Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Anal sphincter injury in vaginal deliveries complicated by shoulder dystocia.

INTRODUCTION AND HYPOTHESIS: Shoulder dystocia is an obstetric emergency that occurs in 0.2-3% of all cephalic vaginal deliveries. We hypothesized that because of the difficult nature of deliveries complicated by shoulder dystocia, the condition may be associated with anal sphincter injury. We sought to identify risk factors for obstetric anal sphincter injury in women with shoulder dystocia. METHODS: This retrospective analysis included all cases of shoulder dystocia from 2007 to 2011 at two large tertiary referral centers, in the USA and Ireland. Details of maternal demographics, intrapartum characteristics, and delivery outcomes in cases of shoulder dystocia were analyzed. Univariate and multivariate analyses were used to describe the association between shoulder dystocia and anal sphincter injury. RESULTS: There were 685 cases of shoulder dystocia, and the rate of shoulder dystocia was similar at both institutions. The incidence of anal sphincter injury was 8.8% (60 out of 685). The rate was 14% (45 out of 324) in nulliparas and 4.2% (15 out of 361) in multiparas. Women with sphincter injury were more likely to be nulliparous (75% [45 out of 60] vs 45% [279 out of 625]; p < 0.0001), have had an operative vaginal delivery (50% [30 out of 60] vs 36% [226 out of 625]; p = 0.03) and require internal maneuvers (50% [30 out of 60] vs 32% [198 out of 625], p = 0.004) than those with an intact sphincter. On multivariate regression analysis, these predictors of sphincter injury remained significant when adjusted for other risk factors. Episiotomy was negatively associated with sphincter injury on multivariate regression analysis. CONCLUSIONS: In a retrospective cohort of 685 women with shoulder dystocia, the risk of anal sphincter injury is 9%. Risk factors include nulliparity, operative vaginal delivery, and use of internal maneuvers, whereas episiotomy was found to have a protective effect against anal sphincter injury during cases of shoulder dystocia.

Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term.

OBJECTIVE: We sought to assess amniotic fluid lactate (AFL) at diagnosis of spontaneous labor at term (≥37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD). STUDY DESIGN: This was a single-institution, prospective cohort study of 905 singleton, cephalic, term (≥37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds. RESULTS: AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n = 118), 5.0-9.9 mmol/L (n = 707), and ≥10.0 mmol/L (n = 80). Increasing AFL was associated with higher total oxytocin dose (P = .001), labor disorders (P = .005), and CD (P ≤ .001). Multivariable regression analysis demonstrated that women with AFL ≥5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06-2.39) and AFL ≥10.0 mmol/L (OR, 1.72; 95% CI, 1.01-2.93) were independent predictors of a labor disorder. AFL ≥5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL ≥10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73-6.46). AFL ≥5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL ≥10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method. CONCLUSION: AFL at diagnosis of labor in spontaneously laboring single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol.

Real increasing incidence of hysterectomy for placenta accreta following previous caesarean section.

OBJECTIVE: Placenta accreta, morbid adherence to the uterus to the myometrium, is commonest in association with placenta previa in women previously delivered by caesarean section (CS). It has become proportionally a greater cause of major maternal morbidity and mortality as the frequency of other serious obstetric complications has declined. The aim of this study was to examine the incidence of placenta accreta in the context of a rising caesarean delivery rate. STUDY DESIGN: Retrospective review of the incidence of placenta accreta in parous women during the 36 years 1975-2010. Cases were identified from hospital records and then correlated with pathological reports. The incidence of placenta accreta was analysed in the context of women previously delivered by CS. RESULTS: During the 36-year period in our unit, 157,162 multiparous women delivered, of whom 15,151 (9.6%) had a previous CS scar. The institutional incidence of CS rose from 4.1% in 1975 to 20.7% in 2010. Twenty-five parous women, all with a previous CS, had placenta accreta requiring hysterectomy. The overall incidence of placenta accreta was 1.65 per 1000 parous women with a previous CS, but was low (1.06/1000) until 2002. From 2003 to 2010 the incidence rose to 2.37/1000 previous CS deliveries (OR 2.2; 95% CI 1.05-5.1). CONCLUSION: The frequency of placenta accreta correlated steadily with the CS rate until 2000. Since then, the incidence has nearly doubled in women with previous CS scars, suggesting an additional causative influence on risk.

Natural history, management, and outcomes of peripartum cardiomyopathy: an Irish single-center cohort study.

