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Background: In March 2020, as community spread of severe acute respiratory syndrome coronavirus 2 became increasingly prevalent, pregnant women seemed to be equally susceptible to developing coronavirus disease 2019. Although the disease course usually appears mild, severe and critical cases of coronavirus disease 2019 seem to lead to substantial morbidity, including intensive care unit admission with prolonged hospital stay, intubation, mechanical ventilation, and even death. Although there are recent reports regarding the impact of coronavirus disease 2019 on pregnancy, there is a lack of information regarding the severity of coronavirus disease 2019 in pregnant vs nonpregnant women., Objective: We aimed to describe the outcomes of severe and critical cases of coronavirus disease 2019 in pregnant vs nonpregnant, reproductive-aged women., Study Design: This is a multicenter, retrospective, case-control study of women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection hospitalized with severe or critical coronavirus disease 2019 in 4 academic medical centers in New York City and 1 in Philadelphia between March 12, 2020, and May 5, 2020. The cases consisted of pregnant women admitted specifically for severe or critical coronavirus disease 2019 and not for obstetrical indications. The controls consisted of reproductive-aged, nonpregnant women admitted for severe or critical coronavirus disease 2019. The primary outcome was a composite morbidity that includes the following: death, a need for intubation, extracorporeal membrane oxygenation, noninvasive positive pressure ventilation, or a need for high-flow nasal cannula O 2 supplementation. The secondary outcomes included intensive care unit admission, length of stay, a need for discharge to long-term acute care facilities, and discharge with a home O 2 requirement., Results: A total of 38 pregnant women with severe acute respiratory syndrome coronavirus 2 polymerase chain reaction-confirmed infections were admitted to 5 institutions specifically for coronavirus disease 2019, 29 (76.3%) meeting the criteria for severe disease status and 9 (23.7%) meeting the criteria for critical disease status. The mean age and body mass index were markedly higher in the nonpregnant control group. The nonpregnant cohort also had an increased frequency of preexisting medical comorbidities, including diabetes, hypertension, and coronary artery disease. The pregnant women were more likely to experience the primary outcome when compared with the nonpregnant control group (34.2% vs 14.9%; P=.03; adjusted odds ratio, 4.6; 95% confidence interval, 1.2-18.2). The pregnant patients experienced higher rates of intensive care unit admission (39.5% vs 17.0%; P<.01; adjusted odds ratio, 5.2; 95% confidence interval, 1.5-17.5). Among the pregnant women who underwent delivery, 72.7% occurred through cesarean delivery and the mean gestational age at delivery was 33.8±5.5 weeks in patients with severe disease status and 35±3.5 weeks in patients with critical coronavirus disease 2019 status., Conclusion: Pregnant women with severe and critical coronavirus disease 2019 are at an increased risk for certain morbidities when compared with nonpregnant controls. Despite the higher comorbidities of diabetes and hypertension in the nonpregnant controls, the pregnant cases were at an increased risk for composite morbidity, intubation, mechanical ventilation, and intensive care unit admission. These findings suggest that pregnancy may be associated with a worse outcome in women with severe and critical cases of coronavirus disease 2019. Our study suggests that similar to other viral infections such as severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, pregnant women may be at risk for greater morbidity and disease severity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Propranolol hydrochloride is a nonselective beta-adrenergic antagonist that has a known activity in the myometrium. Small trials have shown that propranolol decreases the duration of induced labor, although those studies are limited by methodological variability., Objective: Our objective was to determine whether the addition of a single dose of propranolol to induce labor in nulliparous women would decrease total time to vaginal delivery., Study Design: This study was a double-blind, randomized, placebo-controlled trial of nulliparous patients undergoing term induction of labor with a singleton, nonanomalous gestation. Subjects were randomized to 2 mg of intravenous propranolol hydrochloride or an identical-appearing saline placebo, administered 30 minutes after starting the induction of labor. Investigators, labor floor staff, and patients were blinded to the study drug allocation. The primary outcome was time to vaginal delivery. Secondary outcomes included mode of delivery, duration of the phases of labor, time to full dilation, composite maternal morbidity, and composite neonatal morbidity. Data were analyzed by intention-to-treat analysis with a P value of ≤.05 considered significant., Results: In this study, 240 patients were enrolled from December 2017 to December 2018, with 121 patients randomized to the propranolol group and 119 to the placebo group. The 2 groups had similar baseline characteristics. Of the patients randomized, 154 (64.2%) delivered vaginally. There was no significant difference in time from the start of the induction of labor to