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Orthogonal photoreactions provide a unique way to locally and independently control (thermo)mechanical properties and functionality of polymer networks simply by choice of the wavelength. Herein, a library of acrylate functional coumarin monomers is synthesized, which are cured by sequence-dependent wavelength orthogonality. In the presence of a long wavelength absorbing photoinitiator, the monomers undergo rapid curing by visible light induced radical chain growth polymerization. Subsequent irradiation with light in the UV-A region selectively initiates the [2+2] photocycloaddition of the coumarin chromophores, which is confirmed by FTIR and UV-vis experiments. Through a well-targeted design, acrylate-based and thiol-acrylate resin formulations are prepared, whose fast curing rate, low viscosity, and prolonged storage stability enable the one-step fabrication of multi-material structures by digital light processing (DLP) 3D printing. By using a dual-wavelength printer, which operates at two different wavelengths (405 and 365 nm), objects comprising soft (ε = 22%, σ = 7.5 MPa) and stiff (ε = 2%, σ = 8.3 MPa) domains are printed with a single resin vat. Along with tensile properties, the wavelength selective change in the network structure features a local control of the glass transition temperature (ΔT g  = 17 °C) in the 3D-printed objects. Soft active devices are fabricated by dual-wavelength DLP 3D printing, with distinct domains having a higher T g and the local programming of multi shapes is demonstrated., (© 2022 Wiley-VCH GmbH.)

Purpose: Classical type of lobular neoplasia (LN) encompassing both atypical lobular hyperplasia and classical lobular carcinoma in situ of the breast is a lesion with uncertain malignant potential and has been the topic of several studies with conflicting outcome results. The aim of our study was to clarify outcome-relevant factors and treatment options of classical LN., Methods: We performed a pathological re-evaluation of the preoperative biopsy specimens and a retrospective clinical and radiological data analysis of 160 patients with LN from the Breast Center Zurich. Open surgery was performed in 65 patients, vacuum-assisted biopsy (VAB) in 79 patients, and surveillance after breast core needle biopsy (CNB) in 16 patients., Results: The upgrade rate into ductal carcinoma in situ/invasive cancer was the highest in case of imaging/histology discordance (40%). If the number of foci in the biopsy specimen was ≥3, the upgrade rate in the consecutive surgical specimens was increased ( p = 0.01). The association of classical LN with histological microcalcification correlated with shortened disease-free survival ( p < 0.01), whereas other factors showed no impact on follow-up., Conclusions: Surveillance or subsequent VAB after CNB of LN is sufficient in most cases. Careful consideration of individual radiological and histological factors is required to identify patients with a high risk of upgrade into malignancy. In those cases, surgical excision is indicated., Competing Interests: All authors declare that they have no conflict of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Background: Diagnostic delay of breast cancer related to the false-negative assessment of the healthcare provider leads to tumor progression and might worsen the outcome. Previous studies found some factors associated with provider-related diagnostic delay; however, tumor biology has tended not to be considered. The aim of our study was to find differences in diagnostic delay of poorly differentiated breast cancer types., Methods: Data of 970 patients with newly diagnosed moderately/poorly differentiated (G2/3) breast cancer at the age ≥40 years was retrospectively analyzed regarding breast cancer type, diagnostic delay and its consequence, clinical factors and physician's assessment. Multivariate analysis was used to evaluate associated factors with diagnostic delay., Results: We observed a diagnostic delay in 3.8% (n = 37) of all patients. Mean delay time was 128 days, and clinically relevant tumor growth was observed in 43.2% of these cases. Delay was significantly higher in the group of triple-negative breast cancer (9.9% versus 2.7, 5.3 and 1.8% in hormonal receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR-/Her2+ and HR+/Her2+, respectively; P value <0.001). Age, breast density and reason for presentation were not correlated to diagnostic delay., Conclusion: Patients with triple-negative breast cancer are at higher risk of receiving a false-negative assessment and experiencing a diagnostic delay. Our results emphasize the importance of a detailed consideration of clinical risk factors and provider training and suggest a broad indication for a core needle biopsy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Evidence abounds about the beneficial effects of music on patients and healthcare professionals for many medical indications. This study aimed to evaluate the dissemination and use of music in the obstetrical setting., Methods: Invitations to an online survey were sent to physicians and midwives of all obstetrics departments in Germany. The survey gathered descriptive data as well as information about the personal relation to music and the use of it during vaginal birth (VB) and caesarean section (CS) and whether data about positive or negative effects of music were known to the participant., Results: In total, there were 293 respondents. The 47% that had the means to play music during CS stated that music was played in 15% of the cases. Most respondents have the means to play music during VB (97%). Music is played in 38% of VB. Regardless of the mode of delivery, music was estimated to be positive for team communication and patient communication. It was also deemed calming and mood lifting on the respondents. Regarding the patient, music during CS and VB was rated as being positive on all scales. Listening to music was recommended more often during VB (66%) than CS (38%)., Conclusions: Although healthcare professionals are mostly aware of the beneficial effects of music in obstetrics, our study shows that music plays a more important role during VB than during CS in Germanys obstetrical wards. There is a lack of equipment to play music in operation theatres where CS take place., (© 2021. The Author(s).)

We present an experimental and theoretical investigation of the optical diffractive properties of electrically tuneable optical transmission gratings assembled as stacks of periodic slices from a conventional nematic liquid crystal (E7) and a standard photoresist polymer (SU-8). The external electric field causes a twist-type reorientation of the LC molecules toward a perpendicular direction with respect to initial orientation. The associated field-induced modification of the director field is determined numerically and analytically by minimization of the Landau-de Gennes free energy. The optical diffraction properties of the associated periodically modulated structure are calculated numerically on the basis of rigorous coupled-wave analysis (RCWA). A comparison of experimental and theoretical results suggests that polymer slices provoke planar surface anchoring of the LC molecules with the inhomogeneous surface anchoring energy varying in the range 5-20 μJ/m 2 . The investigated structures provide a versatile approach to fabricating LC-polymer-based electrically tuneable diffractive optical elements (DOEs).

