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Purpose: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. Experimental Design: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. Results: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; P = 0.003) than RAD51-High status. Conclusions: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.

PurposeThe appalling abuse healthcare workers have endured from patients is long documented in the popular press and social media. Less explored in the healthcare management literature is workplace abuse that professional nurses experience from their coworkers.Design/methodology/approachThe authors use text-based first-hand accounts from nurses posting on Reddit (N = 75) to better understand the types and context of abusive acts endured by their coworkers in the contemporary healthcare setting. Each account is content analyzed using two raters, and thematic analysis is utilized to summarize findings.FindingsFindings indicate that nurse workplace abuse frequently targets new entrants to a work unit (e.g. recent grads), typically is ongoing, takes verbal and nonverbal forms, mainly stems from coworkers (i.e. lateral mistreatment), and frequently takes place in front of other coworkers, mainly in hospital settings.Practical implicationsBy applying the lens of mindfulness, healthcare organizations can transform these harmful interactions within the nursing profession. The authors offer administrators and frontline workers practical implications for mitigating workplace abuse, including reshaping the culture, bystander interventions and explicit leadership support.Originality/valueFirst-hand accounts from nurses in the frontlines of healthcare provide a rich voice that reveals the reality of ongoing verbal and nonverbal peer abuse in hospitals and healthcare settings.

Flavonoid-nitroxide hybrids were prepared and displayed limited antioxidant protection, performing antagonistically compared to the individual components in a peroxyl radical scavenging assay.

Although the practice of forgiveness is encouraged, the healing properties of this virtue by health care professionals are often overlooked. Forgiveness is the voluntary, conscious decision to abandon negative feelings toward another who has caused hurt and replacing those feelings with unconditional love and compassion. It is not about forgetting the hurt or ignoring the pain; it is an actual transformation of the heart. The Enright Forgiveness Process Model and the Pyramid Model of Forgiveness are 2 models that facilitate the forgiveness process. By utilizing either of these pathways, the forgiver ultimately experiences peace of mind and a "release from emotional prison" that leads to holistic healing. As a result, the forgiver experiences lower levels of depression, anxiety, and aggression, which improves quality of life. In addition, physiological benefits such as decreased stress levels, lower blood pressure, and a lower heart rate have also been reported. Throughout the course of their careers, nurses encounter patients and families in acute or end-of-life care situations who want to forgive or be forgiven. As holistic health care providers, nurses should be able to facilitate and close this gap in patient care. This article attempts to raise awareness to the importance of forgiveness in health and well-being among nurses and other health care professionals.

Visceral adiposity has been established as a predictor of outcomes in various cancers. We aimed to determine the association of radiographic measurements of visceral fat with clinical outcomes in patients with endometrial cancer.A retrospective review of patients with stage III-IV endometrial cancer who underwent surgery between 2004 and 2014 was performed. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT;VAT+SAT) were assessed on preoperative computed tomography (CT) scans. Exploratory analysis was performed to establish the optimal cut-off values for VAT, SAT, and TAT to identify patients with poor prognostic body composition. Survival rates were analyzed using Kaplan-Meier analysis, log-rank tests, and cox-regression.Eighty-three patients were included. Forty-two (51%) patients had a low VAT/SAT ratio (0.45) and 41 (49.4%) had a high VAT/SAT ratio (0.45). There were no significant differences in demographics between the groups. The mean VAT, SAT, and TAT were 176.3 cmVisceral fat measurements are predictive of outcomes in patients with advanced stage endometrial cancer. Specifically, VAT to SAT ratios are predictive of overall survival. Future studies should be pursued to identify potential therapeutic targets and biological mechanisms that underlie obesity's relationship with endometrial cancer.

Patient characteristics of patient-derived ovarian cancer cells

RAD51 expression and platinum chemotherapy response in vitro and in patient tumors

Patient characteristics of patient-derived ovarian cancer organoids

Patient characteristics of FFPE discovery cohort

Summary of Antibodies

Purpose:To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.Experimental Design:RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.Results:RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; P = 0.003) than RAD51-High status.Conclusions:RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.

