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RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients-A prospective single center study.

ABSTRACT: BACKGROUND:Management of cardiac arrest patients includes active body temperature control and strict prevention of fever to avoid further neurological damage. Cold-shock proteins RNA-binding motif 3 (RBM3) and cold inducible RNA-binding protein (CIRP) expressions are induced in vitro in response to hypothermia and play a key role in hypothermia-induced neuroprotection. OBJECTIVE:To measure gene expressions of RBM3, CIRP, and inflammatory biomarkers in whole blood samples from targeted temperature management (TTM)-treated post-cardiac arrest patients for the potential application as clinical biomarkers for the efficacy of TTM treatment. METHODS:A prospective single center trial with the inclusion of 22 cardiac arrest patients who were treated with TTM (33°C for 24 hours) after ROSC was performed. RBM3, CIRP, interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and inducible nitric oxide synthase (iNOS) mRNA expressions were quantified by RT-qPCR. Serum RBM3 protein concentration was quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS:RBM3 mRNA expression was significantly induced in post-cardiac arrest patients in response to TTM. RBM3 mRNA was increased 2.2-fold compared to before TTM. A similar expression kinetic of 1.4-fold increase was observed for CIRP mRNA, but did not reached significancy. Serum RBM3 protein was not increased in response to TTM. IL-6 and MCP-1 expression peaked after ROSC and then significantly decreased. iNOS expression was significantly increased 24h after return of spontaneous circulation (ROSC) and TTM. CONCLUSIONS:RBM3 is temperature regulated in patients treated with TTM after CA and ROSC. RBM3 is a possible biomarker candidate to ensure the efficacy of TTM treatment in post-cardiac arrest patients and its pharmacological induction could be a potential future intervention strategy that warrants further research.

SUBMITTER: Rosenthal LM

PROVIDER: S-EPMC6903712 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients-A prospective single center study.

Rosenthal Lisa-Maria LM Leithner Christoph C Tong Giang G Streitberger Kaspar Josche KJ Krech Jana J Storm Christian C Schmitt Katharina Rose Luise KRL

PloS one 20191210 12

<h4>Background</h4>Management of cardiac arrest patients includes active body temperature control and strict prevention of fever to avoid further neurological damage. Cold-shock proteins RNA-binding motif 3 (RBM3) and cold inducible RNA-binding protein (CIRP) expressions are induced in vitro in response to hypothermia and play a key role in hypothermia-induced neuroprotection.<h4>Objective</h4>To measure gene expressions of RBM3, CIRP, and inflammatory biomarkers in whole blood samples from targ ...[more]

PMID: 31821351

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Project description:BackgroundSedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians. We evaluated differences in patient-level sedation and analgesia dosing in an international multicenter TTM trial to better characterize current practice and clinically important outcomes.MethodsA total 950 patients in the international TTM trial were randomly assigned to a TTM of 33 °C or 36 °C after resuscitation from cardiac arrest in 36 intensive care units. We recorded cumulative doses of sedative and analgesic drugs at 12, 24, and 48 h and normalized to midazolam and fentanyl equivalents. We compared number of medications used, dosing, and titration among centers by using multivariable models, including common severity of illness factors. We also compared dosing with time to awakening, incidence of clinical seizures, and survival.ResultsA total of 614 patients at 18 centers were analyzed. Propofol (70%) and fentanyl (51%) were most frequently used. The average dosages of midazolam and fentanyl equivalents were 0.13 (0.07, 0.22) mg/kg/h and 1.16 (0.49, 1.81) µg/kg/h, respectively. There were significant differences in number of medications (p < 0.001), average dosages (p < 0.001), and titration at all time points between centers (p < 0.001), and the outcomes of patients in these centers were associated with all parameters described in the multivariate analysis, except for a difference in the titration of sedatives between 12 and 24 h (p = 0.40). There were associations between higher dosing at 48 h (p = 0.003, odds ratio [OR] 1.75) and increased titration of analgesics between 24 and 48 h (p = 0.005, OR 4.89) with awakening after 5 days, increased titration of sedatives between 24 and 48 h with awakening after 5 days (p < 0.001, OR > 100), and increased titration of sedatives between 24 and 48 h with a higher incidence of clinical seizures in the multivariate analysis (p = 0.04, OR 240). There were also significant associations between decreased titration of analgesics and survival at 6 months in the multivariate analysis (p = 0.048).ConclusionsThere is significant variation in choice of drug, dosing, and titration when providing sedation and analgesics between centers. Sedation and analgesia dosing and titration were associated with delayed awakening, incidence of clinical seizures, and survival, but the causal relation of these findings cannot be proven.

