Search

There is little evidence evaluating angiogenic growth factor testing in real-world obstetric settings. This investigation evaluated maternal and perinatal pregnancy outcomes associated with maternal PlGF (placental growth factor) levels in real-world clinical care of high-risk pregnancies. From March 2017 to December 2019, 979 pregnant women with suspected risk of placental dysfunction, hypertensive disorders of pregnancy, or fetal growth restriction completed PlGF testing between 20+0 and 35+6 weeks of gestation. Maternal, fetal, and delivery characteristics were extracted through the electronic medical record system. The primary outcome of preterm birth was assessed using Royston-Parmar survival models and summarized with Kaplan-Meier methods. Of the 979 pregnant women, 289 had low PlGF levels (29.5%), and 690 had normal PlGF levels (70.5%). The survival probability of ongoing pregnancy free from preterm birth within 2- and 4-weeks following PlGF testing was significantly reduced in women with low PlGF levels, relative to women with normal PlGF levels (0.57 versus 0.99, standardized survival difference, −0.43 [95% CI, −0.76 to −0.09], and 0.37 versus 0.99, standardized survival difference, −0.62 [95% CI −0.87 to −0.38], respectively). Women with low PlGF levels were more likely to develop early-onset preeclampsia (adjusted odds ratio, 58.2 [95% CI, 32.1–105.4]) and have a stillbirth (adjusted odds ratio, 15.9 [95% CI, 7.6–33.3]). PlGF status distinguished placental from fetal causes of stillbirth. Low PlGF levels in high-risk pregnant women are strongly associated with increased rates of imminent preterm birth, as well as related adverse outcomes, including early-onset preeclampsia and stillbirth.

Background Attempts to reduce the current rate of antepartum stillbirth in the late third trimester have largely focused on the accurate identification of fetal growth restriction. Universal ultrasound significantly increases detection, especially when combined with maternal angiogenic growth factors, but this screening strategy is not well suited to identify umbilical cord pathology. While this poses unique challenges to pregnancy care, the recurrence risk of cord obstruction is low in comparison with many intrinsic placental diseases. Case A 30-year-old woman with normal uterine artery Doppler waveforms, fetal growth ultrasounds, and circulating placental growth factor experienced an unexpected third-trimester stillbirth. Placental pathology demonstrated fetal vascular malperfusion and cord hyper-coiling. Conclusion Despite normal placental function, the otherwise healthy fetus is at risk of antepartum stillbirth due to cord-related pathology.

Patients with complex abdominal wall pathology often present with significant distortion of their umbilicus. Ventral and umbilical hernias often create widening or protrusion of the umbilicus, while obesity and laxity of the skin and subcutaneous tissue of the abdominal wall further exacerbates the deformity. The primary goal of hernia repair is always reduction of the hernia with a tension-free repair; however, an important secondary goal is esthetic improvement of the abdominal wall. Often, in patients with complex hernia defects involving the umbilicus, there is discussion of not salvaging the umbilicus altogether. Although this certainly remains an option for many patients, we present a technique that would not only allow for hernia reduction under direct laparoscopic visualization but also an improved esthetic to the umbilicus.

RESUME Objectif Passer en revue les strategies cliniques les plus efficaces pour desengager une tete fœtale enclavee pendant la cesarienne. Population cible Les femmes qui subissent une cesarienne lorsque la tete fœtale est fortement enclavee. Options La technique par poussee (par le bas) ou par traction (grande extraction du siege par voie abdominale). Resultats La prise en charge adequate de cette situation clinique peut reduire les risques de morbidite et mortalite maternelle et perinatale. Benefices, risques et couts Lorsque l'on anticipe un enclavement de la tete fœtale, il est possible de reduire le risque de complications maternelles et fœtales, les atteintes a court et a long terme ainsi que les couts associes en adoptant une strategie fondee sur des donnees probantes. Les recherches sur la valeur de l'apprentissage par simulation, les evaluations regulieres pendant le travail et la preparation de l’equipe aux interventions possibles aideront a orienter les soins de qualite. Donnees probantes Les termes de recherche suivants ont ete utilises dans les bases de donnees PubMed-Medline, Google Scholar et Cochrane pour la periode de publication de 2012 a 2019 : • “Guidelines” “manual” • “Caesarean Section” • “full dilation” • “operative delivery” • “impacted head” • “Caesarean” AND “full dilation” AND “impacted head” • “Caesarean” AND “second stage of labour” OR “second stage” AND “impacted head” • “Caesarean” OR “operative delivery” AND “impacted head” Au total, 32 articles ont ete recuperes et 24 ont ete juges adequats comme references. Plusieurs de ces articles etaient des opinions d'experts. Les essais cliniques randomises avaient des echantillons de petite taille et ont ete menes dans des contextes qui limitent la generalisabilite de leurs resultats a la population canadienne20. Professionnels cibles Fournisseurs de soins de sante intrapartum

BackgroundThere is growing evidence of sex differences in placental vascular development. The objective of this study was to investigate the effect of fetal sex on uterine artery pulsatility index (PI) throughout gestation in a cohort of normal and complicated pregnancies.MethodsA prospective longitudinal study was conducted in 240 pregnant women. Pulsed wave Doppler ultrasound of the proximal uterine arteries was performed at a 4-weekly interval between 14 and 40 weeks of gestation. The patients were classified retrospectively as normal or complicated (one or more of maternal preeclampsia, preterm birth, or small for gestational age). To assess if the change in uterine artery PI during gestation differed between normal and complicated pregnancies and between fetal sexes, the uterine artery PI was modeled using a linear function of gestational age and the rate of change was estimated from the slope.ResultsWhile the uterine artery PI did not differ over gestation between females and males for normal pregnancies, the trajectory of this index differed by fetal sex for pregnancies complicated by either preeclampsia, preterm birth, or fetal growth restriction (p< 0.0001). The male fetuses in the complicated pregnancy group had an elevated slope compared to the other groups (p< 0.0001), suggesting a more progressive deterioration in uteroplacental perfusion over gestation.ConclusionsThe uterine artery PI is widely used to assess uteroplacental function in clinical settings. The observation that this metric changes more rapidly in complicated pregnancies where the fetus was male highlights the importance of sex when interpreting hemodynamic markers of placental maturation.

To assess patient satisfaction with the use of portable video media (PVM) for the purpose of taking informed consent for common urological outpatient procedures performed under local anaesthesia. Patients undergoing the following procedures were approached for recruitment: flexible cystoscopy with or without biopsy, transrectal ultrasound-guided prostate biopsy or flexible cystoscopy with insertion or removal of a ureteric stent. Audio-visual media were developed for each procedure, with each script translated from English into isiXhosa and Afrikaans. The study involved a cross-over for each patient between standard verbal consent (SVC) and PVM consent, with each patient randomised to start with SVC or PVM consent. Each of these consent arms was assessed via a questionnaire. Sixty patients completed participation, with PVM as the first exposure for 28 patients and 32 patients receiving SVC as their first arm of the study. When comparing the overall satisfaction between SVC and PVM consent (the total scores out of 18 for the questionnaire), patients scored significantly higher for PVM consent (M = 16.3 ± 2.4) compared to SVC (M = 15.4 ± 2.9) (p = 0.002). 92% of the total patient sample preferred PVM consent. Portable video media proved superior to SVC in improving satisfaction in the consent process for common outpatient urological procedures performed under local anaesthesia.

OBJECTIVES: To evaluate the feasibility of using umbilical artery (UA) Doppler waveforms to measure fetal heart rate short term variation (STV) across gestation. METHODS: A prospective longitudinal study was conducted at two study sites in 195 women with pregnancies considered low risk. Pulsed wave Doppler of the UAs was performed at a 4-weekly interval between 14–40 weeks of gestation using a standardized imaging protocol. Up to 12 consecutive UA Doppler waveforms were analyzed using an off-line processing software. Fetal heart rate STV was calculated using average R-to-R intervals extracted from the waveforms and baseline corrected for fetal heart rate. RESULTS: Baseline corrected short term fetal heart rate variation increased significantly with gestational age (conditional R(2) = 0.37, p < 0.0001) and was inversely correlated with fetal heart rate (conditional R(2) = 0.54, p < 0.0001). The short term variation ranged (median (interquartile range)) from 3.5 (2.9–4.1) ms at 14–20 weeks’ gestation to 6.3 (4.8–7.7) ms at 34–40 weeks’ gestation. The change in short term heart rate variation did not differ between study sites, different models of ultrasound machine or individual sonographers. CONCLUSIONS: Umbilical artery Doppler waveforms offer a robust and feasible method to derive short term variation of the fetal heart rate. It needs to be emphasized that the umbilical-Doppler derived short term variation is not interchangeable with measurements derived with computerized cardiotocography. Accordingly, further investigations need to validate associations with outcome to determine the value of concurrent fetal cardiovascular and heart rate evaluation that are possible with the technique described here.

