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-EPICr, CDK-EPICysC, and CKD-EPICr-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

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study

INTRODUCTION: Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. METHODS: Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. RESULTS: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20–2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100–2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in surviving than in nonsurviving sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. CONCLUSION: Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results

Wer gewinnt durch die geplante Föderalismusreform?

Die Föderalismusreform soll die Zuständigkeiten von Bund und Ländern entflechten und für mehr Transparenz sorgen. Wer sind die Gewinner und wer sind die Verlierer der geplanten Änderung? Margret Wintermantel, Präsidentin der Hochschulrektorenkonferenz, befürchtet, dass die Hochschulen die Verlierer der Föderalismusreform sein könnten: "Würde die im Koalitionsvertrag beabsichtigte Föderalismusreform so umgesetzt, wie derzeit geplant, würde dies Nachteile für die Hochschulen in Deutschland mit sich bringen." Auch Hans-Peter Schneider, Universität Hannover, sieht nicht nur Gewinner, sondern auch Verlierer, meist sogar "in beiderlei Gestalt zugleich". Für ihn sind Vor- und Nachteile der Reform bei der einen oder anderen Seite nicht eindeutig zu verbuchen. Für Peter Struck, SPD-Bundestagsfraktion, dagegen werden die Reformziele - stärkere Kompetenztrennung, Abschaffung der Rahmengesetzgebung, Senkung der Zustimmungsquoten von Bundesgesetzen und Neuordnung der Finanzverantwortung von Bund und Ländern, insbes. gegenüber der EU - mit dem vorliegenden Gesamtpaket weitgehend erreicht, so dass sowohl Bund und Länder als auch die Bürger die Gewinner der Reform sind. Diese Ansicht teilt auch Wolfgang Bosbach, CDU/CSU-Bundestagsfraktion. Für ihn ist die Liste derer, die heute objektiv zu den Gewinnern der Reform zu zählen sind, ebenfalls "durchaus stattlich", während Joachim Wieland, Universität Frankfurt, auch Verlierer identifiziert: "Verlierer der Reform werden in gewissem Umfang die Ministerpräsidenten der Länder und ihre Regierungen sein. Ihnen wird die Bühne Bundesrat nur noch in weniger Fällen als gegenwärtig offen stehen."Föderalismus, Reform, Kompetenz, Staat, Hochschule, Gemeinde, Deutschland

Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study

INTRODUCTION: Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores. METHOD: We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay. RESULTS: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3–3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4–5.8) in those with sepsis, 2.3 (1.0–17.6) in those with severe sepsis and 4.5 (0.9–21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21–0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8–21.0]; P < 0.001) than in survivors (1.7 [0.4–17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used. CONCLUSION: MR-proADM may be helpful in individual risk assessment in septic patients

Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration

International audienceABSTRACT: INTRODUCTION: Post cardiac surgery vasodilatation is possibly related to a vasopressin deficiency that could be related to a chronic stimulation of the adeno-hypophysis. To assess vasopressin system activation, perioperative course of copeptin and vasopressin plasma concentrations have been studied in consecutive patients operated on cardiac surgery. METHODS: 64 consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass were studied. Haemodynamic, laboratory and clinical data were recorded before and during cardiopulmonary bypass, and at the 8th post-operative hour (H8). At the same time, point's blood was withdrawn to determine plasma concentrations of arginine-vasopressin (AVP, radioimmunoassay) and copeptin (immunoluminometric assay). Post cardiac surgery vasodilation (PCSV) was defined as a mean arterial blood pressure less than 60 mmHg with a cardiac index [equal to or greater than] 2.2 L * min^-1 * m^-2, and was treated with norepinephrine (NE) in order to restore a mean blood pressure > 60 mmHg. Patients with PCSV were compared to the other patients (controls). Student's t, Fisher's exact test, or non parametric tests (Mann Whitney, Wilkoxon) were used when appropriate. A correlation between AVP and copeptin has been evaluated and a receiver-operator characteristic (ROC) analysis was calculated to assess the utility of preoperative copeptin to distinguish between controls and PCSV patients. RESULTS: Patients who experienced a PCSV have significantly higher copeptin plasma concentration before cardiopulmonary bypass (P <0.001) but lower AVP concentrations at H8 (P <0.01) than controls. PCSV patients had preoperative hyponatremia and decreased left ventricle ejection fraction, and experienced more complex surgery (redo). The area under the ROC curve of preoperative copeptin concentration was 0.86[plus/minus]0.04 [95%CI: 0.78-0.94] (P <0.001). The best predictive value for preoperative copeptin plasma concentration was 9.43 pmol/L with a sensitivity of 90% and a specificity of 77%. CONCLUSIONS: High preoperative copeptin plasma concentration is predictive of PSCV and suggests an activation of the AVP system before surgery that may facilitate depletion of endogenous AVP stores and a relative AVP deficit after surgery

