Surgical Management and Long-Term Evaluation of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNETs) arise from neuroendocrine cells and are a rare class of heterogenous tumors with increasing incidence. The diagnosis, staging, treatment, and prognosis of PNETs depend heavily on identifying the histologic features and biological mechanisms. Here, the authors provide an overview of the diagnostic workup (biomarkers and imaging), grade, and staging of PNETs. The authors also explore associated genetic mutations and molecular pathways and describe updated guidelines on surgical and systemic treatment modalities.

Diet-Induced Severe Hyperhomocysteinemia Promotes Atherosclerosis Progression and Dysregulates the Plasma Metabolome in Apolipoprotein-E-Deficient Mice.

Atherosclerosis and resulting cardiovascular disease are the leading causes of death in the US. Hyperhomocysteinemia (HHcy), or the accumulation of the intermediate amino acid homocysteine, is an independent risk factor for atherosclerosis, but the intricate biological processes mediating this effect remain elusive. Several factors regulate homocysteine levels, including the activity of several enzymes and adequate levels of their coenzymes, including pyridoxal phosphate (vitamin B6), folate (vitamin B9), and methylcobalamin (vitamin B12). To better understand the biological influence of HHcy on the development and progression of atherosclerosis, apolipoprotein-E-deficient (apoE-/- mice), a model for human atherosclerosis, were fed a hyperhomocysteinemic diet (low in methyl donors and B vitamins) (HHD) or a control diet (CD). After eight weeks, the plasma, aorta, and liver were collected to quantify methylation metabolites, while plasma was also used for a broad targeted metabolomic analysis. Aortic plaque burden in the brachiocephalic artery (BCA) was quantified via 14T magnetic resonance imaging (MRI). A severe accumulation of plasma and hepatic homocysteine and an increased BCA plaque burden were observed, thus confirming the atherogenic effect of the HHD. Moreover, a decreased methylation capacity in the plasma and aorta, indirectly assessed by the ratio of S-adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) was detected in HHD mice together with a 172-fold increase in aortic cystathionine levels, indicating increased flux through the transsulfuration pathway. Betaine and its metabolic precursor, choline, were significantly decreased in the livers of HHD mice versus CD mice. Widespread changes in the plasma metabolome of HHD mice versus CD animals were detected, including alterations in acylcarnitines, amino acids, bile acids, ceramides, sphingomyelins, triacylglycerol levels, and several indicators of dysfunctional lipid metabolism. This study confirms the relevance of severe HHcy in the progression of vascular plaque and suggests novel metabolic pathways implicated in the pathophysiology of atherosclerosis.

The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K).

The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders as they are key components in regulating cell signalling pathways. In an effort to make probe molecules available for further exploring these targets, we have previously reported PI5P4Kα-selective and PI5P4Kγ-selective ligands. Herein we report the rational design of PI5P4Kα/γ dual inhibitors, using knowledge gained during the development of selective inhibitors for these proteins. ARUK2007145 (39) is disclosed as a potent, cell-active probe molecule with ADMET properties amenable to conducting experiments in cells.

Models in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions.

Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors derived from multiple neuroendocrine origin cell subtypes. Incidence rates for pNENs have steadily risen over the last decade, and outcomes continue to vary widely due to inability to properly screen. These tumors encompass a wide range of functional and non-functional subtypes, with their rarity and slow growth making therapeutic development difficult as most clinically used therapeutics are derived from retrospective analyses. Improved molecular understanding of these cancers has increased our knowledge of the tumor biology for pNENs. Despite these advances in our understanding of pNENs, there remains a dearth of models for further investigation. In this review, we will cover the current field of pNEN models, which include established cell lines, animal models such as mice and zebrafish, and three-dimensional (3D) cell models, and compare their uses in modeling various disease aspects. While no study model is a complete representation of pNEN biology, each has advantages which allow for new scientific understanding of these rare tumors. Future efforts and advancements in technology will continue to create new options in modeling these cancers.

Gas Phase Emissions of Volatile Organic Compounds Arising from the Application of Sunscreens.

