Case Report of Presumed (In)voluntary Capsaicin Intoxication Mimicking an Acute Abdomen.

BACKGROUND: The clinical features of a presumed capsaicin intoxication have not been reported so far. Case Presentation. A 27-year-old man took part in a qualifying for a competition in spicy food tolerance. During this qualifying, he swallowed 4 chili peppers type Bhut jolokia (about 1 million Scoville units) and other extremely spicy foods; the total amount of capsaicin ingested (roughly calculated retrospectively) accounted for at least 600 mg. After 2½ hours, the patient developed severe abdominal pain, which led to hospital admission. In contrast to the severe symptoms, clinical, laboratory, and imaging examinations (ultrasound and plain X-ray of the abdomen) did not reveal any significant abnormalities. Treatment with analgesics resulted in complete regression of the abdominal pain within 30 hours. CONCLUSIONS: The clinical picture in the view of pharmacological investigations on intestinal capsaicin infusions suggests that excessive doses of capsaicin can induce severe abdominal pain; the prolonged symptoms were probably due to the failure to vomit. Thus, a capsaicin intoxication must be considered in the differential diagnosis of an acute abdomen.

Bilirubin, urobilinogen, pancreas elastase and bile acid in drain fluid. The GBUP-study: Analysis of biomarkers for a colorectal anastomotic leakage.

PURPOSE: A colorectal anastomotic leakage (CAL) is a major complication after colorectal surgery and leads to high rates of morbidity and prolonged hospital stay. The study aims to evaluate the benefit of using bilirubin, urobilinogen, pancreas elastase and bile acid in the drain fluid (DF) as a predictive marker for the CAL. METHODS: From June 2015 to October 2017 100 patients, who underwent left hemicolectomy (LH), sigma resection (SR), high anterior resection (HAR), low anterior resection (LAR) or reversal of Hartmann's Procedure (ROHP) were included in this monocentric non-randomized prospective clinical trial. During the first four postoperative days (POD) the concentration of bilirubin, urobilinogen, pancreas elastase and bile acid in the DF was measured. RESULTS: In total 100 patients were recruited. 17 were excluded due to intraoperative decisions to conduct a protective stoma. 6 patients had a CAL. The patients of the control group (n = 77) and the patients who suffered from a CAL (n = 6) had no increased concentration of urobilinogen and pancreas elastase in the DF. The concentration of bile acid in the DF of the patients who suffered from a CAL differed from those of the control group on the 4th POD (p = 0.055).The concentration of bilirubin in the DF of the patients who suffered from a CAL significantly differed from those of the control group on the 1st POD (p = 0.031) and on the 3rd POD (p = 0.041). CONCLUSION: Bilirubin and bile acid in the DF may function as a predictive marker for a CAL.

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls - a cross-sectional pilot study.

BACKGROUND: Research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the role of Zn in patients with bulimia nervosa (BN) is scarce. OBJECTIVE: We aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls. METHODS: Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years. RESULTS: Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen's d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen's d=0.882). There was no difference between acutely ill and remitted patients with BN in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other two groups. Overall, there were no significant differences in dietary preferences with regard to Zn containing foods between the groups. CONCLUSION: The present study provides preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN do not vary with regard to the stage of illness (acute versus remitted BN). Further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.

CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia.

RATIONALE: We hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. OBJECTIVE: Preeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. METHODS AND RESULTS: We performed whole-genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By reverse transcriptase-polymerase chain reaction, we confirmed this finding in early-onset (<34 gestational week, n=26) and late-onset (≥34 gestational week, n=24) samples from preeclamptic women, compared with healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry, and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared with controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naive and activated macrophages lacking CD74 showed a shift toward a proinflammatory signature with an increased secretion of tumor necrosis factor-α, chemokine (C-C motif) ligand 5, and monocyte chemotactic protein-1, when cocultured with trophoblasts compared with control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFα, and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas, and impaired spiral artery remodeling with fetal growth restriction. CONCLUSIONS: CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation toward a proinflammatory signature and a disturbed crosstalk with trophoblasts.

