Hemodynamic and anatomic changes after fetal aortic valvuloplasty are associated with procedural success and postnatal biventricular circulation.

BACKGROUND: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV). METHODS: This retrospective study included patients who underwent FAV between 2000 and 2019, with echocardiograms performed pre-FAV, immediately post-FAV, and in late gestation. RESULTS: Of 118 fetuses undergoing FAV, 106 (90%) underwent technically successful FAV, of which 55 (52%) had biventricular circulation. Technically successful FAV was associated with improved aortic valve growth (p < 0.001), sustained antegrade aortic arch (AoA) flow (p = 0.02), improved mitral valve (MV) inflow pattern (p = 0.002), and favorable patent foramen ovale (PFO) flow pattern (p = 0.004) from pre-FAV to late gestation. Compared to patients with univentricular outcome, patients with biventricular outcome had less decrement in size of the left ventricle (LV) (p < 0.001) and aortic valve (p = 0.005), as well as more physiologic PFO flow (p < 0.001) and antegrade AoA flow (p < 0.001) from pre-FAV to late gestation. In multivariable analysis, echocardiographic predictors of biventricular outcome were less decline in LV end diastolic dimension (p < 0.001), improved PFO flow (p = 0.004), and sustained antegrade AoA flow (p = 0.002) from pre-FAV to late gestation. CONCLUSION: Stabilization of left heart growth and improved hemodynamics following successful FAV through late gestation are associated with postnatal biventricular circulation.

Noninvasive prenatal testing: from aneuploidy to single genes.

Noninvasive prenatal testing has undergone rapid advances in the last few years. Although researchers have long known about circulating pregnancy-based cell-free fragments of DNA in maternal plasma, it was the introduction of massively parallel sequencing that allowed noninvasive prenatal testing to become a widely used clinical test. This review will begin with an in-depth analysis of the use of noninvasive prenatal testing for aneuploidy, including common causes for inaccurate and/or discordant results. It will also review the ongoing expansion of noninvasive prenatal testing to include copy number variants and select single-gene disorders. Finally, integrated throughout the review is a comparison of noninvasive prenatal testing to more traditional screening methods along with some medical and ethical implications of the widespread use of this new technology.

Fetal cardiac intervention-Perspectives from a single center.

Fetal cardiac intervention was first proposed in the early 1990s to impact cardiac development and survival of fetuses with fetal aortic stenosis and evolving hypoplastic left heart syndrome (HLHS). Although initial attempts of fetal aortic valvuloplasty were unsuccessful and carried a high rate of morbidity and mortality, our collaborative group at the Brigham and Women's Hospital and Boston Children's Hospital have reinvigorated the procedure using improvements in imaging, anesthesia, balloon catheters, and surgical techniques. Two decades of experience have now allowed us to document the safety of in utero intervention and to achieve a better understanding of the impact of midgestation intervention on developing HLHS. Research into underlying genetics, predictive biomarkers, and ways to incorporate stem cell technology will hopefully allow us to further refine the procedure to most benefit children with this historically lethal disease.

Antepartum management and obstetric outcomes among pregnancies with Down syndrome from diagnosis to delivery.

OBJECTIVE: Little is known about the obstetric care of an ongoing pregnancy with trisomy 21. We sought to ascertain an obstetric profile for pregnancies with Down syndrome to help guide prenatal management. METHOD: Pregnancies managed for delivery with trisomy 21 between 2003 and 2014 were analyzed. We reviewed demographic data, diagnostic testing, prenatal surveillance, obstetric outcomes, and placental pathology. T-test, chi-squared test, and Fisher correction were used as indicated. RESULTS: Sixty-eight pregnancies were identified, and four women (5.9%) experienced a loss during the pregnancy. Among the remaining 64 pregnancies, the average gestational age at delivery was 36.9 weeks, growth restriction was present in 12 (17.5%), and major anomalies were present in 51 (75.0%). Delivery was undertaken for non-reassuring fetal surveillance in 35.9% of the pregnancies; 93% of which represented a change from prior reassuring surveillance and 52.6% of which demonstrated histopathologic evidence of placental insufficiency. None among increased maternal age, the presence of an anomaly, or growth restriction were significantly more common in the group with non-reassuring surveillance. CONCLUSION: There are high rates of fetal growth restriction, delivery for non-reassuring fetal status, and evidence of placental insufficiency among affected pregnancies, suggesting a role for antepartum surveillance. © 2017 John Wiley & Sons, Ltd.

How Accurate Is the Dating of Scheduled 39-Week Deliveries?

