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Ramen H Chmait, Eftichia V Kontopoulos, Andrew H Chon, Lisa M Korst, Arlyn Llanes, Rubén A Quintero
OBJECTIVES: Amniopatch is a proposed treatment of iatrogenic preterm premature rupture of membranes (iPPROM). We studied characteristics associated with successful amniopatch treatment of iPPROM after fetoscopic laser surgery for twin-twin transfusion syndrome. METHODS: Patients with iPPROM within 15 days of laser surgery treated with an amniopatch were studied. Factors associated with amniopatch success (i.e. cessation of leakage with normalization of amniotic fluid volume) were tested univariately and in multivariate logistic regression models...
August 10, 2016: Journal of Maternal-fetal & Neonatal Medicine
Andrew H Chon, Gustavo H de Oliveira, Kevin V Lemley, Lisa M Korst, Ryan D Assaf, Ramen H Chmait
INTRODUCTION: Although mortality has decreased for fetuses with lower urinary tract obstruction treated with vesicoamniotic shunt (VAS) placement, survivors remain at risk for long-term renal impairment. We tested the association of fetal serum β2-microglobulin (fsβ2M) with postnatal renal function in these patients, hypothesizing that fsβ2M may predict such renal impairment. MATERIALS AND METHODS: fsβ2M was obtained in patients undergoing VAS placement. The primary outcome was renal function at 3-12 months of life, as assessed by a pediatric nephrologist using medical records...
September 8, 2016: Fetal Diagnosis and Therapy
Jennifer R King, Charlotte L Conturie, Joseph G Ouzounian, Lisa M Korst, Arlyn Llanes, Ramen H Chmait
INTRODUCTION: Umbilical cord occlusion (UCO) utilizing laser photocoagulation is often not considered an option for selective termination after 20 weeks of gestation due to reported limitations of the procedure because of umbilical cord size. We compared outcomes after laser umbilical cord occlusion (L-UCO) before and after 20 weeks of gestation. MATERIALS AND METHODS: We examined all patients with monochorionic- diamniotic twins and higher-order multiples (monoamniotic excluded) that underwent L-UCO at our facility between 2006 and 2014...
August 31, 2016: Fetal Diagnosis and Therapy
D A L Pedreira, E A Reece, R H Chmait, E V Kontopoulos, R A Quintero
No abstract text is available yet for this article.
August 2016: Ultrasound in Obstetrics & Gynecology
Rubén A Quintero, Eftichia Kontopoulos, Ramen H Chmait
OBJECTIVE: Laser ablation of all placental vascular anastomoses is the optimal treatment for twin-twin transfusion syndrome (TTTS). However, two important controversies are apparent in the literature: (a) a gap between concept and performance, and (b) controversy regarding whether all the anastomoses can be identified endoscopically and whether blind lasering of healthy placenta is justified. The purpose of this article is: (a) to address the potential source of the gap between concept and performance by analyzing the fundamental steps needed to successfully accomplish the surgery, and (b) to discuss the resulting competency benchmarks reported with the different surgical techniques...
June 2016: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
Eftichia Kontopoulos, Ramen H Chmait, Ruben A Quintero
OBJECTIVE: The purpose of this article is to review the definition of twin-to-twin transfusion syndrome (TTTS) and the sonographic diagnostic assessment of these cases prior to therapy. MATERIALS AND METHODS: The article addresses the terminology used to refer to the condition and describes the systematic ultrasound assessment of the condition, including the ultrasound diagnosis, the staging of the disease, cervical assessment and pre-operative mapping. RESULTS: From an etymologic and medical point of view, the term 'fetofetal transfusion' is more appropriate than 'TTTS'...
June 2016: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
Li Zhou, Adriana Nicholson Vest, Raymond A Peck, Jonathan P Sredl, Xuechen Huang, Yaniv Bar-Cohen, Michael J Silka, Jay D Pruetz, Ramen H Chmait, Gerald E Loeb
This paper discusses the technical and safety requirements for cardiac pacing of a human fetus with heart failure and hydrops fetalis secondary to complete heart block. Engineering strategies to meet specific technical requirements were integrated into a systematic design and implementation consisting of a novel fetal micropacemaker, a percutaneous implantation system, and a sterile package that enables device storage and recharging maintenance in a clinical setting. We further analyzed observed problems on myocardial fixation and pacing lead fatigue previously reported in earlier preclinical trials...
March 28, 2016: Medical & Biological Engineering & Computing
Jodie K Votava-Smith, Pisit Pitukcheewanont, Linda M Randolph, Ramen H Chmait
Recipients of the twin-twin transfusion syndrome (TTTS) often develop cardiac manifestations, but arterial calcification has rarely been reported. Generalized arterial calcification of infancy (GACI) is a genetic disorder with high infantile mortality. We report the case of a TTTS recipient with moderate cardiomyopathy at diagnosis who developed progressive calcification of the pulmonary arteries and aorta after successful in utero laser therapy. Postnatally, both twins were diagnosed with a heterozygous ABCC6 gene mutation associated with GACI...
