Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease)

Chen, Wei Sheng; Yin, Yuzhi; Chan, Eunice C.; Terai, Kaoru; Long, Lauren; Myers, Timothy G.; Dudek, Arkadiusz Z.; Druey, Kirk M.

doi:10.1002/jlb.5a0817-324r

Cited by 32 publications

(38 citation statements)

References 35 publications

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“…So far, a predictive value of individual MR-proADM measurements has been found in ischemic and congestive heart disease [33][34], after cardiac surgery [8], in sepsis [35], in pneumoniae [13,36] and in other ARDS-related conditions [37]. Despite the low number of cases affected by serious viral pathologies included in previous studies [14,38], we believe that a similar effect can be hypothesized in the context of cohorts of COVID-19 patients. It is hence possible, as already proposed in the context of sepsis [16], that the use of this biomarker could help either to anticipate the escalation of therapy in patients at risk of treatment failure or to suggest a faster discharge of patients with a low risk of unfavorable evolution.…”

Section: Discussionmentioning

confidence: 62%

Effectiveness of Mid-Regional Pro-Adrenomedullin (MR-proADM) as Prognostic Marker in COVID-19 Critically Ill Patients: an Observational Prospective Study

Montrucchio

Sales

Rumbolo

et al. 2020

Preprint

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Background Due to the lack of validated biomarkers to predict disease progression and mortality in COVID-19 ICU-patients, we tested the effectiveness of mid-regional pro-adrenomedullin (MR-proADM) in comparison to C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH) in predicting outcome.Methods All consecutive COVID-19 adult patients admitted between March and June 2020 to the ICU of the ‘Città della Salute e della Scienza’ hospital in Turin (Italy) were enrolled. MR-proADM, clinical and routine laboratory test were measured within 48 hours from ICU admission, on day 3, 7 and 14. Survival curves difference with MR-proADM cut-off set to 1.8 nmol/L were tested using log-rank test. Predictive ability was compared using area under the curve and 95% confidence interval of different receiver-operating characteristics curves. Potential confounding effects were tested using a logistic regression model. Results Fifty-seven patients were enrolled. ICU and overall mortality were 54.4%. Within the first 24 hours, lymphocytopenia was present in 86%; increased D-dimer and CRP levels were found in 84.2% and 87.7% respectively, while PCT values higher than 0.5 μg/L were observed in 47.4%. MR-proADM, CRP and LDH were significantly different between surviving and non-surviving patients and over time, while PCT, D-dimer and NT-pro-BNP did not show any difference between the groups and over time; lymphocytes count was different between surviving and non-surviving patients only.MR-proADM was higher in dying patients (2.65+2.33vs1.18+0.47, p=0.0001) and a higher mortality characterized patients with MR-proADM exceeding 1.8 nmol/L (p=0.0157). The logistic regression model adjusted for age, gender, cardiovascular disease, diabetes mellitus and PCT values confirmed an odds ratio equal to 10.274 (95%CI 1.970-53.578) (p=0.0057) for MR-proADM higher than 1.8 nmol/L and equal to 22.206 (95%CI 1.56-316.960) (p=0.0223) for cardiovascular disease. Overall, MR-proADM was found to have the best predictive ability (AUC=0.846 – 95%CI 0.779-0.899).Conclusions In COVID-19 ICU-patients, MR-proADM seems able to provide a more precise stratification of disease severity and mortality risk than other biomarkers. Repeated MR-proADM measurement may support a rapid and effective decision-making. Further studies are needed to better explain the mechanisms responsible of the increase in MR-proADM observed in COVID-19 patients.

