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Background Direct orthodontic bracket bonding consumes significantly more chairside time in comparison to indirect bonding. The primary drawback of indirect bonding is incomplete penetration of the curing light through transfer trays, leading to bracket bond failure. The primary objective in a clinical setting is to minimize the chairside time. This technique of indirect bonding reduces chairside time, is economical, utilizes minimum armamentarium, and provides adequate light penetration and accuracy. Technique Impressions were made, casts were poured and marked for the desired bracket position as per MBT prescription. Bonding agent was used to stabilize the brackets on the working model. A 3D printing pen and polylactic acid (PLA) filament were used to fabricate transfer trays for indirect bonding. The tray with brackets held in the desired position was transferred to the oral cavity and cured. Conclusions Fabrication of complete or partial transfer trays for indirect bonding using PLA with the help of a 3D printing pen is a precise, easy-to-use, economical, and reliable method that reduces chairside time. Clinical significance When compared with other methods of indirect bonding, the PLA transfer tray made with a 3D printing pen was easy to fabricate with brackets held firmly in the tray for a precisely desired position. The tray fit snugly and permitted light curing of composite from all surfaces of brackets and removal of flash. This method significantly reduced the overall time of the indirect bonding procedure.

Endothelial dysfunction is a prominent feature of preeclampsia, a hypertensive disorder of pregnancy, and contributes to multiple symptoms characteristic of the syndrome. A myriad of growth factors and cytokines are dysregulated in preeclampsia as compared to normal pregnancy, however, a complete appreciation of the effect of changing concentrations of these factors on endothelial function is lacking. In this study, we evaluate the effect of a variety of growth factors and cytokines on Ca2+ signaling and monolayer integrity. We report that VEGF165, TNFα, EGF, and IL-1β either improve or inhibit Ca2+ signaling depending on dose, whereas TNFα and IL-1β reduce monolayer integrity and bFGF increases monolayer integrity. Additionally, to model the effects of combinations of growth factors and cytokines, we screened for Ca2+ signaling changes in response to 16 dose combinations of VEGF165 and TNFα together. This revealed an optimal combination capable of supporting pregnancy-adapted Ca2+ signaling, and that changes in either VEGF165 or TNFα dose would result in a shift toward suppressed function. This study shows in detail how growth factor or cytokine concentration effects endothelial cell function. Such data can be used to model how changing growth factor and cytokine levels in normal pregnancy may contribute to healthy endothelial function and in preeclampsia may promote endothelial dysfunction. The results of VEGF165 and TNFα combination treatments suggest that more complex growth factor and cytokine combination modeling may be important in order to more accurately understand the effects of circulating factors on the endothelial function.

Background 3D chemical shift-encoded (CSE)-MRI techniques enable assessment of ferumoxytol concentration but are unreliable in the presence of motion. Purpose To evaluate a motion-robust 2D-sequential CSE-MRI for R2* and B0 mapping in ferumoxytol-enhanced MRI of the placenta. Study type Prospective. Animal model Pregnant rhesus macaques. Field strength/sequence 3.0T/CSE-MRI. Assessment 2D-sequential CSE-MRI was compared with 3D respiratory-gated CSE-MRI in placental imaging of 11 anesthetized animals at multiple timepoints before and after ferumoxytol administration, and in ferumoxytol phantoms (0 μg/mL-440 μg/mL). Motion artifacts of CSE-MRI in 10 pregnant women without ferumoxytol administration were assessed retrospectively by three blinded readers (4-point Likert scale). The repeatability of CSE-MRI in seven pregnant women was also prospectively studied. Statistical tests Placental R2* and boundary B0 field measurements (ΔB0) were compared between 2D-sequential and 3D respiratory-gated CSE-MRI using linear regression and Bland-Altman analysis. Results In phantoms, a slope of 0.94 (r2 = 0.99, concordance correlation coefficient ρ = 0.99), and bias of -4.8 s-1 (limit of agreement [LOA], -41.4 s-1 , +31.8 s-1 ) in R2*, and a slope of 1.07 (r2 = 1.00, ρ = 0.99) and bias of 11.4 Hz (LOA -12.0 Hz, +34.8 Hz) in ΔB0 were obtained in 2D CSE-MRI compared with 3D CSE-MRI for reference R2* ≤390 s-1 . In animals, a slope of 0.92 (r2 = 0.97, ρ = 0.98) and bias of -2.2 s-1 (LOA -55.6 s-1 , +51.3 s-1 ) in R2*, and a slope of 1.05 (r2 = 0.95, ρ = 0.97) and bias of 0.4 Hz (LOA -9.0 Hz, +9.7 Hz) in ΔB0 were obtained. In humans, motion-impaired R2* maps in 3D CSE-MRI (Reader 1: 1.8 ± 0.6, Reader 2: 1.3 ± 0.7, Reader 3: 1.9 ± 0.6), while 2D CSE-MRI was motion-free (Reader 1: 2.9 ± 0.3, Reader 2: 3.0 ± 0, Reader 3: 3.0 ± 0). A mean difference of 0.66 s-1 and coefficient of repeatability of 9.48 s-1 for placental R2* were observed in the repeated 2D CSE-MRI. Data conclusion 2D-sequential CSE-MRI provides accurate R2* and B0 measurements in ferumoxytol-enhanced placental MRI of animals in the presence of respiratory motion, and motion-robustness in human placental imaging. Level of evidence 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:580-592.