March 17, 2016: Fetal Diagnosis and Therapy
Kristi R Van Winden, Rubén A Quintero, Eftichia V Kontopoulos, Lisa M Korst, Arlyn Llanes, Ramen H Chmait
INTRODUCTION: We examined placental weight characteristics associated with donor selective intrauterine growth restriction (SIUGR) among patients with twin-twin transfusion syndrome (TTTS) who underwent laser surgery. MATERIALS AND METHODS: Fresh placental specimens were studied. Pregnancies with higher-order multiples, fetal demise, or disrupted or nonsubmitted placental specimens were excluded. Placental characteristics prospectively collected included total placental weight, individual placental weight, and placental share...
2016: Fetal Diagnosis and Therapy
Lewis D Pennington, Michael D Bartberger, Michael D Croghan, Kristin L Andrews, Kate S Ashton, Matthew P Bourbeau, Jie Chen, Samer Chmait, Rod Cupples, Christopher Fotsch, Joan Helmering, Fang-Tsao Hong, Randall W Hungate, Steven R Jordan, Ke Kong, Longbin Liu, Klaus Michelsen, Carolyn Moyer, Nobuko Nishimura, Mark H Norman, Andreas Reichelt, Aaron C Siegmund, Glenn Sivits, Seifu Tadesse, Christopher M Tegley, Gwyneth Van, Kevin C Yang, Guomin Yao, Jiandong Zhang, David J Lloyd, Clarence Hale, David J St Jean
The HTS-based discovery and structure-guided optimization of a novel series of GKRP-selective GK-GKRP disrupters are revealed. Diarylmethanesulfonamide hit 6 (hGK-hGKRP IC50 = 1.2 μM) was optimized to lead compound 32 (AMG-0696; hGK-hGKRP IC50 = 0.0038 μM). A stabilizing interaction between a nitrogen atom lone pair and an aromatic sulfur system (nN → σ*S-X) in 32 was exploited to conformationally constrain a biaryl linkage and allow contact with key residues in GKRP. Lead compound 32 was shown to induce GK translocation from the nucleus to the cytoplasm in rats (IHC score = 0; 10 mg/kg po, 6 h) and blood glucose reduction in mice (POC = -45%; 100 mg/kg po, 3 h)...
December 24, 2015: Journal of Medicinal Chemistry
Ramen H Chmait, Andrew H Chon, Sheree M Schrager, Arlyn Llanes, Anita Hamilton, Douglas L Vanderbilt
OBJECTIVE: The cerebroplacental ratio (CPR) is a semi-quantitative marker for fetal brain-sparing. Our purpose was to measure the CPR at the time of treatment with selective laser photocoagulation of communicating vessels in gestations with twin-twin transfusion syndrome (TTTS) to test its association with neurological outcomes at approximately 2 years. METHODS: One-hundred children treated for TTTS with laser surgery underwent neurodevelopmental assessment at age 2 years (within 6 weeks) via the Battelle Developmental Inventory 2nd Edition (BDI-2)...
January 2016: Prenatal Diagnosis
R Agarwal, M E Thornton, A N Fonteh, M G Harrington, R H Chmait, B H Grubbs
OBJECTIVES: There is growing evidence of ongoing, in utero neurological damage in fetuses with myelomeningocele (MMC). Phospholipase A2 (PLA2) has known neurotoxic properties and is predominantly present in its secretory isoform (sPLA2) in meconium, the passage of which is increased in MMC fetuses. The objective of this study was to determine if amniotic fluid (AF) levels of PLA2 are elevated in a rat model of MMC. METHODS: Timed pregnant Sprague-Dawley rats were gavage fed 60 mg/kg/bodyweight retinoic acid (RA) in olive oil at embryonic day 10 (E10)...
September 2016: Journal of Maternal-fetal & Neonatal Medicine
Denise A L Pedreira, Nelci Zanon, Koshiro Nishikuni, Renato A Moreira de Sá, Gregório L Acacio, Ramen H Chmait, Eftichia V Kontopoulos, Rubén A Quintero
BACKGROUND: A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of open spina bifida (OSB) via open fetal surgery was associated with improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity. OBJECTIVE: We sought to report the final results of our phase I trial (Cirurgia Endoscópica para Correção Antenatal da Meningomielocele [CECAM]) on the feasibility, safety, potential benefits, and side effects of the fetoscopic treatment of OSB using our unique surgical technique...
January 2016: American Journal of Obstetrics and Gynecology
Ramen H Chmait, Andrew H Chon, Sheree M Schrager, Eftichia V Kontopoulos, Rubén A Quintero, Douglas L Vanderbilt
OBJECTIVE: To assess fetal growth after laser surgery for TTTS at the time of prenatal diagnosis, birth, and at 2years of age. DESIGN/METHODS: Growth data were collected from surviving children treated between 2007 and 2010 as part of a study to assess neurodevelopment at 24months (±6weeks) corrected age. Fetal weights were obtained via ultrasound using Hadlock's formula at the time of preoperative assessment for laser surgery. Birth weights were recorded by the staff at the delivering institutions...