Purpose: When ipsilateral breast-tumor recurrence (IBTR) following breast-conserving surgery (BCS) occurs, the cure of a potentially life-threatening disease is the main goal. If, however, this is diagnosed early, prognosis is still good and patient-reported outcomes become more important. Despite the fact that many patients would prefer a further BCS, international breast cancer guidelines still recommend mastectomy, mainly because previous radiation implies limited options. Our comparative study evaluates the long-term quality-of-life and outcome in patients with IBTR who received BCS plus intraoperative radiotherapy (IORT) versus mastectomy., Methods: Patients with IBTR were retrospectively divided into three groups according to the local treatment: group 1 (n = 26) was treated with BCS + IORT; group 2 (n = 35) received a standard mastectomy; group 3 (n = 52) had a mastectomy with subsequent reconstruction. Outcomes were analyzed after a mean follow-up of 5 years after IBTR. Quality-of-life was evaluated by the validated questionnaire BREAST-Q in 50 patients who fulfilled the inclusion criteria., Results: Quality-of-life scores varied within the groups, ranging from 51.4 to 91.3 (out of 100 points). We observed satisfactory scores in all items, with no statistical difference within the groups. Disease-free survival of all groups did not statistically differ, and overall mortality was very low (0.9%). The postinterventional complication rate was lower after BCS (19.2% versus 34.3% after mastectomy and 30.8% after mastectomy with reconstruction)., Conclusion: For patients with previous surgery and radiation who demand a second BCS in the recurrent situation, this surgical technique can be offered in combination with IORT. Our long-term results imply oncological safety, lower complication rate, and good patient satisfaction.

A positive birth experience for the mother is an important goal in obstetric health care and is influenced by several factors. For this study, 186 women filled in questionnaires between 24 and 72 hours after giving birth vaginally. We evaluated the Big-Five personality traits (extraversion, neuroticism, openness, conscientiousness and agreeableness), trait anxiety, different dimensions of childbirth experience and pain management. Correlation analysis revealed that trait anxiety and neuroticism were negatively associated with several dimensions of the birth experience. Furthermore, conscientiousness and extraversion were positively correlated with the dimension Participation. Regression analysis for the individual dimensions and overall score respectively, confirmed the independent impact of anxiety trait on Perceived Safety, Participation and Professional Support and the overall score as well as of neuroticism on Perceived Safety and conscientiousness on Participation. The significant regression models showed small R2-scores (.084-.154). The birth experience did not differ whether the women received an epidural or not. Women who did not receive an epidural displayed higher scores on the personality trait conscientiousness. The study highlights small but important associations between personality traits and birth experience in vaginal births which should sensitize the medical staff when supporting women during labor.

Introduction: The daily clinical routine in the operating room includes patient positioning. The number of perioperative positioning-related complications is growing, along with the legal proceedings concerning this topic, and only a few guidelines exist to provide specific recommendations. The aim of this survey was to assess perioperative positioning and associated adverse events during gynecological cancer surgery in Germany., Methods: A total of 633 gynecological departments of primary, secondary, and maximum healthcare hospitals in Germany were invited to participate in this multiple-choice online questionnaire. The survey was conducted anonymously for a period of six months. The survey was divided into five different sections: descriptive information about the respondent department, pre- and postoperative management, management of positioning in the operating room based on two fictional case examples, and quality management., Results: The response rate of our survey was 29.1 % (184/633). Nearly half of the departments (46.7 %) reported to have had one to five patients with positioning-related complications during the prior 12 months, and 29.1 % had experienced a legal dispute due to positioning-related complications. Departments with more than 50 gynecologic-oncological surgeries per year more often reported positioning-related complications (p=0.003). Standard operating procedures exist in almost every department for laparoscopic (97 %) and open surgery (95.1 %), respectively., Discussion: The high number of positioning-related complications throughout all departments of different healthcare levels underlines the relevance of this issue and supports the need for a prospective European registry for further analysis. Training and education for all staff members should be routinely implemented to reduce and prevent positioning-related complications., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Around 30% of births are through caesarean section and repetition rates for receiving a caesarean section are high., Aim: The aim of the prospective study was to compare the course of anxiety in women undergoing their first caesarean section and women experiencing a repeated caesarean section., Participants: 304 women with an indication for an elective caesarean section took part. 155 received their first caesarean section and 149 received a repeated caesarean section., Methods: In order to measure the course of anxiety on the day of the caesarean section subjective anxiety levels were measured and saliva samples for cortisol determination were taken at admission, during skin closure and two hours after the surgery. Blood pressure and heart rate were documented at skin incision and skin closure., Results: Women experiencing their first caesarean section displayed significantly higher anxiety levels compared to women with a repeated caesarean section. Scores of the STAI-State and visual analogue scale for anxiety differed significantly at admission (p=.006 and p<.001) and heart rate and alpha amylase levels were significantly higher at skin closure (p=.027 and p=.029)., Conclusion: The results show that previous experience with a caesarean section has a soothing effect. The study aims to sensitize surgeons, anesthetists, nurses and midwives when treating women receiving a caesarean section and encourage them to incorporate soothing interventions, especially for women receiving their first caesarean section to reduce anxiety levels and consequently improve postoperative recovery and patients' satisfaction., (Copyright © 2019 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Objective: The caesarean section is one of the most frequently performed surgeries. Due to growing economic challenges, hospitals are encouraged to improve their cost-efficiency. One factor that influences hospital costs of caesarean sections is a prolonged hospital stay., Study Design: The aim of the current prospective study was to investigate psychosocial factors, with an emphasis on anxiety, and sociodemographic factors that are associated with longer hospital stay after caesarean sections with no medical complications. Data of 195 women who gave birth by caesarean section was analyzed. As possible predictors anxiety levels measured pre-, peri- and postoperative as well as age, parity (primiparous/multiparous), repeated caesarean (yes/no), BMI (<30/ ≥30), STAI-Trait scores, duration of surgery, PH arterial and Apgar 5 min. were entered into a backward linear regression with duration of hospital stay as the dependent factor., Results: The analysis revealed that higher age, primiparity as well as higher anxiety scores during the postoperative phase are significant factors associated with prolonged hospital stay. The significant model explains 22.1 % of the variance., Conclusion: The results should sensitize the medical team to these risk factors in order to improve patients' recovery and shorten hospital stays., Competing Interests: Declaration of Competing Interest All authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/aim: Triple-negative breast cancer (TNBC) can be divided into subtypes of basal-like (BL), mesenchymal-like (ML), luminal androgen receptor (LAR), and immunomodulatory (IM). The aim of our study was to assess whether there are distinct radiologic features within the different TNBC subtypes and whether this has potential clinical impact., Patients and Methods: Imaging pictures of 135 patients with TNBC were re-evaluated. TNBC subtyping was performed on asservated tumor tissue using a panel of antibodies., Results: Mammographic margins of LAR-TNBC were more often spiculated (24.3% versus 0-4.1%). BL-TNBC presented more frequent a mass without calcification in mammogram than other subtypes (71.4% versus 48.6-57.9%). In ultrasound, ML and LAR were described more often with smooth borders., Conclusion: The histopathological subtype of TNBC influences its presentation in ultrasound and mammogram. This can reflect a different growth pattern of the subtypes and may have an impact on the early diagnosis of TNBC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Designed peptides derived from the islet amyloid polypeptide (IAPP) cross-amyloid interaction surface with Aβ (termed interaction surface mimics or ISMs) have been shown to be highly potent inhibitors of Aβ amyloid self-assembly. However, the molecular mechanism of their function is not well understood. Using solution-state and solid-state NMR spectroscopy in combination with ensemble-averaged dynamics simulations and other biophysical methods including TEM, fluorescence spectroscopy and microscopy, and DLS, we characterize ISM structural preferences and interactions. We find that the ISM peptide R3-GI is highly dynamic, can adopt a β-like structure, and oligomerizes into colloid-like assemblies in a process that is reminiscent of liquid-liquid phase separation (LLPS). Our results suggest that such assemblies yield multivalent surfaces for interactions with Aβ40. Sequestration of substrates into these colloid-like structures provides a mechanistic basis for ISM function and the design of novel potent anti-amyloid molecules., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Background: Triple negative breast cancer (TNBC) harbors a heterogeneous group of carcinomas with poor prognosis and high genetic variability. As a potential aim for targeted therapy, genetic mutations leading to an activation of the phosphoinositide 3-kinase pathway in a catalytic subunit (PIK3CA) in breast cancer have been analyzed currently. Little is known about the clinical impact and prognostic or predictive value of this marker in TNBC subtypes., Methods: Samples from 119 TNBC cases were submitted to immunohistochemical PIK3CA protein expression analysis and scored semi-quantitatively as negative, weak (1 +), or strongly expressed (2 +). Expression scores were correlated to patient's characteristics, imaging features, and TNBC subtypes. TNBC subtypes were categorized into four subtypes: basal like, mesenchymal like, luminal androgen receptor (LAR), and immunomodulatory., Results: We did not observe differences in clinical aspects and imaging features between TNBC with and without PIK3CA expression. PIK3CA expression was in general higher in the LAR subtype. The disease-free survival and overall survival were significantly better in TNBC with PIK3CA protein expression, independent of TNBC subtypes., Conclusion: Despite conflicting results in the literature, our study clearly shows a better outcome of PIK3CA-expressing TNBC, independent of TNBC subtypes. PIK3CA expression in TNBC is not associated with specific clinical or diagnostic features. Further molecular studies and meta-analysis are warranted to clarify the prognostic and predictive role of PIK3CA protein expression.