Objectives: The WHO recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high-burden TB/HIV countries. Design: Retrospective longitudinal cohort. Methods: We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted. Results: Twenty thousand seven hundred and six patients collectively had 316 740 clinic visits, of which 240 161 (75.8%) had documented TB symptom screens. There were 35 701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4--64.0) and 88.8% (95% CI 88.7--88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7--17. Conclusion: Although specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.

The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of the internal iliac arteries. With incremental gains in surgical expertise, described in 5 steps in this review, our teams have witnessed a steady decline in surgical blood loss. Nevertheless, a subset of women has the most severe form of placenta accreta spectrum, namely placenta previa-percreta. Such women are at risk of major hemorrhage during surgery from vessels arising outside the territories of the internal iliac arteries. These additional blood supplies, mostly from the external iliac arteries, pose significant risks of major blood loss even in experienced hands. To address this risk, some centers, principally in China, have adopted an approach of routinely placing an infrarenal aortic balloon, with both impressively low rates of blood loss and an ability to conserve the uterus by resecting the placenta with the affected portion of the uterine wall. We review these literature developments in the context of safely performing elective cesarean hysterectomy for placenta previa-percreta, the most severe placenta accreta spectrum disorder.

With the increasing size of datasets used in medical imaging research, the need for automated data curation is arising. One important data curation task is the structured organization of a dataset for preserving integrity and ensuring reusability. Therefore, we investigated whether this data organization step can be automated. To this end, we designed a convolutional neural network (CNN) that automatically recognizes eight different brain magnetic resonance imaging (MRI) scan types based on visual appearance. Thus, our method is unaffected by inconsistent or missing scan metadata. It can recognize pre-contrast T1-weighted (T1w),post-contrast T1-weighted (T1wC), T2-weighted (T2w), proton density-weighted (PDw) and derived maps (e.g. apparent diffusion coefficient and cerebral blood flow). In a first experiment,we used scans of subjects with brain tumors: 11065 scans of 719 subjects for training, and 2369 scans of 192 subjects for testing. The CNN achieved an overall accuracy of 98.7%. In a second experiment, we trained the CNN on all 13434 scans from the first experiment and tested it on 7227 scans of 1318 Alzheimer’s subjects. Here, the CNN achieved an overall accuracy of 98.5%. In conclusion, our method can accurately predict scan type, and can quickly and automatically sort a brain MRI dataset virtually without the need for manual verification. In this way, our method can assist with properly organizing a dataset, which maximizes the shareability and integrity of the data.

The Erasmus Glioma Database (EGD) contains structural magnetic resonance imaging (MRI) scans, genetic and histological features (specifying the WHO 2016 subtype), and whole tumor segmentations of patients with glioma. Pre-operative MRI data of 774 patients with glioma (281 female, 492 male, 1 unknown, age range 19–86 years) treated at the Erasmus MC between 2008 and 2018 is available. For all patients a pre-contrast T1-weighted, post-contrast T1-weighted, T2-weighted, and T2-weighted FLAIR scan are available, made on a variety of scanners from four different vendors. All scans are registered to a common atlas and defaced. Genetic and histological data consists of the IDH mutation status (available for 467 patients), 1p/19q co-deletion status (available for 259 patients), and grade (available for 716 patients). The full WHO 2016 subtype is available for 415 patients. Manual segmentations are available for 374 patients and automatically generated segmentations are available for 400 patients. The dataset can be used to relate the visual appearance of the tumor on the scan with the genetic and histological features, and to develop automatic segmentation methods.

The present study aimed to evaluate the effectiveness of a school-based multi-activity HIIT on aerobic fitness (AF) and hemodynamic parameters in children. 46 students were randomized into an intervention group (INT) (N=22) and a control group (CON) (N=24). Throughout a 3-month intervention period, both INT and CON participated in the regular physical education classes (PE) twice a week. Only INT received an instructed HIIT during the first 20 min of the PE. In addition to an AF-test, peripheral (pBP) and central (cBP) blood pressure, augmentation pressure (AP), and aortic pulse wave velocity (aPWV) were assessed. Significant differences in intervention effects in favor of INT were detected for AF (7.73, P=0.007), peripheral systolic BP (−6.13 mmHg, P=0.038), central systolic BP (−5.19 mmHg, P = 0.041), AP (−2.02 mmHg, P=0.013), and aPWV (−0.19 m/sec, P=0.031). The regular HITT intervention showed beneficial effects on AF, BP, and parameters of vascular stiffness already in children.

Purpose: Patients with 1p/19q codeleted low-grade glioma (LGG) have longer overall survival and better treatment response than patients with 1p/19q intact tumors. Therefore, it is relevant to know the 1p/19q status. To investigate whether the 1p/19q status can be assessed prior to tumor resection, we developed a machine learning algorithm to predict the 1p/19q status of presumed LGG based on preoperative MRI. Experimental Design: Preoperative brain MR images from 284 patients who had undergone biopsy or resection of presumed LGG were used to train a support vector machine algorithm. The algorithm was trained on the basis of features extracted from post-contrast T1-weighted and T2-weighted MR images and on patients' age and sex. The performance of the algorithm compared with tissue diagnosis was assessed on an external validation dataset of MR images from 129 patients with LGG from The Cancer Imaging Archive (TCIA). Four clinical experts also predicted the 1p/19q status of the TCIA MR images. Results: The algorithm achieved an AUC of 0.72 in the external validation dataset. The algorithm had a higher predictive performance than the average of the neurosurgeons (AUC 0.52) but lower than that of the neuroradiologists (AUC of 0.81). There was a wide variability between clinical experts (AUC 0.45–0.83). Conclusions: Our results suggest that our algorithm can noninvasively predict the 1p/19q status of presumed LGG with a performance that on average outperformed the oncological neurosurgeons. Evaluation on an independent dataset indicates that our algorithm is robust and generalizable.

