Dana R. Gossett

Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells

The PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumour suppressor is mutated in 40–50% of human endometrial cancers. PTEN exerts its effects in part via inhibition of the antiapoptotic protein AKT. We demonstrate that two endometrial cancer cell lines that harbour PTEN mutations, Ishikawa and RL95-2, have high levels of phosphorylated AKT and high AKT kinase activity. Two additional endometrial cancer cell lines that express wild-type PTEN, Hec1A and KLE, have little phosphorylated AKT and minimal demonstrable AKT kinase activity. We tested a potential inhibitor of the AKT pathway, API-59CJ-OMe, in these four cell lines. We found that API-59CJ-OMe inhibits AKT kinase activity and induces apoptosis in the Ishikawa and RL95-2 cell lines with high AKT activity, but has little effect on Hec1A and KLE cells without AKT activity. API-59CJ-OMe may therefore have therapeutic potential for those endometrial cancers that harbour PTEN mutations and AKT activation.

Existing models fail to predict sepsis in an obstetric population with intrauterine infection

OBJECTIVE Multiple scoring systems exist to identify inpatients who are at risk for clinical deterioration. None of these systems have been evaluated in an obstetric population. We examined the Systemic Inflammatory Response syndrome (SIRS) and Modified Early Warning score (MEWS) criteria in pregnant women with chorioamnionitis. STUDY DESIGN This was an 18-month retrospective analysis of patients with chorioamnionitis. SIRS and MEWS scores were calculated; clinical outcomes were ascertained, and test characteristics were calculated for the primary outcome of sepsis, intensive care unit transfer, or death. RESULTS Nine hundred thirteen women with chorioamnionitis were identified. Five women experienced sepsis; there was 1 death. Five hundred seventy-five of the 913 women (63%) met SIRS criteria (95% confidence interval, 59.8-66.2%; positive predictive value, 0.9%). Ninety-two of the 913 women (10.3%) had a MEWS score of ≥ 5 (95% confidence interval, 8.3-12.2%; positive predictive value, 0.05%). CONCLUSION SIRS and MEWS criteria do not identify accurately patients who are at risk for intensive care unit transfer, sepsis, or death among pregnant women with intrauterine infection and should not be used in an obstetric setting.

Antenatal diagnosis of single umbilical artery: Is fetal echocardiography warranted?

OBJECTIVE To estimate the utility of fetal echocardiography in the evaluation of the fetus with isolated single umbilical artery. METHODS A retrospective analysis of fetuses diagnosed with single umbilical artery by sonography was conducted between January 1995 and June 2000 (n = 127). In the 103 patients who had fetal echocardiograms, we examined the frequency of abnormal echocardiographic findings when the initial sonogram demonstrated a normal four‐chamber view and cardiac outflow tracts. RESULTS Approximately 1% of fetal anomaly screens had a diagnosis of single umbilical artery. Of these, 72% were isolated (no other anomalies identified). No fetus in this group had an abnormal echocardiogram. There was one postnatal diagnosis of cardiac disease in this group; it was not predicted by either the four‐chamber and outflow tract views or the echocardiogram. Among the group with other anomalies, the four‐chamber view predicted every abnormal echocardiogram but one. CONCLUSION Fetal echocardiography does not appear to add further diagnostic information to the antenatal evaluation of the fetus with isolated single umbilical artery when normal four‐chamber and outflow tract views of the heart have already been obtained.

