Neighborhood Deprivation and Neural Tube Defects.

BACKGROUND: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. METHODS: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. RESULTS: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. CONCLUSIONS: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.

Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors?

BACKGROUND: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations. METHODS: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. RESULTS: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3). CONCLUSION: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors.

Neighborhood-level Socioeconomic Position During Early Pregnancy and Risk of Gastroschisis.

BACKGROUND: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the un derstudied association between neighborhood-level socioeconomic position during early pregnancy and the risk of gastroschisis, an abdominal birth defect of increasing prevalence. METHODS: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997-2011). To characterize neighborhood-level socioeconomic position, we conducted a principal component analysis to construct two indices-Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputations for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence. RESULTS: Mothers residing in moderate (NDI Tertile 2 aOR = 1.23; 95% CI = 1.03, 1.48 and nSEPI Tertile 2 aOR = 1.24; 95% CI = 1.04, 1.49) or low socioeconomic neighborhoods (NDI Tertile 3 aOR = 1.28; 95% CI = 1.05, 1.55 and nSEPI Tertile 3 aOR = 1.32, 95% CI = 1.09, 1.61) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods. CONCLUSIONS: Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis.

Spontaneous version after preterm prelabor rupture of membranes.

BACKGROUND: Preterm prelabor rupture of membranes (PPROM), defined as rupture of membranes before the onset of labor at < 37 weeks' gestation, affects approximately 3% of all pregnancies. For PPROM prior to 34 weeks' gestation, in the absence of contraindications to expectant management, antibiotics are administered to increase the latency period and reduce the incidence of maternal and neonatal infection. The latency period additionally provides an opportunity for fetal presentation to change, which impacts the mode of delivery. It is important to better understand the incidence of spontaneous version after PPROM to enhance patient counseling with regard to the mode of delivery. OBJECTIVE: To determine the incidence of discordant fetal presentation, resulting from spontaneous version, between admission for PPROM and time of delivery for cephalic and non-cephalic fetuses among patients diagnosed with PPROM prior to 34 weeks' gestation and to compare characteristics of those with and without discordant fetal presentation. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies diagnosed with PPROM identified using ICD-9/10-CM codes, < 34 weeks' gestation, admitted to a tertiary care center's antepartum service from 2011-2018. Patients were included if the fetal presentation was documented by ultrasound within 48 h of admission and PPROM, and delivery occurred >24 h after PPROM. Data are presented as proportions, median (interquartile range) or risk ratio and 95% confidence interval. RESULTS: We included 209 patients. Patient age, body mass index, parity, and race/ethnicity were similar among patients with cephalic and non-cephalic fetal presentations at admission. Patients with cephalic presentation at time of PPROM presented at a later gestational age than patients with a non-cephalic presentation. Among patients with a cephalic presentation at admission, the incidence of non-cephalic presentation at delivery was 11.7% (19/162), whereas with non-cephalic presentation at admission, the incidence of cephalic presentation at delivery was 21.3% (10/47). While there was an increased risk of spontaneous version resulting in a discordant presentation at delivery with non-cephalic presentation, this relationship was attenuated and not significant when adjusted for gestational age at time of PPROM.​ Patients with discordant presentation presented with PPROM at an earlier gestational age and had a longer latency period compared to patients with a concordant presentation. Patient age, body mass index, amniotic fluid assessment at admission, and infant birth weight were similar in those with and without a change in fetal presentation. CONCLUSION: Discordant fetal presentation resulting from spontaneous version from cephalic to non-cephalic presentation after PPROM occurred in 11.7% (19/162) of patients, while discordant presentation from non-cephalic to cephalic presentation occurred in 21.3% (10/47) of patients. Given the limited published data on spontaneous version after PPROM these results may impact patient counseling.

Pelvic Inflammatory Disease Trends Among Emergency Department Visits in North Carolina, 2008 to 2017.

