bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of fisetin and 2′,4′,6′-trihydroxydihyrochalcone 4′-O-β-neohesperidoside based on site-selective deacetylation and deoxygenation
Authors: Tsunekawa Ryuji , Hanaya Kengo , Higashibayashi Shuhei , Sugai Takeshi
Published: April 2018

Fisetin and 2′,4′,6′-trihydroxydihyrochalcone 4′-O-β-neohesperidoside were synthesized from commercially available quercetin and naringin in five steps. The key steps are site-selective deacetylation and subsequent deoxygenation. The target molecules were obtained in 37% and 23% yields from the starting materials, respectively.
New metabolites, sarcopodinols A and B, isolated from deep-sea derived fungal strain Sarcopodium sp. FKJ-0025
Authors: Matsuo Hirotaka , Nonaka Kenichi , Nagano Yuriko , Yabuki Akinori , Fujikura Katsunori , Takahashi Yōko , Ōmura Satoshi , Nakashima Takuji
Published: April 2018

Fungal strain FKJ-0025 was isolated from deep-sea sediment collected at the Wakamiko Caldera in Kagoshima Bay (water depth: 200 m). The fungal strain FKJ-0025 was identified as the genus Sarcopodium based on its morphology and internal transcribed spacer (ITS) sequence. Two new compounds, designated sarcopodinols A (1) and B (2), were isolated together with the known compound SF-227 (3).
Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition
Authors: Samanta Amrita , Kiselar Janna , Pumroy Ruth A. , Han Seungil , Moiseenkova-Bell Vera Y.
Published: April 2018

Pain, though serving the beneficial function of provoking a response to dangerous situations, is an unpleasant sensory and emotional experience. Transient receptor potential ankyrin 1 (TRPA1) is a member of the transient receptor potential (TRP) cation channel family and is localized in “nociceptors,” where it plays a key role in the transduction of chemical, inflammatory, and neuropathic pain. TRPA1 is a Ca2+-permeable, nonselective cation channel that is activated by a large variety of structurally unrelated electrophilic and nonelectrophilic chemical compounds. Electrophilic ligands are able to activate TRPA1 channels by interacting with critical cysteine residues on the N terminus of the channels via covalent modification and/or disulfide bonds. Activation by electrophilic compounds is dependent on their thiol-reactive moieties, accounting for the structural diversity of the group. On the other hand, nonelectrophilic ligands do not interact with critical cysteines on the channel, so the structural diversity of this group is unexplained. Although near-atomic-resolution structures of TRPA1 were resolved recently by cryo-electron microscopy, in the presence of both agonists and antagonists, detailed mechanisms of channel activation and inhibition by these modulators could not be determined. Here, we investigate the effect of both electrophilic and nonelectrophilic ligands on TRPA1 channel conformational rearrangements with limited proteolysis and mass spectrometry. Collectively, our results reveal that channel modulation results in conformational rearrangements in the N-terminal ankyrin repeats, the pre-S1 helix, the TRP-like domain, and the linker regions of the channel.
Determining the Best Immunization Strategy for Protecting African Children Against Invasive Salmonella Disease
Authors: Jeon Hyon Jin , Pak Gi Deok , Im Justin , Owusu-Dabo Ellis , Adu-Sarkodie Yaw , Gassama Sow Amy , Bassiahi Soura Abdramane , Gasmelseed Nagla , Keddy Karen H , Bjerregaard-Andersen Morten , Konings Frank , Aseffa Abraham , Crump John A , Chon Yun , Breiman Robert F , Park Se Eun , Cruz Espinoza Ligia Maria , Seo Hye Jin , May Jürgen , Meyer Christian G , Andrews Jason R , Panzner Ursula , von Kalckreuth Vera , Wierzba Thomas F , Rakotozandrindrainy Raphaël , Dougan Gordon , Levine Myron M , Hombach Joachim , Kim Jerome H , Clemens John D , Baker Stephen , Marks Florian
Published: April 2018

Background

The World Health Organization recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons ≥6 months to 45 years residing in typhoid fever (TF)–endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations.

Methods

The Typhoid Fever Surveillance in Africa Program (TSAP) was a blood culture-based surveillance of febrile patients from defined populations presenting at healthcare facilities in 10 African countries. TF and invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0–10 year-olds in one-year age increments.

Results

Salmonella Typhi and iNTS were the most frequently isolated pathogens; 135 and 94 cases were identified, respectively. Analysis from three countries was excluded (incomplete person-years of observation (PYO) data). Thirty-seven of 123 TF cases (30.1%) and 71/90 iNTS disease cases (78.9%) occurred in children aged <5 years. No TF and 8/90 iNTS infections (8.9%) were observed in infants aged <9 months. The TF incidences (/100 000 PYO) for children aged <1 year and 1 to <2 years were 5 and 39, respectively; the highest incidence was 304 per 100 000 PYO in 4 to <5 year-olds. The iNTS disease incidence in the defined age groups ranged between 81 and 233 per 100 000 PYO, highest in 1 to <2 year-olds. TF and iNTS disease incidences were higher in West Africa.

Conclusions

High burden of TF detected in young children strengthens the need for TCV introduction. Given the concurrent iNTS disease burden, development of a trivalent vaccine against S. Typhi, S. Typhimurium, and S. Enteritidis may be timely in this region.
Microelectrode Recordings Validate the Clinical Visualization of Subthalamic-Nucleus Based on 7T Magnetic Resonance Imaging and Machine Learning for Deep Brain Stimulation Surgery
Authors: Shamir Reuben R , Duchin Yuval , Kim Jinyoung , Patriat Remi , Marmor Odeya , Bergman Hagai , Vitek Jerrold L , Sapiro Guillermo , Bick Atira , Eliahou Ruth , Eitan Renana , Israel Zvi , Harel Noam
Published: April 2018

BACKGROUND

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a proven and effective therapy for the management of the motor symptoms of Parkinson's disease (PD). While accurate positioning of the stimulating electrode is critical for success of this therapy, precise identification of the STN based on imaging can be challenging. We developed a method to accurately visualize the STN on a standard clinical magnetic resonance imaging (MRI). The method incorporates a database of 7-Tesla (T) MRIs of PD patients together with machine-learning methods (hereafter 7 T-ML).