Resume Contexte Les troubles du spectre du placenta accreta (TSPA) constituent une complication de la grossesse potentiellement mortelle et exigent une coordination des soins interdisciplinaires afin d'ameliorer la possibilite d'une issue favorable. La hausse de la frequence des cas est due a l'augmentation du nombre d'interventions chirurgicales uterines, notamment a l'augmentation de la frequence des grossesses apres cesarienne. Objectif Fournir des directives cliniques factuelles courantes sur les methodes optimales pour depister, diagnostiquer et prendre en charge les TSPA de facon efficace. Methode Les membres du comite sur les directives cliniques ont ete selectionnes en fonction de leur milieu de pratique et de leur expertise actuelle en matiere de prise en charge de cette maladie au Canada. Le comite a revu toutes les donnees probantes disponibles dans la litterature medicale en anglais, y compris des lignes directrices publiees ainsi que des tests de diagnostic, des interventions chirurgicales et les issues cliniques evaluees. Donnees probantes La litterature publiee jusqu'en mars 2018, y compris les directives cliniques, a ete puisee dans les bases de donnees Medline et Cochrane Library au moyen d'un vocabulaire controle et de mots cles. Les resultats sont limites aux analyses systematiques, aux essais cliniques randomises et aux etudes observationnelles rediges en anglais. Les recherches ont ete mises a jour regulierement, et les resultats ont ete incorpores a la directive clinique jusqu'en juillet 2018. Criteres La qualite des donnees probantes dans le present document a ete evaluee en fonction des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs. Resultats Le present document passe en revue les donnees probantes relatives aux techniques diagnostiques et chirurgicales utilisees pour favoriser la prise en charge optimale des femmes chez qui l'on suspecte un TSPA, notamment l'anesthesie et les considerations cliniques de la prestation de soins interdisciplinaires. Avantages, prejudices et couts La mise en application des recommandations de la presente directive clinique ameliorera la sensibilisation a cette maladie et augmentera la proportion des femmes atteintes recevant des soins interdisciplinaires dans des centres regionaux. Conclusion La prestation de soins par une equipe interdisciplinaire qui assure de bons services diagnostiques, la planification concertee et les interventions chirurgicales securitaires fournissent des soins qui ameliorent les issues cliniques comparativement aux autres modes de prise en charge. DECLARATIONS SOMMAIRES 1La frequence des troubles du spectre du placenta accreta est en hausse constante dans de nombreux pays, vraisemblablement en raison de l'augmentation de la proportion de femmes qui deviennent enceintes apres avoir subi une ou plusieurs interventions chirurgicales uterines, notamment des cesariennes multiples. 2Les troubles du spectre du placenta accreta dans un contexte d'antecedents de cesarienne decoulent de l'implantation de la grossesse dans la niche au niveau de la cicatrice pres de la jonction cervico-isthmique de l'uterus. Diverses methodes echographiques permettent de diagnostiquer la manifestation precoce d'une « grossesse sur cicatrice de cesarienne ». 3L'echographie peut servir a depister et a diagnostiquer les grossesses avec un placenta praevia anterieur complique par un trouble du spectre du placenta accreta. L'efficacite de l'echographie dans ce contexte depend de la connaissance des facteurs de risque cliniques, de la qualite de l'imagerie, de l'experience de l'echographiste, de l'âge gestationnel, des modalites d'imagerie et du volume vesical adequat. 4L'imagerie par resonance magnetique peut appuyer l'echographie multimodale dans le diagnostic et la classification des troubles du spectre du placenta accreta; cependant, la contre-indication relative de l'utilisation du gadolinium comme agent de contraste limite actuellement son efficacite. 5Les troubles du spectre du placenta accreta sont potentiellement mortels et necessitent la prestation de soins par une equipe interdisciplinaire regionale afin de maximiser les chances d'issue favorable pour la mere et le nourrisson. RECOMMANDATIONS 1Il y a lieu de diriger les femmes enceintes qui presentent un placenta praevia anterieur et des facteurs de risque cliniques des troubles du spectre placenta accreta a l'echographie obstetricale de 18-20 semaines vers des services d'imagerie specialisee afin de diagnostiquer ou d'exclure cette maladie (II-2A). 2Il y a lieu de diriger les femmes qui ont recu un diagnostic de troubles du spectre du placenta accreta vers un centre regional designe a la prise en charge interdisciplinaire de cette maladie (II-3A). 3Les soins interdisciplinaires rattaches a un protocole qui s'etend du diagnostic a l'intervention chirurgicale optimiseront les issues a la fois peroperatoires et postoperatoires (II-3A). 4L'admission prenatale dans un centre de prise en charge regional designe peut etre indiquee, surtout a la suite d'une hemorragie ante partum, ou en fonction de contraintes geographiques ou de transport (III-B). 5Chez les femmes autrement en sante dont l'historique de grossesse ne comporte aucun saignement vaginal, le meilleur moment pour proceder a la cesarienne planifiee se situe entre 34 et 36 semaines de grossesse (II-3B). Il convient d'envisager d'effectuer l'intervention plus tot en cas d'episodes repetes d'hemorragie ante partum ou de contractions afin de reduire le risque d'intervention chirurgicale d'urgence non planifiee; on doit aussi idealement administrer une corticotherapie pour favoriser la maturation pulmonaire fœtale si l'intervention a lieu avant 35+0 semaines de grossesse (II-2A). 6L'anesthesie regionale peut s'averer plus securitaire que l'anesthesie generale etant donne qu'elle est liee a une perte sanguine moindre et que les patientes et leur partenaire la prefere (II-2A). Un protocole de transfusion massive doit etre en place afin de pouvoir reagir en cas de perte sanguine importante (III-B). 7Il y a lieu d'administrer de l'acide tranexamique par voie intraveineuse au debut de l'intervention parce qu'elle diminue la perte sanguine peroperatoire (I-A). 8Il convient de realiser l'intervention chirurgicale en position de lithotomie modifiee, au moyen d'une incision mediane assez haute pour extraire le fœtus sans pratiquer d'incision dans le placenta; l'echographie pre- ou peroperatoire peut etre utilisee afin de determiner l'incision uterine optimale (III-B). Si le placenta ne montre aucun signe de decollement, il convient de ne pas tenter de l'extirper en raison de l'hemorragie importante qui peut en decouler (III-B). 9A l'heure actuelle, il n'y a pas suffisamment de donnees probantes pour recommander ou non l'administration de medicaments uterotoniques apres l'extraction du fœtus (III-C). 10A l'heure actuelle, il n'y a pas suffisamment de donnees probantes pour recommander une methode ou une autre (insertion preoperatoire de ballonnets ou ligature peroperatoire) visant a reduire le debit sanguin des arteres iliaques internes avant l'hysterectomie (II-1C). 11Une atteinte centrale focale peut se preter a la resection cuneiforme (wedge) avec retrait complet du placenta et reparation de l'uterus (triple-P) (II-3B). 12La cesarienne classique avec abandon du placenta envahissant constitue une methode d'accouchement acceptable, mais elle prolongerait le temps de recuperation et presente un risque persistant d'hysterectomie (II-3B). 13Il convient de recommander aux femmes qui demeurent fertiles apres un diagnostic de trouble du spectre de placenta accreta d'obtenir une echographie aupres d'un specialiste tot dans toute grossesse subsequente de sorte que toutes les options de prise en charge demeurent sur la table en cas de grossesse sur cicatrice de cesarienne (III-B). 14Le diagnostic prenatal des formes les plus graves de troubles du spectre du placenta accreta, designees comme des grossesses sur cicatrice de cesarienne, peut rendre possible une prise en charge au moyen de techniques chirurgicales a effraction minimale (II-3D). 15Bien que bon nombre de femmes presentant un trouble du spectre du placenta accreta recoivent des soins securitaires dans les pays bien outilles, il faut pousser la recherche et favoriser le transfert de connaissances encore davantage pour offrir efficacement toutes les options de prise en charge a la population (III-B).

Background Placenta accreta spectrum (PAS) disorders are a potentially life-threatening complication of pregnancy that demand coordinated interdisciplinary care to achieve safer outcomes. The rising incidence of this disease is due to a growing number of uterine surgical procedures, including the rising incidence of pregnancy following Caesarean section. Objective To provide current evidence-based guidelines on the optimal methods used to effectively screen, diagnose, and manage PAS disorders. Methods Members of the guideline committee were selected on the basis of their ongoing expertise in managing this condition across Canada and by practice setting. The committee reviewed all available evidence in the English medical literature, including published guidelines, and evaluated diagnostic tests, surgical procedures, and clinical outcomes. Evidence Published literature, including clinical practice guidelines, was retrieved through searches of Medline and The Cochrane Library to March 2018 using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized controlled trials, and observational studies written in English. Searches were updated on a regular basis and incorporated in the guideline to July 2018. Values The quality of evidence in this document was graded using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Results This document reviews the evidence regarding the available diagnostic and surgical techniques used for optimal management of women with suspected PAS disorders, including anaesthesia and practical considerations for interdisciplinary care. Benefits, Harms, and Costs Implementation of the guideline recommendations will improve awareness of this disease and increase the proportion of affected women receiving interdisciplinary care in regional centres. Conclusions Interdisciplinary team-based care providing accurate diagnostic services, coordinated planning, and safer surgery deliver effective care with improved clinical outcomes in comparison with alternative management. Summary Statements 1The incidence of placenta accreta spectrum disorders is steadily rising in many countries, likely due to the increasing proportion of women becoming pregnant following a variety of surgical procedures to the uterus, including multiple Caesarean sections. 2Placenta accreta spectrum disorders in the setting of prior Caesarean section deliveries arises from pregnancy implantation within the niche created by this surgery near the cervicoisthmic junction of the uterus. This early presentation as a "Caesarean section scar pregnancy" may be diagnosed by ultrasound methods. 3Ultrasound may be used to screen for, and to diagnose, pregnancies with anterior placenta previa that are complicated by placenta accreta spectrum disorders. The effectiveness of ultrasound in this context depends upon awareness of clinical risk factors, imaging quality, operator experience, gestational age, imaging modalities, and adequate bladder filling. 4Magnetic resonance imaging may complement multimodal ultrasound in the diagnosis and staging of placenta accreta spectrum disorders, though its effectiveness is currently limited by the relative contraindication to the use of a gadolinium contrast enhancing agent. 5Placenta accreta spectrum disorders are potentially life-threatening and demand regional interdisciplinary team-based care to deliver the safest outcomes for mothers and infants. Recommendations 1Pregnant women with clinical risk factors for placenta accreta spectrum disorders and anterior placenta previa at the 18–20-week fetal anatomical ultrasound should be referred for specialist imaging to diagnose or exclude this disorder (II-2A). 2Women with a diagnosis of placenta accreta spectrum disorder should be referred to a regional centre dedicated to the interdisciplinary management of this condition (II-3A). 3Protocol-based interdisciplinary care from diagnosis to surgery will optimize both intraoperative and postoperative outcomes (II-3A). 4Antenatal admission to a designated regional management centre may be indicated, especially following an antepartum hemorrhage, or based on considerations of geography or transport conditions (III-B). 5For otherwise healthy women with no history of vaginal bleeding, the optimal timing of elective Caesarean section delivery is around 34–36 weeks gestation (II-3B). Surgery should be considered earlier for repeated episodes of antepartum hemorrhage or contractions to reduce the risks of emergent unplanned surgery and should ideally be preceded by a course of corticosteroids to enhance fetal lung maturation if prior to 35+0 weeks gestation (II-2A). 6Regional anaesthesia may be safer than general anaesthesia as it is associated with reduced blood loss and is preferred by patients and their partners (II-2A). A massive transfusion protocol should be in place to respond to significant blood loss (III-B). 7Intravenous tranexamic acid should be administered at the commencement of surgery because it reduces intraoperative blood loss (I-A). 8Surgery should be performed in the modified lithotomy position, using midline access, sufficiently high so as to deliver the fetus without incising through the placenta; preoperative or intraoperative ultrasound can be used to guide the optimal uterine incision (III-B). No attempt should be made to remove the placenta if it shows no signs of separation as this may cause substantial hemorrhage (III-B). 9Presently there is insufficient evidence to recommend giving or withholding uterotonic drugs after delivery of the fetus (III-C). 10Presently there is insufficient evidence to recommend either approach (preoperative balloon placement or intraoperative ligation) designed to arrest blood flow from the internal iliac arteries prior to hysterectomy (II-1C). 11Focal central disease may be amenable to wedge resection, with complete removal of the placenta and repair of the uterus (the triple-P procedure) (II-3B). 12Classical Caesarean section and non-removal of the invasive placenta is an acceptable method of delivery but is associated with a protracted course of recovery and a persistent risk of hysterectomy (II-3B). 13Women who retain their fertility following a diagnosis of placenta accreta spectrum disorder should be instructed to access specialist ultrasound early in any future pregnancy so that all management options are available should a Caesarean section scar pregnancy be found (III-B). 14Prenatal diagnosis of the more severe forms of placenta accreta spectrum disorder, expressed as a Caesarean section scar pregnancy, may permit management using minimally invasive surgical techniques (II-3B). 15Though many women with placenta accreta spectrum disorder in well-resourced countries receive safe care, more research and knowledge translation are needed to effectively deliver all management options at the population-based level (III-B).

