Gestational hypertension and "severe" disease: time for a change.

Our understanding and management of gestational hypertension and its variants are substantially hindered by a reliance on antiquated terminology and on practice recommendations based largely on tradition rather than outcomes-based evidence. Unsurprisingly, gestational hypertension remains a major contributor to maternal and neonatal morbidity and mortality rates, with little improvement seen over the past half century except as it relates to better newborn care. Reliance on a binary classification of vastly disparate types and degrees of organ dysfunction (severe or not severe) and the use of nonphysiological and largely arbitrary gestational age cutoffs are particularly problematic. If this situation is to improve, it will be necessary to abandon current misleading terminology and non-evidence-based traditional practice patterns and start again, building on management approaches validated by outcomes-based data.

Intrapartum ultrasound measurement of angle of progression at the onset of the second stage of labor for prediction of spontaneous vaginal delivery in term singleton pregnancies: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the diagnostic performance of transperineal ultrasound-measured angles of progression at the onset of the second stage of labor for the prediction of spontaneous vaginal delivery in singleton term pregnancies with cephalic presentation. DATA SOURCES: We performed a predefined systematic search in PubMed, Embase, Scopus, Web of Science, and Google Scholar from inception to February 5, 2021. STUDY ELIGIBILITY CRITERIA: Prospective cohort studies that evaluated the diagnostic performance of transperineal ultrasound-measured angles of progression (index test) at the onset of the second stage of labor (ie, when complete cervical dilation is diagnosed) for the prediction of spontaneous vaginal delivery (reference standard) were eligible for inclusion. Eligible studies were limited to those published as full-text articles in the English language and those that included only parturients with a singleton healthy fetus at term with cephalic presentation. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Summary receiver operating characteristic curves, pooled sensitivities and specificities, area under the curve, and summary likelihood ratios were calculated using the Stata software. Subgroup analyses were done based on angle of progression ranges of 108° to 119°, 120° to 140°, and 141° to 153°. RESULTS: A total of 8 studies reporting on 887 pregnancies were included. Summary estimates of the sensitivity and specificity of transperineal ultrasound-measured angle of progression at the onset of the second stage of labor for predicting spontaneous vaginal delivery were 94% (95% confidence interval, 88%-97%) and 47% (95% confidence interval, 18%-78%), respectively, for an angle of progression of 108° to 119°, 81% (95% confidence interval, 70%-89%) and 73% (95% confidence interval, 57%-85%), respectively, for an angle of progression of 120° to 140°, and 66% (95% confidence interval, 56%-74%) and 82% (95% confidence interval, 66%-92%), respectively, for an angle of progression of 141° to 153°. Likelihood ratio syntheses gave overall positive likelihood ratios of 1.8 (95% confidence interval, 1-3.3), 3 (95% confidence interval, 2-4.7), and 3.7 (95% confidence interval, 1.7-8.1) and negative likelihood ratios of 0.13 (95% confidence interval, 0.07-0.22), 0.26 (95% confidence interval, 0.18-0.38), and 0.42 (95% confidence interval, 0.29-0.60) for angle of progression ranges of 108° to 119°, 120° to 140°, and 141° to 153°, respectively. CONCLUSION: Angle of progression measured by transperineal ultrasound at the onset of the second stage of labor may predict spontaneous vaginal delivery in singleton, term, cephalic presenting pregnancies and has the potential to be used along with physical examinations and other clinical factors in the management of labor and delivery.

Cerebral perfusion pressure and autoregulation in eclampsia-a case control study.

