Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation-a randomized trial.

BACKGROUND: Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis. OBJECTIVE: This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial. STUDY DESIGN: In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters. RESULTS: Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced. CONCLUSION: Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Novel and flexible ultrasound simulation with smartphones and tablets in fetal echocardiography.

PURPOSE: Evaluation of a novel ultrasound-simulation-app for training fetal echocardiography as a possible useful addition for students, residents and specialist doctors. Furthermore, comparison to a conventional learning-method with special attention on orientation and recognition of physiological structures. METHODS: Prospective two-arm study with the participation of 226 clinical students. 108 students were given an extract from a textbook on fetal echocardiography (PDF-group, n = 108) for 30 min to study. 118 students were able to use the new ultrasound-simulator-app (Simulator-group, n = 118) to learn for 30 min. The knowledge of the students was examined both before and after the learning-period by having them identify sonographic structures in videos using single-choice selection. RESULTS: There were no significant differences between the two groups regarding age (p = 0.87), gender (p = 0.28), and the number of previously performed ultrasound-examinations (p = 0.45). In the Simulator-group, there was a significantly higher learning effect regarding the proportion of students with an increase of correct answers in the video test examination (p = 0.005). At the end of learning, the students in the Simulator-group needed significantly less time to display the structures in the app's simulation (median initially 10.9 s vs. 6.8 s at the end; p < 0.001). CONCLUSIONS: The novel ultrasound-simulation-app seems to be a useful addition and improvement to ultrasound training. Previous difficulties such as simultaneously having patients, ultrasound-machines, and professors at disposal can thus be avoided. This means that another important step towards remote learning can be taken, which has been proven increasingly essential lately, due to the COVID-19 pandemic.

Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial.

BACKGROUND: When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients. METHODS: A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety. RESULTS: No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively. CONCLUSION: Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting. TRIAL REGISTRATION: Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.

Quality of life during and after adjuvant anthracycline-taxane-based chemotherapy with or without Gemcitabine in high-risk early breast cancer: results of the SUCCESS A trial.

PURPOSE: In high-risk early breast cancer, adjuvant taxane-Gemcitabine combinations result in a recurrence-free survival similar to single-agent taxanes. However, haematologic toxicities and need for dose reductions are more frequent in combinations. Which option ultimately provides a better quality of life (QoL) is unknown. We compared the QoL curves before, during, and up to one year after three cycles of Fluorouracil-epirubicin-cyclophosphamide followed by three cycles of Docetaxel-Gemcitabine or Docetaxel. METHODS: Overall, 3691 women with recent R0-resection of a primary epithelial breast cancer participated in the nationwide SUCCESS A clinical trial. The centres sent QoL questionnaires of the European Organisation for Research and Treatment of Cancer before and up to 15 months after randomisation to Docetaxel-Gemcitabine versus Docetaxel. Multilevel analysis by chemotherapy arm estimated the QoL time curves, questionnaire return, and dropout. RESULTS: The combination caused one-point higher global QoL (95% confidence ±1; p = 0.05) and 1.1 lower odds of adherence to the outcome (95% confidence 1.0-1.1; p = 0.23) than the monotherapy. In both groups, a 10-point decrease during therapy preceded a 16-point increase after chemotherapy (p < 0.001). The secondary QoL outcomes showed transient superiority of the combination at the end of chemotherapy. Discontinuation from chemotherapy and its reasons were equal in both groups. CONCLUSIONS: While patients perceive a one-point QoL difference as meaningless, a six-point increase is clinically relevant for them. That is, both regimens cause the same relevant long-term QoL improvement. With the similar recurrence-free survival, the lower toxicity, and the shorter chemotherapy duration in mind, taxanes without Gemcitabine are the preference. This challenges previous recommendations supporting combinations.

Prenatally Diagnosed Single Umbilical Artery (SUA) - Retrospective Analysis of 1169 Fetuses.