The speciation of volatile organic compounds (VOCs) emitted from personal care products (PCPs) is complex and contributes to poor air quality and health risks to users via the inhalation exposure pathway. Detailed VOC emission profiles were generated for 26 sunscreen products; consequently, variability was observed between products, even though they were all designed for the same purpose. Some were found to contain fragrance compounds not labelled on their ingredients list. Five contaminant VOCs were identified (benzene, toluene, ethylbenzene, o-xylene, and p-xylene); headspace sampling of an additional 18 randomly selected products indicated that ethanol originating from fossil petroleum was a potential source. The gas phase emission rates of the VOCs were quantified for 15 of the most commonly emitted species using SIFT-MS. A wide range of emission rates were observed between the products. Usage estimates were made based on the recommended dose per body surface area, for which the total mass of VOCs emitted from one full-body application dose was in the range of 1.49 × 103-4.52 × 103 mg and 1.35 × 102-4.11 × 102 mg for facial application (men aged 16+; children aged 2-4). Depending on age and sex, an estimated 9.8-30 mg of ethanol is inhaled from one facial application of sunscreen.

Identification of ARUK2002821 as an isoform-selective PI5P4Kα inhibitor.

The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) play a central role in regulating cell signalling pathways and, as such, have become therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders. Many of the PI5P4Kα inhibitors that have been reported to date have suffered from poor selectivity and/or potency and the availability of better tool molecules would facilitate biological exploration. Herein we report a novel PI5P4Kα inhibitor chemotype that was identified through virtual screening. The series was optimised to deliver ARUK2002821 (36), a potent PI5P4Kα inhibitor (pIC50 = 8.0) which is selective vs. other PI5P4K isoforms and has broad selectivity against lipid and protein kinases. ADMET and target engagement data are provided for this tool molecule and others in the series, as well as an X-ray structure of 36 solved in complex with its PI5P4Kα target.

The Identification of Potent, Selective, and Brain Penetrant PI5P4Kγ Inhibitors as In Vivo-Ready Tool Molecules.

Owing to their central role in regulating cell signaling pathways, the phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive therapeutic targets in diseases such as cancer, neurodegeneration, and immunological disorders. Until now, tool molecules for these kinases have been either limited in potency or isoform selectivity, which has hampered further investigation of biology and drug development. Herein we describe the virtual screening workflow which identified a series of thienylpyrimidines as PI5P4Kγ-selective inhibitors, as well as the medicinal chemistry optimization of this chemotype, to provide potent and selective tool molecules for further use. In vivo pharmacokinetics data are presented for exemplar tool molecules, along with an X-ray structure for ARUK2001607 (15) in complex with PI5P4Kγ, along with its selectivity data against >150 kinases and a Cerep safety panel.

Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunological disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochemical properties of the selective PI5P4Kγ inhibitor, NIH-12848 (1). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kß. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chemical series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.

Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.

PURPOSE: Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes. METHODS: Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening. RESULTS: Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs. CONCLUSION: This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.

Randomized Phase II Trial of Triapine-Cisplatin-Radiotherapy for Locally Advanced Stage Uterine Cervix or Vaginal Cancers.

Uterine cervix or vaginal cancers have inherent overactivity of ribonucleotide reductase (RNR), making these cancers rational targets for therapy based on interruption of cisplatin-radiotherapy-induced DNA damage repair. We conducted a pilot, open-label randomized phase II trial to evaluate the efficacy and safety of cisplatin-radiotherapy with or without triapine, a small molecule with RNR-inhibitory activity, in patients with advanced-stage uterine cervix or vaginal cancers (NCT01835171), as a lead in to a randomized phase III study (NCT02466971). A total of 26 women were randomly assigned to receive 6 weeks of daily radiotherapy followed by brachytherapy (80 Gy) and once-weekly cisplatin (40 mg m-2)-with or without three-times weekly intravenous triapine (25 mg m-2)-in one 56-days cycle. Primary end points were metabolic complete response by positron emission tomography and safety. Additional end points included the rate of clinical response, rate of methemoglobinemia, and progression-free survival. The addition of triapine to cisplatin-radiotherapy improved the rate of metabolic complete response from 69 to 92% (P = 0.32) and raised the 3-year progression-free survival estimate from 77 to 92% (hazard ratio for progression, 0.30; P = 0.27). The most frequent grade 3 or 4 adverse events in either treatment group included reversible leukopenia, neutropenia, fatigue, or electrolyte abnormalities. No significant differences were seen between the two groups in the rate of adverse events. Symptomatic methemoglobinemia was not encountered after triapine infusion. In conclusion, the addition of triapine to cisplatin-radiotherapy improved the rate of metabolic complete response in patients with advanced-stage uterine cervix or vaginal cancers without significant toxicity. A phase III trial adequately powered to evaluate progression-free and overall survival is underway (NCT02466971).

BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004).