Acute myocardial infarction (AMI) resulting in cardiogenic shock continues to be a substantial source of morbidity and mortality despite advances in recognition and treatment. Prior to the advent of percutaneous and more durable left ventricular support devices, prompt revascularization with the addition of vasopressors and inotropes were the standard of care in the management of this critical population. Recent published studies have shown that in addition to prompt revascularization, unloading of the left ventricle with the placement of the Impella percutaneous axillary flow pump can lead to improvement in mortality. Parameters such as the cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi), obtained through pulmonary artery catheterization, can help ascertain the productivity of right and left ventricular function. Utilization of these parameters can provide the information necessary to escalate support to the right ventricle with the insertion of an Impella RP or the left ventricle with the insertion of larger devices, which provide more forward flow. Herein, we present a case of AMI complicated by cardiogenic shock resulting in biventricular failure treated with the percutaneous insertion of an Impella RP and Impella 5.0 utilizing invasive markers of left and right ventricular function to guide the management and escalation of care.

Although DMEK offers speedier recovery, improved visual outcomes, and lower rejection risk compared to DSAEK, the trade-off is an incrementally higher rate of rebubbling. Unlike DSAEK grafts, DMEK tissue rarely displays complete graft separation or severe decentration, which is why injection of an air bubble alone – without any further surgical manipulation – is enough to eliminate fluid from the graft-host interface and achieve complete graft attachment.

Selective replacement of the corneal endothelium was introduced as a theoretical concept and first performed in humans with graft-retaining sutures in the 1950s by Drs. Jose Barraquer and Charles Tillet. In the late 1990s and early 2000s, deep lamellar endothelial keratoplasty (DLEK), which involved painstaking manual dissection of the recipient and donor followed by a graft-supporting air bubble tamponade, was introduced by Drs. Gerrit Melles and Mark Terry. DLEK evolved into Descemet’s stripping endothelial keratoplasty (DSEK) with introduction of the “descemetorhexis” by Dr. Melles to simplify recipient preparation, and further evolved into descemet stripping automated endothelial keratoplasty (DSAEK) with Dr. Mark Gorovoy’s introduction of the microkeratome to speed donor lenticule preparation. By 2011, DSAEK became the standard of care for endothelial disease and surpassed penetrating keratoplasty as the most commonly performed corneal transplant surgery in the United States.

Background For patients that face barriers to filling their prescriptions, the availability of medication access services at their site of care can mean the difference between receiving prescribed drug therapy, and undue interruptions in care. Hospitals often provide medication access services that are not reimbursed by payers; however, they can be challenging to sustain. The 340B Drug Pricing Program allows covered entities to generate savings through discounted pricing for certain outpatient medications, which can then be used to provide more comprehensive services, including medication access services. Objective To characterize medication access services provided at hospitals that participate in the 340B Drug Pricing Program compared to hospitals that do not participate in the 340B Program. Methods Primary questionnaire response data was collected from a national sample of Directors of Pharmacy at non-federal acute care hospitals from March 2019 to May 2019. American Hospital Association Data Viewer was used to collect demographic information on 1,531 hospitals. Hospitals were excluded if they had 199 beds or fewer, did not have a unique Medicare provider ID, were federally owned, were located outside the continental U.S., or were non-acute care hospitals that served niche patient populations. This study utilized a proportional stratified sampling strategy to administer an electronic questionnaire to 340B and non-340B hospitals to assess the number and type of medication access service offerings. A final randomized sample of 500 hospitals were administered the questionnaire, and data was collected through recorded responses in Qualtrics software. Results 340B hospitals provided a significantly higher average number of medication access services compared to non-340B hospitals (6.20 vs. 3.91, p = 0.0001), adjusted for differences in hospital size and ownership type. For all nine medication access services that were assessed, a higher percentage of 340B hospitals reported providing the service compared to non-340B hospitals. This difference was statistically significant for six out of nine programs assessed. Conclusions 340B hospitals provided more medication access services, on average, than comparably sized non-340B hospitals, suggesting that hospitals participating in the 340B Drug Pricing Program may be better positioned to create and administer programs that support medication access services.