High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

PURPOSE: Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. METHODS: Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. RESULTS: rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. CONCLUSION: Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia.

Defining a reference population to determine the 99th percentile of a contemporary sensitive cardiac troponin I assay.

BACKGROUND: Diagnosis of acute myocardial infarction (AMI) according to the universal definition is based on ischemic symptoms, imaging findings and elevated myocardial necrosis markers, preferably cardiac troponin I/T with diagnostic threshold representing the 99th percentile of a reference population. It is not clearly defined if this should be an unselected population-based or a healthy cohort with respect to cardiac diseases. Aim of the current study was to describe the distribution of troponin I using a sensitive assay and to evaluate the impact of cardiac diseases and cardiovascular risk factors in apparently healthy individuals. METHODS: Troponin I was determined using a contemporary sensitive assay (TnI Ultra, Siemens) with 10% coefficient of variation (0.03 ng/mL) below the published 99th percentile (0.04 ng/mL) in 5000 participants (49.2% female) of the Gutenberg Health Study, a community-based, prospective, observational single-center cohort study. The calculated 99 th percentile cut-offs were tested in 1818 patients with suspected AMI. RESULTS: Troponin I concentration representing the 99th percentile of the overall study population was 0.04 ng/mL. Excluding individuals with prevalent cardiovascular disease lowers the 99th percentile to 0.034 ng/mL. Exclusion of individuals with traditional risk factors or elevated natriuretic peptide leads to further reduction with 0.029/0.028 ng/mL. These lower cut-offs detect more patients at risk in individuals with suspected AMI. Correlations of troponin I with age, gender and traditional risk factors were observed. CONCLUSIONS: Troponin I concentrations in apparently healthy individuals are dependent on prevalent cardiovascular diseases, traditional risk factors, gender and age. Application of corresponding cut-offs in diagnosis of AMI alters the group of patients potentially at risk.

N-terminal pro brain natriuretic peptide in the management of patients in the medical emergency department (PROMPT): correlation with disease severity, utilization of hospital resources, and prognosis in a large, prospective, randomized multicentre trial.

AIMS: N-terminal pro brain natriuretic peptide (NT-proBNP) is a potent marker of heart failure and other cardiac diseases. The value of NT-proBNP testing in the medical emergency department (ED) was assessed in patients >65 years old. METHODS AND RESULTS: This large, prospective, randomized, controlled, multicentre trial was conducted in six medical EDs. Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients. Median NT-proBNP was 582 pg/mL. A total of 16% of patients presented with NT-proBNP <150 pg/mL (low), 55% with NT-proBNP between 150 and 1800 pg/mL (intermediate), and 29% with NT-proBNP >1800 pg/mL (high). NT-proBNP was positively correlated with hospital admission [ odds ratio (OR) for high vs. low 2.9, P < 0.0001], length of stay (8.5 days vs. 3.5 days for high vs. low, P < 0.01), in-hospital death (3.9% vs. 0% for high vs. low, P < 0.01), 6 months re-hospitalization (OR for high vs. low 5.1, P < 0.0001), and 6 months death or re-hospitalization (OR for high vs. low 5.7, P < 0.0001). Knowledge of NT-proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit (IMC/ICU) admission, length of stay, re-hospitalization and death, or re-hospitalization in the total cohort. However, patients with high open NT-proBNP (>1800 pg/mL) were more likely to be admitted to the hospital (P < 0.05) and IMC/ICU (P < 0.05), whereas patients with low open NT-proBNP (<150 pg/mL) were less likely to be admitted (P < 0.05) compared with patients with blinded NT-proBNP. CONCLUSION: Although NT-proBNP does not affect overall hospitalization, it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital resources and prognosis.

Evaluation of the Stratus CS Acute Care D-dimer assay (DDMR) using the Stratus CS STAT Fluorometric Analyzer: a prospective multisite study for exclusion of pulmonary embolism and deep vein thrombosis.