OBJECTIVE: We assessed the impact of a policy preventing scheduled repeat cesarean deliveries at less than 39 weeks, accounting for potential inaccuracies in pregnancy dating. STUDY DESIGN: We analyzed a cohort of repeat cesarean deliveries before and after the policy change and used chi-square testing to compare the proportion of deliveries at less than 39 weeks. We assessed whether the reduction in early-term deliveries was different if the gestational age was based on the documented estimated date of delivery (EDD) as compared with best obstetric dating. RESULTS: Our cohort consisted of 213 women; 112 before the policy change and 101 after. Using the EDD assigned at delivery, there was a 12.1% absolute decrease in scheduled deliveries at less than 39 weeks (25.0-12.9%; p = 0.025). However, using the EDD by best obstetric dating, there was no significant change (32.1-25.7%; p = 0.305). Of the 85 discrepant EDDs, providers were more likely to assign an earlier EDD (63.5%; p = 0.013). CONCLUSION: Our institution's policy change led to a 12.1% absolute reduction in documented, scheduled early-term deliveries, however only a 6.4% absolute decline using best obstetric dating. Policy initiatives to reduce early-term deliveries should consider the source and accuracy of the assigned pregnancy dating.

Transitional cell carcinoma of the ovary: a case-control study.

OBJECTIVES: The aim of this study is to compare response to chemotherapy and survival between patients with transitional call carcinoma of the ovary (TCCO) and papillary serous ovarian cancer (PSOC). METHODS: We identified women with both pure and mixed TCCO who were treated between 2000 and 2010. Each case was matched to two women with PSOC by age, grade, stage, and year of diagnosis. Correlation between categorical variables was assessed with chi square test. The Kaplan-Meier survival analysis was used to generate overall survival data (OS). Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. RESULTS: Eighty-one women diagnosed with TCCO were selected as cases and compared to 162 controls. Women with TCCO had a lower rate of platinum resistance compared to controls (9% vs. 25%; p=0.01). When multivariate logistic regression was used to control for other factors independently associated with platinum resistance, patients with TCCO had a significantly lower risk of platinum resistance compared to PSOC. Median progression-free survival was not significantly different (27 months vs. 22 months; p=0.15) for women with TCCO and PSOC, respectively. Median OS, however, was significantly different at 83 months vs. 52 months for the TCCO and PSOC groups, respectively (p=0.01). A Cox proportional hazards model identified optimal cytoreduction, transitional cell histology, age, stage, and platinum and paclitaxel chemotherapy as independent predictors of OS. CONCLUSIONS: Patients with TCCO are less likely to demonstrate resistance to platinum chemotherapy and have improved overall survival when compared to patients with PSOC.

What is the optimal treatment for obese patients with advanced ovarian carcinoma?

OBJECTIVE: The purpose of this study was to compare primary debulking surgery (PDS) vs neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among obese patients. STUDY DESIGN: Medical records of patients with a body mass index (BMI) of ≥30 kg/m(2) with ovarian/fallopian tube/primary peritoneal carcinoma between January 2005 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures, and postoperative and oncologic outcomes were compared. RESULTS: Of 117 patients, 95 women (81.2%) underwent PDS, and 22 women (18.8%) underwent NACT-IDS. Patients who underwent NACT-IDS were more likely to have stage IV disease (63.6% vs 26.3%; P = .001) and a low surgical complexity score (n = 14; 63.6%). There were no other differences between groups with respect to preoperative characteristics or postoperative morbidity. Compared with the NACT-IDS group, the PDS group had an improved progression-free survival (PFS; 15 vs 11 months; P = .006) and overall survival (OS; 53 vs 32 months; P = .036). Seventy-eight patients (66.7%) had a BMI of 30-34.9 kg/m(2). Within this subset of obese patients, the PDS group had an improved PFS (15 vs 10 months; P = .011) and OS (58 vs 32 months; P = .033), compared with the NACT-IDS group. Among patients with a BMI of ≥35 kg/m(2), there was no difference in PFS (14 vs 12 months; P = .316) or OS (38 vs 32 months; P = .640) when the PDS and NACT-IDS groups were compared. CONCLUSION: Patients with a BMI of 30-34.9 kg/m(2) who undergo PDS have improved oncologic outcomes, compared with those women who undergo NACT-IDS. Patients with a BMI of ≥35 kg/m(2) who undergo PDS have similar oncologic outcomes to those who undergo NACT-IDS. Complication rates were similar at all BMIs, regardless of treatment approach.

Technical Success and Serious Adverse Events for Fetal Aortic Valvuloplasty in a Large 20-Year Cohort.