BACKGROUND: Dynamic cerebral autoregulation and cerebral perfusion pressure are altered in pregnancies complicated by preeclampsia compared with normotensive pregnancies, but the connections of dynamic cerebral autoregulation, cerebral perfusion pressure, and cerebral complications in preeclampsia remain unclear. OBJECTIVE: This study aimed to assess dynamic cerebral autoregulation and cerebral perfusion pressure after delivery in women with eclampsia, in women with preeclampsia both with and without severe features, and in normotensive women. STUDY DESIGN: This was a prospective case control study at a large referral hospital in Cape Town, South Africa. The recruitment of participants was done at diagnosis (cases) or at admission for delivery (controls). Transcranial Doppler examinations with continuous noninvasive blood pressure measurements and end-tidal CO2 monitoring were conducted for cases and controls after delivery. Cerebral perfusion pressure and dynamic cerebral autoregulation index were calculated, and values were compared among groups. RESULTS: We included 16 women with eclampsia, 18 women with preeclampsia with severe features, 32 women with preeclampsia without severe features, and 21 normotensive women with uncomplicated pregnancies. Dynamic cerebral autoregulation was depressed in pregnant women with eclampsia; (autoregulation index, 3.9; interquartile range, 3.1-5.2) compared with all other groups (those with preeclampsia with severe features, autoregulation index, 5.6 [interquartile range, 4.4-6.8]; those with preeclampsia without severe features, autoregulation index, 6.8 [interquartile range, 5.1-7.4]; and normotensive controls, autoregulation index, 7.1 [interquartile range, 6.1-7.9]). Pregnant women with eclampsia had increased cerebral perfusion pressure (109.5 mm Hg; interquartile range, 91.2-130.9) compared with those with preeclampsia without severe features and those with normal blood pressure (84 mm Hg [interquartile range, 73.0-122.0] and 80.0 mm Hg [interquartile range, 67.5-92.0], respectively); furthermore, there was no difference in cerebral perfusion pressure between pregnant women with eclampsia and pregnant women with preeclampsia with severe features (109.5 mm Hg [interquartile range, 91.2-130.9] vs 96.5 mm Hg [interquartile range, 75.8-110.5]). CONCLUSION: Cerebral perfusion pressure and dynamic cerebral autoregulation are altered in eclampsia and may be important in the pathophysiological pathway and constitute a therapeutic target in the prevention of cerebral complications in preeclampsia.

Accuracy of Ultrasound to Predict Neonatal Birth Weight Among Fetuses With Gastroschisis: Impact on Timing of Delivery.

OBJECTIVES: To determine the accuracy of ultrasound estimation of fetal weight among fetuses with gastroschisis and how the diagnosis of fetal growth restriction (FGR) affects the timing of delivery. METHODS: This was a retrospective cohort study including all fetuses with a diagnosis of gastroschisis at our institution from November 2012 through October 2017. We excluded multiple gestations, pregnancies with major structural or chromosomal abnormalities, and those for which prenatal and postnatal follow-up were unavailable. Performance characteristics of ultrasound to predict being small for gestational age (SGA) were calculated for the first and last ultrasound estimations of fetal weight. RESULTS: Our cohort included 75 cases of gastroschisis. At the initial ultrasound estimation, 15 of 58 (25.9%) fetuses met criteria for FGR; 48 of 70 (68.6%) met criteria at the time of the last ultrasound estimation (median, 34.7 weeks). Cesarean delivery was performed for 37 of 75 (49.3%), with FGR and concern for fetal distress as the indication for delivery in 17 of 37 (45.9%). Only 6 of 17 (35.3%) of the neonates born by cesarean delivery for an indication of FGR and fetal distress were SGA. The initial ultrasound designation of FGR corresponded to SGA at birth in 8 of 15 (53.3%), whereas the last ultrasound estimation corresponded to SGA in 17 of 48 (35.4%). The initial ultrasound estimation agreed with the last ultrasound estimation before delivery with the diagnosis of FGR in 13 of 15 (86.7%). CONCLUSIONS: Ultrasound in the third trimester was sensitive but had a low positive predictive value and low accuracy for the diagnosis of SGA at birth for fetuses with gastroschisis. A large proportion of fetuses were born by cesarean delivery with indications related to FGR or fetal concerns.

Intravenous labetalol versus oral nifedipine for acute hypertension in pregnancy: effects on cerebral perfusion pressure.