BACKGROUND: D-dimer testing is an integral part of the diagnostic algorithm in excluding patients with venous thromboembolism. In this study, we prospectively evaluated the Stratus DDMR D-dimer test in patients suspected of pulmonary embolism (PE) and deep vein thrombosis (DVT). METHODS: Patients suspected of venous thromboembolism were prospectively enrolled at four different clinical sites, with sodium citrate and lithium heparin plasma was tested using the DDMR D-dimer test on the Stratus CS analyzer. RESULTS: 1,012 patients were enrolled for analysis, with 85/603 (14.1%) patients with PE and 80/443 (18.1%) with DVT, and four of the patients (0.4%) with PE and DVT. For the samples collected in 3.2% sodium citrate, the DDMR method had a sensitivity, specificity, and negative predictive value for VTE of 98.0%, 38.1%, and 99.1%, respectively. For the samples collected in lithium heparin, the DDMR method had a sensitivity, specificity, and negative predictive value (NPV) for VTE of 98.9%, 28.8%, and 99.4%, respectively. In PE, DDMR testing on citrate plasma had a sensitivity, specificity, and NPV of 98.8%, 39.5%, and 99.6%, respectively, while heparin samples had a sensitivity, specificity, and NPV for PE of 98.0%, 28.4%, and 99.1%, respectively. In DVT, citrate plasma had a sensitivity, specificity, and NPV for DVT of 97.5%, 32.0%, and 98.3%, respectively, while heparin samples had a sensitivity, specificity, and NPV for DVT of 100%, 27.8%, and 100%, respectively. CONCLUSION: The Stratus CS DDMR D-dimer can be used in those patients with non-high clinical pre-test probability for the exclusion of PE.

Differences in serum zn levels in acutely ill and recovered adolescents and young adults with anorexia nervosa--a pilot study.

Preliminary evidence suggests that changes in zinc (Zn) metabolism are associated with anorexia nervosa (AN). However, data are scarce regarding potential differences in serum Zn concentrations in adolescent and young adult patients with AN. It was the aim of the present pilot study to compare serum Zn concentrations between acutely ill and remitted adolescent and young adult female patients with AN and female controls. Zn concentrations were higher in remitted compared with acutely ill patients. Zn concentrations were also higher in remitted patients compared with controls, but there was no significant difference in Zn concentrations between acutely ill patients and controls. The present study provides preliminary evidence for differences in serum Zn status in recovered patients with AN. These differences are likely influenced by reported food preferences, in particular as regards Ca²âº and phosphorus-containing foods. However, because of limited statistical power, future research involving larger samples is necessary.

Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with Major Depression.

