Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10-8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

Self-Sampling for Human Papillomavirus Testing: Acceptability in a U.S. Safety Net Health System.

INTRODUCTION: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system. METHODS: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences. RESULTS: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%). CONCLUSIONS: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.

Feasibility and safety of planned early discharge following laparotomy in gynecologic oncology with enhanced recovery protocol including opioid-sparing anesthesia.

Objective: This study aims to evaluate the feasibility and safety of planned postoperative day 1 discharge (PPOD1) among patients who undergo laparotomy (XL) in the department of gynecology oncology utilizing a modified enhanced recovery after surgery (ERAS) protocol including opioid-sparing anesthesia (OSA) and defined discharge criteria. Methods: Patients undergoing XL and minimally invasive surgery (MIS) were enrolled in this prospective, observational cohort study after the departmental implementation of a modified ERAS protocol. The primary outcome was quality of life (QoL) using SF36, PROMIS GI, and ICIQ-FLUTS at baseline and 2- and 6-week postoperative visits. Statistical significance was assessed using the two-tailed Student's t-test and non-parametric Mann-Whitney two-sample test. Results: Of the 141 subjects, no significant demographic differences were observed between the XL group and the MIS group. The majority of subjects, 84.7% (61), in the XL group had gynecologic malignancy [vs. MIS group; 21 (29.2%), p < 0.001]. All patients tolerated OSA. The XL group required higher intraoperative opioids [7.1 ± 9.2 morphine milligram equivalents (MME) vs. 3.9 ± 6.9 MME, p = 0.02] and longer surgical time (114.2 ± 41 min vs. 96.8 ± 32.1 min, p = 0.006). No significant difference was noted in the opioid requirements at the immediate postoperative phase and the rest of the postoperative day (POD) 0 or POD 1. In the XL group, 69 patients (73.6%) were successfully discharged home on POD1. There was no increase in the PROMIS score at 2 and 6 weeks compared to the preoperative phase. The readmission rates within 30 days after surgery (XL 4.2% vs. MIS 1.4%, p = 0.62), rates of surgical site infection (XL 0% vs. MIS 2.8%, p = 0.24), and mean number of post-discharge phone calls (0 vs. 0, p = 0.41) were comparable between the two groups. Although QoL scores were significantly lower than baseline in four of the nine QoL domains at 2 weeks post-laparotomy, all except physical health recovered by the 6-week time point. Conclusions: PPOD1 is a safe and feasible strategy for XL performed in the gynecologic oncology department. PPOD1 did not increase opioid requirements, readmission rates compared to MIS, and patient-reported constipation and nausea/vomiting compared to the preoperative phase.

Cervical cancer screening among English- and Spanish-speaking Hispanic women in an urban safety net health system, 2015-2020.

BACKGROUND: The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system. METHODS: Electronic health records were used to identify 46,094 women aged 30-65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test. RESULTS: Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: 0.93 - 0.96). Further, those with indigent healthcare plans had a higher prevalence of being UTD when compared to those with private insurance (aPR: 1.10, 95% CI: 1.09 - 1.12), while all other health insurance plans were associated with lower UTD screening when compared to private insurance. CONCLUSIONS: These findings suggest screening differences within the Hispanic population, highlighting the need for disaggregated research assessing heterogeneity within racial/ethnic groups, specifically among Hispanic populations.

FKBP51 Contributes to Uterine Leiomyoma Pathogenesis by Inducing Cell Proliferation and Extracellular Matrix Deposition.