Background Pregnancy complications are often associated with poor uteroplacental vascular adaptation and standard diagnostics are unable to reliably quantify flow in all uteroplacental vessels and have poor sensitivity early in gestation. Purpose To investigate the feasibility of using 4D flow MRI to assess total uteroplacental blood flow in pregnant rhesus macaques as a precursor to human studies. Study type Retrospective feasibility study. Animal model Fifteen healthy, pregnant rhesus macaques ranging from the 1st trimester to 3rd trimester of gestation. Field strength/sequence Abdominal 4D flow MRI was performed on a 3.0T scanner with a radially undersampled phase contrast (PC) sequence. Reference ferumoxytol-enhanced angiograms were acquired with a 3D ultrashort echo time sequence with a center-out radial trajectory. Assessment Repeatability of flow measurements was assessed with scans performed same-day and on consecutive days in the uterine arteries and ovarian veins. In-flow was compared against out-flow in the uterus, umbilical cord, and fetal heart with a conservation of mass analysis. Conspicuity of uteroplacental vessels was qualitatively compared between PC angiograms derived from 4D flow data and ferumoxytol-enhanced angiograms. Statistical tests Bland-Altman analysis was used to quantify same-day and consecutive-day repeatability. Results Same-day flow measurements showed an average difference between scans of 13% in both the uterine arteries and ovarian veins, while consecutive-day measurements showed average differences of 22% and 24%, respectively. Comparisons of in-flow and out-flow showed average differences of 15% in the uterus, 8% in fetal heart, and 15% in the umbilical cord. PC angiograms showed similar depiction of main uteroplacental vessels as high-resolution, ferumoxytol-enhanced angiograms. Data conclusion 4D flow MRI could be used in the rhesus macaque for repeatable flow measurements in the uteroplacental and fetal vasculature, setting the stage for future human studies. Level of evidence 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:534-545.

Objective The aim of the study was to assess the clinical outcome of Abluminus DES in patients with small vessels. Background Percutaneous coronary intervention (PCI) of small coronary vessel (≤2.75 mm) associated with more chances of restenosis and repeat revascularization even when drug eluting stent employed. Methods A total of 2,500 patients enrolled in en-ABL e-registry which is a prospective, multicentre observational post market registry. Out of 2,500 patients, 1,253 patients had small vessel (SV, ≤2.75 mm) while 1,247 had large vessel (LV, >3mm) disease. The primary endpoint was major adverse cardiac events (MACE) which is composite of cardiac death, target vessel myocardial infraction (TV-MI) and target lesion/vessel revascularization (TLR) at 1 year follow up. The secondary endpoint were stent thrombosis and MACE up to 2 years. Results Baseline characteristics were well matched in both groups. In the SV group had higher prevalence of diabetes as compared to large vessel 43.0% vs 25.7%. Total 1,400 lesions treated with 1,612 Abluminus DES and 1,569 lesions treated with 1,675 Abluminus DES in SV and LV groups respectively. The mean diameter of stent was 2.61±0.23 and 3.3±0.3 mm in SV and LV groups respectively. There was a significant difference in MACE in treatment groups (3.7% vs. 1.4%, p=0.004 respectively) at 1 year. No significant differences were observed between SV and LV groups in terms of death/myocardial infarction or stent thrombosis. There were increment of only one TLR and no stent thrombosis reported at 2-year follow-up. Conclusion This result suggests the efficacy and safety of novel Abluminus DES in small vessel disease.

Objective To measure pharmacokinetics of hydroxyprogesterone caproate (OHPC) and its major metabolites throughout pregnancy. Study Design Thirty women were prescribed OHPC for recurrent preterm birth prevention. Three cohorts of subjects had blood drawn for 7 consecutive days at one of three times: cohort 1 (n = 6) after the first dose (weeks 16–20), cohort 2 (n = 8) between weeks 24 and 28, and cohort 3 (n = 16) between weeks 32 and 36. We measured serum trough levels after week 1 in cohort 1 or after two consecutive weekly doses in cohorts 2 and 3. In 10 subjects, we estimated OHPC terminal half-life at 28 days after their last dose. Results In cohorts 1, 2, and 3, the areas under curve (ng × h/mL) for OHPC were 571.4 ± 195.2, 1,269.6 ± 285.0, and 1,268.0 ± 511.6, respectively. Maximum OHPC levels (ng/mL) were 5.0 ± 1.5, 12.5 ± 3.9, and 12.3 ± 4.9, respectively. The areas under the curve for mono-hydroxylated metabolites were 208.5 ± 92.4, 157.1 ± 64.6, and 211.2 ± 113.1, and maximum concentrations were 1.9 ± 0.7, 1.5 ± 0.7, and 1.8 ± 1.0, respectively. Di-hydroxylated metabolite levels were significantly lower than mono-hydroxylated metabolites. Estimated terminal half-life of OHPC was 16.3 ± 3.6 days and 19.7 ± 6.2 days for the mono-hydroxylated metabolites. Conclusion After the first injection, OHPC maximum serum level was approximately half steady-state level. Measurable metabolites of unknown activity were detected.

