Inflammatory Biomarkers and Clinical Judgment in the Emergency Diagnosis of Urgent Abdominal Pain.

BACKGROUND: The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP. METHODS: This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory. RESULTS: UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77-0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62-0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65-0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80-0.85) and after imaging to 0.87 (95% CI, 0.84-0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%. CONCLUSIONS: Interleukin-6 significantly improves the early diagnosis of UAP in the ED.

Gastric and lower esophageal sphincter pressures during nausea: a study using visual motion-induced nausea and high-resolution manometry.

Nausea is the subjective unpleasant sensation that immediately precedes vomiting. Studies using barostats suggest that gastric fundus and lower esophageal sphincter (LES) relaxation precede vomiting. Unlike barostat, high-resolution manometry allows less invasive, detailed measurements of fundus pressure (FP) and axial movement of the gastroesophageal junction (GEJ). Nausea was induced in 12 healthy volunteers by a motion video and rated on a visual analog scale. FP was measured as the mean value of the five pressure channels that were clearly positioned below the LES. After intubation, a baseline (BL) recording of 15 min was obtained. This was followed by presentation of the motion video (at least 10 min, maximum 20 min) followed by 30 min recovery recording. Throughout the experiment we recorded autonomic nervous system (ANS) parameters [blood pressure, heart rate (HR), and cardiac vagal tone (CVT), which reflects efferent vagal activity]. Ten out of 12 subjects showed a drop in FP during peak nausea compared with BL (-4.0 ± 0.8 mmHg; P = 0.005), and 8/10 subjects showed a drop in LES pressure (-8.8 ± 2.5 mmHg; P = 0.04). Peak nausea preceded peak fundus and LES pressure drop. Nausea was associated with configuration changes at the GEJ such as LES shortening and esophageal lengthening. During nausea we observed a significantly increased HR and decreased CVT. In conclusion, nausea is associated with a drop in fundus and LES pressure, configuration changes at the GEJ as well as changes in the ANS activity such as an increased sympathetic tone (increased HR) and decreased parasympathetic tone (decreased CVT).

[Functional diarrhea - pathophysiology, investigation and treatment]. / Funktionelle Diarrhoe - Pathophysiologie, Abklärung und Therapie.

The most important reason for functional diarrhea in clinical practice is diarrhea-predominant irritable bowel syndrome (IBS) which is characterized by chronic intermittent diarrhea and abdominal pain. The pathophysiology underlying IBS is complex and includes visceral hypersensitivity, abnormal gut motility and autonomous nervous system dysfunction as well as genetic and psychosocial factors. Treatment should be tailored to the individual's symptoms and involves general measures, pharmacological treatments, dietary interventions, psychotherapy and complementary and alternative approaches. The following manuscript will give an overview over pathophysiology, reasonable investigations and treatment of IBS.

High-sensitivity cardiac troponin in the distinction of acute myocardial infarction from acute cardiac noncoronary artery disease.

BACKGROUND: We hypothesized that high-sensitivity cardiac troponin (hs-cTn) and its early change are useful in distinguishing acute myocardial infarction (AMI) from acute cardiac noncoronary artery disease. METHODS AND RESULTS: In a prospective, international multicenter study, hs-cTn was measured with 3 assays (hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI Siemens) in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain. Accuracy of the combination of presentation values with serial changes was compared against a final diagnosis adjudicated by 2 independent cardiologists. AMI was the adjudicated final diagnosis in 127 patients (15%); cardiac noncoronary artery disease, in 124 (14%). Patients with AMI had higher median presentation values of hs-cTnT (0.113 µg/L [interquartile range, 0.049-0.246 µg/L] versus 0.012 µg/L [interquartile range, 0.006-0.034 µg/L]; P<0.001) and higher absolute changes in hs-cTnT in the first hour (0.019 µg/L [interquartile range, 0.007-0.067 µg/L] versus 0.001 µg/L [interquartile range, 0-0.003 µg/L]; P<0.001) than patients with cardiac noncoronary artery disease. Similar findings were obtained with the hs-cTnI assays. Adding changes of hs-cTn in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver-operating characteristics curve of 0.94 for hs-cTnT (0.92 for both hs-cTnI assays). Algorithms using ST-elevation, presentation values, and changes in hs-cTn in the first hour accurately separated patients with AMI and those with cardiac noncoronary artery disease. These findings were confirmed when the final diagnosis was readjudicated with the use of hs-cTnT values and validated in an independent validation cohort. CONCLUSION: The combined use of hs-cTn at presentation and its early absolute change excellently discriminates between patients with AMI and those with cardiac noncoronary artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays.