BACKGROUND: Pelvic inflammatory disease (PID) is an infection of the upper female reproductive organs that can lead to infertility and ectopic pregnancies. It is a reportable condition in North Carolina (NC) but is likely underreported. We aimed to quantify PID diagnoses in NC emergency department (ED) visits. METHODS: The NC Disease Event Tracking and Epidemiology Collection Tool tracks all ED visits in NC. We identified PID diagnoses among women of reproductive age (15-44 years) between 2008 and 2017 using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, and calculated the yearly proportion with PID diagnoses. We assessed the number of PID visits per patient each year, and the proportion of ED visits with a PID diagnosis by age, proportion of the patient's ZIP code living below the poverty line, insurance coverage, and NC provider region. RESULTS: The percent of women with PID decreased from 6189 (1.0%) in 2008 to 4337 (0.58%) in 2016 before increasing slightly to 4371 (0.61%) in 2017. We identified 54,502 (0.45%) ED visits among 51,847 (0.76%) women with ≥1 PID diagnosis code. Most (95.5%) women with PID had one ED visit during the calendar year. Each year, the proportion with PID was highest among women aged 20 to 24 years, covered under public insurance, from the most impoverished areas, and whose provider was in the Coastal region of NC. CONCLUSIONS: The percent with PID among women visiting EDs decreased between 2008 and 2017 in NC. Although this decline was observed across all demographics, disparities associated with PID continued to persist over time.

Pregnancy-associated changes in cervical noncoding RNA.

Aim: To identify pregnancy-associated changes in cervical noncoding RNA (ncRNA), including miRNA and long noncoding RNA (lncRNA), and their potential effects on biologic processes. Materials & methods: We enrolled 21 pregnant women with term deliveries (≥37 weeks' gestation) in a prospective cohort and collected cervical swabs before 28 weeks' gestation. We enrolled 21 nonpregnant controls. We analyzed miRNA, lncRNA and mRNA expression, applying a Bonferroni correction. Results: Five miRNA and three lncRNA were significantly differentially (>twofold change) expressed. Putative miRNA targets are enriched in genes mediating organogenesis, glucocorticoid signaling, cell adhesion and ncRNA machinery. Conclusion: Differential cervical ncRNA expression occurs in the setting of pregnancy. Gene ontology classification reveals biological pathways through which miRNA may play a biologic role in normal pregnancy physiology.

Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection.

OBJECTIVES: The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI). DESIGN: Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis. METHODS: Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0-4, 12, 48), cerebrospinal fluid (CSF) (weeks 2-4, 24 and 48) and endoscopic biopsies (weeks 4-12 and 36-48). Neuropsychological performance was assessed at weeks 0, 24 and 48. RESULTS: Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure. CONCLUSION: NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment. CLINICALTRIALS.GOV:: NCT00855413.

Local recurrence after breast-conserving therapy for phyllodes tumors: A 15-year retrospective review.

There are few data on the long-term outcomes of patients with phyllodes tumors following breast-conserving surgery with or without radiation therapy (RT). We reviewed 69 patients diagnosed from 2000 to 2015 with surgical specimens available for central pathology assessment for outcome in relation to histopathologic subtype, margin width, and utilization of RT. Median follow-up was 63 months (interquartile range, 35-131 months). Forty-eight patients had benign, 13 borderline, and eight malignant phyllodes tumors, with local recurrence rates of 4%, 0%, and 38%, respectively (P ≤ .04 comparing malignant lesions to both benign and borderline lesions). None of the eight patients who received RT suffered a local recurrence. Two of the 26 (8%) patients with benign phyllodes tumors who did not receive RT with margins that were positive or <1 mm had local recurrence, compared to none of 18 patients with margins 1 mm or wider who did not receive RT. The one patient with a malignant phyllodes tumor who did not receive RT with margins that were positive or <1 mm did not locally recur, while both patients with margins 10 mm or wider who did not receive RT had local recurrence. One patient with a malignant phyllodes tumor developed distant recurrence following local recurrence. Phyllodes histologic type and margin width were both associated with the risk of local recurrence following breast-conserving surgery without RT, though the number of events and patients was too small to show these trends were statistically significant.

Prenatal selective serotonin reuptake inhibitors and therapeutic hypothermia for suspected hypoxic ischemic encephalopathy.

OBJECTIVE: To evaluate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and postnatal therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. STUDY DESIGN: Matched case-control study of singleton deliveries at a tertiary hospital from 2010 to 2016. Cases were infants treated with therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Controls were noncase infants, matched on gestational age, maternal age, obstetric provider group, and hospital shift. RESULT: Prenatal SSRI exposure occurred in 18.4% of cases compared with 4.1% of controls (aOR: 5.9, 95% CI: 1.8-19.7). Among all cases, 36.8% had evidence of hypoxic ischemic encephalopathy on postnatal MRI. In addition, 28.6% of SSRI-exposed cases and 38.7% of SSRI-unexposed cases had MRI confirmation of hypoxic ischemic encephalopathy, respectively. CONCLUSION: Future research to disentangle signs of SSRI exposure from true hypoxic ischemic encephalopathy may facilitate targeting therapeutic hypothermia stewardship toward infants more likely to benefit.

