Insulin- und IGF-Liganden- und Rezeptorspezifität humaner Granulosazellen in vitro:Bedeutung für Proliferation und Apoptose bei der Follikelreifung

Im Ovar kommt es in zyklischer Regelmäßigkeit zum Wachstum mehrerer Follikel, von denen nur einer selektiert wird und ovuliert. Als die wichtigsten Regulatoren von Zellvermehrung, Zelldifferenzierung und Zelltod dienen die Gonadotropine. Ziel der Dissertation ist es, die Beteiligung der verschiedenen Rezeptoren an den durch Liganden des Insulin-/ IGF-Systems induzierten proliferativen und antiapoptotischen Effekten an primären humanen Granulosaluteinzellen zu untersuchen. Durch die Liganden können proliferative und antiapoptotische Stimuli an Granulosazellen ausgelöst werden. Durch Einsatz eines spezifisch am IGF-Rezeptor Typ 2 wirkenden Analogons kann gezeigt werden, dass über diesen Rezeptor die antiapoptotische, aber nicht die proliferative Wirkung vermittelt wird. Die spezifische Blockade des IGF-Rezeptor Typ 1 führt zu keiner verminderten Stimulation der proliferativen Aktivität, so dass hier auch alternative Signalvermittler wie der Insulin-Rezeptor in Betracht kommen

Case Report: Sapien 3 Transcatheter Heart Valve Embolization: Cause, Management, and Redo

The transcatheter heart valve (THV) embolization is a rare but challenging complication in transcatheter aortic valve implantation (TAVI). We report the case of an 81-year-old man with Sapien 3 embolization caused by interrupted rapid pacing. In this setting, we describe the embolized THV management and the technique of the second Sapien 3 implantation

Relationship between the resting heart rate and the extent of coronary artery disease as assessed by myocardial perfusion SPECT

AIM: Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progression of coronary artery disease (CAD). The aim of this paper is to test the hypothesis whether elevated RHR correlates with the presence and the extent of CAD in patients evaluated for CAD. METHODS AND RESULTS: The association between RHR and CAD findings and myocardial perfusion SPECT (MPS) was tested in 1,465 patients. Patients with atrial fibrillation, pacemaker rhythm and treatment with negative chonotropic drugs were excluded. Standard scores for MPS evaluation were used. CAD findings of myocardial ischaemia or scar were present in 408 patients (28%). The prevalence of CAD finding at MPS was not higher among patients with RHR above the median value of 79 bpm compared to patients with lower RHR (28% vs 28%; p = 1.00). The extent of myocardial ischaemia and scar did not increase with higher quartiles of RHR. In contrast, the presence of other established cardiovascular risk factors such as diabetes, male gender, more advanced age and presence of CAD symptoms such as angina and dyspnoea were independent predictors of CAD findings (p <0.05 for all). CONCLUSION: Elevated RHR is not associated with the presence and the extent of CAD in patients evaluated for suspected but previously unknown CAD, suggesting that the impact of a higher RHR on mortality may be linked with other factors than only CAD itself

Five-year outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with acute coronary syndrome: A subgroup analysis of the BIOSCIENCE trial.

BACKGROUND Thin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) have been shown to reduce target lesion failure (TLF) at one-year follow-up compared with durable polymer everolimus-eluting stents (DP-EES) among patients with acute coronary syndrome (ACS). The long-term clinical benefits of thin-strut BP-SES over DP-EES in ACS patients after complete degradation of the polymer coating remain uncertain. METHODS We performed a post-hoc subgroup analysis of ACS patients included into the BIOSCIENCE randomized trial (NCT01443104). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction or clinically indicated target lesion revascularization, at 5 years. RESULTS Among 2119 patients enrolled between March 2012 and May 2013, 1131 (53%) presented with ACS. The 5-year cumulative incidence of TLF was significantly lower in patients with ACS compared to chronic coronary syndrome [16.5% vs. 22.9%; rate ratio (RR), 0.69; 95% confidence interval (CI), 0.57-0.85; p < 0.001]. At 5 years, TLF occurred similarly in ACS patients treated with BP-SES and DP-EES (16.9% vs. 16.0%; RR, 1.04; 95% CI, 0.78-1.41; p = 0.78). The individual components of the primary endpoint did not differ between ACS patients treated with BP-SES or DP-EES at 5 years. Overall, there was no interaction between clinical presentation and treatment effect. CONCLUSIONS In a subgroup analysis of the BIOSCIENCE trial, we found no difference in long-term outcomes between ACS patients treated with BP-SES or DP-EES at 5 years

Continued non-vitamin K antagonist oral anticoagulants versus vitamin K antagonists during transcatheter aortic valve implantation

BACKGROUND One-third of patients undergoing transcatheter aortic valve implantation (TAVI) have an indication for long-term oral anticoagulation (OAC). AIMS We aimed to investigate whether continued non-vitamin K antagonist oral anticoagulant (NOAC) therapy compared with continued vitamin K antagonist (VKA) therapy during TAVI is equally safe and effective.  Methods: Consecutive patients on OAC with either NOAC or VKA undergoing transfemoral TAVI at five European centres were enrolled. The primary outcome measure was a composite of major/life-threatening bleeding, stroke, and all-cause mortality at 30 days. RESULTS In total, 584 patients underwent TAVI under continued OAC with 294 (50.3%) patients receiving VKA and 290 (49.7%) patients receiving NOAC. At 30 days, the composite primary outcome had occurred in 51 (17.3%) versus 36 (12.4%) patients with continued VKA and with continued NOAC, respectively (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.43-1.07; p=0.092). Rates of major/life-threatening bleeding (OR 0.87, 95% CI: 0.52-1.47; p=0.606) and stroke (OR 1.02, 95% CI: 0.29-3.59; p=0.974) were not different between groups. In a multivariate Cox regression analysis, continued NOAC, compared with continued VKA, was associated with a lower risk for all-cause 1-year mortality (hazard ratio [HR] 0.61, 95% CI: 0.37-0.98; p=0.043). The analysis of the propensity score-matched cohort revealed similar results. CONCLUSIONS Continued NOAC compared with continued VKA during TAVI led to comparable outcomes with regard to the composite outcome measure indicating that continued OAC with both drugs is feasible. These hypothesis-generating results need to be confirmed by a dedicated randomised controlled trial

Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation of Vitamin K Antagonists or Direct Oral Anticoagulants.

OBJECTIVES The authors investigated whether transcatheter aortic valve replacement (TAVR) with periprocedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with periprocedural interruption of anticoagulation. BACKGROUND A significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal periprocedural management of such patients is unknown. METHODS Consecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality. RESULTS Of 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89, CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59, 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90, 95% CI: 0.73 to 1.12; p = 0.36). CONCLUSIONS Continuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation

Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections

Pulmonary infections constitute a substantial health problem worldwide. Here the authors show that phagocytes similar to primitive macrophages can be generated from human induced pluripotent stem cells, by the use of industry-compatible, stirred-tank bioreactors, and applied as a cell-based therapy to treat acute bacterial infections in mice