Craniofacial trauma is often associated with orbital and ocular injuries. We report a case of a 21-year-old male with motor vehicular accident, orbital roof blow-in fracture, cerebrospinal fluid (CSF) leak, and left sided globe luxation with corneal abrasion and complete conjunctival denuding. The patient was managed by a multispeciality team and the eyeball was protected by amniotic membrane graft (AMG) biological dressing with novel use of inverted sterile metallic bowl as mechanical protection till the patient stabilized. During surgery, eyeball was reposited and ocular surface was reconstructed using amniotic membrane and symblepharon ring. Surgical correction and plating of the facial fractures and dural repair with autologus tensor fascia lata was done. Post surgery ocular surface was intact, ocular motility was well preserved and the globe was prephthisical. Traumatic eyeball luxation is a rare, but dramatic presentation which may occur in a blow in fracture when the intra orbital volume reduces and expels the eye ball out of the socket. This may be associated with extra ocular muscle rupture or optic nerve avulsion. The visual prognosis is nil in majority cases. However, the management is targeted towards globe preservation in view of psychological benefit and ease of cosmetic or prosthetic rehabilitation. Knowing the mechanism of luxation helps to plan the management. A stepwise approach for globe salvage is recommended. Team efforts to take care of various morbidities with special steps to safeguard the eye help to optimize outcomes. Keywords: Traumatic eyeball luxation, Blow in orbital fractures, Amniotic membrane graft for ocular surface, Globe reposition

OBJECTIVES: To assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model. MATERIALS AND METHODS: In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student’s t-test. RESULTS: In fetuses, a slope of 0.3s(−1)/day (P = 0.008), 0.00ppm/day (P = 0.699) and −0.2s(−1)/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. CONCLUSIONS: This work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.

Ferumoxytol is a superparamagnetic iron oxide nanoparticle (SPION) used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through ferumoxytol-induced image contrast changes. Therefore, ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after ferumoxytol administration. In initial developmental studies, pregnant rhesus macaques were imaged with and without ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of ferumoxytol on the maternal-fetal interface, fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ∼100 gd (gestational day) underwent MRI before and after ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 3-4 days following ferumoxytol administration. A control group that did not receive ferumoxytol or MRI was used for comparison. Iron levels in fetal and maternal-fetal interface tissues did not vary between groups. There was no significant difference in tissue histopathology with or without exposure to ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of ferumoxytol and MRI in pregnant rhesus macaques will not introduce a detectable risk to the mother or fetus at the time of imaging or up to one year following normal vaginal delivery.Summary SentenceFerumoxytol magnetic resonance imaging for non-invasive pregnancy monitoring of the rhesus macaque does not impact histopathology or iron content of the maternal-fetal interface.

The drug-coated balloon is a future treatment device which leaves nothing behind. It delivers the drug in a very short time and provides long-term release of the drug to treat posttreatment shortcomings. Currently paclitaxel and sirolimus are the only choices for drug-coated balloons. Preclinical study findings on paclitaxel are mixed and depend on various factors such as the drug carrier, balloon surface, drug size, coating method etc. The sirolimus-coated balloon is an emerging device and based on certain preclinical reports, it has generated new hope for safe and effective drug delivery.

PURPOSE: To investigate the correspondence between arterial spin labeling (ASL) flow-sensitive alternating inversion recovery (FAIR) and ferumoxytol dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of placental intervillous perfusion. METHODS: Ten pregnant macaques in late 2(nd) trimester were imaged at 3T using a 2D ASL FAIR, with and without outer volume saturation (OVS) pulses used to control the bolus width, and a 3D ferumoxytol DCE MRI acquisition. ASL tagged/control pairs were averaged, subtracted, and normalized to create perfusion ratio maps. Contrast arrival time and uptake slope were estimated by fitting DCE data to a sigmoid function. Macaques (N=4) received interleukin-1β to induce inflammation and disrupt perfusion. RESULTS: FAIR tag modification with OVS reduced median ASL ratio percentage compared to conventional FAIR (0.64±1.42% vs. 0.71±2.00%;p0.05). CONCLUSION: ASL FAIR and ferumoxytol DCE MRI are feasible methods to detect early blood delivery to the macaque placenta. OVS reduced high macrovascular ASL signal. Interleukin-1β exposure did not alter placental intervillous perfusion. An endogenous-labeling perfusion technique is limited due to extended transit times for flow within the placenta beyond the immediate vicinity of the maternal spiral arteries.

Objective The American Institute of Ultrasound in Medicine has described what constitutes a detailed fetal anatomic examination but what comprises an appropriate physician training program has not been described. The purpose of this paper is to describe a highly-structured program developed by our center to train maternal-fetal medicine fellows in a systematic approach to fetal diagnostic imaging. Study Design We describe this approach in three phases. Phase I: Development of Skills as a Perinatal Sonographer, Phase II: Mentored Evolution to a Perinatal Sonologist and Phase III: Supervised Independent Practice as Consultant-in-training. Results This curriculum was implemented in 2006. Of the eight maternal-fetal medicine fellows who completed this program, 100% were capable of following this curriculum and 100% felt comfortable performing and interpreting detailed sonograms including sonograms with significant and uncommon anomalies. Qualitative feedback was also positive. Finally, this structured approach resulted in an increase in the average total number of sonograms interpreted. Conclusion Our curriculum, by following the explicit guidelines and expectations set out by the American Institute of Ultrasound in Medicine and the American Board of Obstetrics and Gynecology for practicing maternal-fetal medicine fellowship graduates, provides an opportunity to explore national standardization for this component of training.

