[Right aortic arch with mirror image branching : a rare cause of dysphagia]. / L'image du mois. Arc aortique droit avec image en miroir : une cause rare de dysphagie.

We report the case of a 36-year-old female whose dysphagia revealed a congenital anomaly of the thoracic aorta: the right aortic arch with mirror image branching. This is a rare embryonic developmental anomaly where the aorta wraps around the right bronchus and the supra-aortic trunks emerge from the arch in the opposite order to normal. Most of the patients are asymptomatic unless there is a significant compression of mediastinal structures. Major compression of the esophagus or trachea, aneurysmal disease, dissection of the thoracic aorta, or the presence of a Kommerell diverticulum larger than 2 cm may require a surgical repair. There is no standard treatment and it must be adapted to the clinical presentation and the anatomic configuration of each patient. Our patient did not receive any treatment for her condition.

Nous rapportons le cas d'une patiente de 36 ans dont le tableau de dysphagie a permis de mettre en évidence une anomalie congénitale de l'aorte thoracique : l'arc aortique droit avec image en miroir. Il s'agit d'une anomalie de développement embryonnaire rare où l'aorte s'enroule autour de la bronche souche droite et où les troncs supra-aortiques émergent de la crosse dans l'ordre inverse et opposé à la normale. La grande majorité des patients est asymptomatique, à moins qu'il existe une compression des structures médiastinales. Une compression majeure de l'oesophage ou de la trachée, une maladie anévrismale, une dissection de l'aorte thoracique ou la présence d'un diverticule de Kommerell de plus de 2 cm peuvent justifier une sanction chirurgicale. Il n'y a pas de traitement standard et celui-ci doit être adapté à la présentation clinique et à la configuration anatomique du patient. Notre patiente n'a bénéficié d'aucun traitement pour son affection.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Impact of Assisted Reproduction Techniques on Adverse Maternal Outcomes and on the Rate of Hospitalization in Maternal Intensive Care.

Background and Objective: The aim of this retrospective cohort study is to evaluate the impact of assisted reproductive treatment (ART) on adverse maternal outcomes and the rate of hospitalization in maternal intensive care (MIC) in a tertiary university center in Liege, Belgium. Materials and Methods: This is a retrospective cohort study comparing two groups, 6557 patients who achieved pregnancy spontaneously and 330 patients who achieved pregnancy after ART, between January 2020 and December 2022. These patients were followed in the academic obstetrics department of Citadelle Hospital, Liège. The database of the ART center was compared with the database of the delivery unit to determine the cohort of patients who conceived after ART. Adverse maternal outcomes and MIC hospitalization rates were compared with between spontaneous pregnancies and ART groups. ART groups were also compared with each other. Results: The rate of hospitalization in maternal intensive care for patients who achieved pregnancy spontaneously was 12.1%, compared to 17.3% after ART. Comparing the rate of pre-eclampsia, 3.5% of spontaneous pregnancies were complicated by pre-eclampsia, while after ART, 10.9% of patients developed this complication during pregnancy. This rate was higher after IVF (12%) compared to intrauterine insemination and particularly after frozen embryo transfer (FET) in artificial cycle (17.9%). The birthweight of newborns after ART was also analyzed. A significant difference was obtained when comparing fresh embryo transfer with FET. Conclusions: Our study confirmed that FET in artificial cycle is a risk factor for pre-eclampsia and that fresh embryo transfer is associated with a higher rate of newborns with a lower percentile of birthweight. Our data showed that the rate of MIC hospitalization was significantly higher after ART but did not differ between groups.

[Etiology of preeclampsia after assisted reproductive treatments]. / Étiologie de la prééclampsie après traitements de procréation médicalement assistée.

