Abstract Background Chronic heart failure (CHF) is associated with reduced quality of life (QoL), but underlying mechanisms are incompletely understood. In this study we aimed to assess determinants of both physical and mental functioning in patients with and without chronic heart failure and investigated the impact of physical capacity (PC). Methods This is a cross-sectional analysis conducted in two cohorts using a case-control design. Both, the case cohort (RoC-HF, n=205) and the control cohort (BioPersMed, n=1022) were prospective, single center cohort studies. The case cohort included patients with diagnosed CHF with a current left ventricular ejection fraction (LVEF) <50%, while the control cohort included apparently healthy individuals with at least one cardiovascular risk factor. Laboratory parameters, transthoracic echocardiography, PC (Biopersmed: 6-minute walking distance [6MWD]; RoC-HF: 4-meter gait speed [4MGS]), and SF-36 health survey parameters as the main read-out of this study, were available in all participants. Results Cases and controls were matched by age, sex and body mass index yielding a study sample of 188 vs. 188 individuals. Medians with interquartile range of NT-proBNP and LVEF were 985 (325 – 2183) pg/dl and 37 (30 – 44) % in cases, and 72 (33 - 118) pg/dl and 64 (60 – 68) % in controls. Cases had lower levels than controls regarding all eight QoL aspects of the SF-36 HS (Figure 1). Both within the case and the control cohort, measures of heart failure severity (LVEF, NT-proBNP, TAPSE) were not or only marginally associated with SF-36 HS scales. PC parameters correlated significantly with physical component summary score (PCS) both within cases and controls, and with mental component summary score (MCS) only in cases (Figure 2). Multivariate linear regression analyses with adjustment for age, sex, eGFR, LVEF, NT-proBNP and TAPSE were conducted in each cohort, respectively. Within cases, 4MGS, but not LVEF, NT-proBNP and TAPSE, was significantly associated with MCS (adjusted beta 0.228, P=0.011) and PCS (beta = 0.318, P<0.001). Within controls, 6MWD was significantly associated with PCS (beta = 0.332, P<0.001), but not with MCS (beta = -0.62, P=0.472). Conclusion In patients with CHF, impairment of both physical and mental functioning is determined by physical capacity, but not by measures of cardiac function and congestion. By contrast, only physical functioning, but not mental functioning, can be explained by PC in healthy controls. Given the increasing relevance of QoL as a patient-oriented outcome in CHF, assessment and improvement of PC should be considered essential aspects in CHF care, besides biomarker-guided improvements in cardiac function and congestion. Whether targeting PC, for instance by medical and device therapies, translates into better physical and mental well-being in CHF should be specifically addressed in randomized controlled trials.

Einleitung LDA wird weltweit zur Prävention der Präeklampsie (PE) empfohlen. Jedoch entwickeln einige Schwangere trotz LDA eine PE. PE gilt aufgrund gemeinsamer pathophysiologischer Mechanismen (z.B.: oxidativer Stress) als eine Frühform der kardiovaskulären Erkrankungsformen (CVD). Da Aspirin, als Eckpfeiler der antithrombozytären Therapie der CVD zur Vermeidung der pathologischen Auswirkungen verwendet wird, dient die Thrombozytenfunktionstestung als Surrogat-Marker. Ziel der Arbeit ist, die Thrombozytenfunktion - mit der „Goldstandardmethode“ der Lichttransmissionsaggregometrie (LTA) nach Gustav Born - entsprechend den Erkenntnissen der kardiovaskulären Forschung zu quantifizieren und falls notwendig die prophylaktische Wirkung zu optimieren. „Aspirin low responsiveness”, ein insuffiziente Thrombozytenhemmung, ist ein bekanntes Phänomen in der Kardiologie mit einer Prävalenz von bis zu 60%.

Preeclampsia still represents a life-threatening pregnancy complication, associated with severe maternal and neonatal morbidity and mortality. Low-dose Aspirin is advised to avoid preeclampsia in high-risk pregnancies worldwide. As Aspirin does not cover all women at risk, the prescription raises questions concerning optimal target population, dosage, and onset of therapy. The aim of this study was to test platelet responsiveness on Aspirin by optical aggegrometry, to gain robust biochemically assessment data of Aspirin in an obstetric cohort. 248 women at high risk for development of preeclampsia were included in the study. Aspirin-prophylaxis was administered either in 100 mg (n = 229) or 150 mg (n = 90) daily. Dosing of 100 mg Aspirin was maintained if testing revealed a sufficient platelet inhibition. If platelet inhibition was insufficient, dosage was increased to 150 mg Aspirin and re-testing was advised. 91 patients (91/229 = 39.7%) presented a sufficient inhibitory Aspirin effect at a dosage of 100 mg, but in 138 patients LTA showed an inadequate Aspirin response (138/229 = 60.3%). In 19 women 150 mg Aspirin was administered as starting dose due to new recommendations. Of all women at 150 mg Aspirin 64 did not properly respond (35.4%). The overall rate of sufficient responding women regardless the Aspirin dose was 64.6%. This study demonstrates still an insufficient inhibition of platelet aggregation in about 1/3 of women even with a dosage of 150 mg Aspirin daily, who might potentially benefit from further increase. These data show, that there is a need for further research to allow a personalized approach for individualized Aspirin therapy, maximizing the preventive benefit for mother and child.

