An Investigation of Metabolic Risk Factors and Gut Microbiota in Unexplained Syncope.

BACKGROUND: The pathogenesis of many syncopal episodes remains unexplained. Intestinal dysbiosis could be involved in the pathophysiological mechanisms of syncope due to its connection with the central nervous system via the microbiota-gut-brain axis. This pilot study aimed to explore the specific cardiometabolic risk factors and gut microbiota in unexplained syncope (US), compared to other types of syncope, to assess their similarity or verify their different origins. METHODS: We studied 86 participants with syncope, who were divided into four groups: an orthostatic syncope group (OH, n = 24), a neuromediated syncope group (NMS, n = 26), a cardiological syncope group (CS, n = 9), and an unexplained syncope group (US, n = 27). We evaluated the anthropometric, clinical, and metabolic characteristics of the four groups; the α- and ß-diversity; and the differences in the abundance of the microbial taxa. RESULTS: The US group had a lower incidence of systolic hypertension at the first visit and a lower frequency of patients with nocturnal hypertension than the CS group. Compared to the OH and NMS groups, the US group had a higher incidence of carotid plaques and greater carotid intima-media thickness, respectively. The microbiota differed significantly between the US and CS groups, but not between the US group and the OH or NMS group. CONCLUSIONS: We observed significant differences in the gut microbiota between CS and US. Future studies are necessary to evaluate the involvement of the gut microbiota in the complex pathogenesis of syncope and whether its analysis could support the interpretation of the pathophysiological mechasnisms underlying some episodes classifiable as US.

Correlation between Chest Computed Tomography Score and Laboratory Biomarkers in the Risk Stratification of COVID-19 Patients Admitted to the Emergency Department.

BACKGROUND: It has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). During the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. However, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. AIM: The main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. Moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. METHODS: Epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. RESULTS AND CONCLUSIONS: The accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources.

Vasovagal syncope: An overview of pathophysiological mechanisms.

Syncope is a short-term transient loss of consciousness, characterized by rapid onset and complete spontaneous recovery. According to the 2018 European Society of Cardiology guidelines, three different types of syncope have been identified. However, all forms of syncope share a common final pathophysiological event, global cerebral hypoperfusion, which results from the inability of the circulatory system to maintain blood pressure at the level required to efficiently supply blood to the brain. The vasovagal syncope (VVS) is the most common form of syncope. Although, VVS is generally harmless, its frequent occurrence can negatively affect quality of life and increase the risk of adverse events. The pathophysiological mechanisms underlying VVS remain obscure. The multifaceted nature of VVS presents a veritable challenge to understanding this condition and developing preventative strategies. Thus, the aim of this review was to discuss the factors contributing to the pathogenesis of VVS and provide guidance for future research.

Assessment of the Stability of Midregional Proadrenomedullin in Different Biological Matrices.

Midregional proadrenomedullin (MR-proADM) has been shown to play a key role in endothelial dysfunction, with increased levels helping to prevent early stages of organ dysfunction. Recent clinical evidence has demonstrated MR-proADM to be a helpful biomarker to identify disease severity in patients with sepsis as well as pneumonia. This biomarker is helpful at triage in emergency departments to assess risk level of patients. The aim of this study is to evaluate the stability of MR-proADM in different biological matrices. The results, obtained by Bland-Altman and scatter plot analyses, demonstrate that deviation of MR-proADM concentration in serum compared to EDTA plasma unequivocally shows that serum should not be used as a sample matrix. Instead, the excellent correlation of heparin plasma vs EDTA plasma samples shows that heparin plasma can be used without reservation in clinical routine and emergency samples.

Evaluation of Hepcidin Level in COVID-19 Patients Admitted to the Intensive Care Unit.