vaginal delivery (13.8±5.4 hours for propranolol vs 14.3±5.3 hours for placebo; P=.58). There was also no difference in the rate of cesarean delivery (38% vs 33.6%; P=.48), time to active labor (11.0±5.0 vs 11.2±4.5 hours; P=.77), or time to full dilation (12.4±5.1 vs 12.8±5.2 hours; P=.60) in patients receiving propranolol compared with those receiving placebo. Subjects randomized to the propranolol group had a significantly lower rate of composite maternal morbidity (28.9% vs 41.2%; risk ratio, 0.70; 95% confidence interval, 0.49-1.00; P=.047). Rates of postpartum hemorrhage (12.4% vs 21.8%; P=.05) and transfusion (0% vs 4.2%; P=.03) were also lower in the treated group. There was no significant difference in neonatal outcomes or composite morbidity (risk ratio, 0.74; 95% confidence interval, 0.44-1.22)., Conclusion: In this study, there is no evidence that the addition of a 1-time dose of propranolol to induce labor in nulliparous women decreases time to delivery or the rate of cesarean delivery. However, propranolol significantly reduced composite maternal morbidity without adverse neonatal effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The placental cord insertion (PCI) to the placental margin has not been well studied as a continuous variable in relation to birth outcomes. We sought to evaluate the impact of PCI distance on outcomes associated with placental function and development of fetal growth restriction (FGR)., Study Design: This was a retrospective study of singleton gestations that underwent a fetal anatomy ultrasound from 2011-2013. The PCI was recorded as the distance in centimeters from the placental margin. Patients had FGR if the overall estimated fetal weight was <10 % for gestational age or abdominal circumference <5 % in the third trimester. Delivery, obstetric, and neonatal outcomes were obtained via medical chart review. Logistic and linear regression models were used to assess the impact of PCI distance on maternal and neonatal delivery outcomes., Results: Of the 1443 women who met inclusion criteria, 93.6 % delivered at term. The mean (±SD) PCI distance was 4.4 ± 1.4 cm. There was no association between PCI and cesarean delivery, peripartum hemorrhage (PPH), pre-eclampsia, 5-min Apgar, or intrauterine fetal demise. PCI distance was statistically significantly shorter in patients requiring neonatal intensive care unit (NICU) admission (4.1 ± 1.5 cm vs. 4.4 ± 1.4 cm, p = 0.02) and was associated with lower birthweight (p = 0.01), though this association was no longer seen when corrected for gestational age. There were 3.5 % of patients who developed FGR; PCI distances from the placental edge were not significantly different for patients who developed FGR compared to those who did not (4.2 ± 1.4 cm vs. 4.5 ± 1.4 cm, p = 0.18). Furthermore, a receiver operating characteristic (ROC) curve for PCI had poor sensitivity (area under the curve [AUC] 0.57, 95 % CI 0.49-0.65)., Conclusion: PCI distance at the time of fetal anatomic survey is significantly associated with NICU admission, though does not appear to impact rates of preterm birth, pre-eclampsia, PPH or cesarean delivery. PCI distance in singleton gestations does not appear to be predictive of FGR., Competing Interests: Declaration of Competing Interest The authors reported no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To evaluate the rate of coronavirus disease 2019 (COVID-19) infection with the use of universal testing in our obstetric population presenting for scheduled deliveries, as well as the concordance or discordance rate among their support persons during the initial 2-week period of testing. Additionally, we assessed the utility of a screening tool in predicting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing results in our cohort., Methods: This was an observational study in which all women who were scheduled for a planned delivery within the Mount Sinai Health system from April 4 to April 15, 2020, were contacted and provided with an appointment for themselves as well as their support persons to undergo COVID-19 testing 1 day before their scheduled delivery. Both the patients and the support persons were administered a standardized screen specific for COVID-19 infection by telephone interview. Those support persons who screened positive were not permitted to attend the birth. All patients and screen-negative support persons underwent SARS-CoV-2 testing., Results: During the study period, 155 patients and 146 support persons underwent SARS-CoV-2 testing. The prevalence of asymptomatic COVID-19 infection was 15.5% (CI 9.8-21.2%) and 9.6% (CI 4.8-14.4%) among patients and support persons, respectively. The rate of discordance among tested pairs was 7.5%. Among patients with COVID-19 infection, 58% of their support persons also had infection; in patients without infection, fewer than 3.0% of their support persons had infection., Conclusion: We found that more than 15% of asymptomatic maternity patients tested positive for SARS-CoV-2 infection despite having screened negative with the use of a telephone screening tool. Additionally, 58% of their asymptomatic, screen-negative support persons also tested positive for SARS-CoV-2 infection. Alternatively, testing of the support persons of women who had tested negative for COVID-19 infection had a low yield for positive results. This has important implications for obstetric and newborn care practices as well as for health care professionals.

