Braden Batkoff, Tyler J Gluckman, Robert Hunter, Michael Ring, Leland Siwek, Branden Reynolds, Matthew Forrester, and Steven Thew
Inverted L Osteotomy for Management of Severe Mandibular Deficiency with Short Posterior Face Height
R. Bryan Bell and Andrew Weeks
From the Publisher:
This trusted, three-volume resource covers the full scope of the field with up-to-date, evidence-based coverage of surgical procedures performed today - including cleft and craniofacial surgeries, oral surgery, oncologic surgery, orthognathic surgery, trauma surgery, surgical pathology, surgery of TMJ disorders, dental implants, dentoalveolar surgery, cosmetic surgery, and reconstructive surgery. More than 4,800 full-color images and illustrations serve as valuable visual references. You'll also find complete guidelines for a wide range of practice issues such as anesthesia, diagnostic imaging, treatment planning, , psychological considerations, office design and ergonomics, plus new information on implants and orthognathic surgery. It's all the information you need to perfect your oral and maxillofacial surgical techniques and provide state-of-the-art care for your patients.
Alisa Bowman, Christine Bartlett, Sarah Gattis, Staci Hartmann, Eddie LeSage, Heidi Mosher, Joya Picket, and Sarah Potts
Purpose: Decrease incidence of Central line Associated Bloodstream Infection (CLABSI) in the ICU/IMCU at Swedish Medical Center by August 31st 2018, with the overall goal of zero CLABSI stemming from the ICU’s.
Synthesis of Evidence: A review of CLABSI costs, the problem as a whole, and products that help decrease CLABSI was completed. Swedish’s current CLABSI state was discussed and ways to improve existing practices investigated. Ideas to engage and educate patients, family and staff in order to bolster infection prevention practices was reviewed.
Change in practice: Based on the evidence and our protocols we began reviewing patient charts for the existence of central line flush orders and discovered they were not being ordered as they should be. We developed a way to catch missing orders by discussing saline flushes during Medical Directed Rounds (MDR’s) and later adopted the intervention. We developed a central line order-set to streamline central line orders. We trialed products making dialysis lines a closed system and educated staff regarding its use. We switched the practice of accessing dialysis catheters using betadine to utilizing alcohol due to its similar efficacy and faster dry time. Many of these changes not only effected ICU practice but the entire First Hill campus.
Implementation: Staff were educated extensively on new products brought in to create a closed dialysis system, products available for patient/family education and documentation in EPIC. We also filmed a series of four short educational videos designed to engage and educate staff. Saline flushes were added to daily rounds sheets to insure they were flushed per protocol and lastly, we required that 1:1 return demonstrations occur for nurses who access dialysis lines.
Evaluation: At nine months post implementation, the Surgical Intensive Care Unit (SICU) had incurred two CLABSI, the Medical ICU (MICU) and Intermediate Care Unit (IMCU) have remained CLABSI free. This is equivalent to an 80% reduction in CLABSI when compared to the same time period the year prior. 93% of RN’s who access dialysis lines were educated and audits of charts show an increase in patient central line education from 41-71%. Target Standardized Infection Ratio (SIR) of < 1 has been met or exceeded and the number of champions recruited has been exceeded as well. Target Standardized Utilization Ratio (SUR) has not been impacted as we had hoped.
Conclusion: Implementing a group of 4 bedside RN’s interested in improving CLABSI rates in the ICU has been effective in decreasing the incidence of CLABSI on the units. Change was affected by educating staff via short videos, posting scrub the hub signage and central line education in patient rooms, implementing saline flush orders during MDRs, the addition of new products keeping the dialysis catheter a closed system and requiring return demonstrations of proper dialysis access. Use of incentives helped to bring about compliance and rewards staff for their excellent work.
