Monochorionic twins discordant for trisomy 13: A case report, systematic literature search and synthesis of available evidence

This article presents the tenth reported case of monochorionic twins discordant for trisomy 13. Discordant aneuploidies in monochorionic twins are rare. Aetiologies include mitotic error in early cell division and “rescue” chromosome loss in an initially trisomic zygote. Clinicians should offer early amniocentesis of both sacs and consider selective termination

Retrieval and Registration of Long-Range Overlapping Frames for Scalable Mosaicking of In Vivo Fetoscopy

Purpose: The standard clinical treatment of Twin-to-Twin Transfusion Syndrome consists in the photo-coagulation of undesired anastomoses located on the placenta which are responsible to a blood transfer between the two twins. While being the standard of care procedure, fetoscopy suffers from a limited field-of-view of the placenta resulting in missed anastomoses. To facilitate the task of the clinician, building a global map of the placenta providing a larger overview of the vascular network is highly desired. Methods: To overcome the challenging visual conditions inherent to in vivo sequences (low contrast, obstructions or presence of artifacts, among others), we propose the following contributions: (i) robust pairwise registration is achieved by aligning the orientation of the image gradients, and (ii) difficulties regarding long-range consistency (e.g. due to the presence of outliers) is tackled via a bag-of-word strategy, which identifies overlapping frames of the sequence to be registered regardless of their respective location in time. Results: In addition to visual difficulties, in vivo sequences are characterised by the intrinsic absence of gold standard. We present mosaics motivating qualitatively our methodological choices and demonstrating their promising aspect. We also demonstrate semi-quantitatively, via visual inspection of registration results, the efficacy of our registration approach in comparison to two standard baselines. Conclusion: This paper proposes the first approach for the construction of mosaics of placenta in in vivo fetoscopy sequences. Robustness to visual challenges during registration and long-range temporal consistency are proposed, offering first positive results on in vivo data for which standard mosaicking techniques are not applicable.Comment: Accepted for publication in International Journal of Computer Assisted Radiology and Surgery (IJCARS

A double dilemma: treatment of stage IV fetal twin-twin transfusion syndrome in the setting of maternal recurrent venous thromoembolism: a case report

Background: Fetal conditions can pose significant challenges in the management of pregnancies complicated by pre-existing maternal medical conditions. Case presentation: We report a case of a 34-year-old woman with Stage IV Twin Twin Transfusion syndrome in the presence of maternal recurrent complex venous thromboembolic disease. Following a previous pregnancy loss, complicated by a third episode of thromboembolic disease, an inferior vena cava filter was placed. One month later, a pregnancy was confirmed and subsequently identified as a monochorionic twin pregnancy. Twin-Twin Transfusion syndrome was identified at 18 weeks’ gestation and progressed rapidly to Quintero Stage IV. In consultation with a multi-disciplinary international team, fetoscopic laser photocoagulation was performed. The pregnancy progressed to delivery of female infants at 33 weeks gestation, who have achieved all developmental milestones at 2 years of age. Conclusions: We describe the multi-disciplinary effort to optimise the maternal condition to allow fetoscopic laser photocoagulation and continued management of the maternal and fetal conditions to a successful pregnancy outcome

Fetal surgery for open spina bifida

Key content: Spina bifida is a congenital neurological condition with lifelong physical and mental effects. Open fetal repair of the spinal lesion has been shown to improve hindbrain herniation, ventriculoperitoneal shunting, independent mobility and bladder outcomes for the child and, despite an increased risk of prematurity, does not seem to increase the risk of neurodevelopmental impairment. Open fetal surgery is associated with maternal morbidity. Surgery at our institution is offered and performed according to internationally agreed criteria and protocols. Further evidence regarding long‐term outcomes, fetoscopic repair and alternative techniques is awaited. Learning objectives: To understand the clinical effects, potential prevention and prenatal diagnosis of spina bifida. To understand the rationale and evidence supporting the benefits and risks of fetal repair of open spina bifida. To understand the criteria defining those who are likely to benefit from fetal surgery. Ethical issues: The concept of the fetus as a patient, and issues surrounding fetal death or the need for resuscitation during fetal surgery. The associated maternal morbidity in a procedure performed solely for the benefit of the fetus/child. The financial implications of new surgical treatments

A Combined EM and Visual Tracking Probabilistic Model for Robust Mosaicking: Application to Fetoscopy