Patient characteristics of FFPE validation cohort

Supplementary Table S1. Comprehensive radiologic, surgical, and pathologic scoring system used to evaluate tumor response to neoadjuvant chemotherapy. Supplementary Table S2. Summary of antibodies used. Supplementary Table S3. Disease characteristics of ovarian cancer patients receiving neoadjuvant chemotherapy and undergoing interval cytoreductive surgery stratified by chemoresponse. Supplementary Table S4. Disease characteristics of ovarian cancer patients receiving neoadjuvant chemotherapy and undergoing interval cytoreductive surgery stratified by high and low serum GAS6 expression prior to neoadjuvant chemotherapy. Supplementary Figure S1. RAD51 foci formation in irradiated ovarian cancer cells. Supplementary Figure S2. GAS6 and AXL expression in four ovarian cancer cell lines. Supplementary Figure S3. Mean combination indexes and dose response curves for paclitaxel and AVB-500 in three ovarian cancer cell lines. Supplementary Figure S4. GAS6/AXL inhibitor AVB-500 improves response to carboplatin and decreases tumor burden in PDX mouse model of ovarian cancer. Supplementary Figure S5. GAS6/AXL inhibitor AVB-500 decreases GAS6 and pAKT expression in mouse tumors. Supplementary Figure S6. Cleaved Caspase 3 levels in OVCAR8 ovarian cancer cells at 24 and 48 hours of treatment. Supplementary Figure S7. Treatment with AVB-500 increases DNA damage. Supplementary Figure S8. Treatment with AVB-500 decreases activation of AKT and does not affect protein expression of 53BP1, AXL, or RAD51. Supplementary Figure S9. Treatment with carboplatin plus AVB-500 decreases pATM and increases pCHK1. Supplementary Figure S10. Treatment with AVB-500 decreases RPA binding and does not affect the cell cycle. Supplementary Figure S11. Treatment with AVB-500 in addition to olaparib increases DNA damage and decreases homologous recombination. Supplementary Figure S12. Proposed mechanism of AVB-500 and carboplatin increasing DNA damage through replication fork perturbation.

Supplementary Figure from GAS6-AXL Inhibition by AVB-500 Overcomes Resistance to Paclitaxel in Endometrial Cancer by Decreasing Tumor Cell Glycolysis

Supplementary Table from GAS6-AXL Inhibition by AVB-500 Overcomes Resistance to Paclitaxel in Endometrial Cancer by Decreasing Tumor Cell Glycolysis

Over 80% of women with high-grade serous ovarian cancer (HGSOC) develop tumor resistance to chemotherapy and die of their disease. There are currently no FDA-approved agents to improve sensitivity to first-line platinum- and taxane-based chemotherapy or to PARP inhibitors. Here, we tested the hypothesis that expression of growth arrest–specific 6 (GAS6), the ligand of receptor tyrosine kinase AXL, is associated with chemotherapy response and that sequestration of GAS6 with AVB-S6–500 (AVB-500) could improve tumor response to chemotherapy and PARP inhibitors. We found that GAS6 levels in patient tumor and serum samples collected before chemotherapy correlated with ovarian cancer chemoresponse and patient survival. Compared with chemotherapy alone, AVB-500 plus carboplatin and/or paclitaxel led to decreased ovarian cancer-cell survival in vitro and tumor burden in vivo. Cells treated with AVB-500 plus carboplatin had more DNA damage, slower DNA replication fork progression, and fewer RAD51 foci than cells treated with carboplatin alone, indicating AVB-500 impaired homologous recombination (HR). Finally, treatment with the PARP inhibitor olaparib plus AVB-500 led to decreased ovarian cancer-cell survival in vitro and less tumor burden in vivo. Importantly, this effect was seen in HR-proficient and HR-deficient ovarian cancer cells. Collectively, our findings suggest that GAS6 levels could be used to predict response to carboplatin and AVB-500 could be used to treat platinum-resistant, HR-proficient HGSOC.Implications:GAS6/AXL is a novel target to sensitize ovarian cancers to carboplatin and olaparib. Additionally, GAS6 levels can be associated with response to carboplatin treatment.