AIM: To describe the natural history, management and outcomes of peripartum cardiomyopathy (PPCM) in an unselected Northern European population. METHODS: A retrospective single-center observational study was performed at a tertiary referral heart failure and transplantation unit. Outcomes measured were baseline demographics, clinical presentation, course, and treatment. Echocardiographic findings were compared at baseline, 2 months, and 6 months. RESULTS: Twelve cases of PPCM were identified between 2002 and 2008. Mean age was 34.7 years. Nine patients were multiparous and nine had preeclampsia. Ten patients presented in the first week postpartum. Two patients required inotropic support. Mean ejection fraction (EF) at presentation was 27% (SD = 8%) which improved to 47% (SD = 13%) at 6 months. At this time, 10 patients were asymptomatic and 6 had recovered normal cardiac function. Left ventricular (LV) function improved but did not reach normal limits in five cases. One case with persistent severe LV dysfunction required cardiac transplantation. One patient suffered an arrhythmic death several years after the 6 months follow-up period. CONCLUSIONS: PPCM is a rare condition. With appropriate therapy, a good clinical outcome is common but not universal. Continued deterioration requiring ventricular support and cardiac transplantation can occur. In our cohort, older maternal age, multiparity, and preeclampsia appeared to be risk factors.

Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further more extensive study of endometrial haematopoietic stem cell populations, as these samples can be collected in a clinical setting without a requirement for general anaesthesia.

Identification of a myometrial molecular profile for dystocic labor.

BACKGROUND: The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. METHODS: Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR. RESULTS: Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3 CONCLUSION: These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.

Cardiotocography as a predictor of fetal outcome in women presenting with reduced fetal movement.

OBJECTIVE: To examine the obstetric and perinatal outcomes of women presenting with reduced fetal movement (RFM) during the third trimester, specifically in relation to the diagnostic capacity of non-stress cardiotocography (CTG) used as the primary investigation in this clinical scenario. STUDY DESIGN: This was a retrospective population-based cohort study of pregnancy outcomes of all women ≥ 28 weeks' gestation with singleton pregnancies presenting during one calendar year with maternal perception of RFM, all of whom underwent CTG at presentation. Main outcome measures included: obstetric intervention (induction of labour, spontaneous vaginal delivery, operative vaginal delivery, emergency caesarean section), and perinatal outcome (subsequent perinatal death, low Apgar scores (<7(5)), neonatal resuscitation and NICU admission). RESULTS: In all, 524 women presented with RFM and a live fetus, representing 7% of the antenatal obstetric population; 284 women (54%) were nulliparous. The reassuring CTG group comprised 482 (92%) women in whom initial CTG was reassuring and 15 (3%) where a repeat tracing within 1h was reassuring. The non-reassuring/abnormal CTG group (n=27, 5%) either underwent emergency delivery or comprehensive serial fetal assessment; this group had significantly higher rates of emergency caesarean delivery, neonatal resuscitation and NICU admission; the incidence of small-for-gestational-age infants did not differ significantly. No perinatal death occurred in either group following CTG. CONCLUSION: Normal non-stress CTG is a reliable screening indicator of fetal wellbeing in women presenting with perception of RFM in the third trimester; abnormal pregnancy outcomes were more common when initial CTG was abnormal or persistently non-reassuring.

Saving Mothers' Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.

In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006­2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

The placenta as a compensatory iodine storage organ.

BACKGROUND: The production of iodine-containing thyroid hormones necessary for brain development in the fetus depends not only on maternal dietary intake but also on placental iodine transport. The optimum level of iodine nutrition during pregnancy and the proportion of the pregnant population reaching this level have previously been evaluated. Little information exists on the ability of the placenta to either accumulate or store iodine. This study aims to investigate iodine uptake and tissue iodine content within placental tissue obtained from women delivering at term. METHODS: Samples (∼1 cm(3)) obtained from placental cotyledons (n = 19), thyroid (n = 4), and uterine myometrial (n = 4) tissue were incubated for 6 hours with (125)I in the presence and absence of potassium perchlorate. To account for variation in tissue composition, results were expressed in cpm (125)I/µg DNA. RESULTS: Placental uptake of (125)I (375 cpm/µg DNA) was significantly higher than that of control myometrial tissue (226 cpm/µg DNA) (p < 0.05) and was ∼25% that of thyroid tissue (1702 cpm/µg DNA). Uptake of (125)I could be partially blocked in the thyroid and placenta, respectively, by potassium perchlorate (100 µM), which had no effect on uptake by myometrial tissue. Iodine content of tissue samples measured using an alkaline ashing technique with Sandell-Kolthoff colorimetry gave a mean value for total iodine of 30.4 ng/g placental tissue (range 21-50 ng/g), 1.74 ng/g myometrial tissue, and 1037 ng/g thyroid tissue. CONCLUSIONS: Placental iodine content was only ∼3% that of the thyroid, but on the basis that neonatal iodine stores are very low and highly sensitive to fluctuations in maternal iodine supply, we postulate that placental iodine bioavailability makes a significant contribution to protection against neonatal hypothyroidism. These findings suggest that the placenta has a role not only in uptake but also in storing iodine as a possible means of protecting the fetus from inadequacies in maternal dietary iodine intake.