Purpose: In developed countries, around 25% of all births involve labour induction. Studies have indicated that labour induction negatively influences the birth experience as well as the birth process. However, the impact of labour induction when only considering vaginal deliveries has not been studied yet, which was the purpose of the present study., Methods: 186 women who gave birth vaginally took part in this prospective study. 95 women gave birth after spontaneous onset of labour (SL-group) and 91 women received a labour induction (LI-group). Eight to 72 h after birth, the women filled in the revised version of the standardised Childbirth Experience Questionnaire, which examines the birth experience in four dimensions (Own Capacity, Perceived Safety, Participation and Professional Support). Medical details regarding birth and fetal outcomes were taken from the medical records., Results: Birth outcomes (the number of epidural anaesthesia, the duration of birth, birth risks and childbirth injuries) as well as fetal outcomes (APGAR after 1 and 5 min and arterial cord pH) did not differ between the groups. Regarding the subjective birth experience, the LI-group indicated significantly lower values for Perceived Safety and Participation compared to the SL-group, while there were no differences for the dimensions Own Capacity and Professional Support., Discussion: Successful labour induction resulting in a vaginal birth did not negatively influence birth and fetal outcomes and only partly affected the women's birth experience. The negative impact of labour induction on the dimensions Perceived Safety and Participation should sensitize midwives in order to provide optimal support.

Transmission optical diffraction gratings composed of periodic slices of a ferromagnetic liquid crystal and a conventional photoresist polymer are demonstrated. Dependence of diffraction efficiencies of various diffraction orders on an in-plane external magnetic field is investigated. It is shown that diffraction properties can be effectively tuned by magnetic fields as low as a few mT. The tuning mechanism is explained in the framework of a simple empirical model and also by numerical simulations based on the rigorous coupled wave analysis (RCWA). The obtained results provide a proof of principle of operation of magnetically tunable liquid crystalline diffractive optical elements applicable in contactless schemes for control of optical signals.

Background: Stress and anxiety during pregnancy and childbirth have negative consequences for both mother and child. There are indications that music has a positive effect in this situation. The present study investigates the influence of music during the caesarean on anxiety and stress of the expectant mother., Methods: The SAMBA study is a single-centre, controlled, randomized study including 304 patients. Women in the intervention group heard music via loudspeakers from one of four self-selected genres. The control group had standard treatment without music. The caesarean was performed in regional Anesthesia. At admission, at skin incision, during skin suture and two hours after completion of surgery, different subjective (State-Trait Anxiety Inventory, visual analogue scale for anxiety) and objective parameters (salivary cortisol/amylase, heart rate, blood pressure) were collected. Mixed-factorial Analysis of variances as well as independent sample t-tests were applied for data analysis., Results: At skin suture, significantly lower anxiety levels were reported in the intervention group regarding State anxiety (31.56 vs. 34.41; p = .004) and visual analogue scale for anxiety (1.27 vs. 1.76; p = .018). Two hours after surgery, the measured visual analogue scale for anxiety score in the intervention group was still significantly lower (0.69 vs. 1.04; p = .018). The objective parameters showed significant differences between the groups in salivary cortisol increase from admission to skin suture (12.29 vs. 16.61 nmol/L; p = .043), as well as systolic blood pressure (130.11 vs. 136.19 mmHg; p = .002) and heart rate (88.40 vs. 92.57/min; p = .049) at skin incision., Conclusions: Music during caesarean is an easy implementable and effective way of reducing stress and anxiety of the expectant mother., Trial Registration: German registry for clinical trials ( DRKS00007840 ). Registered 16/06/2015. Retrospectively registered.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.

Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique β-strand structure distinct from the conventional amyloid β-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation.

Films prepared by cold spray have potential applications as photoanodes in electrochemical water splitting and waste water purification. In the present study cold sprayed photoelectrodes produced with WO 3 (active under visible light illumination) and TiO 2 (active under UV illumination) on titanium metal substrates were investigated as photoanodes for the oxidation of water and methanol, respectively. Methanol was chosen as organic model pollutant in acidic electrolytes. Main advantages of the cold sprayed photoelectrodes are the improved metal-semiconductor junctions and the superior mechanical stability. Additionally, the cold spray method can be utilized as a large-scale electrode fabrication technique for photoelectrochemical applications. Incident photon to current efficiencies reveal that cold sprayed TiO 2 /WO 3 photoanodes exhibit the best photoelectrochemical properties with regard to the water and methanol oxidation reactions in comparison with the benchmark photocatalyst Aeroxide TiO 2 P25 due to more efficient harvesting of the total solar light irradiation related to their smaller band gap energies.

