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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.

Presented is a modified technique for removing a failed endothelial allograft in an aniridic aphakic eye that reduces the risk of posterior dislocation. This technique involves the creation of an artificial iris plane using a Sheets glide by trimming it into the shape of a dagger so that it can be pulled through the anterior chamber and fixated by both its passage through a paracentesis incision and the main incision. The Sheets glide then acts as a physical barrier, or scaffold, to allow safe removal of the failed endothelial allograft and subsequent repeat endothelial keratoplasty while avoiding posterior dislocation of the tissue into the vitreous cavity.

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 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

Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild-type (WT) C57Bl/6 mice were cross-bred: female hAGT × male hREN for preeclampsia (PRE) model and female WT × male WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1, and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF. Eleven PRE and 9 WTP mice were compared. PRE more frequently demonstrated albuminuria, glomerular endotheliosis (80% vs. 11%; P = 0.02), and placental necrosis (60% vs. 0%; P < 0.01). PRE group demonstrated declining BPs with advancing gestation. Plasma sFlt1 increased across pregnancy in PRE; VEGF did not vary. IHC demonstrated the presence of sFlt1 in glomeruli, lymphatics, and collecting tubules of PRE kidneys, suggesting excretion. VEGF immunostaining was increased specifically in the glomeruli of PRE kidneys. Placenta in PRE showed marked immunostaining for sFlt1. We conclude that this transgenic model of preeclampsia recapitulates human preeclamptic state with high fidelity, and that, vascular adaptation to pregnancy is suggested by declining BPs and reduced vascular response to PE and increased response to acetylcholine. Placental damage with resultant increased release of sFlt1, proteinuria, deficient spiral artery remodeling, and glomerular endotheliosis were observed in this model of PRE. Increased VEGF binding to glomerular endothelial cells in this model of PRE is similar to human PRE and leads us to hypothesize that renal injury in preeclampsia may be mediated through local VEGF.

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.

Ferumoxytol is a superparamagnetic iron oxide nanoparticle 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, seven pregnant rhesus macaques were imaged with or 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 (MFI), fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ∼100 gestational day underwent MRI before and after ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 2–3 days following ferumoxytol administration. A control group that did not receive ferumoxytol or MRI was used for comparison. Iron levels in fetal and MFI tissues did not differ between groups, and 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 does not negatively impact the MFI and can be a valuable experimental tool in research with this important animal model.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.

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.

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.

Sustained Ca2+ burst signaling is crucial for endothelial vasodilator production and is disrupted by growth factors and cytokines. Conjugated linoleic acid (CLA), a Src inhibitor in certain preparations, is generally regarded as safe during pregnancy by the FDA. Multiple CLA preparations; t10, c12 or c9, t11 CLA, or a 1:1 mixture of the two were administered before growth factor or cytokine treatment. Growth factors and cytokines caused a significant decrease in Ca2+ burst numbers in response to ATP stimulation. Both t10, c12 CLA and the 1:1 mixture rescued VEGF165 or TNFα inhibited Ca2+ bursts and correlated with Src-specific phosphorylation of connexin 43. VEGF165, TNFα, and IL-6 in combination at physiologic concentrations revealed IL-6 amplified the inhibitory effects of lower dose of VEGF165 and TNFα. Again, the 1:1 CLA mixture was most effective at rescue of function. Therefore, CLA formulations may be a promising treatment for endothelial dysfunction in diseases such as preeclampsia.

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 To explore California local health department leaders’ experiences planning, implementing, and evaluating nutrition promotion and obesity prevention programs for low-income families. Design Qualitative, cross-sectional study using semi-structured in-depth interviews and panel interviews conducted in 2015–2016. Setting California local health departments (LHDs) funded by the California Department of Public Health to implement Supplemental Nutrition Assistance Program–Education (SNAP-Ed). Participants The authors recruited SNAP-Ed leaders from all 58 California LHDs implementing SNAP-Ed. Leaders from 49 LHDs participated: 36 in hour-long, in-depth interviews and 13 in 1 of 3 90-minute group panel interviews. Phenomenon of Interest Processes, facilitators, and barriers connected to delivering SNAP-Ed reported by leaders in planning, implementing, and evaluating local programs. Analysis Interviews were transcribed, coded, and analyzed using Dedoose software. Results Leaders grappled with introducing, implementing, and integrating policy, systems, and environmental change interventions (PSEs). Information used to make planning decisions varied widely across LHDs. Partnership with nontraditional organizations was described as a resource- intensive, nonlinear process with recognized potential for benefit. Rural programs reported specific and different experiences compared with their urban counterparts. Conclusions and Implications Implementing new, complex interventions to improve diet and activity environments and behaviors is both exciting and challenging for local leaders. They expressed a desire for additional resources and capacity building to facilitate success, particularly related to policy, systems, and environmental change programs. Attention to the specific needs of rural counties is needed.