BACKGROUND: Pregnant women with preeclampsia have been found to have elevated cerebral perfusion pressure and impaired cerebral autoregulation compared with normal pregnant women. Transcranial Doppler is a noninvasive technique used to estimate cerebral perfusion pressure. The effects of different antihypertensive medications on cerebral perfusion pressure in preeclampsia are unknown. OBJECTIVE: To compare the change in cerebral perfusion pressure before and after intravenous labetalol vs oral nifedipine in the setting of acute severe hypertension in pregnancy. STUDY DESIGN: This is a prospective cohort study of pregnant women between 24 and 42 weeks' gestation with severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg). Women who consented to the study and received either intravenous labetalol or oral nifedipine were included. Exclusion criteria included active labor or receipt of any antihypertensive medication within 2 hours of initial cerebral perfusion pressure measurement. Peripheral blood pressure and transcranial Doppler studies for middle cerebral artery hemodynamics were performed prior to the administration of antihypertensive medications and repeated 30 minutes after medication administration. RESULTS: A total of 16 women with acute severe hypertension were enrolled; 8 received intravenous labetalol and 8 received oral nifedipine. There were no significant differences between the labetalol and nifedipine groups in baseline characteristics such as maternal age, race and ethnicity, payment, hospital site, body mass index, nulliparity, gestational age, preexisting diabetes mellitus or chronic hypertension, fetal growth restriction, magnesium sulfate administration, and symptomatology (P>.05). When examined 30 minutes after the administration of either intravenous labetalol or oral nifedipine, there was a significantly greater decrease in systolic blood pressure (-9.8 mm Hg vs -39 mm Hg; P=.003), mean arterial pressure (-7.1 mm Hg vs -22.3 mm Hg; P=.02), and cerebral perfusion pressure (-2.5 mm Hg vs -27.7 mm Hg; P=.01) in the nifedipine group. There was no statistically significant decrease in diastolic blood pressure (-12.9 mm Hg vs -5.4 mm Hg; P=.15). The change in middle cerebral artery velocity by transcranial Doppler was compared between the groups and was not different (0.07 cm/s vs 0.16 cm/s; P=.64). CONCLUSION: Oral nifedipine resulted in a significant decrease in cerebral perfusion pressure, whereas labetalol did not, after administration for acute severe hypertension among women with preeclampsia. This decrease seems to be driven by a decrease in peripheral arterial blood pressure rather than a direct change in cerebral blood flow.

Diagnostic Imaging and Outcomes for Nonobstetric Surgery During Pregnancy.

A surgical disease occurring during pregnancy can present a diagnostic dilemma due to the desire to make a timely and accurate diagnosis within the constraints of limiting radiation exposure to the fetus. However, required diagnostic imaging should be pursued when indicated and attempts made to minimize the radiation dose by utilizing abdominal shielding and low-dose protocols when feasible. When surgery is indicated due to disease processes, treatment should not be altered or delayed due to pregnancy as the evidence for adverse pregnancy outcomes including early pregnancy loss and preterm delivery are overall of low quality due to substantial confounding by the disease process itself.

Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort.

PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia. RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.

Clinical Impact of a Restrictive Labor Induction Approval Process.

BACKGROUND/AIMS: The aim of this study was to evaluate the impact of a restrictive labor induction approval process on induction and primary cesarean delivery rates. METHODS: A retrospective cohort study was conducted at a tertiary care academic center from 2006 through 2012. The cohort of deliveries before (pre-intervention) and after (post-intervention) the process included term, singleton pregnancies with no contraindication to vaginal delivery. The primary outcome was induction of labor rates, subgrouped on the basis of whether it was medically or nonmedically indicated. Secondary outcomes included the primary cesarean rate and other maternal and neonatal outcomes. RESULTS: Of 13,753 deliveries, 6,746 met study inclusion criteria. There was a significant decrease in induction rates comparing the pre- and post-intervention periods (21.0 vs. 18.5%, p = 0.01). Nonmedically indicated induction rates also decreased significantly (2.9 vs. 0.6%, p < 0.001). No difference was observed in medically indicated induction (18.1 vs. 17.9%, p = 0.84), the primary cesarean rate (14.4 vs. 15.8%, p = 0.12), or any of the measured neonatal outcomes (p > 0.05). CONCLUSIONS: Implementation of a labor induction approval process was associated with a significant reduction in overall and non-indicated induction rates but did not affect the primary cesarean rate or neonatal outcomes.

