Advantage of Using of High-Sensitivity Troponin I Compared to Conventional Troponin I in Shortening Time to Rule out/in Acute Coronary Syndrome in Chest Pain Patients Presenting to the Emergency Department.

Background and Objectives: We aimed to compare the time to diagnosis for acute coronary syndromes using high-sensitivity troponin I (hsTnI) and conventional troponin I (TnI) in patients presenting to the emergency department (ED) with chest pain. Materials and Methods: This was an observational prospective study involving patients presenting to the ED of Sant'Andrea Hospital University la Sapienza in Rome (Italy) with chest pain from January to December 2014. Serum troponin was drawn at presentation, and at 3, 6, 9, and/or 12 h if clinically indicated. Depending on date of recruitment, patients had either hsTnI (Abbott Laboratories) or TnI (Abbott Laboratories) performed. The primary endpoint was the time to diagnosis at index visit. Results: A total of 1059 patients were recruited, (673 [63.6%] male, median age 60 years [interquartile range 49−73 years]), out of whom 898 (84.8%) patients were evaluated with hsTnI and 161 (15.2%) with TnI. A total of 393 (37.1%) patients had the diagnosis of acute coronary syndrome in ED. The median time to diagnosis for those evaluated with TnI was 400 min, IQR 120−720 min, while the use of hsTnI led to a significantly shorter time to diagnosis (median 200 min, IQR 100−200 min, p < 0.001). Conclusions: This study confirms that in patients presenting to the emergency department with chest pain, the use of hsTnI is associated with a reduced time to ruling in/out ACS, and, consequently, hsTnI should be routinely used over TnI for more rapid identification of ACS with benefits for patients and related costs.

A new point-of-care test for the rapid detection of urinary tract infections.

Urinary tract infections (UTIs) are among the most common infections in all age groups. Fast and accurate diagnosis is essential to ensure a timely and effective therapy. Alongside with reference culture-based methods, several point-of-care tests (POCTs) for early detection of UTIs have been developed, but they have not been significantly implemented in current clinical practice. The Micro Biological Survey (MBS) POCT is a simple test developed by MBS Diagnostics Ltd. (London, UK) for the detection and management of UTIs. The present study has been undertaken to investigate the potentials and limits of the MBS POCT. A total of 349 patients were enrolled in two open-label, monocentric, non-interventional clinical trials in collaboration with an Emergency Medicine department and the outpatient clinic of two hospitals in Rome. Results of urine analysis using the MBS POCT were compared with those of the routine culture-based tests for UTI diagnosis performed by the hospital laboratory. The MBS POCT provided fast results revealing high bacterial count UTIs (≥ 105 CFU/ml) with 97% accuracy, 92% sensitivity, 100% specificity, 99% PPV, and 96% NPV within a 5-h analytical time threshold.

Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study.

OBJECTIVES: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. DESIGN: Multicenter prospective study. SETTING: At emergency department admission in five University hospitals. PATIENTS: Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. CONCLUSIONS: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.

Predictive value for death and rehospitalization of 30-day postdischarge B-type natriuretic peptide (BNP) in elderly patients with heart failure. Sub-analysis of Italian RED Study.

BACKGROUND: Our aim was to determine if, in elderly heart failure (eHF) patients, serial B-type natriuretic peptide (BNP) assessments obtained during follow-up after hospital discharge could have prognostic utility for death and rehospitalizations. In eHF patients, BNP assessment at hospital discharge has been demonstrated to have a high prognostic value; however, its predictive role for future cardiovascular events in eHF patients, when assessed in the period after discharge, both for the correct timing and cut-off levels, has not been completely elucidated. METHODS: This study is a monocentric subanalysis of the Italian RED (Rapid Emergency Department) study. We studied 180 consecutive patients admitted for acute HF through serial BNP assessments: at hospital arrival; at discharge; and at 30, 90, and 180 days follow-up outpatient visit. RESULTS: Both a BNP >400 pg/mL at 30 days after discharge and the percentage variation of BNP from discharge to 30 days (Δ%BNP), compared with a BNP at discharge >400 pg/mL, showed a higher area under the curve (AUC) and odds ratio (OR) in predicting events [AUC=0.842, p<0.0001; OR 7.9 (3.3-19.0), p<0.001 for 30 days BNP and AUC=0.851, p<0.0001; OR 9.5 (4.065-22.572), p<0.0001 for Δ%BNP compared with AUC=0.638, p<0.002; OR 2.4 (1.1-5.3), p=0.032 for BNP at discharge]. CONCLUSIONS: In patients at a high risk for future events, BNP levels assessed 30 days after hospital discharge in the absence of signs and symptoms could be predictive of subsequent hospitalization and death. These patients should be considered for closer monitoring and treatment adjustment.

Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis.

BACKGROUND: We investigated the diagnostic and prognostic utilities of procalcitonin (PCT), B-type natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with suspected sepsis, for whom sepsis was diagnosed clinically or based on PCT concentrations. METHODS: PCT, BNP, and NGAL concentrations were measured in 340 patients and were followed up in 109 patients. All studied biomarkers were analyzed according to the diagnosis, severity, and clinical outcomes of sepsis. RESULTS: Clinical sepsis and PCT-based sepsis showed poor agreement (kappa = 0.2475). BNP and NGAL showed significant differences between the two groups of PCT-based sepsis (P = 0.0001 and P < 0.0001), although there was no difference between the two groups of clinical sepsis. BNP and NGAL were significantly different according to the PCT staging and sepsis-related organ failure assessment subscores (P < 0.0001, all). BNP and PCT concentrations were significantly higher in the non-survivors than in the survivors (P = 0.0002) and showed an equal ability to predict in-hospital mortality (P = 0.0001). In the survivors, the follow-up NGAL and PCT concentrations were significantly lower than the initial values (148.7 ng/mL vs. 214.5 ng/mL, P < 0.0001; 0.61 ng/mL vs. 5.56 ng/mL, P = 0.0012). CONCLUSIONS: PCT-based sepsis diagnosis seems to be more reliable and discriminating than clinical sepsis diagnosis. Multimarker approach using PCT, BNP, and NGAL would be useful for the diagnosis, staging, and prognosis prediction in the critically ill patients with suspected sepsis.

Comparison between white blood cell count, procalcitonin and C reactive protein as diagnostic and prognostic biomarkers of infection or sepsis in patients presenting to emergency department.

BACKGROUND: Procalcitonin (PCT) is currently the most studied infection biomarker and its blood levels seem to mirror the severity of illness and outcome. PCT is widely used together with other biomarkers, such as white blood cells (WBC) count and C reactive protein (CRP), in order to guide antibiotic therapy. This study aimed to verify the diagnostic and prognostic power of WBC, CRP and PCT in patients with suspected infection in emergency department (ED). METHODS: A total of 513 patients presenting to the ED with signs/symptoms of local infections or sepsis were enrolled. APACHEII score and in-hospital death were recorded. Patients were subdivided into quartiles by age, and the biomarkers were measured at baseline. Receiver operating characteristics (ROC) curves for evaluating diagnostic and prognostic role of PCT, CRP and WBC were calculated for each variable alone and combined. RESULTS: When compared each other for PCT, CRP, and WBC there was no significant difference between the four subgroups. A direct correlation between PCT and WBC was found in the II, III, and IV quartiles (the highest correlation, r=0.34, p<0.0003). PCT alone or when combined with WBC showed the best diagnostic and prognostic power at ROC analysis. CONCLUSIONS: Our data demonstrate that WBC, but more CRP and PCT are reliable diagnostic and prognostic biomarkers, when considered in combination and with severity clinical score. PCT confirms its stronger usefulness as a diagnostic marker of sepsis. A multi-diagnostic tools approach is fundamental to perform a correct and rapid diagnosis of infection and sepsis in ED.

Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis.

INTRODUCTION: The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility. METHODS: We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded. RESULTS: ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001). CONCLUSIONS: In patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.