Resume Objectifs Fournir des directives factuelles qui favorisent l'accouchement vaginal assiste securitaire et efficace. Resultats Conditions prealables, indications, contre-indications, ainsi que les morbidites maternelles et neonatales liees a l'accouchement vaginal assiste. Donnees probantes Des recherches ont ete effectuees dans la base de donnees Medline pour trouver des articles publies entre le 1er janvier 1985 et le 28 fevrier 2018 en utilisant les termes anglais suivants : assisted vaginal birth, instrumental vaginal birth, operative vaginal delivery, forceps delivery, vacuum delivery, ventouse delivery. La qualite des donnees probantes indiquees s'appuie sur les criteres d'evaluation des donnees decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs. Validation La presente directive a ete approuvee par le comite de pratique clinique – obstetrique et le conseil d'administration de la Societe des obstetriciens et gynecologues du Canada. RECOMMANDATIONS 1La necessite d'assister un accouchement vaginal peut etre diminuee grâce aux mesures suivantes : soutien dedie et continu durant le travail (I-A), augmentation du travail inadequat par l'administration d'ocytocine (I-A), retarder de la poussee chez les femmes sous peridurale (I-A), augmentation du temps de poussee chez les femmes nullipares sous peridurale (I-B) et optimisation du positionnement de la tete fœtale par rotation manuelle (I-A). 2Le fait de favoriser l'AVA securitaire et efficace aux mains de fournisseurs de soins competents et experimentes peut s'averer une strategie efficace pour diminuer le taux de cesarienne primaire (II-2B). 3Pour qu'un accouchement vaginal assiste s'avere securitaire et efficace, il est necessaire de detenir l'expertise requise avec la methode choisie, d'effectuer une evaluation complete de la situation clinique et de communiquer de facon claire avec la patiente, ses personnes de soutien et le personnel soignant (III-B). 4Les praticiens qui effectuent un accouchement vaginal assiste doivent avoir les connaissances, les competences et l'experience necessaires pour evaluer la situation clinique, utiliser l'instrument choisi et gerer les complications qui peuvent decouler d'un accouchement vaginal assiste (II-2B). 5Les stagiaires en obstetrique devraient recevoir une formation complete sur l'accouchement vaginal assiste; ils doivent egalement etre declares competents avant de pratiquer un accouchement vaginal assiste sans supervision (III-B). 6Lorsque l'on juge que l'accouchement vaginal assiste comporte un risque eleve d'echec, on doit le considerer comme une tentative d'accouchement vaginal assiste et l'effectuer dans un endroit ou il est possible de recourir immediatement a la cesarienne (III-B). 7Le medecin doit choisir l'instrument le mieux adapte aux circonstances cliniques en fonction de son degre de competence. La ventouse et les forceps sont associes a divers risques et avantages a court et a long termes. La ventouse est plus susceptible de conduire a l'echec de l'accouchement que les forceps (I-A). 8Il n'est pas recommande de planifier d'utiliser successivement les instruments puisque cette approche est possiblement liee a un risque accru de trauma perinatal. En cas d'echec d'une tentative d'accouchement avec ventouse, le medecin doit evaluer les risques d'une tentative avec les forceps par rapport a ceux d'une cesarienne (II-2B). 9L'utilisation restreinte de l'episiotomie mediolaterale est indiquee lors d'un accouchement vaginal assiste (II-2B). 10Un retour doit etre effectue avec la patiente et ses personnes de soutien immediatement apres une tentative d'accouchement vaginal assiste, qu'elle soit fructueuse ou non. Si ce n'est pas possible, il faut idealement le faire avant que la patiente n'obtienne son conge et lui faire part des indications pour l'accouchement vaginal assiste, du plan de prise en charge de toute complication et du pronostic pour de futurs accouchements (III-B). 11Les patientes devraient etre encouragees a envisager un accouchement vaginal spontane pour les grossesses subsequentes. Le plan de soins devrait neanmoins etre personnalise et respecter les preferences de la patiente (II-3B).

Objectives To provide evidence-based guidelines for safe and effective assisted vaginal birth. Outcomes Prerequisites, indications, contraindications, along with maternal and neonatal morbidity associated with assisted vaginal birth. Evidence Medline database was searched for articles published from January 1, 1985, to February 28, 2018 using the key words "assisted vaginal birth," "instrumental vaginal birth," "operative vaginal delivery," "forceps delivery," "vacuum delivery," "ventouse delivery." The quality of evidence is described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on Preventive Health Care. Validation These guidelines were approved by the Clinical Practice Obstetrics Committee and the Board of the Society of Obstetricians and Gynaecologists of Canada. Recommendations 1The need for assisted vaginal birth can be reduced by: dedicated and continuous support during labour (I-A), oxytocin augmentation of inadequate labour (I-A), delayed pushing in women with an epidural (I-A), increased time pushing in nulliparous women with an epidural (I-B), as well as optimization of fetal head position through manual rotation (I-A). 2Encouraging safe and effective assisted vaginal birth by experienced and skilled care providers may be a useful strategy to reduce the rate of primary Caesarean delivery (II-2B). 3Safe and effective assisted vaginal birth requires expertise in the chosen method, comprehensive assessment of the clinical situation alongside clear communication with the patient, support people, and health care personnel (III-B). 4Practitioners performing assisted vaginal birth should have the knowledge, skills, and experience necessary to assess the clinical situation, use the selected instrument, and manage complications that may arise from assisted vaginal birth (II-2B). 5Obstetrical trainees should receive comprehensive training in assisted vaginal birth and be deemed competent prior to independent practice (III-B). 6When assisted vaginal birth is deemed to have a higher risk of not being successful, it should be considered a trial of assisted vaginal birth and be conducted in a location where immediate recourse to Caesarean delivery is available (III-B). 7The physician should determine the instrument most suitable to the clinical circumstances and their level of skill. Vacuum and forceps are associated with different short- and long-term benefits and risks. Unsuccessful delivery is more likely with vacuum than forceps (I-A). 8Planned sequential use of instruments is not recommended as it may be associated with an increased risk of perinatal trauma. If an attempted vacuum is unsuccessful, the physician should consider the risks of proceeding to an attempted forceps delivery versus Caesarean section (II-2B). 9Restrictive use of mediolateral episiotomy is supported in assisted vaginal birth (II-2B). 10A debrief should be done with the patient and support people immediately following an attempted or successful assisted vaginal birth. If this is not possible, ideally this should be done prior to hospital discharge and include the indication for assisted vaginal birth, management of any complications, and the prognosis for future deliveries (III-B). 11In a subsequent pregnancy, patients should be encouraged to consider spontaneous vaginal birth. However, care planning should be individualized and patient preference respected (II-3B).

Two-component systems (TCSs) are the largest family of multi-step signal transduction pathways and valuable sensors for synthetic biology. However, most TCSs remain uncharacterized or difficult to harness for applications. Major challenges are that many TCS output promoters are unknown, subject to cross-regulation, or silent in heterologous hosts. Here, we demonstrate that the two largest families of response regulator DNA-binding domains can be interchanged with remarkable flexibility, enabling the corresponding TCSs to be rewired to synthetic output promoters. We exploit this plasticity to eliminate cross-regulation, un-silence a gram-negative TCS in a gram-positive host, and engineer a system with over 1,300-fold activation. Finally, we apply DNA-binding domain swapping to screen uncharacterized Shewanella oneidensis TCSs in Escherichia coli, leading to the discovery of a previously uncharacterized pH sensor. This work should accelerate fundamental TCS studies and enable the engineering of a large family of genetically encoded sensors with diverse applications.