Cardiopulmonary bypass, the extreme of non-obstetric surgery during pregnancy, presents unique challenges to minimize maternal and fetal risk. We present our experience with a woman who was diagnosed with a left atrial myxoma following an ischemic cerebrovascular accident. We discuss clinical management specific to cardiopulmonary bypass during pregnancy and delivery in the context of a multidisciplinary team approach. We recommend using intermittent Doppler ultrasound as a non-invasive real-time assessment of uteroplacental perfusion during non-obstetric surgery in pregnancy. Monitoring of perfusion facilitates active feedback for appropriate in utero resuscitation in these cases.

Patients with diabetes mellitus (DM) have poorer outcomes after percutaneous coronary intervention than those without diabetes. We evaluate the 2-year safety and efficacy profile of the Abluminus DES+ in patients with diabetes within the population enrolled in the large multicenter en-ABL e-registry

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN71416914.

Background The aim of the Nanolute registry was to observe the clinical performance of a novel sirolimus coated balloon (SCB) (Concept Medical Research Private Limited, India) for the treatment of coronary de-novo and restenotic lesions. Methods All patients treated with SCB between July 2012 and September 2015 were enrolled at Indian centres and clinically followed for 1, 3, 6 and 12 months post-procedure. Primary endpoints were procedural success and device-oriented adverse cardiac events (DOCE) at 12 months. DOCE were defined as a composite of cardiac death, target lesion revascularization (TLR) and target vessel-myocardial infarction. Results A total of 394 SCB were used in 332 patients to treat 356 lesions. In-stent restenosis and small coronary vessel disease occurred in 46% and 43% of the patients respectively. Mean balloon length and diameter (average ± SD) were 21.83 ± 6.70 mm and 2.69 ± 0.45 mm respectively. All patients with 1 year follow-up were included. Overall DOCE rate was 4.2% (n = 14) which included death 0.3% (n = 1), TLR 3.6% (n = 12) and myocardial infarction 0.3% (n = 1). Conclusion The Nanolute prospective registry, is the first clinical evidence of the safety and feasibility of this type of SCB, both in patients with in-stent restenosis or de novo lesions.

Fetal malformations of the central nervous system are among the most common major birth defects encounter during prenatal ultrasound screening. Patients with fetal intracranial findings require further work-up for improving the accuracy of the sonographic diagnosis. We developed and advanced fetal neurosonography and related services to improve clinical care and to positively impact the fetal outcome. Currently, dedicated neurosonography in the prenatal period is not routinely offered across all prenatal diagnostic centers. We propose that dedicated neurosonography done in advanced prenatal diagnostic centers improves fetal outcomes. This is directly related to proper counseling, pediatric and neonatal involvement during the prenatal period. We present here our model of dedicated neurosonography adapted to our center in the last 4 years to improve diagnosis and better understand fetal CNS pathology. With commitment of resources and coordination of services, this model is easy to implement and benefits not only parents and babies but also provides the maternal fetal medicine fellows advanced training in fetal neurosonography.

The uterine vasculature undergoes marked changes during pregnancy in order to provide the necessary increase in blood flow to support growth and nutrition of the uterus, placenta, and developing fetus. Pregnancy-associated uterine vascular transformations are orchestrated by a complex array of endocrine and cellular mechanisms to bring about structural modifications at the maternal-fetal interface, which collectively lead to development of the uteroplacental circulation. Understanding intrinsic uterine vascular remodeling in pregnancy is essential for understanding the physiologic and pathophysiologic regulation of maternal uterine blood flow. Aberrations of uterine vascular remodeling are potentially involved in the etiology of several pregnancy disorders, for example, preeclampsia, fetal growth restriction, and preterm labor; therefore, it is essential for subspecialist clinicians and investigators interested in reproductive physiology to fully understand the establishment of uteroplacental circulation. The foundational literature in this area is extensive; thus, a succinct review is likely to be a useful resource. Herein, we present and discuss a historical perspective on uterine vascular anatomy, maternal vascular growth associated with decidualization, trophoblast invasion, intervillous circulation, aberrations in uterine vascular modeling, and the clinical implications of improper development of the uteroplacental circulation.