Background: FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not been reported. Objectives: The purpose of this study was to determine factors associated with fetal aortic valvuloplasty (FAV) technical success (TS) and serious adverse events (SAEs). Methods: Retrospective, single-center, cohort analysis of attempted FAV from March 1, 2000, to December 31, 2020. The primary outcome was the TS of FAV, and the secondary outcome was the presence of an SAE. Results: A total of 165 FAVs were attempted in 163 patients with a median gestational age of 24.6 weeks (IQR: 22.9-27.1 weeks). FAV TS was 85% (141/165) and was higher in the 2010 to 2020 era (94% [85/90] vs 75% [56/75]; P < 0.001). Pre-FAV echocardiographic left ventricle (LV) long axis dimension z-score >-0.10 (P < 0.001) and higher LV ejection fraction (P = 0.037) were independently associated with a higher odds of TS. There were 117 SAEs in 67 attempted FAVs (41%), 13 of which were fetal deaths (7.9%). By classification and regression tree analysis, gestational age <21 weeks or in older fetuses, a procedure time of ≥39.6 minutes was associated with higher SAE rate. In the multivariable logistic regression model correcting for gestational age, fetuses with an LV end-diastolic volume <4.09 mL had an age-adjusted OR of 4.71 (95% CI: 1.67-13.29; P = 0.004) for experiencing an SAE. Conclusions: TS of FAV has improved over time, and failure is associated with smaller fetal left heart sizes. SAEs are common and are associated with smaller left hearts and longer procedure times.

Does neoadjuvant chemotherapy decrease the risk of hospital readmission following debulking surgery?

OBJECTIVE: To compare primary debulking surgery (PDS) vs. neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among elderly patients with ovarian/fallopian tube/primary peritoneal carcinoma. METHODS: Medical records of patients ≥70 years old with epithelial ovarian/fallopian tube/primary peritoneal carcinoma between January 2000 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures and postoperative and oncologic outcomes were compared. Surgical procedures were given a complexity score based on a previously published method. RESULTS: Of 165 patients, 125 (75.8%) underwent PDS and 40 (24.2%) underwent NACT-IDS. Patients undergoing NACT-IDS were more likely to have a pleural effusion (without cytology) and stage 4 disease. Median CA-125 at diagnosis was greater for those undergoing NACT-IDS. The NACT-IDS group was associated with less intraoperative blood loss (250 vs. 400 mL, p=0.001), a greater chance of achieving no residual disease (40% vs. 16%, p=0.005) and a shorter hospital length of stay (LOS) (5 vs. 7 days, p<0.001). PFS (17 vs. 15 months, p=0.708) and OS (29 vs. 33 months, p=0.827) were similar between the two groups. Readmission rates within 30 days of surgery were greater in those undergoing PDS (17.6% vs. 2.5%, p=0.016). After readmission, the median hospital LOS was 6 days (range: 1-41). CONCLUSIONS: Elderly patients undergoing PDS have similar oncologic outcomes when compared to patients undergoing NACT-IDS. The risk of readmission within 30 days of surgery is significantly greater among patients undergoing PDS.

Uterine leiomyosarcoma: an updated series.

OBJECTIVE: The aim of this study was to analyze and compare the clinicopathologic characteristics, treatment, and survival in patients with uterine leiomyosarcoma (ULMS) during the last 10 years in 3 referral academic centers. METHODS: All patients with ULMS who underwent treatment at the participating institutions between January 1, 2000, and December 31, 2010, were identified from the tumor registry database. In each case, the diagnosis was confirmed by a dedicated gynecologic pathologist following postsurgery pathology review. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS: Analysis of 167 women with ULMS with adequate follow-up was performed. One hundred twenty-eight patients (77%) were initially managed at the participating institutions, and 39 (23%) were referred after initial management at a different institution. Ninety-two (55%) had stage I disease, 7 (4%) had stage II, 18 (11%) stage III, and 50 (30%) had stage IV disease. The median OS for women with stage I was 75 months, for stage II 66 months, stage III 34 months, and stage IV 20 months (P < 0.001). For patients with early stage (I and II), race, lower grade, smaller tumor size (<11 cm), low number of mitosis (<25/10 high-power field [HPF]), lymphovascular space invasion, and presence of necrosis were identified as variables with prognostic influence on survival in the univariate analysis. A Cox proportional hazards model identified size 11 cm or greater (hazard ratio, 5.9; P < 0.001) and mitotic count of 25/10 HPF or greater (hazard ratio, 2.3; P = 0.05) as independent predictors of OS. For patients with late stage (stage III and IV), race, stage III versus IV, lower grade, smaller tumor size (<11 cm), and low number of mitosis (<25/10 HPF) were all associated with significantly improved OS. A Cox proportional hazards model identified mitotic count of 25/10 HPF or greater (P = 0.01) as independent predictor of OS. CONCLUSIONS: In early stage, size of the tumor and number of mitosis were associated to survival. In contrast to late stage, only mitotic count was associated to survival.