BACKGROUND: It is unknown whether unstable angina (UA) results in previously nondetectable low-level myocardial necrosis. We compared the pattern of myocardial necrosis between patients with UA, acute myocardial infarction (AMI), and noncardiac chest pain (NCCP) using 3 high-sensitive cardiac troponin (hs-cTn) assays. METHODS: In a multicenter study, we enrolled 842 unselected patients with acute chest pain in the emergency department. Roche hs-cTnT, Beckman Coulter hs-cTnI, and Siemens hs-cTnI were determined in a blinded fashion at presentation and after 1, 2, 3, and 6 hours. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: A change in hs-cTn of ≥2 ng/L within the first hour after presentation as assessed with Roche hs-cTnT, Beckman Coulter hs-cTnI, and Siemens hs-cTnI was observed in 26%, 31%, and 32% of patients with UA (n = 115) compared with 91%, 92%, and 96% in patients with AMI (n = 120) and 12%, 23%, and 16% in patients with NCCP (n = 415; P < .001 for all comparisons between UA and AMI, P > .05 for all comparisons between UA and NCCP). In patients with UA, such a 1-hour change in hs-cTn of ≥2 ng/L was associated with an increased risk of death or AMI during the 30-day follow-up (P = .003, .03, .03) and 2-year follow-up (P < .001, .002, and .006). CONCLUSIONS: In marked contrast to patients with AMI, most patients with UA do not exhibit relevant hs-cTn changes. The minority of UA with hs-cTn changes, however, has a significantly worse short- and long-term outcome.

Early diagnosis of myocardial infarction with sensitive cardiac troponin assays.

BACKGROUND: The rapid and reliable diagnosis of acute myocardial infarction is a major unmet clinical need. METHODS: We conducted a multicenter study to examine the diagnostic accuracy of new, sensitive cardiac troponin assays performed on blood samples obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infarction. Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays (Abbott-Architect Troponin I, Roche High-Sensitive Troponin T, Roche Troponin I, and Siemens Troponin I Ultra) and a standard assay (Roche Troponin T). The final diagnosis was adjudicated by two independent cardiologists. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 123 patients (17%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly higher with the four sensitive cardiac troponin assays than with the standard assay (AUC for Abbott-Architect Troponin I, 0.96; 95% confidence interval [CI], 0.94 to 0.98; for Roche High-Sensitive Troponin T, 0.96; 95% CI, 0.94 to 0.98; for Roche Troponin I, 0.95; 95% CI, 0.92 to 0.97; and for Siemens Troponin I Ultra, 0.96; 95% CI, 0.94 to 0.98; vs. AUC for the standard assay, 0.90; 95% CI, 0.86 to 0.94). Among patients who presented within 3 hours after the onset of chest pain, the AUCs were 0.93 (95% CI, 0.88 to 0.99), 0.92 (95% CI, 0.87 to 0.97), 0.92 (95% CI, 0.86 to 0.99), and 0.94 (95% CI, 0.90 to 0.98) for the sensitive assays, respectively, and 0.76 (95% CI, 0.64 to 0.88) for the standard assay. We did not assess the effect of the sensitive troponin assays on clinical management. CONCLUSIONS: The diagnostic performance of sensitive cardiac troponin assays is excellent, and these assays can substantially improve the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain. (ClinicalTrials.gov number, NCT00470587.)

How safe is the outpatient management of patients with acute chest pain and mildly increased cardiac troponin concentrations?