Coronavirus disease 2019 (COVID-19) presents a clinical spectrum that ranges from a mild condition to critical illness. Patients with critical illness present respiratory failure, septic shock and/or multi-organ failure induced by the so called "cytokine storm". Inflammatory cytokines affect iron metabolism, mainly inducing the synthesis of hepcidin, a hormone peptide not routinely measured. High levels of hepcidin have been associated with the severity of COVID-19. The aim of this study was to analyze, retrospectively, the levels of hepcidin in a group of COVID-19 patients admitted to the intensive care unit (ICU) of the Policlinico Tor Vergata of Rome, Italy. Thirty-eight patients from November 2020 to May 2021 were enrolled in the study. Based on the clinical outcome, the patients were assigned to two groups: survivors and non-survivors. Moreover, a series of routine laboratory parameters were monitored during the stay of the patients in the ICU and their levels correlated to the outcome. Statistical differences in the level of hepcidin, D-dimer, IL-6, LDH, NLR, neutrophils level, CRP, TNF-α and transferrin were observed between the groups. In particular, hepcidin values showed significantly different median concentrations (88 ng/mL vs. 146 ng/mL) between survivors and non-survivors. In addition, ROC curves analysis revealed sensitivity and specificity values of 74% and 76%, respectively, at a cut-off of 127 (ng/mL), indicating hepcidin as a good biomarker in predicting the severity and mortality of COVID-19 in ICU patients.

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

Predictive Value of MR-proADM in the Risk Stratification and in the Adequate Care Setting of COVID-19 Patients Assessed at the Triage of the Emergency Department.

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED.

Sensor array and gas chromatographic detection of the blood serum volatolomic signature of COVID-19.

Volatolomics is gaining consideration as a viable approach to diagnose several diseases, and it also shows promising results to discriminate COVID-19 patients via breath analysis. This paper extends the study of the relationship between volatile compounds (VOCs) and COVID-19 to blood serum. Blood samples were collected from subjects recruited at the emergency department of a large public hospital. The VOCs were analyzed with a gas chromatography mass spectrometer (GC/MS). GC/MS data show that in more than 100 different VOCs, the pattern of abundances of 17 compounds identifies COVID-19 from non-COVID with an accuracy of 89% (sensitivity 94% and specificity 83%). GC/MS analysis was complemented by an array of gas sensors whose data achieved an accuracy of 89% (sensitivity 94% and specificity 80%).

Correlations between chest-CT and laboratory parameters in SARS-CoV-2 pneumonia: A single-center study from Italy.

ABSTRACT: To investigate the relationship between damaged lung assessed by chest computed tomography (CT) scan and laboratory biochemical parameters with the aim of finding other diagnostic tools.Patients who underwent chest CT for suspected Corona Virus Disease-2019 (COVID-19) pneumonia at the emergency department admission in the first phase of COVID-19 epidemic in Italy were retrospectively analyzed. Patients with both negative chest CT and absence of the novel coronavirus in nasopharyngeal or oropharyngeal real-time reverse transcriptase polymerase chain reaction (RT-PCR) swabs were excluded from the study. A total of 462 patients with positive CT scans for interstitial pneumonia were included in the study (250 males and 212 females, mean age 57 ±â€Š17 years, range 18-89). Of these, 344 were positive to RT-PCR test, 118 were negative to double RT-PCR tests.CTs were analyzed for quantification of affected lung volume visually and by dedicated software. Statistical analysis to evaluate the relationship between laboratory analyses and CT patterns and amount of damaged lung related with COVID-19 pneumonia was performed in 2 groups of patients: positive RT-PCR COVID-19 group and negative RT-PCR COVID-19 group, but both with positive CT scans for interstitial pneumonia.Lymphocytopenia, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-dimer, and fibrinogen increased levels occurred in most patients without statistically significant differences between the 2 groups with CT scans suggestive for COVID-19. In fact, in both groups the volume of lung damage was strongly associated with altered laboratory test results, even for patients with negative RT-PCR test.The decreased number of lymphocytes, and the increased levels of CRP, LDH, d-dimer, and fibrinogen levels are associated with SARS-CoV 2 related pneumonia. This may be useful as an additional diagnostic tool in patients with double negative RT-PCR assay and with highly suspected clinic and chest CT features for COVID-19 to isolate patients in a pandemic period.

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department.

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.

Lymphocytes, Interleukin 6 and D-dimer Cannot Predict Clinical Outcome in Coronavirus Cancer Patients: LyNC1.20 Study.