Background: In A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33·3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up., Methods: ARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age ≥18 years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181., Findings: Of 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50·4 months (SD 22·9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3·39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12·32 per 100 patient-years; hazard ratio 0·31, 95% CI 0·17 to 0·56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58·97 vs 78·73 per 100 patient-years; risk difference -19·76, 95% CI -30·33 to -9·19)., Interpretation: After extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain., Funding: National Institute of Neurological Disorders and Stroke for the randomisation phase and Vital Projects Fund for the follow-up phase., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The primary objective was to measure IUD-fundus and IUD-myometrium distances by ultrasound of IUDs placed during cesarean section over the first year of use. The secondary objective was to determine if these distances are associated with risk of expulsion or removal for side effects., Study Design: In this prospective observational study, we performed ultrasounds at six - ten weeks, three months and one year postpartum to measure the distance from the top of the device to the fundal serosa (IUD-fundus) and upper margin of the endometrial cavity (IUD-myometrium). We also assessed IUD expulsion or discontinuation for side effects at each visit., Results: We enrolled 93 women who had copper (n = 77) or levonorgestrel (n = 16) IUDs placed at time of cesarean section. Two patients had complete expulsion, six had partial expulsion and nine requested removal for symptoms. Overall, median IUD-fundus measurements were 2.13 cm (IQR 1.87-2.55) at 6-10 weeks, 1.87 cm (IQR 1.53-2.23) at 3-months and 2.02 cm (IQR 1.67-2.40) at 1-year. Among copper IUD users, distances at six weeks and three months were similar in women who did or did not have expulsion or removal at one year however small numbers limit our ability to assess this relationship., Conclusion: We describe the location on ultrasound of IUDs placed at the time of Cesarean section over the first year. We found similar IUD locations at six weeks and three months for participants who did or did not experience expulsion or removal by one year., Implications: Position of intrauterine devices placed during cesarean section was similar for those who did or did not have expulsion or removal for symptoms in the first year after placement. These data may help in the design of future studies to determine if ultrasound measurement of IUDs predicts IUD complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Acute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains., Methods: Baseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored., Results: PROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores., Conclusion: Pain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response.