About 12 percent of women require assisted reproductive technology (ART) to get pregnant as infertility concerns more and more couples. Recent studies highlight obstetrical complications after ART such as preeclampsia, gestational diabetes or placenta accrete spectrum. Pre-eclampsia is a specific pathology of the pregnancy which can lead to materno-fetal complications including prematurity and intrauterine growth restriction. The aim of this article is to summarize preeclampsia risk factors during ART. We performed a narrative review based on articles published since 2010. Preeclampsia rate is increased after frozen embryo transfer, especially in case of artificial cycle, multiple pregnancies and gamete donation.

Environ 12 % des femmes dans le monde auront recours aux techniques de procréation médicalement assistée (PMA) pour concevoir. L'infertilité concerne de plus en plus de couples. Des études récentes mettent en évidence des complications obstétricales après la PMA telles que la prééclampsie, le diabète gestationnel et le spectre des placenta accreta. La prééclampsie est une pathologie spécifique de la grossesse qui peut entraîner des complications materno-fœtales, notamment la prématurité et le retard de croissance intra-utérin. L'objectif de cet article est de résumer les facteurs de risque de la prééclampsie liés à la PMA. Nous avons réalisé une revue narrative basée sur les articles publiés depuis 2010. Le taux de prééclampsie est augmenté après les transferts d'embryons congelés, en particulier en cas de cycle artificiel, de grossesses multiples, de don de gamètes et d'hyperstimulation ovarienne.

CHECGAIT: A Functional Electrical Stimulation Clinical Pathway to Reduce Foot Drop during Walking in Adult Patients with Upper Motor Neuron Lesions.

Foot drop during the swing phase of gait and at initial foot contact is a current kinematic abnormality that can occur following an upper motor neuron (UMN) lesion. Functional electrical stimulation (FES) of the common peroneal nerve through an assistive device is often used in neuro-rehabilitation to help patients regain mobility. Although there are FES-specific guideline recommendations, it remains a challenge for clinicians to appropriately select patients eligible for the daily use of FES devices, as very few health insurance systems cover its cost in Europe. In Luxembourg, since 2018, successfully completing an FES clinical pathway called CHECGAIT is a prerequisite to receiving financial coverage for FES devices from the national health fund (Caisse Nationale de Santé-CNS). This study describes the structure and steps of CHECGAIT and reports our experience with a cohort of 100 patients enrolled over a three-year period. The clinical and gait outcomes of all patients were retrospectively quantified, and a specific analysis was performed to highlight differences between patients with and without an FES device prescription at the end of a CHECGAIT. Several significant gait differences were found between these groups. These results and CHECGAIT may help clinicians to better select patients who can most benefit from this technology in their daily lives. In addition, CHECGAIT could provide significant savings to public health systems by avoiding unnecessary deliveries of FES devices.

Methotrexate for CSPs.

Expectant management of a cesarean scar pregnancy (CSP) is associated with a high risk of severe maternal morbidity. Therefore, most experts recommend immediate termination after the diagnosis of a CSP. However, there is no consensus about the optimal management of a CSP in terms of efficacy, safety, and preservation of future fertility. Methotrexate (MTX) is a folic acid antagonist that has been largely used to treat tubal ectopic pregnancies. This review summarizes the current knowledge and uncertainties about the administration of MTX as a medical or non-invasive option to terminate a CSP; the preferred injection route (systemic or local/intragestational), the comparison with other treatment modalities, and the prognostic factors for MTX success will be discussed, as well as the recommendations from scientific societies.

[Diagnosis and management of a foetus with congenital high airway obstruction syndrome (CHAOS)]. / Cas clinique. Diagnostic et prise en charge d'un fœtus porteur d'un syndrome d'obstruction congénitale des voies respiratoires supérieures (CHAOS).