In patients with 3-hydroxy-3-methylglutaryl(HMG)-CoA lyase deficiency (OMIM 246450), five pregnancies have been described worldwide, which were either terminated or resulted in severe metabolic sequelae during pregnancy or delivery. Here, we report on a patient with HMG-CoA lyase deficiency, who underwent two uncomplicated pregnancies. The 19-year-old patient was admitted because of recurrent vomiting and nausea. Diagnostics revealed pregnancy at week 8 of gestation. Metabolic analyses revealed normal lactate and blood glucose levels and normal acid-base status. Urine organic acid analysis showed an elevated excretion of 3-CH 3 -glutaric acid, 2,3-CH 3 -glutaconic acid, and 3-CH 3 -3-OH-glutaric acid. Oral treatment with carnitine and glucose wes administered intravenously during the period of nausea and vomiting. After clinical recovery, a diet with 0.89 g/kg of protein/d and 38 kcal/kg body weight/d was given. Meals were taken every 3 h. Additionally, 70 g of starch was given at midnight to maintain normoglycemia at night time. Peripartum, a complete parenteral nutrition, was delivered through a central venous catheter. The patient delivered a healthy male infant by Caesarean section at week 38 of gestation (Apgar 9/10/10) and remained metabolically stable throughout the peripartum period. Postpartum nutrition was gradually changed from parenteral to oral diet. Two years later, the patient became pregnant again and presented with hyperemesis gravidarum. With metabolic monitoring and treatment as before no decompensation occurred. At week 38 of gestation, she delivered a healthy female infant by elective Caesarian section (Apgar 9/10/10). This case report describes the metabolic and obstetric management of two pregnancies in a patient with HMG-CoA lyase deficiency with favorable outcome without metabolic complications.

Introduction: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease., Material and Methods: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015., Results: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials., Conclusion: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.

Objective. The purpose of this prospective study was to investigate the predictive value of single prepartum findings combined with serum biomarkers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor) indicating severity of preeclampsia (PE) for occurrence and extent of impaired postpartum kidney function. Study Design. In this prospective, single center study 44 PE patients were compared to 39 healthy controls (similar in age and gestational age with singleton pregnancy) evaluated at time of delivery and at 6 months and 12 months postpartum. p values below 0.05 are considered statistically significant. Results. The majority of the PE patients had persistence of proteinuria (>120 mg/L after delivery) 6 months (p = 0.02) and 12 months postpartum (p < 0.0001) compared to controls. Also reduced GFR (glomerular filtration rate) persisted up to 6 months postpartum in PE patients compared to controls (p < 0.001). Prepartum sFlt-1 levels indeed correlated with impaired renal function parameters. Conclusion. A significant proportion of our PE patients had lower GFR levels and persistent proteinuria up to 12 months postpartum. Prepartum sFlt-1 is a trend-setting marker for impaired renal function postpartum, but it is not sufficient enough to predict renal impairment after PE. An evaluation of 24-month follow-up data is scheduled.

Gestational trophoblastic diseases (GTD) are a group of pregnancy-related disorders representing rare human tumours. They encompass premalignant disorders including complete (CHM), partial hydatidiform mole (PHM), exaggerated placental site (EPS), and placental-site nodule (PSN) as well as malignant disorders (also known as "gestational trophoblastic neoplasia [GTN]") including invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumour (PSTT), and epitheloid trophoblastic tumours (ETT) ( Fig. 1 ). Originally, GTD develop from abnormal proliferation of trophoblastic tissue and form botryoid arranged vesicles. Premalignant moles are usually treated by suction curettage while persistent and recurrent moles and malignant forms require systemic therapy with methotrexate or combination chemotherapy consisting of etoposide, actimomycin D, methotrexate, vincristine, and cyclophosphamide (EMA-CO). β-human chorion gonadotropin (β-hCG) plays a crucial role in diagnosis and monitoring therapeutic effects. Since the definitive diagnosis cannot be obtained by histology in most cases, persistent or recurrent disease is diagnosed by elevated or persistent serum levels of β-hCG. While curing rates are described to be as high as 98 %, GTD may initially present, recur, or end up as a metastasising systemic disease. This underlines the importance of a regular and consistent follow-up after treatment.

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover.

Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists., Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2., Design, Setting, and Participants: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk., Exposures: Mutations of BRCA1 or BRCA2., Main Outcomes and Measures: Breast and ovarian cancer risks., Results: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers., Conclusions and Relevance: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Introduction: Radical resection of deep infiltrating endometriosis (DIE), including bladder and bowel resection, provides relief from pain in symptomatic patients. The laparoscopic approach to treatment is well established for bowel resection but normally requires additional abdominal incisions for specimen retrieval. Here we describe our technique of laparoscopically assisted rectal resection and transvaginal specimen retrieval (LARRT) and provide follow-up information on pain scores and complications., Materials and Methods: Retrospective observational monocentric study on all DIE patients with rectal infiltration treated between 2008 and 2010 with LATRR at our department. Follow-up was obtained for at least 3 years, including baseline 1-year and 3-year pain scores., Results: We identified four patients undergoing LARRT available for follow-up. DIE was confirmed by histology in all cases. There were no intraoperative complications. Two patients had transient postoperative urinary retention, one patient developed recto-vaginal fistula and required transient colostomy. One patient suffered from persistent vaginal dryness. All patients, however, reported persistent pain relief, including at the end of follow-up period., Conclusion: LARRT is a feasible variation of laparoscopic bowel resection for DIE with rectal infiltration. In our study it has promising results with respect to pain control. Larger studies will, however, be required to determine the safety of this procedure.

Introduction: In 2002, gynecology residents in North Rhine-Westfalia (NRW) were asked how satisfied they were with their working and training conditions. A new extended survey of gynecology residents aimed to evaluate whether changes to specialist training regulations had affected residents' levels of job satisfaction and to identify areas where training conditions still urgently required improvement. Material and Methods: A total of 1223 questionnaires with 52 questions were sent to the 159 gynecology clinics in NRW. Responses could be dichotomous, multi-level or quantitative. The results were analyzed with regard to age, gender, family status and type of clinic and were additionally compared with the results of a previous survey. Results: The percentage of women residents has increased to 84.6 %. A workload of more than 48 hours per week has resulted in decreased motivation and lower levels of satisfaction during training, although overall levels of satisfaction have clearly improved compared to the previous survey. Use of a logbook to create a more structured training program has not achieved the desired effect. Nevertheless, seven of eight gynecology residents would study medicine again, although 28 % of the budding gynecologists are considering working abroad or in private industry. Conclusion: Both training and overall satisfaction with working conditions must be improved to preserve the appeal of gynecology for young academics. This survey aims to identify key factors which are responsible for (dis)satisfaction with working conditions.