HIV-associated morbidity and mortality in a setting of high ART coverage: prospective surveillance results from a district hospital in Botswana.

INTRODUCTION: Antiretroviral therapy (ART) has significantly improved survival in Africa in recent years. In Botswana, where adult HIV prevalence is 21.9%, AIDS-related mortality is estimated to have declined by 58% between 2005 and 2013 following the initial wide-spread introduction of ART, and ART coverage has steadily increased reaching 84% in 2016. However, there remains little data about the burden of HIV and its impact on mortality in the hospital setting where most deaths occur. We aimed to describe the burden of HIV and related morbidity and mortality among hospitalized medical patients in a district hospital in southern Botswana in the era of widespread ART coverage. METHODS: We prospectively reviewed medical admissions to Scottish Livingstone Hospital from December 2015 to November 2017 and recorded HIV status, demographics, clinical characteristics and final diagnoses at discharge, death or transfer. We ascertained outcomes and determined factors associated with mortality. Results were compared with similar surveillance data collected at the same facility in 2011 to 2012. RESULTS: A total of 2316 admissions occurred involving 1969 patients; 42.4% were of HIV-positive patients, 46.9% of HIV-negative patients and 10.7% of patients with unknown HIV status. Compared to HIV-negative patients, HIV-positive patients had younger age (mean 42 vs. 64 years, p < 0.0001) and higher mortality (22.2% vs. 18.0%, p = 0.03). Tuberculosis was the leading diagnosis among mortality cases in both groups but accounted for a higher proportion of deaths among HIV-positive admissions (44.5%) compared with HIV-negative admissions (19.4%, p < 0.0001). Compared with similar surveillance in 2011 to 2012, HIV prevalence was lower (42.4% vs. 47.6%, p < 0.01), and among HIV-positive admissions: ART coverage was higher (72.2% vs. 56.2%, p < 0.0001), viral load suppression was similar (78.6% vs. 80.3%, p = 0.77), CD4 counts were higher (55.0% vs. 44.6% with CD4 ≥200 cells/mm3 , p < 0.001), mortality was similar (22.2 vs. 22.7%, p = 0.93), tuberculosis diagnoses increased (27.5% vs. 20.1%, p < 0.01) and tuberculosis-associated mortality was higher (35.9% vs. 24.7%, p = 0.05). CONCLUSIONS: Despite high ART-coverage in Botswana, HIV-positive patients continue to be disproportionately represented among hospital admissions and deaths. Deaths from tuberculosis may be contributing to lack of reduction in inpatient mortality. Our findings suggest that control of HIV and tuberculosis remain top priorities for reducing inpatient mortality in Botswana.

Comparing postoperative voiding dysfunction after mid-urethral sling using either a Babcock or Kelly clamp tensioning technique.

INTRODUCTION AND HYPOTHESIS: The objective was to compare postoperative urinary retention using the Babcock and Kelly clamps for retropubic midurethral sling (RPS) tensioning. METHODS: This was a retrospective cohort of isolated RPS procedures from December 2010 through April 2016 by five fellowship-trained surgeons at two institutions. Slings were tensioned with a Babcock clamp by grasping a 3-mm midline fold of mesh (RPS-B) or a Kelly clamp as a spacer between the sling and suburethral tissue (RPS-K). Assessment of urinary retention included the primary outcome of postoperative catheterization and several secondary outcomes, including discharge home with a catheter, within 1 year of surgery. Analysis of covariance was used to compute the mean difference in duration of catheterization and log-binomial regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: We included 240 patients. The RPS-B group had a lower body mass index and was more likely to be menopausal, have had pelvic organ prolapse surgery, and have a lower maximum urethral closure pressure than the RPS-K group. The mean duration of catheterization was similar, as demonstrated by the crude (0.21 days [-0.30-0.71]) and BMI-adjusted (0.07 days [-0.41-0.55]) mean difference in duration of catheterization. The incidence of postoperative OAB symptoms was comparable between the groups (BMI-adjusted RR: 0.95 (0.80-1.1)), and the incidence of revision did not differ (p = 0.7). CONCLUSIONS: The Babcock and Kelly clamp tensioning techniques appear comparable, with a low incidence of prolonged postoperative catheterization. Most catheters were removed on the day of the surgery. It is reasonable to tension retropubic midurethral slings with either method.

