Fibrodysplasia Ossificans Progressiva and Pregnancy: A Case Series and Review of the Literature.

Objective: To evaluate maternal and fetal outcomes in pregnant patients with fibrodysplasia ossificans progressiva (FOP; OMIM#135100), an ultrarare genetic disorder characterized by progressive heterotopic ossification of soft tissues and cumulative disability. Methods: This is a retrospective case series of three patients with FOP who were admitted to Grady Memorial Hospital in Atlanta, Georgia, from to February 2011 to July 2021. Results: Three women delivered preterm infants at our institution. These cases posed unique anesthetic and obstetric technical challenges, particularly when securing the airway and performing cesarean delivery. Importantly, each patient received perioperative glucocorticoids for prevention of further heterotopic ossification. Conclusion: FOP is a unique clinical diagnosis encountered by obstetricians and requires multidisciplinary management for optimal outcomes.

Partnering of Public, Academic, and Private Entities to Reestablish Maternal Mortality Review in Georgia.

The pregnancy-related mortality ratio in the United States has increased over the past 25 years. Georgia's pregnancy-related mortality ratio is among the highest in the United States. Confronted with this harsh reality, Georgia reestablished maternal mortality review as one strategy to address its high maternal mortality. To achieve a comprehensive process for review of maternal deaths involved securing the knowledge, resources, and support of physician experts, public health agencies and professional organizations as well as representatives in the state legislature. The six key steps in successfully reinstating maternal mortality review were 1) establishing a maternal mortality advisory committee, 2) developing a defined methodology for comprehensive case identification, 3) convening an introductory maternal mortality review committee meeting, 4) securing legislative protection for the committee, 5) conducting a mock mortality review, and 6) completing a formal first-year case review and producing a summary report of initial findings. This first case review revealed the leading causes of pregnancy-related deaths in Georgia as hemorrhage, hypertension, cardiac disease, embolism, and seizures. Our objective in this commentary is to share our experiences and advocate for engaging public, private, and academic partners in working on complex and multifactorial public health issues such as high maternal mortality.

Development, Implementation, and Evaluation of an Interdisciplinary Women's Health and Laboratory Course.

OBJECTIVES: To describe the creation, implementation, and evaluation of a case-based, interdisciplinary course that highlights laboratory principles for students who have selected a career in obstetrics and gynecology. METHODS: We developed four case-based modules with questions that emphasize laboratory principles required to establish a diagnosis and treat and monitor each case-based scenario. The cases were offered as a 4-hour elective course during the medical school capstone. A clinician and a clinical pathologist pair facilitated the case discussions with groups of six to nine medical students during 2 consecutive years. Pre- and postknowledge quizzes were given to the students. In addition, a structured evaluation of the course was performed. RESULTS: Twenty-two students participated in the courses. Most found the format effective and the information useful. There was a significant increase in their related knowledge as established by pre- and posttesting. CONCLUSIONS: Case-based discussions gave learners a better understanding of the function and complexity of the clinical laboratories, and multidisciplinary facilitation highlighted the value of interacting with laboratory professionals to enhance clinical care.

Pregnancy-Associated Deaths in Rural, Nonrural, and Metropolitan Areas of Georgia.