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a significant risk of recurrence despite adjuvant intravesical therapy. OBJECTIVE: To determine whether celecoxib, a cyclo-oxygenase 2 inhibitor, reduces the risk of recurrence in NMIBC patients receiving standard treatment. DESIGN, SETTING, AND PARTICIPANTS: BOXIT (CRUK/07/004, ISRCTN84681538) is a double-blinded, phase III, randomised controlled trial. Patients aged ≥18 yr with intermediate- or high-risk NMIBC were accrued across 51 UK centres between 1 November 2007 and 23 July 2012. INTERVENTION: Patients were randomised (1:1) to celecoxib 200mg twice daily or placebo for 2 yr. Patients with intermediate-risk NMIBC were recommended to receive six weekly mitomycin C instillations; high-risk NMIBC cases received six weekly bacillus Calmette-Guérin and maintenance therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to disease recurrence. Analysis was by intention to treat. RESULTS AND LIMITATIONS: A total of 472 patients were randomised (236:236). With median follow-up of 44 mo (interquartile range: 36-57), 3-yr recurrence-free rate (95% confidence interval) was as follows: celecoxib 68% (61-74%) versus placebo 64% (57-70%; hazard ratio [HR] 0.82 [0.60-1.12], p=0.2). There was no difference in high-risk (HR 0.77 [0.52-1.15], p=0.2) or intermediate-risk (HR 0.90 [0.55-1.48], p=0.7) NMIBC. Subgroup analysis suggested that time to recurrence was longer in pT1 NMIBC patients treated with celecoxib compared with those receiving placebo (HR 0.53 [0.30-0.94], interaction test p=0.04). The 3-yr progression rates in high-risk patients were low: 10% (6.5-17%) and 9.7% (6.0-15%) in celecoxib and placebo arms, respectively. Incidence of serious cardiovascular events was higher in celecoxib (5.2%) than in placebo (1.7%) group (difference +3.4% [-0.3% to 7.2%], p=0.07). CONCLUSIONS: BOXIT did not show that celecoxib reduces the risk of recurrence in intermediate- or high-risk NMIBC, although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib. PATIENT SUMMARY: Celecoxib was not shown to reduce the risk of recurrence in intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC), although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib.

Chondrogenic differentiation of synovial fluid mesenchymal stem cells on human meniscus-derived decellularized matrix requires exogenous growth factors.

The objective of this study was to investigate whether meniscus-derived decellularized matrix (DCM) has the capacity to induce differentiation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) towards a meniscus fibrochondrocyte (MFC) phenotype. The potential roles of transforming growth factor beta-3 (TGF-ß3) and insulin-like growth factor 1 (IGF-1) in the differentiation of SF-MSCs towards an MFC phenotype were also investigated. SF-MSCs were isolated via plastic adherence cell culture from the synovial fluid of five donors (5 male, average age 34 years). Porous DCM was generated by homogenizing and freeze-drying fresh normal human cadaveric meniscus tissue. SF-MSCs were seeded and cultured on the DCM scaffold in a defined serum-free media (SFM) supplemented with or without the combination of TGF-ß3 and IGF-1. Cell pellets of SF-MSCs were cultured in SFM with either TGF-ß3 or IGF-1 or their combination as controls. The duration of culture was 3 weeks for both experimental configurations. We assessed newly-formed tissues by biochemical assays, scanning electron microscopy (SEM), immunofluorescence and quantitative real-time PCR (qPCR). The combination of TGF-ß3 and IGF-1 induced production of the cartilaginous matrix in DCM and upregulated the expression of aggrecan, collagens I and II. Moreover, the SF-MSCs exhibited a round morphology in the DCM scaffolds in the presence of the growth factors. In pellets, combined TGF-ß3 and IGF-1 synergistically enhanced cartilaginous matrix production. In contrast to bone marrow mesenchymal stem cells (BM-MSCs), the differentiated SF-MSCs showed little evidence of the expression of the hypertrophic differentiation marker, collagen X. In conclusion, meniscus-derived DCM appears to require exogenous growth factor supplementation to direct differentiation of SF-MSCs. STATEMENT OF SIGNIFICANCE: Meniscus tears are the most common injury of the knee joint. These tears pose a major risk factor for the early development of knee osteoarthritis. Unfortunately, the majority of these tears occur in the inner region of the meniscus and lacks blood supply with no reparative or regenerative capacity. The goal of this study was to determine if the native extracellular matrix (ECM) of human meniscus has the capacity to differentiate human knee synovial fluid resident mesenchymal stem cells (SF-MSCs) towards a meniscus phenotype as a potential strategy to repair avascular meniscal tears. Our findings show that the human meniscus-derived ECM without supplementation with growth factors (TGF-ß3 and IGF-1) cannot differentiate SF-MSCs towards a meniscus phenotype. The use of meniscus-derived scaffolds as a material to stimulate endogenous repair of meniscus tears via differentiation of SF-MSCs may require supplementation with TGF-ß3 and IGF-1.

