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Open accessJournal ArticleDOI: 10.1038/S41598-021-84478-1

MR-proADM as prognostic factor of outcome in COVID-19 patients.

04 Mar 2021-Scientific Reports (Springer Science and Business Media LLC)-Vol. 11, Iss: 1, pp 5121-5121
Abstract: Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893-11.413], together with increased neutrophil count (OR = 1.029 [1.011-1.049]) and WHO disease severity class (OR = 7.632 [5.871-19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771-0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728-0.987] and a specificity of 0.687 [95% Cl 0.587-0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.

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Topics: SOFA score (56%), Septic shock (51%), Odds ratio (51%) ... show more
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Open accessJournal ArticleDOI: 10.1016/J.JCRC.2021.07.017
Abstract: Purpose: We assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Methods: Biomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score. Results: In 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76–0.92), p < 0.001 and 0.79, (95% CI 0.69–0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12–14.84, p < 0.001 and HR 3.72, 95% CI 1.71–8.08, p 0.01). Conclusion: Baseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia. Trial registration: NEDERLANDS TRIAL REGISTER, NL8460.

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Topics: Prospective cohort study (52%), SOFA score (50%)

1 Citations


Open accessJournal ArticleDOI: 10.1080/14737159.2021.1902312
Abstract: INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. AREAS COVERED: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting. EXPERT OPINION: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.

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1 Citations



Open accessJournal ArticleDOI: 10.3390/BIOMEDICINES9081068
23 Aug 2021-Biomedicines
Abstract: Adrenomedullin (AM) is a bioactive peptide with various physiological functions, including vasodilation, angiogenesis, anti-inflammation, organ protection, and tissue repair. AM suppresses inflammatory cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function, mucosal epithelial repair, and immune function in the intestinal bacteria of animal models with intestinal inflammation. We have been promoting translational research to develop novel therapeutic agents for inflammatory bowel disease (IBD) using AM and have started clinical research for IBD patients since 2010. A multicenter clinical trial is currently underway in Japan for patients with refractory ulcerative colitis and Crohn's disease. Moreover, since current AM administration is limited to continuous intravenous infusion, the development of a subcutaneous formulation using long-acting AM is underway for outpatient treatment.

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Topics: Inflammatory bowel disease (61%), Intestinal mucosa (60%), Crohn's disease (56%) ... show more

Open accessJournal ArticleDOI: 10.3390/NU13114085
Andrea Da Porto1, Carlo Tascini1, Maddalena Peghin1, Emanuela Sozio1  +7 moreInstitutions (1)
15 Nov 2021-Nutrients
Abstract: Background: Little is known on the clinical relevance of the nutritional status and body composition of patients hospitalized with SARS-CoV-2 infection. The aim of our study was to assess the prevalence of malnutrition in patients with COVID-19 pneumonia using bioelectrical impedance vector analysis (BIVA), and to evaluate the relationship of their nutritional status with the severity and outcome of disease. Methods: Among 150 consecutive patients who were hospitalized with COVID-19 pneumonia, 37 (24.3%) were classified as malnourished by BIVA, and were followed-up for 60 days from admission. Outcome measures were differences in the need for invasive mechanical ventilation, in-hospital mortality, and the duration of hospital stay in survivors. Results: During 60 days of follow-up, 10 (27%) malnourished patients and 13 (12%) non-malnourished patients required invasive mechanical ventilation (p = 0.023), and 13 (35%) malnourished patients and 9 (8%) non-malnourished patients died (p < 0.001). The average duration of the hospital stay in survivors was longer in patients with malnutrition (18.2 ± 15.7 vs. 13.2 ± 14.8 days, p < 0.001). In survival analyses, mechanical ventilation free (log-rank 7.887, p = 0.050) and overall (log-rank 17.886, p < 0.001) survival were significantly longer in non-malnourished than malnourished patients. The Cox proportional ratio showed that malnutrition was associated with an increased risk of mechanical ventilation (HR 4.375, p = 0.004) and death (HR 4.478, p = 0.004) after adjusting for major confounders such as age, sex, and BMI. Conclusions: Malnutrition diagnosed with BIVA was associated with worse outcomes in hospitalized patients with COVID-19 pneumonia.

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Topics: Mechanical ventilation (52%), Pneumonia (50%)

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21 results found


Open accessJournal Article
01 Jan 2014-MSOR connections
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.

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Topics: R Programming Language (78%)

229,202 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2016.0287
23 Feb 2016-JAMA
Abstract: Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

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Topics: Sepsis Six (75%), Surviving Sepsis Campaign (73%), Septic shock (63%) ... show more

9,896 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30628-0
Puja Mehta1, Daniel F. McAuley2, Michael Brown3, Emilie Sanchez3  +3 moreInstitutions (5)
28 Mar 2020-The Lancet
Abstract: www.thelancet.com Published online March 13, 2020 https://doi.org/10.1016/S0140-6736(20)30628-0 1 Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/ However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events. A multicentre, randomised con trolled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19: consider cytokine storm syndromes and immunosuppression

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5,489 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.5394
28 Apr 2020-JAMA
Abstract: Importance In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2was greater than 50% in 89% of patients. The median Pao2/Fio2was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0];P = .94). Median Fio2was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%];P = .006), and median Pao2/Fio2was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22];P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68];P Conclusions and Relevance In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

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Topics: Intensive care (53%)

3,154 Citations


Open accessJournal ArticleDOI: 10.1172/JCI137244
Guang Chen, Di Wu, Wei Guo, Yong Cao  +16 moreInstitutions (1)
Abstract: BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

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2,445 Citations