OBJECTIVE

To validate the clinical application accuracy of the 7 T-ML method by comparing it with identification of the STN based on intraoperative microelectrode recordings.

METHODS

Sixteen PD patients who underwent microelectrode-recordings guided STN DBS were included in this study (30 implanted leads and electrode trajectories). The length of the STN along the electrode trajectory and the position of its contacts to dorsal, inside, or ventral to the STN were compared using microelectrode-recordings and the 7 T-ML method computed based on the patient's clinical 3T MRI.

RESULTS

All 30 electrode trajectories that intersected the STN based on microelectrode-recordings, also intersected it when visualized with the 7 T-ML method. STN trajectory average length was 6.2 ± 0.7 mm based on microelectrode recordings and 5.8 ± 0.9 mm for the 7 T-ML method. We observed a 93% agreement regarding contact location between the microelectrode-recordings and the 7 T-ML method.

CONCLUSION

The 7 T-ML method is highly consistent with microelectrode-recordings data. This method provides a reliable and accurate patient-specific prediction for targeting the STN.
The Effect of Monitoring Viral Load and Tracing Patients Lost to Follow-up on the Course of the HIV Epidemic in Malawi: A Mathematical Model
Authors: Estill Janne , Kerr Cliff C , Blaser Nello , Salazar-Vizcaya Luisa , Tenthani Lyson , Wilson David P , Keiser Olivia
Published: April 2018

Background

Antiretroviral therapy (ART) reduces HIV transmission, but treated patients may again become infectious. We used a mathematical model to determine whether ART as prevention is more effective if viral load (VL) is routinely monitored and patients lost to follow-up (LTFU) traced.

Methods

We simulated ART cohorts to parameterize a deterministic transmission model calibrated to Malawi. We investigated the following strategies for improving treatment and retention: monitoring VL every 12 or 24 months, tracing patients LTFU, or a generic strategy leading to uninterrupted treatment. We tested 3 scenarios, where ART scale-up continues at current (Universal ART), reduced (Failed scale-up), or accelerated speed (Test&Treat).

Results

In the Universal ART scenario, between 2017 and 2020 (2050), monitoring VL every 24 months prevented 0.5% (0.9%), monitoring every 12 months prevented 0.8% (1.4%), tracing prevented 0.3% (0.5%), and uninterrupted treatment prevented 5.5% (9.9%) of HIV infections. Failed scale-up resulted in 25% more infections than the Universal ART scenarios, whereas Test&Treat resulted in 7%–8% less.

Conclusions

Test&Treat reduces transmission of HIV, despite individual cases of treatment failure and ART interruption. Whereas viral load monitoring and tracing have only a minor impact on transmission, interventions that aim to minimize treatment interruptions can further increase the preventive effect of ART.
Accuracy of Activity Trackers in Parkinson Disease: Should We Prescribe Them?
Authors: Wendel Nicholas , Macpherson Chelsea E , Webber Karoline , Hendron Kathryn , DeAngelis Tamara , Colon-Semenza Cristina , Ellis Terry
Published: April 2018

Background

Wearable, consumer-grade activity trackers have become widely available as a means of monitoring physical activity in the form of step counts. However, step counts may not be accurate in persons with Parkinson disease (PD) due to atypical gait characteristics.

Objective

This study aimed to investigate the accuracy of 4 consumer-grade activity trackers in individuals with PD while ambulating during continuous and discontinuous walking tasks.

Design

This study used a cross-sectional design.

Methods

Thirty-three persons with PD (Hoehn & Yahr stages 1–3) donned 4 models of activity trackers on the less affected side of their bodies. Participants performed 2 continuous walking tasks (2-minute walk tests at comfortable and fast speeds) and 2 discontinuous walking tasks (a simulated household course and an obstacle negotiation course) in an outpatient setting. Bland-Altman plots and intraclass correlation coefficients [ICC(2,1)] were computed as a measure of agreement between actual steps taken (reference standard: video recording) and steps recorded by each tracker.

Results

The accuracy of the activity trackers varied widely, with ICCs ranging from −0.03 to 0.98. Overall, the most accurate device across all tasks was the Fitbit Zip, and the least accurate was the Jawbone Up Move during the simulated household course. All activity trackers were more accurate for continuous walking tasks compared with discontinuous walking tasks. Waist-mounted devices were more accurate than wrist-mounted devices with continuous tasks. Bland-Altman plots revealed that all activity trackers underestimated step counts.

Limitations

All walking tasks were measured over relatively short distances.

Conclusions

In persons with mild-to-moderate PD, waist-worn activity trackers may be prescribed to monitor bouts of continuous walking with reasonable accuracy; however, activity trackers have little utility in monitoring discontinuous walking common in household settings.
Persistent vs Resolved Intrauterine Growth Restriction: A Retrospective, Cohort Study Assessing Neonatal Outcome [3A]
Authors: Lupea Ilinca , Saeed Haleema , Roberts Robyn
Published: April 2018

INTRODUCTION:

Intrauterine growth restriction (IUGR) is a common complication of pregnancy that has been shown to be associated with adverse perinatal outcomes. Once the diagnosis is made, antenatal monitoring becomes intensive and can cause parental stress and anxiety. The purpose of this study is to evaluate and compare neonatal outcomes in pregnancies which were diagnosed with IUGR that subsequently resolve in comparison to those with persistent IUGR.

