Longitudinal analysis of maternal plasma apolipoproteins in pregnancy: a targeted proteomics approach.

Minimally invasive diagnostic tests are needed in obstetrics to identify women at risk for complications during delivery. The apolipoproteins fluctuate in complexity and abundance in maternal plasma during pregnancy and could be incorporated into a blood test to evaluate this risk. The objective of this study was to examine the relative plasma concentrations of apolipoproteins and their biochemically modified subtypes (i.e. proteolytically processed, sialylated, cysteinylated, dimerized) over gestational time using a targeted mass spectrometry approach. Relative abundance of modified and unmodified apolipoproteins A-I, A-II, C-I, C-II, and C-III was determined by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in plasma prospectively collected from 11 gravidas with uncomplicated pregnancies at 4-5 gestational time points per patient. Apolipoproteins were readily identifiable by spectral pattern. Apo C-III(2) and Apo C-III(1) (doubly and singly sialylated Apo C-III subtypes) increased with gestational age (r(2)>0.8). Unmodified Apo A-II, Apo C-I, and Apo C-III(0) showed no correlation (r(2) = 0.01-0.1). Pro-Apo C-II did not increase significantly until third trimester (140 ± 13% of first trimester), but proteolytically cleaved, mature Apo C-II increased in late pregnancy (702 ± 130% of first trimester). Mature Apo C-II represented 6.7 ± 0.9% of total Apo C-II in early gestation and increased to 33 ± 4.5% in third trimester. A label-free, semiquantitative targeted proteomics approach was developed using LTQ-Orbitrap mass spectrometry to confirm the relative quantitative differences observed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in Apo C-III and Apo C-II isoforms between first and third trimesters. Targeted apolipoprotein screening was applied to a cohort of term and preterm patients. Modified Apo A-II isoforms were significantly elevated in plasma from mothers who delivered prematurely relative to term controls (p = 0.02). These results support a role for targeted proteomics profiling approaches in monitoring healthy pregnancies and assessing risk of adverse obstetric outcomes.

A Case Report of Transient Amnesia Following Spontaneous Intracerebral Hemorrhage of the Fornix.

In this report, we share the case of a 65-year-old male with a remote history of brain concussion who presented to the emergency department for evaluation of transient amnesia that lasted 30 minutes to one hour. He was found to have spontaneous intracerebral hemorrhage of the fornix as a cause of his amnesic episode. To date from the creation of this case report (January 2023), spontaneous hemorrhage of the fornix resulting in transient amnesia has not been previously described in the literature. The fornix is an unusual location for spontaneous hemorrhage to occur. The differential diagnosis of transient amnesia is broad and includes, but is not limited to, transient global amnesia, traumatic injury, hippocampal infraction, and various metabolic derangements. Determination of the etiology of transient amnesia can result in changes in treatment decisions. Because of this unique patient presentation, we propose that spontaneous hemorrhage of the fornix should be considered in patients who present with transient amnesia.