Neonatal brachial plexus injury: comparison of incidence and antecedents between 2 decades.

OBJECTIVE: We sought to compare the incidence and antecedents of neonatal brachial plexus injury (BPI) in 2 different 5-year epochs a decade apart following the introduction of specific staff training in the management of shoulder dystocia. STUDY DESIGN: All infants with BPI were prospectively identified during 2004 through 2008. Injuries were correlated with maternal details and intrapartum events and compared with the earlier series. RESULTS: Of 41,828 deliveries during 2004 through 2008, 72 infants with BPI were identified (1.7/1000), compared to 54 cases (1.5/1000) from 1994 through 1998 (P = .4); 9 injuries (12.5%) were persistent from 2004 through 2008, compared with 10 (18.5%) earlier (P = .4). There were no significant differences between the 2 time periods with respect to maternal parity, obesity, or prolonged pregnancy, although the cesarean section rate had increased from 10.7 to 18.4%. CONCLUSION: Despite training in the management of shoulder dystocia and a rising institutional cesarean section rate, the incidence of BPI has remained unchanged compared with 10 years earlier.

The singleton, cephalic, nulliparous woman after 36 weeks of gestation: contribution to overall cesarean delivery rates.

OBJECTIVE: To examine the contribution of singleton, cephalic, term (37 weeks or later) nulliparous cesarean rates to overall cesarean incidence in a single institution during a 35-year period. METHODS: Cesarean rates were examined for 1974, 1984, 1994, 1999, 2005, and 2008, applying a 10-group classification system. Groups 1 (spontaneously laboring, term nulliparous women) and 2 (prelabor cesarean and induced term nulliparous women) were combined as a composite variable-the term, singleton, cephalic nulliparous woman. RESULTS: Overall and term, singleton, cephalic nulliparous cesarean rates correlated throughout the 35-year period (r=0.93, P<.001). Between 1974 and 2008, overall cesarean rates increased from 5% to 19.1% and from 4.4% to 15.8% among term, singleton, cephalic nulliparous women. Term, singleton, cephalic nulliparous inductions increased from 19.7% to 32.7% (P<.001) and the intrapartum cesarean rate in term, singleton, cephalic nulliparous inductions rose from 4.1% to 27.3%. The cesarean rate in group 1 increased from 2.3% to 7.2%. CONCLUSION: The increase in term, singleton, cephalic nulliparous cesarean rates correlated with the increase in overall cesarean rates throughout 35 years in an institution with standard management of labor. This relationship was due to an increase in both the incidence and rate of cesarean delivery within term, singleton, cephalic nulliparous inductions. Examination of the different term, singleton, cephalic nullipara components (spontaneous labor, induction, or prelabor cesarean) can help to identify major variations in practice between institutions. LEVEL OF EVIDENCE: III.

Dystocia correlates with body mass index in both spontaneous and induced nulliparous labors.

OBJECTIVE: To assess the influence of body mass index (BMI) on labor outcome in both induced and actively managed spontaneous nulliparous labors. METHODS: This is a prospective observational study of all consecutive nulliparous women who delivered in the National Maternity Hospital, Dublin in 2008. Labor outcome variables examined in relation to BMI included duration of labor, oxytocin requirements, epidural use, mode of delivery, and infant birthweight. RESULTS: Of 4162 nulliparous women who labored during the study period, accurate BMI data were available on 3158, who constituted the study group. Of these women, 2143 (68%) were in spontaneous labor and 1015 (32%) had labor induced. A statistically significant association was found between maternal BMI at first antenatal visit and the need for intrapartum cesarean section (CS) in both spontaneous and induced labors (p < 0.05). A significantly poorer response to oxytocin augmentation was observed in women with a higher BMI, as indicated by an increased intrapartum CS rate for dystocia despite oxytocin augmentation. There was a linear relationship between maternal BMI and gestational age at onset of spontaneous labor. CONCLUSION: Our results in a large consecutive series of nulliparous labors confirm the potent influence of increasing maternal BMI on intrapartum events.