The FK506-binding protein 51 (FKBP51) binds progesterone receptor (PR), glucocorticoid receptor (GR), and androgen receptor (AR) to coregulate their transcriptional activity. We evaluated FKBP51 expression and function in human leiomyoma vs. myometrial tissues and primary cultures to discover FKBP51 role(s) in the pathogenesis of leiomyomas. Quantification of in situ FKBP51 mRNA and protein levels inpaired myometrial vs. leiomyoma tissues from proliferative and secretory phases were analyzed by qPCR (n = 14), immunoblotting (n = 20), and immunohistochemistry (n = 12). Control (scramble) vs. FKBP5 siRNA-transfected leiomyoma cell cultures were assessed for proliferation, apoptosis, and mRNA levels of genes involved in cell survival and extracellular matrix (ECM) formation. Significantly higher FKBP5 mRNA levels were detected in leiomyoma vs. paired myometrium (P < 0.001). Immunoblot (P = 0.001) and immunostaining (P ≤ 0.001) confirmed increased FKBP51 levels in leiomyoma vs. paired myometrium. Compared to control siRNA transfection, FKBP5-silenced leiomyoma cell cultures displayed significantly decreased cell survival factors and reduced proliferation (P < 0.05). Moreover, qPCR analysis revealed significantly lower mRNA levels of ECM, TIPM1, and TIPM3 proteins in FKBP5-silenced leiomyoma cell cultures (P < 0.05). Increased FKBP51 expression in leiomyoma likely involves dysregulation of steroid signaling by blocking GR and PR action and promoting proliferation and ECM production. Evaluating the effect of FKBP51 inhibition in preclinical studies will clarify its significance as a potential therapeutic approach against leiomyoma.

Oxidized Regenerated Cellulose Mimicking a Retained Laparotomy Sponge.

Oxidized regenerated cellulose (ORC) is an absorbable hemostat commonly used during gynecologic surgery. We present a case in which ORC was used in a patient undergoing posterior pelvic exenteration with ureteroneocystostomy for excision of a malignant pelvic mass. At the conclusion of these procedures, the laparotomy pad count was reported as incomplete likely due to the large number of laparotomy pads used and changes in nursing staff. Abdominal radiographs were obtained to verify no pads were retained in the abdominal cavity. These identified a poorly defined radiolucency deep in the patient's pelvis, requiring the surgical incision be reopened. Upon reexploration, no evidence of a retained surgical sponge could be identified. However, ORC was identified at the site of the radiolucency in question. Radiographs of this material, once removed, confirmed its radiolucent appearance. This experience clearly demonstrates that oxidized regenerated cellulose can mimic a retained surgical sponge on intraoperative radiographs. Dissemination of this knowledge will hopefully help to avoid radiographic misidentification of ORC in the perioperative window and minimizing the risk of unnecessary surgical interventions in the future.

Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of hematological toxicities during cervical cancer treatment. METHODS: Patients treated for cervical carcinoma with definitive chemoradiation were identified. Toxicities were assessed during weeks 1 to 6 of concurrent external beam radiation and chemotherapy. Outcomes were analyzed using Cox regression analysis. RESULTS: One hundred twenty-one patients with Federation of Gynecology and Obstetrics stage I-III disease were eligible for analysis. Median age at diagnosis was 45 years (interquartile range, 40-52) with median follow-up time of 34 months (95% confidence interval, 30.8-37.2). All patients experienced some grade of hematologic toxicity. The most common grade 3+ toxicities were low absolute lymphocyte count (n=115, 95%), low white blood cell count (n=21, 17%), and anemia (n=11, 9%). The most common grade 4 toxicity was lymphopenia, experienced by 36% of patients (n=44). Grade 4 lymphopenia was associated with reduced overall survival (hazard ratio [HR], 4.5; P=0.005), progression-free survival (HR, 3.4; P=0.001), and local control (HR, 4.1; P=0.047). Anemia grade 3, 4 was also associated with reduced overall survival (HR, 4.1; P=0.014). After controlling for disease and treatment variables, grade 4 lymphopenia remained significantly associated with reduced overall survival (HR, 9.85; P=0.007). The association with grade 4 lymphopenia only remained significant in women of Hispanic ethnicity. CONCLUSION: Severe lymphopenia was associated with reduced overall survival and progression-free survival in Hispanic women undergoing definitive chemoradiation for cervical cancer, but not associated with outcomes in non-Hispanic women.

The Intersection of Palliative Care and Genetic Counseling in Cancer Care: A Case Discussion.

Up to 10% of cancers have a strong hereditary component. The diagnosis of a hereditary cancer may alter treatment recommendations for the patient. However, the optimal timing and best practices for integrating genetic counseling and testing into the care of women diagnosed with cancer remains unclear. In this study, we demonstrate the potential benefits of discussing genetic testing and counseling in the context of palliative care through two cases. Incorporating referrals for genetic testing into the palliative care context is important. This provides an opportunity to perform previously missed genetic testing. It is also a chance for the patient to leave a legacy while also potentially allowing for alternate targeted treatment possibilities that may be well tolerated and provide a better quality of life for the patients themselves. The benefits of referral to palliative care by the genetics team includes assisting patients with the management of not only physical but also psychological symptoms as well as conducting advanced care planning in patients and families with hereditary mutations.

