Michael Behnes

Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment

IntroductionThe aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment.MethodsIn total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models.ResultsPresepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC.ConclusionsIn patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment.Trial registrationClinicalTrials.gov NCT01535534. Registered 14 February 2012.

Alterations of leptin in the course of inflammation and severe sepsis

BackgroundThe adipokine leptin regulates energy expenditure, vascular function, bone and cartilage growth as well as the immune system and systemic inflammatory response. Several activating effects towards T cells, monocytes, endothelium cells and cytokine production have been reported suggesting a protective role of leptin in the setting of an acute systemic inflammation. However, the pathophysiological role of leptin during severe sepsis is currently not elucidated in detail. This study aims to investigate leptin expression in cultured human adipocytes within an inflammatory model and in patients suffering from severe sepsis and evaluates treatment effects of drotrecogin alpha (activated) (DAA), the recombinant form of human activated protein C.MethodsIn an in-vitro inflammatory model of adipocyte cell-culture the effect of DAA on leptin mRNA expression was evaluated. Synthesis of mRNA was measured by quantitative polymerase chain reaction (qPCR). Additionally, supernatants of these adipocytes as well as serum levels of adiponectin were measured in blood of 104 severe septic patients by ELISA-method. 26 patients were treated with DAA (DAA+), 78 patients were not treated with DAA (DAA-).ResultsStimulation of human adipocytes with TNF alpha over 6 and 24 hours resulted in a significant decrease by 46% and 59% of leptin mRNA transcripts compared to un-stimulated controls (p < 0.05). Leptin levels of supernatants of adipocyte culture decreased by 25% and 23% (p < 0.05) after incubation with TNF alpha after 6 and 24 hours. Incubation with DAA at 50 ng/ml DAA and 5 μg/ml doubled mRNA expression significantly at 24 hours (p < 0.05) but not at 6 hours. From day 1 to day 3 of sepsis, leptin levels increased in DAA+ compared to DAA- patients (p<0.10).ConclusionsLeptin appears to be involved in the pathogenesis of a systemic inflammatory response during sepsis. Administration of DAA significantly increased leptin expression. The specific mechanism or even benefit of DAA towards leptin needs further ongoing research.

Long-term prognostic value of midregional pro-adrenomedullin and C-terminal pro-endothelin-1 in patients with acute myocardial infarction

Abstract Background: Midregional pro-adrenomedullin (MR-proADM) and endothelin-1 have been shown to predict mortality of patients with acute myocardial infarction. However, the prognostic value of both biomarkers in predicting long-term clinical events after acute myocardial infarction remains unclear. Methods: In a prospective study, 30 patients suffering from acute ST elevation myocardial infarction or non-ST elevation myocardial infarction were enrolled. Measurements of MR-proADM and CT-pro-endothelin-1 (CT-proET-1) were performed at initial presentation, 2 or 3 days and 4 months after acute myocardial infarction. Long-term clinical events (e.g., recurrent myocardial infarction, percutaneous transluminal coronary angioplasty, aorto-coronary venous bypass or cardiogenic shock) were documented over a period from the 4th until the 10th month. Results: Both MR-proADM and CT-proET-1 were able to differentiate patients with subsequent long-term clinical events (n=11) from those without (n=19). At the time of acute myocardial infarction, median MR-proADM level of the event group was 0.69 nmol/L as compared to 0.59 nmol/L of the no-event group (p=0.036). A difference was still observed after 3 days (event group median 0.66 nmol/L; no-event group median 0.57 nmol/L; p=0.022). Accordingly, median CT-proET-1 level was 72.9 pmol/L in the event group as compared to a median of 54.4 pmol/L in patients in the no-event group (p=0.009) 3 days after acute myocardial infarction. Within the acute phase, patients with MR-proADM levels ≥0.67 nmol/L were 3 times more likely (relative risk 2.8; 95% confidence interval 1.2–6.9; p=0.042) to suffer from a future clinical event. The area under the curve (AUC) was 0.71 (95% confidence interval 0.51–0.86; p=0.046). After 3 days, patients with CT-proET-1 levels ≥57 pmol/L were 6 times more likely (relative risk 5.9; 95% confidence interval 0.9–40.4; p=0.036) to suffer from a future clinical event. The AUC was 0.76 (95% confidence interval 0.55–0.90; p=0.015). Conclusions: Elevated levels of MR-proADM and CT-proET-1 during the acute phase of myocardial infarction may predict an adverse long-term clinical outcome. Clin Chem Lab Med 2008;46:204–11.

