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Human cortical organoids have become important tools for studying human brain development, neurodevelopmental disorders, and human brain evolution. Studies analyzing gene function by overexpression or knockout have been instrumental in animal models to provide mechanistic insights into the regulation of neocortex development. Here, we present a detailed protocol for CRISPR/Cas9-mediated acute gene knockout by electroporation of sliced human cortical organoids. The slicing of cortical organoids aids the identification of ventricle-like structures for injection and subsequent electroporation, making this a particularly well-suited model for acute genetic manipulation during human cortical development. We describe the design of guide RNAs and the validation of targeting efficiency in vitro and in cortical organoids. Electroporation of cortical organoids is performed at mid-neurogenic stages, enabling the targeting of most major cell classes in the developing neocortex, including apical radial glia, basal progenitor cells, and neurons. Taken together, the electroporation of sliced human cortical organoids represents a powerful technique to investigate gene function, gene regulation, and cell morphology during cortical development.

Background : Placenta accreta spectrum (PAS) can be the cause of major morbidity and its optimal management is still controversial. The aim of this study was to compare the traditional one-step surgery with a two-step surgical approach in which the placenta is left in situ and the second final operation is delayed to minimise blood loss. Methods : We conducted a single-centre retrospective cohort study including all patients managed for PAS between 2007 and 2023. The number of units of red blood cells (RBCs) needed during surgery was the primary outcome used to compare these two approaches. Results : A total of 43 cases were included in this analysis. Twenty of these were managed with the delayed two-step surgical approach, whereas 23 received one-step surgery. The median estimated blood loss during surgery was 2000 mL and 2800 mL for two-step and one-step surgery, respectively ( p = 0.095). In the two-step surgical approach, the median number of RBC units transfused during surgery was significantly lower ( p = 0.049) and the odds ratio for needing more than four units of RBCs was 0.28 (95%-CI: 0.08-0.98, p = 0.043). A longer interval between the caesarean section and the second operation showed a trend toward lower blood loss ( p = 0.065) and was associated with a significantly lower number of RBC units needed during surgery ( p = 0.019). Conclusions : Two-step surgery for the treatment of PAS was safe in our cohort and could lead to a reduction in blood transfusion. Leaving the placenta in situ and delaying the final operation represents a possible alternative to traditional caesarean hysterectomy.

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone. Treatment of cortical organoids with EPIREGULIN promotes a further increase in proliferation of gorilla but not of human basal progenitor cells. EPIREGULIN competes with the epidermal growth factor (EGF) to promote proliferation, and inhibition of the EGF receptor abrogates the EPIREGULIN-mediated increase in basal progenitor cells. Finally, we identify putative cis-regulatory elements that may contribute to the observed inter-species differences in EREG expression. Our findings suggest that species-specific regulation of EPIREGULIN expression may contribute to the increased neocortex size of primates by providing a tunable pro-proliferative signal to basal progenitor cells in the subventricular zone., (© 2024. The Author(s).)

Pomace as a side stream from black currant juice production is mostly discarded, even though it is rich in nutrients like protein, fiber, sugars, anthocyanins, polyphenols, and other secondary metabolites. Fungi from the division of Basidiomycota have a great enzymatic toolbox to recycle these complex mixtures of nutrients. In particular, the edible medicinal fungus Wolfiporia cocos has been described as a suitable biocatalyst to form pleasant aroma compounds in fermentation processes. Therefore, medium optimization, upscaling, and filtration were performed to produce a beverage based on black currant pomace fermented with W. cocos . A trained panel described the beverage as highly pleasant, reminiscent of honey, flowers and berries with a well-balanced sour and sweet taste. The flavor compounds linalool (citrus), geraniol (flowery), phenylacetic acid (honey), methyl phenylacetate (honey), eugenol (clove), and 2-phenylethanol (rose) were produced during fermentation and the concentrations exceeded their respective odor thresholds. The produced beverage was evaluated with 8.0 ± 1.4 from 10 for the question of whether panelists would buy the product. Fungal fermentation with the edible fungus W. cocos enabled the production of a highly pleasant beverage and additionally may reduce waste by using pomace and table sugar as sole ingredients., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05677-4., Competing Interests: Conflict of interestWe declare to have no conflict of interest., (© The Author(s) 2023.)