Trends in ureteral surgery on an academic gynecologic oncology service.

OBJECTIVE: To describe the incidence, complications, and trends associated with ureteral surgeries on a gynecologic oncology service in the context of a fellowship training program over a 24-year period. METHODS: We conducted a retrospective cohort analysis of ureteral surgeries by gynecologic oncologists at either Moffitt Cancer Center or Tampa General Hospital from 1997 to 2020. Patient characteristics, predisposing factors, location and type of injury, repair method, postoperative management and complications were abstracted from the medical record. The recent cohort (2005-2020) was compared to our prior series (1997-2004). RESULTS: Eighty-eight cases were included. The average number of ureteral surgeries per year decreased from 5.75 (1997-2004) to 2.63 (2005-2020). Of 46 iatrogenic injuries, 45 were recognized and repaired intraoperatively. Ureteral transection was the most common type (85% [39 of 46]) and the distal 5 cm was the most common location of injury (63% [29 of 46]). Ureteroneocystostomy was the most common method of repair (83% [73 of 88]). Postoperative management, including stenting and imaging, has not changed significantly. Length of urinary catheter usage decreased in the recent cohort without associated complications. Five patients had major postoperative complications and 4 involved the urinary tract. Of those with follow-up, 96% (66 of 69) of ureteroneocystostomies and 75% (9 of 12) of ureteroureterostomies had radiologically normal urinary tracts. CONCLUSIONS: Ureteral surgery is necessary in the case of injury or involvement with invasive disease. There has been a decrease in number of procedures. Ureteroneocystostomy has remained the most common method of reconstruction for both injury and resection with acceptable postoperative complication rates.

Mailed self-sample HPV testing kits to improve cervical cancer screening in a safety net health system: protocol for a hybrid effectiveness-implementation randomized controlled trial.

BACKGROUND: Almost 20% of U.S. women remain at risk for cervical cancer due to their inability or unwillingness to participate in periodic clinic-based screening. Self-sampling has been shown to be an effective strategy for screening women for high-risk human papillomavirus (HR-HPV) infection in specific contexts. However, its effectiveness among medically underserved women in safety net health systems has not been evaluated. Furthermore, it is also unclear whether implementation strategies such as patient navigation can be used to improve the success of self-sample screening programs by addressing patient-level barriers to participation. METHODS/DESIGN: The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) trial is a hybrid type 2 effectiveness-implementation pragmatic randomized controlled trial of mailed self-sample HPV testing. The aim is to assess the effectiveness of mailed self-sample HPV testing kits to improve cervical cancer screening participation among patients in a safety net health system who are overdue for clinic-based screening, while simultaneously assessing patient navigation as an implementation strategy. Its setting is a large, urban safety net health system that serves a predominantly racial/ethnic minority patient population. The trial targets recruitment of 2268 participants randomized to telephone recall (enhanced usual care, n = 756), telephone recall with mailed self-sample HPV testing kit (intervention, n = 756), or telephone recall with mailed self-sample HPV testing kit and patient navigation (intervention + implementation strategy, n = 756). The primary effectiveness outcome is completion of primary screening, defined as completion and return of mailed self-sample kit or completion of a clinic-based Pap test. Secondary effectiveness outcomes are predictors of screening and attendance for clinical follow-up among women with a positive screening test. Implementation outcomes are reach, acceptability, fidelity, adaptations, and cost-effectiveness. DISCUSSION: Hybrid designs are needed to evaluate the clinical effectiveness of self-sample HPV testing in specific populations and settings, while incorporating and evaluating methods to optimize its real-world implementation. The current manuscript describes the rationale and design of a hybrid type 2 trial of self-sample HPV testing in a safety net health system. Trial findings are expected to provide meaningful data to inform screening strategies to ultimately realize the global goal of eliminating cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03898167 . Registered on 01 April 2019. TRIAL STATUS: Study start data: February 13, 2020. Recruitment status: Enrolling by invitation. Estimated primary completion date: February 15, 2023. Estimated study completion date: May 31, 2024. Protocol version 1.6 (February 25, 2020).

ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment.

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

Qualitative assessment of knowledge and attitudes towards cervical cancer screening among male Latino immigrants in Houston, Texas.

BACKGROUND: Male spouses and partners play an important role in determining a woman's willingness to participate in cervical cancer screening. However, the attitudes and behaviors by which they influence a woman's decision to undergo Pap testing remain poorly understood. METHODS: A series of semi-structured, qualitative interviews were conducted in Spanish with 19 recent Latino immigrants in Houston, Texas. The interview format was designed to establish each individual's pattern of engagement with the United States healthcare system, assess baseline knowledge of cervical cancer screening and evaluate attitudes and patterns of communication with their female partners regarding health care. Interview questions were constructed using principles of the Theory of Reasoned Action. All interviews were conducted in Spanish. After translation, responses were coded and scored with the goal of identifying themes and key observations. RESULTS: Most subjects reported few, if any, interactions with the healthcare system since their arrival in the United States. Although most participants reported being aware that women should be seen by their doctors regularly, fewer than half could clearly indicate the purpose of a Pap test or could state with certainty the last time their female partner had undergone screening. Multiple subjects expressed a general distrust of the health care system and concern for its costs. Approximately half of subjects reported that they accompanied their female partner to the health care provider's office and none of the participants reported that they were present in examination rooms at the time their partner underwent screening. Multiple participants endorsed that there may be some concerns within their community regarding women receiving frequent gynecologic care and distrust of the healthcare system. Almost all interviewed subjects stated that while they would allow their female partners to see male physicians, they also expressed the opinion that other men might be uncomfortable with this and that women would likely be more comfortable with female physicians. CONCLUSIONS: Strategies to enhance knowledge of HPV and cancer screening and improve trust in the health care system among male spouses or partners should be explored with the goal of promoting cervical cancer screening among immigrant Latinx populations.

Association Between Metabolic Syndrome and Endometrial Cancer Survival in a SEER-Medicare Linked Database.

BACKGROUND: Metabolic syndrome has previously been linked to increased risk of endometrial cancer. This study examines the association between metabolic syndrome and cancer-specific survival (CSS) in early stage and locoregionally advanced endometrial cancer. METHODS: The SEER-Medicare linked database was used to identify a cohort of patients with endometrial cancer between 1992 and 2011 who underwent hysterectomy. Patients with incomplete stage or grade information were excluded. Patients were stratified into early stage (stage I to II) or locoregionally advanced (stage III to IVa) disease. Metabolic syndrome status was determined through Medicare claims 1 year before diagnosis. The relationship between metabolic syndrome and CSS was evaluated using univariable and multivariable Cox proportional hazards regression analyses. RESULTS: A total of 10,090 patients with endometrial cancer were identified. The mean age was 75 and the majority (91.5%) were white. At diagnosis, 86.6% of patients were early stage and 13.4% were locoregionally advanced. Sixteen percent of patients had metabolic syndrome. On stage stratified multivariable analysis, race, income quartile, year of diagnosis, histopathology, and adjuvant treatment were associated with CSS in early stage disease. Presence of metabolic syndrome was associated with worse CSS in early stage disease (hazard ratio=1.28, 95% confidence interval: 1.09-1.53); this difference did not exist for locoregionally advanced disease (hazard ratio=1.18, 95% confidence interval: 0.93-1.49). CONCLUSIONS: In elderly early stage endometrial cancer patients, metabolic syndrome is associated with worse CSS. Control of metabolic syndrome through lifestyle and pharmacologic therapies may improve cancer prognosis in this population.

Dynamic transcriptome, accessible genome, and PGR cistrome profiles in the human myometrium.

The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq, and PGR ChIPseq assays to profile transcriptome, assessible genome, and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory, and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to the altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors, and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD, and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.

Pilot survey of mosquitoes (Diptera: Culicidae) from southeastern Georgia, USA for Wolbachia and Rickettsia felis (Rickettsiales: Rickettsiaceae).