Additive value of blood neutrophil gelatinase-associated lipocalin to clinical judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the emergency department.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients. The aim of this study was to evaluate the utility of blood neutrophil gelatinase-associated lipocalin (NGAL) assessment as an aid in the early risk evaluation for AKI development in admitted patients. METHODS: This is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED. RESULTS: Blood NGAL and serum creatinine (sCr) were determined at ED presentation (T0), and at: 6 (T6), 12 (T12), 24 (T24) and 72 (T72) hours after hospitalization. A preliminary assessment of AKI by the treating ED physician occurred in 218 out of 665 patients (33%), while RIFLE AKI by expert nephrologists was confirmed in 49 out of 665 patients (7%). The ED physician's initial judgement lacked sensitivity and specificity, overpredicting the diagnosis of AKI in 27% of the cohort, while missing 20% of those with AKI as a final diagnosis. CONCLUSIONS: Our study demonstrated that assessment of a patient's initial blood NGAL when admitted to hospital from the ED improved the initial clinical diagnosis of AKI and predicted in-hospital mortality. Blood NGAL assessment coupled with the ED physician's clinical judgment may prove useful in deciding the appropriate strategies for patients at risk for the development of AKI.See related commentary by Legrand et al., http://ccforum.com/content/17/2/132.

A new point-of-care test for the rapid antimicrobial susceptibility assessment of uropathogens.

Bacterial resistance to antimicrobials is considered a major issue worldwide. This condition may account for treatment failure of urinary tract infections, which are among the most common infections both in community and healthcare settings. Therapy against uropathogens is generally administered empirically, possibly leading to unsuccessful therapy, recurrence and development of antibiotic resistance. The reduction in analytical time to obtain antimicrobial susceptibility test (AST) results could play a key role in reducing the cost of healthcare, providing information about antibiotic efficacy and thus preventing from either exploiting new and expensive antibiotics unnecessarily or using obsolete and ineffective ones. A more rational choice among treatment options would hence lead to more effective treatment and faster resolution. In this paper we evaluated the performance of a new Point Of Care Test (POCT) for the rapid prediction of antimicrobial susceptibility in urine samples performed without the need of a laboratory or specialized technicians. 349 patients were enrolled in two open-label, monocentric, non-interventional clinical trials in partnership with an Emergency Medicine ward and the Day Hospital of two large healthcare facilities in Rome. Antibiogram was carried out on 97 patients. Results from analysis of urine samples with the POCT were compared with those from routine AST performed on culture-positive samples, displaying high accuracy (>90%) for all tested antimicrobial drugs and yielding reliable results in less than 12 hours from urine collection thus reducing analytical and management costs.

In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study.

INTRODUCTION: Our aim was to evaluate the role of B-type natriuretic peptide (BNP) percentage variations at 24 hours and at discharge compared to its value at admission in order to demonstrate its predictive value for outcomes in patients with acute decompensated heart failure (ADHF). METHODS: This was a multicenter Italian (8 centers) observational study (Italian Research Emergency Department: RED). 287 patients with ADHF were studied through physical exams, lab tests, chest X Ray, electrocardiograms (ECGs) and BNP measurements, performed at admission, at 24 hours, and at discharge. Follow up was performed 180 days after hospital discharge. Logistic regression analysis was used to estimate odds ratios (OR) for the various subgroups created. For all comparisons, a P value < 0.05 was considered statistically significant. RESULTS: BNP median (interquartile range (IQR)) value at admission was 822 (412 - 1390) pg\mL; at 24 hours was 593 (270 - 1953) and at discharge was 325 (160 - 725). A BNP reduction of >46% at discharge had an area under curve (AUC) of 0.70 (P < 0.001) for predicting future adverse events. There were 78 events through follow up and in 58 of these patients the BNP level at discharge was >300 pg/mL. A BNP reduction of 25.9% after 24 hours had an AUC at ROC curve of 0.64 for predicting adverse events (P < 0.001). The odds ratio of the patients whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was <46% compared to the group whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was >46% was 4.775 (95% confidence interval (CI) 1.76 - 12.83, P < 0.002). The odds ratio of the patients whose BNP level at discharge was >300 pg/mL and whose percentage decrease at discharge was <46% compared to the group whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was >46% was 9.614 (CI 4.51 - 20.47, P < 0.001). CONCLUSIONS: A reduction of BNP >46% at hospital discharge compared to the admission levels coupled with a BNP absolute value < 300 pg/mL seems to be a very powerful negative prognostic value for future cardiovascular outcomes in patients hospitalized with ADHF.

Cardiovascular health of nonagenarians in southern Italy: a cross-sectional, home-based pilot study of longevity.