Quality of Information Available Online for Abortion Self-Referral.

OBJECTIVE: To assess the quality of information available online for abortion self-referral and to determine whether quality varies by region or distance to an abortion provider. METHODS: This was a cross-sectional study. We used a standard protocol to perform internet searches from August 2016 to June 2017 for abortion services in the 25 most populous U.S. cities and the 43 state capitals that were not one of the 25 most populous cities. We classified the first 10 webpage results and the first five map results and advertisements as facilitating abortion referral (local independent abortion provider, local Planned Parenthood facility, national abortion provider or organization, prochoice website, or abortion directory), not facilitating abortion referral (nonproviding physician office, nonmedical website, abortion provider greater than 50 miles from the location, news article, general directory, other), or hindering abortion referral (crisis pregnancy center or antichoice website). We used U.S. Census Bureau subregions to examine geographic differences. We made comparisons using a χ test. RESULTS: Overall, from 612 searches from 68 cities, 52.9% of webpage results, 67.3% of map results, and 34.4% of advertisements facilitated abortion referral, whereas 12.9%, 21.7%, and 29.9%, respectively, hindered abortion referral. The content of the searches differed significantly based on U.S. Census Bureau subregion (all P≤.001) and distance to an abortion provider (all P≤.02). CONCLUSION: Two thirds of map results facilitated abortion self-referral, whereas only half of webpage results did so. Advertisements were the least likely to facilitate and the most likely to hinder self-referral. Quality was lowest in areas that were farthest from abortion providers.

Long noncoding RNA expression in the cervix mid-pregnancy is associated with the length of gestation at delivery.

Infants born preterm are at increased risk of multiple morbidities and mortality. Why some women deliver preterm remains poorly understood. Prior studies have shown that cervical microRNA expression and DNA methylation are associated with the length of gestation. However, no study has examined the role of long noncoding RNAs (lncRNAs) in the cervix during pregnancy. To determine whether expression of lncRNAs is associated with length of gestation at delivery, we analyzed RNA from cervical swabs obtained from 78 women during pregnancy (mean 15.5, SD 5.0, weeks of gestation) who were participating in the Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) Study in Boston, MA, USA. We used a PCR-based platform and found that 9 lncRNAs were expressed in at least 50% of the participants. Of these, a doubling of the expression of TUG1, TINCR, and FALEC was associated with shorter lengths of gestation at delivery [2.8 (95% CI: 0.31, 5.2); 3.3 (0.22, 6.3); and 4.5 (7.3, 1.6) days shorter respectively]. Of the lncRNAs analyzed, none was statistically associated with preterm birth, but expression of FALEC was 2.6-fold higher in women who delivered preterm vs. term (P = 0.051). These findings demonstrate that lncRNAs can be measured in cervical samples obtained during pregnancy and are associated with subsequent length of gestation at delivery. Further, this study supports future work to replicate these findings in other cohorts and perform mechanistic studies to determine the role of lncRNAs in the cervix during pregnancy.

Treatment Strategies in Octogenarians with Early-Stage, High-Risk Breast Cancer.

BACKGROUND: Octogenarians with early-stage breast cancer often have low-risk tumor biology. However, optimal treatment strategies for those with high-risk biology remain unclear. METHODS: We reviewed the records of women ages 80-89 years with biopsy-proven, Stage I-II invasive breast cancer who were referred for surgical evaluation from January 2001 through December 2010. High-risk was defined as human epidermal growth factor receptor-positive (HER2+), triple-negative (TN), or histologic grade 3 disease. RESULTS: Among 178 patients, 40 (22%) were high-risk: 12 were grade 1-2 (10 HER2 + , 2 TN); 28 were grade 3 (7 HER2+, 6 TN, 15 estrogen receptor-positive (ER+)/HER2-). The high-risk group had larger tumors and more often had ductal histology and lymphovascular invasion than the low-risk group and was more likely to undergo mastectomy (18 vs. 5%, p = 0.02), radiotherapy (55 vs. 36%, p = 0.03), and chemotherapy (10 vs. 0%, p = 0.002). Endocrine therapy use was similar among ER+ patients in both groups. The four patients in the high-risk group given chemotherapy were HER2+ and received trastuzumab-based regimens, without any reported toxicities. At median follow-up of 67 months, 10% of the high-risk group had a recurrence (3 distant-only, 1 simultaneous locoregional and distant in a patient treated with mastectomy without radiotherapy). CONCLUSIONS: Tailored locoregional and systemic therapy resulted in low incidence of failure in these octogenarians with high-risk cancers with low morbidity. Modern adjuvant therapies should be considered for elderly women with high-risk cancers in the absence of significant comorbidities.

