Sleep and Wakefulness Evaluation in Critically Ill Patients. One Step Forward.
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ABSTRACT:
SUBMITTER: Georgopoulos D
PROVIDER: S-EPMC6515880 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
Sleep and Wakefulness Evaluation in Critically Ill Patients. One Step Forward.
Georgopoulos Dimitris D Vaporidi Katerina K
American journal of respiratory and critical care medicine 20190501 9
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Project description:A dysregulated response to systemic inflammation is a common pathophysiological feature of most conditions encountered in the intensive care unit (ICU). Recent evidence indicates that a dysregulated inflammatory response is involved in the pathogenesis of various ICU-related disorders associated with high mortality, including sepsis, acute respiratory distress syndrome, cerebral and myocardial ischemia, and acute kidney injury. Moreover, persistent or non-resolving inflammation may lead to the syndrome of persistent critical illness, characterized by acquired immunosuppression, catabolism and poor long-term functional outcomes. Despite decades of research, management of many disorders in the ICU is mostly supportive, and current therapeutic strategies often do not take into account the heterogeneity of the patient population, underlying chronic conditions, nor the individual state of the immune response. Fatty acid-derived lipid mediators are recognized as key players in the generation and resolution of inflammation, and their signature provides specific information on patients' inflammatory status and immune response. Lipidomics is increasingly recognized as a powerful tool to assess lipid metabolism and the interaction between metabolic changes and the immune system via profiling lipid mediators in clinical studies. Within the concept of precision medicine, understanding and characterizing the individual immune response may allow for better stratification of critically ill patients as well as identification of diagnostic and prognostic biomarkers. In this review, we provide an overview of the role of fatty acid-derived lipid mediators as endogenous regulators of the inflammatory, anti-inflammatory and pro-resolving response and future directions for use of clinical lipidomics to identify lipid mediators as diagnostic and prognostic markers in critical illness.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-28 | GSE197259 | GEO
Project description:The regulatory network of genes and molecules in sleep/wakefulness remains to be elucidated. Here we describe the methodology and workflow of the dominant screening of randomly mutagenized mice and discuss theoretical basis of forward genetics research for sleep in mice. Our high-throughput screening employs electroencephalogram (EEG) and electromyogram (EMG) to stage vigilance states into a wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS). Based on their near-identical sleep/wake behavior, C57BL/6J (B6J) and C57BL/6N (B6N) are chosen as mutagenized and counter strains, respectively. The total time spent in the wake and NREMS, as well as the REMS episode duration, shows sufficient reproducibility with small coefficients of variance, indicating that these parameters are most suitable for quantitative phenotype-driven screening. Coarse linkage analysis of the quantitative trait, combined with whole-exome sequencing, can identify the gene mutation associated with sleep abnormality. Our simulations calculate the achievable LOD score as a function of the phenotype strength and the numbers of mice examined. A pedigree showing a mild decrease in total wake time resulting from a heterozygous point mutation in the Cacna1a gene is described as an example.
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Project description:Objective: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill ICU patients positive for COVID19 vs. those negative for COVID19 to better understand the COVID19 associated host response. Design: Transcriptome profiling of buffy coat cells via ribonucleic acid sequencing (RNAseq) at the time of admission to the ICU. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Interventions: None. Measurement and Main Results: Age- and sex-matched ICU patients that were either COVID19+ (PCR positive, 2 genes) or COVID19- (PCR negative) were enrolled. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia compared to COVID19- patients. Further, the mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signaling, and protein SUMOylation/ubiquitination. Conclusions: COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients. Identification of this profile provides guidance for future targeted studies exploring novel prognostic/therapeutic aspects of COVID19.
