ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock

Aletti, Federico; Conti, Costanza; Ferrario, Manuela; Ribas, Vicent; Pinto, Bernardo Bollen; Herpain, Antoine; Post, Emiel Hendrik; Medina, Eduardo Romay; Barlassina, Cristina; Oliveira, Eliandre de; Pastorelli, Roberta; Tedeschi, Gioacchino; Ristagno, Giuseppe; Taccone, Fabio Silvio; Schmid‐Schönbein, Geert W.; Ferrer, Ricard; Backer, Daniel De; Bendjelid, Karim; Baselli, Giuseppe

doi:10.1186/s13049-016-0197-4

Cited by 21 publications

(30 citation statements)

References 39 publications

(24 reference statements)

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“…This study is part of the prospective observational trial 'ShockOmics' (ClinicalTrials.gov Identifier NCT02141607) 11 and was approved by: the Geneva Regional Research Ethics Committee (study number 14-041); the Ethical committee of Hôpital Erasme-Universit e Libre De Bruxelles (study number P2014/171), and the Mutua Terrassa Hospital Institutional Review Board (study number EO/1407).…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…Patients at high risk of death within the first 24 h after admission, systemic immunosuppression, haematological diseases, metastatic cancer, pre-existing dialysis, decompensated cirrhosis, or who received more than four units of red blood cells or any fresh frozen plasma were excluded. 11 Given the stringency of the exclusion criteria, the thresholds on SOFA and lactate were chosen to include severe enough septic shock patients, while ensuring adequate patient enrolment and recruitment rate.…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…A convenience sampled cohort of patients with sepsis (infection with inflammatory response and one organ dysfunction), 11,12 but not in shock, was included as control. Healthy donors were enrolled at Mutua Terrassa Hospital, Terrassa, Spain for an additional non-sepsis control.…”

Section: Study Design and Participantsmentioning

confidence: 99%

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Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality

Bauzá‐Martinez

Aletti

Pinto

et al. 2018

British Journal of Anaesthesia

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Background: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome. Methods: Intensive care patients with septic shock (n¼29) or sepsis (n¼6) and non-hospitalised subjects (n¼9) were recruited as part of the prospective observational trial 'ShockOmics' (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects. Results: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n¼6) than in survivors (n¼23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation. Conclusions: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients. Clinical trial registration: NCT02141607.

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Section: Study Design and Participantsmentioning

confidence: 99%

Section: Study Design and Participantsmentioning

confidence: 99%

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Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality

Bauzá‐Martinez

Aletti

Pinto

et al. 2018

British Journal of Anaesthesia

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“…The complete database integrates blood samples and hemodynamic recordings from 146 septic shock and cardiogenic shock patients, and from septic patients, obtained in the 147 ICU [34]. Clinical data and blood samples were collected for analysis at: 1) T1 < 16 h 148 from T0; 2) T2 = 48 h after T0; 3) T3 = day 7 or before discharge or before 149 discontinuation of therapy in case of fatal outcome [35]. Since a lot of patients either 150 died or were discharged during the study, the dataset has a lot of missing values at later 151 time-steps (especially at T3).…”

mentioning

confidence: 99%

Feature selection for the accurate prediction of septic and cardiogenic shock ICU mortality in the acute phase

Aushev

Ripoll

Vellido

et al. 2018

Preprint

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Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission.1 Shock (or circulatory shock) is a life-threatening medical condition that requires 2 immediate treatment. It is prevalent in the Intensive Care Unit (ICU) and a major 3 concern in Critical Care in general. This condition occurs when the organs and tissues 4 of the body do not receive enough blood and, as a result, cells see their oxygen and 5 nutrients supply restricted so that organs become damaged. Hypotension, tissue 6 hypoperfusion and hyperlactatemia are amongst the most common symptoms [28]. The 7 outcome of an individual case depends on the stage of shock, the underlying condition 8 and the general medical state of the patient [28]. 9Four types of shock are commonly defined: hypovolaemic shock (e.g. hemorrhagic 10 shock), cardiogenic shock, distributive shock (e.g. septic shock) and obstructive shock. 11 The mortality rate of the condition remains very high and depends on its type. It is 12 quantified at 30% for septic shock (according to the new definition of such condition [29]) 13 and between 35.9% and 64.7% for in-hospital mortality in patients with cardiogenic 14 shock (depending on the stage, [30]). Usually, shock is treated in the ICU, where it is 15 carefully monitored. As a result, large amounts of data are produced for each patient. 16 Machine Learning (ML) techniques can help find a list of attributes to predict the 17 outcome of shock patients from clinical data (i.e. data routinely monitored in the ICU). 18 However, there is a large amount of attributes that characterize each patient, ranging 19 from base pathology information, to lab procedures or hemodynamic data and 20 treatment, to name a few. As a result, data are likely to be very high di...

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“…This stimulation from the betaadrenergic effects can bring out the unwanted consequences, including an increase in the cellular metabolism and immunosuppressive effects [5]. Besides, dopamine arouses dopaminergic receptors, which leads to a uniformly bigger rise in renal and splanchnic perfusion, which can expedite lung edema tenacity.…”

Section: Introductionmentioning

confidence: 99%

Comparing the Use of Dopamine and Norepinephrine in Shock Treatment

Jalalyazdi¹,

Parvizian²,

Abyaneh³

2016

Cardiovasc Pharm Open Access

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IntroductionCardiovascular shock refers to a critical condition that occurs when a patient's heart suddenly fails to pump blood as required by the body. This rare but fatal condition is mostly caused by heart attack and is linked to high death rate [1,2]. The fluid administration that forms the firstline of therapeutic strategy does not offer enough stability for the condition of the patient, and the adrenergic agents are regularly needed to correct hypertension [3]. Among the most frequently used agents are dopamine and norepinephrine. Both dopamine and norepinephrine affect the alpha-adrenergic and beta-adrenergic receptors, though to varying degrees. The effects of alpha-adrenergic receptors lead to increased vascular tone. However, it could decrease the cardiac output as well as the regional flow of blood, particularly in cutaneous, renal, and splanchnic beds [4].On the other hand, beta-adrenergic effects assist in the maintenance of blood flow through inotropic and chronotropic effects as well as increasing splanchnic perfusion. This stimulation from the betaadrenergic effects can bring out the unwanted consequences, including an increase in the cellular metabolism and immunosuppressive effects [5]. Besides, dopamine arouses dopaminergic receptors, which leads to a uniformly bigger rise in renal and splanchnic perfusion, which can expedite lung edema tenacity. Conversely, the stimulation caused by dopamine could lead to negative immunological effects by modifying hypothalamic-pituitary function, leading to a patent drop of prolactin as well as the level of hormones [6].Hypothetically, norepinephrine and dopamine have varying effects in the splanchnic, kidney and pituitary axis, though the medical consequences of the implied differences are not certain [7]. Experts have recommended that any of the two compounds may be chosen first and applied as a vasopressor in patients suffering from shock. Studies have Comparing the Use of Dopamine and Norepinephrine in Shock Treatment AbstractBackground: The vasopressor agents, such as norepinephrine and dopamine have been endorsed as the standard choice for shock treatment. However, there is controversy regarding the use of vasopressor agents for shock treatment. Considering the use of norepinephrine over dopamine, the present study aimed at assessing the reasons for the reduced death rate among the patients who were in shock.

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ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock

Cited by 21 publications

References 39 publications

Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality

Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality

Feature selection for the accurate prediction of septic and cardiogenic shock ICU mortality in the acute phase

Comparing the Use of Dopamine and Norepinephrine in Shock Treatment

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