Quantitation of Niraparib in Human Plasma by LC-MS/MS.

Polyadenosine diphosphate-ribose polymerase 1 (PARP-1) and 2 (PARP-2) are key DNA repair enzymes that promote single-strand break repair via the base excision pathway. Niraparib, a PARP inhibitor, has shown clinical efficacy with the reduction of disease progression or death and progression-free survival benefit across multiple clinical trials, leading to the Food and Drug Administration (FDA) approval for the treatment of advanced and recurrent ovarian cancers. This study presents a robust and simple 5-min assay designed for the quantitation of the single agent niraparib in human plasma utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Ovarian cancer risk and survival according to tumor sex hormone receptor expression: An ovarian Cancer association consortium and ovarian tumor tissue analysis consortium pooled analysis.

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases).

Cost-Effectiveness Analysis of Tumor Testing for BRCA Pathogenic Variants in Epithelial Ovarian Cancer.

Objectives: Approximately 15% of women with epithelial ovarian cancer (EOC) have a germline BRCA1/2 pathogenic variant. Genetic testing for BRCA is recommended for all EOC patients, but not routinely performed. This study estimates the cost-effectiveness of BRCA screening with primary tumor testing versus routine germline testing.

Adjuvant Therapy in Early Uterine Serous Carcinoma.

Objective: Uterine serous carcinoma (USC) is a rare diagnosis but associated with high mortality. There is limited data to guide adjuvant treatment decisions in early stage disease. The purpose of this study is to evaluate the impact of adjuvant therapy on recurrence-free survival (RFS) and overall survival (OS) in early stage USC.

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).

Background: The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.

Methods: We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer.

Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.

Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) tumors are uniquely aggressive, suggesting that the primary tumor is intrinsically equipped to disseminate and metastasize. Previous work identified mutational hotspots within PPP2R1A, which encodes the Aα scaffolding subunit of protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine phosphatase. Two recurrent heterozygous PPP2R1A mutations, P179R and S256F, occur exclusively within high-grade subtypes of uterine cancer and can drive tumorigenesis and metastasis.

Variables impacting prolonged post-anesthesia care unit length of stay in gynecologic cancer patients in the era of same day minimally invasive hysterectomy.

Objectives: Minimally invasive surgery for treatment of gynecologic malignancies is associated with decreased pain, fewer complications, earlier return to activity, lower cost, and shorter hospital stays. Patients are often discharged the day of surgery, but occasionally stay overnight due to prolonged post-anesthesia care unit (PACU) stays. The objective of this study was to identify risk factors for prolonged PACU length of stay (LOS).

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

Preliminary study of proton magnetic resonance spectroscopy to assess bone marrow adiposity in the third metacarpus or metatarsus in Thoroughbred racehorses.

Background: Magnetic resonance spectroscopy (MRS) has been used to investigate metabolic changes within human bone. It may be possible to use MRS to investigate bone metabolism and fracture risk in the distal third metacarpal/tarsal bone (MC/MTIII) in racehorses.

Objectives: To determine the feasibility of using MRS as a quantitative imaging technique in equine bone by using the H spectra for the MC/MTIII to calculate fat content (FC).

Clinical outcomes following identification of an incidental p53 signature in the fallopian tube.

Fallopian tube pathology in patients with and mutations suggests a possible pathway to high grade serous ovarian carcinoma originates with a p53 signature, which is thought to represent a potential precursor to serous tubal intraepithelial carcinoma (STIC). The clinical implications of an isolated p53 signature in the average-risk population has not been well-established. This study aims to describe clinical outcomes in patients with incidentally noted p53 signature lesions.

The role of obesity in treatment planning for early-stage cervical cancer.