In Major Depressive Disorder, a growing data base suggests that the onset of antidepressants' action can be detected by improvement of depressive symptoms in the first 10-14 days of treatment. Previous studies showed that the mean concentration of the brain-derived neurotrophic factor (BDNF) in blood increases during antidepressant treatment and positively correlates with amelioration of MDD symptoms. We previously showed an association between very early changes of the serum BDNF concentration and treatment outcome (Tadic et al., 2011. Prog Neuropsychopharmacol Biol Psychiatry 35, 415-420). However, no study has yet investigated whether BDNF concentration in plasma increases in the early course of treatment and enables the prediction of final treatment outcome. The goal of this study was to investigate in MDD patients, whether the change of pBDNF in the early course of treatment is a specific and sensitive marker for final treatment outcome. For this purpose, we performed a naturalistic pilot study with 39 inpatients with MDD according to DSM-IV. Depression severity and pBDNF were measured in weekly intervals from baseline (EP) to endpoint (EP, max. week six) with the 21-item Hamilton Depression Rating Scale (HAMD-21) and enzyme-linked immunosorbent assay (ELISA), respectively. According to ROC-analysis, the best cut-off value for the prediction of response at EP is an increase of 338 pg/ml or 126%, respectively, of pBDNF between BL and day 7. The single markers pBDNF change and HAMD-21 improvement from BL-d7 predicted later treatment outcome with moderate to high sensitivity and specificity (pBDNF: 42% and 96%, resp.; HAMD improvement: 83% and 65%, resp.). The combined marker early pBDNF change plus HAMD-21 improvement at day 7 increased the specificity for response to 100%. Our data provide first preliminary evidence that an early change of pBDNF in conjunction with early improvement might be a peripheral marker predictive for treatment outcome in patients with MDD. This has to be confirmed in further investigations. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the AtheroGene study.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation. METHODS: We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years. RESULTS: The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individuals presenting with SAP had only slightly lower plasma MR-proADM concentrations than those with ACS (0.53 vs 0.55 nmol/L, P=0.006). MR-proADM showed a moderate association with age, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, serum C-reactive protein, hypertension, diabetes, and prevalent multivessel disease (all P<0.0005). Individuals suffering from a cardiovascular event had higher MR-proADM concentrations at baseline in both groups (SAP 0.63 vs 0.53 nmol/L and ACS 0.65 nmol/L vs 0.55 nmol/L, both P<0.0005). Cox regression analysis incorporating various variables of cardiovascular risk and NT-proBNP revealed a hazard ratio of 1.4 (95% CI 1.2-1.6; P<0.0005) per increment of MR-proADM by 1SD. In risk models for secondary prevention, MR-proADM provided information comparable to that of NT-proBNP. CONCLUSIONS: MR-proADM is an independent predictor for future cardiovascular events in patients with symptomatic coronary artery disease, providing information comparable to NT-proBNP for secondary risk stratification.

Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction.

CONTEXT: Introduction of highly sensitive troponin assays into clinical practice has substantially improved the evaluation of patients with chest pain. OBJECTIVE: To evaluate the diagnostic performance of a highly sensitive troponin I (hsTnI) assay compared with a contemporary troponin I (cTnI) assay and their serial changes in the diagnosis of acute myocardial infarction (AMI). DESIGN, SETTING, AND PATIENTS: A total of 1818 patients with suspected acute coronary syndrome were consecutively enrolled at the chest pain units of the University Heart Center Hamburg, the University Medical Center Mainz, and the Federal Armed Forces Hospital Koblenz, all in Germany, from 2007 to 2008. Twelve biomarkers including hsTnI (level of detection, 3.4 pg/mL) and cTnI (level of detection, 10 pg/mL) were measured on admission and after 3 and 6 hours. MAIN OUTCOME MEASURES: Diagnostic performance for AMI of baseline and serial changes in hsTnI and cTnI results at 3 hours after admission to the emergency department. RESULTS: Of the 1818 patients, 413 (22.7%) were diagnosed as having AMI. For discrimination of AMI, the area under the receiver operating characteristic (ROC) curve was 0.96 (95% CI, 0.95-0.97) for hsTnI on admission and 0.92 (95% CI, 0.90-0.94) for cTnI on admission. Both were superior to the other evaluated diagnostic biomarkers. The use of hsTnI at admission (with the diagnostic cutoff value at the 99th percentile of 30 pg/mL) had a sensitivity of 82.3% and a negative predictive value (for ruling out AMI) of 94.7%. The use of cTnI (with the diagnostic cutoff value at the 99th percentile of 32 pg/mL) at admission had a sensitivity of 79.4% and a negative predictive value of 94.0%. Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both hsTnI and cTnI assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value (for ruling in AMI) for hsTnI increased from 75.1% at admission to 95.8% after 3 hours, and for cTnI increased from 80.9% at admission to 96.1% after 3 hours. CONCLUSIONS: Among patients with suspected acute coronary syndrome, hsTnI or cTnI determination 3 hours after admission may facilitate early rule-out of AMI. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours after admission may facilitate an early diagnosis of AMI.

Effect of autologous blood transfusion on cerebral cytokine expression.