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Section: Discussionmentioning

confidence: 62%

Effectiveness of Mid-Regional Pro-Adrenomedullin (MR-proADM) as Prognostic Marker in COVID-19 Critically Ill Patients: an Observational Prospective Study

Montrucchio

Sales

Rumbolo

et al. 2020

Preprint

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“…In particular, they suggested that the cooperation of these vasoactive peptides might be necessary to counterbalance the vasodilatory activity of bradykinin and to terminate the attacks. Recently, Xie and collegaues (37), confirmed these data in acute Systemic Capillary Leak Syndrome (SCLS), characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues.…”

Section: Discussionmentioning

confidence: 80%

“…ADM could act as an endogenous immunomodulatory factor, with predominant anti-inflammatory effects (35). It is produced in many types of tissue, but the endothelium (36) and the monocytes (37) are the principal source, in particular in response to proinflammatory cytokines (38). ADM reduces endothelial hyper-permeability and is an apoptosis survival factor (39).…”

Section: Discussionmentioning

confidence: 99%

A transcriptomics study of hereditary angioedema attacks

Castellano¹,

Divella²,

Sallustio

et al. 2018

Journal of Allergy and Clinical Immunology

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“…Hence a key aim of this study focused on the comparison of biomarker and clinical score performance according to the location of initial infection development, following activation of an in-hospital sepsis code. Based on recent publications, the use of MR-proADM was of especial interest within our investigation, with previous studies showing elevated concentrations resulting from increased levels of microcirculatory and endothelial damage, resulting in the early stages of subsequent organ dysfunction [26][27][28][29]. The use of a biomarker to identify developing microcirculatory damage may contribute significant information following the activation of a local, in-hospital sepsis code.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers and clinical scores to aid the identification of disease severity and intensive care requirement following activation of an in-hospital sepsis code

Baldirà

Ruiz‐Rodríguez

Wilson

et al. 2020

Ann. Intensive Care

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Background: Few validated biomarker or clinical score combinations exist which can discriminate between cases of infection and other non-infectious conditions following activation of an in-hospital sepsis code, as well as provide an accurate severity assessment of the corresponding host response. This study aimed to identify suitable blood biomarker (MR-proADM, PCT, CRP and lactate) or clinical score (SOFA and APACHE II) combinations to address this unmet clinical need. Methods: A prospective, observational study of patients activating the Vall d'Hebron University Hospital sepsis code (ISC) within the emergency department (ED), hospital wards and intensive care unit (ICU). Area under the receiver operating characteristic (AUROC) curves, logistic and Cox regression analysis were used to assess performance. Results: 148 patients fulfilled the Vall d'Hebron ISC criteria, of which 130 (87.8%) were retrospectively found to have a confirmed diagnosis of infection. Both PCT and MR-proADM had a moderate-to-high performance in discriminating between infected and non-infected patients following ISC activation, although the optimal PCT cutoff varied significantly across departments. Similarly, MR-proADM and SOFA performed well in predicting 28-and 90-day mortality within the total infected patient population, as well as within patients presenting with a community-acquired infection or following a medical emergency or prior surgical procedure. Importantly, MR-proADM also showed a high association with the requirement for ICU admission after ED presentation [OR (95% CI) 8.18 (1.75-28.33)] or during treatment on the ward [OR (95% CI) 3.64 (1.43-9.29)], although the predictive performance of all biomarkers and clinical scores diminished between both settings. Conclusions: Results suggest that the individual use of PCT and MR-proADM might help to accurately identify patients with infection and assess the overall severity of the host response, respectively. In addition, the use of MR-proADM could accurately identify patients requiring admission onto the ICU, irrespective of whether patients

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Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease)

Abstract: Since ADM has established hypotensive effects, differentiating between these dual actions of ADM is crucial for therapeutic applications aimed at more common diseases associated with increased ADM levels.

Cited by 32 publications

References 35 publications

Effectiveness of Mid-Regional Pro-Adrenomedullin (MR-proADM) as Prognostic Marker in COVID-19 Critically Ill Patients: an Observational Prospective Study

Effectiveness of Mid-Regional Pro-Adrenomedullin (MR-proADM) as Prognostic Marker in COVID-19 Critically Ill Patients: an Observational Prospective Study

A transcriptomics study of hereditary angioedema attacks

Biomarkers and clinical scores to aid the identification of disease severity and intensive care requirement following activation of an in-hospital sepsis code

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