The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

Study Objective: The aim of this study was to estimate the benefit of excision of the endocervix during laparoscopic supracervical hysterectomy (LSH) with regard to postoperative cyclical bleeding., Design: Cohort study from 2 centers (Canadian Task Force classification II-2)., Setting: Two surgical teams at the University of Duesseldorf Medical Center and PAN Clinic, Cologne, Germany., Patients: Women with menstrual bleeding disorders resistant to medical treatment, symptomatic leiomyomata, dysmenorrhea., Intervention: Laparoscopic supracervical hysterectomy. The uterus was transsected from the cervix with 2 techniques with and without excision of cervical canal., Measurements and Main Results: We evaluated 300 patients who underwent consecutive LSH procedures. In 150 patients the uterus was transsected from the cervix using a monopolar loop. In a second series of 150 patients a unipolar needle electrode was used for the uterine amputation and the excision of cervical canal. The mean duration of the transsection was 65 seconds (monopolar loop) versus 168 seconds (monopolar needle). The excision of the endocervix was performed without any complications in 148 procedures. Histologic examination of the removed tissue revealed endocervical tissue in 83.3% (n = 125), endometrium in 9.4% (n = 14), cervicoisthmic mucosa in 3.3% (n = 5), and myometrium only in 4% (n = 4). All 300 patients were contacted 12 months after surgery to inquire about bleeding status, and 282 (94%) responded. In patients who underwent excision of the endocervix, postoperative cyclical bleeding was significantly reduced compared with the control group (1.4% vs 10.7%)., Conclusion: The results of this study indicate that the routine excision of the endocervix is a quick safe procedure which allows a significant reduction of postoperative cyclical bleeding in patients who undergo LSH., (Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

A delicate balance in estrogen and progesterone signaling through their cognate receptors is characteristic for the physiologic state of the endometrium, and a shift in receptor isotype expression can be frequently found in human endometrial pathology. In this study, using a transgenic mouse model, we examined the mechanisms whereby alterations in progesterone receptor (PR) isotype expression leads to endometrial pathology. For an experimental model, we used transgenic mice (PR-A transgenics) carrying an imbalance in the native ratio of the two PR isoforms A and B (PR-A and PR-B) through the expression of additional A form and examined their uterine phenotype under different hormonal regimens, using various criteria. Uterine epithelial cell proliferation was augmented in PR-A transgenics and was abolished by PR antagonists. In particular, proliferative response to progesterone, independent of signaling through estrogen, was enhanced. Upon continuous exposure to estradiol and progesterone, the uteri in PR-A transgenics displayed gross enlargement, endometrial hyperplasia including atypical lesions, endometritis and pelvic inflammatory disease. Imbalanced expression of the two isoforms of PR in a transgenic model reveals multiple derangements in the regulation of uterine physiology, resulting in various pathologies including hyperplasias.

Background: Patients requiring assisted reproductive techniques may have a higher rate of congenital malformations. Some rare complications of pregnancy might be related to such abnormalities. Torsions of the umbilical cord resulting in fetal death have previously been described exclusively in pregnancies following spontaneous conception., Case: The case of 37 year old gravida I, para O woman with a twin pregnancy after intracytoplasmatic sperm injection and intrauterine death of one twin at approximately 30 weeks' gestation is presented. The surviving twin was delivered by cesarean section at 31 weeks after spontaneous onset of labor and recurrent fetal bradycardia. The intraoperative situs showed that the demised twin had suffered from multiple umbilical cord torsions leading to intrauterine hypoperfusion., Conclusion: Umbilical torsion leading to fetal death might represent a previously unrecognized complication in women requiring assisted reproductive techniques, but this problem is known to occur in pregnancies achieved by natural methods.

A 30-year-old gravida 2 para 1 was admitted to hospital 2 years after cesarean section at 20 weeks' gestation with acute onset of abdominal pain and hypovolaemic shock. Emergency laparotomy revealed a uterine rupture located in the anterior uterine wall caused by a placenta percreta and supracervical hysterectomy was performed. This site of invasion and finally rupture was in projection of the previous lower-segment cesarean section. This report illustrates the dramatic consequences of abnormal placentation after prior uterine surgery, which can already occur early during pregnancy and prior to the onset of labour., ((c) 2008 S. Karger AG, Basel.)

Purpose: To compare the effects on heart rate (HR), on left ventricular (LV) or arterial pressures, and the general safety of a non-ionic low-osmolar contrast medium (CM) and a non-ionic iso-osmolar CM in patients undergoing cardiac angiography (CA) or peripheral intra-arterial digital subtraction angiography (IA-DSA)., Materials and Methods: Two double-blind, randomized studies were conducted in 216 patients who underwent CA (n=120) or peripheral IA-DSA (n=96). Patients referred for CA received a low-osmolar monomeric CM (iomeprol-350, n=60) or an iso-osmolar dimeric CM (iodixanol-320; n=60). HR and LV peak systolic and end-diastolic pressures were determined before and after the first injection during left and right coronary arteriography and left ventriculography. Monitoring for all types of adverse event (AE) was performed for 24 h following the procedure. t-tests were performed to compare CM for effects on HR. Patients referred for IA-DSA received iomeprol-300 (n=49) or iodixanol-320 (n=47). HR and arterial blood pressure (BP) were evaluated before and after the first 4 injections. Monitoring for AE was performed for 4 h following the procedure. Repeated-measures ANOVA was used to compare mean HR changes across the first 4 injections, whereas changes after the first injection were compared using t-tests., Results: No significant differences were noted between iomeprol and iodixanol in terms of mean changes in HR during left coronary arteriography (p=0.8), right coronary arteriography (p=0.9), and left ventriculography (p=0.8). In patients undergoing IA-DSA, no differences between CM were noted for effects on mean HR after the first injection (p=0.6) or across the first 4 injections (p=0.2). No significant differences (p>0.05) were noted in terms of effects on arterial BP in either study or on LV pressures in patients undergoing CA. Non-serious AE considered possibly CM-related (primarily headache and events affecting the cardiovascular and digestive systems) were reported more frequently by patients undergoing CA and more frequently after iodixanol (14/60 [23.3%] and 2/47 [4.3%]; CA and IA-DSA, respectively) than iomeprol (10/60 [16.7%] and 1/49 [2%], respectively)., Conclusions: Iomeprol and iodixanol are safe and have equally negligible effects on HR and LV pressures or arterial BP during and after selective intra-cardiac injection and peripheral IA-DSA., Clinical Application: Iomeprol and iodixanol are safe and equally well tolerated with regard to cardiac rhythm and clinical preference should be based on diagnostic image quality alone.