BACKGROUND & OBJECTIVES: Mosquito surveillance is one of the critical functions of local health departments, particularly in the context of outbreaks of severe mosquito-borne viral infections. Unfortunately, some viral and parasitic infections transmitted by mosquitoes, manifests non-specific clinical symptoms which may actually be of rickettsial etiology, including Rickettsia felis infections. This study tested the hypothesis that mosquitoes from southeastern Georgia, USA may be infected with Rickettsia felis and Wolbachia, an endosymbiotic bacterium of the order Rickettsiales. METHODS: Specimens of the five most common mosquito species occurring in the region were collected using gravid and light-traps and identified using morphological keys. Mosquitoes were then pooled by species, sex, trap and collection site and their DNA was extracted. Molecular methods were used to confirm mosquito identification, and presence of Wolbachia and R. felis. RESULTS: Wolbachia DNA was detected in 90.8% of the mosquito pools tested, which included 98% pools of Cx. quinquefasciatus Say (Diptera: Culicidae), 95% pools of Ae. albopictus Skuse (Diptera: Culicidae), and 66.7% of pools of Cx. pipiens complex. Samples of An. punctipennis Say (Diptera: Culicidae) and An. crucians Wiedemann (Diptera: Culicidae) were tested negative for Wolbachia DNA. Three genotypes of Wolbachia sp. belonging to Group A (1 type) and Group B (2 types) were identified. DNA of R. felis was not found in any pool of mosquitoes tested. INTERPRETATION & CONCLUSIONS: This study provides a pilot data on the high presence of Wolbachia in Cx. quinque-fasciatus and Ae. albopictus mosquitoes prevalent in the study region. Whether the high prevalence of Wolbachia and its genetic diversity in mosquitoes affects the mosquitoes' susceptibility to R. felis infection in Georgia will need further evaluation.

Molecular Survey for Pathogens and Markers of Permethrin Resistance in Human Head Lice (Phthiraptera: Pediculidae) from Madagascar.

Human infestation with head lice, Pediculus humanus capitis De Geer, is the most prevalent ectoparasitic condition in the modern world. The purpose of this study was to test human head lice from Madagascar for infection with 2 louse-borne bacteria, Bartonella quintana and Acinetobacter spp. including Acinetobacter baumannii, to assess the potential risk of exposure to these pathogens in rural populations experiencing head-louse pediculosis. A second aim was to determine the occurrence of a biomarker for permethrin resistance in head lice from 6 isolated human communities in Madagascar. Deoxyribonucleic acid (DNA) of B. quintana was detected using species-specific Fab3 gene TaqMan in 12.6% of lice from 4 villages. DNA of Acinetobacter spp. was detected using rpoB TaqMan in 42.1% of lice collected from all locations; 58.3% of rpoB-positive lice had the blaOXA51-like enzyme gene specific for A. baumannii. The kdr-resistant allele was detected in 70% of lice tested and was found in lice from each location. These results provide the first information regarding these combined characteristics of head-louse infestations in Madagascar. This approach can be applied to larger and broader surveys of lice from pediculosis capitis occurring in other geographic locations.

Inversely and adaptively planned interstitial brachytherapy: A single implant approach.

OBJECTIVE: To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. METHODS: Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. RESULTS: Forty women with an overall median follow-up of 18 months (range: 6-54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V100: 98%, HR-CTV EQD2: 85.1 Gy, D90: 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1-1.8] (p = .046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. CONCLUSIONS: A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease.

Distinct molecular pathways in ovarian endometrioid adenocarcinoma with concurrent endometriosis.