Chlorhexidine-Alcohol Compared with Povidone-Iodine Preoperative Skin Antisepsis for Cesarean Delivery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare chlorhexidine-alcohol with povidone-iodine solutions for skin antisepsis prior to cesarean delivery for the prevention of surgical site infection. STUDY DESIGN: Electronic databases MEDLINE, Embase, Scopus, and Clinicaltrials.gov were searched from inception to August 2017. Eligible studies included randomized controlled trials comparing chlorhexidine-alcohol with povidone-iodine skin preparation solutions for women undergoing cesarean delivery. The primary outcome was surgical site infection including superficial or deep wound infection. Meta-analysis was performed, and risk ratios (RRs) with 95% confidence interval (CI) were calculated using the Mantel-Haenszel random effects model. Statistical heterogeneity was assessed using Higgin's I 2. RESULTS: Of 61 abstracts identified in the primary search, four studies (3,059 women) met the eligibility criteria. The risk of surgical site infection was significantly reduced with chlorhexidine-alcohol (RR: 0.72; 95% CI: 0.52-0.98). No heterogeneity across studies was observed with I 2 = 0%. Subgroup analysis of superficial infection only or deep infection only showed no statistically significant difference (RR: 0.76, 95% CI: 0.54-1.08; and RR: 0.50, 95% CI: 0.23-1.10, respectively). CONCLUSION: Preoperative skin cleansing prior to cesarean delivery with chlorhexidine-alcohol reduces surgical site infection as compared with povidone-iodine solutions.

Standardizing Second-Trimester Medical Termination: Effects on Clinical Outcomes.

OBJECTIVE: The objective of this study was to evaluate length of induction and postdelivery complications before and after implementation of a standardized approach to second-trimester medical termination of pregnancy. STUDY DESIGN: This was a retrospective cohort study of all women undergoing medical termination of pregnancy between 130/7 and 266/7 weeks of gestation at a single, academic institution from July 1, 2012, through June 30, 2015. The primary outcome was the time from the start of induction of labor to delivery of the fetus. Postdelivery complications including the need for dilation and curettage (D&C), blood transfusion, and readmission to the hospital were secondary outcomes of interest. RESULTS: A total of 62 women met inclusion criteria; 38 before and 24 after the intervention. There were no differences in measured baseline characteristics (p > 0.05). There was a significant decrease in induction time after the intervention (12.3 compared with 8.6 hours, p = 0.031). There was no significant difference in rates of D&C or other measured complications (p > 0.05). CONCLUSION: Implementation of a standardized clinical guideline for second-trimester medical termination was associated with a decrease in length of induction. There was no significant difference in need for D&C or postdelivery complications; however, we were underpowered for these secondary outcomes.

Impact of USPSTF recommendations for aspirin for prevention of recurrent preeclampsia.

BACKGROUND: The US Preventive Services Task Force recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September 2014. OBJECTIVES: The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. STUDY DESIGN: This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2-hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. RESULTS: A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34-2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15-3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37-3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44-2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52-0.95). CONCLUSION: Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention.

Intrapartum factors associated with neonatal hypoxic ischemic encephalopathy: a case-controlled study.