Twin-to-Twin Transfusion Syndrome (TTTS) is a progressive pregnancy complication in which inter-twin vascular connections in the shared placenta result in a blood flow imbalance between the twins. The most effective therapy is to sever these connections by laser photo-coagulation. However, the limited field of view of the fetoscope hinders their identification. A potential solution is to augment the surgeon’s view by creating a mosaic image of the placenta. State-of-the-art mosaicking methods use feature-based ap- proaches, which have three main limitations: (i) they are not robust against corrupt data e.g. blurred frames, (ii) tem- poral information is not used, (iii) the resulting mosaic suf- fers from drift. We introduce a probabilistic temporal model that incorporates electromagnetic and visual tracking data to achieve a robust mosaic with reduced drift. By assuming planarity of the imaged object, the nRT decomposition can be used to parametrize the state vector. Finally, we tackle the non-linear nature of the problem in a numerically stable manner by using the Square Root Unscented Kalman Filter. We show an improvement in performance in terms of robustness as well as a reduction of the drift in comparison to state-of-the-art methods in synthetic, phantom and ex vivo datasets

FetReg: Placental Vessel Segmentation and Registration in Fetoscopy Challenge Dataset

Fetoscopy laser photocoagulation is a widely used procedure for the treatment of Twin-to-Twin Transfusion Syndrome (TTTS), that occur in mono-chorionic multiple pregnancies due to placental vascular anastomoses. This procedure is particularly challenging due to limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to fluid turbidity, variability in light source, and unusual position of the placenta. This may lead to increased procedural time and incomplete ablation, resulting in persistent TTTS. Computer-assisted intervention may help overcome these challenges by expanding the fetoscopic field of view through video mosaicking and providing better visualization of the vessel network. However, the research and development in this domain remain limited due to unavailability of high-quality data to encode the intra- and inter-procedure variability. Through the \textit{Fetoscopic Placental Vessel Segmentation and Registration (FetReg)} challenge, we present a large-scale multi-centre dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms for the fetal environment with a focus on creating drift-free mosaics from long duration fetoscopy videos. In this paper, we provide an overview of the FetReg dataset, challenge tasks, evaluation metrics and baseline methods for both segmentation and registration. Baseline methods results on the FetReg dataset shows that our dataset poses interesting challenges, offering large opportunity for the creation of novel methods and models through a community effort initiative guided by the FetReg challenge

FetReg: Placental Vessel Segmentation and Registration in Fetoscopy Challenge Dataset

Fetoscopy laser photocoagulation is a widely used procedure for the treatment of Twin-to-Twin Transfusion Syndrome (TTTS), that occur in mono-chorionic multiple pregnancies due to placental vascular anastomoses. This procedure is particularly challenging due to limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to fluid turbidity, variability in light source, and unusual position of the placenta. This may lead to increased procedural time and incomplete ablation, resulting in persistent TTTS. Computer-assisted intervention may help overcome these challenges by expanding the fetoscopic field of view through video mosaicking and providing better visualization of the vessel network. However, the research and development in this domain remain limited due to unavailability of high-quality data to encode the intra- and inter-procedure variability. Through the \textit{Fetoscopic Placental Vessel Segmentation and Registration (FetReg)} challenge, we present a large-scale multi-centre dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms for the fetal environment with a focus on creating drift-free mosaics from long duration fetoscopy videos. In this paper, we provide an overview of the FetReg dataset, challenge tasks, evaluation metrics and baseline methods for both segmentation and registration. Baseline methods results on the FetReg dataset shows that our dataset poses interesting challenges, offering large opportunity for the creation of novel methods and models through a community effort initiative guided by the FetReg challenge

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis

The anti-interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years.Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2-17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group).Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] μg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was - 17.4 in patients younger than 2 and - 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group).Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years.Juvenile idiopathic arthritis.ClinicalTrials.gov, NCT01455701 . Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012

The Effect of Polyhydramnios on Cervical Length in Twins: A Controlled Intervention Study in Complicated Monochorionic Pregnancies

Objective: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume. Study Design: Prospective cohort study of 40 women with monochorionic twins undergoing interventional procedures between 16-26 weeks. Cervical length was assessed via transvaginal sonography pre-procedure, 1 and 24 hours postprocedure, and results compared between amnioreduction and control procedures. Amniotic fluid index (AFI) was measured pre- and post-procedure. Results: Pre-procedural cervical length correlated with AFI (linear fit = 5.07 -0.04x, R2 = 0.17, P = 0.03) in patients with polyhydramnios (n = 28). Drainage of 2000ml fluid (range 700-3500ml), reduced AFI from 42cm to 21cm (P>0.001). Their pre-procedural cervical length did not change at one (mean Δ:-0.1cm, 95%CI, -0.4 to 0.2) or 24 hours (0.2cm, -0.1 to 0.6) after amnioreduction. There was no change in cervical length at control procedures. Conclusion: Cervical shortening in twins with polyhydramnios does not appear to be an acute process; cervical length can be measured before or after therapeutic procedures. © 2008 Engineer et al