BACKGROUND: Autologous blood transfusion (ABT), for example, by means of cell saver equipment, is used to reduce the need for allogenic blood transfusion in patients with high perioperative blood loss. This study investigated the effect of blood/extracorporal surface interaction during withdrawal and retransfusion of shed autologous blood on cerebral inflammation in rats. Rats subjected to hypotension with cerebral ischemia served as positive controls. METHODS: Eighty-eight male Sprague-Dawley rats were anesthetized with sevoflurane, instrumented, and randomly assigned to the following groups: sham-operation (SHAM), autologous blood withdrawal/transfusion only (ABT), or bilateral carotid artery occlusion and autologous blood withdrawal/transfusion (BCAO/ABT). Inflammatory gene expression was investigated with real-time RT-polymerase chain reaction at 6, 12, and 24 hours after SHAM, ABT, or BCAO/ABT in brain hippocampal tissue. Naive rats were investigated as reference. RESULTS: ABT alone had no impact on hippocampal inflammatory gene expression, whereas after BCAO/ABT tumor necrosis factor-alpha (10.7 fold at 24 h), interleukin-1ß (2.1 fold at 6 h), interleukin-6 (35.7 fold at 24 h), COX-2 (9.3 fold at 6 h), and inducible nitric oxide synthase (3.4 fold at 24 h) increased compared with SHAM. CONCLUSIONS: ABT by itself did not provoke an inflammatory reaction in the healthy brain. However, in combination with cerebral ischemia the induction of a broad spectrum of inflammatory parameters indicates an inflammatory reaction of the hippocampus beginning after 6 hours and being most pronounced after 24 hours. Therefore, this study shows that cerebral inflammation is not induced by ABT after contact with extracorporal surfaces in rats.

Influence of 8 and 24-h storage of whole blood at ambient temperature on prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin and D-dimer.

This study evaluates the effect of whole blood storage on common coagulation parameters in order to confirm or revise acceptable storage limits as defined by current guidelines and diverse study reports. Aliquots were taken from the citrated whole blood of inpatients and outpatients (n = 147) within 4 h after blood withdrawal and after extended storage of whole blood for 8 and 24 h at ambient temperature. Aliquots were centrifuged and analyzed for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), antithrombin (AT), thrombin time (TT) and D-dimer. For each parameter, samples from 33-56 patients were investigated covering a wide range of normal and pathological values. Samples from patients receiving heparin were excluded from analyses of APTT and TT. All assays were performed using reagents and an analyzer from Siemens Healthcare Diagnostics Products GmbH. The mean percentage change after 8 and 24-h storage was below 10% for all parameters. Considering the changes in individual samples, all parameters can be reliably tested after 8-h storage, since less than 15% of the samples demonstrated individual changes of above 10%. The acceptable storage time can be extended to 24 h for PT, TT and D-dimer. Clinically relevant changes were detected after 24-h storage for APTT: 41% of the investigated samples demonstrated changes of above 10%. After 24-h storage, changes for Fbg and AT values were more than 15% in five out of 49 and in three out of 45 samples, respectively. This sporadic increase of values is clinically acceptable except for borderline samples.

The early non-increase of serum BDNF predicts failure of antidepressant treatment in patients with major depression: a pilot study.

