Evaluating the Association Between Fibrinogen and Rotational Thromboelastometry and the Progression to Severe Obstetric Hemorrhage.

AIM: This study aims to investigate the ability of fibrinogen and rotational thromboelastometry (ROTEM) parameters measured at obstetric hemorrhage protocol initiation to predict severe hemorrhage. METHODS: In this retrospective study we included patients whose hemorrhage was managed with an obstetric massive transfusion protocol. Fibrinogen and ROTEM parameters EXTEM clotting time (CT), clot formation time (CFT), alpha angle, A10, A20, lysis index 30 min after CT (LI30), FIBTEM A10, A20, were measured at initiation of the protocol with transfusion based on a predefined algorithm. Patients were grouped into either severe or nonsevere hemorrhage based on: peripartum fall in hemoglobin ≥4 g/dL, transfusion of ≥4 units of blood product, invasive procedures for hemorrhage control, intensive care unit admission, or death. RESULTS: Of the 155 patients included, 108 (70%) progressed to severe hemorrhage. Fibrinogen, EXTEM alpha angle, A10, A20, FIBTEM A10, A20 were significantly lower in the severe hemorrhage group while the CFT was significantly prolonged in the severe hemorrhage group. In univariate analysis, predicted progression to severe hemorrhage yielded areas under the receiver operating characteristic curve (95% confidence interval [CI]) of: fibrinogen: 0.683 (0.591-0.776), CFT: 0.671 (0.553, 0.789), EXTEM alpha angle: 0.690 (0.577-0.803), A10: 0.693 (0.570-0.815), A20: 0.678 (0.563-0.793), FIBTEM A10: 0.726 (0.605-0.847), and A20: 0.709 (0.594-0.824). In a multivariable model, fibrinogen was independently associated with severe hemorrhage (odds ratio [95% CI] = 1.037 [1.009-1.066]) for every 50 mg/dL decrease in fibrinogen drawn at obstetric hemorrhage massive transfusion protocol initiation. CONCLUSION: Both fibrinogen and ROTEM parameters measured at the initiation of an obstetric hemorrhage protocol are useful parameters for predicting severe hemorrhage.

Sonographic Evaluation of the Placenta in Fontan Patients: A Case Series.

Due to the advancements in pediatric cardiothoracic surgery and medical management, more individuals with congenital heart disease are reaching reproductive age. It is well established that individuals with Fontan circulation are at an increased risk for maternal and fetal adverse outcomes including maternal cardiovascular complications, hypertensive disorders of pregnancy, preterm birth, and fetal growth restriction. Early onset of poor placental health likely related to chronically elevated central venous pressure/low cardiac output inherited to Fontan circulation may play a role in the development of these outcomes. In this case series, we present second-trimester placental imaging findings and pregnancy outcomes of three individuals with Fontan circulation who delivered at a tertiary center in the Southeastern United States.

Risk Factors for Adverse Maternal Outcomes following Expectantly Managed Preterm Prelabor Rupture of Membranes.