BACKGROUND: The appropriate management of patients discharged from the emergency department (ED) with increased high-sensitivity cardiac troponin T (hs-cTnT) but normal or borderline-high conventional cardiac troponin concentrations is unknown. METHODS: We investigated 643 consecutive ED patients with acute chest pain who had been discharged for outpatient management after acute myocardial infarction (AMI) had been ruled out by serial measurements of conventional cardiac troponin. hs-cTnT was measured blindly, and we calculated the rates of all-cause mortality (primary endpoint) and subsequent AMI (secondary endpoint) at 30, 90, and 360 days. RESULTS: hs-cTnT concentrations were increased (>14 ng/L) in 114 patients (18%) but <30 ng/L in 95% of these patients. Of those 114 patients, 96 (84%) had an adjudicated noncoronary cause of chest pain. Thirty-day mortality (95% CI) was 0.9% (0.1%-6.1%), 90-day mortality was 2.7% (0.9%-8.1%), and 360-day mortality was 5.2% (2.2%-11.9%) in patients with increased hs-cTnT; respective rates (95% CI) of AMI were 0.0%, 1.9% (0.5%-7.2%), and 7.6% (3.7%-15.3%). Increased hs-cTnT was associated with increased mortality and AMI at 90 days (P = 0.006 and P = 0.081, respectively) and 360 days (P = 0.001 for both). CONCLUSIONS: hs-cTnT is a strong prognosticator of intermediate and long-term mortality and AMI in low-risk patients discharged from the ED after AMI has been ruled out. The relatively low rate of 30-day events may suggest that patients without acute coronary syndrome and small increases in cardiac troponin are in need of further investigations and treatments, but not necessarily immediate hospitalization.

Growth differentiation factor-15 in the early diagnosis and risk stratification of patients with acute chest pain.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is a stress-responsive marker that might aid in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI). METHODS: In a prospective, international multicenter study, GDF-15, high-sensitivity cardiac troponin T (hs-cTnT), and B-type natriuretic peptide (BNP) were measured in 646 unselected patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. The primary prognostic end point was all-cause mortality during a median follow-up of 26 months. RESULTS: AMI was the adjudicated final diagnosis in 115 patients (18%). GDF-15 concentrations at presentation were significantly higher in AMI patients compared to patients with other diagnoses. The diagnostic accuracy of GDF-15 at presentation for the diagnosis of AMI as quantified by the area under the ROC curve (AUC) was lower (AUC 0.69, 95% CI 0.64-0.74) compared to hs-cTnT (AUC 0.96, 95% CI 0.94-0.98, P < 0.001) and BNP (AUC 0.74, 95% CI 0.69-0.80, P = 0.02). A total of 55 deaths occurred during follow-up. GDF-15 predicted all-cause mortality independently of and more accurately than hs-cTnT [AUC 0.85 (95% CI 0.81-0.90) vs 0.77 (95% CI 0.72-0.83), P = 0.002] and BNP (AUC 0.75, 95% CI 0.68-0.82, P = 0.007). Net reclassification improvement was 0.15 (P = 0.01), and the absolute integrated discrimination improvement was 0.07, yielding a relative integrated discrimination improvement of 0.36 (P = 0.07). CONCLUSIONS: GDF-15 predicts all-cause mortality in unselected patients with acute chest pain independently of and more accurately than hs-cTnT and BNP. However, GDF-15 does not seem to help in the early diagnosis of AMI.

Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction.

