Twin Reversed Arterial Perfusion Research Articles

A case of acardiac acephalus: Variant of trap sequence

The incidences of twin gestation and higher order multi-fetal pregnancies are on increasing trend. There are increased use of ovulation induction drugs and assisted reproductive technology in this era owing to higher incidences of infertility and better diagnostics and treatment modalities. And with increased use of these methods, comes increased incidence of complications. Incidences of complications are more in monozygotic pregnancies than in dizygotic twin. Acardiac twin is a rare, severe congenital malformation seen in monozygotic twin gestation, which is incompatible with life. Acardiac twin, also known as TRAP (Twin Reversed Arterial Perfusion Sequence); results from abnormal placental vasculature.Early diagnosis of acardiac twin by ultrasonography and colordoppler is essential for timely management and preventing complications like preterm delivery, cardiac failure and intrauterine fetal death of ‘ pump’co-twin. Here we are reporting a case of an antenatally diagnosed mono-chorionic twin pregnancy with acardiac twin, which was managed conservatively. Proper monitoring and timely decision for terminationresulted in preterm delivery of a live, normal twin along with an acardiac co-twin.

Acardiac twin: a commonly missed diagnosis

Twin reversed arterial perfusion syndrome is a rare condition seen in monochorionic twin gestation. The incidence is 1 in 35000 births and 1 in 100 monozygotic twin pregnancies. It is a complication of twin pregnancy that occurs due to preferential blood flow within the vascular communication between the two fetuses. We hereby report a case of 24-year-old primigravida referred in view of twin pregnancy with demise of one twin. On serial ultrasound it was misinterpreted as missed abortion of one twin and twin papyruses in further scans. But the consistent growth of the demised fetus made us think of acardiac twin as a differential diagnosis. When she presented in labour to our hospital, she delivered an acardiac anceps fetus along with a normal fetus.

Synthesis of the Taxol Core via Catalytic Asymmetric 1,4-Addition of an Alkylzirconium Nucleophile.

The Taxol core was prepared in five steps via a key copper-catalyzed asymmetric conjugate addition trapping sequence. The use of a bromodiene-derived alkylzirconium nucleophile followed by trapping with POCl3/DMF gave a highly functionalized intermediate featuring a quaternary center in 69% yield with 92% ee. After 1,2-addition, Suzuki-Miyaura cross-coupling, allylic oxidation, and a type II intramolecular Diels-Alder reaction, the taxol core was obtained in 11% overall yield with 92% ee.

TRAP) Secuencia de perfusión arterial reversa en embarazo gemelar monocoriónico con feto acárdico. Caso Clínico.

Objetive: Develop a review of the pathophysiology, diagnosis, treatment and management of reversed arterial perfusion.The reversed arterial perfusion sequence, known in English literature as TRAP sequence (twin reversed arterial perfusion (1), pathology associated with complications of monochorionic twin pregnancy, (2) is the absence of a well-defined cardiac structure on a twin (the acardiac twin), which is kept alive by his co-twin (the pump twin) through an arterial-arterial surface placental anastomosis. (3) the normal twin accompanying the acardiac has a mortality of 60% ; morbidity is mainly associated with congestive heart failure (4) while the acardiac twin has a mortality of 100% Apropos of a case reversed arterial perfusion syndrome TRAP diagnosed in the second trimester of pregnancy will be displayed and evaluate it. Management made in the service of Gynecology, service image and Pathology service and the associated perinatal outcomes. Keywords: acardic Fetus, perfusion sequence reversed arterial, sequence TRAP, monochorionic pregnancy twin

Twin Reversed Arterial Perfusion Sequence: Current Treatment Options.

Twin reversed arterial perfusion (TRAP) sequence is a specific and severe complication of monochorionic multiple pregnancy, characterized by vascular anastomosis and partial or complete lack of cardiac development in one twin. Despite its rarity, interest in the international literature is rising, and we aimed to review its pathogenesis, prenatal diagnostic features and treatment options. Due to the parasitic hemodynamic dependence of the acardiac twin on the pump twin, the management of these pregnancies aims to maximize the pump twin’s chances of survival. If treatment is needed, the best timing of intervention is still debated, although the latest studies encourage intervention in the first trimester of pregnancy. As for the technique of choice to interrupt the vascular supply to the acardiac twin, ultrasound-guided laser coagulation and radiofrequency ablation of the intrafetal vessels are usually the preferred approaches.

