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

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

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

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

Radiofrequency ablation for selective reduction in complex monochorionic pregnancies

Monochorionic pregnancies present unique challenges for selective fetal reduction, as vaso-occlusive procedures are required to ablate blood flow, usually in the umbilical cord, to achieve asystole in the selected fetus. We describe a case series of 35 monochorionic pregnancies (27 twins and eight triplets) undergoing selective fetal reduction using radiofrequency ablation. All procedures were performed under local anaesthesia. The procedure was technically successful in all cases. The live born rate was 88.6%. One (2.9%) woman miscarried within 2 weeks of the procedure, and two (5.7%) babies were stillborn. The median gestation at delivery was 36 weeks of gestation (range 24-41 weeks). There were no maternal complications. The median gestational age at procedure was 17 + 3 weeks (range from 12 + 5 to 27 + 4 weeks). All women had antenatal magnetic resonance imaging (MRI) post procedure. There were two (5.7%) cases of abnormal brain imaging. Our experience suggests that radiofrequency ablation is a safe and effective procedure for fetal reduction in complicated monochorionic pregnancies