BACKGROUND/AIM: Knowledge of Coronavirus 19 (COVID19) pathogenetic mechanisms is necessary to provide new treatment strategies. This study aims to assess how oncological disease impacts on the clinical course of COVID-19 patients. PATIENTS AND METHODS: From 1st March to 30th April 2020, 96 COVID-19 patients were classified according to clinical outcome as severe (n=67) and moderate (n=29). Demographic data, medical history, admission lymphocytes, procalcitonin (PCT), c-reactive-protein (CRP), D-dimer, and Interleukin-6 (IL-6) were collected. RESULTS: A statistically significant association was found between hypertension (p=0.007) and three or more comorbidities with severe outcomes (p=0.034). No statistical differences were found between the severe and moderate groups with regards to the rate of patients with past oncological history. However, no patient allocated in the moderate group had received oncological treatment within 12 months. Higher values of CRP, IL-6, D-Dimer and lower values of lymphocytes were reported in the severe group (p=0.0007, p=0.00386, p=0.041, and p=0.007, respectively). Using binary logistic regression, higher values of CRP (OR=8.861; p=0.012) and PCT were associated with a higher risk of severe outcome (OR=21.075; p=0.008). Within the oncological population, D-Dimer and IL-6 did not confirm their prognostic significance as in the general population (p>0.05). CONCLUSION: Specific prognostic factors for oncological patients should be designed for COVID-19 clinical practice.

Post-exercise Hypotension in Patients With Coronary Artery Disease.

Background: Blood pressure (BP) and hemodynamic changes occurring in the recovery phase after a single bout of exercise have not been extensively studied in coronary artery patients, despite the potential clinical implications of reducing BP through exercise. This study aimed at investigating the hemodynamic and arterial baroreflex mechanisms possibly involved in post-exercise hypotension (PEH) in patients with coronary artery disease. Methods: In 42 normotensive coronary artery patients undergone a Cardiac Rehabilitation Program, we evaluated before and after their daily exercise training session: blood pressure (BP) and heart rate (HR). In a subgroup (n = 29), daily BP profile was also evaluated by ambulatory BP monitoring. In those patients showing PEH (n = 15), we evaluated: Cardiac Output (CO), Stroke Volume (SV), total peripheral resistances (TPR), forearm (FVR) and calf (CVR) vascular resistances, and spontaneous baroreflex sensitivity (BRS). Results: After exercise TPR was significantly reduced with a similar contribution from CVR and FVR, whereas CO and SV significantly increased. BRS showed a significant reduction mainly due to a BRS decrease in response to hypertensive stimuli. Systolic BP (SBP) was significantly reduced for 12 h after the end of a single exercise session. Conclusion: These findings indicate that in coronary artery patients, the recovery phase after exercise is characterized by PEH which is mediated mainly by a generalized peripheral vasodilation and appears to influence BP behavior throughout the daily life. Finally, the cardiac component of the arterial baroreflex seems to contribute indirectly to BP reduction occurring after exercise.

Epidemiology of Hypoalbuminemia in Hospitalized Patients: A Clinical Matter or an Emerging Public Health Problem?

Serum albumin levels are strongly associated with the morbidity, prognosis, and mortality rates of patients with hypoalbuminemia, which is a frequent problem during hospitalization. An observational retrospective study was carried out to analyze changes in albumin levels in hospitalized patients at the "Fondazione Policlinico Tor Vergata-PTV" in 2018. The prevalence of preexisting hypoalbuminemia at the time of discharge from hospital was investigated using a sample of 9428 patients. Information was collected from the discharge files recorded in the central informatics system of the hospital. Analysis of albumin levels at admission and at discharge was conducted by classes of albuminemia and then stratified by age. At the time of admission, hypoalbuminemia was found to be present in more than half of the sample, with no sex differences. The serum albumin level tended to decrease with age, with pathologic levels appearing from 50 years and progressive worsening thereafter. The condition of marked and mild hypoalbuminemia was more prevalent in patients over 65 years of age. Our findings suggest that hypoalbuminemia should be considered a dangerous condition in itself and a serious public health problem. We aimed to emphasize the role of albumin as useful marker of the in-hospital malnutrition and frailty, to be integrated in the routinely assessment of patients for reconsidering ad hoc healthcare pathways after discharge from hospital, especially when dealing with fragile populations.