Purpose of study: The need for forgiveness education for nursing self-care and forgiveness facilitation has risen. Therefore, the present pilot study tested the efficacy of an 8-week forgiveness bibliotherapy with a small number of undergraduate nursing students. Design of study: Matched pairs of nursing students were randomly assigned to either the experimental group or no-contact control group. The experimental group, using 8 keys to forgiveness by R. Enright (2015) as the treatment manual, read one chapter a week for 8 weeks and provided weekly reflections. Forgiveness and forgiveness-related outcome measures were administered at pretest, posttest, and one-month follow-up. Findings: At the posttest, the experimental group had significantly greater improvement in forgiveness compared to the control group with a large effect size, which was maintained at one month follow-up. There was no other significant difference between the two groups. Within-group comparisons of the experimental group showed improvement in forgiveness, anxiety, depression, and fatigue from pre to post testing periods and forgiveness, anger, anxiety, depression, and fatigue from pre to follow-up testing periods. Conclusion: Use of bibliotherapy may be a cost-effective way to promote the virtue of forgiveness for students in nursing programs.

Background Falls are the most commonly reported incident in the Health Service Executive (HSE). Inappropriate medications and polypharmacy in the elderly can contribute to increased falls risk. Our aim was to assess whether a medication review was being completed at the time of the post-fall clinician review. Methods We completed a retrospective chart review using an audit tool of consecutive inpatient falls, resulting in serious injury, from March–December 2019. Standards measured against were: HSE Guideline—Service User Falls: A Practical Guide for Review, Medicines and Falls in Hospital: British Society Guidelines, STOPP & START criteria and NICE Guidelines: Falls in Older People 2013. Results We identified 33 charts for review (n = 33)—54.55% (18) female and 45.45% (15) male. Average age was 81 ± 11.2 years. The immediate post-fall review was mainly completed by interns (48.49% (16)) and SHO’s (39.39% (13)). A medication review was carried out 9.09% (3) of the time. A total of n = 28 (84.85%) had poly pharmacy. When analysed for medications known to increase risk of falling, 51.52% (n = 17) were on anti-hypertensives, 45.45% (n = 15) on laxatives, 24.24% (n = 8) on sedative medications, 18.18% (n = 6) on hypnotics/anxiolytics, 15.15% (n = 5) on opioids and 15.15% (n = 5) on diuretics at the time of fall. The majority of these medications (77.42% (n = 24)) were commenced prior to admission. None of these medications were discontinued or the dose changed on review post fall. Conclusion Our audit demonstrates that in a cohort of patients who had an inpatient fall medication discontinuation and dose reductions were not performed. Yet, a high burden of polypharmacy and high-risk falls medication were found. This may result in missing a pertinent opportunity to prevent future falls. We advise a structured medication review is carried out for each patient who suffers an in-patient fall to efficiently modify such an easily identifiable risk factor.

Background– Since publication of the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain, there have been growing concerns that providers, including those in primary care, are tapering opioids too quickly and without concomitant use of non-opioid strategies for pain, leading to inadequate pain management. As a result, in November 2022 the CDC published Clinical Practice Guidelines for Prescribing Opioids for Pain, emphasizing the importance of creating comprehensive care plans for pain management and developing a consensual plan between provider and patient when tapering opioids. Objective–Determine the impact of a pharmacist-assisted approach aimed at helping primary care providers minimize opioid use while improving management of chronic, non-malignant pain (CNMP). Methods – This quality improvement project focused on one primary care provider partnering with a pharmacist to reassess the management of patients on long-term opioid therapy (LTOT) for CNMP. The intervention included a letter informing patients of the provider’s intent, pharmacist outreach to intervention patients, and pharmacist development of a patient registry, updated regularly with clinical data, recommendations, and outcomes for the provider to reference throughout the project. The intervention group was compared to patients prescribed opioids for CNMP by the remaining providers at the clinic who did not engage in the quality initiative. Results – The intervention group had a mean effective daily morphine milligram equivalent (MME) reduction of 73.7% (17.2% control) after 18 months and 60% of patients discontinued opioids (14.3% control). In a subset of patients with functional assessment scores, 93.3% were either improved or unchanged, despite a 62.5% decrease in their mean effective daily MME. In both groups, one patient transferred care to a new provider. Conclusions – With targeted recommendations and assistance from a pharmacist, a primary care provider can make significant progress in improving management of CNMP while reducing opioid prescribing.