METHODS:

This is a retrospective, cohort of singleton pregnancies complicated by IUGR (EFW < 10th percentile) from 2013 -2017 from Henry Ford Health System in Detroit, MI. There are approximately 1000 new IUGR diagnoses every year at Henry Ford. Neonatal outcomes were compared in pregnancies that IUGR resolved versus those with IUGR persisted throughout the pregnancy.

RESULTS:

The primary neonatal outcomes that will be compared between the two cohorts are: fetal birth weight, fetal APGAR scores (1 and 5 minutes), fetal umbilical cord gases, necrotizing enterocolitis, need for respiratory support, and length of stay in NICU. Secondary outcomes will assess route of delivery and gestational age at delivery. A descriptive analysis of the results obtained will be presented.

CONCLUSION:

Growth restriction has been shown to be a risk factor for adverse perinatal outcomes. Our study aims to analyze if this stands true for those pregnancies that had growth restriction that spontaneously resolved. The results may impact future guidelines in regards to antenatal testing for the pregnancies with spontaneous resolution of the fetal growth restriction.
Gestational Weight Changes in Obese Women: Where Do We Stand? [7A]
Authors: Chavan Niraj R. , McDaniel Honour , Williams Corrine M.
Published: April 2018

INTRODUCTION:

This study was undertaken to evaluate gestational weight changes among obese women in comparison to the 2009 IOM recommendations for a gestational weight gain (GWG) of 11 – 20 lbs.

METHODS:

Using the 2015 vital statistics (birth) data collected by the National Center for Health Statistics (NCHS) for singleton pregnancies, gestational weight changes were calculated and categorized as GWG of < 11 lbs, 11- 20 lbs (reference group), 21 – 30 lbs, 30 – 40 lbs, > 40lbs and gestational weight loss (GWL) of 0 – 10 lbs, and 11 – 20 lbs for women with class 1, 2 and 3 obesity. Multivariable logistic regression analyses were used to evaluate likelihood of gestational weight changes (GWG/GWL) across obesity classes accounting for age, race/ethnicity, education, marital status, insurance, WIC, prenatal care and smoking status.

RESULTS:

Of 859,996 obese women – 55.28%, 26.54% and 18.18% had class 1, 2 and 3 obesity respectively. Overall – 23.95% obese women achieved recommended GWG of 11 – 20 lbs, with 24.29% having GWG of 21 - 30 lbs and 30.27% having GWG of >30 lbs. While 16.68% obese women had GWG <11 lbs, only 4.79% experienced GWL. Obese women with excess GWG were more likely to be younger (OR = 1.61, 95% CI 1.56 – 1.68), unmarried (OR = 1.43, 95% CI 1.40 – 1.45), and smokers (OR = 1.19, 95% CI 1.16 – 1.22).

CONCLUSION:

Distinct gestational weight changes are seen across the maternal obesity spectrum with several key sociodemographic characteristics associated with excess and inadequate GWG.
Avoiding Hospital Admission for Rupture of Amniotic Membrane (ROM) screening: Role of at Home/Point of Care Testing [8A]
Authors: Bachmann Gloria A. , Lu Chi-Wei , Yeung Percy , Wiita Brinda , Abreu Kenneth
Published: April 2018

INTRODUCTION:

Rising health care costs are a major focus today. We examined the costs incurred in pregnant women presenting to a perinatal center to rule out rupture of membranes and the potential savings that would have occurred if this condition 1) could have been assessed at home or 2) inexpensively and quickly at the medical center site where they present.

METHODS:

A WIRB approved, retrospective review of medical records was performed in obstetrical patients presenting to rule out spontaneous rupture of membranes, in order to evaluate potential cost savings by screening at home prior to hospital admission. Hospital billing records and medical records were utilized to assess overall costs, including ancillary testing, incurred.

RESULTS:

Preliminary data indicates that 1) 50% of obstetrical patients presenting at a medical center have intact membranes and sent home undelivered and 2) 25% who are negatively screened come to L&D via the emergency department, increasing overall costs. From 214 records analyzed to date, admissions of women without ruptured membranes cost the health care system $359,315.59 dollars, or $1473.45 dollars per hospital encounter.

CONCLUSION:

These preliminary findings confirm data from other countries including England, that home/point of care testing for amniotic fluid leakage with a consumer-friendly diagnostic would be a cost-effective addition to healthcare. In addition to reducing costs by decreasing hospital encounters, this may alert women with ruptured membranes to appropriately visit the hospital for assessment and care and not assume urinary leakage as the cause.
Racial Disparities in Severe Maternal Morbidities Across the Pregnancy Continuum in the United States [17A]
Authors: Liese Kylea L. , Mogos Mulubrhan , Abboud Sarah , DeCocker Karen , Geller Stacie
Published: April 2018

INTRODUCTION:

This study investigates racial disparities in severe maternal morbidities (SMM) among antepartum (AP), intrapartum (IP) and postpartum (PP) U.S. hospital admissions between 2002 and 2014.

METHODS:

AP, IP and PP hospitalizations were identified in the National Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project for 2002-2014. ICD-9 codes indicating severe complications were used to identify hospitalizations with SMM. Individual-level co-morbidities, sociodemographic and behavioral characteristics were extracted from the NIS databases. The distribution of sociodemographic, behavioral, hospital characteristics, insurance, and comorbidities by whether a SMM occurred was summarized using descriptive statistics across the pregnancy continuum. Joinpoint regression was used to examine temporal trends of SMM during the study period by timing of hospitalization and stratified by race. Multivariate logistic regression was used to assess the association between race and SMM.

