Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage.

Synergistic effect of myocardial injury and mid-regional proAdrenomedullin elevation in determining clinical outcomes of SARS-CoV-2 patients.

Objective: Coronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients. Materials and methods: All patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS). Results: A total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87-21.30; p < 0.001). Conclusion: The study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.

Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit.

Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer's instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.