Background and Objectives: We wanted to identify factors which allow predicting long-term survival after pelvic exenteration (PE) for locally advanced or recurrent gynecologic malignancies., Methods: All patients undergoing PE at our institution from 1983 to 2002 were screened. In 203 cases data were obtainable and analyzed with respect to factors predicting outcome considering morbidity, mortality, and survival. Follow-up data and data concerning late complications not documented in our records were obtained by telephone interviews., Results: Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure was palliation in the remaining cure. Procedures performed were anterior (n = 91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6 units of packed red blood cells were perioperatively transfused. Microscopically complete resection was achievable in n = 69 patients. Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow-up. Five-year overall survival in patients treated with a curative intent was 21%, 5-year survival in those patients with complete resection was 32%. Forty-two percent of patients with a complete resection without lymph node involvement, age 30-50, curative intention, and the absence of a pelvic sidewall infiltration survived 5 years or longer., Conclusion: In our series a 5-year survival rate of over 40% could be achieved for nodal-negative patients without pelvic sidewall infiltration when treated with curative intent and after complete resection., (Copyright 2007 Wiley-Liss, Inc.)

Background/aims: Demonstration of unresectability often requires diagnostic laparotomy with high co-morbidity in pancreatic carcinoma. The value of detected peritoneal tumor cells and influence on outcome should be determined., Methodology: In a prospective study 150 consecutive patients with pancreatic carcinoma were evaluated. Improvement of diagnostic accuracy in diagnosing unresectability was calculated for combination of CT, endoscopic ultrasonography and peritoneal cytology., Results: Unexpected subglissonian metastases were found in 10%. 87 patients with peritoneal washings were included in the study, 20 patients with detected peritoneal tumor cells (n=22) were inoperable. In all patients of this group the ventral integrity of pancreas was damaged. In 23 patients with preoperative existent ascites, only in 4 cases could peritoneal tumor cells be detected. In patients with positive cytology together with disrupted ventral pancreatic margin as predictors of unresectability, sensitivity was 100% and specificity 96%., Conclusions: Addition of diagnostic laparoscopy combined with peritoneal cytology and minimally invasive palliation procedures (endoscopic biliary prosthesis, laparoscopic gastrojejunostomy) to the staging-protocol for pancreatic carcinoma may decrease operative lethality and unnecessary laparotomies may be avoided safely. As unexpected subglissonian micrometastases may additionally be present in 5-10%, perioperative laparoscopy is always advisable.

Purpose: To assess the diagnostic value of three-dimensional coronary magnetic resonance (MR) angiography with fat saturation and navigator echo in the setting of restenosis after percutaneous transluminal coronary angioplasty (PTCA)., Materials and Methods: Thirty consecutive patients who had PTCA and were referred for elective coronary reangiography underwent MR imaging and coronary angiography. The pulse sequence was a cardiac triggered, single-slab, three-dimensional, gradient-echo sequence, employing a spin-echo navigator echo measurement to track the variation of the diaphragm during the scan. The following segments of the coronary arteries were included in this prospective study: left main coronary artery, proximal and middle left anterior descending, proximal and middle left circumflex, proximal and middle right coronary artery, and intermediate branch, if present. The quality of the MR images was graded from 0 to 5., Results: In total, 221 coronary artery segments could be identified. Mean image quality was 3.3. Overall accuracy for segments with an image quality of grade 2 or more was 90%. To achieve a positive predictive value >70% for a significant stenosis/restenosis, only segments with quality >/=3 could be assessed, whereas an acceptable negative predictive value could be achieved for nearly all segments., Conclusion: Our preliminary data suggest that MR coronary angiography may be most helpful as a screening test in selected patients to exclude clinically relevant stenoses or to assess restenoses after PTCA or in patients in whose coronary angiography is relatively contraindicated., (Copyright 2004 Wiley-Liss, Inc.)

Surgery of diseases of the pelvis minor and retroperitoneum such as inflammatory disease, malignant tumours, or trauma of pelvic organs need the close interdisciplinary collaboration of visceral surgeons, gynaecologists, and urologists. This collaboration begins in planning diagnostic and therapeutic procedures. It has to be clear who performs which operative step and when. Excellent long-term results in malignant disease show that the greater effort is worthwhile. The rate of postoperative morbidity after these multivisceral resections is high also in specialised centers, but mortality is below 5%. Because of the growing number of long-term survivors, preservation of quality of life becomes more and more important.

Objectives: In this study, we sought to assess safety of symptom-limited exercise stress tests the day after coronary stenting., Background: Isolated cases of coronary stent thrombosis have been linked to early exercise stress testing, thereby questioning the safety of unrestricted physical activity after the coronary procedure., Methods: At a single center, 1,000 patients were randomized to a symptom-limited stress test the day after coronary stenting or no stress test. The antiplatelet regimen consisted of acetylsalicylic acid and postprocedural ticlopidine or clopidogrel. The primary end point of the study was the incidence of clinical stent thrombosis at 14 days. The secondary end point was the occurrence of access site complications., Results: Clinical stent thrombosis occurred in five patients (1%) undergoing stress test and in five patients (1%) randomized to no stress test (p = 1.0). Access site complications were detected in 4% and 5.2% of cases, respectively (p = 0.37)., Conclusions: Symptom-limited exercise stress testing the day after coronary stenting does not increase the risk of clinical stent thrombosis or access site complications. Further investigations on safety of early vigorous exercise after coronary stenting in a non-supervised setting are warranted.

A randomized study was conducted to assess the feasibility of 4 Fr catheters for diagnostic coronary angiograms. A total of 1,114 consecutive patients were randomized to 4 or 5 Fr catheters. Ease of use of catheters was subjectively assessed by the primary operator and the picture quality was assessed by two independent observers with a good interobserver variability (r = 0.94; P < 0.001). Predischarge local complications were recorded by the attending physician. No statistically significant difference was observed in the picture quality for the left coronary artery, right coronary artery, aorta, left ventricle, venous grafts, or renal arteries between the two groups. Fluoroscopy time (7.1 +/- 5.6 for 4 Fr vs. 6.7 +/- 5.7 min for 5 Fr) and contrast quantity (140 +/- 58 vs. 144 +/- 57 ml) were comparable between the two groups. There was a statistically significant difference in favor of the 5 Fr group as regards maneuverability of catheters (93% vs. 79%; P < 0.001), and 5 Fr pigtail catheters crossed the aortic valve easier than the 4 Fr pigtail catheters (91% vs. 81%; P < 0.001). Crossover to the other catheter size or a larger sheath was more frequent with 4 Fr catheters (33/522 vs. 3/592; P < 0.001). Median time to hemostasis was 9 min for 4 Fr and 14 min for 5 Fr (P < 0.001). Of the 4 Fr patients, 84% could be mobilized at 1 hr and 86% of 5 Fr patients at 2 hr. Significant hematomas were observed in 2% with 4 Fr or 5 Fr and small hematomas in 10% and 16%, respectively (P = NS). Time to discharge was comparable in both groups (4.0 +/- 3.2 with 4 Fr vs. 4.3 +/- 3.7 hr with 5 Fr). The 4 Fr catheters are a good alternative for diagnostic coronary angiograms. The increased difficulty in maneuverability and a need for catheter changes in 70% are compensated for in part by easier hemostasis. With increasing use and finesse of these catheters, the difficulty in maneuverability are likely to be overcome., (Copyright 2003 Wiley-Liss, Inc.)