Chest Computed Tomography Scoring in Patients With Novel Coronavirus-infected Pneumonia: Correlation With Clinical and Laboratory Features and Disease Outcome.

BACKGROUND/AIM: This study investigated the correlation of chest computed tomography (CT), findings, graded using two different scoring methods, with clinical and laboratory features and disease outcome, including a novel clinical predictive score, in patients with novel coronavirus-infected pneumonia (NCIP). PATIENTS AND METHODS: In this retrospective, observational study, CT scan of 92 NCIP patients admitted to Policlinico Tor Vergata, were analyzed using a quantitative, computed-based and a semiquantitative, radiologist-assessed scoring system. Correlations of the two radiological scores with clinical and laboratory features, the CALL score, and their association with a composite adverse outcome were assessed. RESULTS: The two scores correlated significantly with each other (ρ=0.637, p<0.0001) and were independently associated with age, LDH, estimated glomerular filtration rate, diabetes, and with the composite outcome, which occurred in 24 patients. CONCLUSION: In NCIP patients, two different radiological scores correlated with each other and with several clinical, laboratory features, and the CALL score. The quantitative score was a better independent predictor of the composite adverse outcome than the semiquantitative score.

Effect of Lockdown in Surgical Emergency Accesses: Experience of a COVID-19 Hospital.

BACKGROUND/AIM: SARS-CoV-2 pandemic imposed extraordinary restriction measures and a complete reorganization of the Health System. The aim of the study was to evaluate the impact of COVID-19 on emergency surgical department accesses. PATIENTS AND METHODS: Patients admitted to surgical emergency departments was retrospectively recorded during the Lockdown (March 11, 2020-May 3, 2020) and compared with the same number of days in 2019 and immediately before Lockdown (January 16, 2020-March 10, 2020). Diagnoses, priority levels, modes of patient's transportation, waiting times and outcomes were analysed. RESULTS: During the lockdown phase, we ob-served a reduction in the access to emergency surgical departments of 84.45% and 79.78%, com-pared with the Pre-Lockdown2019 and Pre-Lockdown2020 groups, respectively. Patient's transportation, hospitalization and patients discharge with indications to an outpatient visit, waiting and total times exhibited a significant difference during the lockdown (p<0.005). CONCLUSION: We observed a reduction of surgical emergency accesses during the lockdown. Implementing the use of the regional systems and preventing overcrowding of emergency departments could be beneficial for reducing waiting times and improving the quality of treatments for patients.

Female Sex as a Thromboembolic Risk Factor in the Era of Nonvitamin K Antagonist Oral Anticoagulants.

Sex-specific differences have been definitively demonstrated in cardiovascular (CV) diseases. These differences can also impact on the effects of CV therapies. Female sex is recognized as an independent predictor of thromboembolic risk, particularly in older patients. Most of strokes are due to atrial fibrillation (AF). Women affected by AF have higher stroke risk compared to men. The introduction of novel oral anticoagulants (NOACs) for long-term anticoagulation completely changed the anticoagulant therapeutic approach and follow-up of patients affected by nonvalvular atrial fibrillation (NVAF). CHA2DS2-VASc stroke risk scoring in use in the current international guidelines attributes 1 point to "female sex". Besides, no anticoagulation is indicated for AF female patients without other risk factors. Interestingly, NOACs seem to normalize the differences between males and females both in terms of safety and efficacy, whereas residual higher stroke risk and systemic embolism persist in AF women treated with vitamin K antagonist anticoagulants VKA with optimal time in therapeutic range. Based on the CHA2DS2-VASc score, NOACs represent the preferred choice in NVAF patients. Moreover, complete evaluation of apparently lower risk factor along with concomitant clinical conditions in AF patients appears mandatory, particularly for female patients, in order to achieve the most appropriate anticoagulant treatment, either in male or in female patients. The present review was performed to review sex differences in AF-related thromboembolic risk reported in the literature and possibly highlight current knowledge gaps in prevention and management that need further research.

Complete blood count might help to identify subjects with high probability of testing positive to SARS-CoV-2.