The use of Poly ADP ribose polymerase inhibitors (PARPi) has revolutionized the treatment of homologous recombination (HR) deficient ovarian cancer tumors. A subset of these tumors exhibit genetic and acquired resistance to PARPi treatment. We have previously shown histone deacetylase inhibitors (HDACi) resensitizes ovarian cancer cells to PARPi. The objective of this study is to examine the effectiveness of combination HDACi and PARPi treatment in two in vitro models of mouse ovarian cancer cells. To investigate these effects, we used the following three ID8 murine ovarian cancer epithelial cell lines: TP53− / − (HR deficient), TP53− / −/BRCA2− / − (HR proficient), and an olaparib resistant line TP53− / −/BRCA2− / −-OR (ID8_OR). We also created ovarian cancer organoids from these three lines. In short, 8-week old female C57BL/6 mice were injected with 7 million untreated cells in PBS. Following the formation of ascites, mice were sacrificed and organoids were derived from both ascites and tumors. For viability assays, cells were pretreated with entinostat (Ent, 0.25uM) for 24h, followed by 72h (2D cells) or 7 days (organoids) of Ent (0-2uM), olaparib (Ola, 0-40uM), or in combination. Cell proliferation and viability was assessed using MTS and ATP-based assays. For immunofluorescence and western blotting analysis, cells were treated with 0.5uM Ent, 10uM Ola or the combination.TP53 adherent cells and organoids treated with 0.5uM Ent + 10uM of Ola significantly reduced cell proliferation when compared to Ola alone (p= 0.0028, 0.0021 Two-Way ANOVA). When compared to Ola and Ent alone, TP53/BRCA2 adherent cells treated with 0.125uM of Ent + 2.5uM of Ola also reduced cell proliferation (p=0.0011 and p=0.0072, 0.0845). Lastly, ID8_OR adherent cells and organoids treated with 0.125uM of Ent + 2.5μM of Ola significantly reduced cell proliferation when compared to Ola alone (p=0.0018, 0.0264).Immunofluorescences analysis revealed, when treated with Ola and Ent combination, adherent TP53 (p= 0.002, n.s), TP53/BRCA2 (p=0.0033, 0.0315), and ID8_OR (n.s) cells displayed increased expression of DNA damage marker gH2AX when compared to Control and Ola alone. We also observed decreased expression of RAD51 in cells treated with combination when compared to control and Ola alone, TP53 (p= Citation Format: Bisiayo E. Fashemi, Lilian N. van Biljon1, Tyler Woodard, Vijayalaxmi Gupta, Mary M. Mullen, Benjamin Bitler, Dineo Khabele. Entinostat restores sensitivity to olaparib in two in vitro models of PARPi resistant ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB164.

Granular cell tumors (GCTs) can be diagnostically challenging due to their rarity, diverse anatomic locations, and clinical and radiologic similarities to other more common entities. GCTs involving the breast are rare and are most commonly encountered in premenopausal cisgender women. We report an unusual case of a breast GCT in a young transgender man.A 20-year-old transgender man who was on testosterone therapy for about 1 year presented with a painless, palpable mass in the right breast which radiologically resembled a lymph node. A fine needle aspiration showed morphology and immunohistochemistry consistent with a GCT. The tumor was excised by a mastectomy for therapeutic and gender-affirming purposes which confirmed the diagnosis of a breast GCT.Breast GCTs are most commonly found in cisgender women, however the mechanisms behind this relationship and whether transgender persons have an altered risk profile are not well understood. Breast GCTs are typically benign lesions with a low chance of recurrence following excision.GCTs are rare and poorly understood entities which have not been previously documented in transgender patients and can resemble other benign or malignant lesions.