BACKGROUND: Neonatal encephalopathy (NE) affects 2-4/1000 live births with outcomes ranging from negligible neurological deficits to severe neuromuscular dysfunction, cerebral palsy and death. Hypoxic ischemic encephalopathy (HIE) is the sub cohort of NE that appears to be driven by intrapartum events. Our objective was to identify antepartum and intrapartum factors associated with the development of neonatal HIE. METHODS: Hospital databases were searched using relevant diagnosis codes to identify infants with neonatal encephalopathy. Cases were infants with encephalopathy and evidence of intrapartum hypoxia. For each hypoxic ischemic encephalopathy case, four controls were randomly selected from all deliveries that occurred within 6 months of the case. RESULTS: Twenty-six cases met criteria for hypoxic ischemic encephalopathy between 2002 and 2014. In multivariate analysis, meconium-stained amniotic fluid (aOR 12.4, 95% CI 2.1-144.8, p = 0.002), prolonged second stage of labor (aOR 9.5, 95% CI 1.0-135.3, p = 0.042), and the occurrence of a sentinel or acute event (aOR 74.9, 95% CI 11.9-infinity, p < 0.001) were significantly associated with hypoxic ischemic encephalopathy. The presence of a category 3 fetal heart rate tracing in any of the four 15-min segments during the hour prior to delivery (28.0% versus 4.0%, p = 0.002) was more common among hypoxic ischemic encephalopathy cases. CONCLUSION: Prolonged second stage of labor and the presence of meconium-stained amniotic fluid are risk factors for the development of HIE. Close scrutiny should be paid to labors that develop these features especially in the presence of an abnormal fetal heart tracing. Acute events also account for a substantial number of HIE cases and health systems should develop programs that can optimize the response to these emergencies.

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

BACKGROUND: The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. OBJECTIVE: The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. STUDY DESIGN: This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. RESULTS: During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43). For low-risk pregnancies, there was no significant difference in the levels for any of the measured indices over the study period (P = .61, P = .41, and P = .34 for the Modified Adverse Outcomes Index, Modified Weighted Adverse Outcomes Index, and Modified Severity Index, respectively). Among the high-risk pregnancies, the monthly Modified Weighted Adverse Outcomes Index decreased by 4.2 ± 1.8 (P = .03). The monthly Modified Severity Index decreased by 53.9 ± 17.7 points from the pre- to the postintervention periods (P = .01) and was < 50% of the predicted Modified Severity Index had the intervention not been implemented. The cesarean delivery rate was increasing prior to the intervention, but the rate was stable after the intervention, and the absolute rate did not differ between the pre- and the postintervention periods (28.4% vs 30.0%, P = .20). CONCLUSION: Overall and for high-risk pregnancies, the implementation of the labor and delivery care bundle had a positive impact on the Modified Weighted Adverse Outcomes Index and Modified Severity Index but not the Modified Adverse Outcomes Index.

Do not throw the baby out with the bath water: a guide for using non-significant results in practice.

Acting on results that are not statistically significant is challenging for clinicians. Such results are often interpreted as evidence of lack of association or as useless evidence. We provide a framework for interpreting and applying non-significant results at the point of care using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Characterization of precursor lesions in the endometrium and fallopian tube epithelium of early-stage uterine serous carcinoma.

To determine if selected cases of uterine serous carcinoma (USC) arise from tubal rather than endometrial epithelium. Bilateral fallopian tubes from 38 women with pure USC were entirely submitted for histopathologic examination using the protocol Sectioning and Extensively Examining the FIMbria (SEE-FIM). Non-neoplastic endometrium was extensively sampled. Immunohistochemistry for p53 was performed on all paraffin blocks of fallopian tube and non-neoplastic endometrium. Endometrial intraepithelial carcinoma (EIC) was present in 22 cases (58%). Endometrial p53 foci were identified in 3 patients. There were 11 cases (29%) with fallopian tube involvement; 9 of 11 had tubal wall invasion or lymphatic involvement without serous tubal intraepithelial carcinoma (STIC) and were, therefore, classified as metastatic from the endometrium. STIC was identified in 3 patients (8%). There were 3 cases with tubal p53 foci in non-neoplastic epithelium. EIC was present in 58% of patients, further supporting EIC as a precursor lesion to USC. STIC was present in 8%, suggesting that the fallopian tube may in fact represent the primary lesion in a minority of patients with USC. This finding may account for the early multifocal disease distribution observed in these patients.

Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas.

Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2-targeted treatment in a small series of women with recurrent HER2-amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non-amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2-overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2-targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.