OBJECTIVE: To characterize pregnancy-associated deaths and examine the relationship between area of residence and pregnancy-associated deaths and pregnancy-related mortality ratios in Georgia from 2010 to 2012. METHODS: The cohort of pregnancy-associated deaths was reviewed and categorized as pregnancy-related or resulting from other medical conditions not related to pregnancy, suicide, drug toxicity, homicide, or motor vehicle accident. Georgia Online Analytical Statistical Information System data were used to calculate pregnancy-related mortality ratio by rural, nonrural, and metropolitan Atlanta area and by race. Causes of death and pregnancy-related mortality ratio were compared by area of residence and race using χ tests; a P value <.05 was considered significant. RESULTS: There were 262 pregnancy-associated deaths; 40.1% (n=105) were pregnancy-related. The 2010-2012 pregnancy-related mortality ratio was 26.5 per 100,000 live births and the pregnancy-related mortality ratio did not differ statistically among rural (27.1), nonrural (24.4), and metropolitan Atlanta (27.7) areas (P=.845). Most pregnancy-related deaths were the result of hemorrhage and cardiovascular factors. In aggregate, the pregnancy-related mortality ratio for black women was 49.5 compared with 14.3 for white women (P<.001). The gap in pregnancy-related mortality ratio between black and white women was highest for metropolitan Atlanta (51.6 compared with 12.4, P<.001), less in nonrural areas (50.3 compared with 12.0, P<.001), and comparable in rural areas (39.4 compared with 22.4, P=.281). CONCLUSION: Although the pregnancy-related mortality ratio was similar for rural, nonrural, and metropolitan Atlanta areas, it was significantly higher for black compared with white women living outside of rural areas.

Fetal cord blood mononuclear cells that are collected at term from HIV-1 infected women harbor transcriptionally active integrated proviral DNA.

OBJECTIVE: The purpose of this study was to determine levels of intrauterine infection and transcriptional activity in cord blood mononuclear cells that were collected at term from fetuses who were born to women who were infected with human immunodeficiency virus (HIV) and who received highly active antiretroviral therapy (HAART). STUDY DESIGN: RNA and DNA were isolated from maternal placental tissues and fetal cord blood specimens that were obtained at term from pregnant women who were infected with HIV and who received HAART. Levels of integrated HIV provirus and messenger RNA transcripts were determined by real-time polymerase chain reaction. RESULTS: Detectable levels of transcriptionally active integrated provirus were present in approximately 27% of cord blood samples (n = 22) that were collected from fetuses who born to HIV-positive mothers who received HAART. Levels of HIV-p24 antigen in cultures that were detected in randomly selected cord blood samples confirmed the presence of inducible infectious virus. CONCLUSION: These findings suggest that some fetuses from HIV-infected mothers who receive HAART and who may be HIV-negative infants after delivery can harbor circulating leukocytes that are infected productively by intrauterine transmission of HIV.

Human tissue mast cells are an inducible reservoir of persistent HIV infection.

We have proposed that, unlike other HIV-vulnerable cell lineages, progenitor mast cells (prMCs), cultured in vitro from undifferentiated bone marrow-derived CD34(+) pluripotent progenitors (PPPs), are susceptible to infection during a limited period of their ontogeny. As infected prMCs mature in culture, they lose expression of viral chemokine coreceptors necessary for viral entry and develop into long-lived, latently infected mature tissue mast cells (MCs), resistant to new infection. In vivo recruitment of prMCs to different tissue compartments occurs in response to tissue injury, growth, and remodeling or allergic inflammation, allowing populations of circulating and potentially HIV-susceptible prMCs to spread persistent infection to diverse tissue compartments. In this report, we provide in vivo evidence to confirm this model by demonstrating that HIV-infected women have both circulating prMCs and placental tissue MCs (PLMCs) that harbor inducible infectious HIV even after highly active antiretroviral therapy (HAART) during pregnancy. Furthermore, infectious virus, capable of infecting alloactivated fetal cord blood mononuclear cells (CBMCs), could be induced in isolated latently infected PLMCs after weeks in culture in vitro. These data provide the first in vivo evidence that tissue MCs, developed from infected circulating prMCs, comprise a long-lived inducible reservoir of persistent HIV in infected persons during HAART.

Emerging infectious disease outbreaks: old lessons and new challenges for obstetrician-gynecologists.

OBJECTIVE: The purpose of this study was to summarize 3 recent high-profile infectious disease threats that have affected the United States: severe acute respiratory syndrome, West Nile virus, and anthrax. STUDY DESIGN: A systematic review was conducted with the use of Medline searches, searches of the Centers for Disease Control and Prevention website, and review by experts at the Centers for Disease Control and Prevention. RESULTS: The 3 emerging infectious diseases pose very different threats: Severe acute respiratory syndrome is a newly identified pathogen that caused an international pandemic; the West Nile virus investigation involved an old pathogen that was identified in a new location; and the anthrax attacks involved the intentional introduction of a pathogen. CONCLUSION: All 3 outbreaks highlight the importance of obstetrician-gynecologists keeping current with new information as it emerges. In this global environment, it is likely that novel disease threats will continue to emerge in the United States.