2020-10-01 | GSE154998 | GEO
Project description:Protein binding of valproate is variable in ICU patients, and the total valproate concentration does not predict the free valproate concentration, even when correcting for albumin. We sought to quantify valproate free concentration among ICU patients, identify risk factors associated with an increasing free valproate concentration, and evaluate the association between free valproate concentration with potential adverse drug effect.DesignRetrospective multicenter cohort study.SettingTwo academic medical centers.PatientsPatients greater than or equal to 18 years of age with concomitant free and total valproate concentrations collected in the ICU.InterventionsNone.Measurements and main resultsTwo-hundred fifty-six patients were included in the study, with a median age of 56 years (42-70) and 65% of patients were male. The median total valproate concentration was 53 µg/mL (38-70 µg/mL), the free valproate concentration was 12 µg/mL (7-20 µg/mL), and the free fraction was 23.6% (17.0-33.9%). Therapeutic discordance between the free and total valproate concentration occurred in 70% of patients. On multivariable analysis, increased free valproate concentration was associated with higher total valproate concentration (per 5 µg/mL increase, increase 1.72 µg/mL, 95% CI, 1.48-1.96) and lower serum albumin (per 1 g/dL decrease, increase 4.60 µg/mL, 95% CI, 2.71-6.49). There was no association between free valproate concentration and adverse effects.ConclusionsThe valproate total and free concentration was discordant in the majority of patients (70%). Increased valproate free concentration was associated with hypoalbuminemia and total valproate concentration. Clinical decisions based on total valproate concentration may be incorrect for many ICU patients. Prospective, controlled studies are needed to confirm these findings and their clinical relevance.
| S-EPMC10631734 | biostudies-literature
Project description:IntroductionIn times of short health care budgets, reimbursement for self-monitoring of blood glucose (SMBG) in diabetes patients without insulin treatment is subject to debate. The Structured Testing Program (STeP) trial found a positive correlation of test frequency and improved hemoglobin A1c (HbA1c) levels in poorly controlled type 2 diabetes patients not treated with insulin.MethodsA structured literature search for other clinical studies reporting on SMBG frequency was performed.ResultsThere is scarce evidence: three trials, including STeP, noted a significant and relevant correlation between testing frequency and improved HbA1c levels (FA effect), whereas two studies did not. The comparability between the identified studies is problematic.ConclusionFuture research should consider correlations between testing frequency and level of glycemic control. More emphasis should be placed on a structured approach to use SMBG and to address adherence to testing and therapy.
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Project description:Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients. Even patients who are normoglycemic can develop hyperglycemia in response to acute metabolic stress. An expanding body of literature describes the benefits of normalizing hyperglycemia with insulin therapy in hospitalized patients. As a result, both the American Diabetes Association and the American College of Endocrinology have developed guidelines for optimal control of hyperglycemia, specifically targeting critically ill, hospitalized patients. Conventional blood glucose values of 140-180 mg/dL are considered desirable and safely achievable in most patients. More aggressive control to <110 mg/dL remains controversial, but has shown benefits in certain patients, such as those in surgical intensive care. Intravenous infusion is often used for initial insulin administration, which can then be transitioned to subcutaneous insulin therapy in those patients who require continued insulin maintenance. This article reviews the data establishing the link between hyperglycemia and its risks of morbidity and mortality, and describes strategies that have proven effective in maintaining glycemic control in high-risk hospitalized patients.
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Project description:Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response to stress, but hyperglycemia is no longer considered a benign condition in patients with critical illnesses. Indeed, hyperglycemia can increase morbidity and mortality in critically ill patients. Correction of hyperglycemia may improve clinical outcomes. To date, a definite answer with regard to glucose management in general intensive care unit patients, including treatment thresholds and glucose target is undetermined. Meta-analyses of randomized controlled trials suggested no survival benefit of tight glycemic control and a significantly increased incidence of hypoglycemia. Studies have shown a J- or U-shaped relationship between average glucose values and mortality; maintaining glucose levels between 100 and 150 mg/dL was likely to be associated with the lowest mortality rates. Recent studies have shown glycemic control < 180 mg/dL is not inferior to near-normal glycemia in critically ill patients and is clearly safer. Glycemic variability is also an important aspect of glucose management in the critically ill patients. Higher glycemic variability may increase the mortality rate, even in patients with the same mean glucose level. Decreasing glucose variability is an important issue for glycemic control in critically ill patients. Continuous measurements with automatic closed-loop systems could be considered to ensure that blood glucose levels are controlled within a specific range and with minimal variability.
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