Background Mirror Syndrome, also known as Ballantyne syndrome, is a rare condition with fewer than 120 cases described in the literature. A simultaneous edematous state of the mother, fetus and placenta is pathognomonic, with the maternal condition frequently presenting with signs and symptoms similar to that of preeclampsia. Objective Our aim was to add to the international body of literature through identification of all cases of Mirror Syndrome at two Canadian tertiary obstetric centres and characterize the maternal presentation, laboratory findings, and perinatal outcomes. Methodology We performed a retrospective chart review of all cases of fetal hydrops from two tertiary centres in Winnipeg (Manitoba, Canada) between 2000 and 2019. There were 276 cases of fetal hydrops during this period, of which 10 cases satisfied the diagnostic criteria for Mirror Syndrome where maternal and perinatal outcomes were analysed. Results The median gestational age at diagnosis with Mirror Syndrome was 23 weeks and 3 days of gestation and at birth was 25 weeks and 0 days of gestation. The majority of women were multiparous (80%) and had elevated maternal body mass index (median 33 kg/m2). The most common maternal clinical findings included weight gain (100%) and hypertension (90%). The most common laboratory findings included low hematocrit (100%), hypoalbuminemia (80%), anemia (70%) and hyperuricemia (70%). Structural anomalies were observed in 50% of cases, over half of the fetuses were stillborn (66.7%) and one quarter of pregnancies resulted in neonatal deaths (25%). The median time until maternal improvement of Mirror Syndrome was 2 days postpartum. Conclusion Mirror Syndrome affected 3.6% of all cases of fetal hydrops in our cohort, and showed associations with multiparity, elevated BMI, hemodilution, hypoalbuminemia, anemia and hyperuricemia. Delivery is frequently required for fetal and/or maternal indications and symptoms usually improved rapidly after delivery.

OBJECTIVES—: To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs). METHODS—: Pulsed wave Doppler of both UAs and the descending aorta was performed at 4-weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI. RESULTS—: Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008). CONCLUSIONS—: The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto-placental circulation where discordant UA PIs are found.

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B.1.617.2, emerged in India and has spread to over 80 countries. B.1.617.2 replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.617.2 to control by antibodies elicited by vaccines and used for coronavirus disease 2019 (COVID-19) therapy. We show, using pseudotyping, that B.1.617.2 evades control by antibodies induced upon infection and BNT162b2 vaccination, although to a lesser extent as compared to B.1.351. We find that B.1.617.2 is resistant against bamlanivimab, a monoclonal antibody with emergency use authorization for COVID-19 therapy. Finally, we show increased Calu-3 lung cell entry and enhanced cell-to-cell fusion of B.1.617.2, which may contribute to augmented transmissibility and pathogenicity of this variant. These results identify B.1.617.2 as an immune evasion variant with increased capacity to enter and fuse lung cells., Graphical abstract, The B.1.617.2 (Delta) variant challenges efforts to control the COVID-19 pandemic. Arora et al. provide evidence that B.1.617.2 may enter human lung cells and fuse neighboring cells more efficiently than the initially circulating virus. Further, the study suggests that B.1.617.2 may evade neutralization by antibodies elicited upon infection and vaccination.

Patients at high risk of severe preeclampsia and fetal growth restriction have low circulating levels of placental growth factor and features of maternal vascular malperfusion placental pathology at delivery. Multimodal screening and commencement of aspirin prophylaxis at 11 to 13 weeks' gestation markedly reduces the risk of preterm delivery with preeclampsia. However, the additional role of low-molecular-weight heparin and mechanisms of action remain uncertain. Because low-molecular-weight heparin augments the production and release of placental growth factor in vitro by both placental villi and vascular endothelium, it may be effective to suppress the risk of severe preeclampsia in a niche group of high-risk patients with low circulating placental growth factor in the early second trimester.This study aimed to define a gestational age-specific reference range for placental growth factor and to test the hypothesis that prophylactic low-molecular-weight heparin administered in the early second trimester may restore deficient circulating placental growth factor levels and thereby prolong pregnancy.Centile curves for circulating placental growth factor levels from 12 to 36 weeks' gestation were derived using quantile regression of combined data from a published cohort of 4207 unselected nulliparous patients in Cambridge, United Kingdom, at 4 sampling time points (12, 20, 28, and 36 weeks' gestation) and the White majority (n=531) of a healthy nulliparous cohort in Toronto, Canada, at 16 weeks' gestation using the same test platform. Within a specialty high-risk clinic in Toronto, a niche group of 7 patients with a circulating placental growth factor at the10th centile in the early second trimester received daily prophylactic low-molecular-weight heparin (enoxaparin; 40 mg subcutaneously) and were followed up until delivery (group 1). Their baseline characteristics, delivery details, and placental pathologies were compared with 5 similar patients who did not receive low-molecular-weight heparin during the observation period (group 2) and further with 21 patients who delivered with severe preeclampsia (group 3) in the same institution.A gestational age-specific reference range for placental growth factor levels at weekly intervals between 12 and 36 weeks was established for White women with singleton pregnancies. Within group 1, 5 of 7 patients demonstrated a sustained increase in circulating placental growth factor levels, whereas placental growth factor levels did not increase in group 2 or group 3 patients who did not receive low-molecular-weight heparin. Group 1 patients receiving low-molecular-weight heparin therapy exhibited a later gestation at delivery, relative to groups 2 and 3 (36 weeks [33-37] vs 23 weeks [22-26] and 28 weeks [27-31], respectively), and consequently had higher birthweights (1.93 kg [1.1-2.7] vs 0.32 kg [0.19-0.39] and 0.73 kg [0.52-1.03], respectively). The incidence of stillbirth was lowest in group 1 (14% [1 of 7]), relative to groups 2 and 3 (80% [4 of 5] and 29% [6 of 21], respectively). Maternal vascular malperfusion was the most common placental pathology found in association with abnormal uterine artery Doppler.In patients at high risk of a serious adverse pregnancy outcome owing to placental disease, the addition of low-molecular-weight heparin to aspirin prophylaxis in the early second trimester may restore deficient circulating placental growth factor to mediate an improved perinatal outcome. These data support the implementation of a multicenter pilot randomized control trial where patients are recruited primarily based on the assessment of placental function in the early second trimester.

Background: The umbilical artery (UA) Doppler pulsatility index is used clinically to detect elevated feto-placental vascular resistance. However, this metric is confounded by variation in fetal cardiac function and is only moderately predictive of placental pathology. Our group developed a novel ultrasound methodology that measures wave reflections in the UA, thereby isolating a component of the Doppler signal that is specific to the placenta. The present study examined whether wave reflections in the UA are predictive of placental vascular pathology. Methods: Standard clinical Doppler ultrasound of the UAs was performed in 241 pregnant women. Of these, 40 women met narrowly defined preset criteria for the control group, 36 had maternal vascular malperfusion (MVM) and 16 had fetal vascular malperfusion (FVM). Using a computational procedure, the Doppler waveforms were decomposed into a pair of forward and backward propagating waves. Findings: Compared to controls, wave reflections were significantly elevated in women with either MVM (p

Background Several studies reported a correlation between anatomic location and genetic background of low-grade gliomas (LGGs). As such, tumor location may contribute to presurgical clinical decision-making. Our purpose was to visualize and compare the spatial distribution of different WHO 2016 gliomas, frequently aberrated single genes and DNA copy number alterations within subgroups, and groups of postoperative tumor volume. Methods Adult grade II glioma patients (WHO 2016 classified) diagnosed between 2003 and 2016 were included. Tumor volume and location were assessed with semi-automatic software. All volumes of interest were mapped to a standard reference brain. Location heatmaps were created for each WHO 2016 glioma subgroup, frequently aberrated single genes and copy numbers (CNVs), as well as heatmaps according to groups of postoperative tumor volume. Differences between subgroups were determined using voxelwise permutation testing. Results A total of 110 IDH mutated astrocytoma patients, 92 IDH mutated and 1p19q co-deleted oligodendroglioma patients, and 22 IDH wild-type astrocytoma patients were included. We identified small regions in which specific molecular subtypes occurred more frequently. IDH-mutated LGGs were more frequently located in the frontal lobes and IDH wild-type tumors more frequently in the basal ganglia of the right hemisphere. We found no localizations of significant difference for single genes/CNVs in subgroups, except for loss of 9p in oligodendrogliomas with a predilection for the left parietal lobes. More extensive resections in LGG were associated with frontal locations. Conclusions WHO low-grade glioma subgroups show differences in spatial distribution. Our data may contribute to presurgical clinical decision-making in LGG patients.