Purpose: Psychosocial and biological factors influence the perception of physical changes during pregnancy. Some pregnant women present to the obstetric emergency department (ED) with diverse symptoms not requiring urgent medical action. These visits result in over-consultation, tying up resources and inflating health care expenses. This study outlines factors associated with multiple ED visits during pregnancy, measures the prevalence of anxiety and depression, and explores the choice of maternity clinic for delivery aiming to elucidate options for care strategies., Methods: This prospective, cross-sectional, questionnaire-based bicentric study was performed in the obstetric outpatient departments of two university hospitals in Germany and recruited pregnant women between 12/2016 and 11/2017. The questionnaire included socio-demographics, obstetric history, anxiety (GAD-7), depression (PHQ-9), and health status (WHO-5, SF-12)., Results: This analysis included 496 women and showed that women with numerous ED visits were significantly younger (p < 0.0001), less educated (p = 0.0002), and more likely to be unemployed and single. Different prevalences for anxiety and depression were detected correlating with the number of ED visits although each showing only low effect sizes (0.024 resp. 0.015)., Conclusions: Pregnant women attending the ED more often might benefit from health education, psychosomatic interventions, and social support to overcome their depression and anxiety to avoid non-urgent ED consultations. Further prospective studies are needed to support these findings.

Introduction: Lower uterine segment (LUS) thickness measurement is frequently used to select patients for trial of labor after a previous cesarean section (TOLAC). To date no significant benefit of LUS measurement has ever been proven, and no standard protocol or clear cut-off value exists. The aim of this study was to evaluate the benefit of LUS measurement in a daily routine setting., Material and Methods: In this retrospective study, we evaluated 631 pregnancies after previous cesarean section (CS). Ultrasound measurements of myometrial (mLUS) and/or full LUS (fLUS) thickness were performed in 399 (63%) patients. The incidence, time, and mode of detection of uterine defects were studied. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated for different cut-off values of LUS thickness., Results: Uterine defects were diagnosed in 28 (4.4%) patients. Detection rate of ultrasound was low (13.6%), with better sensitivity, specificity, PPV, and NPV at lower (2 mm (fLUS) / 1 mm (mLUS): 75/96/48.3/98.7%) than at higher cut-off values (3 mm (fLUS) / 2 mm (mLUS): 15.8/93.2/10.4/68.7%)., Discussion: The benefit of LUS thickness measurement appears overestimated. As a large number of methodological factors trigger inaccuracy, a consistent protocol including both a transabdominal and a transvaginal scan performed by a trained examiner might improve accuracy. Exclusion of uterine defects might be more useful for prenatal selection after CS., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Prenatal risk stratification of women with previous cesarean section (CS) by ultrasound thickness measurement of the lower uterine segment (LUS) is challenging. There is a wide range of proposed cutoff values and a valuable algorithm for selection before birth is not available. Using 3 T magnetic resonance imaging (MRI), we aimed to identify possible shortcomings of the current protocols used for birth selection after CS. Therefore, we evaluated anatomic and morphologic differences of the LUS and its thickness in patients with CS and those without. Possible impact factors on LUS thickness were studied., Methods: We retrospectively analyzed 3 T MRI scans of 164 pregnant women in their second or third trimester, with (patient group, n = 60) and without previous CS (control group, n = 104). Sagittal T2-weighted images were studied. Normal findings of the LUS in MRI, reliability of MRI measurements, as well as factors influencing LUS thickness were assessed. MRI findings were compared to intraoperative findings., Results: MRI provided good intra- (ICC 0.872) and fair inter-rater reliability (ICC 0.643). The relationship of the LUS and the cesarean scar to the surrounding anatomical structures and also its morphology varied strongly in patients and controls. Scar identification was possible in only 9/60 (15.0%) patients. The LUS was thinner in patients (1.9 ± 0.7 mm) than in controls (2.7 ± 1.3 mm). An LUS thinning up to 1 mm was observed in 23% of women without a previous CS and in 34% of women with normal intraoperative findings. Suspicion of a uterine dehiscence (LUS thickness < 1 mm) was only found in the patient group (5/59 (8.5%)) and was intraoperatively confirmed. In controls, LUS thickness was influenced by fetal weight, gestational age and amniotic fluid amounts., Conclusion: Variability in anatomy, thickness and morphology seem to limit common prenatal LUS imaging diagnostics. Therefore, we consider that diagnostic protocols must be re-evaluated and imaging should be adjusted to the individual patient conditions. Due to its independency of ultrasound limitations, an additional MRI might be useful for altered anatomy and impaired ultrasound conditions. An LUS thinning up to 1 mm might be a normal finding and should be further investigated as reference value.