BACKGROUND: The Cilento region of southern Italy has a high prevalence of nonagenarians and centenarians. Few studies of the oldest old have included echocardiographic and/or electrocardiographic data, in a home-based setting. OBJECTIVES: The objective of this pilot study was to delineate the key lifestyle, medical, echocardiographic, and electrocardiographic features of a sample of nonagenarians and centenarians and their younger cohabitants from Cilento, via a comprehensive, home-based cardiovascular assessment. The ultimate aim is to identify the cardiovascular profile and lifestyle factors associated with longevity. METHODS: Twenty-six nonagenarians and centenarians (mean age 94 ±â€Š3 years) and 48 younger cohabitants aged 50-75 years (mean 62 ±â€Š5) underwent a comprehensive cardiovascular evaluation in their homes. RESULTS: In contrast to their younger cohabitants, nonagenarians and centenarians did not smoke, had lower fasting glucose levels, and lower LDL cholesterol despite being half as likely to be taking statins, and showing similar adherence to a Mediterranean diet. Over half of nonagenarians and centenarians (15/26) remained autonomous with their activities of daily living. Prevalence of self-reported coronary artery disease and stroke among nonagenarians and centenarians was low (11.5%), though a significant number had atrial fibrillation (31%) or congestive heart failure (27%). Although 62% of nonagenarians and centenarians had at least moderate valvular disease on echocardiography, less than 25% of those affected reported dyspnea. CONCLUSION: Nonagenarians and centenarians in the Cilento region had a healthy metabolic profile and a low prevalence of clinical cardiovascular disease. Even among nonagenarians and centenarians with structural heart abnormalities, report of symptoms is low. Larger studies in the Cilento population may help elucidate the mechanisms underlying cardiovascular health in the oldest old.

The Integration of qSOFA with Clinical Variables and Serum Biomarkers Improves the Prognostic Value of qSOFA Alone in Patients with Suspected or Confirmed Sepsis at ED Admission.

BACKGROUND: The prognostic value of quick sepsis-related organ failure assessment (qSOFA) outside intensive care units has been criticized. Therefore, we aimed to improve its ability in predicting 30-day all-cause mortality, and in ruling out the cases at high risk of death among patients with suspected or confirmed sepsis at emergency department (ED) admission. METHODS: This study is a secondary analysis of a prospective multicenter study. We built three predictive models combining qSOFA with the clinical variables and serum biomarkers that resulted in an independent association with 30-day mortality, in both 848 undifferentiated patients (Group 1) and in 545 patients definitively diagnosed with sepsis (Group 2). The models reaching the highest negative predictive value (NPV) with the minimum expenditure of biomarkers in Group 1 and in Group 2 were validated in two cohorts of patients initially held out due to missing data. RESULTS: In terms of the area under the receiver-operating characteristic curve, all six models significantly exceeded qSOFA in predicting prognosis. An "extended" qSOFA (eqSOFA1) in Group 1 and an eqSOFA2 integrated with C-reactive protein and mid-regional proadrenomedullin (eqSOFA2+CRP+MR-proADM) in Group 2 reached the best NPV (0.94 and 0.93, respectively) and ease of use. eqSOFA1 and eqSOFA2+CRP+MR-proADM performed equally well in both the inception and validation cohorts. CONCLUSIONS: We have derived and validated two prognostic models that outweigh qSOFA in predicting mortality and in identifying the low risk of death among patients with suspected or confirmed sepsis at ED admission.

An Italian registry of chest pain patients in the emergency department: clinical predictors of acute coronary syndrome.