The dual influences of age and obstetric history on fecal continence in parous women.

OBJECTIVE: To assess whether women who underwent forceps delivery were more likely than those who delivered either normally (spontaneous vaginal delivery [SVD]) or by cesarean to experience deterioration in fecal continence as they aged. METHODS: The study investigated fecal continence assessment among women who gave birth to their first child 10, 20, or 30 years previously. Women who had undergone forceps delivery in the selected years were matched with women who had SVD in the same year. Two additional cohorts (1 premenopausal, 1 postmenopausal), who had only ever delivered by pre-labor cesarean, were identified for comparison. RESULTS: Of the 85 women who participated, 36 had undergone forceps delivery, 35 SVD, and 14 cesarean delivery only. The mode of vaginal delivery had no significant effect on continence scores or manometry pressures. Premenopausal women who had undergone cesarean delivery had significantly higher manometry pressures than those who delivered vaginally, but this protective effect was lost after the menopause. Multivariate analysis of pudendal nerve conduction found that the adverse effect of duration since delivery was greater than the adverse effect of forceps compared with vaginal delivery. CONCLUSION: Mode of delivery and aging affect pelvic floor function. Women who deliver via cesarean are not immune to age-related deterioration of anal sphincter function.

Comparison of the contractile properties, oxidative capacities and fibre type profiles of the voluntary sphincters of continence in the rat.

The external urethral sphincter (EUS) and external anal sphincter (EAS) are the principal voluntary striated muscles that sustain continence of urine and faeces. In light of their common embryological origin, shared tonic sphincteric action and synchronized electrical activity in vivo, it was expected that they would exhibit similar physiological and structural properties. However, the findings of this study using paired observations of both sphincters isolated from the rat show clearly that this is not the case. The anal sphincter is much more fatigable than the urethral sphincter. On completion of a fatigue protocol, the amplitude of the last twitch of the EAS had declined to 42 +/- 3% of the first twitch, whereas the last twitch of the EUS was almost identical to that of the first (95 +/- 3%). Immunocytochemical detection of myosin heavy-chain isoforms showed that this difference was not due to the presence of more slow-twitch oxidative type 1 fibres in the EUS compared with the EAS (areal densities 4 +/- 1% and 5 +/- 1%, respectively; P = 0.35). In addition, the fatigue difference was not explained by a greater contribution to force production by fast oxidative type 2A fibres in the urethral sphincter. In fact, the anal sphincter contained a higher areal density of type 2A fibres (56 +/- 5% vs. 37 +/- 4% in the EUS, P = 0.017). The higher oxidative capacity of the EUS, measured histochemically, explained its fatigue resistance. These results were surprising because the fatigue-resistant urethral muscle exhibited faster single-twitch contraction times compared with the anal sphincter (56 +/- 0.87 ms vs. 72.5 +/- 1.16 ms, P < 0.001). Neither sphincter expressed the type 2X myosin isoform but the fast-twitch isoform type 2B was found exclusively in the EUS (areal density 16 +/- 2%). The type 2B fibres of the EUS were small (diameter 19.5 +/- 0.4 mum) in comparison to typical type 2B fibres of other muscles. As a whole the EUS is a more oxidative than glycolytic muscle. In conclusion, analysis of the twitch mechanics and fatigue of two sphincters showed that the EUS contained more fatigue-resistant muscle fibres compared with the EAS.

Levator ani injury in primiparous women with forceps delivery for fetal distress, forceps for second stage arrest, and spontaneous delivery.

OBJECTIVE: To compare levator ani muscle injury rates in primiparous women who had a forceps delivery owing to fetal distress with women delivered by forceps for second stage arrest; and to compare these injury rates with a historical control group of women who delivered spontaneously. METHODS: Primiparous women who delivered by forceps were recruited retrospectively into 2 groups: forceps for fetal distress with short second stage (25±11 minutes; n=19); and forceps delivery for second stage arrest (137±26 minutes; n=19). MR images of the levator ani muscles were compared with a historical control group of women from a previous study who had delivered spontaneously (n=129). RESULTS: Major defect rates were: 42% for forceps and short second stage; 63% for forceps and second stage arrest; and 6% for spontaneous delivery. The odds ratios for major injury were: 11.0 for forceps and short second stage compared with spontaneous delivery; 25.9 for forceps and second stage arrest compared with spontaneous delivery; and 2.3 for forceps and second stage arrest compared with short second stage (P=0.07). CONCLUSION: Women delivered by forceps have a higher rate of levator ani injury compared with spontaneous delivery controls; the difference between the forceps groups did not reach significance.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat.