Background: Epiaortic ultrasound detects and localizes ascending aortic atherosclerosis. In this analysis we investigated the association between epiaortic ultrasound-based atheroma grade during surgical aortic valve replacement (SAVR) and perioperative adverse outcomes., Methods: SAVR patients in a randomized trial of 2 embolic protection devices underwent a protocol-defined 5-view epiaortic ultrasound read at a core laboratory. Aortic atherosclerosis was quantified with the Katz atheroma grade, and patients were categorized as mild (grade I-II) or moderate/severe (grade III-V). Multivariable logistic regression was used to estimate associations between atheroma grade and adverse outcomes, including death, clinically apparent stroke, cerebral infarction on diffusion-weighted magnetic resonance imaging, delirium, and acute kidney injury (AKI) by 7 and 30 days., Results: Precannulation epiaortic ultrasound data were available for 326 of 383 randomized patients (85.1%). Of these, 106 (32.5%) had moderate/severe Katz atheroma grade at any segment of the ascending aorta. Although differences in the composite of death, stroke, or cerebral infarction on diffusion-weighted magnetic resonance imaging by 7 days were not statistically significant, moderate/severe atheroma grade was associated with a greater risk of AKI by 7 days (adjusted odds ratio, 2.63; 95% confidence interval, 1.24-5.58; P = .01). At 30 days, patients with moderate/severe atheroma grade had a greater risk of death, stroke, or AKI (adjusted odds ratio, 1.97; 95% confidence interval, 1.04-3.71; P = .04)., Conclusions: Moderate/severe aortic atherosclerosis was associated with an increased risk of adverse events after SAVR. Epiaortic ultrasound may serve as a useful adjunct for identifying patients who may benefit from strategies to reduce atheroembolic complications during SAVR., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Erythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare photodermatoses presenting with severe phototoxicity. Although anecdotally, providers who treat EPP patients acknowledge their life-altering effects, tools that fully capture their impact on quality of life (QoL) are lacking., Methods: Adult patients with EPP/XLP were given four validated QoL tools: the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), the Hospital Anxiety and Depression Scale (HADS), the Illness Perception Questionnaire Revised (IPQR), and an EPP-Specific tool. All patients received the PROMIS-57 while the HADS, IPQR, and EPP-Specific tools were introduced at a later date. Associations between responses and clinical phenotypes were explored., Results: Two hundred and two patients were included; 193 completed PROMIS-57, 104 completed IPQR, 103 completed HADS, and 107 completed the EPP-Specific tool. The IPQR showed that patients strongly believed EPP/XLP had a negative impact on their lives. Mean scores in anxiety and depression domains of both HADS and PROMIS-57 were normal; however, anxiety scores from HADS were borderline/abnormal in 20% of patients. The EPP-Specific tool revealed a decreased QoL in most patients. The PROMIS-57 showed that 21.8% of patients have clinically significant pain interference. Several tool domains correlated with measures of disease severity, most being from the PROMIS-57., Conclusions: Impaired QoL is an important consequence of EPP/XLP. PROMIS-57 was most sensitive in evaluating impaired QoL in EPP/XLP. Further research is needed to compare the effectiveness of it for assessing response to treatment., Competing Interests: Hetanshi Naik reports consultancies with Alnylam. Jessica R. Overbey, Bruce Wang, Ashwani Singal, and Joseph Bloomer declare no conflict of interest. Robert J. Desnick reports consultancies from Alnylam Pharmaceuticals, Recordati Rare Diseases, and Mitsubishi Tanabe. Karl E. Anderson reports consultancies from Alnylam and grant (clinical trial) support from Alnylam and Mitsubishi Tanabe. D. Montgomery Bissell reports honoraria from Recordati and grant (clinical trial) support from Alnylam and Mitsubishi Tanabe. Herbert L. Bonkovsky reports consultancies form Alnylam, and Recordati Rare diseases and grant (clinical trial) support from Alnylam and Mitsubishi Tanabe. John D. Phillips reports consultancies from Alnylam, Recordati, and Agios and grant (clinical trial) support from Mitsubishi Tanabe. Manisha Balwani reports consultancies Alnylam, Recordati, and Mitsubishi Tanabe, and grant (clinical trial) support from Alnylam and Mitsubishi Tanabe., (© 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Objective: To investigate whether the duration of estrogen administration before euploid embryo transfer affects clinical outcome., Design: Retrospective cohort study., Setting: Private, academic fertility center., Patient(s): Patients (n = 1,439) undergoing autologous freeze-only in vitro fertilization with preimplantation genetic testing (PGT) followed by endometrial preparation with estrogen and progesterone in a frozen, euploid blastocyst transfer cycle., Intervention(s): None., Main Outcome Measure(s): Primary outcome