| 1. |
- Heinze, Karolin, et al.
(author)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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In: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Journal article (peer-reviewed)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 2. |
- Bisch, Steven P., et al.
(author)
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Ferric derisomaltose and Outcomes in the Recovery of Gynecologic oncology : ERAS (Enhanced Recovery After Surgery) (FORGE) - a protocol for a pilot randomised double-blinded parallel-group placebo-controlled study of the feasibility and efficacy of intravenous ferric derisomaltose to correct preoperative iron-deficiency anaemia in patients undergoing gynaecological oncology surgery
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Iron-deficiency anaemia is common in gynaecological oncology patients. Blood transfusions are immunosuppressive and carry immediate and long-term risks. Oral iron replacement remains the standard of care but requires prolonged treatment courses associated with gastrointestinal side effects, poor compliance and variable absorption in cancer patients. Intravenous iron has been shown to decrease the need for allogeneic blood transfusion in gynaecological oncology patients undergoing chemotherapy, but the efficacy of this treatment in the preoperative period is unknown. The goal of this pilot study is to determine the effect of intravenous ferric derisomaltose on preoperative haemoglobin in patients undergoing surgery for gynaecological malignancy.METHODS AND ANALYSIS: We will conduct a pilot single-centre, parallel-arm randomised controlled trial of intravenous ferric derisomaltose versus placebo among consenting patients with iron-deficiency anaemia having elective major surgery on the gynaecological oncology service. Patients, clinicians and outcome assessors will be blinded. The intervention consists of a single infusion of 500-1000 mg of intravenous ferric derisomaltose administered a minimum of 21 days prior to the planned operation. The primary outcome is mean preoperative haemoglobin concentration measured 0-3 days prior to surgery in patients receiving intravenous ferric derisomaltose compared with those receiving placebo. Secondary outcomes include the following: change in haemoglobin concentration, postoperative haemoglobin concentration, perioperative blood transfusion rates, patient-reported quality of life scores (Quality of Recovery 15, Modified Short Form 36 v1, EuroQol 5-dimension 5-level and Functional Assessment of Cancer Therapy - Anaemia), surgical site infection, complication rates, length of hospital stay and readmission rate. Analyses will follow intention-to-treat principles for all randomised participants. All patients will be followed up to 60 days following surgery.ETHICS AND DISSEMINATION: Ethical approval has been granted by Health Research Ethics Board of Alberta (Project ID: HREBA.CC-22-0187) and Health Canada (HC6-024-c264013). Results will be disseminated through presentation at scientific conferences, peer-reviewed publication and social and traditional media.TRIAL REGISTRATION NUMBER: NCT05407987.
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| 3. |
- Gommenginger, Christine, et al.
(author)
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SEASTAR: A mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUL
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Journal article (other academic/artistic)abstract
- High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere e.g. freshwater, pollutants. As numerical models continue to evolve towards finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed towards spaceborne implementation within Europe and beyond.
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| 4. |
- Gramlich, Leah M., et al.
(author)
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Implementation of Enhanced Recovery After Surgery : a strategy to transform surgical care across a health system
- 2017
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In: Implementation Science. - : BioMed Central. - 1748-5908. ; 12
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Journal article (peer-reviewed)abstract
- Background: Enhanced Recovery After Surgery (ERAS) programs have been shown to have a positive impact on outcome. The ERAS care system includes an evidence-based guideline, an implementation program, and an interactive audit system to support practice change. The purpose of this study is to describe the use of the Theoretic Domains Framework (TDF) in changing surgical care and application of the Quality Enhancement Research Initiative (QUERI) model to analyze end-to-end implementation of ERAS in colorectal surgery across multiple sites within a single health system. The ultimate intent of this work is to allow for the development of a model for spread, scale, and sustainability of ERAS in Alberta Health Services (AHS).Methods: ERAS for colorectal surgery was implemented at two sites and then spread to four additional sites. The ERAS Interactive Audit System (EIAS) was used to assess compliance with the guidelines, length of stay, readmissions, and complications. Data sources informing knowledge translation included surveys, focus groups, interviews, and other qualitative data sources such as minutes and status updates. The QUERI model and TDF were used to thematically analyze 189 documents with 2188 quotes meeting the inclusion criteria. Data sources were analyzed for barriers or enablers, organized into a framework that included individual to organization impact, and areas of focus for guideline implementation.Results: Compliance with the evidence-based guidelines for ERAS in colorectal surgery at baseline was 40%. Post implementation compliance, consistent with adoption of best practice, improved to 65%. Barriers and enablers were categorized as clinical practice (22%), individual provider (26%), organization (19%), external environment (7%), and patients (25%). In the Alberta context, 26% of barriers and enablers to ERAS implementation occurred at the site and unit levels, with a provider focus 26% of the time, a patient focus 26% of the time, and a system focus 22% of the time.Conclusions: Using the ERAS care system and applying the QUERI model and TDF allow for identification of strategies that can support diffusion and sustainment of innovation of Enhanced Recovery After Surgery across multiple sites within a health care system.