In-stent restenosis is associated with high recurrences after implantation of a DES. The drug-coated balloon is a novel approach to treat in-stent restenosis characterized by the absence of an additional metal scaffold at lesion site. The aim of this study is to assess the safety and efficacy of

Plateaued rate of decline in neonatal mortality rate is one of the major obstacles in achieving Millennium Development Goal 4 especially in developing countries. Even in India, nationwide interventions targeting safe mother and newborn care have not yielded the desired impact, indicating the necessity to combat neonatal mortality rate at population specific level. The objective of this study is to identify the newborn care practices and beliefs, analyze their harmful or beneficial characteristics, describe the deviations from the essential newborn care practices during hospital/home delivery, explain barriers to care seeking and identify areas of potential resistance for behavior change; and utilize study findings to tailor-make cost-effective essential newborn care package. The study uses qualitative data from in-depth interview of mothers who had experienced neonatal death and key-informant interviews with healthcare personnel and birth attendants. 33 cases were randomly selected from the registered neonatal deaths across Bharuch district of Gujarat, India. Key finding of this study is less prevalent practice of essential newborn care among all cases irrespective of place of delivery and the health-care personnel facilitating delivery. Habitual traditional/tribal newborn care methods challenge the practice of prescribed essential newborn care. Clustering of deaths in few households added significantly to the existing burden of neonatal deaths, attributed to superstition “Ratewa” by tribal. Study has concluded that the introduction and implementation of essential newborn care at hospital and community/ household level are the need of the hour. Quality home based neonatal care through cost effective interventions is deemed necessary where accessing institutional care is not possible in the immediate term. Community health workers can contribute to the eradication of harmful newborn care practices and the sustenance of essential practices through community education and behavior change communication.

Mortality among neonates has long been largely neglected by research in all developing nations of world including India. This study aims to identify the primary and secondary causes of neonatal deaths among the tribes of Gujarat by retrospectively analyzing 106 neonatal deaths that occurred during the year 2008 and 2009. The socio-economic, biological and traditional newborn care practices impacting newborn survival were also studied. Case studies including in-depth interviews of 33 women who had experienced neonatal deaths in period of 2008 and 2009 have also been conducted. The results show that the main causes of neonatal deaths in the study area were birth asphyxia, prematurity, aspiration, infection and congenital anomalies, irrespective of place of delivery. Absence of trained and skilled personnel for newborn resuscitation was the main cause of perinatal birth asphyxia related deaths. Around 36% mothers had a history of infant deaths. Low birth weight is one of the important causes of neonatal deaths among mothers who had a history of child loss. Cyclicality of neonatal deaths continued among clustered families with social factors initiating the cycle. Qualified trained birth attendants practicing essential newborn care are necessary during home deliveries.

Drug-coated balloons are developed to address the in-stent restenosis (ISR) and stenosis in small coronary vessels. The present study aimed to investigate the immediate performance, mid and long-term results of Magic touch Sirolimus coated balloon (SCB) (Concept Medical) for the treatment coronary

This registry aims to evaluate the safety and effectiveness of the sirolimus eluting stent with unique fusion coating (coated on stent and exposed parts of balloon), Abluminus DES+ (Envision Scientific), in all-comers real-world population. This prospective, multi-centre, real world, all-comers

The aim of this registry is to evaluate the clinical performance the Abluminus DES+ (Envision Scientific), Novel Abluminal coated sirolimus eluting stent coated on stent and parts of balloon in a large patient population. Between January 2012 and October 2017, 2372 patients were enrolled

Over past the decade, drug-coated balloons have emerged as an effective treatment for coronary stenosis with and advantage of delivering the anti-proliferative agent to the clogged vessel without any metallic implant. We sought to assess the world’s first sirolimus-coated balloon (SCB) -Magictouch

BACKGROUND: The possible role of heme oxygenase and its byproduct carbon monoxide (CO) in the regulation of blood pressure is under investigation. The aim of this study was to compare end tidal breath CO (ETCO) levels in women with gestational hypertension (GH) or pre-eclampsia to the levels in healthy pregnant and nonpregnant women. MATERIALS AND METHODS: We prospectively performed ETCO measurements corrected for ambient CO (ETCOc) in two medical centers (Stanford, CA and Cleveland, OH). A Natus® CO-Stat® End Tidal Breath Analyzer (Natus Medical Inc., San Carlos, CA) was used. The study group included a convenience sample of 31 women with GH/pre-eclampsia (PE). Control groups included 46 nonpregnant healthy women, 44 first-trimester and 48 third-trimester pregnant healthy women. RESULTS: Mean±SD ETCOc measurements were significantly lower in the GH/PE group compared to first-trimester (p=0.004) and third-trimester (p=0.001) normotensive pregnant and nonpregnant women (p=0.002) (1.36±0.30 vs 1.76±0.47, 1.72±0.42 and 1.78±0.54 ppm, respectively). The ETCOc values were ≤1.6 ppm in 89% of GH/PE women compared with, respectively, only 45, 54, and 46% of nonpregnant, first- and third-trimester normotensive pregnant women (p

Objective: We sought to examine the current perinatal correlates and neonatal morbidity associated with intrauterine growth failure among neonates born at term gestation. Study Design: We compared 372 small for gestational age (SGA, birth weight

Hypertensive disorders of pregnancy are prototypical of maternal conditions associated with reduced uteroplacental blood flow. Hypertensive disorders in pregnancy include chronic hypertension, preeclampsia-eclampsia, superimposed preeclampsia, and gestational hypertension. Pathophysiology of these disorders include deficient uterine vascular modeling in the process of placentation and aberrations of vasomotor regulation. Aberrations of uterine renin-angiotensin system may play a proximate role in the pathogenesis of preeclampsia syndrome. Clinical manifestations are explained in this review based on resultant vasoconstriction and ischemia in systemic and regional circulations. Perinatal implications of hypertensive disorders both in terms of early neonatal outcome and long-term neurodevelopmental effects are described. Methods of antenatal assessment of the fetus and, briefly, principles of clinical management are described.