Pharmacologic venous thromboembolism prophylaxis for preterm prelabor rupture of membranes.

BACKGROUND: Pregnant patients with preterm prelabor rupture of membranes (PPROM) may experience prolonged hospitalization, which is an indication for pharmacologic venous thromboembolism (VTE) prophylaxis according to certain international guidelines. The proportion of patients who deliver unexpectedly and within a period during which pharmacologic prophylaxis would be expected to impact coagulation is unknown. OBJECTIVE: To estimate the proportion of patients with PPROM who would deliver within 12 hours of typical dosing of pharmacologic VTE prophylaxis if administered routinely for antepartum admissions >72 hours. STUDY DESIGN: This is a retrospective cohort study from a database including patients admitted for expectant management of PPROM January 2011 to September 2020. The outcome of the study was the proportion of patients who remained undelivered 72 hours after admission and experienced an unplanned delivery potentially within 12 hours of enoxaparin administration. We evaluated patients undelivered after 72 hours due to international recommendations to initiate VTE prophylaxis in hospitalized patients after 72 hours. Unplanned delivery was defined as onset of spontaneous labor or other indication for immediate delivery. Timing of delivery was analyzed based on usual timing of enoxaparin administration daily at approximately 8 am and the recommendation to withhold regional anesthesia until 12 hours after a prophylactic dose. RESULTS: 1381 deliveries were identified as PPROM out of the 49,322 deliveries in our database. 139 cases were included after the following exclusions: delivery >35 weeks (N=641), rupture of membranes >34 weeks (N=145), delivery <72 hours after admission (N=409), insufficient data (N=35), and duplicates (N=12). Sixty of the 139 (43%) had an unplanned delivery, while 33 of these (24% of total) occurred within 12 hours of enoxaparin administration. CONCLUSION: A quarter of patients admitted for PPROM had an unplanned delivery within 12 hours of typical enoxaparin dosing. This cohort may experience harm (ineligibility for regional anesthesia, risks of general anesthesia, increased risk of bleeding) if given routine pharmacologic VTE prophylaxis. Risk/benefit considerations should be discussed with patients in considering pharmacologic versus mechanical prophylaxis during prolonged hospitalization for PPROM.

Hepatic encephalopathy precipitated by preeclampsia in the setting of cirrhosis: A case report.

Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications. A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved promptly post-delivery. Preeclampsia can trigger acute hepatic dysfunction, including hepatic encephalopathy, in the setting of previously compensated preexisting liver disease. Recognizing this association has important implications for management and treatment.

Safety of culdotomy as a surgical approach: implications for natural orifice transluminal endoscopic surgery.

OBJECTIVE: To evaluate the efficacy and safety of culdotomy as a surgical approach to access the peritoneal cavity and discuss its implications for natural orifice transluminal endoscopic surgery (NOTES). METHODS: A retrospective chart review of women undergoing culdotomy for tubal sterilization (N 219) between January 1995 and December 2005 was performed. The Accordion Grading System was used for the severity of complications. RESULTS: No intraoperative complications were noted. Postoperative complications occurred in 7 patients (3.2%): 6 infections (grade 2) and 1 case of hemorrhage (grade 3). Conversion to laparoscopy was necessary in 10 patients (2.2%) due to anatomical constraints or pelvic adhesions; however, culdotomy with entry into the abdominal cavity was nevertheless successful in all 10 cases. The difference in the proportion with a history of pelvic surgery between the conversion and nonconversion groups was not statistically significant (P = .068). Patients with BMI ≥30 had a higher conversion rate compared to patients with BMI <30 (11.4% versus 1.5%, P = .011). Tubal sterilization via culdotomy was successfully performed in all 11 women with no prior vaginal deliveries. CONCLUSION: Culdotomy appears to be a safe surgical approach to access the peritoneal cavity and is associated with a low complication rate. These data support the feasibility and safety of utilizing the cul-de-sac as an access portal for natural orifice transluminal endoscopic surgery.