PURPOSE: The incidence of a fetal single umbilical artery (SUA) is about 0.5 % and has been associated with an increased risk of congenital malformations, fetal aneuploidy and intrauterine growth restriction (IUGR). MATERIALS AND METHODS: A retrospective analysis of 1169 women with singleton pregnancies diagnosed with fetal SUA between 1997 and 2014 in a specialized practice for prenatal diagnostics has been performed. Data was obtained on maternal and fetal findings as well as pregnancy outcome. RESULTS: 989 (84.6 %) fetuses showed an isolated SUA (iSUA) while 180 (15.4 %) presented with SUA and additional structural and/or chromosomal abnormalities. Structural malformations were distributed as follows: 9.0 % cardiovascular, 3.5 % urogenital, 2.9 % musculoskeletal, 3.0 % gastrointestinal and 2.1 % cerebral. 2.1 % of the fetuses had chromosomal aberrations. 50.8 % (49.2 %) of the fetuses were female (male) and right vs. left SUA was found in 64.2 % (35.8 %) of the cases. Fetuses with SUA and additional abnormalities showed lower rates of live births (85.0 % vs. 98.5 %, p < 0.001), a lower median birth weight (2825 g vs. 3220 g, p < 0.001), higher rates of preterm delivery before week 34 + 0 (13.7 % vs. 3.8 %, p < 0.001) and weighed less than the 5th growth percentile in 21.6 % vs. 9.3 % (p < 0.001) of the fetuses with iSUA. In 5.1 % (60) of the children, chromosomal or structural abnormalities were detected post-partum. CONCLUSION: Once fetal SUA is diagnosed, intense sonoanatomy of the fetus is required and, if associated malformations are found, genetic testing must be offered. In iSUA intermittent biometry is recommended for the early detection of IUGR but additional genetic testing is not necessarily recommended.

Seroma in breast surgery: all the surgeons fault?

BACKGROUND: Despite a trend for less radical surgical approaches in breast cancer due to better understanding of tumour biology and new treatment options such as neoadjuvant chemotherapy (NAC) and intra-operative radiotherapy (IORT), seroma production remains one of the main surgical side effects that can result in prolonged recovery, delay of radiotherapy and patient discomfort. The aim of this study is to provide an update on risk factors for seroma production after breast cancer surgery considering the latest treatment options. METHODS: A retrospective analysis of seroma production in primary breast cancer patients treated between 01.01.2010 and 31.12.2014 at the Breast Cancer Centre, University Hospital Ulm, was performed. Patients with previous breast/axillary surgery or more than one intervention were excluded. Seroma formation was measured using wound drains placed in breast and axilla. RESULTS: In total, 581 patients met the inclusion criteria. Median age at diagnosis was 60 years, and median BMI 25.6 kg/m2. 60 (10.3%) patients had a mastectomy, 175 (30.1%) patients received IORT, and 72 (12.4%) patients received NAC. Median amount of seroma production was 82.5 ml (range 0-3012.5 ml). Multivariate analysis revealed that most of the observed variation in seroma production was due to type of surgery (mastectomy vs. breast conserving), length of surgery and number of removed lymph nodes. Both NAC and IORT explained a significant but very small amount of the observed variation in seroma production. CONCLUSION: The most important factors for seroma production are extent and duration of breast surgery.

CA27.29 as a tumour marker for risk evaluation and therapy monitoring in primary breast cancer patients.

Several trials showed that tumour markers are associated with an impaired prognosis for breast cancer. Whether earlier treatment can improve the course of the disease remains controversial. The SUCCESS Trial compares FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) as well as 2 vs. 5 years of zoledronate in high-risk primary breast cancer patients. In 2669 patients, CA27.29 was measured before and after chemotherapy with the ST AIA-PACK CA27.29 reagent for the AIA-600II automated enzyme immunoassay (Tosoh Bioscience, Belgium). Values above 31 U/ml were considered positive. Of the patients, 7.6 % (n = 202, mean 19, range 3-410) and 19.1 % (n = 511, mean 21, range 3-331) had elevated marker levels before and after chemotherapy, respectively. Of the patients, 4.9 and 78 % showed elevated and low CA27.29, respectively, at both time points. After treatment, 35 % of the pre-therapy positive patients were negative, and 15 % of the initially negative patients became positive. The correlation between both time points was significant (p < 0.0001). No correlations among nodal status, grading, hormonal status, HER2 status and CA27.29 levels were found. However, tumour size (p = 0.02), older age (p < 0.001) and post-menopausal status (p = 0.006) were significantly associated with higher CA27.29 levels. Before treatment, the prevalence of elevated CA27.29 was equally distributed between both treatment arms, whereas after chemotherapy, 13.7 % of the patients in the FEC-doc arm showed an increased level vs. 25.4 % of the patients in the FEC-doc/gemcitabine arm (p < 0.0001). However, we could not show a significant association between the G-CSF application (yes vs. no) and CA27.29 status before/after chemotherapy (p = 0.75). These results indicate a close relationship between CA27.29 levels and tumour mass. Increased values after the completion of chemotherapy might be attributed to treatment effects and should be considered with caution.