Use of electronic health record data to evaluate overuse of cervical cancer screening

BACKGROUND National organizations historically focused on increasing use of effective services are now attempting to identify and discourage use of low-value services. Electronic health records (EHRs) could be used to measure use of low-value services, but few studies have examined this. The aim of the study was to: (1) determine if EHR data can be used to identify women eligible for an extended Pap testing interval; (2) determine the proportion of these women who received a Pap test sooner than recommended; and (3) assess the consequences of these low-value Pap tests. METHODS Electronic query of EHR data identified women aged 30-65 years old who were at low-risk of cervical cancer and therefore eligible for an extended Pap testing interval of 3 years (as per professional society guidelines). Manual chart review assessed query accuracy. The use of low-value Pap tests (ie, those performed sooner than recommended) was measured, and adverse consequences of low-value Pap tests (ie, colposcopies performed as a result of low-value Pap tests) were identified. RESULTS Manual chart review confirmed query accuracy. Two-thirds (1120/1705) of low-risk women received a Pap test sooner than recommended, and 21 colposcopies were performed as a result of this low-value Pap testing. CONCLUSION Secondary analysis of EHR data can accurately measure the use of low-value services such as Pap testing performed sooner than recommended in women at low risk of cervical cancer. Similar application of our methodology could facilitate efforts to simultaneously improve quality and decrease costs, maximizing value in the US healthcare system.

Surgeon Volume and Outcomes in Benign Hysterectomy

Annual surgeon case volume has been linked to patient outcome in a variety of surgical fields, although limited data focus on gynecologic surgery performed by general gynecologists. Herein we review the literature addressing the associations between intraoperative injury, postoperative morbidity, and resource use among surgeons performing a low vs high volume of hysterectomies. Although study design and populations differ, individual and composite morbidity outcomes consistently favored high-volume surgeons. Given the growing emphasis on competency-based evaluation in surgery, gynecology departments may soon consider volume requirements a component of privileging.

Simulation Training for Forceps-Assisted Vaginal Delivery and Rates of Maternal Perineal Trauma.

OBJECTIVE: To evaluate the association of a forceps simulation training curriculum for obstetrics residents on rates of severe perineal lacerations after forceps deliveries. METHODS: This was a retrospective cohort study. We created a novel simulation curriculum for forceps-assisted vaginal delivery based on the best practices of local experts, and trained all residents beginning in 2013. We then retrospectively reviewed all forceps deliveries performed in the 2.5 years after initiation of the training and the 7.5 years before the training program. We identified patients who experienced a severe perineal laceration (third- or fourth-degree) and examined the relationship of resident training status and perineal laceration. Known risk factors for lacerations were identified and a multilevel multivariable model was created including these factors as well as resident training. RESULTS: During the study period, we identified 6,058 forceps-assisted vaginal deliveries. We examined temporal trends in rates of forceps of severe perineal laceration. We identified a decrease in severe lacerations between 2005 and 2008, ending 5 years before the initiation of the training curriculum. These years were censored from the data, yielding a baseline observational period of 4,279 deliveries with no significant trend in laceration rate. Univariate analysis reveals a 22% reduction in severe perineal laceration (odds ratio [OR] 0.78; P=.005) among women delivered by residents who had completed forceps simulation training compared with women delivered by residents who had not. After adjusting for known maternal and delivery risk factors for perineal laceration, the magnitude of the reduction increased to 26% in the full data set model (OR 0.74; P=.002). CONCLUSION: A forceps simulation curriculum for obstetrics residents was associated with a significant reduction in severe perineal lacerations.

Acute diabetes insipidus mediated by vasopressinase after placental abruption.

CONTEXT Postpartum, diabetes insipidus (DI) can be part of Sheehans syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. CASE PRESENTATION This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. OBJECTIVE The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. METHODS AND RESULTS Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patients serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patients postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. CONCLUSIONS Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

Pediatricians' Beliefs and Prescribing Patterns of Adolescent Contraception: A Provider Survey