RESULTS:

Compared to Non-Hispanic White women, Black women hospitalized during the AP period are 70% more likely to experience SMM after adjusting for demographic, behavioral, hospital characteristics, insurance, and comorbidities (aOR = 1.7, 95% CI: [1.6-1.8]). The increased risk among Black women persisted during IP (aOR= 1.4, 95% CI: [1.3-1.5] and PP hospitalizations (aOR = 1.2, 95% CI: [1.1-1.2]. Hispanic women demonstrated comparable SMM risk during AP and slightly higher SMM risk during IP (aOR- 1.2 (1.1-1.3) to Non-Hispanic Whites. Interestingly, they had 20% less risk of SMM during PP hospitalization when compared to Non-Hispanic White women.

CONCLUSION:

Race significantly impacts both the timing and type of SMM a woman may experience, implicating further research on mechanisms and interventions to address disparities.
Outcomes of Robotic vs. Total Abdominal Hysterectomy Stratified by Age Group for Patients with Endometrial Cancer [19A]
Authors: Javadian Pouya , Juusela Alexander , Anderson Patrick
Published: April 2018

INTRODUCTION:

To compare clinical and pathologic features, surgical morbidity, and outcomes stratified by age in patients with endometrial cancer who underwent Robotic-assisted laparoscopic total hysterectomy (RALTH) vs. Total Abdominal Hysterectomy

METHODS:

All women with surgically treated endometrial cancer at the Newark Beth Israel Medical Center between January 2004 and December 2015 were eligible; 353 patients met criteria and underwent retrospective chart review. Patients were stratified into 3 groups based on age the ranges <45, 46-64 and >65 years. Demographic data, pathologic, surgical treatment and complications were retrospectively reviewed. Statistical analysis was performed by SPSS.

RESULTS:

There were no statistically significant differences regarding operation characteristics and complications in patients with age <45 years. In patients of age between 46-64 years, there was a statistically significant increased estimated blood loss (EBL), median (range), (400 (50-6000) cc vs. 100 (20-7000) cc, p: <0.001) and length of stay (LOS) 4 (1-51) vs. 1.5 (1-41) days, p: <0.001 in the TAH group compared to the RALTH group. Patients who underwent RALTH experienced longer operative time than the TAH group (234.3±81.2 vs. 259.5±68.4, p:0.039). In patients with age >65 years, LOS [7 (2-39) vs. 2 (1-43) days, p<0.001] and intra-operative hemorrhage [14/79 (17.7%) vs. 1/78 (1.2%), p<0.001] were significantly higher in TAH than the RALTH patients.

CONCLUSION:

Older patients with endometrial cancer benefit from the lower rate of postoperative complications with RALTH than TAH. Patients undergoing RALTH benefit from decreased postoperative morbidity.
Effect of Peri-Operative Selective and Nonselective Beta Blocker Use on Survival in Ovarian Cancer Patients [20A]
Authors: Mattappally Nidha , Korets Sharmilee , Hughes Sarah , Zweizig Susan , Bradford Leslie
Published: April 2018

INTRODUCTION:

Preclinical studies have demonstrated that adrenergic agonists mediate tumor growth and invasiveness in ovarian cancer models via the beta-2 adrenergic receptor. Studies have also investigated the clinical impact of beta blocker use on epithelial ovarian cancer (EOC) survival with conflicting results. We aim to understand the association between peri-operative beta blockade and clinical outcomes in EOC patients.

METHODS:

We conducted an institutional retrospective chart review and examined the effects of beta blocker use on overall survival (OS) and progression free survival (PFS) when looking at peri-operative timing of beta blocker use in EOC.

RESULTS:

In a cox survival model, women who took a selective beta blocker (SBB) in the peri-operative period were four times more likely to die compared to nonusers when looking at OS (adjusted SBB HR 5.82, 95% CI 1.17-28.91, p=0.031). Although there was no difference in PFS between nonselective beta blocker (NSBB) users and nonusers (adjusted NSBB HR 1.88, 95% CI 0.41-8.60, p=0.414), SBB users were four times more likely to have recurrence of disease compared to nonusers (adjusted SBB HR 4.24, 95% CI 1.23-14.55, p=0.022).

CONCLUSION:

Compared to never use, SBB use peri-operatively was associated with poorer OS and ever SBB use was associated with poorer PFS in patients with EOC. This is an area that warrants further investigation as preclinical studies would suggest a potential survival benefit, but reports in the literature are conflicting and our data seem to suggest a potential harm with SBB use.
Impact of a Documentation Intervention on Health-Assessment Metrics on an Inpatient Gynecologic Oncology Service [24A]
Authors: Marquiette Jaclyn , Moss Haley , Truong Tracy , Havrilesky Laura
Published: April 2018

INTRODUCTION:

Severity of illness (SOI) and risk of mortality (ROM) scores are determined from specific medical diagnoses and procedures during admission; without proper documentation, scores may not accurately reflect patients’ medical complexity. Our quality improvement study aimed to improve the accuracy of SOI and ROM capture within the electronic medical record (EMR) through implementation of documentation initiatives.

METHODS:

Documentation interventions were introduced on an inpatient gynecologic oncology service in January 2017 as follows: educational in-service for faculty and residents; introduction of problem-based assessment/plans in EMR progress notes; distribution of a documentation tip badge to residents and fellows; production of a high-yield documentation tip video. Admission/discharge SOI and ROM (scaled 1 to 4) and admission type/diagnosis were collected from gynecologic oncology inpatients pre-(2015) and post-(2017) intervention. 528 inpatient encounters from 349 unique patients were queried. A one-sided Wilcoxon rank sum test queried the hypothesis that SOI and ROM scores were higher post- compared to pre-intervention.