The objective of this study was to investigate the use of potassium chloride (KCl) and tapioca starch (TS) to reduce salt levels below 1.5% in sausages manufactured using previously high pressure (HP) processed pork (150 MPa). A 3 × 2 × 1 factorial design was used to formulate breakfast sausages with three salt levels (0.5%, 1.0%, and 1.5%), two ingredient levels (no added ingredient or added as a combination of KCl\TS), and one pressure level (150 MPa). Partial replacement of NaCl with KCl and addition of TS had beneficial effects on the water binding abilities of sausage batters by decreasing (p < 0.05) total expressible fluid (%) and increasing water holding capacity (%). Overall, results indicated that the use of KCl\TS imparted some beneficial effects to salt-reduced low fat breakfast sausages and has the potential to reduce salt levels in the breakfast sausages to 1.0% while still maintaining the organoleptic and functional properties traditionally associated with these meat products.

Introduction: Food insecurity (FI), defined as “limited or uncertain availability of nutritionally adequate and safe foods, or limited or uncertain ability to acquire acceptable foods in socially acceptable ways,” affects over 12% of US households. Embarrassment persists for patients with FI, and due to the potential consequences of FI, including increased utilization of the health care system, it is important to find causes and potential interventions for FI. The purpose of this project was to better understand FI from the patient perspective, including contributing factors, perceived health effects, and helpful interventions. Methods: Interviews (N=21) were conducted with suburban community residency clinic patients who screened positive for FI in the last 12 months. Six open-ended questions and a ranking question examined contributors to FI, effects of FI, perceptions of clinic intervention helpfulness, and ideas for novel interventions. Results: Patients identified lack of income (85.7%) as the primary issue they faced. Secondary identified issues were lack of transportation (38.1%), too much debt (33.3%), and food assistance programs not providing for all needs (33.3%). FI effects on patients’ health included difficulty adhering to specialized diets and the need to modify eating patterns due to lack of food. Surprisingly, 28.6% perceived no FI related-health effects. Patients felt that the most valuable clinic intervention was provision of urgent need food boxes, followed by FI screening and referrals to community food resources. Conclusions: Frequent FI screening is in itself useful to patients. Screening paired with community food resource referrals and urgent-need food boxes are the most helpful interventions according to patients.

Simple Summary Uterine serous cancer (USC) is an aggressive form of endometrial cancer. USC constitutes less than 10% of endometrial cancer cases but is responsible for up to 40% of endometrial cancer deaths. Response to standard platinum and taxane therapy is modest, particularly in the recurrent setting. Thus, novel therapeutic strategies are needed to overcome this drug resistance. We hope that our findings provide strong preclinical support for the combination of an AXL inhibitor with bevacizumab in USC clinical trials in the recurrent setting. Abstract Endometrial cancer remains the most prevalent gynecologic cancer with continued rising incidence. A less common form of this cancer is uterine serous cancer, which represents 10% of endometrial cancer cases. However, this is the most aggressive cancer. The objective was to assess whether inhibiting the receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve response in uterine serous cancer. To prove this, we conducted multiple angiogenesis assays including tube formation assays and angiogenesis invasion assays. In addition, we utilized mouse models with multiple cells lines and subsequently analyzed harvested tissue through immunohistochemistry CD31 staining to assess microvessel density. The combination treatment arms demonstrated decreased angiogenic potential in each assay. In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis.

