Faculty Bibliography

The Centers for Disease Control and Prevention awarded funding to the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about ovarian cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in February 2022. This article is the executive summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of ovarian cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.

Health disparity, defined by the Centers for Disease Control and Prevention (CDC) as "preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations," is seen across multiple diseases. We conducted an evidence review of health disparities and inequities and their mitigation strategies related to ovarian cancer as part of a CDC-sponsored project to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. Our review found profound disparities in outcomes such as survival, treatment, and stage at diagnosis by factors such as race and ethnicity, insurance, socioeconomic status, and geographic location. We found little direct evidence on mitigation strategies. Studies support equivalent response to equivalent treatment between groups, suggesting that adherence to National Comprehensive Cancer Network guidelines can at least partially mitigate some of the differences.

Background: Maternal tenofovir disoproxil fumarate (TDF) in combination with an infant's passive-active immunoprophylaxis is recommended by WHO for mothers with HBV-DNA >200,000 IU/mL. Because of the shortage of immunoglobulin (HBIg) in many developing countries, we aimed to study maternal TDF therapy initiated in the second trimester with an infant's HBV vaccination and omission of HBIg for preventing mother-to- child transmission (MTCT).
Method(s): In a multicenter RCT from 6/4/2018 to 2/8/2022, we randomly assigned CHB mothers with HBV-DNA >200,000 IU/mL (ratio, 1:1) to receive TDF from gestational weeks 14-16 (experimental group) or week 28 (control) to delivery. All infants received active immunoprophylaxis and HBIg was only given to infants in the control group. The primary outcomes were the congenital defects/malformation rates and MTCT rates (i.e., HBsAg+ or HBV-DNA >20 IU/mL) at the infant's age of 28 weeks. Secondary assessments were safety analyses (ClinicalTrials.gov: NCT03476083).
Result(s): Of the 280 HBeAg+ mothers enrolled, 265 mothers and 269 infants completed the study (95% retention). The participants' characteristics are shown in Table 1. At delivery, a significantly lower median (IQR) HBV-DNA level (log10 IU/mL) was noted in the experimental group (2.37 [1.88, 3.08] vs 3.62 [2.86,4.59]; p< 0.001), with a similar trend in the percentage of mothers with HBV-DNA <200,000 IU/ mL (99.2% vs 94.2%; p=0.04). The congenital defect rates did not differ significantly between groups (3.1% [4/131] vs 6.4% [9/141]; p=0.22). At the postpartum week 28, 128/128 and 137/141 mother/infant dyads in the experiment and the control groups were analyzed, respectively. The per-protocol analysis revealed 0% of MTCT in both groups. The maternal HBeAg/HBsAg (-) rates did not differ significantly between groups. TDF was well-tolerated without discontinuation from severe adverse events (SAEs). Safety parameters were comparable both in frequency and severity between the two groups including estimated glomerular filtration rates during treatment, postpartum ALT flares, and SAEs.
Conclusion(s): In highly viremic CHB mothers, we observed that TDF initiated at gestational weeks 14-16 reduced MTCT to 0% when infants received HBV vaccines without HBIg, which also had similar safety outcomes when compared to those of mothers who initiated TDF at gestational week 28. Our data support the approach of simplifying the prevention of MTCT with early maternal TDF therapy and HBV vaccine for infants. (Table Presented)

BACKGROUND:Primary gynecologic neuroendocrine tumors are uncommon malignant neoplasms associated with poor prognosis. Clinically, these tumors present a significant challenge because of the lack of standardized management guidelines. OBJECTIVE:The objective of this study is to evaluate the clinicopathologic features, incidence, and survival trends in gynecologic neuroendocrine tumors. MATERIALS AND METHODS:Tests, Pearson correlation, and Kaplan-Meier curves were used for statistical analysis. RESULTS:In all, 559 cases of gynecologic neuroendocrine tumors were identified during the study period: 242 cervical, 160 ovarian, 118 uterine, and 39 vulvar/vaginal. The majority of patients in all subsets of gynecologic neuroendocrine tumors presented with poorly differentiated tumors, extrauterine disease spread, and advanced-stage disease. Poorly differentiated tumors represented 65.0% of cervical tumors, 45.3% of ovarian tumors, and 57.4% of uterine tumors. Extrauterine disease at the time of diagnosis was present in the case of 66.9% of cervical tumors, 83.5% of ovarian tumors, and 83.6% of uterine tumors. The overall incidence of gynecologic neuroendocrine tumors increased 4-fold during the study period, from 0.3 in 1987 to 1.30 per million in 2012. The study period was divided into two 13-year periods (1987-1999 and 2000-2012) for time trend mean survival analysis. We observed no significant change in overall survival across all gynecologic neuroendocrine tumor subtypes. The mean survival time of cervical neuroendocrine tumors was 74.3 vs 45.4 months (P = .31), ovarian neuroendocrine tumors 47.8 vs 41.2 months (P = .56), and uterine neuroendocrine tumors 42.9 vs 47.7 months (P = .44) for each time period, respectively. CONCLUSION:Neuroendocrine tumors of the gynecologic tract are uncommon aggressive malignancies. These poorly differentiated tumors present at advanced stage, with a high incidence of extrauterine disease. Despite 25 years of advances in cancer therapy, we observed no improvement in overall survival.