BACKGROUND: The aim of this study was to describe the population of patients arriving in several Italian Emergency Departments (EDs) complaining of chest pain suggestive of acute coronary syndrome (ACS) in order to evaluate the incidence of ACS in this cohort and the association between ACS and different clinical parameters and risk factors. METHODS: This is an observational prospective study, conducted from the 1st January to the 31st December 2014 in 11 EDs in Italy. Patients presenting to ED with chest pain, suggestive of ACS, were consecutively enrolled. RESULTS: Patients with a diagnosis of ACS (N.=1800) resulted to be statistically significant older than those without ACS (NO ACS; N.=4630) (median age: 70 vs. 59, P<0.001), and with a higher prevalence of males (66.1% in ACS vs. 57.5% in NO ACS, P<0.001). ECG evaluation, obtained at ED admission, showed new onset alterations in 6.2% of NO ACS and 67.4% of ACS patients. Multiple logistic regression analysis showed that the following parameters were predictive for ACS: age, gender, to be on therapy for cardio-vascular disease (CVD), current smoke, hypertension, hypercholesterolemia, heart rate, ECG alterations, increased BMI, reduced SaO2. CONCLUSIONS: Results from this observational study strengthen the importance of the role of the EDs in ruling in and out chest pain patients for the diagnosis of ACS. The analysis put in light important clinical and risk factors that, if promptly recognized, can help Emergency Physicians to identify patients who are more likely to be suffering from ACS.

Usefulness of serial assessment of natriuretic peptides in the emergency department for patients with acute decompensated heart failure.

The value of natriuretic peptides, both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NTproBNP), for determining diagnosis, severity, and prognosis of emergency department (ED) patients with acute decompensated heart failure (ADHF) has been well documented. Emerging data support the hypothesis that repeated natriuretic peptide determinations in the acute phase of ADHF may assist in confirming the diagnosis, monitoring drug therapy, and evaluating the adequacy of patient stabilization. Data from the authors' group demonstrate that in patients admitted to the ED for acute dyspnea, serial NTproBNP measurement at admission and 4, 12, and 24 hours later was useful in confirming the diagnosis of ADHF compared with patients with chronic obstructive pulmonary disease. Moreover, in the same patients receiving intensive intravenous diuretic therapy, there was a progressive reduction of NTproBNP blood levels from hospitalization to discharge (P<.001), accompanied by clinical improvement and stabilization of heart failure. More recently, the authors also demonstrated that in ADHF patients improving with diuretics, a progressive reduction in BNP levels was observed, starting 24 hours after ED admission and continuing until discharge. Comparing BNP and NTproBNP, there was a significant correlation between NTproBNP and BNP levels but not between NTproBNP's and BNP's percent variation compared with baseline. In ADHF, serial ED measurements of BNP are useful for monitoring the effects of treatment. A reduction in BNP from admission to discharge is indicative of clinical improvement.

Brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide show a different profile in response to acute decompensated heart failure treatment.

Brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are currently used for the diagnosis, prognosis, and therapeutic decision making in heart failure patients. The aim of the study was to compare BNP and NT-proBNP plasma concentration profiles in 42 patients with decompensated heart failure who underwent treatment in the emergency department. A significant decrease in both peptide concentrations fell beyond 24 hours of therapy. BNP concentration underwent a more responsive change from admission (-54.1%+/-8.6% at 72 hours and -57.4%+/-7.6% at discharge) than NT-proBNP concentration (-17.6%+/-5.4% at 72 hours and -18.6%+/-5.6% at discharge). Although BNP and NT-proBNP concentrations were highly correlated, no correlation in their variations was found, a finding that suggests a different kinetic behavior in response to treatment. Sequential measurements of BNP and NT-proBNP provide a reliable marker to confirm clinical improvement after 24 hours of treatment. BNP may show some advantages over NT-proBNP as a more sensitive marker of early stabilization in response to therapy.

Altered mental status predicts mortality in cardiogenic shock - results from the CardShock study.

BACKGROUND: Altered mental status is among the signs of hypoperfusion in cardiogenic shock, the most severe form of acute heart failure. The aim of this study was to investigate the prevalence of altered mental status, to identify factors associating with it, and to assess the prognostic significance of altered mental status in cardiogenic shock. METHODS: Mental status was assessed at presentation of shock in 215 adult cardiogenic shock patients in a multinational, prospective, observational study. Clinical picture, biochemical variables, and short-term mortality were compared between patients presenting with altered and normal mental status. RESULTS: Altered mental status was detected in 147 (68%) patients, whereas 68 (32%) patients had normal mental status. Patients with altered mental status were older (68 vs. 64 years, p=0.04) and more likely to have an acute coronary syndrome than those with normal mental status (85% vs. 74%, p=0.04). Altered mental status was associated with lower systolic blood pressure (76 vs. 80 mmHg, p=0.03) and lower arterial pH (7.27 vs. 7.35, p<0.001) as well as higher levels of blood lactate (3.4 vs. 2.3 mmol/l, p<0.001) and blood glucose (11.4 vs. 9.0 mmol/l, p=0.01). Low arterial pH (adjusted odds ratio 1.6 (1.1-2.2), p=0.02) was the only factor independently associated with altered mental status. Ninety-day mortality was significantly higher (51% vs. 22%, p<0.001) among patients with altered mental status. CONCLUSIONS: Altered mental status is a common clinical sign of systemic hypoperfusion in cardiogenic shock and is associated with poor outcome. It is also associated with several biochemical findings that reflect inadequate tissue perfusion, of which low arterial pH is independently associated with altered mental status.

