Contemporary Obstetric and Neonatal Outcomes in Sickle Cell Disease: A Retrospective Cohort Study.

OBJECTIVE: Sickle cell disease is associated with adverse perinatal outcomes. Aspects of sickle cell disease in pregnancy, such as health care utilization and neonatal abstinence syndrome, are understudied. We aimed to describe contemporary sickle cell disease outcomes in a U.S. hospital system to improve perinatal counseling. STUDY DESIGN: We conducted a retrospective cohort study of patients with sickle cell disease who delivered at >20 weeks' gestation at two sites within the University of Pennsylvania Health System from May 1, 2017 to August 30, 2020. Descriptive statistics were utilized. RESULTS: Over the study period, 48 patients with sickle cell disease had 52 deliveries of 53 neonates. Sickle cell disease-related morbidity was prevalent prior to pregnancy; 27% had a history of avascular necrosis, and 58% had experienced acute chest syndrome. In the year prior to pregnancy, 52% used daily opioids. During pregnancy, more than half of patients were admitted at least once for sickle cell disease-related complications, spending a median 3 days admitted interquartile range (0-23); >10% spent >70 days of pregnancy admitted. New daily opioids were prescribed during pregnancy for 10% to manage pain crises. Acute chest syndrome was experienced by 23% of patients during pregnancy, and 8% required placement of long-term intravenous access. Preterm delivery <37 weeks occurred in 48%. The primary cesarean rate in nulliparas was 43%. Additionally, 50% experienced a hypertensive disorder of pregnancy, 35% underwent transfusion during delivery admission, and 10% had a perinatal venous thromboembolism. Finally, 53% of neonates were admitted to the intensive care unit. Low birth weight was noted in 34%, severe respiratory distress in 15% of infants, and neonatal abstinence syndrome in 21%. CONCLUSION: Sickle cell disease remains associated with significant perinatal morbidity and need for hospitalization. These data provide contemporary outcomes to target improvements in the care of patients with sickle cell disease. KEY POINTS: · SCD was associated with significant perinatal morbidity and healthcare utilization.. · Most patients with SCD required hospitalization during pregnancy.. · Neonates of patients with SCD experienced preterm birth, NICU admission, and neonatal abstinence syndrome..

Challenges in sample preparation for swellable core technology tablets: Approaches for the removal of polyethylene oxide and optimization of API recovery.

Swellable Core Technology (SCT) tablets, a solid oral dosage formulation designed for the controlled release of Active Pharmaceutical Ingredient (API), are made up of two distinct layers; an active layer containing the active ingredient (10-30%wt) and up to 90%wt polyethylene oxide (PEO); and a sweller layer which contains up to 65%wt PEO. The objective of this study was to develop a process to remove PEO from analytical test solutions and optimize API recovery using physicochemical properties of the API. Quantitation of PEO was performed by liquid chromatography (LC) using an evaporative light scattering detector (ELSD). This was used to build an understanding of removal of PEO using solid-phase extraction and liquid-liquid extraction techniques. A workflow was proposed to allow efficient development of analytical methods for SCT tablets with optimized sample clean-up.

Genomic evidence for adaptation to tuberculosis in the Andes before European contact.

Most studies focusing on human high-altitude adaptation in the Andean highlands have thus far been focused on Peruvian populations. We present high-coverage whole genomes from Indigenous people living in the Ecuadorian highlands and perform multi-method scans to detect positive natural selection. We identified regions of the genome that show signals of strong selection to both cardiovascular and hypoxia pathways, which are distinct from those uncovered in Peruvian populations. However, the strongest signals of selection were related to regions of the genome that are involved in immune function related to tuberculosis. Given our estimated timing of this selection event, the Indigenous people of Ecuador may have adapted to Mycobacterium tuberculosis thousands of years before the arrival of Europeans. Furthermore, we detect a population collapse that coincides with the arrival of Europeans, which is more severe than other regions of the Andes, suggesting differing effects of contact across high-altitude populations.

Immunoarray Measurements of Parathyroid Hormone-Related Peptides Combined with Other Biomarkers to Diagnose Aggressive Prostate Cancer.

Parathyroid hormone-related peptide (PTHrP) is related to bone metastasis and hypercalcemia in prostate and breast cancers and should be an excellent biomarker for aggressive forms of these cancers. Current clinical detection protocols for PTHrP are immunoradiometric assay and radioimmunoassay but are not sensitive enough to detect PTHrPs at early stages. We recently evaluated a prostate cancer biomarker panel, including serum monocyte differentiation antigen (CD-14), ETS-related gene protein, pigment epithelial-derived factor, and insulin-like growth factor-1, with promise for identifying aggressive prostate cancers. This panel predicted the need for patient biopsy better than PSA alone. In the present paper, we report an ultrasensitive microfluidic assay for PTHrPs and evaluate their diagnostic value and the value of including them with our prior biomarker panel to diagnose aggressive forms of prostate cancer. The immunoarray features screen-printed carbon sensor electrodes coated with 5 nm glutathione gold nanoparticles with capture antibodies attached. PTHrPs are bound to a secondary antibody attached to a polyhorseradish peroxidase label and delivered to the sensors to provide high sensitivity when activated by H2O2 and a mediator. We obtained an unprecedented 0.3 fg mL-1 limit of detection for PTHrP bioactive moieties PTHrP 1-173 and PTHrP 1-86. We also report the first study of PTHrPs in a large serum pool to identify aggressive malignancies. In assays of 130 human patient serum samples, PTHrP levels distinguished between aggressive and indolent prostate cancers with 83-91% clinical sensitivity and 78-96% specificity. Logistic regression identified the best predictive model as a combination of PTHrP 1-86 and vascular endothelial growth factor-D. PTHrP 1-173 alone also showed a high ability to differentiate aggressive and indolent cancers.