Congenital high airway obstruction syndrome is a rare malformation whose prognosis is very poor resulting in foetal or perinatal death if no perinatal intervention is performed. However, ultrasound and magnetic resonance enable an accurate prenatal diagnosis and optimal choice of interventional foetal medicine techniques (transtracheal puncture, fetoscopy). These approaches reduce foetal side effects related to the pathological process, and avoid the mother ex utero intrapartal treatment and its deleterious effects. If it becomes indispensable ex utero intrapartal treatment allows optimal management of the new born by securing the foetal airways while minimizing risk for hypoxic damage through the maintenance of maternal-foetal circulation. We present the story of a couple with a suspected case of CHAOS at 21 weeks of amenorrhea, the diagnostic and the management until the birth of the child.

Le syndrome d'obstruction congénitale des voies respiratoires supérieures est une malformation rare dont le pronostic est très péjoratif sans intervention périnatale, entraînant un décès in utero ou à la naissance. L'échographie et la résonance magnétique nucléaire permettent de poser un diagnostic prénatal précis et de choisir les techniques de médecine fœtale interventionnelle les mieux adaptées (ponction trachéale sous contrôle échographique, reperméabilisation sous fœtoscopie). Ces approches réduisent les effets secondaires fœtaux liés au processus pathologique, et évitent à la mère le traitement intrapartal ex utero et ses effets délétères. S'il devient indispensable, le traitement intrapartal ex utero permet une prise en charge optimale du nouveau-né en sécurisant ses voies respiratoires, tout en minimisant les dommages hypoxiques, grâce au maintien de la circulation materno-foetale. Nous présentons l'histoire d'un couple confronté à une suspicion de CHAOS à 21 semaines d'aménorrhée, le parcours diagnostique et la prise en charge jusqu'à la naissance de l'enfant.

Classification of Stiff-Knee Gait Kinematic Severity after Stroke Using Retrospective k-Means Clustering Algorithm.

Nowadays, a classification system for unilateral stiff-knee gait (SKG) kinematic severity in hemiparetic adult patients after stroke does not exist. However, such classification would be useful to the clinicians. We proposed the use of the k-means method in order to define unilateral SKG severity clusters in hemiparetic adults after stroke. A retrospective k-means cluster analysis was applied to five selected knee kinematic parameters collected during gait in 96 hemiparetic adults and 19 healthy adults from our clinical gait analysis database. A total of five discrete knee kinematic clusters were determined. Three clusters of SKG were identified, based on which a three-level severity classification was defined: unbend-knee gait, braked-knee gait, and frozen-limb gait. Preliminary construct validity of the classification was obtained. All selected knee kinematic parameters defining the five clusters and the majority of usual kinematic parameters of the lower limbs showed statistically significant differences between the different clusters. We recommend diagnosing SKG for values strictly below 40° of knee flexion during the swing phase. Clinicians and researchers are now able to specify the level of kinematic severity of SKG in order to optimize treatment choices and future clinical trial eligibility criteria.

Investigation of discrepancies obtained during 15 years of non-invasive fetal RHD genotyping in apparent serologic RhD-negative pregnant women.

OBJECTIVES: In some European countries, non-invasive fetal RHD genotyping is the first step of anti-D allo-immunized pregnant women management but presence of RHD variant alleles may interfere with the results accuracy. We developed an algorithm allowing solving discordant results (due to the presence of RHD variant) in fetal RHD genotyping assay. METHOD: This study gathered the results of fetal RHD genotyping performed between 2006 and 2020 in the Medicine Laboratory of CHR Liège. Exons 4, 5 and 10 of the fetal RHD were profiled in maternal plasma using real time polymerase chain reaction (PCR). When the results were discrepant, maternal RHD variant was further explored by sequence-specific primer PCR on maternal buffy coat. RESULTS: A total of 11,630 pregnant women (mainly of both Caucasian and African origins) were tested during the study period and RHD variant alleles were detected in 247 women. The most frequent variant was RHD*08N.01 found in 66 women mainly of Black African origin. We identified 45 women with weak RHD variant type 1, 2 or 3. CONCLUSION: Women with weak RHD variant type 1, 2 or 3 can safely be considered as RhD positive in terms of RhIg prophylaxis and/or transfusion of blood components. Therefore, identification of RHD allele variants in women with discordant fetal RHD genotyping results contributes to save RhIg prophylaxis and RhD negative blood components.