Simple Summary Most children infected with HIV live in Sub-Sahara Africa (SSA). These children are at risk of cancers related to HIV infection, but the degree of this risk and how it is influenced by antiretroviral therapy (ART) is unknown. In this study, we determined the subtypes, incidence, and risk factors of cancers in children with HIV in SSA and receiving ART with the goal of learning how we may prevent these cancers. We found that Kaposi sarcoma and lymphoma are the most common, comprising about 77% and 19% of cancers in these children, respectively. For every 100,000 person-years, 47.6 children developed cancer. Waiting to start ART until after 2 years old and having had severe immunosuppression were the two biggest risk factors for cancer that we identified. The findings justify the recommendations to start children on ART as soon as they are diagnosed with HIV regardless of their CD4 immune status. Abstract Approximately 91% of the world’s children living with HIV (CLWH) are in sub-Saharan Africa (SSA). Living with HIV confers a risk of developing HIV-associated cancers. To determine the incidence and risk factors for cancer among CLWH, we conducted a nested case-control study of children 0–18 years from 2004–2014 at five centers in four SSA countries. Incident cases of cancer and HIV were frequency-matched to controls with HIV and no cancer. We calculated the incidence density by cancer type, logistic regression, and relative risk to evaluate risk factors of cancer. The adjusted incidence density of all cancers, Kaposi sarcoma, and lymphoma were 47.6, 36.6, and 8.94 per 100,000 person-years, respectively. Delayed ART until after 2 years of age was associated with cancer (OR = 2.71, 95% CI 1.51, 4.89) even after adjusting for World Health Organization clinical stage at the time of enrolment for HIV care (OR = 2.85, 95% CI 1.57, 5.13). The relative risk of cancer associated with severe CD4 suppression was 6.19 (p = 0.0002), 2.33 (p = 0.0042), and 1.77 (p = 0.0305) at 1, 5, and 10 years of ART, respectively. The study demonstrates the high risk of cancers in CLWH and the potential benefit of reducing this risk by the early initiation of ART.

Objective To describe the evolution and evaluation of protocol-based multidisciplinary quality improvement (QI) in women undergoing cesarean hysterectomy for radiologically suspected and pathologically confirmed placenta accreta spectrum (PAS) disorders. Methods A single-center, retrospective cohort study was conducted of all patients undergoing cesarean hysterectomy for PAS disorders between March 2009 and June 2018. Two distinct periods were defined to compare outcomes: 2009-2011 (initial period) and 2017-2018 (current period). Primary outcomes included blood loss and administration of blood products. Secondary outcomes included perioperative levels of hemoglobin, adverse events and complications, time to mobilization, and length of hospitalization. Results Among the 105 consecutive patients identified, there were 26 in the initial period and 32 in the current period. With the implementation of all QI care bundles, median estimated surgical blood loss halved from 2000 mL in the initial period to 1000 mL in the current period, and fewer patients required allogenic blood transfusion (61.5% vs 25%). Patients in the current period demonstrated improved postoperative levels of hemoglobin compared to those in the initial period (101 g/L vs 89 g/L) and had a shorter median postoperative hospital stay (3 days vs 5 days). Conclusion These results support the implementation of a multifaceted QI and patient care initiative for women with PAS disorders.

Background Fetal sex is known to affect pregnancy outcomes. In current clinical practice, monitoring of fetal well-being is based on Doppler ultrasound measurements of major placental and fetal vessels. The objective of this study was to investigate the effect of fetal sex on Doppler parameters throughout gestation in healthy pregnancy. Methods A prospective study was conducted in 240 pregnant women with ultrasound examinations at a 4-weekly interval between 12 and 38 weeks of gestation. Pulsed Doppler spectra were collected for the umbilical arteries (UAs), middle cerebral artery (MCA), descending abdominal aorta (DAo), and ductus venosus (DV). Linear mixed effects models were used to determine if the pulsatility indices (PIs) of these vessels depended on gestational age and fetal sex. Results While there were no differences in the MCA PI and DV PIV over gestation between female and male fetuses, the trajectory of the UA and DAo PIs differed by fetal sex (p = 0.02 and p = 0.01, respectively). Conclusions Doppler ultrasound parameters were found to be dependent on fetal sex for some vessels and not for others in healthy pregnancies. Further investigations are needed to understand the physiological mechanisms for these sex differences and the relevance for disease processes in pregnancy.

PROPAG-AGEING consortium., A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had, This project has received funding from the European Union’s Horizon 2020 research and innovation program Propag‐Ageing under grant agreement no. 634821.

Introduction A growing number of Liaison Committee on Medical Education–accredited allopathic medical schools offer formal bilingual (English and Spanish) medical education, and numerous other schools offer medical Spanish through elective workshops as part of their curricula. One significant health disparity in the Hispanic community is the incidence of HIV among Spanish-speaking men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) has emerged as an effective strategy to reduce the risk of HIV transmission. Methods We developed an education module to train clinicians to discuss PrEP with Spanish-speaking MSM. Our module is adapted from an English module on PrEP education. It includes a Spanish-language PowerPoint slide deck with information about PrEP as well as a Spanish-language videotaped scripted clinical encounter. Results The module was implemented on three occasions with 18 participants, and learners reported increased comfort in discussing and confidence in prescribing PrEP with Spanish-speaking patients. Discussion This workshop can be incorporated within medical Spanish curriculums offered at health professional schools and community-based organizations dedicated to reducing the HIV burden in the Spanish-speaking Hispanic community.

Objective To review the most effective clinical approaches to disengage an impacted fetal head during cesarean delivery. Target Population Women who undergo cesarean delivery of an infant with a deeply impacted head. Options The "push" technique (from below) or the "pull" technique (reverse breech extraction). Outcomes Proper management of this clinical scenario can reduce maternal and perinatal morbidity and mortality. Benefits, Harms, and Costs Using an evidence-informed approach when an impacted fetal head is anticipated has the potential to reduce maternal and fetal complications and short- and long-term harm and their associated costs. Research into the value of simulation learning, regular labour assessments, and team preparedness for possible interventions will help inform quality care. Evidence The following search terms were entered into PubMed/Medline, Google Scholar, and Cochrane for the publication period 2012–2019: • ‘Guidelines' ‘manual' • ‘Caesarean Section' • ‘full dilation' • ‘operative delivery' • ‘impacted head' • ‘Caesarean' AND ‘full dilation' AND ‘impacted head' • ‘Caesarean' AND ‘second stage of labour' OR ‘second stage' AND ‘impacted head' • ‘Caesarean' OR ‘operative delivery' AND ‘impacted head' A total of 32 articles were retrieved and 24 were deemed appropriate to include as references. Many of these articles represented expert opinion. Randomized controlled trials had small sample sizes and were conducted in settings that limit the generalizability of their findings to the Canadian population.20 Intended Users Intrapartum health care providers.

Bilateral ligation of the anterior division of the internal iliac arteries can be a lifesaving intervention for severe pelvic hemorrhage. The procedure results in decreased pelvic perfusion and promotes coagulation. The classical method of internal iliac artery ligation involved extensive retroperitoneal dissection with complete circumferential isolation of the vessel to allow the passage of a suture around the artery. This can be surgically challenging and fraught with risks of inadvertent injury to the surrounding iliac veins. We propose a contemporary technique that requires limited dissection of the anterior division of the internal iliac artery. A few millimeters of space is created on either side of the artery by spreading right-angle forceps parallel to the vessel. The artery is occluded by 2 large vascular clips. Because circumferential vessel dissection is not necessary with this technique, there is limited disruption of the delicate underlying internal iliac vein. In addition, this approach may decrease the risk of inadvertent injury to the adjacent external iliac vein. By showcasing the ease of our approach to internal iliac artery ligation, we hope to empower surgeons with an alternative approach to this lifesaving procedure.

Histopathological growth patterns (HGPs) are independent prognosticators for colorectal liver metastases (CRLM). Currently, HGPs are determined postoperatively. In this study, we evaluated radiomics for preoperative prediction of HGPs on computed tomography (CT), and its robustness to segmentation and acquisition variations. Patients with pure HGPs [i.e. 100% desmoplastic (dHGP) or 100% replacement (rHGP)] and a CT-scan who were surgically treated at the Erasmus MC between 2003–2015 were included retrospectively. Each lesion was segmented by three clinicians and a convolutional neural network (CNN). A prediction model was created using 564 radiomics features and a combination of machine learning approaches by training on the clinician’s and testing on the unseen CNN segmentations. The intra-class correlation coefficient (ICC) was used to select features robust to segmentation variations; ComBat was used to harmonize for acquisition variations. Evaluation was performed through a 100 × random-split cross-validation. The study included 93 CRLM in 76 patients (48% dHGP; 52% rHGP). Despite substantial differences between the segmentations of the three clinicians and the CNN, the radiomics model had a mean area under the curve of 0.69. ICC-based feature selection or ComBat yielded no improvement. Concluding, the combination of a CNN for segmentation and radiomics for classification has potential for automatically distinguishing dHGPs from rHGP, and is robust to segmentation and acquisition variations. Pending further optimization, including extension to mixed HGPs, our model may serve as a preoperative addition to postoperative HGP assessment, enabling further exploitation of HGPs as a biomarker. Supplementary Information The online version contains supplementary material available at 10.1007/s10585-021-10119-6.