Targeting tachykinin receptors in neuroblastoma

Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma

Endothelin-1 precursor peptides correlate with severity of disease and outcome in patients with community acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>Circulating levels of endothelin-1 are increased in sepsis and correlate with severity of disease. A rapid and easy immunoassay has been developed to measure the more stable ET-1 precursor peptides proET-1. The objective of this study was to assess the diagnostic and prognostic value of proET-1 in a prospective cohort of mainly septic patients with community-acquired pneumonia.</p> <p>Methods</p> <p>We evaluated 281 consecutive patients with community acquired pneumonia. Serum proET-1 plasma levels were measured using a new sandwich immunoassay.</p> <p>Results</p> <p>ProET-1 levels exhibited a gradual increase depending on the clinical severity of pneumonia as assessed by the pneumonia severity index (PSI) and the CURB65 scores (p < 0.001 and p < 0.01). The diagnostic accuracy to predict bacteraemia of procalcitonin (AUC 0.84 [95% 0.74–0.93]) was superior than C-reactive protein (AUC 0.67 [95%CI 0.56–0.78]) and leukocyte count (AUC 0.66 [95%CI 0.55–0.78]) and in the range of proET-1(AUC of 0.77 [95%CI 0.67–0.86]). ProET-1 levels on admission were increased in patients with adverse medical outcomes including death and need for ICU admission. ROC curve analysis to predict the risk for mortality showed a prognostic accuracy of proET-1 (AUC 0.64 [95%CI 0.53–0.74]), which was higher than C-reactive protein (AUC 0.51 [95%CI 0.41–0.61]) and leukocyte count (AUC 0.55 [95%CI 0.44–0.65]) and within the range of the clinical severity scores (PSI AUC 0.69 [95%CI 0.61–0.76] and CURB65 0.67 [95%CI 0.57–0.77]) and procalcitonin (AUC 0.59 [95% 0.51–0.67]). ProET-1 determination improved significantly the prognostic accuracy of the CURB65 score (AUC of the combined model 0.69 [95%CI 0.59–0.79]). In a multivariate logistic regression model, only proET1 and the clinical severity scores were independent predictors for death and for the need for ICU admission.</p> <p>Conclusion</p> <p>In community-acquired pneumonia, ET-1 precursor peptides correlate with disease severity and are independent predictors for mortality and ICU admission. If confirmed in future studies, proET-1 levels may become another helpful tool for risk stratification and management of patients with community-acquired pneumonia.</p> <p>Trial registration</p> <p>ISRCTN04176397</p

Proenkephalin and risk of developing chronic kidney disease:The Prevention of Renal and Vascular End-stage Disease study

BACKGROUND: Proenkephalin (pro-ENK) was recently found to be associated with low estimated glomerular filtration rate (eGFR). The association of pro-ENK with urinary albumin excretion (UAE), another marker for chronic kidney disease (CKD), has not been investigated. We examined the association of pro-ENK with eGFR and UAE as markers of CKD. METHODS: We included 4375 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. CKDeGFR was defined as development of eGFR <60 ml/min/1.73 m2 and CKDUAE as albuminuria >30 mg/24 h. RESULTS: Baseline median pro-ENK was 52.2 (IQR: 44.9-60.5) pmol/L. After a median follow-up of 8.4 (IQR: 7.9-8.9) years, 183 subjects developed CKDeGFR and 371 developed CKDUAE. The association of pro-ENK with CKDeGFR was modified by sex (Pinteraction < 0.1), in such a way that after adjustment, the association only remained significant in men (adjusted hazard ratio per SD increase in 10log-transformed pro-ENK, 1.65; 95% CI: 1.15-2.36) and not in women (0.83; 0.58-1.20). No significant association was observed between pro-ENK and CKDUAE risk (0.83; 0.58-1.20). CONCLUSIONS: High pro-ENK is associated with increased risk of CKDeGFR in men, but not in women. No association of pro-ENK with CKDUAE was observed. These results should be interpreted with caution, since residual confounding and potential overfitting of models could have influenced the results