Emerging infections and pregnancy: West Nile virus, monkeypox, severe acute respiratory syndrome, and bioterrorism.

As new infectious diseases, such as West Nile virus, monkeypox, and severe acute respiratory syndrome (SARS) are recognized in the United States, there are critical questions about how these infectious diseases will affect pregnant women and their infants. In addition, the implications of bioterrorist attacks for exposed pregnant women need to be considered. In this article, the authors address the following questions for a number of infectious disease threats: (1) does pregnancy affect the clinical course of these novel infectious diseases?, (2) what are the implications for prophylaxis and treatment of exposed or infected pregnant women?, and (3) are these novel infectious diseases transmitted during pregnancy, labor and delivery, or breastfeeding?

Inhibition of progenitor dendritic cell maturation by plasma from patients with peripartum cardiomyopathy: role in pregnancy-associated heart disease.

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF-beta were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

Signaling through Toll-like receptors triggers HIV-1 replication in latently infected mast cells.

Evidence that human progenitor mast cells are susceptible to infection with CCR5-tropic strains of HIV-1 and that circulating HIV-1-infected FcepsilonRIalpha(+) cells with a similar progenitor phenotype have been isolated from AIDS patients has led to speculation that mast cells may serve as a potential reservoir for infectious HIV-1. In this study, progenitor mast cells, developed in vitro from CD34(+) cord blood stem cells, were experimentally infected with the CCR5-tropic strain HIV-1Bal after 28 days in culture as they reached their HIV-1-susceptible progenitor stage. HIV-1 p24 Ag levels were readily detectable by day 7 postinfection (PI), peaked at 2-3 wk PI as mature (tryptase/chymase-positive) HIV-1 infection-resistant mast cells emerged, and then steadily declined to below detectable limits by 10 wk PI, at which point integrated HIV-1 proviral DNA was confirmed by PCR quantitation in ( approximately 34% of) latently infected mast cells. Stimulation by ligands for Toll-like receptor (TLR) 2, TLR4, or TLR9 significantly enhanced viral replication in a dose- and time-dependent manner in both HIV-1-infected progenitor and latently infected mature mast cells, without promoting degranulation, apoptosis, cellular proliferation, or dysregulation of TLR agonist-induced cytokine production in infected mast cells. Limiting dilution analysis of TLR activated, latently infected mature mast cells indicated that one in four was capable of establishing productive infections in A301 sentinel cells. Taken together, these results indicate that mast cells may serve both as a viral reservoir and as a model for studying mechanisms of postintegration latency in HIV infection.

Hand preferences in captive gorillas, orang-utans and gibbons.

Hand preference was assessed in 12 gorillas (Gorilla gorilla gorilla), 13 orang-utans (Pongo pygmaeus abelii), and 9 gibbons (Hylobates lar) by using a floor retrieval task and a mesh retrieval task. Hand preference was also assessed in 8 gorillas and 8 orang-utans by using a task involving the unfastening of a hasp. A bipedal requirement during testing (mesh retrieval task) facilitated detection of hand preferences. A significant left-hand preference was found for the gibbons with 6 of 6 gibbons preferring their left hand on the mesh retrieval task. Similarly, a significant right-hand preference was found for the gorillas with 10 of 12 gorillas preferring their right hand on the mesh retrieval task. The data for the orang-utan suggest a bimodal distribution on all tasks. Since the gibbon and gorilla in the wild engage in bipedal locomotion more frequently than the orangutan, one possible interpretation for these results correlates the degree of bipedal behavior of a species in its natural environment with its readiness to exhibit a unilateral population-level hand preference.