Comparison Between Soluble ST2 and High-Sensitivity Troponin I in Predicting Short-Term Mortality for Patients Presenting to the Emergency Department With Chest Pain.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. METHODS: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. RESULTS: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P<0.0001). In all patients, the sST2 level at arrival showed higher independent predictive power than hs-cTnI (odds ratio [OR] 20.13, P<0.0001 and OR 2.61, P<0.0008, respectively). sST2 at ED arrival showed a greater prognostic value for cardiovascular events in STEMI (area under the curve [AUC] 0.80, P<0.001) than NSTEMI patients (AUC 0.72, P<0.05). Overall, 51% of the STEMI patients with an sST2 value>35 ng/mL at ED arrival died during the 30-day follow-up. CONCLUSIONS: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality.

IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytes in vitro and its plasma levels correlate with B-type natriuretic peptide in non-overloaded acute heart failure patients.

BACKGROUND: An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic, and profibrotic activities. B-type natriuretic peptide is a cardiac hormone produced in response to cardiac filling to regulate cardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients. METHODS AND RESULTS: We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line to express the B-type natriuretic peptide gene, synthesize the relative protein through a PI3K-AKT-dependent transduction, and induce a cell secretory phenotype with B-type natriuretic peptide release. A correlation between IL-18 and B-type natriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patients with diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levels than patients without. IL-18 plasma levels were correlated with C-reactive protein plasma levels. CONCLUSIONS: This study provides the first evidence of the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status.

Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

BACKGROUND: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.

The association of admission blood glucose level with the clinical picture and prognosis in cardiogenic shock - Results from the CardShock Study.

BACKGROUND: Critically ill patients often present with hyperglycemia, regardless of previous history of diabetes mellitus (DM). Hyperglycemia has been associated with adverse outcome in acute myocardial infarction and acute heart failure. We investigated the association of admission blood glucose level with the clinical picture and short-term mortality in cardiogenic shock (CS). METHODS: Consecutively enrolled CS patients were divided into five categories according to plasma glucose level at the time of enrolment: hypoglycemia (glucose <4.0mmol/L), normoglycemia (4.0-7.9mmol/L), mild (8.0-11.9mmol/L), moderate (12.0-15.9mmol/L), and severe (≥16.0mmol/L) hyperglycemia. Clinical presentation, biochemistry, and short-term mortality were compared between the groups. RESULTS: Plasma glucose level of 211 CS patients was recorded. Glucose levels were distributed equally between normoglycemia (26% of patients), mild (27%), moderate (19%) and severe (25%) hyperglycemia, while hypoglycemia (2%) was rare. Severe hyperglycemia was associated with higher blood leukocyte count (17.3 (5.8) E9/L), higher lactate level (4.4 (3.3-8.4) mmol/L) and lower arterial pH (7.23 (0.14)) compared with normoglycemia or mild to moderate hyperglycemia (p<0.001 for all). In-hospital mortality was highest among hypoglycemic (60%) and severely hyperglycemic (56%) patients, compared with 22% in normoglycemic group (p<0.01). Severe hyperglycemia was an independent predictor of in-hospital mortality (OR 3.7, 95% CI 1.19-11.7, p=0.02), when adjusted for age, gender, LVEF, lactate, and DM. CONCLUSIONS: Admission blood glucose level has prognostic significance in CS. Mortality is highest among patients with severe hyperglycemia or hypoglycemia. Severe hyperglycemia is independently associated with high in-hospital mortality in CS. It is also associated with biomarkers of systemic hypoperfusion and stress response.