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| 5. |
- Ljungqvist, Olle, 1954-, et al.
(author)
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ERAS-Value based surgery
- 2017
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In: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 116:5, s. 608-612
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Research review (peer-reviewed)abstract
- This paper reviews implementation of ERAS and its financial implications. Literature on clinical outcomes and financial implications were reviewed. Reports from many different surgery types shows that implementation of ERAS reduces complications and shortens hospital stay. These improvements have major impacts on reducing the cost of care even when costs for implementation, and investment in time for personnel and training is accounted for. The conclusion is that ERAS is an excellent example of value based surgery.
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| 6. |
- Ljungqvist, Olle, 1954-, et al.
(author)
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Opportunities and Challenges for the Next Phase of Enhanced Recovery After Surgery : A Review
- 2021
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In: JAMA Surgery. - : American Medical Association. - 2168-6254 .- 2168-6262. ; 56:8, s. 775-784
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Research review (peer-reviewed)abstract
- Importance: Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement initiative now firmly entrenched within the field of perioperative care. Although ERAS is associated with significant clinical outcome improvements and cost savings in numerous surgical specialties, several opportunities and challenges deserve further discussion.Observations: Uptake and implementation of ERAS Society guidelines, together with ERAS-related research, have increased exponentially since the inception of the ERAS movement. Opportunities to further improve patient outcomes include addressing frailty, optimizing nutrition, prehabilitation, correcting preoperative anemia, and improving uptake of ERAS worldwide, including in low- and middle-income countries. Challenges facing enhanced recovery today include implementation, carbohydrate loading, reversal of neuromuscular blockade, and bowel preparation. The COVID-19 pandemic poses both a challenge and an opportunity for ERAS.Conclusions and Relevance: To date, ERAS has achieved significant benefit for patients and health systems; however, improvements are still needed, particularly in the areas of patient optimization and systematic implementation. During this time of global crisis, the ERAS method of delivering care is required to take surgery and anesthesia to the next level and bring improvements in outcomes to both patients and health systems.
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| 7. |
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| 8. |
- Lovely, Jenna K., et al.
(author)
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Clinical pharmacist perspectives for optimizing pharmacotherapy within Enhanced Recovery After Surgery (ERAS (R)) programs
- 2019
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In: International Journal of Surgery. - : Elsevier. - 1743-9191 .- 1743-9159. ; 63, s. 58-62
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Research review (peer-reviewed)abstract
- One of the most durable approaches to perioperative enhanced recovery programming has culminated in the formation of perioperative organizations devoted to improvements in the quality of the surgical patient experience, such as the Enhanced Recovery After Surgery (ERAS (R)) Society. Members of the American College of Clinical Pharmacy (ACCP) Perioperative Care Practice and Research Network (PRN) and officials from the ERAS (R) Society present an opinion that: (1) identifies therapeutic options within each pharmacotherapy-intensive area of ERAS (R); (2) generates applied research questions that would allow for comparative analyses of pharmacotherapy options within ERAS (R) programs; (3) proposes collaborative practice opportunities between key stakeholders in the surgical journey and clinical pharmacists to manage drug therapy problems and research questions; and (4) highlights examples of pharmacist-led cost savings attributed to ERAS (R) implementation. Clinical pharmacists, working in this manner with the perioperative team across the care continuum, have optimized pharmacotherapy towards measurable outcomes improvements, and stand ready to partner with inter-professional stakeholders and organizations to advance the care of our mutual patients.
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| 9. |
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| 10. |
- Nelson, Gregg, et al.
(author)
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Guidelines for perioperative care in gynecologic/oncology : Enhanced Recovery After Surgery (ERAS) Society recommendations-2019 update
- 2019
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In: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 29:4, s. 651-668
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Research review (peer-reviewed)abstract
- BACKGROUND: This is the first updated Enhanced Recovery After Surgery (ERAS) Society guideline presenting a consensus for optimal perioperative care in gynecologic/oncology surgery.METHODS: A database search of publications using Embase and PubMed was performed. Studies on each item within the ERAS gynecologic/oncology protocol were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.RESULTS: All recommendations on ERAS protocol items are based on best available evidence. The level of evidence for each item is presented accordingly.CONCLUSIONS: The updated evidence base and recommendation for items within the ERAS gynecologic/oncology perioperative care pathway are presented by the ERAS® Society in this consensus review.
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