was live birth, and secondary outcomes included implantation, clinical pregnancy, early pregnancy loss, live birth, infant birthweight, low birth weight, infant gestational age at delivery, and preterm birth., Result(s): The duration of estrogen administration (mean: 17.5 ± 2.9 days; range: 10-36 days) before frozen embryo transfer did not impact implantation (odds ratio [OR] 0.99; 95% confidence interval [CI], 0.95-1.03), clinical pregnancy (OR 0.98; 95% CI, 0.94-1.01), early pregnancy loss (OR 1.03; 95% CI, 0.95-1.12), or live birth (OR 0.99; 95% CI, 0.95-1.03). The duration of estrogen exposure did not affect infant birthweight (in grams) (β= -10.65 ± 8.91) or the odds of low birth weight (OR 0.87; 95% CI, 0.68-1.13). For every additional day of estrogen administration, we observed a reduction in gestational age at delivery (in weeks) (β= -0.07 ± 0.03), but the odds of preterm delivery were not affected (OR 1.05; 95% CI, 0.95-1.17)., Conclusion(s): Variation in the duration of estradiol supplementation before progesterone initiation does not impact frozen, euploid blastocyst transfer outcome. The duration of estrogen administration was inversely correlated with gestational age at delivery, but this did not translate into an increase in preterm delivery. Further studies are required on the downstream effects of endometrial preparation on the placental-endometrium interface., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigated sex-based differences in outcomes after mitral valve (MV) surgery for severe ischemic mitral regurgitation (SIMR)., Background: Whether differences in outcomes exist between men and women after surgery for SIMR remains unknown., Methods: Patients enrolled in a randomized trial comparing MV replacement versus MV repair for SIMR were included and followed for 2 years. Endpoints for this analysis included all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE) (defined as the composite of death, stroke, hospitalization for heart failure, worsening New York Heart Association functional class or MV re-operation), quality of life (QOL), functional status, and percentage of change in left ventricular end-systolic volume index (LVESVI) from baseline through 2 years., Results: Of 251 patients enrolled in the trial, 96 (38.2%) were women. Compared with men, women had smaller LV volumes and effective regurgitant orifice areas (EROA) but greater EROA/left ventricular (LV) end-diastolic volume ratios. At 2 years, women had higher rates of all-cause mortality (27.1% vs. 17.4%, respectively; adjusted hazard ratio [adjHR]: 1.85; 95% confidence interval [CI]: 1.05 to 3.26; p = 0.03) and of MACCE (49.0% vs. 38.1%, respectively; adjHR: 1.58; 95% CI: 1.06 to 2.37; p = 0.02). Women also reported worse QOL and functional status at 2 years. There were no significant differences in the percentage of change over 2 years in LVESVI between women and men (adjβ: -10.4; 95% CI: -23.4 to 2.6; p = 0.12)., Conclusions: Women with SIMR displayed different echocardiographic features and experienced higher mortality and worse QOL after MV surgery than men. There were no significant differences in the degree of reverse LV remodeling between sexes. (Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation [Severe Ischemic Mitral Regurgitation]; NCT00807040)., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Objective: The alpha2C adrenoreceptor deletion 322-325 (ADRA2C del 322-325) polymorphism has been associated with autonomic activity and thermoregulation, which are implicated in the vasomotor symptom (VMS) mechanism. The ADRA2C del (322-325) has higher prevalence in African American women, a group known to experience more frequent and bothersome VMS. We assessed whether the ADRA2C del (322-325) genotype is associated with increased frequency of VMS in African American women., Methods: DNA samples from African American (N = 400) women participating in the Study of Women's Health Across the Nation (SWAN) were genotyped for the ADRA2C del (322-325) polymorphism. Longitudinal data on VMS were obtained from the SWAN repository. The relation of ADRA2C del (322-325) genotypes (deletion/deletion [D/D]; insertion/deletion [I/D]; insertion/insertion [I/I]) with VMS over the menopausal transition for up to 12 years of follow-up was examined using generalized estimating equations. Primary models considered the outcome of frequent VMS (6 or more days in the prior 2 wk vs VMS <6 d in the prior 2 wk) by stage of menopause., Results: Four hundred DNA samples from African American women were included. Seventy-five women (18.8%) were found to carry the homozygous variant allele (D/D). There was no significant difference in the trajectory of frequent VMS over the menopausal transition between women with D/D and I/I + I/D genotypes (P = 0.39)., Conclusions: In this preliminary study among African American women in SWAN, ADRA2C del (322-325) was not significantly related to self-reported VMS. Further studies are warranted to help us understand the role of the adrenergic system in the physiology of VMS to tailor medical therapy to patient needs.

