[Future of interventional cardiology : Does everything revolve around AI and robotics?] / Zukunft der interventionellen Kardiologie : Dreht sich alles um KI und Robotik?

In recent years, software-assisted imaging systems, such as computed tomography, have contributed to the improvement of noninvasive options for the diagnostics of coronary heart disease (CHD). In addition, the possibilities of individual morphological and functional atherosclerotic plaque evaluation could be further refined, e.g. by the use of optical coherence tomography or the quantitative flow ratio (QFR). Due to the development of robotic-assisted catheter systems, it has been possible to make coronary interventions more precise and with less radiation exposure for the examiner. It is to be expected that in the future even better algorithms will be developed by the analysis of very large amounts of data. These will enable a more exact, dynamic and personalized prediction of, e.g. treatment success or individual risk profiles, in order to positively and sustainably influence the treatment of patients with cardiovascular diseases.

Effect of mifepristone on the transcriptomic signature of endometrial receptivity.

STUDY QUESTION: How does a single dose of mifepristone on Day 2 after the LH peak (LH + 2) affect the endometrial receptivity transcriptome as assessed by the receptive signature established by the endometrial receptivity analysis (ERA)? SUMMARY ANSWER: A single dose of mifepristone on day LH + 2 renders the endometrium non-receptive by altering the transcriptome associated with endometrial receptivity. WHAT IS KNOWN ALREADY: Mifepristone is a progesterone receptor modulator that has been shown to alter endometrial receptivity. The ERA is a computational predictor that utilizes gene expression data of 248 genes from next generation sequencing to identify endometrial receptivity status. STUDY DESIGN, SIZE, DURATION: Endometrial biopsies were collected on day LH + 7 from controls (n = 11) and from women treated with mifepristone (n = 7). For further comparative analysis, samples were also obtained from women in the proliferative phase (n = 7). PARTICIPANTS/MATERIALS, SETTING, METHODS: Mifepristone treatment consisted of 200 mg administered on day LH + 2. Endometrial biopsies were treated for RNA isolation and cDNA conversion and sequencing. Endometrial receptivity status was assessed by the ERA computational predictor. Differential gene expression between groups was also assessed. Ingenuity Pathway Analysis was used for network analysis. Validation of gene expression results was done by qPCR. MAIN RESULTS AND THE ROLE OF CHANCE: Control samples were all staged around 'receptive' as would be clinically expected for LH + 7. Treatment samples were all staged as non-receptive (all but one was classified as 'proliferative' and the last as 'pre-receptive'). Differential gene expression analysis yielded 60 differentially expressed genes between the control and treatment groups. Bioinformatic pathway analysis for differential expression showed inactivation of the progesterone and glucocorticoid receptors, consistent with mifepristone action. LIMITATIONS, REASONS FOR CAUTION: The primary limitations are the relative small number of subjects and the use of a limited gene panel. WIDER IMPLICATIONS OF THE FINDINGS: This study sheds further light on the endometrial receptivity altering effects of mifepristone and on progesterone action. It further shows the capacity of the ERA to identify pharmacologically induced non-receptive endometrium, which expands its possible use clinically and in research. STUDY FUNDING/COMPETING INTEREST(S): C.v.G. and N.R.B. have no conflicts of interest. P.G.L. reports honorarium from University of HK/Shenzhen, other from NIF, India, outside the submitted work. K.G.D. reports consultancy for Bayer AG, Exelgyn, HRA-Pharma, Gedeon Richter, MSD, Mithra, Exeltis and Natural cycles, payment for lectures from Bayer AG, NSD, Ferring, HRA-Pharma, Exelgyn and Exeltis and clinical trials for Bayer AG, MSD, Exeltis, Mithra, HRA-Pharma and Sun Pharma. C.S. has a patent gene expression profile (ERA) issued to Igenomix and is scientific director of Igenomix S.L. M.R., R.N. and J.M.V. are employees of Igenomix S.L. TRIAL REGISTRATION NUMBER: N/A.

Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system.

