Faculty Bibliography

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/METHODS: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/CONCLUSIONS: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.

PURPOSE/OBJECTIVE:Routine neonatal circumcision is one of the most commonly performed procedures in a neonate. Residents are expected to acquire the skills to properly evaluate the neonate and gain proficiency in performing circumcision despite significant variability in training. We performed a needs assessment to evaluate obstetric-gynecology residency training in neonatal circumcision. MATERIALS AND METHODS/METHODS:We performed an online self-assessment survey of obstetric-gynecology residents at Prentice Hospital, Chicago, from November 2008 to February 2009. Using images of uncircumcised penises residents were asked to identify which patients were candidates for routine neonatal circumcision. RESULTS:Of 36 obstetric-gynecology residents 27 responded to the survey. Most respondents planned to perform neonatal circumcision when in practice, 44% had no formal training in circumcision and most were comfortable performing routine neonatal circumcision. Overall respondents were less comfortable evaluating whether the a newborn penis could undergo circumcision safely. When presented with 10 pictures of penises and asked to determine whether the neonate should undergo circumcision, 0% of respondents correctly identified all contraindications to neonatal circumcision with an average of 42% of contraindications identified correctly. Of the respondents 77% listed practical experience as the first choice to learn a procedure with an online module preferred by 55% as the second choice. CONCLUSIONS:Although most residents feel competent to technically perform the procedure, they are not confident in their ability to judge the appropriate contraindications to neonatal circumcision. This needs assessment highlights the necessity for further curriculum development and formalized training in this domain.

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/CONCLUSIONS: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/METHODS:II.

OBJECTIVE:Episiotomy practice in the United States has changed dramatically over the past 20 years, and recent studies have questioned the utility of routine episiotomy. Our objective was to evaluate current episiotomy practice in a community hospital. STUDY DESIGN/METHODS:We reviewed vaginal deliveries at a community hospital from January 1, 2004, to December 31, 2005. Maternal,fetal, labor and provider data were collected. Data were analyzed with t test, chi2 and logistic regression. RESULTS:A total of 2,959 deliveries by 17 practitioners were evaluated. The episiotomy rate increased for younger patients, with estimated fetal weight > 4,000 g, when presentation was not occiput anterior and with decreasing parity. Provider characteristics, such as a greater number of years in practice or when the delivering physician was not the outpatient physician, increased episiotomy rates. The overall episiotomy rate declined from 20.6% to 17.7% during the study; however, this did not reach statistical significance, and some practitioners had unchanged or increased rates. CONCLUSION/CONCLUSIONS:Practitioner characteristics were the strongest predictors of episiotomy. Overall, the rate at this community hospital was within published recommendations, but wide variations in practice (range, 2-43%) suggest that education needs to target community physicians remote from training to ensure that all women receive optimal, evidence-based delivery care.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Overactivation of AKT1 and gene amplification of AKT2 are frequently detected in ovarian cancer. Activated AKT kinases provide a cell survival signal that may confer resistance to apoptosis induced by conventional therapies in cancer cells. Therefore, development of potent inhibitors that block AKT pathway is an attractive therapeutic strategy for treating ovarian carcinoma. METHODS:Ovarian cancer cell lines, A2780, MDAH2774, OVCAR-8, Caov-3, and normal murine fibroblasts (NIH3T3) were used. Cells were treated with different doses of a non-peptide small molecule compound, 9-methoxy-2-methylellipticinium acetate (termed API-59-OME) that potentially inhibit AKT pathway. Kinase assays and the phosphorylation of AKT, GSK-3alpha/beta, PDK1, ERK1/2, SGK, p38, FAK, EGFR, JAK2, PKC isoforms, and the cleavage of poly (ADP-ribose) polymerase (PARP) were examined in treated and untreated cell lines. Further, cells treated with API-59-OME were analyzed for induction of apoptosis using sub-G1 profile with propidium iodide staining. RESULTS:API-59-OME inhibited AKT kinase activity but did not inhibit ERK or JNK kinase activities in A2780, MDAH2774, and OVCAR-8 cell lines. API-59-OME did not reduce phosphorylation of other protein kinases in these cell lines. API-59-OME induced apoptosis and the cleavage of PARP in A2780, MDAH2774, and OVCAR-8 ovarian cancer cell lines that express elevated levels of phosphorylated AKT. In contrast, in Caov-3 and NIH3T3 cell lines, which lack constitutive AKT activity, API-59-OME only had minimal effect to induce apoptosis. CONCLUSION/CONCLUSIONS:These data suggest that API-59-OME may be a potent agent to target constitutively activated AKT pathway in ovarian cancer cells.