The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial.

INTRODUCTION: Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. METHODS: This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0-29.9), slightly obese (BMI 30.0-34.9), moderately obese (BMI 35.0-39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. RESULTS: Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71-4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63-4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. CONCLUSIONS: Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. TRIAL REGISTRATION: Clinicaltrials.gov NCT02181101 . Registered September 2005.

Laparoscopic Transabdominal Needle-free Emergency Cerclage in the Early Second Trimester of Pregnancy after Failed Transvaginal Cerclage: Two Case Reports and a Review of the Literature.

Purpose: The aim of the study was to describe the preventive option and safety of laparoscopic transabdominal emergency cerclage in pregnant women with advanced cervical shortening after failed vaginal cerclage or in whom vaginal cerclage is no longer possible. Method: Laparoscopic isthmo-cervical emergency cerclage was carried out in two patients at 13+0 and 15+5 weeks of gestation (GW) respectively. Both patients had cervical shortening and it was no longer possible to expose the cervix after conization or re-conization. The attempts to carry out transvaginal cerclage were unsuccessful. The technical aspects, feasibility, safety, and pregnancy outcomes after laparoscopic transabdominal cerclage are presented here, based on two case reports. Results: The cerclages were placed after blunt dissection of the uterine vessels and careful introduction of a KELLY forceps through the avascular space between the ascending and descending branches of the uterine vessels without using a needle. The operating times were 93 and 134 minutes (min), respectively. The estimated blood loss during the procedure was less than 50 ml and neither perioperative nor postoperative complications occurred. The subsequent course of both pregnancies was uneventful and fetal development in both cases was normal. In the first case, the baby was delivered by secondary cesarean section following premature rupture of membranes in week 35+4 of gestation. The baby had a birthweight of 2786 g, APGAR scores of 8/9/10 and an umbilical cord arterial pH of 7.36. In the second case, delivery was by primary cesarean section in week 39+5 of gestation. The infant had a birth weight of 4160 g, APGAR scores of 5/9/10 and an umbilical cord arterial pH of 7.20. Conclusion: Laparoscopic transabdominal cerclage is a safe and effective treatment option, even early in the second trimester of pregnancy, for patients in whom transvaginal cerclage is no longer possible due to anatomical factors. The method is technically very feasible and is associated with positive obstetric outcomes. The overall risk of perioperative complications is within acceptable limits.

Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial.

BACKGROUND: This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. OBJECTIVE: We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. STUDY DESIGN: The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. RESULTS: Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. CONCLUSION: The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

The role of preoperative ultrasound evaluation of inguinal lymph nodes in patients with vulvar malignancy.

OBJECTIVES: Inguinal lymphadenectomy in vulvar malignancies is associated with significant morbidity, especially in patients over 70 years old. Under certain conditions, surgical guidelines recommend biopsy and evaluation of the sentinel node in early vulvar cancer. The purpose of our study is to evaluate ultrasonography as a predictor of inguinal lymph node involvement. METHODS: A retrospective study was performed with 60 patients who had vulvar malignancies (92% of which were squamous cell carcinomas) and who were treated at our hospital between 2002 and 2012. The patients ranged in age from 35 to 89 years, with a median age of 76 years. In total, 118 groin scans were retrospectively evaluated for sonographic evidence of lymph node involvement (i.e., absence of fatty hilum, irregular shape, cortical region diameter and vascularization pattern). The results were then compared with histopathologically confirmed lymph node status. RESULTS: Histopathologically confirmed lymph node status was available for 107 of the inguinal nodes examined by ultrasound, and lymph node metastases were found in 38 (35.5%) cases. The presence or absence of inguinal lymph node metastases was correctly identified by sonography in 92 (86.0%) of the scanned areas. Sensitivity was 76.3%, specificity was 91.3%, and positive and negative predictive values were 82.9% and 87.5%, respectively. CONCLUSIONS: Ultrasonography of the inguinal lymph nodes showed a relatively high sensitivity and specificity for predicting inguinal tumor metastases. However, our results indicate that surgical lymph node staging is still needed to precisely determine inguinal lymph node status in vulvar cancer, especially because a missed lymph node-metastasis is often fatal.

Novel Method for Three-Dimensional Facial Expression Recognition Using Self-Normalizing Neural Networks and Mobile Devices.