Presenting Author: Alisa Bowman RN, CCRN, Nurse Quality Leader for Infection Prevention, Swedish Medical Center, FH ICU
Basia Delawska-Elliott and Wm. Brian Elliot
Program Description: Despite our profession’s constant evolution to address the changing needs of our users, many health sciences libraries, particularly hospital libraries, are under scrutiny by their institutions. Many of these libraries are facing closure. In fact, a recent study of health sciences library closings [Schwartz, Elkin 2017] found that from 1989-2006 approximately 23-34% of US health sciences libraries closed. Furthermore, between 2011 and 2015, 613 libraries closed, for an average of 115 closings per year [Thibodeau, Funk 2009]. But why? What was the rationale for these closings? Was the decision based solely on economic reasons, or were there other underlying motives? How will providers who lack library services fill their information needs? How can we prevent the closing of additional libraries? This Special Content Session will focus on the ongoing challenges faced by health sciences libraries to remain relevant in an ever-changing world. A panel of speakers will share their experiences with library closures and strategies and best practices for remaining vigilant and promoting library staff, resources, and services effectively. The panel will be followed by an open forum discussion of health sciences library closings in general.
Deborah Eldredge and Mary Waldo
Sheri Feeney, Liga Mezaraups, Douglas Meyer, Glenda Battey, and Linda Severs
Experience how the 3rd largest nonprofit health-system is becoming a learning organization. Engaging frontline staff in high reliability and improvement skills is critical to a High Reliability Learning Organization (HRLO). Leaders and staff pursuing daily improvement deliver greater value to patients, each other, business operations, and their communities. Participants will learn how to combine HRO and improvement science so everyone has the skills, will, and freedom to provide more affordable care and attain zero harm.
- Identify successful elements and challenges of implementation and spread of our high reliability behaviors.
- Demonstrate how HRO behaviors are the foundation for daily improvement across a large organization.
- Apply Clinical Value Improvement to empower employees to improve their job, quality, and affordability.
- Learn how HRO and CVI are integral to PSJH’s strategic plan and leadership development.
Caring for Newborns With Transitional Hypoglycemia: Best Practices for Education Healthcare Providers and Families
Emelia C. Garcia, JoAnn D. Long, and Monica T. Foster
A number of fetal-maternal conditions predispose infants to hypoglycemia. Consensus on postnatal glucose screening and management is mixed contributing to ineffective communication during level of care transition. This project presents evidence informing best practices in how to educate healthcare providers and families of newborns with hypoglycemia.
Moving Slow to Move Fast-Nursing Handovers-Implementing Electronic to ED Report to Improve Throughput
Dawn Gilbert, Roni Lyons, Patrick Mugrage, and Linda Severs
Katie Gilligan and Heidi Beazizo
This interactive session will describe the changes being tested by 10 hospitals in the Integrating Behavioral Health in the ED and Upstream Learning Community, convened by IHI and Well Being Trust, to achieve meaningful improvements for patients with mental health and substance abuse conditions, their families, and ED staff. Participants will learn from experts and participating team members, share learning with other participants, and develop action plans for bringing this critical work to their organizations.
After this presentation you will be able to:
- Describe a theory of change and set of core measures to improve patient outcomes, experience, and staff safety while reducing avoidable ED re-visits
- Explain key changes tested by a range of health care organizations and results that can be achieved
- Identify strategies and ideas to test at any organization
Implementation of an EMR-based continuous electrocardiographic monitoring (CEM) order to reduce inappropriate utilization
Ty J. Gluckman, Maulin P. Shah, Nicole E. Ondoworth, Stephanie C. Fine, Jonathan V. Laius, Wendy W. Yu, Janelle D. Stevens, Shelley L. Schoepflin Sanders, Ruben O. Halperin, Braden W. Batkoff, Robert M. Dressler, and Mark L. Sanz
Tyler J Gluckman, Maulin P. Shah, Elizabeth A. Widhalm, Daniel J. Weidert, Stephanie C. Fine, Jonathan V. Laius, Braden Batkoff, and Mark L. Sanz
John Handy Jr., Courtney Wood, Erika Rauch, Kevin Olson, Roshanthi Weerasinghe, Rachel Sanborn, and Micheal Skokan
Objective: Since the National Lung Screening Trial (NLST), lung cancer screening (LCS) has been widely implemented but little is known about LCS finances. We describe revenues associated with screening and immediate downstream clinical activity.