Sonographic detection of fetal abnormalities before 11 weeks of gestation.

Sonographic detection of fetal abnormalities before 11 weeks of gestation.

Morphology, intrafetal vascular pattern, and umbilical artery Doppler indices of acardiac twins.

Twin reversed arterial perfusion (TRAP) sequence consists of acardiac twin (A) paradoxically perfused by pump twin (P) through an umbilical artery (UA). We proposed characterization of acardiac twins with intrafetal vascular pattern (IVP), and assessed its correlation with morphology and UA Doppler indices. We prospectively evaluated 21 cases of TRAP sequence. Morphology (acardia vs hemicardia) and IVP (simple vs complex) of acardiac twins were characterized with ultrasound and color Doppler. Twins weight ratio (A/P Wt) and UA Doppler indices of acardiac and pump twins including (1) difference of systolic/diastolic ratio (UA ∆S/D), (2) difference of resistance index (UA ∆RI), and (3) ratio of pulsatility index (UA PI A/P) were calculated. The median (min, max) gestational age at diagnosis was 18 (11, 27) weeks. Acardia (n = 14) were associated with simple IVP (n = 16) (P < .05). After exclusion of acardia with complex IVP (n = 1), the A/P Wt, UA ∆S/D, UA ∆RI, and UA PI A/P of acardia with simple IVP (n = 13), hemicardia with simple IVP (n = 3), and hemicardia with complex IVP (n = 4) were not significantly different (P > .05). Most of acardiac twins were acardia with simple IVP. Morphology and IVP of acardiac twins were not associated with UA Doppler indices.

Intrafetal laser for midtrimester TRAP sequence-experience from a single center.

To report our experience and evaluate outcomes in monochorionic pregnancies with Twin Reversed Arterial Perfusion sequence with intrafetal laser therapy. Retrospective review of records of all pregnancies with TRAP sequence treated by intrafetal laser therapy between 2011 January and 2015 December that were retrieved and analysed. Electronic search of the scan database retrieved 57 cases of TRAP sequence during the study period, 7 triplets and 50 monochorionic twins. Intrafetal laser was done in 27 cases, 22 cases of twins and 5 cases of triplets. In the twins group, median gestational age at intervention was 22.5 weeks, the earliest done at 16.3 weeks. The median gestational age at delivery and birth weight was 37 weeks and 2.5 Kgs. The median procedure and delivery interval was 14 weeks. Live birth rate was 17/22 (77%) the pump survival rate was 16/22 (73%). Pregnancies with non-surviving pump were 5 in numbers (5/22). A repeat procedure was warranted in one case. In the triplet group, median gestational age at intervention, delivery and procedure delivery interval was 18, 35 and 17 weeks. Intrafetal laser is simple, effective and the treatment of choice to interrupt the vascular supply to acardiac twin.

Study of birth anomalies in twin pregnancies

Introduction: Twin pregnancies with congenital malformations in foetuses is associated with higher morbidity and mortality both for the mother as well as the child Its incidence is 4 times more common than single births. This study highlights rare anomalies and complications in twins Materials and Methods: This is a prospective study which includes women with twin pregnancies diagnosed in first trimester by sonography. The cases were collected from a maternity hospital over a period of one year. Details of gestational age, gender, zygosity, chorionicity, anomalies and complications of the twins were taken into account along with age and parity of the mother. Results: Out of 2023 pregnancies 41 were twin pregnancies in which 23 were dizygotic twins and 18 were monozygotic twins based on Weinberg formula. Congenital anomalies and fetal complications were observed in 4 cases (17.39%) of dizygotic twins and 8 cases (44.44%) of monozygotic twins. The affected twins predominantly belonged to female sex. Monozygotic twins showed TRAP Sequence with Acephaly and Twin to twin transfusion syndrome in 2 and 3 pairs respectively. Pregnant women with twins were between 25 to 40 years of age group. Conclusion: Twining rate was 20.26/1000 deliveries. Central nervous system anomalies were seen in women with no folic acid intake preconceptionly. Complications and anomalies were among monozygotic twins. Therefore chorionicity of the placenta should be detected in first trimester of pregnancy in order to prevent fetal deaths by undertaking appropriate medical measures. Keywords: Monozygotic (MZ), Dizygotic (DZ), Twin to twin transfusion syndrome, (TTTS), Twin reversed arterial perfusion, Sequence (TRAP sequence), Congenital anomalies (CAs).