Purpose: Uterine rupture during labor is a rare but life-threatening complication after previous cesarean section (CS). Prenatal risk is assessed using ultrasound thickness measurement of the lower uterine segment (LUS). Due to inhomogeneous study results, however, clinical obstetrics still lacks for standard protocols and reliable reference values. As 3 T magnetic resonance imaging (MRI) has not yet been sufficiently studied regarding LUS diagnostics after previous CS, we sought to evaluate its feasibility focusing on thickness measurements and typical characteristics of the CS-scar region in comparison to ultrasound and the intraoperative status., Methods: In this prospective study, 25 asymptomatic patients with one previous CS and inconspicuous ultrasound findings were included. An additional 3 T MRI with either a T2-weighted Turbo-Spin-Echo or a Half Fourier-Acquired-Single-shot-Turbo-spin-Echo sequence in a sagittal orientation was performed. We analyzed categorical image quality, inter- and intra-rater reliability as well as anatomy, morphology and thickness of the LUS. Results were compared to ultrasound and intraoperative findings., Results: MRI provided good to excellent image quality in all patients. The imaged structures presented with a high variability in anatomy and morphology. Image characteristics indicating the uterine scar were only found in 11/25 (44%) patients. LUS thickness measurements with MRI showed good inter- and intra-rater reliability but poor agreement with ultrasound., Conclusions: MRI is appropriate for additional LUS diagnostics in patients with previous CS. The strong individual variability of LUS-anatomy and morphology might explain the difficulties in establishing uniform diagnostic standards after CS.

Background: Pregnancy can be distressing, particularly if expectant mothers are worried about the well-being of their fetus. Consequently, the desire for reassurance and frequent fetal monitoring is often pronounced. Smart wearable devices and telemedicine are promising tools that could assist women in self-monitoring their pregnancy at home, hence disburdening emergency departments (EDs). They present the possibility to clarify the need for urgent care remotely and offer tighter pregnancy monitoring. However, patients' acceptance of such new technologies for fetal monitoring has not yet been explored extensively., Objective: This survey aimed to elucidate the attitudes of women toward self-monitoring of their pregnancy using noninvasive electronic devices. The technical details of the proposed devices were not specified., Methods: A cross-sectional multicenter study was conducted at the departments of obstetrics of the University Hospitals of Heidelberg and Leipzig, Germany. All patients seen in the obstetrics clinic who were above 18 years were offered participation. We designed a survey questionnaire including validated instruments covering population characteristics, issues in current and past pregnancies, as well as attitudes toward self-monitoring of pregnancy with smart devices., Results: A total of 509 pregnant women with no previous experience in telemedicine participated. Only a small minority of 5.9% (29/493) regarded self-monitoring with wearable devices as an alternative to consulting their physicians. Along these lines, only 7.7% (38/496) strongly believed they would visit the ED less often if such devices were readily available. However, if the procedure were combined with a Web-based telemetric physician consult, 13.5% (66/487) would be highly motivated to use the devices. Furthermore, significantly more women regarded it as an alternative prior to seeing a doctor when they perceived a decline in fetal movements (P<.001). Interestingly, women with university degrees had a higher propensity to engage in pregnancy self-monitoring compared with women without one (37% vs 23%; P=.001). Of the participants, 77.9% (381/489) would like smart wearable devices to measure fetal heart sounds, and 62.6% (306/489) wished to use the devices on their own. Feedback from a doctor or midwife was also very important in their choice of such devices (61.8%, 301/487 wished feedback). The intended frequency of use differed vastly among women, ranging from 13.8% (65/471) who would like to use such a device several times per day to 31.6% (149/471) who favored once per week at most., Conclusions: Our results point to a skeptical attitude toward pregnancy self-monitoring among pregnant women. Nevertheless, many women are open to using devices for pregnancy monitoring in parallel to consulting their physician. The intention to use such devices several times daily or weekly, expressed by more than half of the participants, highlights the potential of such technologies., (©Katharina Schramm, Niklas Grassl, Juliane Nees, Janine Hoffmann, Holger Stepan, Thomas Bruckner, Markus W Haun, Imad Maatouk, Markus Haist, Timm C Schott, Christof Sohn, Sarah Schott. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 07.01.2019.)

Background: Dental and cervical controls are two established screening programs in Germany. Compliance to orthodontic treatment in childhood is essential for dental health and one of the first health interventions that requires adherent behavior; therefore, it may be associated with participation in further screening programs in adulthood. However, it is not yet known whether early orthodontic treatment influences long-term screening adherence., Methods: Using a questionnaire administered during a visit to a special dysplasia outpatient service, this case-control study evaluated women's personal history of orthodontic care, long-term satisfaction, and dental and gynecological screening adherence. Oral health status and dental anxiety were assessed with validated instruments. Cases were categorized as cervical dysplasia only (S2) or cervical dysplasia with conization (S1) and compared to healthy controls with a normal PAP smear., Results: A study population of 233 participants included 132 cases and 101 controls. The control group had had orthodontic treatment during childhood more often than our study population with abnormal PAP smears (68.3% controls versus 56.1% subjects; p < 0.005). Orthodontic treatment was not associated with attending dental appointment or gynecological check-ups. However, women with an orthodontic treatment in childhood were significantly more often vaccinated against human papillomavirus than women without orthodontic treatment (p < 0.03)., Conclusion: Data suggest that women with orthodontic treatment in childhood are more conscious about prevention strategies in adulthood; therefore, compliant behavior might be established in childhood.