Evolution of maternal and neonatal outcomes before and after the adoption of the IADPSG/WHO guidelines in Belgium: A descriptive study of 444,228 pregnancies.

Objectives: To appraise adverse pregnancy outcomes after the adoption of IADPSG/WHO guidelines in Belgium. Methods: A retrospective study of the Center for Perinatal Epidemiology registry was conducted. Demographic changes and adverse pregnancy outcomes were compared between a pre- and post-guideline period in women with and without hyperglycemia in pregnancy (HIP). Adjusted odds ratios with a 95% confidence interval (CI) were used to compare maternal and neonatal outcomes controlling for potential confounders (maternal age, body mass index (BMI), hypertension, parity, and multiple births). Results: The prevalence of HIP increased (6.0%-9.2%). In the overall population regardless of glycemic status, gestational weight gain (12.3 ± 5.7 vs 11.9 ± 5.8; p < 0.001), hypertension (0.92; 95% CI, 0.89-0.94; p < 0.001), and neonatal intensive care unit/special care nursery (0.89; 95% CI, 0.87-0.91; p < 0.001) decreased despite increasing maternal age and pre-pregnancy BMI. Emergency cesarean section rates (1.07; 95% CI, 1.05-1.09; p < 0.001) increased, but not in the HIP population (1.02; 95% CI, 0.95-1.10; ns). The overall incidence of preterm birth (1.09; 95% CI, 1.06-1.12; p < 0.001), stillbirth (1.10; 95% CI, 1.01-1.21; p < 0.05), and perinatal mortality (1.10; 95% CI, 1.01-1.19; p < 0.05) increased, except in the HIP population (1.03; 95% CI, 0.95-1.11; ns), (1.04; 95% CI, 0.74-1.47; ns) and (1.09; 95% CI, 0.80-1.49; ns), respectively. The overall incidence of small- for-gestational-age remained unchanged (0.99; 95%CI, 0.97-1.01; ns) regardless of glycemic status. In the HIP population, large-for-gestational age (0.90; 95% CI, 0.84-0.95; p < 0.001) and macrosomia (0.84; 95% CI, 0.78-0.92; p < 0.001) decreased. Conclusion: After the implementation of IADPSG/WHO guidelines, the prevalence of HIP increased by 53.7% and the incidence of major HIP-related pregnancy complications appears to be lower. However, we cannot conclude that the reduction of LGA-macrosomia is due to a better management of diabetes or due to greater recruitment of women with mild HIP associated with a lower risk of obstetrical complications.

Metabolic Energy Expenditure and Accelerometer-Determined Physical Activity Levels in Post-Stroke Hemiparetic Patients.

BACKGROUND: Assessment of metabolic energy expenditure in post-stroke patients using accelerometers is clinically important. However, understanding of the best placement of accelerometers on the body and methods for calculating activity counts are limited. METHODS: Thirty hemiparetic post-stroke patients participated in this cross-sectional study. Four triaxial accelerometers were attached to the hemiplegic and contralateral sides of the waist and ankles during various activities: lying, sitting, standing, stepping in place, and walking on a treadmill (1-5 kmh-1). Activity counts and metabolic energy expenditure of the patients were recorded simultaneously. Simple linear regression analyses were performed between the activity counts and energy expenditure. Activities were classified according to their intensity, using the definition of energetic sedentary behavior of post-stroke patients and a low fitness level group. RESULTS: The best estimate of energy expenditure was obtained when the accelerometer was worn on the contralateral ankle and the activity counts was calculated using the vertical and anteroposterior axes (R2=0.812). Six classes of activity intensity (sedentary: ≤1.5 METs, very light: 1.51-1.79, light: 1.80-2.59, moderate: 2.60-3.39, hard: 3.40-4.39, and very hard: ≥4.40) and corresponding activity counts cut-off points are presented. CONCLUSION: A triaxial accelerometer worn on the contralateral ankle and a method of calculating activity counts that includes at least the vertical and anteroposterior axes are recommended for estimating metabolic energy expenditure in post-stroke patients. The new activity counts cut-off points provide a significant advance in the interpretation of post-stroke monitoring in patients outside the hospital or rehabilitation center.