Functional magnetic resonance imaging (fMRI) techniques highlight cerebral vascular responses which are coupled to changes in neural activation. However, two major difficulties arise when employing these techniques in animal studies. First is the disturbance of cerebral blood flow due to anaesthesia and second is the difficulty of precise reproducible quantitative measurements. These difficulties were surmounted in the current study by using propofol and quantitative arterial spin labelling (QASL) to measure relative cerebral blood volume of labelled water (rCBV(lw),) mean transit time (MTT) and capillary transit time (CTT). The ASL method was applied to measure the haemodynamic response in the primary somatosensory cortex following forepaw stimulation in the rat. Following stimulation an increase in signal intensity and rCBV(lw) was recorded, this was accompanied by a significant decrease in MTT (1.97+/-0.06s to 1.44+/-0.04s) and CTT (1.76+/-0.06s to 1.39+/-0.07s). Two animals were scanned repeatedly on two different experimental days. Stimulation in the first animal was applied to the same forepaw during the initial and repeat scan. In the second animal stimulation was applied to different forepaws on the first and second days. The control and activated ASL signal intensities, rCBVlw on both days were almost identical in both animals. The basal MTT and CTT during the second scan were also very similar to the values obtained during the first scan. The MTT recorded from the animal that underwent stimulation to the same paw during both scanning sessions was very similar on the first and second days. In conclusion, propofol induces little physiological disturbance and holds potential for longitudinal QASL fMRI studies.

Central representation of the inferior rectal nerve of the rat.

PURPOSE: Obstetric injury to the pudendal nerve contributes significantly to fecal incontinence. The inferior rectal nerve, a terminal branch of the motor division of the pudendal nerve, innervates the external anal sphincter. Animal models have been developed to establish the scientific basis of sacral neuromodulation. The aims of this study were to determine the spinal location of inferior rectal nerve motoneurons projecting to the external anal sphincter and whether the inferior rectal nerve carries sensory fibers. METHODS: Ten female virgin Wistar rats were used; 7 underwent bilateral inferior rectal nerve section and application of the neuronal tracer fluorogold. Five days later dorsal root ganglia L5 to S2 and the lumbosacral spinal cord were harvested and stained for activating transcription factor 3, a molecular marker of nerve injury. Three animals were used to confirm the specificity of activating transcription factor 3 nuclear labeling as a marker of axotomy. RESULTS: Fluorogold-labeled motoneurons were found exclusively at L6 in the dorsomedial sections of Onuf's nuclei (left and right), which contained 30 +/- 9 motoneurons with a median diameter of 28.3 microm (24.4-31.0) (25th-75th centiles). Double-labeled sensory neurons (fluorogold-labeled cytoplasm and activating transcription factor 3-labeled nuclei) were found in dorsal root ganglia L6 to S2 and were smaller in diameter (20.5 microm (17.8-26.7); median (25th-75th centiles)) than motoneurons (P < .0,001). CONCLUSIONS: The external anal sphincter receives both motor and sensory innervation from the inferior rectal nerve. Activating transcription factor 3 nuclear staining may prove useful for quantifying the degree of nerve injury in animal models of fecal incontinence.

Comparative analysis of international cesarean delivery rates using 10-group classification identifies significant variation in spontaneous labor.

OBJECTIVE: Cesarean section (CS) rates continue to rise throughout the developed world. The aim of this study was to highlight variations in obstetric populations and practices and to identify variations in CS rates in different institutions. STUDY DESIGN: Data from 9 institutional cohorts (total, 47,402; range, 1962-7985) from 9 different countries were examined using a 10-group classification system based on 4 characteristics of every pregnancy, namely single/multiple, nulliparity/multiparity, multiparity with CS scar, spontaneous/induced labor onset and term (>or=37 weeks) gestation. RESULTS: Overall CS rates correlated with CS rates in singleton cephalic nullipara (r = 0.992; P < .001). Whereas CS rates in induced labor were similar, greatest institutional variation were seen in spontaneously laboring multiparas (6.7-fold difference) and nulliparas (3.7-fold difference). CONCLUSION: Ten-group analysis of international obstetric cesarean practice identifies wide variations in women in spontaneous cephalic term labor, a low-risk cohort amenable to effective intrapartum corrective intervention.