RESULTS:

Among 349 included patients, 254 (72.8%) were admitted in 2015 and 95 (27.2%) in 2017. Median admission and discharge SOIs each increased from 2 to 3 after intervention; P=0.002 and P=0.002, respectively. Median admission and discharge ROMs each remained at 2 but with improvement in the IQR following intervention; P=0.005 and P=0.02, respectively. Stratified by admission type, a significant increase was observed in scores for surgical, but not medical, admissions.

CONCLUSION:

A robust educational intervention to improve physician coding accuracy resulted in higher SOI and ROM scores for surgical admissions.
Is There a Synthetic Lethality Between FANCM-U and SMARCAL1? [27A]
Authors: Sabet Liliya , Zhang Dong
Published: April 2018

INTRODUCTION:

Our oncology lab recent results showed that there is a strong synthetic lethal interaction between BRCA1 and FANCM. We observed a similar synthetic lethal interaction between BLM, a DNA helicase, and FANCM, albeit somewhat weaker than that of BRCA1 and FANCM. Furthermore we showed that BRCA1 recruits BLM to the replication stress sites induced by the depletion of FANCM. Our data suggest that a FANCM inhibitor may be used to potentially kill cancers with BRCA1 mutations. Most recently another DNA helicase, SMARCAL1, was shown to resolve replication stress.

METHODS:

We proposed to test whether there is a synthetic lethal interaction between SMARCAL1 and FANCM-U by performing a Crystal Violet Cell Viability Assay. We transfected U2-OS, a human osteosarcoma cell line, with siRNA targeting Luciferase (serves as the negative control siRNA), FANCM-U, SMARCAL1, and both FANCM-U and SMARCAL1. Then we seeded 4,000 cells per well on a 12-well plate. 7 to 10 days later we stained the cells with Crystal Violet, a blue dye, to visualize viable cells. Finally we quantitated the amount of viable cells with a spectrometer. We repeated the Crystal Violet Cell Viability Assay three times to obtain a reproducible result.

RESULTS:

Based on spectrometer results the amount of viable cells or intensity of light detected in the control and FANCM-U and SMARCAL1 wells were similar.

CONCLUSION:

This study did not show synthetic lethal interaction between FANCM-U and SMARCAL1. Further research is ongoing to support or oppose our hypothesis.
High Risk Anal and Cervical HPV Infections Among Sexual Minority Women [28A]
Authors: Forner Elizabeth , Combs Shanna , Felini Martha
Published: April 2018

INTRODUCTION:

To examine anal and cervical high-risk HPV (hr-HPV) infections among women having sex with women, and women having sex with men and women.

METHODS:

We conducted a cross-sectional study of women ages 18-70 in treatment at the largest substance use disorders center in North Texas who participated in a cancer prevention program providing well woman exams. Demographics, past trauma, sexual practices, and risky behaviors were collected using self-administered questionnaires. Chi-square tests and logistic regression controlling for age (AOR) were used to compare hr-HPV infection prevalence rates by sexual minority status.

RESULTS:

A total of 757 women with histories of trauma were included in this study; 84% were smokers, 53% self-reported previous incarceration and 25% traded sex for drugs. Nearly one-quarter reported having oral, vaginal, or anal sex with women only, or with men and women. Among this sexual minority group, 40% tested positive for anal hr-HPV vs 34% of heterosexual women (P=.18). Cervical hr-HPV was present in 31% of sexual minority women and 27% of heterosexual women (P=.20). Sexual minority status was not significantly associated with anal hr-HPV (AOR 1.23 95% CI .85-1.77) or cervical hr-HPV (AOR 1.09 95% CI .76-1.55) compared to heterosexual women. Cervical hr-HPV was significantly associated with anal hr-HPV among both groups (P<.01). Nearly 20% of sexual minority women tested positive for both anal and cervical hr-HPV.

CONCLUSION:

These findings inform providers about HPV infections among sexual minority women, and the appropriateness of anal pap and HPV co-testing exams in this population.
Pathogenic Variants Identified in Women with Epithelial Ovarian Cancer Diagnosed Before Age 31 [35A]
Authors: Marshall Megan , Carter Natalie J. , Murphy Patricia D. , Fagbemi Adebanke , Klein Rachel T. , Hruska Kathleen S.
Published: April 2018

INTRODUCTION:

Ten to 18% of ovarian cancer (OC) can be attributed to a hereditary predisposition. The frequency of pathogenic variants (PVs) among women with epithelial ovarian cancer (EOC) diagnosed at an early age has not been well-described. We present the yield of PVs in women with EOC diagnosed ≤30 years (y) who have undergone genetic testing at a commercial laboratory.

METHODS:

Results for women with OC submitted for multi-gene hereditary cancer panel testing of at least ATM, BRCA1/2, BRIP1, CHEK2, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, and RAD51D were reviewed. Yields were compared using two-tailed Fisher exact test.

RESULTS:

One hundred fifty-three women with OC were diagnosed ≤30y, and 65 (42%) had EOC. Family history of OC was reported for 35 women (26.9%). Five PVs, in BRIP1, CHEK2 (3) and PALB2, were identified in the women with EOC for a positive yield of 7.7%, which is similar to the yield in all women with OC diagnosed ≤30y regardless of histopathologic subtype (5.9%, 9/153, P=.77; ATM, BRIP1, CHEK2 (6), PALB2). The yield of PVs in women with OC diagnosed >30y was significantly higher than either yield in the early-onset group (14.7%, 546/3,704, P<.0013).