First-line noninvasive management of cytomegalovirus primary infection in pregnancy.

OBJECTIVES: To introduce a first-line noninvasive antenatal management of maternal cytomegalovirus (CMV) primary infection based on ultrasound (US) and magnetic resonance imaging (MRI). Amniocentesis (AC) is used as a second-line tool in cases of abnormalities compatible with fetal CMV infection on US and/or MRI screening. METHODS: Between January 2011 and October 2018, pregnant women referred with a CMV primary infection on antibody screening were followed up by monthly US scans and a brain MRI at approximately 32 weeks. In cases with US and/or MRI abnormalities compatible with congenital CMV infection, AC was performed to confirm the diagnosis. RESULTS: Ninety pregnant women with a primary CMV infection were included (89 singleton and one twin pregnancy). The first-line screening by US and/or MRI was normal for 72 of 91 fetuses (79%). At birth, 19 of these 72 neonates (26%) had a positive urine sample for CMV but were asymptomatic. US and/or MRI abnormalities were identified in 19 fetuses (21%). AC confirmed a fetal CMV infection in 16 fetuses (84%); 12 pregnancies were terminated, and four were continued, with three symptomatic neonates at birth and one poor neurodevelopmental outcome at postnatal follow-up. CONCLUSIONS: First-line noninvasive management of maternal CMV primary infection based on serial US scans and brain MRI can be offered to identify fetuses with severe symptomatic congenital CMV infection and reduce the number of ACs without compromising the fetal outcome.

Enhancing the value of the sFlt-1/PlGF ratio for the prediction of preeclampsia: Cost analysis from the Belgian healthcare payers' perspective.

OBJECTIVE: To evaluate the economic impact of introducing the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test into clinical practice in Belgium for the prediction of preeclampsia (PE). STUDY DESIGN: We developed a one-year time-horizon decision tree model to evaluate the short-term costs associated with the introduction of the sFlt-1/PlGF test for guiding the management of women with suspected PE from the Belgian public healthcare payers' perspective. The model estimated the costs associated with the diagnosis and management of PE in pregnant women managed in either a test scenario, in which the sFlt-1/PlGF test is used in addition to current clinical practice, or a no test scenario, in which clinical decisions are based on current practice alone. Test characteristics were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of PE. Unit costs were obtained from Belgian-specific sources. The main model outcome was the total cost per patient. RESULTS: Introduction of the sFlt-1/PlGF ratio test is expected to result in a cost saving of €712 per patient compared with the no test scenario. These savings are generated mainly due to a reduction in unnecessary hospitalizations. CONCLUSIONS: The sFlt-1/PlGF test is projected to result in substantial cost savings for the Belgian public healthcare payers through reduction of unnecessary hospitalization of women with clinical suspicion of PE that ultimately do not develop the condition. The test also has the potential to ensure that women at high risk of developing PE are identified and appropriately managed.

When a rare condition creates a scientific society: The history of the International Society for Placenta Accreta Spectrum (IS-PAS).

Almost 10 years ago, clinicians at multiple locations all over Europe observed an increased number of antenatally undiagnosed cases of placenta accreta spectrum (PAS) resulting in significant morbidity and the occasional maternal death. Even with an improvement in antenatal imaging, the management of severe PAS remains challenging. One solution to improve understanding in rare but potentially lethal conditions is international collaboration. Consequently, a European working group was formed, which over the next few years grew into an international society, the IS-PAS. The collective goals are to develop a large shared database of cases, generate high-quality research into all aspects of PAS, and improve education of both healthcare professionals and patients. The first results of this collaboration are presented within this supplement.