Purpose: In this case-control study, the impact on quality of life and sexual function in women with cervical dysplasia and conization will be evaluated, in order to address coping with such a premalignant lesion and to improve strategies for salutogenesis., Methods: This multicenter case-control study evaluates women at special dysplasia outpatient clinic (T1) as well as 3 (T2) and 6 (T3) months after the diagnosis of a dysplasia. The women were subgrouped upon dysplasia only (S2) or dysplasia with conization (S1). Sexual function as well as cervix-related and general quality of life was assessed using validated instruments (FSFI-d, EORTC-QLQ-CX24, SF-36)., Results: Women with dysplasia had a lower sexual functioning than controls (FSFI: S1: 23.8 ± 9.7 (p < 0.003); S2: 25.3 ± 7.5 (p < 0.03); K: 29.1 ± 4.5) as well as a lower physical component score (SF-36: S1: 51.3 ± 8.6 (p < 0.02); S2: 51.7 ± 7.8 (p < 0.05); K: 54.2 ± 6.6) and had a significantly reduced body image (EORTC-QLQ-CX24: S1: 75.7 (p < 0.001); S2: 76.5 (p < 0.001), K:89.2). Sexual functioning was not affected by conization in the observational period over 6 months; however, sexual worry was impacted. Over temporal progression women who underwent conization worried more. Regression analysis revealed a cervical dysplasia to impact sexual function., Conclusion: Data suggest that women with the diagnosis of a cervical dysplasia are impaired in their sexual function as well as general and cervix-related quality of life, mostly independent of conization or further observation. To improve salutogenesis in the long run, the communication on dysplasia and its treatment strategy at the beginning, as well as part of aftercare, or psychosomatic intervention, might be treatment options for women at risk.

Purpose: Dilatation of the thoracic aorta is a well-known finding in corrected Tetralogy of Fallot. Complications are rare but can be life-threatening. Standard 1-dimensional (1D) measurements have several limitations. We sought to establish contrast-enhanced magnetic resonance angiography cross-sectional areas of the aorta that could serve as reference values and to identify parameters that are associated with aortic dilatation., Materials and Methods: We enrolled 101 children and adolescents. The aortic areas were measured at the level of the aortic sinus (AS), the sinotubular junction (STJ), the ascending aorta (AA), the brachiocephalic trunk (TBC), and the descending aorta (DA). Sex-specific aortic dimensions were presented as percentile curves as well as regression equations. Furthermore volumetric and functional parameters as well as clinical data were analyzed to identify parameters that are associated with aortic dilatation., Results: Aortic areas (mm) for female subjects were 139+366×body surface area (BSA) for the AS, 134+255×BSA for the STJ, 113+239×BSA for the AA, 88+185×BSA proximal to the TBC, and 2.9+88×BSA for the DA. Aortic areas (mm) for male subjects were 162+403×BSA for the AS, 171+258×BSA for the STJ, 151+233×BSA for the AA, 73+206×BSA proximal to the TBC, and 21+80×BSA for the DA. The postoperative interval and age at examination were parameters associated with aortic size., Conclusions: We provide aortic areas in children and adolescents after correction of Tetralogy of Fallot measured by contrast-enhanced magnetic resonance angiography. Our 2D data may better depict the geometry of enlarged aortae than standard 1D diameters and serve as reference values for evaluating aortic disease in these patients.

