Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery.

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12-48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.

Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study.

OBJECTIVES: There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD). METHODS: In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55-65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV. RESULTS: Copeptin was associated with TBI (ß-0.0020, CI-0.0035- (-0.0005), p = 0.010) and aPWV (ß 0.023, CI 0.002-0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking. CONCLUSIONS: Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders. TRIAL REGISTRATION:  ClinicalTrials.gov identifier NCT010497377.

Usefulness of mid-regional proadrenomedullin levels in the resuscitation phase of severely burned patients and its utility in early sepsis detection.

INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM) reflects the adrenomedullin level, which has vasodilatory activity, decreases endothelial permeability, and downregulates proinflammatory cytokines. Sepsis diagnosis in these patients is difficult, and MR-proADM is a widely studied sepsis biomarker. This study evaluates MR-proADM levels during the resuscitation phase, considering the potential influence of haemodynamic changes and its usefulness for the early sepsis detection in burn patients. METHODS: A prospective observational study performed in the Critical Burn Unit. Demographic data, burn characteristics, comorbidities, prognostic/severity scales, and haemodynamic parameters were collected. The resuscitation protocol guided by diuresis, transpulmonary thermodilution, and lactate levels was followed. Blood samples were collected at various time points for biomarker measurement. Biomarker levels, including MR-proADM, C-reactive protein, and procalcitonin were measured during the resuscitation phase and septic episodes. RESULTS: Twenty-seven patients were included, with a mean age of 51 years, a mean total body surface area burn of 41.8%, a mean Abbreviated Burn Severity Index of 9.7, and a mean Baux score of 92. MR-proADM levels were elevated on admission (0.9 ± 0.5 nmol/l) and continued to increase slightly during the resuscitation phase (2.4 ± 2.2 nmol/l). Haemodynamic changes during resuscitation did not significantly affect MR-proADM levels. Twelve of the 27 patients developed sepsis, whose MR-proADM levels were significantly elevated on the day of clinical diagnosis (3.91 ± 2.99 nmol/l) and even the day before (2.57 ± 3.37). Higher MR-proADM levels were associated with greater severity as measured by the Sequential Organ Failure Assessment score. The mean MR-proadrenomedullin values during resuscitation in the patients who died was 3.51 ± 2.30 nmol/l, whereas in the survivors it was 1.28 ± 1.10 nmol/l (p = 0.0001). CONCLUSION: MR-proadrenomedullin values are elevated after thermal injury but are not affected by haemodynamic changes. During septic episodes in burn patients, MR-proADM rises early (the day before sepsis diagnosis). Higher levels of MR-proADM are associated with greater organ dysfunction and mortality.

Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Factors associated with hyperglycemia and low insulin levels in children undergoing cardiac surgery with cardiopulmonary bypass who received a single high dose of methylprednisolone

OBJECTIVES: Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model. METHODS: This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery. RESULTS: IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals. CONCLUSION: The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.