Patterns of recurrence in patients treated with bevacizumab in the primary treatment of advanced epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to compare the distribution of the first site of recurrence in patients with epithelial ovarian cancer (EOC) who received first-line treatment with bevacizumab compared with patients who did not receive bevacizumab. METHODS: From the Cancer Registry database at our institutions, we identified a group of patients with recurrent EOC who underwent treatment from January 1, 2005, to December 31, 2010. Each patient record was evaluated to classify the site of first recurrence. Correlation between categorical variables was assessed with χ² test. RESULTS: Two hundred ninety-two patients with advanced EOC (stage III or IV) who originally responded to chemotherapy and had a recurrence were identified. Of these, 37 (12.5%) had received postoperative chemotherapy bevacizumab, and 255 (87.5%) did not. Compared with those not treated with bevacizumab, there was a lower incidence of liver recurrence (0% vs 9%; P = 0.05) and a higher rate of lung and/or pleural recurrence (22% vs 5%; P = 0.001) and recurrence at distant sites (22% vs 9%; P = 0.03) in patients who received bevacizumab. There was no difference in the incidence of ascites at the time of recurrence between these groups. CONCLUSIONS: Patients who received bevacizumab as part of primary treatment for EOC had a higher rate of lung and/or pleural recurrence and a lower rate of liver recurrence. There was no difference in the rate of ascites at the time of recurrence.

Can enriching emotional intelligence improve medical students' proactivity and adaptability during OB/GYN clerkships?

OBJECTIVE: The purpose of this pilot study was to examine our hypothesis that enriching workplace emotional intelligence through resident coaches could improve third-year medical students' adaptability and proactivity on the Obstetrics and Gynecology clerkship. METHODS: An observational pilot study was conducted in a teaching hospital. Fourteen 3rd year medical students from two cohorts of clerkships were randomly divided into two groups, and equally assigned to trained resident coaches and untrained resident coaches. Data was collected through onsite naturalistic observation of students' adaptability and proactivity in clinical settings using a checklist with a 4-point Likert scale (1=poor to 4=excellent). Wilcoxon rank-sum test was used to compare the differences between these two groups. RESULTS: A total of 280 data points were collected through onsite observations conducted by investigators. All (n=14) students' adaptability and proactivity performance significantly improved from an average of 3.04 to 3.45 (p=0.014) over 6-week clerkship. Overall, students with trained resident coaches adapted significantly faster and were more proactive in the obstetrics and gynecology clinical setting than the students with untrained coaches (3.31 vs. 3.24, p=0.019). CONCLUSIONS: Findings from our pilot study supported our hypothesis that enriching workplace emotional intelligence knowledge through resident coaches was able to help medical students adapt into obstetrics and gynecology clinical settings faster and become more proactive in learning. Clerkship programs can incorporate the concept of a resident coach in their curriculum to help bridge medical students into clinical settings and to help them engage in self-directed learning throughout the rotation.

Urinary excretion of C5b-9 is associated with the anti-angiogenic state in severe preeclampsia.

PROBLEM: Severe preeclampsia has been independently linked to complement dysregulation and angiogenic imbalance; however, the relationship between complement and angiogenic factors in human pregnancy is unclear. METHOD OF STUDY: Utilizing existing biomarkers, our study sought to better understand this relationship in active disease. We performed a case-control study, enrolling 25 cases with severe preeclampsia, 25 controls with chronic hypertension, and 25 healthy controls without hypertension. Levels of complement components (C3a, C5a, and C5b-9) and angiogenic markers [basic fibroblast growth factor (bFGF), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)] were measured simultaneously. RESULTS: Compared to both hypertensive and non-hypertensive controls, severe preeclampsia was associated with increased plasma sFlt-1, decreased plasma VEGF and PlGF, decreased urinary PlGF, and increased urinary C5b-9. Urinary marker C5b-9 correlated strongly with the anti-angiogenic condition. In subjects with detectable urinary excretion of C5b-9, median plasma levels of sFlt-1 were significantly greater (32,029 versus 4556 pg/mL, P < 0.0001) and levels of PlGF (15.6 versus 226 pg/mL, P < 0.0001) and VEGF (119 versus 153 pg/mL, P = 0.001) were significantly lower. CONCLUSION: More so than plasma complement markers, urinary C5b-9 may a useful measure to link complement dysregulation with angiogenic imbalance in severe preeclampsia.