CONCLUSION:

Women with early-onset OC were less likely to have a PV than those diagnosed >30y, though the detected yield was still appreciable. No PVs were identified in BRCA1/2 or the Lynch syndrome genes, highlighting the utility of panel testing and including genes beyond BRCA1/2 for women with OC regardless of age and histopathology.
Defining the Sociodemographic Impact on the Latency Period Following Preterm Premature Rupture of Membranes [37A]
Authors: Lambert Calvin , Ranjit Anju , McDonald Vanessa
Published: April 2018

INTRODUCTION:

Traditionally antibiotics have been viewed as the primary intervention promoting latency (the period between confirmed rupture and delivery) following preterm premature rupture of membranes (PPROM). While most studies have investigated immediate risks to a shortened latency period, few have elucidated the impact of predisposed social disadvantages. The objective of our study is to establish a sociodemographic predictive model among a cohort of patients with the diagnosis of PPROM and their risk of preterm delivery.

METHODS:

Centers for Disease Control (CDC) birth-certificate data (2012-2013) were used to identify women with PPROM. Sociodemographic and clinical characteristics of women, who delivered <34 weeks, 34-36 weeks, and ≥37weeks of gestation were compared using chi-squared tests. These included health insurance source, number of prenatal visits, and education. Multinomial logistic regression models were used to calculate the relative risk ratios (RRR) of delivery <34 weeks and 34-36 weeks compared to delivery at ≥37 weeks.

RESULTS:

A total of 242,290 women with PPROM were identified; 16.1%, 19.7% and 64.2% delivered at <34weeks, between 34-36 weeks, and ≥37 weeks, respectively. Black race was more likely to have delivery at <34 weeks (28.2%) and 34-36 weeks (19.4%) compared to ≥37 weeks (14.2%)(p<0.001). Black race (<34weeks:RRR:1.99;CI:1.94-2.06; 34-36weeks: RRR:1.35;CI:1.31-1.39), high school education or less(<34weeks:RRR:1.19;CI:1.15-1.23; 34-36weeks: RRR:1.16;CI:1.13-1.19), Medicaid insurance(<34weeks:RRR:1.13;CI:1.10-1.17; 34-36weeks: RRR:1.09;CI:1.05-1.12), and 1-3 prenatal visits(<34weeks:RRR:1.45;CI:1.35-1.56; 34-36weeks: RRR:1.03;CI:0.95-1.12) were more likely to have preterm delivery.

CONCLUSION:

Correlates of social disadvantage were associated with a decreased latency period among those patients with PPROM. Targeted interventions among socially disadvantaged groups could help decrease this incidence of preterm birth.
Time Interval from Delivery to Maternal First Neonatal ICU Contact. Are We Doing a Good Job? [39A]
Authors: Thompson Benjamin , Promecene-Cook Pamela , Byrd Teresa , Adler Michael
Published: April 2018

INTRODUCTION:

To determine the interval between delivery and first maternal NICU contact, and to correlate this with maternal conditions and therapies.

METHODS:

Mothers delivered at our institution and whose infants were admitted to the NICU were identified. A retrospective chart review was performed to collect demographic data, date and time of delivery, maternal antepartum, intrapartum, and postpartum diagnoses, and therapies. NICU sign-in logs were used to determine the time of first maternal contact. Mother’s admitted to the ICU and/or whose infants were transitioned back to the low-risk nursery were excluded.

RESULTS:

The mean interval time to first maternal NICU contact was 18.3 hours. Factors associated with delayed maternal visitation includes mode of delivery (13.3 hours for vaginal vs. 21.1 hours for cesarean, P<.001), the diagnosis of pre-eclampsia with severe features/HELLP (23.9 hours vs. 16.3 hours, P=.003), medications outside routine orders including I.V. antibiotics (21.3 hours, P=.033), PCA pain control (23.5 hours, P=.024), magnesium sulfate (23.5 hours, P<.001), and blood transfusion (26.8 hours, P=.03). There was no correlation found for delayed maternal visitation for infant gender, nursing shift at time of delivery, or having any diagnosis other than pre-eclampsia with severe features/HELLP.

CONCLUSION:

The interval for first maternal NICU contact at our institution leaves much room for improvement. The highest risks populations for delayed NICU contact include cesarean deliveries, patients diagnosed with pre-eclampsia with severe features/HELLP syndrome, and patients receiving infusions such as magnesium sulfate, PCA delivery pain medications, I.V. antibiotics, or blood transfusions. Quality improvement initiatives are in development to decrease this time interval.
Clomiphene Citrate and Intrauterine Insemination: Analysis of 1,531 Cycles by Time Trying to Conceive [6B]
Authors: Stewart Joshua , Panchap Latha , Spandorfer Steven D.
Published: April 2018

INTRODUCTION:

Clomiphene citrate and intrauterine insemination (CC/IUI) is often a first-line treatment for infertile couples. While it is well established that fecundity rates decrease with age, outcomes of CC/IUI cycles have not been well stratified by time trying to conceive (TTC).

METHODS:

All CC/IUI cycles performed under a single physician from January 1, 2010 to December 31, 2016 were included, totaling 1,531 cycles in 536 unique couples. The following data were collected from an electronic medical record: age, obstetrical history, semen parameters, time TTC at cycle start, and cycle outcome. Stata IC 15 was used to calculate pregnancy rates. Chi-squared test was used to calculate p-values.

RESULTS:

The positive pregnancy rate (PPR) for couples TTC <1 year was 16.5%; 14.7% when TTC for 1-2 years, 15.4% when TTC for 2-3 years, and 8.6% when TTC for >3 years (p<0.05). The corresponding ongoing pregnancy rates (OPR) were as follows: 11.2%, 9.8%, 7.5%, 3.7% (p<0.05). In women <35 years old at cycle start, the corresponding OPRs were as follows: 13.1%, 11.3%, 8.6%, 4.3% (p<0.05); for women >35 years old at cycle start: 7.4%, 6.1%, 5.9%, 1.7% (p<0.05).