OBJECTIVE: We sought to characterize the incidence and risk factors associated with developing maternal morbidity following preterm prelabor rupture of membranes. STUDY DESIGN: Retrospective case-control study of patients with preterm prelabor rupture of membranes at a single institution from 2013 to 2019 admitted at ≥23 weeks gestational age. The primary outcome was a composite of maternal morbidity which included: death, sepsis, intensive care unit (ICU) admission, acute kidney injury, postpartum dilation and curettage, postpartum hysterectomy, venous thromboembolism, postpartum hemorrhage, postpartum wound complication, postpartum endometritis, pelvic abscess, postpartum pneumonia, readmission, and/or need for blood transfusion were compared with patients without above morbidities. Severe morbidity was defined as: death, ICU admission, venous thromboembolism, acute kidney injury, postpartum hysterectomy, sepsis, and/or transfusion >2 units. Demographics, antenatal, and delivery characteristics were compared between patients with and without maternal morbidity. Bivariate statistics and regression models were used to compare outcomes and calculate adjusted odd ratios. RESULTS: Of 361 included patients, 64 patients (17.7%) experienced maternal morbidity and nine (2.5%) had severe morbidity. Patients who experienced maternal morbidity were significantly (p < 0.05) more likely to be older, have private insurance, have BMI ≥40, have chorioamnionitis at delivery, and undergo cesarean or operative vaginal delivery when compared with patients who did not experience morbidity. After controlling for confounders, cesarean delivery (aOR 2.38, 95% CI[1.30,4.39]), body mass index ≥40 at admission (aOR 2.54, 95% CI[1.12,5.79]), private insurance (aOR 3.08, 95% CI[1.54,6.16]), and tobacco use (aOR 3.43, 95% CI[1.58,7.48]) were associated with increased odds of maternal morbidity. CONCLUSION: In this cohort, maternal morbidity occurred in 17.7% of patients with preterm prelabor rupture of membranes. Private insurance, body mass index ≥40, tobacco use, and cesarean delivery were associated with higher odds of morbidity. These data can be used in counseling and to advocate for smoking cessation. KEY POINTS: · 17.7% of patients with PPROM experienced maternal morbidity.. · BMI ≥40 was associated with higher odds of maternal morbidity.. · Tobacco use and cesarean delivery were associated with higher odds of maternal morbidity..

Obstetrics and Gynecology Residents Can Accurately Classify Benign Ovarian Tumors Using the International Ovarian Tumor Analysis Rules.

OBJECTIVES: Recognition of benign versus malignant tumors is essential in gynecologic ultrasound (US). The International Ovarian Tumor Analysis (IOTA) rules have been proposed as part of resident US training. The objective of this study was to examine whether they could be accurately used by obstetrics and gynecology residents in Rwanda. METHODS: Patients undergoing explorative laparotomy for adnexal masses at the University Teaching Hospital of Kigali were included. Before the study, a didactic lecture on the IOTA rules for classifying adnexal masses was performed. Preoperative transabdominal US examinations were performed by residents at different levels of training, who were blinded to the results of prior US examinations. The IOTA classification was compared to the final pathologic diagnosis. RESULTS: There were 72 patients who underwent 116 US examinations. Only 15.5% of US examinations were considered inconclusive. First-year residents (12) correctly diagnosed 18 of 20 masses (90%) as benign and 4 of 4 as malignant. Second-year residents (9) classified 29 of 29 masses correctly. Third-year residents (10) accurately identified 21 of 22 (95.5%) as benign and 5 of 5 as malignant. Fourth-year residents (13) accurately identified 11 of 12 (91.7%) as benign and 6 of 6 as malignant. Therefore, 74 of 78 tumors (94.9%) considered benign by IOTA rules were confirmed by histologic results. Similarly, all 20 tumors classified as malignant were confirmed. Overall, the sensitivities to diagnose benign and malignant tumors by the IOTA rules were 83.3% and 100%, respectively. The positive and negative predictive values were 100% and 94.9%. There were no significant differences noted between residency years. CONCLUSIONS: All levels of Rwandan obstetrics and gynecology residents were able to use the IOTA rules to accurately distinguish benign from malignant tumors.

Maternal near miss and mortality due to postpartum infection: a cross-sectional analysis from Rwanda.

BACKGROUND: The objective of this study is to evaluate 'near miss' and mortality in women with postpartum infections. METHODS: We performed a retrospective review of all patients referred to the University Teaching Hospital of Kigali (CHUK) between January 2012 and December 2013. We identified 117 patients with postpartum infections. Demographic data, length of admission, location of referral, initial surgery and subsequent treatment modalities including antibiotic administration and secondary surgery were recorded. The primary outcome of interest was a composite of maternal mortality and "near miss" defined as more than one laparotomy with/without hysterectomy and prolonged hospitalization. RESULTS: Diagnoses at CHUK were: pelvic peritonitis (56 %), deep surgical site infection including fasciitis (17 %), and endometritis (15 %). The primary procedures performed prior to transfer were: cesarean section (81 %), septic abortion management (12 %), and vaginal delivery (7 %). Antibiotics were initiated prior to transfer in 66 % of women. Surgery was required in 73 % of patients. Hysterectomies were performed in 22 % of patients. Maternal death occurred in 5 % of the patient population. The primary outcome of severe maternal morbidity and mortality occurred in 90 patients (77 %). CONCLUSION: Peritonitis-primarily as a result of cesarean deliveries-is associated with significant morbidity and mortality in our population.