Characteristics and long-term outcome of right ventricular involvement in Takotsubo cardiomyopathy

OBJECTIVE Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy (SCM) resembles a reversible cardiomyopathy that is characterized by localized wall motion abnormalities in the absence of stenotic coronary vascular disease. Patients typically present with apical ballooning of the left ventricle (LV), however the right ventricle (RV) is also affected in up to 50.0% of patients. Long-term prognosis of classical SCM resembles that of patients after ST elevation myocardial infarction. Data on long-term prognosis of biventricular compared to classical SCM is controversial. The aim of this study was therefore to analyze patients with biventricular SCM regarding in-hospital outcome and long-term prognosis. MATERIALS AND METHODS 114 consecutive patients with SCM were retrospectively analyzed. 88 patients presented with classical SCM, 26 patients (22.8%) were diagnosed with biventricular SCM. Follow-up was conducted for a total of 4.4years. Mean age was 67.1years with 83.3% of patients being female. The primary endpoint was a composite of all-cause mortality, recurrence of SCM and re-hospitalization due to heart failure. RESULTS Although patients with biventricular SCM presented with a tendency towards an increased rate of cardiogenic shock (30.8% vs. 15.9%; p=0.09) and significantly more usage of inotropic support upon hospital admission (34.6% vs. 13.6%; p=0.01), there was no difference concerning the primary endpoint in both groups (50.0% vs. 44.3%; p=0.31). Furthermore, there was no difference in mortality both in-hospital (7.7% vs. 7.9%; p=0.66) and during long-term follow-up (27.3% vs. 23.1%; p=0.46). CONCLUSION Patients with biventricular SCM have the same in-hospital and long-term outcome compared to classical SCM.

Endothelial cell-specific molecule-1/endocan: Diagnostic and prognostic value in patients suffering from severe sepsis and septic shock.

PURPOSE This study aims to assess the diagnostic and prognostic value of endocan in patients with severe sepsis or septic shock on a medical intensive care unit (ICU). METHODS 150 patients suspected for at least severe sepsis were enrolled on a medical ICU. On days 1, 3, and 8, plasma levels of endocan, procalcitonin (PCT), and interleukin (IL)-6 were measured. Follow-up on all-cause mortality was performed after 30 days and 6 months. RESULTS Endocan correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II) (P < .006). Endocan was higher in patients with at least severe sepsis compared with systemic inflammatory response syndrome (SIRS) or sepsis patients (P = .0006) on days 1, 3, and 8. With a minimum sensitivity of 70%, uniform cutoff levels were set for ≥ sepsis at 1.8 ng/mL, for ≥ severe sepsis at 2.6 ng/mL, for ≥ septic shock at 2.9 ng/mL. On day 1, endocan levels of the fourth quartile were significantly associated with 30-days and 6-months mortality compared to lower levels. After adjustment in Cox regressions, endocan still revealed prognostic value. CONCLUSIONS Endocan showed diagnostic capacity to diagnose patients with severe sepsis and septic shock and revealed prognostic information for 30-days and 6-months all-cause mortality.

Diagnostic and prognostic value of osteopontin in patients with acute congestive heart failure

To evaluate the diagnostic and prognostic value of osteopontin in patients with acute dyspnoea and/or peripheral oedema suspected of having acute congestive heart failure (aCHF).

Takotsubo Cardiomyopathy after Systemic Consolidation Therapy with High-Dose Intravenous Cytarabine in a Patient with Acute Myeloid Leukemia

Background: Takotsubo cardiomyopathy (TC) is characterized by the abrupt onset of cardiac dysfunction, with transient apical and midventricular hypo-/akinesia with a compensatory hypercontractility of the remaining segments. The clinical presentation appears to be similar to acute myocardial infarction (AMI). However, the myocardial dysfunction is reversible. Case Report: We report on the case of a 58-year-old man with acute myeloid leukemia (AML) who was admitted to our hospital to receive the second course of consolidation chemotherapy with intravenous cytarabine. Subsequently, the patient developed severe dyspnea at rest, with cardiogenic shock after the central venous catheter was removed. Echocardiography revealed severe dyskinesia of the mid and apical portions of both ventricles, accompanied by a highly reduced left ventricular function (LVF). 5 months later, 12-lead electrocardiography (ECG) did not show any evidence of repolar-ization disorders and echocardiographic evaluation revealed a normal LVF. We suppose that the underlying mechanism was TC. Conclusions: TC can occur in patients with AML under systemic chemotherapy, which possibly represents a triggering factor for TC development. Cardiogenic shock is a serious life-threatening complication of TC. Nevertheless, the prognosis of TC is favorable and a complete recovery of the LVF is possible.