Background Maternally administered corticosteroids are routinely used to accelerate fetal lung maturation in pregnancies at risk of early preterm delivery. Although, among the subgroup with growth restriction, a majority show a temporary improvement in umbilical artery Doppler waveforms that may be sustained up to 7 days, a minority will acutely decompensate in response to corticosteroids in association with deteriorating umbilical and fetal Doppler waveforms. The basis for such acute Doppler changes is presently unknown. Our group has developed a noninvasive ultrasound methodology to measure wave reflections in the umbilical artery and have established that wave reflection metrics are sensitive to structural changes in the placental vasculature and to acute changes in vascular tone. Using this approach, we demonstrated in healthy pregnant mice that fetoplacental vascular resistance decreased in betamethasone-treated mice compared with saline-treated controls. Objective This study aimed to investigate the effects of betamethasone administration on the wave reflection metrics in a mouse model of fetal growth restriction and to compare these findings with equivalent measurements in human fetuses. Study Design Pregnant CD-1 mice were housed from embryonic day 14.5 to embryonic day 17.5 in either a normoxic (21% O2, n=24) or hypoxic environment (11% O2, n=22), the latter being an established mouse model of fetal growth restriction. To investigate the effect of maternally administered betamethasone on the fetoplacental vasculature, ultrasound imaging was performed at baseline and 4 hours after treatment (either betamethasone or sterile saline). Umbilical artery wave reflection metrics were compared between the groups and for the effect of fetal sex. In addition, a cohort of 10 pregnant women with elevated umbilical artery pulsatility index and evidence of fetal growth restriction and 6 controls were imaged before and after corticosteroid administration. Results In the mouse model, after betamethasone administration, the female fetuses from the hypoxia group showed a 15% increase in umbilical artery diameter, a 98% increase in umbilical artery blood flow, and a 27% decrease in umbilical artery reflection coefficient, whereas the males from the hypoxia group showed no substantial changes. In agreement with our mouse findings, umbilical artery reflections were found to be larger in human growth-restricted fetuses than controls in women at risk of preterm birth. Conclusion Our studies provide insight into the mechanism whereby the human growth-restricted fetus may exhibit a temporary favorable fetoplacental vascular response to maternally administered corticosteroids. Further investigations are needed to understand why the male growth-restricted fetus seems unable to mount this favorable vascular response.

Glucocerebrosidase (GCase) deficiency due to mutations of the glucosidase acid beta (GBA) gene causes autosomal-recessive Gaucher’s disease, the most frequent lysosomal storage disorder. Over the past two decades,GBAmutations have been established as the most frequent genetic risk factor to develop Parkinson’s Disease. In dystonia, the underlying aetiology in a relevant proportion of cases remains unknown, hampering the development of causative treatment strategies. Here, we explored the possible role of lysosomal dysfunction in clinical (n=130) and post mortem (n=10) patients with dystonia.As part of extensive diagnostic evaluations (screening for structural, acquired and degenerative causes of dystonia), lysosomal enzyme activity was measured in n=79 retrospectively collected cases of patients with combined dystonia and n=51 prospectively collected cases of patients with cervical dystonia using a clinically validated, fluorescence-based assay. Clinical information on all cases was extensively reviewed and an alternative aetiology of dystonia was identified in n=14 cases on follow-up. Of the remaining n=116 cases of dystonia of unknown origin, complete Sanger Sequencing ofGBAexons 1-11 was performed using an established protocol in all n=97 of cases with available DNA. Where there was suspicion based on clinical examination or family history, nigro-striatal degeneration was excluded in n=19 (17.2%) cases with dystonia of unknown origin. Furthermore, lysosomal enzyme activity was measured in different brain regions of age-, sex- and post-mortem delay-matched cases with dystonia of unknown origin (n=10) and healthy controls (n=10) from the Queen Square brain bank.Among cases with dystonia of unknown origin, decreased white cell Glucocerebrosidase activity was measured in a range typical for homozygous (n=2; 1.7%) or heterozygous (n=23; 19.8%) GBA mutation carriers. The frequency ofGBAmutations (5/80=6.25%) was significantly higher in patients than in controls (3/257=1.17%) of a historical control group from the same ethnic background (P=0.02; Odds Ratio=5.64, 95% Confidence Interval=1.44 – 21.58) – known pathogenic mutations E326K, T369M and N370S were found. We also identified lower Glucocerebrosidase activity in the cerebellar dentate nucleus (P=0.048) of dystonia patients than healthy controls.This study provides evidence for peripheral and central lysosomal dysfunction in a significant proportion and across the clinical spectrum of dystonia. As in Parkinson’s disease, this was found irrespective ofGBAmutation status, indicating a possible role of lysosomal dysfunction as a more general disease mechanism in dystonia.

Background: The association between contrast enhanced (CE) and non-contrast enhanced (NCE) tumor resection and survival in patients with glioblastoma in relation to molecular subtypes is poorly understood. The aim of this study was to assess the association between CE and NCE tumor resection and survival in light of MGMT promoter methylation in newly diagnosed IDH-wildtype glioblastoma.Materials and methods: Patients with newly diagnosed IDH-wildtype glioblastoma who underwent surgery were eligible. CE and NCE tumor volumes were assessed on pre- and post-operative MRI scans and extent of resection was calculated. The association between CE and NCE tumor resection and survival was evaluated using multivariable Cox proportional hazards models and Kaplan Meier estimates.Results: Three hundred and twenty-six patients were included: 177 (54.3%) with and 149 (45.7%) without MGMT methylation. Multivariable Cox proportional hazards models stratified for MGMT methylation identified age ≤ 65y (HR 0.63; 95% CI, 0.49–0.81; p < 0.0001), chemoradiation (HR 0.13; 95% CI, 0.09–0.19; p < 0.0001), maximal CE tumor resection (HR 0.58; 95% CI, 0.39–0.87; p = 0.009), ≥ 30% NCE tumor resection (HR 0.71; 95% CI, 0.53–0.93; p = 0.014), and minimal residual CE tumor volume (HR 0.64; 95% CI, 0.46–0.88 p = 0.007) as being associated with longer overall survival. Kaplan Meier estimates showed that extensive surgery was more beneficial for patients with MGMT methylated glioblastoma.Conclusions: This study shows an association between maximal CE tumor resection, ≥30% NCE tumor resection, minimal residual CE tumor volume, and longer overall survival in patients with newly diagnosed IDH wildtype glioblastoma. Intraoperative imaging and stimulation mapping may be used to pursue safe and maximal resection. In future research, the safety aspect of maximizing tumor resection needs to be addressed.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7&ndash, 28, range: 1&ndash, 119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6&ndash, 33.7, range: 19.0&ndash, 41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p &lt, 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%, 51/118) and recipients (37%, 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1&ndash, 8.3, p &lt, 0.001), and GA at birth (OR = 0.8, 95%CI 0.7&ndash, 0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3&ndash, 1.7, p &lt, 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.

Introduction Mentorship, a supportive relationship that actively provides knowledge and insight, has many benefits. Although not extensively studied, medical students pursuing various specialties have diverse experiences with mentorship. Objective To understand how mentorship impacts medical student decisions involving rotation choices, residency programs, field of practice, interest in research, and career trajectory. Methods We hypothesized that effective mentor-mentee relationships would strongly impact medical students' decisions. Distributed to fourth-year osteopathic medical students at a single medical school, this study used a survey design to assess mentorship’s impact on their aforementioned decisions. Results Sixty-one students responded to this survey. Fifty-nine percent of respondents said they did not receive enough mentorship in medical school while 63.9% of respondents said their quality of mentorship was good/very good. Most survey respondents strongly agreed/agreed that the amount and quality of mentorship impacted their decisions involving rotation choices, residency programs, field of practice, and career trajectory. Qualitative data analysis led to the emergence of three themes: students pursuing primary care had positive mentorship experiences as compared to students pursuing non-primary care careers, female students stated they did not receive enough mentorship, and a majority of students cited the lack of formal mentorship as an area of improvement. Conclusions Our study demonstrates the profound impact mentorship has on a medical student’s career. Respondents believed their mentorship experiences strongly impacted their decisions involving rotation choices, residency programs, field of practice, and career trajectory. Participants also believed availability in the amount and quality of mentorship could be improved. The perceived lack in the amount and quality of mentorship may have negative implications on medical students’ career prospects.