Population pharmacokinetic and pharmacodynamic modeling of different formulations of ONO-5334, cathepsin K inhibitor, in Caucasian and Japanese postmenopausal females.

ONO-5334, a selective inhibitor of cathepsin K, is a potential new treatment for osteoporosis. The objectives of this study were to (1) develop population pharmacokinetic-pharmacodynamic (PK-PD) models for ONO-5334 using dose-ascending data from healthy postmenopausal females, (2) examine comparability of PK and/or PD profile between Caucasian and Japanese, and (3) compare PK-PD profile between immediate release tablet (IRT) and sustained release tablet (SRT). The population PK-PD models were developed for each formulation for post-dose levels of bone resorption markers (serum CTX and NTX). The data were provided from 4 phase 1 studies with total of 201 Caucasian and 94 Japanese subjects. Plasma concentrations of ONO-5334 and bone resorption markers were thoroughly evaluated in those studies. An indirect response model described relationships between bone resorption markers and plasma concentrations of ONO-5334. There was no significant difference in PK and pharmacodynamic potency (IC50 ) between Caucasian and Japanese. Based on the developed model, serum CTX and NTX after administration of ONO-5334 IRT or SRT were simulated, and the results showed that ONO-5334 SRT would provide comparable PD effect on bone resorption markers with lower dose relative to IRT.

Serum and urine bone resorption markers and pharmacokinetics of the cathepsin K inhibitor ONO-5334 after ascending single doses in post menopausal women.

AIMS: To investigate the safety, pharmacokinetics and pharmacodynamics of the new cathepsin K inhibitor, ONO-5334. METHODS: A double-blind, placebo-controlled, randomized study was carried out in 52 healthy post menopausal females. Single ascending doses of ONO-5334 (3-600 mg) were evaluated in six cohorts. The effect of food was studied at ONO-5334 100 mg. RESULTS: Across the doses tested, mean ONO-5334 C(max) occurred 0.5-1.0 h after dosing and the the t(1/2) ranged from 9.1 to 22 h. Linear increases in C(max) and AUC(0,∞) were observed in the 3-300 mg and 3-600 mg dose range, respectively. After food, the geometric mean ratio (95% CI) C(max) and AUC(0,∞) for ONO-5334 were 0.78 (0.31, 1.94) and 0.95 (0.67, 1.35)-fold greater than fasted, respectively. ONO-5334 significantly reduced serum bone resorption markers within 4 h vs. placebo. Statistical significance was achieved for ONO-5334 doses ≥30 mg for C-terminal telopeptide of type 1 collagen (CTX) and ≥300 mg for N-terminal telopeptide of type 1 collagen (NTX). Statistical significance was still evident at 24 h for ONO-5334 100 mg with serum CTX and 600 mg with serum NTX. The maximum suppression in serum CTX occurred at 4 h post dose with difference compared with placebo of -32%, -59%, -60% and -66% for 30, 100, 300 and 600 mg ONO-5334, respectively. Second morning urine void 24 h post dose showed statistically significant suppression of urinary CTX and NTX at 100 mg and above vs. placebo. ONO-5334 600 mg showed statistically significant suppression up to 72 h for serum CTX, urinary CTX and urinary NTX and 48 h for serum NTX vs. placebo. Adverse events were transient with no evidence of dose relationship. CONCLUSIONS: ONO-5334 displayed linear plasma pharmacokinetics over the (predicted therapeutic) dose range, 3-300 mg, with clear suppression of urinary bone resorption markers at doses ≥100 mg for serum markers at 24 h. ONO-5334 was well tolerated up to 600 mg day(-1) when administered to healthy post menopausal women.