Purpose: Interactions of hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) have been proposed as being important in promoting tumour progression and dissemination. This comparative study was designed to investigate the RHAMM expression patterns in endometrial carcinoma., Methods: We examined a series of 89 endometrial carcinomas and 15 normal endometrial tissues by immunohistochemistry, using a RHAMM-specific polyclonal antibody. Expression of RHAMM was assessed according to the pattern and intensity within (overall cytoplasm, center/periphery of tumours) and between the tumours. The staining results were compared to the corresponding clinical data (age, menopause status, histological staining, histological grading, lymph node status)., Results: RHAMM-expression was detectable in 58% of the 89 tumours [Histological stage: pT1a (8/12); pT1b (16/37); pT1c (18/26); pT2 (6/9); pT3a (4/5)] and 13% (2/15) of the normal endometrial tissues. The positivity rates for RHAMM were 100% in patients with positive lymph nodes but only 50.7% in patients with negative lymph nodes ( P<0-01). Additionally, the expression pattern showed a highly significant correlation ( P<0.01) with the histological grade of the tumours [G1 (6/42), G2 (33/34), G3 (13/13)] and occurrence of lymph node metastases., Conclusions: Our results suggest that RHAMM expression may enhance and improve the invasion and metastasis of endometrial carcinomas.

The purpose of the present study was to determine whether postprocedural antithrombotic therapy with prolonged heparin infusion followed by 6 months of oral anticoagulation in addition to acetylsalicylic acid (ASA) reduces the incidence of angiographic restenosis after successful PTCA. One hundred ninety-one patients with uncomplicated PTCA were randomized into two groups: one group was discharged with ASA 100 mg only (G1) and the other group was additionally treated with 12-24 hr of heparin infusion and overlapping oral anticoagulation with coumadin for 6 months (G2). The two groups were comparable with respect to age, gender, coronary risk profile, clinical presentation, and angiographic lesion characteristics. Stents were implanted in 33% and 36% of the G1 and G2 patients, respectively. In-hospital myocardial infarction occurred in 4% of the G1 and 3% of the G2 patients. One patient in G1 died of subacute stent thrombosis (day 3). Six-month angiographic follow-up was obtained in 90% of G1 patients and 94% of G2 patients. Restenosis occurred in 30% and 33% of the patients and mean diameter stenoses at follow-up were 40% +/- 28% and 39% +/- 24%, respectively. Thrombin inhibition with heparin infusion followed by 6 months of oral anticoagulation did not reduce angiographic restenosis among patients undergoing PTCA with or without stent implantation. The occurrence of acute ischemic complications was also comparable in the two groups., (Copyright 2002 Wiley-Liss, Inc.)

Background: The wide range of closure devices for arterial access sites still leaves room for improvement., Methods and Results: We report our initial experience with a novel, cost-effective, suture-mediated device (6 French X-PRESS device, X-SITE Medical, Blue Bell, Pennsylvania) for closure of the arterial access site after both diagnostic and therapeutic interventions. A total of 51 consecutive patients are reported. The closure was performed immediately after the procedure. No patient had more than 5,000 U heparin administered during the procedure. The closure device was used in 36 patients (73%) after diagnostic angiography and in 15 patients (27%) after therapeutic intervention. The device could be successfully deployed in 48 patients (94%). In the remaining 3 cases (6%), hemostasis was achieved with standard manual compression without any further event. Immediate total hemostasis was achieved with the device in 44 of 48 patients (92%). Four devices (8%) could not be deployed correctly due to technical problems and the patients needed additional manual compression. The average time to achieve complete hemostasis was 5.5 +/- 3.5 minutes (range, 3-26 minutes). The patients were ambulated after a period of 1.3 +/- 0.4 hours of bedrest (range, 0.8-3.5 hours). Time to possible discharge was 4.2 +/- 3.4 hours (range, 0.9-12.5 hours). One patient experienced a minor complication (hematoma < 6 cm) and was treated with manual compression without clinical sequelae. Telephone follow-up was carried out 2 weeks after deployment and revealed no sequelae., Conclusion: The 6 French X-PRESS device is safe and effective in providing rapid hemostasis following interventional or diagnostic catheterization procedures. Use of the device is associated with a low rate of complications and facilitates quick hemostasis, mobilization and discharge.

Introduction: There is still no evidence whether human peritoneal mesothelial cells (HPMC) from patients with end-stage renal failure are altered in cell viability or show a different pattern of the release of proinflammatory cytokines. Also the serum of patients with uremia may contain substances stimulating the cytokine release of HPMC., Study Design: The IL-1beta-induced IL-6/IL-8 release of HPMC from healthy donors and from patients with end-stage renal disease (ESRD) were measured before the start of chronic peritoneal dialysis (PD) and during PD therapy. Additionally the influence of uremic and non-uremic serum on IL-6 and IL-8 release of normal HPMC was studied. Cell viability was assessed by MTT assay and by the measurement of intracellular ATP (chemoluminescence assay). HPMC were obtained from the following patient groups: (1) non-uremic control patients (n = 7); (2) patients with ESRD undergoing PD catheter implantation for the first time (n = 7), and (3) patients on PD undergoing catheter exchange for noninfectious reasons (n = 6). Pooled human serum from PD patients and normal controls were used for stimulation experiments. HPMC from different donors were grown to confluence (second passage) and then stimulated with IL-1beta (1,000 pg/ml in M199) for 24 h. IL-6 and IL-8 concentrations were measured in the supernatant by ELISA. Additionally uremic and non-uremic sera were incubated with HPMC from normal donors for 24 h with a subsequent 24-hour IL-1beta stimulation. Mesothelial cell protein mass was determined by the Bradford reagent., Results: Non-uremic patients and ESRD patients did not differ with regard to the global cell viability of HPMC according to MTT assay activity or the intracellular ATP concentration. However, HPMC from uremic patients produced more IL-8 on IL-1beta stimulation than the non-uremic controls (group 2, 53.5 +/- 15.7 pg/microg; group 3, 70.5 +/- 27.3 pg/microg vs. group 1, 24.0 +/- 11.8 pg/microg). HPMC from patients on chronic PD additionally released significantly more IL-6 (30.5 +/- 13.8 pg/microg) on IL-1beta stimulation than uremic patients before the onset of PD (6.2 +/- 2.6 pg/microg; p < 0.01). Incubation of normal HPMC with the serum from uremic donors produced an enhanced stimulated IL-8 release compared to the exposition with normal control serum (50.6 +/- 6.1 vs. 20.8 +/- 2.9 pg/microg; p < 0.01)., Conclusion: HPMC from uremic patients more readily release IL-8 on stimulation with IL-1beta. On chronic PD treatment IL-6 release was further enhanced. Not further classified serum components in uremia also enhance IL-6 and IL-8 release of HPMC., (Copyright 2002 S. Karger AG, Basel)