The acromiohumeral centre edge angle: A new radiographic measurement and its association with rotator cuff pathology.

BACKGROUND: Various radiographic measurements that describe humeral head coverage by the acromion and the effect on rotator cuff pathology have been reported. This study aimed to describe and validate a new radiographic measurement, the acromiohumeral centre edge angle (ACEA). METHODS: We compared the ACEA on computed tomography (CT) and plain X-ray to determine whether X-ray is accurate for measuring this angle. We then compared the results from this control population with 107 patients with acute rotator cuff tears. We compared functional outcomes in rotator cuff tear patients to determine whether the ACEA has any effect on outcome after surgery. An intra- and inter-observer variability analysis was performed and we compared the ACEA to the acromial index (AI) on rotation X-rays. RESULTS: The ACEA was comparable on CT and plain X-ray and was most accurate when true anteroposterior glenohumeral X-rays were used (15.94° vs. 15.87° on CT, p = 0.476). The ACEA showed high intra- and inter-observer reproducibility and was unchanged on internal and external rotation X-rays (20.48 vs. 20.47, p = 0.842), whereas the AI was significantly different (0.74 vs. 0.70, p < 0.001). The ACEA was significantly higher in our rotator cuff tear patients than the control population (23.9° vs. 16.6°, p < 0.001), although a higher ACEA was not associated with poorer outcomes. CONCLUSION: The ACEA is a valid measurement for describing humeral head coverage by the acromion and can be accurately measured on plain radiographs with good reproducibility. It is unaffected by shoulder rotation and was significantly higher in patients with acute rotator cuff tears.

Strategies to Mitigate Variability in Engineering Human Nasal Cartilage.

Skin cancer and its associated treitments can have devastating consequences for survivors; this is particularly true when cancer occurs on the nose. Recent work has applied cell-based tissue engineering (TE) strategies to develop nasal cartilage constructs for reconstruction of the nose. In this study, we have generated human nasal cartilage on a clinically approved collagen scaffold to investigate the donor-to-donor variability of TE cartilage and evaluated strategies to mitigate it. We also evaluated the gene expression of the family of fibroblast growth factor receptors (FGFR1-4) and their association with tissue quality. FGFR 1 was significantly positively correlated with GAG/DNA; a measure of chondrogenic capacity. We implemented two strategies: hypoxic culture and co-culture with mesenchymal stromal cells (MSCs) to increase tissue quality. Total glycosaminoglycan (GAG) content varied significantly between donors initially, with >10-fold difference between the best and worst donor tissue. Our co-culture strategy was able to increase TE construct quality from poor quality donor tissue while supressing hypertrophy relative to MSCs alone. However, no differences were observed with the use of hypoxic culture. Tissues generated using co-culture with MSCs became vascularized and calcified in vivo, demonstrating a non-stable cartilage phenotype in co-culture and MSCs cartilage constructs.

Crystal structure of the GLP-1 receptor bound to a peptide agonist.

Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes.

Structurally Enabled Discovery of Adenosine A2A Receptor Antagonists.

Over the past decade there has been a revolution in the field of G protein-coupled receptor (GPCR) structural biology. Many years of innovative research from different areas have come together to fuel this significant change in the fortunes of this field, which for many years was characterized by the paucity of high-resolution structures. The determination to succeed has been in part due to the recognized importance of these proteins as drug targets, and although the pharmaceutical industry has been focusing on these receptors, it can be justifiably argued and demonstrated that many of the approved and commercially successful GPCR drugs can be significantly improved to increase efficacy and/or reduce undesired side effects. In addition, many validated targets in this class remain to be drugged. It is widely recognized that application of structure-based drug design approaches can help medicinal chemists a long way toward discovering better drugs. The achievement of structural biologists in providing high-resolution insight is beginning to transform drug discovery efforts, and there are a number of GPCR drugs that have been discovered by use of structural information that are in clinical development. This review aims to highlight the key developments that have brought success to GPCR structure resolution efforts and exemplify the practical application of structural information for the discovery of adenosine A2A receptor antagonists that have potential to treat multiple conditions.