Fetal therapies as standard prenatal care in Japan.

With recent advances in fetal medicine, various attempts have been made to save fetuses facing perinatal death or devastating consequences despite optimal management after birth. The concept of the fetus as a patient has been established through the application of in utero treatments. This paper reviews fetal therapies in order to highlight the role of perinatal medicine as standard prenatal care. Fetal therapies consist of medical therapy, percutaneous ultrasound-guided surgery, fetoscopic surgery, and open fetal surgery. In the 1980s, with advances in ultrasound imaging, percutaneous ultrasound-guided surgeries such as vesicoamniotic shunting for lower urinary tract obstruction and thoracoamniotic shunting (TAS) for fetal hydrothorax (FHT) were started. In the 1990s, fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) was introduced, and later, a fetoscopic approach for congenital diaphragmatic hernia was also established. The revival of open fetal surgery, introduced in the 1980s by pediatric surgeons, began in the 2010s after a successful clinical study for myelomeningocele. Although many fetal therapies are still considered experimental, some have proven effective, such as FLS for TTTS, TAS for primary FHT, and radiofrequency ablation (RFA) for twin reversed arterial perfusion (TRAP) sequence. These three fetal therapies have been approved for coverage by Japan National Health Insurance as a result of clinical studies performed in Japan. FLS for TTTS, TAS for primary FHT, and RFA for TRAP sequence have become standard prenatal care approaches in Japan. These three minimally invasive fetal therapies will help improve the perinatal outcomes of fetuses with these disorders.

Oplr16 serves as a novel chromatin factor to control stem cell fate by modulating pluripotency-specific chromosomal looping and TET2-mediated DNA demethylation.

Formation of a pluripotency-specific chromatin network is a critical event in reprogramming somatic cells into pluripotent status. To characterize the regulatory components in this process, we used ‘chromatin RNA in situ reverse transcription sequencing’ (CRIST-seq) to profile RNA components that interact with the pluripotency master gene Oct4. Using this approach, we identified a novel nuclear lncRNA Oplr16 that was closely involved in the initiation of reprogramming. Oplr16 not only interacted with the Oct4 promoter and regulated its activity, but it was also specifically activated during reprogramming to pluripotency. Active expression of Oplr16 was required for optimal maintenance of pluripotency in embryonic stem cells. Oplr16 was also able to enhance reprogramming of fibroblasts into pluripotent cells. RNA reverse transcription-associated trap sequencing (RAT-seq) indicated that Oplr16 interacted with multiple target genes related to stem cell self-renewal. Of note, Oplr16 utilized its 3′-fragment to recruit the chromatin factor SMC1 to orchestrate pluripotency-specific intrachromosomal looping. After binding to the Oct4 promoter, Oplr16 recruited TET2 to induce DNA demethylation and activate Oct4 in fibroblasts, leading to enhanced reprogramming. These data suggest that Oplr16 may act as a pivotal chromatin factor to control stem cell fate by modulating chromatin architecture and DNA demethylation.

Additional benefits of three-dimensional ultrasound for prenatal assessment of twins.

Three-dimensional ultrasound (3DUS) may provide additional information for prenatal assessment of twins. It may improve the diagnostic confidence of dating, nuchal translucency (NT) and chorionicity assignment in twin pregnancies. The "virtual 3DUS placentoscopy" can guide selective fetoscopic laser photocoagulation (SFLP) to treat twin-twin transfusion syndrome (TTTS). Volumetric assessment of the dysmorphic acardiac twin with the Virtual Organ Computer-aided Analysis (VOCAL) software is more accurate than the conventional ultrasound measurement. Twin anemia polycythemia (TAP) sequence and selective intrauterine growth restriction (sIUGR) may be clinically monitored with 3DUS placental volume (PV) and power Doppler vascular indices. Congenital anomalies are more common in twins. Evaluation of fetal anomalies with 3DUS could assist perinatal management. The 3DUS power Doppler can provide a better understanding of true and false umbilical cord knots, which are commonly found in monoamniotic (MA) twins. Single demise in monochorionic (MC) twin pregnancies can cause severe neurologic morbidity in the surviving co-twin. Prenatal prediction of brain injury in the surviving co-twin with unremarkable neurosonographic examination is difficult. The 3DUS power Doppler may aid in prenatal detection of subtle abnormal cerebral perfusion. Prenatal assessment of conjoined twins with 3DUS is important if emergency postnatal surgical separation is anticipated. There is no significant additional advantage in using real-time 3DUS to guide prenatal interventions. Assessment of the cervix and pelvic floor during twin pregnancies is enhanced with 3DUS. Due to lack of high-quality studies, routine prenatal 3DUS in twin pregnancies needs to be balanced with risks of excessive ultrasound exposure.