Objectives: Optimal management of obese patients with early-stage cervical cancer is debated despite evidence of non-inferior survival in obese patients undergoing radical hysterectomy with pelvic lymphadenectomy (RH) compared to primary radiation with or without radiosensitizing chemotherapy (RT). Objectives included describing patient factors affecting disposition to RH versus RT; comparing RH outcomes for obese (BMI >30 mg/m) and non-obese patients; and comparing differences in recurrence free survival (RFS) and overall survival (OS).

Methods: This was a single institution cohort study of all cervical cancer patients who underwent RH or were candidates for RH based on clinical stage.

Emotional functioning in long COVID: Comparison to post-concussion syndrome using the Personality Assessment Inventory.

Recent studies on Long COVID found that patients report prominent emotional distress and significant correlations between distress and cognitive performance have been identified, raising the question of how to manage or treat these issues. To understand psychological functioning in Long COVID further, this study examined personality responses on the Personality Assessment Inventory (PAI) to compare psychological functioning in a Long COVID group with a post-concussion syndrome (PCS) group, a syndrome with a significant psychological component. Participants included 201 consecutive Long COVID outpatients (Mean age = 48.

QCT-based computational bone strength assessment updated with MRI-derived 'hidden' microporosity.

Microdamage accumulated through sustained periods of cyclic loading or single overloading events contributes to bone fragility through a reduction in stiffness and strength. Monitoring microdamage in vivo remains unattainable by clinical imaging modalities. As such, there are no established computational methods for clinical fracture risk assessment that account for microdamage that exists in vivo at any specific timepoint.

Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer.

Objective: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer.

Methods: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected.

Cost-effectiveness analysis of tumor molecular testing in stage III endometrial cancer.

Background: Standard of care for adjuvant treatment of stage III endometrial cancer includes chemotherapy and radiation. In addition to stage, tumor molecular profiles may predict treatment outcomes, and prospective clinical trials are ongoing. However, tumor molecular testing is costly and time-consuming.

Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

Background: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

Investigation of MicroRNA Biomarkers in Equine Distal Interphalangeal Joint Osteoarthritis.

Osteoarthritis of the equine distal interphalangeal joint is a common cause of lameness. MicroRNAs from biofluids are promising biomarkers and therapeutic candidates. Synovial fluid samples from horses with mild and severe equine distal interphalangeal joint osteoarthritis were submitted for small RNA sequencing.

T2 mapping of cartilage in the equine distal interphalangeal joint with corresponding histology using 0.27 T and 3.0 T magnetic resonance imaging.

Background: Low-field magnetic resonance imaging (MRI) is widely available to equine veterinarians yet is insensitive at detecting cartilage damage in the distal interphalangeal joint (DIPJ). T2 mapping is a quantitative imaging technique that can detect cartilage damage before morphological change is apparent.

Objectives: Validation of a T2 mapping sequence on a low-field MR system.

Effects of the Perceived Risk of Contracting COVID-19 on Nursing Students' Well-Being.

Background: Although mental health symptoms increased during the coronavirus disease 2019 (COVID-19) pandemic, little is known about the associations between nursing students' perceived risk of contracting COVID-19 and their academic and psychological well-being. This study examined associations between perceived COVID-19 risk, likelihood of completing nursing education, and mental health factors of nursing students.

Method: A total of 979 nursing students completed self-report measures of perceived COVID-19 risk, anticipated academic completion, anxiety and depressive symptoms, stress, coping self-efficacy, hope, and social support.

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

Background: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.

Methods: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively).

Clinical factors associated with failed sentinel lymph node mapping in endometrial cancer.

Objective: Sentinel lymph node (SLN) mapping is a highly accurate surgical technique for detecting metastases in endometrial cancer. The objective of this study was to identify clinical factors associated with failed mapping.

Methods: All patients with endometrial cancer undergoing minimally-invasive staging and planned SLN biopsy from 1/1/2017 to 12/31/2020 at a single institution were identified retrospectively.

Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer.

BACKGROUNDNew therapeutic combinations to improve outcomes of patients with ovarian cancer are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.