Introduction To date, most ways to perform facial expression recognition rely on two-dimensional images, advanced approaches with three-dimensional data exist. These however demand stationary apparatuses and thus lack portability and possibilities to scale deployment. As human emotions, intent and even diseases may condense in distinct facial expressions or changes therein, the need for a portable yet capable solution is signified. Due to the superior informative value of three-dimensional data on facial morphology and because certain syndromes find expression in specific facial dysmorphisms, a solution should allow portable acquisition of true three-dimensional facial scans in real time. In this study we present a novel solution for the three-dimensional acquisition of facial geometry data and the recognition of facial expressions from it. The new technology presented here only requires the use of a smartphone or tablet with an integrated TrueDepth camera and enables real-time acquisition of the geometry and its categorization into distinct facial expressions. Material and Methods Our approach consisted of two parts: First, training data was acquired by asking a collective of 226 medical students to adopt defined facial expressions while their current facial morphology was captured by our specially developed app running on iPads, placed in front of the students. In total, the list of the facial expressions to be shown by the participants consisted of "disappointed", "stressed", "happy", "sad" and "surprised". Second, the data were used to train a self-normalizing neural network. A set of all factors describing the current facial expression at a time is referred to as "snapshot". Results In total, over half a million snapshots were recorded in the study. Ultimately, the network achieved an overall accuracy of 80.54% after 400 epochs of training. In test, an overall accuracy of 81.15% was determined. Recall values differed by the category of a snapshot and ranged from 74.79% for "stressed" to 87.61% for "happy". Precision showed similar results, whereas "sad" achieved the lowest value at 77.48% and "surprised" the highest at 86.87%. Conclusions With the present work it can be demonstrated that respectable results can be achieved even when using data sets with some challenges. Through various measures, already incorporated into an optimized version of our app, it is to be expected that the training results can be significantly improved and made more precise in the future. Currently a follow-up study with the new version of our app that encompasses the suggested alterations and adaptions, is being conducted. We aim to build a large and open database of facial scans not only for facial expression recognition but to perform disease recognition and to monitor diseases' treatment progresses.

A Scary Complication: Single-center Study on Management and Outcome of Cesarean Scar Pregnancy.

A cesarean scar pregnancy (CSP) is a scary and life-threatening complication of cesarean section (CS). Nevertheless, the incidence of CS is constantly growing. The CSP incidence is 0,15% of pregnancies after CS which represents 6,1% of all ectopic pregnancies in women with condition after CS. Therefore, it should be more present in the clinical daily routine. From mild nonspecific symptoms to hypovolemic shock, diagnosis and therapy must be performed quickly. With the progressive growth of the scar pregnancy, a uterine rupture involves the risk of severe bleeding, and an emergency hysterectomy could be necessary. Prolongation of pregnancy has been successful only in a few cases. We report 11 cases from our hospital in the past 10 years. In the discussion, treatment options of this complication with an increasing incidence, which is associated with serious morbidity and mortality, are presented based on the current literature. Treatment options include drug therapy, but also surgical or combined procedures with radiological intervention.

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) and Epoetin (EPO) on Hematologic Toxicities and Quality of Life in Patients During Adjuvant Chemotherapy in Early Breast Cancer: Results From the Multi-Center Randomized ADEBAR Trial.

BACKGROUND: Hematologic toxicities are one of the greatest challenges in adjuvant chemotherapy for breast cancer. This analysis of the ADEBAR trial aims to evaluate application and effect of granulocyte colony-stimulating factor (G-CSF) and epoetin alfa (EPO) on hematologic parameters and fatigue in patients with breast cancer during chemotherapy. PATIENTS AND METHODS: In the ADEBAR trial, 1493 patients with node-positive primary breast cancer were randomized to either 6 × 5-fluorouracil, epirubicin, and cyclophosphamide (FEC120) or 4 × epirubicin and cyclophosphamide followed by 4 × docetaxel (EC-DOC). Co-medication with G-CSF or EPO was applied to treat chemotherapy-induced leukopenia or anemia. Fatigue was assessed at baseline and after one-half of the chemotherapy. RESULTS: In total, 899 patients could be included in the analysis. There was no evidence for an association between leucocyte or hemoglobin levels and application of G-CSF and EPO in the preceding cycle, respectively. Hemoglobin levels (B = -0.41; P < .001) were affected by treatment regimen. Fatigue during chemotherapy was mostly affected by the level of fatigue before the start of chemotherapy (B = 0.41; P < .001). Patients with G-CSF application in the preceding cycle showed an increased fatigue score (B = 5.43; P = .02). CONCLUSION: We showed that fatigue during adjuvant chemotherapy was mostly affected by the level of fatigue present before the start of chemotherapy. This result suggests that the level of fatigue before the start of treatment should be included as an important factor when deciding on type and toxicity of chemotherapy in early breast cancer.