English

English

Twinning and birth defects: Rachipegal heteropagal twins and acardiac twins

Twin pregnancies are associated with multiple birth defects. The increase in twinning was attributed to fertility treatments. Twins were supposed to be associated with increased risk of congenital malformations. Among the twins, monozygotic twins were associated with more malformations then dizygotic twins. Heteropagus conjoined twins are asymmetrical conjoined twins where one twin is normal and the other is anatomically incomplete and grossly defective, attached externally, with or without internal connection. Heteropagal Conjoined twins were classified based on the site of their union, and when the fusion occurs at the level of the spine it is called Rachipagal heteropagal twin. One of the most important complication of Monochorionic placenta is Twin to twin transfusion syndrome. The major major defect is in recipient twin there was lack of well developed cardiac structure, and the blood supply was maintained through placental vascular anastomosis with normal twin. This sequence was described as the twin reversed arterial perfusion ,also known as Acardiac Twinning. Here we are going to present two rare cases of Rachipegal Heteropagal twin and Acardiac twin.

Acardiac Twin: The Overlooked Diagnosis. A Recent Case Report and Review of Literature

Acardiac twin or Twin Reversed Arterial Perfusion sequence (TRAPS) is a unique and extreme complication seen in monochorionicmultifetal pregnancies. It comprises an often normal twin pumping deoxygenated arterial blood in retrograde through an acardiac, dysmorphic counterpart. Recently, a 2.6% incidence among monochorionic twins has been cited. For the pump/donor twin, mortality often exceeds 50% commonly from heart failure and prematurity. Acardiac twinning with a surviving donor twin has yet to be described in our setting. We describe a 28-year-old para 0+1 presenting in the second trimester with a twin pregnancy complicated by polyhydramnios of the donor viable twin and a non-viable recipient twin inadvertently diagnosed as a single fetal demise of a grossly malformed twin. The case was expectantly managed resulting in spontaneous preterm delivery and survival of the donor twin. TRAPS necessitates a high index of suspicion and a thorough sonographic evaluation in monochorionicmultifetal pregnancies.

Twin Reversed Arterial Perfusion (TRAP) Sequence: A Rare Case Report of an “Acardiac” Twin

A 32 year-old-pregnant female, presented to the labour and delivery department with contractions and leaking fluid. A vaginal mass was noted on digital examination. Obstetrical ultrasound demonstrated a twin pregnancy with a normal male fetus and a dysmorphic fetus with cardiac activity. Cesarean section was performed due to premature rupture of membranes (PROM) and ultrasound findings. A normal live male infant was delivered, required minimal neonatal care, and is healthy to date. A non-viable anomalous twin and the shared placenta was sent for autopsy. Pathology diagnosis was twin reversed arterial perfusion (TRAP) sequence and hemiacardius twin. TRAP sequence was a prenatal differential diagnosis but seemed unlikely with uncharacteristic findings and rare incidence. This case report emphasizes the importance of early and accurate ultrasound detection of multiple pregnancies, fetal autopsy, and the complexity of TRAP sequence.

Genome-wide interaction target profiling reveals a novel Peblr20-eRNA activation pathway to control stem cell pluripotency.