Objective. To investigate the association between fetal echogenic bowel (FEB) during the second trimester and perinatal outcome.Methods. A retrospective chart review of FEB during the second trimester over 3 years.Results. A total of 56 women were identified of 9067 screened (0.6%) women. Forty-seven agreed to genetic counseling (84%). Of those, 22 (39%) agreed to an amniocentesis. There were three cases of trisomy 21, one case of trisomy 18 and one case of fetal CMV infection. Twelve fetuses had an adverse outcome (21%), with only three of them having an echogenic bowel as the only finding.Conclusions. In our study, almost 80% of the fetuses had an uncomplicated perinatal outcome. FEB was present as the only finding in only 5% of the fetuses with an adverse outcome. A potential association with placental abnormalities and a low prevalence of viral infections was observed. These findings may be of use in counseling parents.

Cocaine-induced myocardial infarction has been well reported. Likewise, there are numerous reports of patients with cocaine-induced myocardial infarction being treated conservatively with nitroglycerin, verapamil, and thrombolytics. However, based on a Medline search from 1977 to 1998 (with the keywords cocaine and angioplasty), there have been no reports in English of cocaine-induced myocardial infarction being treated with catheter-based intervention. We report such a case, as well as review what is known about the pathophysiology of cocaine-induced coronary arteriopathy and myocardial infarction.

Routine anatomic ultrasound performed in the second trimester has a detection rate of approximately 70-90% for fetal congenital abnormalities (Nyberg and Souter, J Ultrasound Med 2001;6:655-674). The central nervous system abnormalities are one of the most common ones detected. Chiari malformation is among the CNS abnormalities diagnosed in the fetal period (Bianchi et al., Fetology - diagnosis and management of the fetal patient, McGraw-Hill, 2000). The Arnold-Chiari malformation was first described in 1883 by Cleland (Romero et al., Prenatal diagnosis of congenital anomalies, Appleton and Lange, 1988). It is characterised by the prolapse of the hindbrain structures below the level of the foramen magnum. It can be associated with skeletal abnormalities and neurological dysfunction. In type I, a lip of cerebellum is downwardly displaced with the tonsils, but the fourth ventricle remains in the posterior fossa. This condition may coexist with syringomyelia, which is a cyst formation on the cervical portion of the spinal cord (Creasy et al., Maternal fetal medicine principles and practice, 2004). We present a case where Chiari type 1 and syringomyelia detected at 18 weeks of gestation. The reason for referral to our center was an abnormal inward posturing of both upper and lower extremities (minimal gross movement and almost inexistent range of motion on fetal joints). On further fetal evaluation, an abnormal brain ultrasound was identified. Prenatal diagnosis of Chiari type 1 malformation and syringomyelia is almost nonexistent when reviewing the literature is the reason why this case is presented.

Noninvasive prenatal testing utilizing free fetal DNA is commonly used in pregnancy to screen for trisomy 13, 18, 21 and also fetal sex aneuploidy. We report on two cases of discrepancy between phenotypic and genotypic sex and potential medical implications. In our first case, a patient with known male gender via cell free fetal DNA (cffDNA) testing had an ultrasound at 18 weeks' gestation, which identified Dandy-Walker malformation and female-appearing ambiguous genitalia. As Dandy-Walker malformation could not be considered isolated in the presence of ambiguous genitalia, this finding allowed for more complete counseling of the parents as well as extensive genetic workup. Our second case involved a fetus with intrauterine growth restriction diagnosed by ultrasound and normal-appearing female genitalia. After birth, adrenal insufficiency was diagnosed and chromosome analysis identified normal male chromosomes. These two cases showed that fetal sex determination by cffDNA can be used as a tool for earlier identification of affected pregnancies, allowing for parental decision-making, genetic testing and earlier intervention.