BACKGROUND: Plaque erosion and plaque rupture occur early in the pathophysiology of acute myocardial infarction (AMI). We hypothesized that markers of plaque instability might be useful in the early diagnosis and risk stratification of AMI. METHODS: In this multicenter study, we examined 4 markers of plaque instability, myeloperoxidase (MPO), myeloid-related protein 8/14 (MRP-8/14), pregnancy-associated plasma protein-A (PAPP-A), and C-reactive protein (CRP) in 398 consecutive patients presenting to the emergency department with acute chest pain and compared them to normal and high-sensitivity cardiac troponin T (cTnT and hs-cTnT). The final diagnosis was adjudicated by 2 independent cardiologists. Primary prognostic end point was death during a median follow-up of 27 months. RESULTS: The adjudicated final diagnosis was AMI in 76 patients (19%). At emergency department presentation, concentrations of all 4 biomarkers of plaque instability were significantly higher in patients with AMI than in patients with other diagnoses. However, their diagnostic accuracy as quantified by the area under the ROC curve (AUC) was low (MPO 0.63, MRP-8/14 0.65, PAPP-A 0.62, CRP 0.59) and inferior to both normal and high-sensitivity cardiac troponin T (cTnT 0.88, hs-cTnT 0.96; P<0.001 for all comparisons). Thirty-nine patients (10%) died during follow-up. Concentrations of MPO, MRP-8/14, and CRP were higher in nonsurvivors than in survivors and predicted all-cause mortality with moderate accuracy. CONCLUSIONS: Biomarkers of plaque instability do not seem helpful in the early diagnosis of AMI but may provide some incremental value in the risk stratification of patients with acute chest pain.

Effect of Season of Birth on Hippocampus Volume in a Transdiagnostic Sample of Patients With Depression and Schizophrenia.

Psychiatric disorders share an excess of seasonal birth in winter and spring, suggesting an increase of neurodevelopmental risks. Evidence suggests season of birth can serve as a proxy of harmful environmental factors. Given that prenatal exposure of these factors may trigger pathologic processes in the neurodevelopment, they may consequently lead to brain volume alterations. Here we tested the effects of season of birth on gray matter volume in a transdiagnostic sample of patients with schizophrenia and depression compared to healthy controls (n = 192). We found a significant effect of season of birth on gray matter volume with reduced right hippocampal volume in summer-born compared to winter-born patients with depression. In addition, the volume of the right hippocampus was reduced independent from season of birth in schizophrenia. Our results support the potential impact of season of birth on hippocampal volume in depression.

Incremental value of high-sensitivity cardiac troponin T for risk prediction in patients with suspected acute myocardial infarction.

BACKGROUND: High-sensitivity cardiac troponin assays have better analytical precision and sensitivity than earlier-generation assays when measuring cardiac troponin at low concentrations. We evaluated whether use of a high-sensitivity assay could further improve risk stratification compared with a standard cardiac troponin assay. METHODS: We enrolled consecutive patients presenting with acute chest pain, 30% of whom were diagnosed with acute coronary syndrome. Blood samples were drawn at the time of presentation. We measured cardiac troponin T with a standard fourth-generation assay (cTnT) and a high-sensitivity assay (hs-cTnT) (both Roche Diagnostics) and followed the patients for 24 months. RESULTS: Of the 1159 patients, 76 died and 42 developed an acute myocardial infarction (AMI). Prognostic accuracy of hs-cTnT for death was significantly higher [area under ROC curve (AUC) 0.79, 95% CI 0.74-0.84] than that of cTnT (AUC 0.69, 95% CI 0.62-0.76; P < 0.001). After adjustment for Thrombolysis in Myocardial Infarction (TIMI) risk score (that included the cTnT assay result), hs-cTnT above the 99th percentile (0.014 µg/L) was associated with a hazard ratio for death of 2.60 (95% CI 1.42-4.74). Addition of hs-cTnT to the risk score improved the reclassification of patients (net reclassification improvement 0.91; 95% CI 0.67-1.14; P < 0.001). Subgroup analyses showed that this effect resulted from the better classification of patients without AMI at time of testing. hs-cTnT outperformed cTnT in the prediction of AMI during follow-up (P=0.02), but was not independently predictive for this endpoint. CONCLUSIONS: Concentrations of hs-cTnT >0.014 µg/L improve the prediction of death but not subsequent AMI in unselected patients presenting with acute chest pain.

Value of arterial blood gas analysis in patients with acute dyspnea: an observational study.

INTRODUCTION: The diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown. METHODS: We performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea. RESULTS: We enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to intensive care unit (28% vs 12% in the first tertile, P < 0.001) and had higher in-hospital (14% vs 5%, P = 0.003) and 30-day mortality (17% vs 7%, P = 0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P = 0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P = 0.043) and non-pulmonary disorders (P = 0.038). CONCLUSIONS: ABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality.