Research Question: Does the composite morphology score or a particular developmental component (expansion stage, inner cell mass [ICM] or trophectoderm [TE]) of euploid blastocysts undergoing single frozen embryo transfer (FET) impact ongoing pregnancy/live birth (OP/LB) rates?, Design: Retrospective cohort study including a total of 2236 embryos from 1629 patients who underwent single euploid FET between 2012 and 2017., Results: Embryos with an ICM grade of A compared with C had a higher OP/LB rate (55.6% versus 32.3%, P < 0.001). Blastocysts with a TE grade of A or B compared with C had a higher likelihood of OP/LB (A versus C: odds ratio [OR] 1.6, 99% confidence interval [CI] 1.1-2.3, B versus C: OR 1.5, 99% CI 1.1-2.1), and blastocysts with a developmental stage of 4 or 5 compared with 6 had higher odds of OP/LB (4 versus 6: OR 1.6, 99% CI 1.2-2.2, 5 versus 6: OR 1.6, 99% CI 1.2-2.3)., Conclusions: Among euploid embryos, ICM morphology is the best predictor of sustained implantation; however, a composite score may provide additional guidance. While there is a known benefit in genomic screening prior to embryo selection, morphology provides individualized, prognostic information about implantation potential., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In this study, women at risk for BRCA were surveyed to understand their choice of prophylactic surgery and associated risk of uterine cancers. The study was conducted as an anonymous online web-based survey that assessed personal and family histories and choice of prophylactic surgery. Respondents were targeted through social media groups that bring awareness to hereditary breast and ovarian cancer. The study cohort included an international group of 601 respondents. The majority were female (99.3%), in their 40s (34.2%), and had completed college or graduate school (68.8%). 87% of respondents carry BRCA gene mutation. Of 339 respondents who underwent risk-reducing salpingo-oophorectomy (RRSO), 55.8% had a hysterectomy at time of RRSO. Most common reasons for hysterectomy at time of RRSO included: 39% provider recommendation, 27.6% personal desire, 9.7% benign indications, 1.6% cancer in uterus, 1.1% precancerous uterine lesion, and 21.1% other (N = 185). In this cohort, nine were diagnosed with uterine cancer. Three were diagnosed after risk-reducing surgery. Both patients with uterine serous carcinoma were BRCA1 carriers. Two thirds of BRCA carriers surveyed had undergone RRSO. Of these, more than half had hysterectomy at time of RRSO. One third chose to have hysterectomy based on surgeon recommendation. <1% (2 out of 258) of BRCA1 gene mutation carriers reported being diagnosed with uterine serous carcinomas. While this incidence is low, it may be an underestimate based on the limitations of this study. Additional studies are needed to select which patients will benefit from concurrent hysterectomy and RRSO.

Objective: We studied cervical cancer patients who presented to the Public Hospital System in ethnically-diverse Queens, New York from 2000 to 2010 with the purpose of examining the relationship between nativity (birthplace) and survival., Methods: A retrospective review of tumor registries was used to identify patients diagnosed with cervical cancer between January 1, 2000 and December 31, 2010. Using electronic medical records, data from 317 patients were available for this analysis., Results: The majority of patients were born outside the United States (US) (85.5% versus 14.5%). One hundred patients (31.5%) were born in Latin America, 105 in the Caribbean Islands (33.1%), 48 in Asia (15.1%), 8 in the South Asia (2.5%), 10 in Russia/Eastern Europe (3.2%) and 46 (14.5%) in the United States. Patients presented at varying stages of disease: 51.4% at stage I, 19.6% at stage II, 19.6% at stage III, and 8.5% at stage IV. Kaplan-Meier estimated survival curves stratified by birthplace demonstrated significant differences in survival distributions among the groups using the log-rank test (P<0.0001). The most favorable survival curves were observed among patients born in Latin America and Asia whereas the least favorable was demonstrated in US-born patients. Time to death was analyzed using the Cox proportional hazards model. Adjusting for age at diagnosis, insurance status, stage and treatment modality, nodal metastases and hydronephrosis, birthplace was significantly associated with survival time (P<0.0001)., Conclusion: An immigrant health paradox was defined for foreign-born Latino and Asian patients presenting with cervical cancer to the Public Hospital System of Queens, New York as patients born in Latin America and Asia were less likely to die at any given time compared to those born in the United States., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)., Methods: We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013., Results: After a median of 33.3 months of follow-up (interquartile range 16.3-49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11-0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04-0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT ( p < 0.001)., Conclusion: Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades., Clinicaltrialsgov Identifier: NCT00389181., Classification of Evidence: This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years., (© 2017 American Academy of Neurology.)