Development and implementation results of an interactive computerized surgical checklist for robotic-assisted gynecologic surgery.

To address surgical complications, the World Health Organization (WHO) developed the Safe Surgery Saves Lives Checklist. With the foundation of the WHO's checklist, a robotic-specific checklist (RORCC) was developed using standardized content and face validity methods. The RORCC was implemented in a high volume gynecological (GYN) specialty group using minimally invasive robotic-assisted surgery. Data were abstracted from patients undergoing GYN procedures from four GYN surgeons at an urban, community hospital during November 16, 2010 to May 15, 2011 (pre-RORCC) n = 89 and from the period May 16, 2011 to November 16 2011 (post-RORCC) n = 121. Thirty-day readmissions pre-checklist and post-checklist were 12 and 5, respectively, which is a significant (p = 0.02) reduction. The duration of surgery was not significantly affected (p = 0.40) with pre-RORCC surgery time at 110.1 (35.7) min versus post-RORCC surgery time at 112.9 (37.4) min. This study demonstrated the feasibility of integrating an electronic, interactive, and robotic-specific checklist for gynecologic robotic-assisted surgery which resulted in a significant reduction in readmissions at the 30-day without significantly impacting operating room times.

Feasibility of a lifestyle intervention for overweight/obese endometrial and breast cancer survivors using an interactive mobile application.

OBJECTIVE: The study aimed to assess a one-month lifestyle intervention delivered via a web- and mobile-based weight-loss application (app) (LoseIt!) using a healthcare-provider interface. METHODS: Early-stage overweight/obese (body mass index [BMI]≥25kg/m(2)) cancer survivors (CS) diagnosed in the past three years, and without recurrent disease were enrolled and received exercise and nutrition counseling using the LoseIt! app. Entry and exit quality of life (FACT-G) and Weight Efficacy Lifestyle Questionnaire (WEL) measuring self-efficacy were measured along with anthropometrics, daily food intake, and physical activity (PA) using the app. RESULTS: Mean participant age was 58.4±10.3years (n=50). Significant reductions (p<0.0006) in anthropometrics were noted between pre- and post-intervention weight (105.0±21.8kg versus 98.6±22.5kg); BMI (34.9±8.7kg/m(2) versus 33.9±8.4kg/m(2)); and waist circumference (108.1±14.9cm versus 103.7±15.1cm). A significant improvement in pre- and post-intervention total WEL score was noted (99.38±41.8 versus 120.19±47.1, p=0.043). No significant differences were noted in FACT-G, macronutrient consumption, and PA patterns. CONCLUSION: These results indicate that a lifestyle intervention delivered via a web- and mobile-based weight-loss app is a feasible option by which to elicit short-term reductions in weight. Though these results parallel the recent survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED) trial, it is notable that they were achieved without encumbering significant cost and barrier-access issues (i.e. time, transportation, weather, parking, etc.).

Safety culture in the gynecology robotics operating room.

STUDY OBJECTIVE: To measure the safety culture in the robotics surgery operating room before and after implementation of the Robotic Operating Room Computerized Checklist (RORCC). DESIGN: Prospective study. SUBJECTS: Gynecology surgical staff (n = 32). SETTING: An urban community hospital. INTERVENTIONS: The Safety Attitudes Questionnaire domains examined were teamwork, safety, job satisfaction, stress recognition, perceptions of management, and working conditions. Questions and domains were described using percent agreement and the Cronbach alpha. Paired t-tests were used to describe differences before and after implementation of the checklist. MEASUREMENTS AND MAIN RESULTS: Mean (SD) staff age was 46.7 (9.5) years, and most were women (78%) and worked full-time (97%). Twenty respondents (83% of nurses, 80% of surgeons, 66% of surgical technicians, and 33% of certified registered nurse anesthetists) completed the Safety Attitudes Questionnaire; 6 were excluded because of non-matching identifiers. Before RORCC implementation, the highest quality of communication and collaboration was reported by surgeons and surgical technicians (100%). Certified registered nurse anesthetists reported only adequate levels of communication and collaboration with other positions. Most staff reported positive responses for teamwork (48%; α = 0.81), safety (47%; α = 0.75), working conditions (37%; α = 0.55), stress recognition (26%; α = 0.71), and perceptions of management (32%; α = 0.52). No differences were observed after RORCC implementation. CONCLUSION: Quality of communication and collaboration in the gynecology robotics operating room is high between most positions; however, safety attitude responses are low overall. No differences after RORCC implementation and low response rates may highlight lack of staff support.