Objective: The sFlt-1/PlGF ratio is a valid marker in diagnosing or excluding preeclampsia. The currently used cut offs frame an intermediate zone of 33-85 (<34 0 weeks) or 33-110 (≥34 0 weeks), respectively. In this study we sought to evaluate the relevance of an intermediate sFlt-1/PlGF ratio for the clinical pregnancy course and outcome., Material and Methods: We retrospectively analysed 533 consecutive patients with sFlt-1/PlGF ratio measurements for suspected preeclampsia. In patients with an intermediate sFlt-1/PlGF ratio, fetal and maternal characteristics and also pregnancy outcome were documented. Furthermore, we compared the patient groups with <34 0 /34 0 -36 6 /≥37 0 gestational weeks at first visit., Results: 83/533 (15.6%) patients had an intermediate sFlt-1/PlGF ratio. Maternal or fetal diseases or twin pregnancies occurred in 87.9%. Preeclampsia/HELLP syndrome developed in 31.3% but were mostly mild or moderate (65.4%). However, severe adverse outcome was observed in 36.1% with severe preeclampsia in 10.8%. Even if further pregnancy duration and gestational week correlated negatively (r=-0.424; p<0.001), 92% of patients, tested with <34 0 weeks delivered prematurely. The overall preterm birth rate was 27.7%., Conclusions: Patients with an intermediate sFlt-1/PlGF ratio are at risk for severe adverse outcome. An intermediate sFlt-1/PlGF ratio indicates a risk for preterm birth, independent from the occurrence of preeclampsia., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Even if lower vaginal delivery success rates and impaired neonatal short-term outcomes have been reported for primiparous women with breech presentation, vaginal breech delivery remains an option for carefully selected patients. Because Magnetic resonance imaging (MRI) pelvimetry can provide additional information on maternal pelvic morphology, we sought to identify new MRI parameters that predict successful vaginal breech delivery., Methods: In this retrospective unicentre study, 240 primiparous women with breech presentation at term underwent MRI pelvimetry. For all patients vaginal delivery was planned, according to German guidelines and if the conjugata vera (CV) was ≥12 cm. The patients with uneventful vaginal deliveries and the patients who underwent a secondary caesarean section were compared according to pelvimetric parameters and outcomes. Regression analyses were performed., Results: In the vaginal delivery group (n = 162, (67.5%)), the distance between the spinae ischiadicae (interspinous diameter, ISD) was significantly enlarged. The ISD significantly influenced the mode of delivery in the regression analyses. The CV did not significantly differ between the groups. The patients with successful vaginal deliveries were significantly younger than the patients who underwent caesarean section. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for ISD was 67.7% (p<0.001, 95% CI [0.303-0.642]) and was higher considering the mother's age (AUC = 73.1%, p<0.001, 95% CI [0.662-0.800]). The neonatal short-term outcomes were comparable in both groups., Conclusion: The additional use of ISD may predict successful vaginal breech delivery and may be superior to the CV, which is more commonly used., Trial Registration: DRKS00009957.

Introduction: Dilatation of the ascending aorta is a common finding in Tetralogy of fallot (TOF). We sought to provide aortic dimensions in children and adolescents after corrected TOF obtained by contrast-enhanced cardiac-magnetic-resonance angiography (CE-CMRA) that could serve as reference values., Materials and Methods: We enrolled 101 children and adolescents (56 male) with a median age of 10.9 years. All patients underwent CE-CMRA imaging using a 3-dimensional spoiled gradient-echo-sequence. Aortic diameters were measured at the level of the aortic valve (AV), aortic sinus (AS), sino-tubular junction (STJ) and the ascending aorta (AA) and compared with normal values obtained from literature. Sex-specific aortic dimensions are given as percentile curves as well as z scores. Furthermore CMR volumetric and functional parameters as well as clinical and anamnestic data were analyzed to identify parameters that are associated with aortic dilatation., Results: Diameters for aortic size for males were 3.6 + 16.6*BSA(0.5) at the AV level, 7.0 + 19.5*BSA(0.5) at the AS level, 7.0 + 14.4*BSA(0.5) at the STJ level and 7.3 + 15.5*BSA(0.5) at the AA level. Diameters for females were 5.8 + 14.1*BSA(0.5) at the AV level, 7.2 + 17.6*BSA(0.5) at the AS level, 5.2 + 15.4*BSA(0.5) at the STJ level and 2.0 + 17.8*BSA(0.5) at the AA level. All diameters in TOF patients were larger compared with normal values. The postoperative interval and age at examination were the only parameters associated with aortic size at all measured levels., Conclusion: We provide CE-CMRA data of aortic dimensions in children and adolescents after correction of TOF. Our data might be useful for an estimation of the "normal" aortic size in this patient cohort and can serve as a basis for future longitudinal studies adding prognostic data.

Objective: To test the hypothesis that myocardial scars after repair of tetralogy of Fallot are related to impaired cardiac function and adverse clinical outcome., Methods: A total of 53 patients were retrospectively analysed after repair of tetralogy of Fallot. The median patient age was 20 years (range 2-48). Cardiac MRI with a 1.5 T magnet included cine sequences to obtain volumes and function, phase-sensitive inversion recovery delayed enhancement imaging to detect myocardial scars, and flow measurements to determine pulmonary regurgitation fraction. In addition, clinical parameters were obtained., Results: An overall 83% of patients were in NYHA class I. All patients with the exception of 2 (96%) had pulmonary insufficiency. Mean ejection fraction and end-diastolic volume index were 46% and 128 ml/m2 for the right ventricle and 54% and 82 ml/m² for the left ventricle, respectively. Excluding enhancement of the septal insertion and prosthetic patches, delayed enhancement was seen in 11/53 cases (21%). Delayed enhancement of the right ventricle was detected in 6/53 patients (11%) and of the left ventricle in 5/53 patients (9%). The patient group with delayed enhancement was significantly older (p=0.003), had later repair (p=0.007), and higher left ventricular myocardial mass index (p=0.009) compared with the group without delayed enhancement., Conclusions: This study reveals that scarring is common in patients after surgical repair of tetralogy of Fallot and is associated with older age and late repair. However, there was no difference in right ventricular function, NYHA class, or occurrence of clinically relevant arrhythmias between patients with and those without myocardial scars.