In the treatment of patients with major depressive disorder (MDD), early non-improvement of symptoms after initiation of antidepressant treatment is a highly sensitive and specific marker for final treatment failure. On the other hand, meta-analyses of clinical studies investigating serum BDNF (sBDNF) concentration before and after antidepressant treatment showed an increase of sBDNF during treatment, which was correlated with amelioration of depressive symptoms. No study has yet investigated the predictive value of early changes of sBDNF for final treatment outcome of the individual patient. The aim of this study was to investigate in patients with MDD, whether i) the non-increase of sBDNF in the early course of treatment is a specific and sensitive marker for final treatment failure, ii) whether the sensitivity and specificity of early non-improvement for treatment failure can be increased by combining it with the marker "early non-increase of sBDNF". For this purpose, we performed a pilot study with 41 inpatients with MDD according to DSM-IV, who were treated in a naturalistic setting. Depression severity and sBDNF were measured in weekly intervals from baseline to week six with the 21-item Hamilton Depression Rating Scale (HAMD-21) and ELISA, respectively. The individual markers sBDNF non-increase and HAMD-21 non-improvement from baseline to day 7 or 14 predicted later non-response and non-remission with moderate to high specificity. The combined marker sBDNF non-increase plus HAMD-21 non-improvement at day 14 increased the specificity for non-response and non-remission to 100%. Our data provide the first evidence that the absence of an early increase of sBDNF in conjunction with early non-improvement might be a highly specific peripheral marker predictive for treatment failure in patients with MDD. If replicated, this combined marker could be considered useful for prospective confirmatory trials in patients with MDD.

WITHDRAWN: Association analysis between the early change of serum brain-derived neurotrophic factor (sBDNF) and final change of depression severity during antidepressant treatment: A pilot study.

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Multiple marker approach to risk stratification in patients with stable coronary artery disease.

AIMS: multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina. METHODS AND RESULTS: we investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic peptide (Nt-proBNP)] in 1781 stable angina patients in relation to non-fatal myocardial infarction and cardiovascular death (n = 137) over 3.6 years. Using Cox proportional hazards models and C-indices, the strongest association with outcome for log-transformed biomarkers in multivariable-adjusted analyses was observed for Nt-proBNP [hazard ratio (HR) for one standard deviation increase 1.65, 95% confidence interval (CI) 1.28-2.13, C-index 0.686], GDF-15 (HR 1.59, 95% CI 1.25-2.02, C-index 0.681), MR-proANP (HR 1.46, 95% CI 1.14-1.87, C-index 0.673), cystatin C (HR 1.39, 95% CI 1.10-1.75, C-index 0.671), and MR-proADM (HR 1.63, 95% CI 1.21-2.20, C-index 0.668). Each of these top single markers and their combination (C-index 0.690) added predictive information beyond the baseline model consisting of the classical risk factors assessed by C-index and led to substantial reclassification (P-integrated discrimination improvement <0.05). CONCLUSION: comparative analysis of 12 biomarkers revealed Nt-proBNP, GDF-15, MR-proANP, cystatin C, and MR-proADM as the strongest predictors of cardiovascular outcome in stable angina. All five biomarkers taken separately offered incremental predictive ability over established risk factors. Combination of the single markers slightly improved model fit but did not enhance risk prediction from a clinical perspective.

Copeptin improves early diagnosis of acute myocardial infarction.

OBJECTIVES: Early identification of myocardial infarction in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation. BACKGROUND: The aim of the current investigation is to test whether determination of copeptin, an indirect marker for arginin-vasopressin, adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infarction. METHODS: Between January 2007 and July 2008, patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study. Copeptin, troponin T (TnT), myoglobin, and creatine kinase-myocardial band were determined at admission and after 3 and 6 h. RESULTS: Of 1,386 (66.4% male) enrolled patients, 299 (21.6%) had the discharge diagnosis of acute myocardial infarction, 184 (13.3%) presented with unstable angina, and in 903 (65.2%) an acute coronary syndrome could be excluded. Combined measurement of copeptin and TnT on admission improved the c-statistic from 0.84 for TnT alone to 0.93 in the overall population and from 0.77 to 0.9 in patients presenting within 3 h after chest pain onset (CPO) (p < 0.001). In this group the combination of copeptin with a conventional TnT provided a negative predictive value of 92.4%. CONCLUSIONS: In triage of chest pain patients, determination of copeptin in addition to troponin improves diagnostic performance, especially early after CPO. Combined determination of troponin and copeptin provides a remarkable negative predictive value virtually independent of CPO time and therefore aids in early and safe rule-out of myocardial infarction.