Background: While sex-based differences in outcomes after hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) are often recorded, no studies have been dedicated to analyzing the literature as a whole. Purpose: To investigate whether sex is a predictor of outcomes in studies evaluating hip arthroscopic surgery for FAIS. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched the PubMed, Embase, Cochrane, Ovid, and PubMed Central databases for English-language studies that evaluated sex-specific outcomes in human populations. The search terms used were as follows: (“Hip Arthroscopy”) AND (“Femoroacetabular Impingement” OR “FAI”) AND (“Sex” OR “Gender” OR “Male” OR “Female”). Studies with evidence levels 2 through 4 were included. The studies were then screened, followed by data extraction. Modified Harris Hip Score (mHHS) outcomes and return-to-sport (RTS) rates were recorded. These were analyzed using random-effects meta-analysis. Heterogeneity was calculated using the I 2 statistic. Results: Of 256 full-text articles screened, 48 articles were included in this analysis; of these, 14 studies (29%) concluded that female sex was a negative predictor of postoperative outcomes, while 6 studies (13%) found female sex to be positive predictor. The remaining 28 studies (58%) found no sex-based differences in postoperative outcomes. Of 7 studies (416 male and 519 female) included in the mHHS analysis, 2 studies concluded that male patients had significantly higher postoperative mHHS scores. Of 6 studies (502 male and 396 female) included in the RTS analysis, 1 study concluded that male patients had a significantly higher RTS rate. Conclusion: Almost one-third of the included studies determined that female sex was a negative predictor of postoperative outcomes, 13% found female sex to be a positive predictor, and 58% found no sex-based differences. Our study illustrates an insufficiency of high-level evidence supporting sex-specific differences in outcomes after hip arthroscopic surgery, but findings indicated that the postoperative mHHS score and RTS rate may be influenced by sex.

Objective/Background: Chemotherapy is often ineffective in advanced stage and aggressive histologic subtypes of endometrial cancer. Overexpression of the receptor tyrosine kinase AXL has been found to be associated with therapeutic resistance, metastasis, and poor prognosis in endometrial cancer. Our objective was to identify whether inhibition of AXL through a novel, selective targeted agent, AVB-500, would improve sensitivity to paclitaxel. Additionally, we sought to determine whether the mechanism for this improved sensitivity was through metabolic regulation. Methods: Immunohistochemistry (IHC) was performed on a tissue microarray containing specimens from patients with primary and metastatic uterine serous carcinoma. Blind scoring was performed by two reviewers. Kaplan-Meier methods were used to generate time-to-event curves. Cell viability was performed with high-grade endometrial, chemo-resistant cell lines, ARK1 and PUC198. Cells were treated with paclitaxel and with AVB-500+paclitaxel. Intraperitoneal (IP) ARK1 or PUC198 tumors were treated with vehicle, AVB-500, paclitaxel, or AVB-500+paclitaxel. A Seahorse Analyzer was used for glycolytic rate assays. Isotope tracing was used for in vivo metabolite abundance quantification. Results: We found that both GAS6 and AXL expression were higher by IHC in tumors with a poor response to chemotherapy compared to tumors with a good response to chemotherapy (GAS6: 40.9% vs. 30.4%, P=0.012; AXL: 60.7% vs. 42.7%, P=0.013). Median PFS and OS were longer in patients with low GAS6 expressing tumors compared to high GAS6 expressing tumors (PFS: 33.6 mo vs. 10.6 mo, P=0.003; OS: 39.5 mo vs. 27.7 mo, P=0.003). We showed that chemotherapy resistant endometrial cancer cell lines, ARK1 and PUC198 had improved sensitivity and synergy with paclitaxel when treated in combination with AVB-500. ARK1 and PUC198 in vivo IP models had significantly fewer tumors (ARK1: P=0.007; PUC198: P=0.029) and decreased tumor weight (ARK1: P Conclusions: Our study provides strong pre-clinical rationale for combining AVB-500 with paclitaxel in aggressive endometrial cancer models. Additionally, continued identification of viable biomarkers is critical to the success of targeted therapies such as AVB-500. Given AXL’s role in glucose homeostasis, one or more glycolytic intermediates may prove to be a useful biomarker to help predict sensitivity in patients, thus tailoring who would benefit from this treatment combination. Citation Format: Shaina F. Bruce, Kevin Cho, Hollie Noia, Elena Lomonosova, Elizabeth Stock, Alyssa Oplt, Barbara Blachut, Mary M. Mullen, Lindsay M. Kuroki, Andrea R. Hagemann, Carolyn K. McCourt, Premal H. Thaker, Dineo Khabele, Matthew A. Powell, David G. Mutch, Leah P. Shriver, Gary J. Patti, Katherine C. Fuh. GAS6-AXL inhibition by AVB-500 overcomes resistance to paclitaxel in endometrial cancer by decreasing tumor cell glycolysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB081.