Background: Long non-coding RNAs (lncRNAs) constitute an important component of the regulatory apparatus that controls stem cell pluripotency. However, the specific mechanisms utilized by these lncRNAs in the control of pluripotency are not fully characterized.Methods: We utilized a RNA reverse transcription-associated trap sequencing (RAT-seq) approach to profile the mouse genome-wide interaction targets for lncRNAs that are screened by RNA-seq.Results: We identified Peblr20 (Pou5F1 enhancer binding lncRNA 20) as a novel lncRNA that is associated with stem cell reprogramming. Peblr20 was differentially transcribed in fibroblasts compared to induced pluripotent stem cells (iPSCs). Notably, we found that Peblr20 utilized a trans mechanism to interact with the regulatory elements of multiple stemness genes. Using gain- and loss-of-function experiments, we showed that knockdown of Peblr20 caused iPSCs to exit from pluripotency, while overexpression of Peblr20 activated endogenous Pou5F1 expression. We further showed that Peblr20 promoted pluripotent reprogramming. Mechanistically, we demonstrated that Peblr20 activated endogenous Pou5F1 by binding to the Pou5F1 enhancer in trans, recruiting TET2 demethylase and activating the enhancer-transcribed RNAs.Conclusions: Our data reveal a novel epigenetic mechanism by which a lncRNA controls the fate of stem cells by trans-regulating the Pou5F1 enhancer RNA pathway. We demonstrate the potential for leveraging lncRNA biology to enhance the generation of stem cells for regenerative medicine.

233: Prenatal ultrasound morphology and angioarchitecture of acardiac twin

Twin-reversed arterial perfusion (TRAP) sequence is characterized by paradoxical perfusion of the acardiac (A) by the pump twin (P). Ultrasound morphology (acardia vs hermicardia) and arteriovenous shunting (AVS) (single vs multiple) of A may be prognosticative for perinatal outcomes. Prospective Observational Study – Primary. Twenty-one TRAP sequence cases were evaluated. Weight ratio between A and P (A/P Wt), differences of systolic/diastolic ratio (UA ΔS/D), resistance index (UA ΔRI), and pulsatility index ratio (UA PI A/P) of the umbilical arteries between A and P were assessed. Radiofrequency ablation (RFA) was performed at 16-24 weeks of gestation. The median (min, max) gestational age at diagnosis (GA Dx) was 18 (11, 27) weeks. Acardia (n=14) and hemicardia (n=7) correlated with single (n=16) and multiple AVS (n=5), respectively. (p< 0.05) The A/P Wt, UA ΔS/D, UA ΔRI, and UA PI A/P in acardia with single AVS (n=13), acardia with multiple AVS (n=1), hemicardia with single AVS (n=3), and hemicardia with multiple AVS (n=4) were not different. (p >0.05) Seven cases were diagnosed at < 16 weeks’ (5/7 were acardia with single AVS (1/5 P died before RFA)). Their morphology and AVS remained unchanged until RFA. There were significant inversed correlations between GA Dx and intervention, and GA at delivery and birth weight. (r=-0.62--0.82, p< 0.05) The UA DSD and UA DRI inversely correlated with UA PI A/P (r=-0.71--0.88, p< 0.05), but not with A/P Wt. (p >0.05) Acardia with single AVS may have poor prognosis. Ultrasound morphology and AVS patterns of A may augment the prognostication for TRAP sequence.

Functionalization of 3‐Iodo‐N,N‐Diisopropylferrocene‐Carboxamide, a Pivotal Substrate to Open the Chemical Space to 1,3‐Disubstituted Ferrocenes

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First-trimester intervention in twin reversed arterial perfusion sequence.

To report the outcome of monochorionic twins with twin reversed arterial perfusion (TRAP) sequence following interstitial laser therapy in the first trimester. This was a retrospective cohort study of all consecutive cases of TRAP that underwent interstitial laser therapy at ≤ 14 + 3 weeks' gestation between January 2014 and April 2016. Interstitial laser treatment was performed under ultrasound guidance using a 400-nm Nd:YAG laser fiber. Hospital records were reviewed to ascertain perinatal survival and morbidity. Twelve monochorionic twin pregnancies underwent interstitial laser treatment of the umbilical artery of the acardiac fetus, at a median gestational age of 13 + 5 (interquartile range (IQR), 13 + 4 to 14 + 0) weeks. In all cases, one treatment was sufficient to achieve complete interruption of the perfusion of the acardiac twin. There were no procedure-related complications during or within 48 h after the procedure. In one (8.3%) case, intrauterine death of the pump twin occurred 2 weeks after the intervention. All other cases (91.7%) resulted in a live birth at a median gestational age of 39 + 6 (IQR, 37 + 1 to 41 + 2) weeks and with a median birth weight of 3370 (IQR, 2980-3480) g. No neonatal mortality or serious morbidity occurred. Our results support the use of interstitial laser therapy in the first trimester of pregnancy complicated by TRAP sequence, showing a live birth rate of 92%. The results of a randomized controlled trial, evaluating early vs late intervention in pregnancy with TRAP sequence, are awaited. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.