Einleitung Die Präeklampsie gehört weltweit zu den häufigsten und schwerwiegendsten Schwangerschaftskomplikationen. Niedrig dosierte Acetylsalicylsäure (LDA) ist derzeit als einzig effektive medikamentöse Präeklampsie- Prävention etabliert, jedoch fehlt der endgültige Beweis einer lückenlosen Wirksamkeit. Auch in der Kardiologie wird Aspirin seit Jahrzehnten als (Sekundär)-Prophylaxe bei kardiovaskulären Erkrankungen eingesetzt und stellt den Eckpfeiler der antithrombozytären Therapie dar. Das Auftreten von (atherothrombotischen) Komplikationen trotz Prophylaxe ist ein bekanntes Phänomen; es wird in der Literatur als „Aspirin-Resistenz“ oder „Aspirin low responsiveness“ bezeichnet und kann labordiagnostisch als insuffiziente Thrombozytenhemmung nachgewiesen werden. Ziel dieser Studie war die auch bei einem Teil der Hochrisikoschwangeren unter Aspirinprophylaxe vermutete klinische Aspirinresistenz- analog dem kardiologischen Vorgehen- mittels optischer Aggregometrie labordiagnostisch zu evaluieren.

Fragestellung: In letzten Jahren wurde viel über biochemische und biophysikalische Marker berichtet, die alleine oder in Kombination zur Früherkennung der Präeklampsie (PE) beitragen können. Dazu zählen unter anderem die beiden angiogenen bzw. anti-angiogenen Faktoren sFlt-1 und PlGF, welche bereits seit ein paar Jahren in der Routinediagnostik eingesetzt werden. Die kontinuierliche 24-Stunde-Blutdruckmessung ist ein wesentlicher Teil bei der Betreuung von Frauen mit hypertensiven Schwangerschaftserkrankungen. Im Rahmen dieser Untersuchungen können neben dem Blutdruck und dem Puls auch spezielle Parameter der Gefäßsteifigkeit gemessen werden, wie z. B. die Pulswellengeschwindigkeit/PWV, der Augmentationsindex/AI und der periphere Pulsdruck (PPA).

Bei Frauen mit einem Systemischen Lupus Erythematodes (SLE) sowie einem Antiphospholipid Syndrom (APS) kann eine Schwangerschaft in bis zu 35% durch eine teilweise sehr früh auftretende und schwerwiegende Präeklampsie verkompliziert werden. Obwohl die genauen pathophysiologischen Mechanismen der Präeklampsie immer noch unklar sind, ist eine Imbalance der angiogenen Plazentafaktoren Endoglin, soluble fms-like tyrosine kinase 1 (sFlt-1) und placental growth factor (PlGF) ein wesentlicher Bestandteil in der Entstehung der Präeklampsie. Die Möglichkeit eine Präeklampsie in diesen Hochrisikoschwangerschaften frühzeitig zu detektieren, könnte zu einer Verbesserung des geburtshilflichen Managements führen.

•The increased levels of ET-1, ADMA and SDMA support the theory of inflammation as part of the pathophysiology in Antiphospholipid Syndrome.•These anti-angiogenic factors with impaired angiogenesis might give a new insight in the mechanisms of adverse obstetric outcome in APS.•It seems that even if OAPS and TPS are two different clinical entities, the dimension of aPl-induced endothelial dysfunction is similar.

The neutrophil–lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Several studies suggest a negative impact of increased NLR for patient's survival in different types of cancer. However, previous findings from small-scale studies revealed conflicting results about its prognostic significance with regard to different clinical end points in non-metastatic renal cell carcinoma (RCC) patients. Therefore, the aim of our study was the validation of the prognostic significance of NLR in a large cohort of RCC patients. Data from 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single centre, were evaluated retrospectively. Cancer-specific, metastasis-free, as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of NLR, multivariate Cox regression models were applied for all three different end points. Influence of the NLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrell's concordance index. Multivariate analysis identified increased NLR as an independent prognostic factor for overall (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.10–2.31, P=0.014), but not for cancer-specific (HR=1.59, 95% CI=0.84–2.99, P=0.148), nor for metastasis-free survival (HR=1.39, 95% CI=0.85–2.28, P=0.184). The estimated concordance index was 0.79 using the Leibovich risk score and 0.81 when NLR was added. Regarding patients' OS, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. Adding the NLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.

MicroRNA-143 (miRNA-143) is frequently down-regulated in colorectal cancer (CRC) and may influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of miRNA-143. However, the prognostic significance of miRNA-143 expression and the ability to predict patient response to epidermal growth factor receptor (EGFR)-targeted agents have not yet been explored. We examined 77 CRC patients who were identified by pyrosequencing to have wild-type KRAS and were subsequently treated with EGFR-targeted therapy with the monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured in CRC tissue and corresponding non-neoplastic colon tissue by RT–PCR and its expression level was correlated with clinico-pathological characteristics. Univariate and multivariate analyses were used to calculate cancer-specific survival (CSS). The progression-free survival (PFS) and objective response rates on EGFR-targeted therapy were also evaluated. Down-regulation of miRNA-143 was observed in 47 out of 77 (61%) tumours. Multivariate Cox regression analysis identified low levels of miRNA-143 expression as an independent prognostic factor with respect to CSS (hazard ratio=1.92, confidence interval=1.1–3.4, P=0.024). A significant difference was also observed with regard to PFS on EGFR-targeted therapy (P=0.031), but there were no significant differences with regard to the objective response rates. Our data indicate that miRNA-143 expression levels serve as an independent prognostic biomarker for CRC in KRAS wild-type patients. No role for miRNA-143 expression as a predictive biomarker for EGFR-targeted agents could be identified. Given its negative impact on CSS and PFS, miRNA-143 represents a novel prognosticator and a promising drug target for patients with CRC.