OBJECTIVE:To compare the clinicopathologic features and survival outcomes of neuroendocrine tumor of the uterine corpus (NET-U) to endometrioid type endometrial carcinoma (EC). METHODS:From 1993 to 2012, the Surveillance, Epidemiology and End Results cancer registry was queried for women diagnosed with EC or NET-U. Data regarding stage, grade, presence of extra-uterine disease, lymph node metastasis, receipt of adjuvant radiation, surgical intervention and overall survival (OS) was extracted. Chi-square tests, t-tests and Kaplan Meir curves were used for statistical analysis. RESULTS:A total of 98,363 patients were identified: 98,245 with EC and 118 with NET-U. The mean age at diagnosis for EC was 61.7 years and 64.8 years for NET-U (p=0.01). NET-U cases were more likely to be poorly differentiated (97.0% vs. 15.6%; p≤0.01) and have nodal metastasis (56.4% vs. 11.1%; p≤0.01) when compared to EC. Presence of extrapelvic disease at the time of diagnosis was observed more frequently in NET-U compared to EC, 49.1% vs. 4.8%, respectively (odds ratio=18; 95% confidence interval=13.1-27.2; p≤0.01). Significant improvement in OS was observed in NET-U patient who received radiation (OS: 7.7 vs. 3.3 years; p≤0.01) or underwent surgical management (5.6 vs. 0.9 years; p≤0.01). The OS for EC was 14.4 vs. 4.6 years for NET-U (p≤0.01). CONCLUSION/CONCLUSIONS:NET-U represents an aggressive form of uterine malignancy. When compared to EC, patients with NET-U present at more advanced stage, have more frequent extra-uterine disease and lower OS.

BACKGROUND:Excitotoxicity (the toxic overstimulation of neurons by the excitatory transmitter Glutamate) is a central process in widespread neurodegenerative conditions such as brain ischemia and chronic neurological diseases. Many mechanisms have been suggested to mediate excitotoxicity, but their significance across diverse excitotoxic scenarios remains unclear. Death Associated Protein Kinase (DAPK), a critical molecular switch that controls a range of key signaling and cell death pathways, has been suggested to have an important role in excitotoxicity. However, the molecular mechanism by which DAPK exerts its effect is controversial. A few distinct mechanisms have been suggested by single (sometimes contradicting) studies, and a larger array of potential mechanisms is implicated by the extensive interactome of DAPK. RESULTS:Here we analyze a well-characterized model of excitotoxicity in the nematode C. elegans to show that DAPK is an important mediator of excitotoxic neurodegeneration across a large evolutionary distance. We further show that some proposed mechanisms of DAPK's action (modulation of synaptic strength, involvement of the DANGER-related protein MAB-21, and autophagy) do not have a major role in nematode excitotoxicity. In contrast, Pin1/PINN-1 (a DAPK interaction-partner and a peptidyl-prolyl isomerase involved in chronic neurodegenerative conditions) suppresses neurodegeneration in our excitotoxicity model. CONCLUSIONS:Our studies highlight the prominence of DAPK and Pin1/PINN-1 as conserved mediators of cell death processes in diverse scenarios of neurodegeneration.

A Large scale of full-thickness skin defects is lack of auto-grafts and which requires the engineered skin substitutes for repair and regeneration. One major obstacle in skin tissue engineering is to expand epidermal stem cells (ESCs) and develop functional substitutes. The other one is the scaffold of the ESCs. Here, we applied type I collagen-modified chitin membrane to form collagen-chitin biomimetic membrane (C-CBM), which has been proved to have a great biocompatibility and degraded totally when it was subcutaneously transplanted into rat skin. ESCs were cultured, and the resulting biofilm was used to cover full-thickness skin defects in nude mice. The transplantation of ESCs- collagen- chitn biomimetic membrane (ESCs-C-CBM) has achieved in situ skin regeneration. In nude mice, compared to controls with collagen-chitin biomimetic membrane (C-CBM) only, the ESCs-C-CBM group had significantly more dermatoglyphs on the skin wound 10 w after surgery, and the new skin was relatively thick, red and elastic. In vivo experiments showed obvious hair follicle cell proliferation in the full-thickness skin defect. Stem cell markers examination showed active ESCs in repair and regeneration of skin. The results indicate that the collagen-modified chitin membrane carry with ESCs has successfully regenerated the whole skin with all the skin appendages and function.