OBJECTIVES: We wanted to explore the effects of two different low doses (0.5µM and 0.05µM) of mifepristone, exposed during the receptive period, on the human embryo implantation process, using a well-established three-dimensional in vitro cell culture model, specifically developed to study this process. METHODS: An in vitro three-dimensional cell culture model was constructed using human endometrial cells isolated from the endometrium of proven fertile women, collected on cycle day LH+4. After 5 days of culture, supernumerary human embryos were added and cultured for another 5 days with mifepristone 0.5µM (n=8) or 0.05µM (n=10) or vehicle as control (n=10). The cultures were checked for embryo attachment and terminated. We studied the expression of 16 reported endometrial receptivity markers in the endometrial constructs using real-time polymerase chain reaction. RESULTS: None of the embryos in 0.5µM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05µM (p=.3698) and 7 out of 10 embryos in the control group attached to the cultures. We found that most of the studied receptivity markers were significantly altered with mifepristone exposure in a similar direction in both treatment groups. Only IL6 was significantly differentially expressed between the treatment groups (p=.017). CONCLUSION: We report for the first time that exposure to a low concentration (0.5µM) of mifepristone during the receptive period successfully inhibits human embryo implantation process in vitro. Further, we observed a dose-dependent effect of mifepristone on endometrial receptivity at the functional level. IMPLICATION: This study contributes new knowledge that low dose of mifepristone during the short period of receptive phase can inhibit endometrial receptivity, which further promotes mifepristone as a contraceptive agent. This could give women a treatment choice to avoid unwanted pregnancy with high efficacy and minimal side effects.

[Mid-term outcome of cardiac surgery patients with prolonged postoperative intensive care treatment]. / Mittelfristiges Outcome kardiochirurgischer Patienten mit einer verlängerten postoperativen Intensivtherapie.

BACKGROUND: The number of patients of advanced age and with severe comorbidities undergoing cardiac surgery is rising. Therefore, in addition to the cardiac surgery procedure itself, postoperative intensive care treatment plays an increasingly important role. The mid-term outcome of patients with postoperative long-term stays in intensive care and perioperative risk factors for an adverse outcome have not been sufficiently evaluated. MATERIAL AND METHODS: All patients who underwent cardiac surgery in our institution between 2000 and 2004 and who required intensive care treatment on our cardiac surgery intensive care unit for at least 1 week were analyzed. Patients who received heart or lung transplantation or surgery for congenital heart failure were excluded. A total of 31 perioperative variables were evaluated for 230 patients. Follow-up was performed 1 year postoperatively. RESULTS: In all, 4.3% of our patients required a prolonged stay in intensive care following cardiac surgery. Overall 1-year mortality among patients with a long-term stay in intensive care was 26.9%. The logistic regression identified postoperative renal failure requiring dialysis (OR 4.98) as the strongest predictor for mortality within the first year after surgery, followed by postoperative tracheotomy and preoperatively known atrial fibrillation. CONCLUSION: Mid-term survival among patients who underwent cardiac surgery followed by a complicated postoperative course is encouragingly high. The risk factors identified for an adverse prognosis may be helpful in improving therapy strategies and general therapy decision-making.

The MIDCAB approach in its various dimensions.

INTRODUCTION: Minimally invasive direct coronary artery bypass grafting (MIDCAB) offers arterial revascularization of the left anterior descending coronary artery especially in lesions unsuitable for percutaneous coronary interventions. By avoidance of sternotomy and cardiopulmonary bypass its invasivity is less than that of conventional bypass surgery. METHODS: A literature search of all published minimal invasive direct coronary artery bypass grafting studies was performed for the period from January 1995 through November 2011. Additionally, the authors reviewed their experience in more than one thousand patients treated by minimal invasive direct coronary artery bypass grafting within the last 14 years at their institution. RESULTS: Early mortally ranged from 1.2 to 1.3%. Midterm mortality ranged up to 3.2%. At 6-month follow up 3.6% grafts were occluded and 7.2% had a significant stenosis which resulted in target vessel revascularization in 3.3% of cases. The conversion rate to sternotomy or cardiopulmonary bypass ranged between 1.2 and 6.2%. CONCLUSIONS: In the past MIDCAB was predominantly used in patients with isolated lesions of the left anterior descending coronary artery. In combination with percutaneous interventions it provides an attractive option for full revascularization in multi vessel disease especially in older patients with significant comorbidities. Overall minimal invasive direct coronary artery bypass grafting is associated with few perioperative complications and with high graft patency rates in the mid-term and long-term course.