CONCLUSION:

Patients TTC with CC/IUI for <1 year have a higher PPR and OPR as compared to patients TTC for >1 year. Ongoing pregnancy rates further decline with each additional year TTC, and by 3 years of TTC, success rates dramatically decrease at all ages. This data provides important information to the clinician counseling infertile patients regarding when referral to a specialist and more aggressive treatments may be warranted.
Serum IL-1RA Levels Predict IVF Outcome in Caucasian But Not African American Women [10B]
Authors: Elder Simone , Irani Mohamad , Witkin Steven S. , Spandorfer Steven D.
Published: April 2018

INTRODUCTION:

A growing body of evidence has shown that some cytokines are implicated in embryo development and implantation. Previous studies have suggested that serum levels of interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1RA) can predict IVF outcome. However, the majority of included patients were Caucasian (C). Therefore, we investigated whether IL-1β and IL-1RA are expressed differently and have different predictive values of IVF outcome between C and African American (AA) women.

METHODS:

A retrospective study including 129 C and 88 AA women undergoing fresh IVF cycles. Serum levels of IL-1β and IL-1RA on cycle day (CD) 2 (before starting ovarian stimulation) and CD28 (14 days after oocyte retrieval) were compared between those who did or did not become pregnant. Values were expressed as mean±SEM. t-test was used as appropriate.

RESULTS:

C women had higher serum IL-1β levels compared to AA patients on CD2 (23.3±8.1 vs. 15.3±12.9 pg/mL, P=0.02). The IL-1RA level on CD 28 in C women, who achieved a pregnancy was higher as compared to those who did not become pregnant (488.2±83.9 vs. 183.4±45.3 pg/mL, P=0.02). In contrast, IL-1RA levels on CD28 were comparable between AA women who did or did not become pregnant (343.8±83.9 vs. 627.4±404.9, P=0.5).

CONCLUSION:

C women have different levels of IL-1 family cytokines as compared to AA women. Serum IL-1RA levels can predict IVF outcome in C but not in AA women. We are currently conducting a prospective study to examine the racial differences in additional cytokines among women undergoing IVF.
IVF Pregnancy after Cytoreductive Surgery and HIPEC of Diffuse Malignant Peritoneal Mesothelioma [12B]
Authors: de Assis Viviana , Adams Jaye , Saunders Rhiana
Published: April 2018

INTRODUCTION:

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare yet aggressive neoplasm arising from mesothelial cells of the peritoneum. It spreads extensively within the abdominal cavity with substantial associated morbidity and mortality. Expertise in cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal perfusion chemotherapy (HIPEC) has led to increased overall survival for patients. With improving survival rates and possibility of cure, it is unknown what impact CRS and HIPEC have on the future fertility of reproductive-aged women. We report the case of a successful pregnancy achieved with in-vitro fertilization (IVF) following CRS and HIPEC treatment for epithelioid subtype DMPM.

METHODS:

Data collected from Essentris and Altha, Department of Defense Electronic Medical records for outpatient and inpatient care.

RESULTS:

A 28 year old female with primary infertility and recurrent ascites was found to have fleshy- appearing peritoneal nodules on laparoscopy with histologic findings of epithelioid subtype DMPM. She elected ovarian suppression with a GnRH-agonist prior to undergoing CRS, HIPEC, and adjuvant chemotherapy. Spontaneous return of menses occurred 18 months after completion of chemotherapy. After two years of remission, she pursued fertility treatment with IVF, and has an ongoing uncomplicated singleton gestation.

CONCLUSION:

Median survival for patients with DMPM has improved to approximately 50% at five years with CRS and HIPEC treatment. We report the first known case of a successful pregnancy achieved with IVF following CRS, HIPEC, and adjuvant chemotherapy for DMPM. Of interest, GnRH pre-treatment offered an approach to ovarian suppression. In light of urgency to initiate expeditious treatment, this approach possibly optimized fertility preservation and post-treatment childbearing potential.
Accurate Assessment of Blood Loss During Cesarean Delivery Improves Estimate of Postoperative Hemoglobin [17B]
Authors: Rubenstein Andrew , Tully Griffeth , Thurer Robert
Published: April 2018

INTRODUCTION:

The need for red blood cell transfusion for patients having cesarean delivery is ideally based on an evaluation of both clinical indicators and laboratory studies. In practice, transfusions are often given to women based on estimated intraoperative blood loss (EBL) and/or the postoperative hemoglobin level. Since visual estimation is known to be inaccurate, we postulated that a more accurate determination using a novel colorimetric device would be better correlated with postoperative day one hemoglobin than visual estimation.

METHODS:

A formula incorporating both height and weight was used to estimate blood volume and, by including preoperative hemoglobin, red cell mass. Assuming a constant blood volume either the visual EBL (n=32) or EBL using a novel colorimetric device (Triton System™, Gauss Surgical) that incorporates a mobile application to photograph sponges and canisters and calculate their hemoglobin content (n=53) was used to predict the postoperative day one hemoglobin value in patients where either the visual estimate or colorimetric estimate was >1,000 ml (a common definition of hemorrhage).

RESULTS:

The predicted postoperative day one hemoglobin level using the device was better correlated with the actual value (R squared=0.319) than the predictions using visual EBL (R squared=0.035) (P=.027).