The SARS-CoV-2 pandemic has dramatically increased the workload for health systems and a consequent need to optimise resources has arisen, including the selection of patients for swab tests. We retrospectively reviewed consecutive patients presenting to the emergency department with symptoms suggestive of COVID-19 and undergoing swab tests for SARS-CoV-2. Complete blood counts (CBCs) were analysed looking for predictors of test positivity. Eight significant predictors were identified and used to build a 'complete' CBC score with a discriminatory power for COVID-19 diagnosis of AUC 92% (p<0.0001). When looking at the weight of individual variables, mean corpuscular volume (MCV), age, platelets and eosinophils (MAPE: MCV ≤90 fL, 65 points; age ≥45 years, 100 points; platelets ≤180×103/µL, 73 points; eosinophils <0.01/µL, 94 points) gave the highest contribution and were used to build a 'simplified' MAPE score with a discriminatory power of AUC 88%. By setting the cut-off MAPE score at ≥173 points, sensitivity and specificity for COVID-19 diagnosis were 83% and 82%, respectively, and the actual test positivity rate was 60% as compared to 6% of patients with MAPE score <173 points (odds ratio 23.04, 95% confidence interval [CI] 9.1-58.3, p-value <0.0001). In conclusion, CBC-based scores have potential for optimising the SARS-CoV-2 testing process: if these findings are confirmed in the future, swab tests may be waived for subjects with low score and uncertain symptoms, while they may be considered for asymptomatic or oligosymptomatic patients with high scores.

How biomarkers can improve pneumonia diagnosis and prognosis: procalcitonin and mid-regional-pro-adrenomedullin.

Aim: The diagnostic and prognostic role of procalcitonin (PCT) and mid-regional-pro-adrenomedullin (MR-proADM) were investigated in patients with pneumonia. Material & methods: A total of 168 and 77 patients with pneumonia enrolled in two different hospital settings, an internal medicine unit and an emergency unit were included in the study. PCT and MR-proADM plasma concentrations and pneumonia severity index score were measured. Median values were compared by Mann-Whitney's test. Receiver operating characteristic analysis and rank correlation were used to define the diagnostic and prognostic accuracy. Results: PCT confirmed the diagnostic role at values 0.08-0.10 ng/ml and MR-proADM the prognostic role for severe pneumonia. Significant correlation (p < 0.0001) between MR-proADM and pneumonia severity index score indicated expression of pneumonia severity. Conclusion: This combination of biomarkers presents a high positive predictive value in pneumonia diagnosis and prognosis.

Procalcitonin and MR-proAdrenomedullin combination in the etiological diagnosis and prognosis of sepsis and septic shock.

Procalcitonin and Mid-regional pro Adrenomedullin have been proposed for sepsis diagnosis, antibiotic therapy guidance and prognosis. A retrospective analysis of PCT and MR-proADM on 571 consecutive patients with sepsis diagnosis was performed. Median values were compared using the non-parametric Mann-Whitney's test. Receiver operating characteristic analysis was performed to define cutoff points for sepsis diagnosis. Pretest odds, posttest odds, and posttest probability have been calculated. Data were analyzed using Med-Calc 11.6.1.0 software. PCT resulted excellent in gram-negative, but less performant in gram-positive and fungal etiologies. MR-proADM values resulted homogenously distributed within the different microbial classes and increased significantly in septic shock. PCT highest PPV value was found to distinguish gram-negative from fungal sepsis and septic shock (>3. 57 ng/mL, PPV 0.96 and > 8.77 ng/mL, PPV 0.96, respectively). Good diagnostic accuracy was evidenced to discriminate gram-negative from gram-positive septic shock (>3.88 ng/mL PPV 0.89). Lower diagnostic accuracy was evidenced to discriminate gram-negative and gram-positive sepsis (>0.80 ng/mL, PPV 0.78) and gram-positive from fungal septic shock (>1.74 ng/mL PPV 0.75). The lowest PCT PPV (0.28) was found in gram-positive and fungal sepsis distinction. MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and were higher in septic shock, but not influenced by pathogen etiologies. MR-proADM cut-off values > 3.39 nmol/L in sepsis and >4.33 nmol/L in septic shock were associated with significant higher risk of 90-days mortality. In conclusion, PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.