Use of myeloperoxidase for risk stratification in acute heart failure.

BACKGROUND: Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF). METHODS: We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses. RESULTS: MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (< or = 99 vs >99 pmol/L) and BNP (median of < or = 847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045). CONCLUSIONS: MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.

Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study.

INTRODUCTION: The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea. METHODS: We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea. RESULTS: MR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P < 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P < 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate). CONCLUSIONS: MR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease.

Incremental value of multiplex real-time PCR for the early diagnosis of sepsis in the emergency department.

BACKGROUND: Delayed recognition of sepsis and inappropriate initial antibiotic therapy are associated with increased mortality and morbidity. The early detection of the causative organism in sepsis is an unmet clinical need. A novel multiplex real-time polymerase chain reaction (MRT-PCR) (SeptiFast®) technique may provide the microbiological diagnosis within six hours. METHODS: We assessed the diagnostic accuracy of blood cultures and MRT-PCR in a comparative diagnostic cohort study in 110 consecutive adult patients presenting to the emergency department (ED) with suspected sepsis. RESULTS: We collected 205 corresponding PCR samples and blood culture (BC) pairs from the 110 patients. There was moderate to high concordance between PCR and BC with 181 (88%) matching and 24 (12%) mismatching samples. The diagnostic accuracy of MRT-PCR in detecting sepsis and its causative organism was comparable to that of BCs. The additional use of MRT-PCR significantly reduced the time to microbiological diagnosis as compared to the use of conventional microbiological methods alone (mean time gained 3.9 hours, range 0-66 hours, p <0.001). CONCLUSION: Diagnostic accuracy of BCs and MRT-PCR in the early diagnosis of sepsis and its causative organism in the ED are comparable. However, MRT-PCR reduces the time to microbiological diagnosis. Whether a more rapid detection of the organism by MRT-PCR could improve the outcome of patients has to be assessed in large prospective randomised trials.

Addressing unmet clinical needs in the early diagnosis of sepsis.

The incidence of sepsis and the number of sepsis-related deaths are increasing, making sepsis the leading cause of death in critically ill patients in Europe and the U.S.A. Delayed recognition of sepsis and inappropriate initial antibiotic therapy are associated with an increase in mortality and morbidity. Rapid and accurate identification of sepsis and its causative organisms are a prerequisite for successful therapy. The current gold standard for the diagnosis of sepsis is culture of blood and other body fluids or tissues. However, even in severe sepsis, blood cultures (BC) yield the causative microorganism in only 20-40% of patients. Moreover, at least 24 hours are needed to get preliminary information about the potential organism. Therefore, novel laboratory methods for the diagnosis of sepsis, such as multiplex real-time polymerase chain reaction (PCR), matrix-assisted laser desorption ionisation (MALDI) time-of-flight (TOF) mass spectrometry (MS) (MALDI-TOF MS) and calorimetry, have been developed and evaluated.

Determinants of absolute and relative exercise-induced changes in B-type natriuretic peptides.

BACKGROUND: Exercise is associated with changes in circulating B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP). However, the biological relevance of this phenomenon is poorly examined. We sought to assess determinants of absolute (Δ) and relative (Δ%) exercise-induced changes in BNP and NT-proBNP. METHODS: BNP (n = 418) and NT-proBNP (n = 478) at rest and peak exercise were measured in patients undergoing symptom-limited cycle ergometer tests. Multivariate logistic regression was performed to identify predictors of high ΔBNP/ΔNT-proBNP and high ΔBNP/Δ%NT-proBNP defined as their highest quartiles (Q4). RESULTS: The median (interquartile range) ΔBNP and ΔNT-proBNP was 12 (0-28) pg/ml and 7 (2-21) pg/ml respectively, and Δ%BNP and Δ%NT-proBNP was 21 (0-46) % and 7 (3-12) % respectively. Higher BNP [odds ratio (OR) 3.92 per ln unit; p < 0.001] or NT-proBNP [OR 4.88 per ln unit; p<0.001] at rest was the strongest predictor of ΔBNP in Q4 (≥ 28 pg/ml) or ΔNT-proBNP in Q4 (≥ 21 pg/ml). In contrast, higher maximal work rate expressed as the percentage of the predicted value (OR 1.015 per %; p = 0.007) was the only independent predictor of Δ%BNP in Q4 (≥ 46%), and lower resting heart rate (OR 0.97 per bpm; p = 0.001) and lower age (OR 0.95 per year; p = 0.001) were the only independent predictors of Δ%NT-proBNP in Q4 (≥ 12%). CONCLUSIONS: Higher ΔBNP and ΔNT-proBNP primarily reflected higher BNP and NT-proBNP plasma levels at rest. In contrast, higher Δ%BNP and Δ%NT-proBNP were associated with several prognostically favorable features, indicating that higher Δ%BNP and Δ%NT-proBNP may be markers of health rather than disease.