December 2015: Early Human Development
Anita J Moon-Grady, Shaine A Morris, Michael Belfort, Ramen Chmait, Joanna Dangel, Roland Devlieger, Stephen Emery, Michele Frommelt, Alberto Galindo, Sarah Gelehrter, Ulrich Gembruch, Sofia Grinenco, Mounira Habli, Ulrike Herberg, Edgar Jaeggi, Mark Kilby, Eftichia Kontopoulos, Pablo Marantz, Owen Miller, Lucas Otaño, Carlos Pedra, Simone Pedra, Jay Pruetz, Ruben Quintero, Greg Ryan, Gurleen Sharland, John Simpson, Emanuel Vlastos, Wayne Tworetzky, Louise Wilkins-Haug, Dick Oepkes
BACKGROUND: Invasive fetal cardiac intervention (FCI) has been reported in single-institution series, promoting technical and physiologic success. OBJECTIVES: This study describes the creation of an international registry of cases presenting for FCI, intended to compile technical and outcome data from a multicenter cohort. METHODS: For this initial analysis, the entire database of the International Fetal Cardiac Intervention Registry (IFCIR) was queried for details of diagnoses, procedures, and outcomes...
July 28, 2015: Journal of the American College of Cardiology
Ramen H Chmait, Eftichia V Kontopoulos, Marc Jackson, Janet Horenstein, Ilan Timor-Tritsch, Rubén A Quintero
Selective reduction (SR) via intravascular potassium chloride (KCl) injection is contraindicated in monochorionic twins due to the presence of placental vascular communications, which may serve as a conduit for inter-twin passage of KCl or allow exsanguination of the living twin into the demised twin. After successful selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS), the twins' circulatory systems are rendered independent. Theoretically, intravascular KCl injection into one twin after successful SLPCV should not result in passage of the feticidal agent nor cause hemodynamic alterations in the co-twin...
2016: Fetal Diagnosis and Therapy
Jay D Pruetz, Sheree M Schrager, Tiffany V Wang, Arlyn Llanes, Ramen H Chmait, Douglas L Vanderbilt
OBJECTIVE: Twin survivors of twin-twin transfusion syndrome (TTTS) may be at risk for early onset of cardiovascular disease. The aim of this study was to determine prevalence and risk factors for elevated blood pressure (BP) among children treated with selective laser photocoagulation of communicating vessels. STUDY DESIGN: Data were prospectively collected from surviving children treated for TTTS with laser surgery from 2008 through 2010. Systolic BP (SBP) and diastolic BP (DBP) were obtained from 91 child survivors at age 24 months (±6 weeks) and evaluated based on age, sex, and height percentile...
September 2015: American Journal of Obstetrics and Gynecology
Nuria A Tamayo, Mark H Norman, Michael D Bartberger, Fang-Tsao Hong, Yunxin Bo, Longbin Liu, Nobuko Nishimura, Kevin C Yang, Seifu Tadesse, Christopher Fotsch, Jie Chen, Samer Chmait, Rod Cupples, Clarence Hale, Steven R Jordan, David J Lloyd, Glenn Sivits, Gwyneth Van, David J St Jean
The glucokinase-glucokinase regulatory protein (GK-GKRP) complex plays an important role in controlling glucose homeostasis in the liver. We have recently disclosed a series of arylpiperazines as in vitro and in vivo disruptors of the GK-GKRP complex with efficacy in rodent models of type 2 diabetes mellitus (T2DM). Herein, we describe a new class of aryl sulfones as disruptors of the GK-GKRP complex, where the central piperazine scaffold has been replaced by an aromatic group. Conformational analysis and exploration of the structure-activity relationships of this new class of compounds led to the identification of potent GK-GKRP disruptors...
June 11, 2015: Journal of Medicinal Chemistry
Shivani Patel, Rubén A Quintero, Eftichia V Kontopoulos, Lisa M Korst, Arlyn Llanes, Ramen H Chmait
OBJECTIVES: In twin-twin transfusion syndrome (TTTS), persistent absent or reversed end-diastolic flow in the umbilical artery is a rare finding in the recipient twin, and the clinical implications of this finding are not well characterized. We sought to study the clinical importance of abnormal umbilical artery Doppler waveforms in recipient twins and determine the perinatal survival of these twins after laser surgery. METHODS: A retrospective study of patients with TTTS treated with laser surgery between 2006 and 2012 was conducted...
May 2015: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
Yaniv Bar-Cohen, Gerald E Loeb, Jay D Pruetz, Michael J Silka, Catalina Guerra, Adriana N Vest, Li Zhou, Ramen H Chmait
No abstract text is available yet for this article.
July 2015: Heart Rhythm: the Official Journal of the Heart Rhythm Society
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