Women with endometriosis, a benign growth of endometrial tissue outside the uterine cavity, are at increased risk of specific histotypes of epithelial ovarian cancer, such as ovarian endometrioid adenocarcinoma (OEA). Women with OEA who have endometriosis at time of surgical staging demonstrate improved clinical prognosis compared to women with OEA without evidence of endometriosis. However, the molecular contributions of the endometriotic tumor microenvironment to these ovarian cancers remain poorly understood. As a starting point, we used a platform for genome-wide transcriptomic profiling to compare specimens of OEA from women with and without concurrent endometriosis and benign reproductive tract tissues, including proliferative endometrium and typical and atypical endometrioma samples (n = 20). Principle component analysis revealed distinct clustering between benign and malignant samples as well as malignant samples with and without concurrent endometriosis. Examination of gene signatures revealed that OEA with concurrent endometriosis contained a unique molecular signature compared to OEA without concurrent endometriosis, distinguished by 682 unique genes differentially expressed (fold change < or >1.5, p < 0.01). Bioinformatic analysis of these differentially expressed gene products using ingenuity pathway analysis revealed activation of NFkB signaling, an inflammatory signaling pathway constitutively active in endometriosis. DAVID functional annotation clustering further revealed enrichment in RAS signaling as both cytoskeleton organization and GTPase regulator activity relied heavily on RAS protein signal transduction. Gene set enrichment analysis highlighted immune and inflammatory nodes involved in OEA with concurrent endometriosis. These observations provide novel resources for understanding molecular subtleties potentially involved in OEA within the context of the endometriotic tumor microenvironment.

An analysis of the effect of statins on the risk of Non-Hodgkin's Lymphoma in the Women's Health Initiative cohort.

Statins have been shown to induce a phosphoprotein signature that modifies MYC (myelocytomatosis viral oncogene) activation and to have anti-inflammatory activity that may impact the risk of Non-Hodgkin's lymphoma (NHL). We analyzed the relationship between statins and risk of NHL using data from the Women's Health Initiative (WHI). The study population included 161,563 postmenopausal women ages 50-79 years from which 712 cases of NHL were diagnosed after 10.8 years of follow-up. Information on statin use and other risk factors was collected by self- and interviewer-administered questionnaires. Multivariable-adjusted HR and 95% CI evaluating the relationship between statin use at baseline, as well as in a time-dependent manner and risk of NHL, were computed from Cox proportional hazards analyses. A separate analysis was performed for individual NHL subtypes: diffuse large B-Cell lymphoma (DLBCL) (n = 228), follicular lymphoma (n = 169), and small lymphocytic lymphoma (n = 74). All statistical tests were two-sided. There was no significant association between use of statins at baseline and risk of NHL (HR 0.85, 95% C.I. 0.67-1.08). However, in the multivariable-adjusted time-dependent models, statin use was associated with a borderline lower risk of NHL (HR 0.81, 95% C.I. 0.66-1.00). Considering subtypes of NHL, statin use was associated with a lower risk of DLBCL (HR 0.62, 95% C.I. 0.42-0.91). This effect was driven by lipophilic statins (HR 0.62, 95% C.I. 0.40-0.96). In the WHI, statins were associated with a lower overall risk of DLBCL, particularly attributable to lipophilic statins. These results may have impact on primary or secondary prevention of NHL, particularly DLBCL.

An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative.

BACKGROUND: Statins have anti proliferative activity in vitro against endometrial and ovarian cancer and can affect levels of reproductive hormones. We analyzed data from the Women's Health Initiative (WHI) to assess whether statins are associated with risk of endometrial and ovarian cancer. METHODS: The WHI study included 161,808 postmenopausal women in which incident cases of endometrial (n = 1377) and ovarian cancer (n = 763) were identified over an average of 10.8 (SD + 3.3) years. Information on statin use and risk factors was collected at baseline and follow-up. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of statin use and risk of endometrial and ovarian cancer. All statistical tests were two-sided. RESULTS: Statins were used at baseline by 7.5% women and by up to 25% at year nine. The multivariable adjusted HR for risk of endometrial cancer for baseline statin use was 0.74, 95% C.I. 0.59-0.94 and for ovarian cancer was 1.15, 95% C.I. 0.89-1.50. In time-dependent models, statins were not associated with endometrial cancer (HR 0.91, 95% C.I. 0.76-1.08) however there was an increased risk of ovarian cancer (HR 1.30, 95% CI 1.04-1.62), largely attributed to the effect of the hydrophilic statin, pravastatin (1.89, 95% CI 1.24-2.88). CONCLUSIONS: There was a reduction in risk of endometrial cancer among statin users at baseline but not in time-dependent models. Pravastatin use was associated with an increased risk of ovarian cancer. Analyses of larger numbers of cases are needed to evaluate these findings.