OBJECTIVE:HSP90 is a cellular chaperone that is overexpressed in many cancers. HSP90 assists in proper folding of a variety of clients, many of which are oncoproteins. HSP90 has been shown to be elevated in endometrial, ovarian, and breast cancer. Furthermore, HSP90 is known to stabilize the oncoprotein Akt; disruptions of the Akt pathway are common in gynecologic malignancies. We sought to evaluate the effectiveness of HSP90 inhibitors in gynecologic cancer. METHODS:We tested two HSP90 inhibitors, 17-AAG and 17-DMAG, against gynecologic cancer cell lines (four endometrial, one cervical, one ovarian, and one breast cancer line). We performed Western blots to determine effects of treatment on levels of HSP90 client proteins and PARP cleavage. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess cell viability, and flow cytometry to quantitate cell-cycle distribution and apoptosis. RESULTS:After treatment with 17-AAG or 17-DMAG, we detected no decrease in HSP90 levels. Levels of other oncoproteins did decrease with treatment: phosphorylated and total Akt, and Met. One cell line underwent G(1) arrest, and five showed G(2) arrest. All showed some level of apoptotic cell death, which was confirmed by detection of PARP cleavage. Sensitivity to the drugs varied among cell lines, ranging from 20% to 90% apoptosis after treatment. Our data suggest that 17-DMAG may be more potent than 17-AAG. CONCLUSIONS:HSP90 inhibitors are effective cytotoxic agents in gynecologic cancer cells. Further testing in in vivo model systems is warranted, with the goal of eventual translation to clinical trials in gynecologic oncology patients.

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/CONCLUSIONS: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.

OBJECTIVES/OBJECTIVE:The objectives of this study were to characterize the prognostic features of micropapillary serous ovarian carcinoma (MPSC), examine the clinical impact of surgical staging, and define the role of cytoreductive surgery for patients with advanced disease. METHODS:Fifty-one patients with MPSC were identified from hospital and tumor registry databases. Demographic, operative, pathologic, and follow-up data were abstracted retrospectively. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using the log rank test, logistic regression analysis, and the Cox proportional hazards regression model. RESULTS:The median age at diagnosis was 45 years, and follow-up extended to a median of 43.0 months. Stage I/II disease was present in 25.5% of patients and no disease-related deaths were observed in this group. Stage III disease was discovered in 29.4% of patients with tumor clinically confined to the ovaries. Stage III/IV disease (74.5% of cases) was associated with median progression-free and overall survival times of 32.8 and 114.2 months, respectively. Menopausal status and the anatomic extent of disease were significantly associated with survival outcome. However, the strongest independent predictor of survival for patients with advanced disease was the amount of residual tumor. Median overall survival for patients with optimal cytoreduction (residual disease </=1 cm) was 115.4 months compared to 43.1 months for those with >1 cm residual tumor (P < 0.0002). CONCLUSIONS:MPSC carries a significant risk of extraovarian spread; however, adequately sampled Stage I/II disease is associated with a favorable prognosis. Optimal cytoreduction is associated with improved survival and should be the primary therapeutic objective for patients with advanced-stage MPSC.