Creating Flexible and Sustainable Work Models for Academic Obstetrician-Gynecologists Engaged in Global Health Work.

OBJECTIVE: To describe various work models for obstetrics and gynecology global health faculty affiliated with academic medical centers and to identify barriers and opportunities for pursuing global health work. METHODS: A mixed-methods study was conducted in 2016 among obstetrics and gynecology faculty and leaders from seven academic medical institutions in Boston, Massachusetts. Global health faculty members were invited to complete an online survey about their work models and to participate in semistructured interviews about barriers and facilitators of these models. Department chairs and residency directors were asked to participate in interviews. RESULTS: The survey response rate among faculty was 65.6% (21/32), of which 76.2% (16/21) completed an interview. Five department leaders (45.5% [5/11]) participated in an interview. Faculty described a range of work models with varied time and compensation, but only one third reported contracted time for global health work. The most common barriers to global health work were financial constraints, time limitations, lack of mentorship, need for specialized training, and maintenance of clinical skills. Career satisfaction, creating value for the obstetrics and gynecology department, and work model flexibility were the most important facilitators of sustainable global health careers. CONCLUSION: The study identified challenges and opportunities to creating flexible and sustainable work models for academic obstetrics and gynecology clinicians engaged in global health work. Additional research and innovation are needed to identify work models that allow for sustainable careers in global women's health. There are opportunities to create professional standards and models for academic global health work in the obstetrics and gynecology specialty.

Down-regulation of soluble fms-like tyrosine kinase 1 expression in invasive placentation.

PURPOSE: To confirm reduced expression of soluble fms-like tyrosine kinase 1 (sFlt-1) in accreta/increta. METHODS: Formalin-fixed tissue sections from 11 peripartum hysterectomies with invasive placentation and 5 controls were stained for sFlt-1. Stain intensity was scored in selected 100× microscopic fields. We compared sFlt-1 expression in invasive areas among cases, non-invasive areas among cases and areas from control placentas. RESULTS: Chorionic villi displayed significantly decreased sFlt-1 expression in invasive areas of cases compared to control placentas (p = 0.003), as well as in non-invasive areas of cases compared to control placentas (p = 0.01). There was no difference in sFlt-1 expression between invasive and non-invasive areas among cases. CONCLUSIONS: Expression of sFlt-1 is diminished in villous trophoblasts from patients with placenta increta or percreta. Local depth of invasion was not associated with sFlt-1 expression, suggesting a more global abnormality across the implantation site rather than localized to areas of histologic invasion.

Homologous Recombination and Translesion DNA Synthesis Play Critical Roles on Tolerating DNA Damage Caused by Trace Levels of Hexavalent Chromium.

Contamination of potentially carcinogenic hexavalent chromium (Cr(VI)) in the drinking water is a major public health concern worldwide. However, little information is available regarding the biological effects of a nanomoler amount of Cr(VI). Here, we investigated the genotoxic effects of Cr(VI) at nanomoler levels and their repair pathways. We found that DNA damage response analyzed based on differential toxicity of isogenic cells deficient in various DNA repair proteins is observed after a three-day incubation with K2CrO4 in REV1-deficient DT40 cells at 19.2 µg/L or higher as well as in TK6 cells deficient in polymerase delta subunit 3 (POLD3) at 9.8 µg/L or higher. The genotoxicity of Cr(VI) decreased ~3000 times when the incubation time was reduced from three days to ten minutes. TK mutation rate also significantly decreased from 6 day to 1 day exposure to Cr(VI). The DNA damage response analysis suggest that DNA repair pathways, including the homologous recombination and REV1- and POLD3-mediated error-prone translesion synthesis pathways, are critical for the cells to tolerate to DNA damage caused by trace amount of Cr(VI).

Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes.

BACKGROUND: Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. METHODS: This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80-89 years and 50-59 years were compared. RESULTS: The study identified 178 eligible women ages 80-89 years and 169 women ages 50-59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. CONCLUSIONS: The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age.