Purpose: To assess if real-time magnetic resonance (MR) imaging-guided radiofrequency (RF) ablation for atrial flutter is feasible in patients., Materials and Methods: The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients were informed about the investigational nature of the procedures and provided written informed consent. Ten patients (six men; mean age ± standard deviation, 68 years ± 10) with symptomatic atrial flutter underwent isthmus ablation. In all patients, two MR imaging conditional steerable diagnostic and ablation catheters were inserted into the coronary sinus via femoral sheaths and into the right atrium with fluoroscopic guidance. The patients were then transferred to a 1.5-T whole-body MR imager for an ablation procedure, in which the catheters were manipulated by an electrophysiologist by using a commercially available interactive real-time steady-state free precession MR imaging sequence., Results: All catheters were placed in standard positions successfully. Furthermore, simple programmed stimulation maneuvers were performed. In one of 10 patients, a complete conduction block was performed with MR imaging guidance. In nine of 10 patients, creating only a small number of additional touch-up lesions was necessary to complete the isthmus block with conventional fluoroscopy (median, three lesions; interquartile range, two to four lesions)., Conclusion: Real-time MR imaging-guided placement of multiple catheters is feasible in patients, with subsequent performance of stimulation maneuvers and occasional complete isthmus ablation.

Purpose: To determine the time course of enhancement patterns in the aorta and endoleaks at dynamic computed tomographic (CT) angiography as well as their effect on the endoleak detection rate in patients who have undergone abdominal aortic endovascular aneurysm repair (EVAR)., Materials and Methods: This retrospective study was approved by the local ethics committee and compliant with the Declaration of Helsinki. All patients gave written informed consent for the scientific analysis of their data. Seventy-one patients (mean age, 72 years ± 8 [standard deviation]) were retrospectively included after EVAR of the abdominal aorta. All patients underwent dynamic CT angiography with 10 unidirectional scan phases, followed by a venous phase. Endoleaks were detected visually in all scan phases; the magnitude of enhancement was assessed by using region-of-interest measurements in the aorta and the detectable endoleaks. Statistical analysis was performed with the χ(2) test, the paired t test, and analysis of variance with repeated measurements., Results: The highest mean aortic enhancement was achieved 12 seconds after the bolus-tracking threshold, and the highest mean endoleak enhancement was achieved 22 seconds after the bolus-tracking threshold. In total, 44 endoleaks were detected. The detection rates differed significantly in between the dynamic CT angiography phases (minimum, seven endoleaks at 2 seconds after the bolus-tracking threshold; maximum, 44 endoleaks at 27 seconds after the bolus-tracking threshold; P = .001). The highest detection rate was achieved when the contrast between aortic and endoleak enhancement reached its maximum., Conclusion: Dynamic CT angiography revealed that the peak enhancement of endoleaks is significantly different than that of the aorta and that endoleaks may not be adequately evaluated with conventional biphasic CT protocols. The use of dynamic CT angiography is associated with a significantly increased detection rate of endoleaks compared with the detection rates at the time points of conventional biphasic CT.

Objectives: To test the hypothesis that myocardial scars cause systolic dysfunction in patients with transposition of the great arteries and a systemic right ventricle., Methods: We retrospectively analyzed 20 consecutive patients (10 male, mean age 27.3 years) with a systemic right ventricle who underwent cardiac magnetic resonance imaging with 1.5 T. Cine steady-state free-precession sequences were performed to obtain volumes and function. Phase-sensitive inversion-recovery (PSIR) delayed-enhancement imaging was performed to detect myocardial scars. Tricuspid insufficiency was detected with echocardiography. Furthermore, the presence of arrhythmias and New York Heart Association (NYHA) class were assessed., Results: Mean ejection fraction of systemic right ventricles was 43 ± 11 %, mean end-diastolic volume index was 111 ± 37 ml/m(2). Delayed-enhancement imaging revealed only one myocardial scar in the wall of a right ventricular aneurysm. All patients but one (95 %) presented with tricuspid insufficiency. Clinically relevant arrhythmias were present in 13/20 patients (65 %). The majority of patients (90 %) were NYHA class I or II. Arrhythmias, tricuspid insufficiency and NYHA class were not associated with right ventricular ejection fraction., Conclusions: Although right ventricular function was clearly impaired in our patient cohort, there was only one myocardial scar. Our results show that myocardial scarring assessed by PSIR delayed-enhancement imaging is not the underlying pathology of systemic right ventricular failure.