The relation between maternal obesity and placenta accreta spectrum: A multinational database study.

INTRODUCTION: It has been suggested that women with obesity have increased risk of developing placenta accreta spectrum (PAS). It is unclear if this is independent of the increased risk of cesarean delivery seen with obesity itself. The aim of this study was to explore the association between maternal obesity and PAS, particularly severe PAS (percreta). MATERIAL AND METHODS: This is a cohort study based on cases recorded in the International Society for Placenta Accreta Spectrum (IS-PAS) database between April 2008 and May 2019. Multivariable logistic regression was used to explore the effect of maternal obesity on severity of PAS; this model was adjusted for other known risk factors including previous cesarean deliveries, maternal age, and placenta previa. The estimated rate of obesity in a hypothetical cohort with similar characteristics (previous cesarean delivery and same parity) was calculated and compared with the observed rate of obesity in the women of the PAS cohort (one sample test of proportions). RESULTS: Of the 386 included women with PAS, 227 (58.8%) had severe disease (percreta). In univariable analysis, maternal obesity initially appeared to be associated with increased odds of developing the most severe type of PAS, percreta (odds ratio [OR] 1.87; 95% CI 1.14-3.09); however, this association was lost after adjustment for other risk factors including previous cesarean delivery (OR 1.44; 95% CI 0.85-2.44). There was no difference in the observed rate of obesity and the rate estimated based on the risk of cesarean delivery from obesity alone (31.3% vs 36.8%, respectively; P = .07). CONCLUSIONS: Obesity does not seem to be an independent risk factor for PAS or severity for PAS. These findings are relevant for clinicians to provide accurate counseling to women with obesity regarding increased risks related to pregnancy.

Gestational Age-Specific Reference Ranges for the sFlt-1/PlGF Immunoassay Ratio in Twin Pregnancies.

OBJECTIVE: Establish reference ranges for the Elecsys® soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies. METHODS: Data analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies. RESULTS: The reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks' gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks' gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days' gestation. CONCLUSIONS: Reference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks' gestation but appear higher in twin pregnancies thereafter.

A multicenter observational survey of management strategies in 442 pregnancies with suspected placenta accreta spectrum.

INTRODUCTION: Management options for women with placenta accreta spectrum (PAS) comprise termination of pregnancy before the viable gestational age, leaving the placenta in situ for subsequent reabsorption of the placenta or delayed hysterectomy, manual removal of placenta after vaginal delivery or during cesarean section, focal resection of the affected uterine wall, and peripartum hysterectomy. The aim of this observational study was to describe actual clinical management and outcomes in PAS in a large international cohort. MATERIAL AND METHODS: Data from women in 15 referral centers of the International Society of PAS (IS-PAS) were analyzed and correlated with the clinical classification of the IS-PAS: From Grade 1 (no PAS) to Grade 6 (invasion into pelvic organs other than the bladder). PAS was usually diagnosed antenatally and the operators performing ultrasound rated the likelihood of PAS on a Likert scale of 1 to 10. RESULTS: In total, 442 women were registered in the database. No maternal deaths occurred. Mean blood loss was 2600 mL (range 150-20 000 mL). Placenta previa was present in 375 (84.8%) women and there was a history of a previous cesarean in 329 (74.4%) women. The PAS likelihood score was strongly correlated with the PAS grade (P < .001). The mode of delivery in the majority of women (n = 252, 57.0%) was cesarean hysterectomy, with a repeat laparotomy in 20 (7.9%) due to complications. In 48 women (10.8%), the placenta was intentionally left in situ, of those, 20 (41.7%) had a delayed hysterectomy. In 26 women (5.9%), focal resection was performed. Termination of pregnancy was performed in 9 (2.0%), of whom 5 had fetal abnormalities. The placenta could be removed in 90 women (20.4%) at cesarean, and in 17 (3.9%) after vaginal delivery indicating mild or no PAS. In 34 women (7.7%) with an antenatal diagnosis of PAS, the placenta spontaneously separated (false positives). We found lower blood loss (P < .002) in 2018-2019 compared with 2009-2017, suggesting a positive learning curve. CONCLUSIONS: In referral centers, the most common management for severe PAS was cesarean hysterectomy, followed by leaving the placenta in situ and focal resection. Prenatal diagnosis correlated with clinical PAS grade. No maternal deaths occurred.