Purpose: The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort., Methods: The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review., Results: Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children., Conclusion: Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.Genet Med advance online publication 13 October 2016.

Both familial and sporadic porphyria cutanea tarda (PCT) are iron dependent diseases. Symptoms of PCT resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y, c.843G>A, rs1800562) that enhances iron aborption by reducing hepcidin expression is a risk factor for PCT. Recently, a polymorphic variant (D519G, c.1556A>G, rs11558492) of glyceronephosphate O-acyltransferase (GNPAT) was shown to be enriched in male patients with type I hereditary hemochromatosis (HFE C282Y homozygotes) who presented with a high iron phenotype, suggesting that GNPAT D519G, like HFE C282Y, is a modifier of iron homeostasis that favors iron absorption. To challenge this hypothesis, we investigated the frequency of GNPAT D519G in patients with both familial and sporadic PCT. Patients were screened for GNPAT D519G and allelic variants of HFE (both C282Y and H63D). Nucleotide sequencing of uroporphyrinogen decarboxylase (URO-D) identified mutant alleles. Patients with low erythrocyte URO-D activity or a damaging URO-D variant were classified as familial PCT (fPCT) and those with wild-type URO-D were classified as sporadic PCT (sPCT). GNPAT D519G was significantly enriched in the fPCT patient population (p = 0.0014) but not in the sPCT population (p = 0.4477). Both HFE C282Y and H63D (c.187C>G, rs1799945) were enriched in both PCT patient populations (p<0.0001) but showed no greater association with fPCT than with sPCT., Conclusion: GNPAT D519G is a risk factor for fPCT, but not for sPCT., Competing Interests: The authors have declared that no competing interests exist.

Background: Chronic injury in kidney transplants remains a major cause of allograft loss. The aim of this study was to identify a gene set capable of predicting renal allografts at risk of progressive injury due to fibrosis., Methods: This Genomics of Chronic Allograft Rejection (GoCAR) study is a prospective, multicentre study. We prospectively collected biopsies from renal allograft recipients (n=204) with stable renal function 3 months after transplantation. We used microarray analysis to investigate gene expression in 159 of these tissue samples. We aimed to identify genes that correlated with the Chronic Allograft Damage Index (CADI) score at 12 months, but not fibrosis at the time of the biopsy. We applied a penalised regression model in combination with permutation-based approach to derive an optimal gene set to predict allograft fibrosis. The GoCAR study is registered with ClinicalTrials.gov, number NCT00611702., Findings: We identified a set of 13 genes that was independently predictive for the development of fibrosis at 1 year (ie, CADI-12 ≥2). The gene set had high predictive capacity (area under the curve [AUC] 0·967), which was superior to that of baseline clinical variables (AUC 0·706) and clinical and pathological variables (AUC 0·806). Furthermore routine pathological variables were unable to identify which histologically normal allografts would progress to fibrosis (AUC 0·754), whereas the predictive gene set accurately discriminated between transplants at high and low risk of progression (AUC 0·916). The 13 genes also accurately predicted early allograft loss (AUC 0·842 at 2 years and 0·844 at 3 years). We validated the predictive value of this gene set in an independent cohort from the GoCAR study (n=45, AUC 0·866) and two independent, publically available expression datasets (n=282, AUC 0·831 and n=24, AUC 0·972)., Interpretation: Our results suggest that this set of 13 genes could be used to identify kidney transplant recipients at risk of allograft loss before the development of irreversible damage, thus allowing therapy to be modified to prevent progression to fibrosis., Funding: National Institutes of Health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)