Purpose: We describe the implementation of quality improvement measures in a quality management system., Methods: With questionnaires for radiologists and patients, we investigated the relations between patient preparation and diagnostic quality serving the main purpose, to improve diagnostic quality with the help of more detailed patient information (e.g., changing preparation sheets and handling out "peri-med" information sheets to the patients). Furthermore, a comparative data ascertainment at other institutes was integrated., Results: For the group of outpatients, increasing process quality (patient information) and outcome (diagnostic quality) could be achieved. Taking aspects of quality costs into consideration, a decrease in costs due to failures was achieved., Conclusion: More detailed patient information has positive effects on diagnostic quality of the double contrast (barium) enema.

Background: Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug. Thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD., Methods: Coronary blood flow velocity was measured with the Doppler flow wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n = 15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area., Results: Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p < 0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p = 0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p < 0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/- 2.0 to 2.3 +/- 0.7 mm Hg x s/cm (p < 0.02)., Conclusions: The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic CFVR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (= increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD.

Objective: To investigate the hypothesis that the time to washout of radiographic contrast medium trapped distal to an occluded collateral receiving vessel is inversely related to collateral flow, and that this provides an accurate method for characterising coronary collaterals., Methods: An intracoronary pressure derived collateral flow index was determined in 54 patients undergoing percutaneous transluminal coronary balloon angioplasty (PTCA). The study group was subdivided according to whether the collateral vessels were sufficient (n = 17) or insufficient (n = 37) to prevent ECG signs of myocardial ischaemia during PTCA. Washout collaterometry-an angiographic washout method-was carried out simultaneously; after injection of radiographic contrast medium into the collateral receiving vessel followed immediately by vascular occlusion, the number of heart beats was counted until approximately half the length of the epicardial vessel was cleared of contrast., Results: The collateral flow index was higher (0.28 (0.09) v 0.12 (0.07); p < 0.0001) and the contrast washout time shorter (8.0 (2.9) v 17.5 (6.7) heart beats; p < 0.0001) in patients with sufficient versus insufficient collaterals. There was an inverse correlation between contrast washout time and collateral flow index (r = 0.72, p < 0.0001). Washout of contrast distal to the occluded vessel within 11 heart beats correctly determined sufficient and insufficient collaterals with 88% sensitivity and 81% specificity., Conclusions: Washout collaterometry is a new radiographic contrast washout method based on the inverse relation between collateral flow and the time to clearance of radiographic dye injected into the ipsilateral vessel during PTCA. It appears to be an accurate method of characterising coronary collateral vessels.

Unlabelled: Advanced breast biopsy instrumentation (ABBI) experiences and critical comments., Purpose: To describe our three-years' experience with advanced breast biopsy instrumentation (ABBI)., Materials and Methods: Considering lesion size, type and location as well as patient specific criteria 89 patients were selected for an ABBI. The documented data like duration, complication and change of the procedure, size of the lesions and biopsy cannulas, histologic outcome and further treatment were analysed retrospectively., Results: ABBI was successful in 63 of 89 patients. Cancer was found in 18 patients (29 %) with a surgical re-excision to achieve tumour-free margins in 89 %. 45 patients had benign lesions (71 %) with a benign to malignant ratio of 2.5 : 1. ABBI was unsuccessful or had to be replaced by other biopsy techniques in 26 patients (29 %). In four of these patients the localization needle was already placed. Analysing the three-year period ABBI frequency dropped each year with an overall reduction of 63 %. Despite a good benign to malignant ratio the surgical re-excision rate in cancer patients is disappointing. Although using precise selection criteria for ABBI the rate of failed biopsies and changeover to another biopsy procedure was too high. The reduction of ABBI procedures during the three-year period is assumed to be an expression of the negative experiences with the method but also a refusal of the assigning colleagues to use ABBI., Conclusion: For the evaluation of suspected breast lesions ABBI is too invasive and too expensive. On the other hand ABBI is too ineffective as a therapeutic tool to remove suspected lesions. Therefore it is not warranted to use ABBI instead of other concurrent biopsy techniques.

Conventional lactate (Lac)-buffered peritoneal dialysis (PD) solutions have turned out to be detrimental to human peritoneal cells, especially because of a low pH. In the present study, we focus on potential differences between Lac and bicarbonate (Bic) as a buffer when adjusted to a physiological pH. All test fluids were buffered with either 40 mmol/L of Lac or 34 mmol/L of Bic, sterile filtered, and adjusted to a pH of 7.4. Osmotic agents used were 1.36% glucose (Glu), 3.86% Glu, 1% amino acids (AA), and 7.5% Glu polymer (Glupoly). Human peritoneal mesothelial cells (HPMCs) were isolated from the omentum majus, grown to confluence, and incubated after the second passage for 15 minutes (37 degrees C and 5% carbon dioxide) with the test fluids. Cytotoxicity was controlled by measuring apoptotic and necrotic cells with cytofluorometry. Aerobic cell metabolism (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay) and intracellular adenosine triphosphate (ATP) concentrations were measured to assess cell viability. Release of interleukin-6 (IL-6) from HPMCs was determined as a parameter of cellular host defense. No significant difference in apoptosis or necrosis rates was found between the solutions adjusted to normal pH. However, in the MTT assay, Bic solutions were superior to corresponding Lac pendants at an identical pH of 7.4 (P < 0.01). Intracellular ATP concentrations reflected a very similar pattern (P < 0.05). Glupoly in combination with Lac showed an impaired pattern with both the MTT and ATP assays. Regarding IL-1beta-stimulated IL-6 release, there was a small, but not significantly better, response for Bic. Differences in manifest cell cytotoxicity reflected by apoptosis and necrosis rates could not be detected comparing PD solutions buffered with Lac or Bic at a physiological pH. However, distinct parameters of cell metabolism were superior with Bic compared with Lac. Especially Glupoly was inferior in combination with Lac as a buffer.

Objective: To assess the effect of recanalisation on collateral flow in a case-control study in patients with and without chronic total coronary occlusions., Design: In 54 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (mean (SD) age 61 (6) years), coronary collateral flow was measured by intracoronary pressure or Doppler guide wires at the end of repeated balloon occlusions. Coronary collateral flow index (collateral flow relative to normal antegrade flow) during the first two balloon inflations in 27 patients with a chronic total occlusion (occlusion group) was compared with that of 27 patients matched for age, sex, and collateral flow index at the first occlusion and with a coronary artery diameter stenosis