CONCLUSION:

In mothers with high blood loss, EBL using the novel device was a more accurate predictor of the postoperative day one hemoglobin than visually estimated blood loss. Clinical use of this information has the potential to improve transfusion practice in cesarean delivery patients and positively impact maternal health.
Current Inpatient Antenatal Fetal Surveillance Paradigms and the Effect on Clinical Decision Making [23B]
Authors: Racusin Diana , Adimorah Nesochi , Piro Mica , Heye Kristen , Sharp Charlotte , Blackwell Sean C. , Refuerzo Jerrie S.
Published: April 2018

INTRODUCTION:

While outpatient biophysical profiles (BPPS) are routinely used to prevent intrauterine fetal demise, the clinical utility of BPPs performed inpatient with scheduled electronic fetal monitoring (EFM) is uncertain. Our objective was to determine whether BPPs performed in the hospital on the antepartum unit result in prolonged duration of EFM or in delivery.

METHODS:

A retrospective cohort review was performed among women who had a BPP during their antepartum hospital admission. Women were divided into two groups (BPPs 8/8 or 6/8 or less) and their outcomes compared. The primary outcome was the need for prolonged EFM greater than 2 hours or decision to proceed with delivery. Maternal demographics, pregnancy characteristics, and neonatal outcomes were compared. Indications for hospitalization and delivery were collected. Student-t test and chi-square test were used for statistical analysis.

RESULTS:

Among our high-risk cohort (n=325), delivery management was altered in one case (0.3%) by the BPP findings. There were no BPPs that resulted in need for prolonged monitoring. Need for delivery or prolonged monitoring was primarily dictated by either change in clinical scenario or EFM abnormalities. Compared to women with BPP 8/8, women with BPP 6/8 or less were admitted and delivered at significantly earlier gestational ages, had higher corticosteroid rates, lower birthweight neonates and required more frequent NICU admissions.

CONCLUSION:

In our analysis, hospital BPPs alter clinical decision making in less than 1% of cases. An intervention trial is warranted to assess the potential benefits of BPPs in an inpatient antepartum setting.
Prevalence of Chronic and Pregnancy-Induced Cardiovascular Conditions in Severe Maternal morbidity in Texas [24B]
Authors: Salahuddin Meliha , Mandell Dorothy , Lakey David , Patel Divya
Published: April 2018

INTRODUCTION:

In 2011-2012, the three leading causes of maternal mortality in Texas were cardiac events, drug overdose, and hypertension/eclampsia, with two out of the three being cardiovascular-related conditions. While chronic conditions likely contribute to mortality, severe maternal morbidity (SMM) metrics only include eclampsia and do not include chronic cardiovascular conditions such as preexisting hypertension. To better understand the contribution of both pregnancy-induced and chronic cardiovascular conditions to SMM, the prevalence of comorbid cardiovascular conditions among women with SMM was assessed.

METHODS:

Delivery-related hospitalizations between 2011-2014 were classified as SMM, based on the CDC’s coding scheme. Cardiovascular comorbidities among SMM were classified using the obstetric comorbidity coding scheme identified by Bateman et al (2013). Prevalence was assessed by age to examine whether older women with SMM had higher prevalence of these comorbidities.

RESULTS:

SMM prevalence remained consistent between 2011 and 2014 (19.6-19.8 per 1,000 deliveries, p=0.57). Overall, SMM showed a quadratic relationship with age, with the youngest and oldest age groups having the highest prevalence (p<0.01). Among comorbidities assessed in SMM, the youngest and oldest age groups had the highest prevalence of severe preeclampsia/eclampsia. However, the prevalence of preexisting hypertension increased linearly with age.

CONCLUSION:

Older women with SMM were comorbid for both pregnancy-induced and chronic cardiovascular conditions, whereas younger women had pregnancy-induced conditions. This finding suggests a need to assess the role of chronic cardiovascular conditions in SMM, especially among older women. Results also suggest that the narrowly defined SMM metric may underestimate the contribution of chronic cardiovascular conditions to severe maternal morbidity.
Phase 3 Study Evaluating Brexanolone, a GABAA Receptor Modulator, in Severe Postpartum Depression [29B]
Authors: Meltzer-Brody Samantha , Kanes Stephen , Riesenberg Robert , Rubinow David , Maximos Bassem , Colquhoun Helen
Published: April 2018

INTRODUCTION:

A double-blind, placebo-controlled Phase 2 study of brexanolone (USAN; formerly SAGE-547 Injection), a positive allosteric modulator of GABAA receptors, demonstrated rapid and durable improvements in postpartum depression (PPD). The current study (NCT02942004) is one of two randomized, double-blind, placebo-controlled Phase 3 studies that evaluated the efficacy and safety of brexanolone in women with PPD.

METHODS:

Approximately 120 women with severe PPD (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) were randomized 1:1:1 to 60-hour infusions of blinded placebo or brexanolone at 60 or 90 µg/kg/h. The primary endpoint was the change from baseline in the mean HAM-D total score at Hour 60 following brexanolone compared with placebo. Durability of effect and safety were assessed through Day 30. Safety and tolerability were assessed by adverse events, vital signs, laboratory evaluations, electrocardiogram, and the Columbia Suicide Severity Rating Scale. Secondary efficacy endpoints included change from baseline in the Montgomery-Åsberg Depression Rating Scale, HAM-D response, HAM-D remission, and Clinical Global Impression-Improvement.

RESULTS:

This Phase 3 study will be completed in 2017. This presentation will be the first comprehensive reporting of primary and secondary endpoints. These data seek to validate and expand upon the Phase 2 results, which showed a rapid reduction in mean HAM-D score (Hour 60, brexanolone -21.0 vs. placebo -8.8, p=0.008) and durability through Day 30 (20.8 vs. -8.8, p=0.010).

CONCLUSION:

This study, along with a companion Phase 3 study with brexanolone in subjects with moderate PPD, seeks to validate and expand upon the earlier Phase 2 data.