Impact of concomitant atrial fibrillation on the prognosis of Takotsubo cardiomyopathy

Aims Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. Supraventricular tachycardia is a well-known complication of TTC. This study was performed to determine the short- and long-term prognostic impact of atrial fibrillation associated with TTC patients. Methods and results Our institutional database constituted a collective of 114 patients diagnosed with TTC from 2003 to 2015. The patients were divided into two groups according to the presence (n = 21, 18.4%) or absence (n = 93, 81.5%) of atrial fibrillation. The endpoint was a composite of in-hospital events (thromboembolic events and life-threatening arrhythmias), all-cause mortality, rehospitalization due to heart failure, stroke, and the recurrence of TTC. The in-hospital mortality, 30-day mortality, and long-term mortality were significantly higher in the atrial fibrillation group. Kaplan-Meier analysis indicated a significantly lower event-free survival rate over a mean follow-up of 3 years in the atrial fibrillation group than that in the non-atrial fibrillation group (log-rank, P < 0.01). In a multivariate cox regression analysis, atrial fibrillation (hazard ratio, HR 2.3, 95% confidence interval, CI: 1.1-4.9, P < 0.05) and EF ≤ 35% (HR 2.0, 95% CI: 1.1-3.8, P < 0.05) were the only independent predictors of a primary endpoint. Conclusion Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTC patients suffering from atrial fibrillation compared with patients without atrial fibrillation.

Prevalence, Clinical Characteristics, and Predictors of Patients with Thromboembolic Events in Takotsubo Cardiomyopathy

Background Several acute complications related to takotsubo cardiomyopathy (TTC) have been documented recently. However, the incidence and clinical significance of acute thromboembolic events in TTC is not well established. Methods A detailed investigation of the clinical characteristics and in-hospital complications of 114 consecutive patients diagnosed with TTC between January 2003 and September 2015 was carried out. This study was initiated to reveal the predictors, clinical significance, and short-term and long-term outcomes of patients with TTC associated with acute thromboembolic events on index presentation. Results The incidence of acute thromboembolic events related to TTC was around 12.2%, and these included ventricular thrombi, cerebrovascular events, retinal and brachial artery pathologies, renal, splenic, and aortic involvement. The most frequent complication on initial presentation was cardiogenic shock (20%) accompanied with pulmonary congestion (20%). Interestingly, patients experiencing thromboembolic events had higher C-reactive protein (CRP) levels as compared to the non-thromboembolic group (P = 0.02). Certain thromboembolic events were characterized by the presence of ST-segment elevation in electrocardiogram (P 0.02). Chest pain was the primary symptom in these patients (P 0.09). Furthermore, there was significant right ventricular involvement (as assessed by transthoracic echocardiography) in patients presenting with an acute thromboembolic event (P 0.08). A Kaplan–Meier analysis indicated a significantly higher mortality rate over a mean follow-up of three years in the thromboembolic group than the non-thromboembolic group (log-rank, P = 0.02). Conclusions Our results confirmed the relative common occurrence of thromboembolic events in the setting of TTC. Inflammation might play an important role in the development of thromboembolic events, and a right ventricular involvement and ST-segment elevation could be positive predictors for this occurrence. In order to circumvent the risk of a negative outcome, it is recommended that an anticoagulation therapy be initiated in all high-risk patients.

The P-Selectin Gene Polymorphism Val168Met: A Novel Risk Marker for the Occurrence of Primary Ventricular Fibrillation During Acute Myocardial Infarction

The P‐Selectin Gene Polymorphism Val168Met. Aims: Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death (SCD). Family history of SCD is described as risk factor for primary VF during acute AMI. Genetic factors may be associated with primary VF. We examined polymorphisms in genes related to the activation and adhesion of blood platelets in patients with and without VF in the setting of AMI and among healthy controls.