STUDY OBJECTIVE Teen pregnancy and sexually transmitted infection (STI) rates continue to be significant public health problems in the United States. While general pediatricians are in a unique position to improve these issues by addressing contraception with their adolescent patients, there are no data describing their current prescribing patterns. This study sought to elucidate the beliefs and prescribing patterns of general pediatricians and pediatrics residents and to distinguish whether these were affected by practice setting, level of training, or gender. DESIGN, SETTING, PARTICIPANTS General pediatricians and pediatrics residents affiliated with Lurie Childrens Hospital in Chicago, IL, were asked to complete a survey regarding adolescent contraception. MAIN OUTCOME MEASURES Questions were related to obtaining information about contraception, contraceptive counseling, knowledge of contraceptive methods, prescribing patterns of contraceptives, and concerns about individual contraceptive methods. RESULTS 120 physicians of an eligible 411 physicians participated in this study (29%). 79% of participants had prescribed at least 1 contraceptive method. The most commonly prescribed method was oral contraceptive pills at 72%. We noted few differences in prescribing patterns based on above criteria. Numerous misconceptions existed among participants, including a high rate of concern about infertility with IUD use (29% among physicians who prescribed at least 1 method of contraception). CONCLUSIONS General pediatricians can improve their rates of prescribing contraception to adolescents, and could utilize more of the approved methods. One way to do so may be to implement educational interventions among general pediatricians.

Subsequent pregnancy Outcomes After Obstetric Anal Sphincter Injuries (OASIS)

Objectives To describe obstetric outcomes in women with a prior obstetric anal sphincter injury (OASIS) and to identify risk factors for recurrence. Methods A retrospective chart review of women who sustained an OASIS between November 2005 and March 2010 at a tertiary care hospital was performed to identify risk factors for recurrence. Results One thousand six hundred twenty-nine patients had an OASIS. Of these, 758 patients (90%) subsequently delivered during the aforementioned timeframe; 685 patients had a subsequent vaginal delivery. Of the women, 3.2% had a recurrent OASIS. Recurrence was associated with larger birth weight (27% ≥4000 g vs 11.6% <4000 g; P = 0.04) and delivery mode (25.0%, 12.5%, and 2.7% for forceps-assisted, vacuum-assisted, and spontaneous deliveries, respectively (P = 0.0001)), whereas a history of fourth-degree laceration, prior wound complication, or episiotomy at subsequent delivery were not (P = 0.5, P = 0.5, and P = 0.4, respectively). Conclusions Recurrent OASIS occurred in a small percentage of women (3.2%) who subsequently delivered vaginally. Recurrent OASIS was associated with operative vaginal delivery and birth weight 4000 g or greater. Neither episiotomy at first delivery nor at subsequent delivery conferred an increased recurrence risk.

Epistaxis of pregnancy and association with postpartum hemorrhage.

OBJECTIVE: To estimate the prevalence of epistaxis among pregnant women and to investigate if epistaxis of pregnancy is associated with an increased risk of postpartum hemorrhage. METHODS: A cohort of 1,475 pregnant women presenting to labor and delivery at term were asked to complete a survey about epistaxis and other traditional risk factors for bleeding. Results were compared with those from a cohort of 275 nonpregnant women presenting for routine gynecologic care to estimate the effect of pregnancy on the prevalence of epistaxis. The association between epistaxis of pregnancy and risk of bleeding was estimated by comparing rates of postpartum hemorrhage between pregnant women with and without epistaxis. RESULTS: Final data analysis was performed on 1,470 pregnant women and 275 nonpregnant women. The prevalence of epistaxis was significantly increased in pregnant women compared with nonpregnant women (20.3% compared with 6.2%; P<.001). Women with epistaxis of pregnancy were at increased risk of postpartum hemorrhage compared with women without epistaxis (10.7% compared with 6.7%; P=.02). The increased risk of hemorrhage remained after controlling for cesarean delivery and after exclusion of women who reported epistaxis before pregnancy. Other traditional risk factors for bleeding such as gingival bleeding, O blood type, and easy bruising were not associated with increased risk of postpartum hemorrhage. CONCLUSION: Epistaxis is a common problem during pregnancy that may be associated with an increased risk of postpartum hemorrhage. As in the nonpregnant population, eliciting a history of epistaxis may help to identify women at risk of disordered hemostasis. LEVEL OF EVIDENCE: II