Maternal Serum VEGF Predicts Abnormally Invasive Placenta Better than NT-proBNP: a Multicenter Case-Control Study.

The aim of this study was to test if maternal serum vascular endothelial growth factor (VEGF) or N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts abnormally invasive placenta (AIP) better. Secondary objective was to test whether the serum levels of VEGF and NT-proBNP can predict the degree of invasion. In a multicenter case-control study design, gestational age-matched serum samples from pregnant women with AIP (n = 44) and uncomplicated pregnancies (n = 55) who had been enrolled at Charité - Universitätsmedizin Berlin, Germany and Centre Hospitalier Régional de la Citadelle in Liège, Belgium were analyzed. Maternal blood serum VEGF and NT-proBNP levels were immunoassayed from samples taken immediately before delivery (GA median: 35 weeks). Biomarker levels were compared between AIP and control group. The correlation of biomarker levels with the clinical AIP degree was assessed. The predictive biomarker ability was characterized through a multivariate regression model and receiver operating characteristic curves. Women with AIP had significantly lower maternal serum VEGF levels (AIP mean 285 pg/ml, 95% CI 248-322, vs. control: 391 pg/ml, 95% CI 356-426, p < 0.01) and higher NT-proBNP levels (AIP median 329 pg/ml, IQR 287-385, vs. control 295 pg/ml, IQR 273-356, p = 0.03). Maternal serum VEGF levels were able to predict AIP better (AUC = 0.729, 0.622-0.836, p < 0.001; VEGF + number of previous cesarean deliveries: AUC = 0.915, 0.853-0.977, p < 0.001). Maternal serum VEGF levels correlated inversely with the clinical AIP degree (r = - 0.32, p < 0.01). In short, maternal serum VEGF, more than NT-proBNP, can help in predicting AIP and hints at the degree of invasion.

Benefits of nonlinear analysis indices of walking stride interval in the evaluation of neurodegenerative diseases.

Indices characterising the long-range temporal structure of walking stride interval (SI) variability such as Hurst exponent (H) and fractal dimension (D) may be used in addition to indices measuring the amount of variability like the coefficient of variation (CV). We assess the added value of the former indices in a clinical neurological context. Our aim is to demonstrate that they provide a clinical significance in aging and in frequent neurodegenerative diseases such as Parkinson's disease, Huntington, and amyotrophic lateral sclerosis. Indices assessing the temporal structure of variability are mainly dependent on SI time series length and algorithms used, making quantitative comparisons between different studies difficult or even impossible. Here, we recompute these indices from available SI time series, either from our lab or from online databases. More precisely, we recompute CV, H, and D in a unified way. The average SI is also added to the measured parameters. We confirm that variability indices are relevant indicators of aging process and neurodegenerative diseases. While CV is sensitive to aging process and pathology, it does not discriminate between specific neurodegenerative diseases. H, which measures predictability of SI, significantly decreases with age but increases in patients suffering from amyotrophic lateral sclerosis. D, catching complexity of SI, is correlated with total functional capacity in patients with Huntington's disease. We conclude that the computation of H complements the clinical diagnosis of walking in patients with neurodegenerative diseases and we recommend it as a relevant supplement to classical CV or averaged SI. Since H and D indices did not lead to the same observations, suggesting the multi-fractal nature of SI dynamics, we recommend to open clinical gait analysis to the evaluation of more parameters.