Background: Patients with a congenitally corrected transposition of the great arteries show an increasing incidence of cardiac failure with age. In other systemic right ventricles, such as in dextro-transposition after atrial switch, excessive hypertrophy is a potential risk factor for impaired systolic function. In this trial, we sought to compare systemic function and volumes between patients with congenitally corrected transposition and those with dextro-transposition after atrial switch by using cardiac magnetic resonance imaging., Methods and Results: A total of 19 patients (nine male) with congenitally corrected transposition and 31 patients (21 male) with dextro-transposition after atrial switch were studied using a 1.5-Tesla scanner. Cine steady-state free-precession sequences in standard orientations were acquired for volumetric and functional imaging. Patient parameters were compared with those of a group of 25 healthy volunteers. Although patients with congenitally corrected transposition were older, they presented with higher right ventricular ejection fractions (p = 0.04) compared with patients with dextro-transposition. Patients with congenitally corrected transposition showed a weak negative correlation between age at examination and systemic ejection fraction (r = −0.18, p = 0.04) but no correlation between right ventricular myocardial mass index and ejection fraction. There was no significant difference in the right ventricular end-diastolic volumes between both patient groups., Conclusion: Although patients with congenitally corrected transposition had a longer pressure load of the systemic right ventricle, ventricular function was better compared with that in patients with dextro-transposition after atrial switch. The results suggest that the systemic ventricles might have partly different physiologies. One difference could be the post-operative situation after atrial switch, which results in impaired atrial contribution to ventricular filling.

Background: Systemic right ventricle (RV) hypertrophy and impaired function occur after atrial switch for dextro-transposition of the great arteries (d-TGA). Echocardiography is limited in its ability to assess the RV. We sought to evaluate systemic RV myocardial-mass index (MMI) and function after atrial switch and to analyse the role of hypertrophy for ventricular function with special consideration of the interventricular septal (IVS) movement., Methods: Thirty-seven consecutive patients (median age 22.9 years) after atrial switch were studied using cardiac magnetic resonance imaging (1.5T Intera, Philips) with a dedicated 5-channel phased-array surface cardiac coil. Cine steady-state free-precession sequences were acquired to obtain myocardial masses and function. The systolic movement of the IVS was defined as positive when moving towards the centroid of the RV and was defined as non-positive otherwise. Patient parameters were compared to controls., Results: The systemic RVs were significantly larger (p < 0.001) than the left ventricles of the control group, systolic function was significantly impaired (p < 0.001) and MMI including the IVS was comparable (p = n.s.). RV-MMI excluding the IVS and RV ejection fraction (EF) demonstrated a quadratic correlation (r = 0.6, p < 0.001), meaning that patients with RV-MMI ≤29 g/m(2) and >68 g/m(2) had a reduced level of systolic function. Positive septal movement improved RV function compared with non-positive septal movement (p = 0.024)., Conclusions: There seems to be a range of beneficial RV hypertrophy after atrial switch in which a sufficient RV-EF can be expected. A positive septal movement, probably the result of hypertrophic septal RV fibres, improves RV function and might be regarded as a beneficial contraction pattern.

Objectives: To analyse the value of cardiovascular magnetic resonance (CMR)-derived myocardial parameters to differentiate left ventricular non-compaction cardiomyopathy (LVNC) from other cardiomyopathies and controls., Methods: We retrospectively analysed 12 patients with LVNC, 11 with dilated and 10 with hypertrophic cardiomyopathy and compared them to 24 controls. LVNC patients had to fulfil standard echocardiographic criteria as well as additional clinical and imaging criteria. Cine steady-state free precession and late gadolinium enhancement (LGE) imaging was performed. The total LV myocardial mass index (LV-MMI), compacted (LV-MMI(compacted)), non-compacted (LV-MMI(non-compacted)), percentage LV-MM(non-compacted), ventricular volumes and function were calculated. Data were compared using analysis of variance and Dunnett's test. Additionally, semi-quantitative segmental analyses of the occurrence of increased trabeculation were performed., Results: Total LV-MMI(non-compacted) and percentage LV-MM(non-compacted) were discriminators between patients with LVCN, healthy controls and those with other cardiomyopathies with cut-offs of 15 g/m(2) and 25 %, respectively. Furthermore, trabeculation in basal segments and a ratio of non-compacted/compacted myocardium of ≥3:1 were criteria for LVNC. A combination of these criteria provided sensitivities and specificities of up to 100 %. None of the LVNC patients demonstrated LGE., Conclusions: Absolute CMR quantification of the LV-MMI(non-compacted) or the percentage LV-MM(non-compacted) and increased trabeculation in basal segments allows one to reliably diagnose LVNC and to differentiate it from other cardiomyopathies., Key Points: Cardiac magnetic resonance imaging can reliably diagnose left ventricular non-compaction cardiomyopathy. Differentiation of LVNC from other cardiomyopathies and normal hearts is possible. The best diagnostic performance can be achieved if combined MRI criteria for the diagnosis are used.