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.

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.

International audience; Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging; 2) sexual dimorphism; 3) placenta and development of other organs; 4) trophoblast cell lines.

Objective This study aimed to describe brain development during the first (B1) and second trimester (B3) in human fetuses. Design Ten brains from 10 to 18 weeks of gestational age (GA) were collected, and the RNA was used for transcriptome analysis (Affymetrix 1.0 ST microarray chip). Differences in brain development within 10 to 18 GA were investigated by dividing the sample into 10 to 12 (B1), 13 to 15(B2) and 16 to 18(B3) weeks. A fold change of 2 or above, with a false discovery rate of 5%, was used as cut-off to determine differential gene expression for individual genes. Quantitative real-time PCR was used to confirm differences. Tests for enrichment procedures (using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were then used to identify functional groups of mRNA. Results At 10 to 12 weeks, brains showed neuronal migration to be upregulated. From 10 to 18 weeks, brains showed genes coding for neuronal migration, differentiation and connectivity upregulated. ALDH1A1 and NPY genes, marker of spinal cord and striatum, were upregulated in B1 and B3 brains, respectively. Also, SLITRK6-HAS2 and CRYAB-PCDH18 genes for ear and eye sensory input were upregulated in B1. Conclusions For the first time, brain global gene expression was described in human samples. Period B1 was dominated by genes coding for neuronal migration, differentiation, programmed cell death and sensory organs. B3 was dominated by neuronal proliferation, branching and myelination. Creating such a database will allow comparison with abnormals in future studies. © 2014 John Wiley & Sons, Ltd.

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

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

Approximately 8% of pregnancies are complicated by preeclampsia (PE), a hypertensive condition characterized by widespread endothelial dysfunction. Reduced nitric oxide (NO) output in PE subjects has been inferred but not directly measured, and there is little understanding of why this occurs. To address this we have used direct imaging of changes in intracellular Ca2+concentration ([Ca2+]i) and NO in umbilical vein endothelium of normal and PE subjects that is still intact and on the vessel luminal surface. This was achieved by dissection and preloading with fura 2 and DAF-2 imaging dyes, respectively, before subsequent challenge with ATP (100 μM, 30 min). As a control to reveal the content of active endothelial nitric oxide synthase (eNOS) per vessel segment, results were compared with a maximal stimulus with ionomycin (5 μM, 30 min). We show for the first time that normal umbilical vein endothelial cells respond to ATP with sustained bursting that parallels sustained NO output. Furthermore, in subjects with PE, a failure of sustained [Ca2+]ibursting occurs in response to ATP and is associated with blunted NO output. In contrast, NO responses to maximal [Ca2+]ielevation using ionomycin and the levels of eNOS protein are more similar between groups than the responses to ATP. When the endothelial cells from PE subjects are isolated and allowed to recover in culture, they regain the ability under fura 2 imaging to show multiple [Ca2+]ibursts otherwise seen in the cells from normal subjects. Thus novel clinical therapy aimed at restoring function in vivo may be possible.

Objective To investigate the effects of ginger root juice on contractibility of resistance blood vessels from mice and on activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and endothelial nitric oxide synthase (eNOS) in human endothelial cells. Methods Juice was prepared from semi-dry ginger roots. Mesenteric artery rings were dissected from healthy adult C57BL/J6 mice. Primary human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords of normal full-term babies. The contractibility of the dissected vessel rings in the presence or absence of ginger root juice at 0.1% (v/v) after potassium (100 mM KCL) stimulation was measured by wire myography. The phosphorylation levels of ERK1/2 and eNOS in the presence of ginger root juice in the culture medium at 0, 0.025%, 0.05%, 0.1%, and 0.2% (v/v) in HUVECs were assessed by western blotting analysis. Results An immediate sharp increase in the contractile activity was observed in mesenteric artery rings in response to KCL stimulation. Ginger root juice effectively attenuated the KCL-mediated vessel contraction. Moreover, ginger root juice significantly increased phosphorylation of ERK1/2 and eNOS in a dose-dependent manner. Conclusions Ginger root juice is capable of relaxing resistance blood vessels. Activation of ERK1/2 and eNOS through phosphorylation in endothelial cells may be a mechanism underlying the vasodilator activity of ginger root.

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.

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.

