Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd-5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock.

Existing therapies against infectious diseases may only be effective in limited subpopulations during specific phases of diseases, incorporating theranostics, and there is a clear need to individualize different therapeutic approaches depending on the host. Influenza A virus infection evolves into a severe respiratory failure in some young adult patients, related to an exaggerated inflammatory response. Mortality rates remain high despite antiviral treatment and aggressive respiratory support. The influenza A virus (IAV) infection will induce a proinflammatory innate immune response through recognition of viral RNA by Toll-like receptor (TLR) 7 and retinoic acid-inducible gene 1 (RIG-I) molecules by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB route). Anti-inflammatory therapies focused on modulating this inflammatory response to "all patients" have not been satisfactory. Steroids should be avoided because they do not improve survival and promote superinfections. Since clinical judgment has often been proven inadequate, interest in the use of biomarkers to monitor host response and to assess severity and complications is growing. It is well known that, if used appropriately, these can be helpful tools to predict not only severity but also mortality. We need more biomarkers that predict host response: it is time to change lactate measurement to proteomics and transcriptomics. Theranostics describes an approach covering both diagnosis and coupled therapy. Death is usually a fatal complication of a dysregulated immune response more than the acute virulence of the infectious agent. Future research demonstrating the usefulness of adjunctive therapy in a subset of critically ill patients with IAV pneumonia is an unmet clinical need.

Early identification of severe viral pneumonia in influenza virus A (H1N1pdm09) patients is extremely important for prompt admission to the ICU. The objective is to evaluate the usefulness of MR-proadrenomedullin (MR-proADM) compared to C reactive protein (CRP), procalcitonin (PCT), and ferritin in the prognosis of influenza A pneumonia. This prospective, observational, multicenter study included one hundred thirteen patients with confirmed influenza virus A (H1N1pdm09) admitted to an Emergency Department and ICUs of six hospitals in Spain. Measurements and Main Results: one-hundred thirteen patients with confirmed influenza virus A (H1N1pdm09) were enrolled. Seventy-five subjects (mortality 29.3%) with severe pneumonia caused by influenza A H1N1pdm09 virus (H1N1vIPN) were compared with 38 controls (CG).The median MR-proADM levels at hospital admission were 1.2 nmol/L (IQR (0.8–2.6) vs. 0.5 nmol/L (IQR 0.2–0.9) in the CG (p = 0.01), and PCT levels were 0.43 μg/L (IQR 0.2–1.2) in the H1N1vIPN group and 0.1 μg/L (IQR 0.1–0.2) in the CG (p < 0.01). CRP levels at admission were 15.5 mg/dL(IQR 9.2–24.9) in H1N1vIPN and 8.6 mg/dL(IQR 3–17.3) in the CG (p < 0.01). Ferritin levels at admission were 558.1 ng/mL(IQR 180–1880) in H1N1vIPN and 167.7 ng/mL(IQR 34.8–292.9) in the CG (p < 0.01). A breakpoint for hospital admission of MR-proADM of 1.1 nmol/L showed a sensitivity of 55% and a specificity of 90% (AUC-ROC0.822). Non-survivors showed higher MR-proADM levels: median of 2.5 nmol/L vs. 0.9 nmol/L among survivors (p < 0.01). PCT, CRP, and ferritin levels also showed significant differences in predicting mortality. The MR-proADM AUC-ROC for mortality was 0.853 (p < 0.01). In a Cox proportional hazards model, MR-proADM levels > 1.2 nmol/L at hospital admission were significant predictive factors for ICU and 90-day mortality (HR: 1.3). Conclusions: the initial MR-proADM, ferritin, CRP, and PCT levels effectively determine adverse outcomes and risk of ICU admission and mortality in patients with influenza virus pneumonia. MR-proADM has the highest potency for survival prediction.

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