Couples in sub-Saharan Africa are the largest group in the world at risk for HIV infection. Couples counseling and testing programs have been shown to reduce HIV transmission, but such programs remain rare in Africa. Before couples counseling and testing can become the norm, it is essential to increase demand for the services. We evaluated the effectiveness of several promotional strategies during a two -year program in Kitwe and Ndola, Zambia. The program attracted more than 7,600 couples through the use of radio broadcasts, billboards, and other strategies. The most effective recruiting technique was the use of local residents trained as “influence agents” to reach out to friends, neighbors, and others in their sphere of influence. Of the estimated 2.5 million new cases of HIV in adults and children in 2009, more than two-thirds occurred in sub-Saharan Africa.1 In Zambia, the prevalence of HIV among adults in urban and rural areas is estimated at 19 and 10 percent, respectively.2 Most HIV transmission in sub-Saharan Africa is heterosexual and occurs between cohabiting partners with discordant HIV test results3–5—that is, only one partner is HIV-positive. Thus, most new cases of HIV occur when someone infects his or her heterosexual partner. Sub-Saharan African couples with discordant HIV test results are the world’s largest risk group for HIV.6 Approximately 20 percent of Zambian couples have discordant HIV results, a rate consistent with estimates from Uganda, Rwanda, Tanzania, and Kenya.7–14

Background Enzymes involved in the metabolism of free fatty acids are essential for the proper use of caloric intake. Abnormal enzymes unable to degrade fatty acids will result in an accumulation of fatty acids in organs like the liver, impairing its function. Case A 28-year-old primigravid woman underwent induction of labour because of severe preeclampsia. She was subsequently found to be a carrier for mutations in several fatty acid enzymes as well as the angiotensin converting enzyme. Conclusion During pregnancy, the increased need for fatty acid degradation will expose women who are carriers of mutations in these enzymes. The clinical manifestations in such women include acute fatty liver of pregnancy that may mimic severe preeclampsia. Strict metabolic control to avoid excess fatty acid degradation may allow for better pregnancy outcomes and newborn assessment.

Infants with trisomy 18 have severe mental retardation along with anomalies of the nervous, cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems; survival beyond 1 year of age is rare. Even with successful repair of the cardiac defects, the prognosis would not be altered greatly. The most common cardiac malformations described in association with trisomy 18 are ventricular septal defect, tetralogy of Fallot, double-outlet right ventricle, and abnormalities of the atrioventricular and semilunar valves.1 Prenatal diagnosis of pulmonary atresia with intact ventricular septum has been reported.2–7 We report a case of pulmonary atresia with intact ventricular septum in association with trisomy 18 and a coronary fistula demonstrated by fetal echocardiography. CASE REPORT

PURPOSE OF REVIEW Preeclampsia is a disorder of gestation characterized by hypertension and proteinuria and can be complicated by eclamptic seizures. This review describes recent advances in the role of the renin-angiotensin system and angiogenic and anti-angiogenic factors of placental origin in its pathogenesis. RECENT FINDINGS Deficient uteroplacental perfusion has been recognized to be a feature in all preeclampsia syndromes. Increased renin expression observed in humans and animal models supports the concept that activation of the decidual renin-angiotensin system may mediate the pathogenesis of preeclampsia. Novel angiotensin II-related biomolecular mechanisms, angiotensin II type 1-B2 receptor heterodimerization and autoantibody against angiotensin II type 1 have recently been described in preeclampsia. New evidence suggests that vascular endothelial growth factor and its receptors, antagonists, and reduced placental growth factor may play a role in the development of proteinuria and other renal injury-mediated manifestations in preeclampsia. SUMMARY Vascular maladaptation, with increased vasomotor tone, endothelial dysfunction, increased sensitivity to angiotensin II and norepinephrine, and multiorgan dysfunction seen in preeclampsia, may be explained by angiotensin II-mediated mechanisms. Future investigations need to define the mechanism of activation of the decidual renin-angiotensin system and the release of placental factors in the pathogenesis of preeclampsia.

Objectives We evaluated role of sFlt-1 and VEGF in a preeclampsia model driven by RAS activation. We hypothesized as transgenic crossbreeds develop preeclampsia, features of hypertension, proteinuria, kidney and placenta end-organ damage will occur concurrently with (1) sFlt1 rising higher in preeclamptic mice, (2) VEGF remaining high in preeclamptic mice but equivalent to controls; and, (3) preeclamptic kidneys demonstrating increased VEGF binding. Methods Transgenic hAGT and hREN, or wild type (WT) mice were used. Non-gravid females underwent telemetric transmitter implantation for blood pressure (BP) measurements. Mice were cross-bred: hAGT × hREN for RAS preeclamptic model and pregnant controls (WT × WT). Blood and urine collected on days (GD) 12, 15, and 18. Vascular reactivity in mesenteric arteries investigated by wire myography using KCl, acetylcholine (ACH), phenylephrine (PE). ELISA performed on urine for albumin and on plasma for VEGF and sFlt-1. Necropsies were performed GD 18-19. Kidneys and placenta were sectioned for HE and immunostain. Results 11 RAS pregnancies and 9 WT pregnancies (WTP) compared. 12,414 h of BP data analyzed. RAS mice demonstrated higher BP and proteinuria. RAS mice had glomerular endotheliosis (80% vs. 11%; p = 0.02), and placental necrosis (60% vs. 0%; p Conclusions While RAS model of preeclampsia recapitulates human preeclamptic state with high fidelity, renal injury may actually be mediated by increased VEGF binding. Disclosures J.M. Denney: None. C.E. Shaw: None. A. Gendron-Fitzpatrick: None. I. Bird: None. D. Shah: None.