Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles.

OBJECTIVE: To circumvent the complex protein milieu of plasma and discover robust predictive biomarkers for preeclampsia (PE), we investigate if phospholipid-binding ligands can reduce the milieu complexity by extracting plasma extracellular vesicles for biomarker discovery. STUDY DESIGN: Cholera toxin B chain (CTB) and annexin V (AV) which respectively binds GM1 ganglioside and phosphatidylserine were used to isolate extracellular vesicles from plasma of PE patients and healthy pregnant women. The proteins in the vesicles were identified using enzyme-linked immunosorbent assay, antibody array, and mass spectrometry. RESULTS: CTB and AV were found to bind 2 distinct groups of extracellular vesicles. Antibody array and enzyme-linked immunosorbent assay revealed that PE patients had elevated levels of CD105, interleukin-6, placental growth factor, tissue inhibitor of metallopeptidase 1, and atrial natriuretic peptide in cholera toxin B- but not AV-vesicles, and elevated levels of plasminogen activator inhibitor-1, pro-calcitonin, S100b, tumor growth factor ß, vascular endothelial growth factor receptor 1, brain natriuretic peptide, and placental growth factor in both cholera toxin B- and AV-vesicles. CD9 level was elevated in cholera toxin B-vesicles but reduced in AV vesicles of PE patients. Proteome analysis revealed that in cholera toxin B-vesicles, 87 and 222 proteins were present only in PE patients and healthy pregnant women respectively while in AV-vesicles, 104 and 157 proteins were present only in PE and healthy pregnant women, respectively. CONCLUSION: This study demonstrated for the first time that CTB and AV bind unique extracellular vesicles, and their protein cargo reflects the disease state of the patient. The successful use of these 2 ligands to isolate circulating plasma extracellular vesicles for biomarker discovery in PE represents a novel technology for biomarker discovery that can be applied to other specialties.

An Unusual Case of Placenta Abruption Leading to Couvelaire Uterus in a Previable Pregnancy.

Couvelaire uterus or uteroplacental apoplexy is a rare complication of abruptio placentae whose etiology is unknown. It is a clinical diagnosis made during visual inspection of the uterus. Immediate management is usually conservative and hysterectomy is usually not required. Our case highlights the importance of early recognition of a clinically unstable previable pregnant patient with suspected placenta abruption and early surgical recourse with successful emergency hysterotomy.

Undiagnosed Abdominal Term Pregnancy with Good Neonatal Outcome.

Abdominal pregnancy is a rare occurrence and it represents only 1% of ectopic pregnancy. We report a case of an abdominal pregnancy that resulted in a term live baby. Diagnosis is unsurprisingly difficult in advanced gestation. A high index of suspicion detailed clinical and imaging examinations are needed to make the diagnosis. Multidisciplinary team involvement is crucial in the management of abdominal pregnancy.

Primary malignant mixed Müllerian tumour (MMMT) of the vagina and review of the literature.

Primary malignant mixed Müllerian tumour (MMMT) of the vagina is a rare entity. We report a case of a 62-year-old woman who presented with a fixed and hard anterior vaginal wall mass with contact bleeding. She proceeded to have an anterior infralevator pelvic exenteration with urethrectomy and anterior vaginectomy, creation of an ileal conduit and bilateral lymph node dissection. Histopathological examination and immunohistochemistry confirmed the diagnosis of primary MMMT of the vagina. The patient was stage IVA at diagnosis. Despite chemotherapy and radiotherapy, she had progressive disease and eventually passed away at the age of 65 years.