The role increased vascular endothelial growth factor (VEGF) plays in vascular function during normal vs. preeclamptic pregnancy has been a source of some controversy of late. In this study, we seek to understand how VEGF165 influences vasodilator production via Ca2+ signaling mechanisms in human endothelial cells. We utilize human umbilical vein endothelial cells (HUVEC) as well as intact ex vivo human umbilical vein (HUV Endo) to address direct stimulation of Ca2+ and NO by VEGF165 alone, as well as the effect of VEGF165 on subsequent ATP-stimulated Ca2+ signaling and NO production. We show that VEGF165 stimulates Ca2+ responses in both HUVEC and HUV Endo, which results in a corresponding increase in NO production in HUV Endo. Longer-term VEGF165 pretreatment then inhibits sustained Ca2+ burst responses to ATP in HUVEC and HUV Endo. This is paralleled by a corresponding drop in ATP-stimulated NO production in HUV Endo, likely through inhibition of Cx43 gap-junction function. Thus, although VEGF165 makes a small initial positive impact on vasodilator production via direct stimulation of Ca2+ responses, this is outweighed by the greater subsequent negative impact on Ca2+ bursts and vasodilator production promoted by more potent agonists such as ATP. Overall, elevated levels of VEGF165 associated with preeclampsia could contribute to the endothelial dysfunction by preventing Ca2+ bursts to other agonists including but not limited to ATP. NEW & NOTEWORTHY In this manuscript, we show that VEGF levels associated with preeclampsia are a net negative contributor to potential vasodilator production in both a human ex vivo and in vitro endothelial cell model. Therefore, pharmacological targeting of VEGF-stimulated signaling pathways could be a novel treatment modality for preeclampsia-related hypertension.

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

Diabetes (DM) complicates 3%-10% of pregnancies, resulting in significant maternal and neonatal morbidity and mortality. DM pregnancies are also associated with vascular dysfunction, including blunted nitric oxide (NO) output, but it remains unclear why. Herein we examine changes in endothelial NO production and its relationship to Ca(2+) signaling in endothelial cells of intact umbilical veins from control versus gestational diabetic (GDM) or preexisting diabetic subjects. We have previously reported that endothelial cells of intact vessels show sustained Ca(2+) bursting in response to ATP, and these bursts drive prolonged NO production. Herein we show that in both GDM and DM pregnancies, the incidence of Ca(2+) bursts remains similar, but there is a reduction in overall sustained phase Ca(2+) mobilization and a reduction in NO output. Further studies show damage has occurred at the level of NOS3 protein itself. Since exposure to DM serum is known to impair normal human umbilical vein endothelial cell (HUVEC) function, we further studied the ability of HUVEC to signal through Ca(2+) after they were isolated from DM and GDM subjects and maintained in culture for several days. These HUVEC showed differences in the rate of Ca(2+) bursting, with DM > GDM = control HUVEC. Both GDM- and DM-derived HUVEC showed smaller Ca(2+) bursts that were less capable of NOS3 activation compared to control HUVEC. We conclude that HUVEC from DM and GDM subjects are reprogrammed such that the Ca(2+) bursting peak shape and duration are permanently impaired. This may explain why ROS therapy alone is not effective in DM and GDM subjects.

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

Abnormal growth in one or both twins may contribute to the increased morbidity and mortality observed in twin gestation. Our objective in this retrospective study of all twin pregnancies delivered at our hospital (n = 240) over a 2-year period was to study the relationship between placental lesions and abnormal growth. Standardized placental examinations were performed in 192 cases (80%), which constituted the study population. Two growth abnormalities were studied: discordant growth as defined by >15% difference in birth weight and small-for-gestational-age (SGA) birth as defined by birth weight less-than the 10th percentile for gestational age. The majority of twin pregnancies with either discordant growth (41/57 cases) or SGA birth (26/35 cases) had dichorionic placentas. In monochorionic placentas studied by injection there was no significant relationship between vascular anastomoses and discordant growth. Placental weight for small discordant and SGA twins was equivalent or increased relative to infant weight, a pattern not suggestive of maternal vascular underperfusion. Eight lesions, five considered to represent chronic placental disease and three considered to represent intrauterine adaptation, were studied as possible predictors of abnormal growth. The overall prevalence of these lesions in twin placentas was less than that seen in singleton births. Concordance between twin placentas for most lesions was higher than would be expected, based on their prevalence in singleton placentas. Two lesions were associated with discordant growth in both univariate and multivariate analyses: peripheral cord insertion (OR 3.6, 95% CI 1.7–7.6) and avascular villi (AV; OR 3.2, 95% CI 1.0–10.3). Three placental lesions were associated with SGA infants at the univariate level: peripheral cord insertion, avascular villi, and maternal vascular underperfusion. Only peripheral cord insertion (OR 9.8, 95% CI 4.1–23.4) and AV (OR 3.7, CI 1.0–13.7) were significant in the multivariate analysis. The relative increase in peripheral cord insertion and AV with abnormal growth was observed for both monochorionic and dichorionic placentas. Subgroups of discordant infants with and without SGA were both associated with peripheral cord insertion while only those with SGA had an increase in AV. Both peripheral cord insertion and AV were increased in the subgroup with SGA but no discordancy. In summary, two placental lesions, peripheral cord insertion indicating a spatially limited intrauterine compartment and AV indicating occlusion of fetal vessels in the placenta, were associated with abnormal growth in twins.

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.