Use of neutrophil count in early diagnosis and risk stratification of AMI.

BACKGROUND: Neutrophils are rapidly released into the circulation upon acute stress such as trauma or acute myocardial infarction (AMI). We hypothesized that neutrophil count might provide incremental value in the early diagnosis and risk stratification of AMI. METHODS: We conducted a prospective observational multicenter study to examine the diagnostic accuracy of the combination of neutrophil count and cardiac troponin T from 1125 consecutive patients who presented to the Emergency Department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: Neutrophil count was higher in patients with acute myocardial infarction compared with other diagnoses (median 6.7 vs. 5.0×10(9)/L, respectively, P <.001). The accuracy of the neutrophil count for diagnosing acute myocardial infarction, quantified by the area under the receiver operating characteristic curve (AUC) was 0.69, which was significantly lower than that of cardiac troponin T (AUC 0.89, P <.001). The combination of the neutrophil count and cardiac troponin T did not improve the early diagnosis of acute myocardial infarction versus cardiac troponin T alone (P=.79). The prognostic accuracy of neutrophil count for death and AMI was significantly lower than that of cardiac troponin T. However, patients in the highest tertile of neutrophil count had a significantly increased risk of death and AMI at 90 and 360 days compared with patients in the lowest tertile (hazard ratios 2.47 [95% confidence interval, 1.63-3.72] and 2.28 [95% confidence interval, 1.55-3.36], respectively). CONCLUSION: The neutrophil count does not improve the early diagnosis of AMI in patients presenting with chest pain but identifies patients at increased risk of death.

Systolic blood pressure at Emergency Department presentation and 1-year mortality in acute chest pain patients.

BACKGROUND: High blood pressure at rest has been an established risk factor for cardiovascular disease. However the relationship between Systolic Blood Pressure (SBP) and 1-year-mortality among acute chest pain patients presenting to Emergency Department (ED); and effects of preexisting renal insufficiency, hemodynamic stress - as quantified by Brain Natriuretic Peptide (BNP) and chest pain duration, on this relationship is unknown. METHODS: Data was used from APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation), a prospective observational multicenter study of 1240 ED chest pain patients. SBP at presentation was categorized into quartiles: Q1≤127mmHg; Q2 128-142mmHg; Q3 143-160mmHg; Q4≥161mmHg. RESULTS: 60 deaths occurred during 1-year. One-year-mortality-rate showed lower Hazard Ratios for Q2, Q3 and Q4 vs Q1 (HR [95% CI]; 0.39 (0.19-0.78), 0.34 (0.17-0.70), 0.35 (0.17-0.72); p<0.01 respectively). Cox model adjusted for various demographic and treatment variables showed that participants in Q3 and Q4 had better prognoses than Q1. Patients showed progressively better prognosis from Q2 through Q4 vs Q1 only in patients who presented to ED with for more than 12h of chest pain duration. Patients with renal insufficiency had lower SBP at presentation than others (p=0.001). There was no association between the outcome and interaction variable of SBP quartiles and BNP (p=0.27). CONCLUSION: Acute chest pain patients presenting to ED exhibit an inverse association between SBP at presentation and 1-year-mortality; a relationship which appears stronger in those who present with chest pain of greater than 12h duration.