Project description:BackgroundPrognostication after cardiac arrest (CA) needs a multimodal approach, but the optimal method is not known. We tested the hypothesis that the combination of neuron-specific enolase (NSE) and neuroimaging could improve outcome prediction after CA treated with targeted temperature management (TTM).MethodsA retrospective observational cohort study was performed on patients who underwent at least one NSE measurement between 48 and 72 hr; received both a brain computed tomography (CT) scan within 24 hr and diffusion-weighted magnetic resonance imaging (DW-MRI) within 7 days after return of spontaneous circulation (ROSC); and were treated with TTM after out-of-hospital CA between 2009 and 2017 at the Seoul St. Mary's Hospital in Korea. The primary outcome was a poor neurological outcome at 6 months after CA, defined as a cerebral performance category of 3-5.ResultsA total of 109 subjects underwent all three tests and were ultimately included in this study. Thirty-four subjects (31.2%) experienced good neurological outcomes at 6 months after CA. The gray matter to white matter attenuation ratio (GWR) was weakly correlated with the mean apparent diffusion coefficient (ADC), PV400 and NSE (Spearman's rho: 0.359, -0.362 and -0.263, respectively). NSE was strongly correlated with the mean ADC and PV400 (Spearman's rho: -0.623 and 0.666, respectively). Serum NSE had the highest predictive value among the single parameters (area under the curve (AUC) 0.912, sensitivity 70.7% for maintaining 100% specificity). The combination of a DWI parameter (mean ADC or PV400) and NSE had better prognostic performance than the combination of the CT parameter (GWR) and NSE. The addition of the GWR to a DWI parameter and NSE did not improve the prediction of neurological outcomes.ConclusionThe GWR (≤ 24 hr) is weakly correlated with the mean ADC (≤ 7 days) and NSE (highest between 48 and 72 hr). The combination of a DWI parameter and NSE has better prognostic performance than the combination of the GWR and NSE. The addition of the GWR to a DWI parameter and NSE does not improve the prediction of neurological outcomes after CA treatment with TTM.

Project description:BackgroundDefinition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.MethodsSerum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).ResultsOf 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log2(FC) between 0.33 and 0.88), one reduced protein (log2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest.ConclusionsSerum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.

Project description:Hyperglycemia is commonly observed in critically ill patients and postcardiac arrest patients, with higher glucose levels and variability associated with poorer outcomes. In this study, we aim to compare glucose control in diabetic and nondiabetic patients using glycated hemoglobin (HbA1c) levels, providing insights for better glucose management strategies. This retrospective observational study was conducted at Seoul St. Mary's Hospital from February 2009 to May 2022. Blood glucose levels were measured hourly for 48 h after return of spontaneous circulation (ROSC), and a glucose management protocol was followed to maintain arterial blood glucose levels between 140 and 180 mg/dL using short-acting insulin infusion. Patients were categorized into four groups based on diabetes status and glycemic control. The primary outcomes assessed were neurological outcome and mortality at 6 months after cardiac arrest. Among the 332 included patients, 83 (25.0%) had a previous diabetes diagnosis, and 114 (34.3%) had an HbA1c of 6.0% or higher. At least one hyperglycemic episode was observed in 314 patients (94.6%) and hypoglycemia was found in 63 patients (19.0%) during 48 h. After the categorization, unrecognized diabetes was noticed in 51 patients with median HbA1c of 6.3% (interquartile range [IQR] 6.1-6.6). Patients with inadequate diabetes control had the highest initial HbA1c level (7.0%, IQR 6.5-7.8) and admission glucose (314 mg/dL, IQR 257-424). Median time to target glucose in controlled diabetes was significantly shorter with the slowest glucose reducing rate. The total insulin dose required to reach the target glucose level and cumulative insulin requirement during 48 h were different among the categories (p <0.001). Poor neurological outcomes and mortality were more frequently observed in patients with diagnosed diabetes. Occurrence of a hypoglycemic episode during the 48 h after ROSC was independently associated with poor neurologic outcomes (odds ratio [OR] 3.505; 95% confidence interval [CI], 2.382-9.663). Surviving patients following cardiac arrest exhibited variations in glucose hemodynamics and outcomes according to the categories based on their preexisting diabetes status and glycemic condition. Specifically, even experiencing a single episode of hypoglycemia during the acute phase could have an influence on unfavorable neurological outcomes. While the classification did not directly affect neurological outcomes, the present results indicate the need for a customized approach to glucose control based on these categories.

Dataset Information

RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients-A prospective single center study.

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RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients-A prospective single center study.

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