammation. Albumin might be of importance because of its association with disease severity and mortality in patients infected with SARS-CoV-2.

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Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I)

Critical Care Medicine ◽

10.1097/ccm.0000000000002737 ◽

2017 ◽

Vol 45 (12) ◽

pp. 2078-2088 ◽

Cited By ~ 95

Author(s):

Djillali Annane ◽

Stephen M. Pastores ◽

Bram Rochwerg ◽

Wiebke Arlt ◽

Robert A. Balk ◽

...

Keyword(s):

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Diagnosis And Management ◽

Corticosteroid Insufficiency

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Association Effects Of Comorbid Versus Uncomorbid Diabetes And Blood Glucose Concentrations On Short-term Outcomes In Patients With Critical Illness: A Real-World Study Based On Propensity Score Analyses

10.21203/rs.3.rs-44274/v1 ◽

2020 ◽

Author(s):

Shan Lin ◽

Shanhui Ge ◽

Wanmei He ◽

Mian Zeng

Keyword(s):

Critical Illness ◽

Glycemic Control ◽

Critically Ill ◽

Critically Ill Patients ◽

Cox Model ◽

Inverse Probability Weighting ◽

Probability Weighting ◽

Optimal Range ◽

Short Term ◽

Inverse Probability

Abstract Background: The effects of combined diabetes and glycemic control strategies on the short-term prognosis in patients with a critical illness are currently ambiguous. The objectives of our study were to determine whether comorbid diabetes affects short-term prognosis and the optimal range of glycemic control in critically ill patients.Methods: We performed this study with the critical care database. The primary outcomes were 28-day mortality in critically ill patients with comorbid diabetes and the optimal range of glycemic control. Association of comorbid diabetes with 28-day mortality was assessed by multivariable Cox regression model with inverse probability weighting. Smooth curves were applied to fit the association for glucose and 28-day mortality.Results: Of the 33,680 patients enrolled in the study, 8,701 (25.83%) had diabetic comorbidity. Cox model with inverse probability weighting showed that the 28-day mortality rate was reduced by 29% (HR=0.71, 95% CI 0.67-0.76) in the group with diabetes in comparison to the group without diabetes. The E value of 2.17 indicated robustness to unmeasured confounders. The effect of the association between comorbid diabetes and 28-day mortality was generally in line for all subgroup variables, significant interactions were observed for glucose on first day, admission type, and use of insulin or not (Interaction P <0.05). A V-shaped relationship was observed between glucose concentrations and 28-day mortality in patients without diabetes, with the lowest 28-day mortality corresponding to the glucose level was 101.75 mg/dl (95% CI 94.64-105.80 mg/dl); whereas in patients with comorbid diabetes, the effect of glucose concentration on 28-day mortality was structurally softer than in those with uncomorbid diabetes. Lastly, of all patients, hyperglycemia had the greatest deleterious effect on patients admitted to CSRU.Conclusions: Our study further confirmed the protective effect of comorbid diabetes on the short-term prognosis of critically ill patients, resulting in an approximately 29% reduction in 28-day mortality. Besides, we also demonstrated the personalized glycemic control strategy for critically ill patients. Lastly, clinicians should be aware of the occurrence and the prompt management of hyperglycemia in critically ill patients admitted to the CSRU.

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