Purpose: To evaluate the influence of different heart rates and arrhythmias on scanner performance, image acquisition and applied radiation exposure in prospectively ECG triggered computed tomography (pCT)., Materials and Methods: An ECG simulator (EKG Phantom 320, Müller & Sebastiani Elektronik GmbH, Munich, Germany) was used to generate different heart rhythms and arrhythmias: sinus rhythm (SR) at 45, 60, 75, 90 and 120/min, supraventricular arrhythmias (e.g. sinus arrhythmia, atrial fibrillation) and ventricular arrhythmias (e.g. ventricular extrasystoles), pacemaker-ECGs, ST-changes and technical artifacts. The analysis of the image acquisition process was performed on a 64-row multidetector CT (Brilliance, Philips Medical Systems, Cleveland, USA). A prospectively triggered scan protocol as used for routine was applied (120 kV; 150 mAs; 0.4s rotation and exposure time per scan; image acquisition predominantly in end-diastole at 75% R-R-interval, in arrythmias with a mean heart rate above 80/min in systole at 45% of the R-R-interval; FOV 25 cm). The mean dose length product (DLP) and its percentage increase from baseline (SR at 60/min) were determined., Result: Radiation exposure can increase significantly when the heart rhythm deviates from sinus rhythm. ECG-changes leading to a significant DLP increase (p<0.05) were bifocal pacemaker (61%), pacemaker dysfunction (22%), SVES (20%), ventricular salvo (20%), and atrial fibrillation (14%). Significantly (p<0.05) prolonged scan time (>8 s) could be observed in bifocal pacemaker (12.8 s), pacemaker dysfunction (10.7 s), atrial fibrillation (10.3 s) and sinus arrhythmia (9.3 s)., Conclusion: In prospectively ECG triggered CT, heart rate and rhythm can provoke different types of scanner performance, which can significantly alter radiation exposure and scan time. These results might have an important implication for indication, informed consent and contrast agent injection protocols., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with right ventricular injury (RVI) complicating ST-elevation myocardial infarction (STEMI) have impaired prognosis, but it is unclear which patients are at risk of developing RVI. Cardiac magnetic resonance can identify these patients and might add important information on risk stratification, prognosis, and treatment. Aims were to determine the predictors and the prognostic significance of RVI assessed by wall motion abnormalities, edema, myocardial salvage index, and delayed enhancement in acute reperfused STEMI., Methods and Results: We studied 450 patients 1-4 days after primary angioplasty in STEMI. T2-weighted and delayed-enhancement cardiac magnetic resonance was used for visualizing edema and scar to calculate myocardial salvage index. Cine-imaging was performed to assess wall motion abnormalities, which, in combination with edema, were considered diagnostic for RVI. Patients with RVI were compared with matched patients with isolated left ventricular infarction. The primary end point was the occurrence of a major adverse cardiac event: a composite of death, reinfarction, and congestive heart failure after a median follow-up period of 20.9 months. RVI was present in 69 patients, and 41 of 69 showed myocardial necrosis. In a multivariable stepwise forward logistic regression analysis, a high RV myocardial mass (odds ratio, 2.06; 95% confidence interval, 1.18-3.58; P=0.012) and a low Thrombolysis In Myocardial Infarction flow before angioplasty (odds ratio, 0.50; 95% confidence interval, 0.32-0.76; P=0.011) were associated with RVI. Cox regression analysis revealed RVI as the most statistically significant predictor of time to major adverse cardiac events (hazard-ratio, 3.36; 95% confidence interval, 1.99-5.66; P<0.001)., Conclusions: RVI detected by cardiac magnetic resonance is a strong and independent predictor of clinical outcome after acute reperfused STEMI., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01359306.

Background and Aim: Chemoresistance often leads to loss of the last treatment option for cancer. 2-Methoxyestradiol (2-ME2) has been shown to inhibit tumor growth. The aim was to examine the efficacy of 2-ME2 on multidrug-resistant human cells from pancreatic and gastric cancer., Methods: We investigated the impact of 2-ME2 on multidrug-resistant cells derived from human pancreatic and gastric cancer cells that were positive or negative for the MDR1-gene., Results: In pancreatic cancer cells, growth inhibition was 57% in parental, 72% in MDR1-negative and 87% in MDR1-positive cells after 1 micromol/L 2-ME2. In gastric cancer cells we found a growth inhibition of 75% in parental, 82% in MDR1-positive and 95% in MDR1-negative cells. Strong induction of apoptosis was induced after a low dose of 2-ME2. No significant difference in the amount of apoptotic cells was observed between parental and multidrug-resistant cells of both tumor types. The number of apoptotic cells after 2-ME2 ranged from 7.5% in parental gastric cancer cells to 20.1% in MDR1-negative gastric cancer cells., Conclusion: 2-ME2 may therefore have clinical application for chemoresistant cancer.