Objectives: The purpose of this article was to further elucidate the pathophysiology of Mirror (Ballantyne) syndrome within the context of known biomarkers for preeclampsia.Methods: This novel insight from clinical practice involved a case of post-twin-to-twin transfusion syndrome-laser hydrops in an ex-donor twin, corroborated by histopathologic placental territory edema and maternal sequelae of Mirror syndrome. We serially measured the levels of activin A, follistatin, endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), soluble fms-like tyrosine kinase 1 (sFlt), and von Willebrand factor (vWF) in the maternal serum from disease evolution through to recovery.Results: The paired finding of hydropic ex-donor twin and placenta, supports the theory of placental injury as the source of potential molecular mediators, leading to local placental edema, associated fetal hydrops and the maternal preeclamptic picture. Notably, we elucidated a temporal spectrum of maternal serum mediators (soluble Flt-1, endothelin-1, 8-isoprostane, activin-A, ICAM-1, and vWF) involved in the pathogenesis of Mirror syndrome.Conclusion: Better understanding of the pathogenesis of Mirror syndrome has important implications for clinical management.

Placental dysfunction is a major contributing factor to fetal growth restriction. Placenta-mediated fetal growth restriction occurs through chronic fetal hypoxia owing to poor placental perfusion through a variety of mechanisms. Maternal vascular malperfusion is the most common placental disease contributing to fetal growth restriction; however, the role of rare placental diseases should not be overlooked. Although the features of maternal vascular malperfusion are identifiable on placental pathology, antepartum diagnostic methods are evolving. Placental imaging and uterine artery Doppler, used in conjunction with angiogenic growth factors (specifically placenta growth factor and soluble fms-like tyrosine kinase-1), play an increasingly important role.

Uterine tachysystole (TS) is a potentially significant intrapartum complication seen most commonly in induced or augmented labors but may also occur in women with spontaneous labor. When it occurs, maternal and perinatal complications can arise if not identified and managed promptly by obstetric care providers. Over recent years, new definitions of the condition have facilitated further research into the field, which has been synthesized to inform clinical management guidelines and protocols. We propose a set of recommendations pertaining to TS in line with contemporary evidence and obstetric practice.

Understanding the effect intermolecular interactions have on the electronic properties of highly conjugated/aromatic organic networks is important for optimizing these materials for optoelectronic device applications. Here, dispersion inclusive density functional theory (DFT + vdW) is used to study the effect of pressure up to 20 GPa on the intermolecular interactions of 40 herringbone polycyclic aromatic hydrocarbons. In the first part of this two-part study (10.1021/acs.jpcc.8b07209), we reported the pressure-induced structural changes. Here, we elucidate the relation between those structural changes and the electronic properties, where it is shown that increased pressure leads to variations in the intermolecular interactions and molecular conformations, resulting in alterations of the band dispersion, band gap (magnitude as well as direct/indirect), and semiconductor polarity (n-type vs p-type). Specifically, increased pressure increases the C–H···π and π···π interactions, typically leading to increase...

PURPOSE OF REVIEW: Neuroimaging in Parkinson's disease is an evolving field, providing in-vivo insights into the structural and biochemical changes of the condition, although its diagnosis remains clinical. Here, we aim to summarize the most relevant recent advances in neuroimaging in Parkinson's disease to assess the underlying disease process, identify a biomarker of disease progression and guide or monitor therapeutic interventions. RECENT FINDINGS: The clinical applications of imaging technology increasingly allow to quantify pigments (iron, neuromelanin) on MRI, proteins (tau), cell markers (phosphodiesterases, microglia) and neurotransmitter receptors (dopamine, serotonin, noradrenalin, cholin) via PET protocols, activity maps by resting-state and task-dependent functional MRI, as well as microstructural changes (free water) through diffusion-based assessments. Their application provides increasing insight on the temporal and spatial dynamics of dopaminergic and other neurotransmitter systems as well as anatomical structures and circuits in Parkinson's disease. An expanding list of PET tracers increases the yield of functional studies. SUMMARY: This review summarizes the most recent, relevant advances in neuroimaging technology in Parkinson's disease. In particular, the combination of different imaging techniques seems promising to maximize the scope of future work, which should, among others, aim at identifying the best imaging marker of disease progression.

Mit der Entwicklung des hochintensiven Magnetresonanztomographie(MRT)-gesteuerten fokussierten Ultraschalls (MRTgFUS) steht der lasionellen stereotaktischen funktionellen Neurochirurgie eine neue Behandlungstechnik zur Verfugung. Hieraus ergeben sich neue, inzisionslose Interventionsansatze in der Therapie von Tremorerkrankungen, deren Sicherheit und Wirksamkeit durch erste Studienergebnisse belegt sind. Dieser Artikel umfasst eine Beschreibung der zugrunde liegenden Ultraschalltechnik, des Ablaufs einer MRTgFUS-Behandlung, einen orientierenden Vergleich zu alternativen offenen und inzisionslosen Interventionstechniken sowie eine Zusammenfassung der aktuellen Evidenz der MRTgFUS-Behandlung im Kontext der lasionellen Tremortherapie. Narrativer Literaturvergleich. In Abhangigkeit von Zielpunkt und Tremoratiologie zeigen bisherige publizierte Ergebnisse der MRTgFUS-Behandlung eine bis zu 80 %ige Reduktion der Tremorintensitat nach 6 bis 12 Monaten Nachkontrolle ohne die Nachteile einer offenen Schadeloperation. Die MRTgFUS-Technologie wird in der funktionellen Neurochirurgie bislang nur an wenigen Studienzentren weltweit angewandt. Neben dem thalamischen ventralen intermediaren Nukleus (V.im.) als Zielpunkt liegen auch erste Studien zur Ablation subthalamischer Faserbahnen vor. Bisherige Studienergebnisse deuten auf eine effektive und sichere Tremortherapie durch die MRTgFUS-Behandlung hin. Die inzisionslose lasionelle Chirurgie mittels MRTgFUS stellt eine wesentliche Erweiterung des Interventionsspektrums fur die funktionelle stereotaktische Neurochirurgie und eine potenziell relevante Alternative zu etablierten interventionellen Therapieoptionen fur Tremor dar.

BackgroundThis work evaluates the consistency, effect size and incidence of persistent side effects of lesional neurosurgical interventions in the treatment of tremor due to Parkinson’s disease (PD), essential tremor (ET), multiple sclerosis (MS) and midbrain lesions.MethodsSystematic review and meta-analysis according to PRISMA-P guidelines. Random effects meta-analysis of standardised mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049).ResultsFrom 1249 abstracts screened, 86 peer-reviewed studies reporting 102 cohorts homogeneous for tremor aetiology, surgical target and technique were included.Effect on PD tremor was better when targeted at the ventral intermediate nucleus (V.im.) by radiofrequency ablation (RF) (Hedge’s g: −4.15;) over V.im. by Gamma Knife (GK) (−2.2), subthalamic nucleus (STN) by RF (−1.12) and globus pallidus internus (GPi) by RF (−0.89). For ET MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (−2.35) and V.im. (−2.08) showed similar mean tremor reductions to V.im. ablation by RF (−2.42) or GK (−2.13). In MS V.im. ablation by GK (−1.96) and RF (−1.63) were similarly effective.Mean rates of persistent side effects after unilateral lesions in PD were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0% (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7% (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral tremor 30.3% (RF V.im.).ConclusionThis meta-analysis quantifies safety, consistency and efficacy of lesional neurosurgical interventions for tremor by target, technique and aetiology.

While previous viral pandemics showed that pregnancy was a risk factor for susceptibility and adverse outcomes, current evidence is conflicting whether SARS-CoV-2 infection during pregnancy is more severe than in the general population, with relatively low maternal and fetal/neonatal mortality rates. SARS-CoV-2 is known to enter host cells via the ACE-2 receptors, competitively occupying their binding sites. In theory, viral invasion can lead to a reduction in available ACE-2 receptors and consequently an unbalanced regulation between the ACE-AngII-AT1 axis and the ACE-2-Ang-(1-7)-MAS axis, thus enhancing pathological vasoconstriction, fibrosis, inflammation and thrombotic processes. We hypothesize that the normal pregnant state of highly expressed ACE-2 receptors leads to higher Ang-(1-7) levels and consequently more vasodilation and anti-inflammatory response to SARS-COV-2 infection. We suggest that this up-regulation of ACE-2 receptors in human gestation may actually be clinically protective and propose a potential research line to investigate this hypothesis, which may lead to future novel therapeutics.

BACKGROUND Simulation-based programs are increasingly being used to teach obstetrics and gynaecology examinations, but it is difficult to establish student learning acquired through them. Assessment may test student learning but its role in learning itself is rarely recognised. We undertook this study to assess medical and midwifery student learning through a simulation program using a pre-test and post-test design and also to evaluate use of assessment as a method of learning. METHODS The interprofessional simulation education program consisted of a brief pre-reading document, a lecture, a video demonstration and a hands-on workshop. Over a 24-month period, 405 medical and 104 midwifery students participated in the study and were assessed before and after the program. Numerical data were analysed using paired t-test and one-way analysis of variance. Students' perceptions of the role of assessment in learning were qualitatively analysed. RESULTS The post-test scores were significantly higher than the pre-test (P