Effect of an Augmented Reality Ultrasound Trainer App on the Motor Skills Needed for a Kidney Ultrasound: Prospective Trial.

BACKGROUND: Medical education is evolving from "learning by doing" to simulation-based hands-on tutorials. OBJECTIVE: The aim of this prospective 2-armed study was to evaluate a newly developed augmented reality ultrasound app and its effect on educational training and diagnostic accuracy. METHODS: We recruited 66 medical students and, using imaging and measuring a kidney as quality indicators, tested them on the time they needed for these tasks. Both groups used textbooks as preparation; in addition, the study group had access to a virtual ultrasound simulation app for mobile devices. RESULTS: There was no significant difference between the study arms regarding age (P=.97), sex (P=.14), and previous ultrasound experience (P=.66). The time needed to complete the kidney measurements also did not differ significantly (P=.26). However, the results of the longitudinal kidney measurements differed significantly between the study and control groups, with larger, more realistic values in the study group (right kidney: study group median 105.3 mm, range 86.1-127.1 mm, control group median 92 mm, range 50.4-112.2 mm; P<.001; left kidney: study group median 100.3 mm, range 81.7-118.6 mm, control group median 85.3 mm, range 48.3-113.4 mm; P<.001). Furthermore, whereas all students of the study group obtained valid measurements, students of the control group did not obtain valid measurements of 1 or both kidneys in 7 cases. CONCLUSIONS: The newly developed augmented reality ultrasound simulator mobile app provides a useful add-on for ultrasound education and training. Our results indicate that medical students' use of the mobile app for training purposes improved the quality of kidney measurements.

Foetal Doppler Parameters as a Prognostic Marker Before Induction of Labour.

Introduction The value of foetal Doppler ultrasonography before induction of labour for prognostic assessment of the duration of labour and foetal outcome is presented. Patients and Methods Doppler ultrasound of the foetal middle cerebral artery (MCA) and of the umbilical artery (UA) was performed in addition to evaluation of the Bishop score in 49 women around the expected date of confinement (38 + 0 - 42 + 0 weeks of gestation) prior to planned pharmacological induction of labour. These parameters were studied using non-parametric statistical methods for associations with the duration of induction until delivery, the mode of delivery and foetal outcome. Results The resistance index (RI) of the MCA (rs = 0.547, p < 0.001), but not the RI of the UA (rs = - 0.055, p = 0.707) correlated positively with the duration of induction. Moreover, a negative correlation was found between the RI of the UA and the baby's arterial cord pH at birth (rs = - 0.287, p = 0.046). No differences in the RI of MCA or UA were found between babies born vaginally and those delivered by secondary section. Conclusion The present data show that Doppler measurement of the foetal MCA and UA before pharmacological induction of labour at term can be a further parameter for prognostic estimation of the duration and success of induction and of foetal outcome in addition to the established Bishop score.

Association of Circulating Tumor Cell Status With Benefit of Radiotherapy and Survival in Early-Stage Breast Cancer.

Importance: Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown. Objective: To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer. Design, Setting, and Participants: The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017. Exposure: Adjuvant RT. Main Outcomes and Measures: Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Results: A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients. Conclusions and Relevance: Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.

Mosaic genome-wide maternal isodiploidy: an extreme form of imprinting disorder presenting as prenatal diagnostic challenge.

BACKGROUND: Uniparental disomy of certain chromosomes are associated with a group of well-known genetic syndromes referred to as imprinting disorders. However, the extreme form of uniparental disomy affecting the whole genome is usually not compatible with life, with the exception of very rare cases of patients with mosaic genome-wide uniparental disomy reported in the literature. RESULTS: We here report on a fetus with intrauterine growth retardation and malformations observed on prenatal ultrasound leading to invasive prenatal testing. By cytogenetic (conventional karyotyping), molecular cytogenetic (QF-PCR, FISH, array), and methylation (MS-MLPA) analyses of amniotic fluid, we detected mosaicism for one cell line with genome-wide maternal uniparental disomy and a second diploid cell line of biparental inheritance with trisomy X due to paternal isodisomy X. As expected for this constellation, we observed DNA methylation changes at all imprinted loci investigated. CONCLUSIONS: This report adds new information on phenotypic outcome of mosaic genome-wide maternal uniparental disomy leading to an extreme form of multilocus imprinting disturbance. Moreover, the findings highlight the technical challenges of detecting these rare chromosome disorders prenatally.