Methods: A lung cancer screening (LCS) program began in November 2013 incorporating 7 hospitals (2 non-university tertiary and 5 community medical centers) and 3 free standing imaging centers. Candidates were referred by primary care providers (PCP). LCS was carried out using the Center for Medicare & Medicaid Services modified NLST eligibility criteria. Dedicated radiologists at the tertiary centers interpreted all LCS, assigning Lung RADS categories. Every Lung RADS 4 LCS was reviewed by the multidisciplinary thoracic disease conference, generating management recommendations. The program coordinator recorded all imaging, procedures, adverse events, pathology, staging and ensured follow up LCS. Clinical and administrative data bases were combined, examining 2013 - May 2017. Weighted average payment (to account for payer differences) and average total costs (direct + indirect) were analyzed. Downstream clinical activity was identified from the index event (LCS) and examining subsequent clinical encounters using relevant ICD10 codes (neoplasm, tobacco use, oncology, etc).
Results: 1950 people underwent initial CT screening, 1160 underwent follow up LCS, totaling 3110 scans. Payers comprised Medicare-65%, commercial-20% and Medicaid-14%. 55 cancers were diagnosed, including 40 non-small cell (stage I-26; stage II-5; stage III- 4 and stage IV-5), 6 small cell and 9 extra-thoracic cancers. Lung cancer detection rate was 2.3%. Intervention included additional imaging (CT, XR, PET, US, MRI, bone scan, mammogram) in 483 (15.5%) and 111 procedures (5.6%). Invasive diagnostic procedures included bronchoscopy (27), CT-guided biopsy (19) and ultrasound guided biopsy (18). 47 surgeries were performed (1.5%). Thoracic surgeries included thoracoscopic lobectomy (21), thoracoscopic wedge resection (6), thoracoscopic anatomic segmentectomy (4) and thoracoscopic pneumonectomy (1). Adverse event rate for procedures was 10.8% (0.6% of all screened patients). One lobectomy patient died, yielding a 2.1% surgical mortality. LCS Revenues Events Average Total Cost Average Total Payment Net Margin LCS 2781 $357,493 $393,491 9.1% Additional imaging resulting from LCS 483 $129,492 $187,138 30.8% Downstream clinical activity 263 $654,340 $703,448 7%
Of the downstream clinical activity, thoracic surgery contributed 34%, medical oncology 21%, general surgery 19%, and pulmonology 14%.
Conclusion: Beyond the substantial human and financial benefits of identifying curable early stage lung cancer, a low dose CT lung cancer screening program is profitable. 55% of payment results from downstream clinical activity while the LCS itself and additionally generated imaging generated 45%. This information can be used to allocate costs of a LCS program to clinical services and radiology.
Robin Henderson and Mary Renouf-Hanson
Improving mental health and emotional well-being is the focus of many community health assessments and prevention efforts. This session will focus on innovative ideas that engage youth and their families where they are—in schools, communities and while seeking healthcare. Learn from healthcare leaders at Bellin Health, Cincinnati Children’s, Providence St Joseph Health and East London NHS Foundation Trust and their community partners as they share their successful efforts to change the conversation with today’s youth.
Jennifer Hoople, Gale Arnold, Jennifer Bletscher, Shawna Bolgen, Andy Branca, Tana Case, Matthew Dietz, Jennifer Ferenczy, Heather Haake, Janine Holbrook, Ingrid Jonely, Liga Mezaraups, Jessica Osantowski, Jessica Sehorn, Linda Severs, and Dina Shepelyuk
An inpatient unit in an acute care hospital was designated as an Innovation Unit. This unit was challenged with the creation of culture change in regards to process improvement. The team learned to use Improvement Science to facilitate rapid and innovative process improvements. These changes have enhanced the quality of healthcare provided while decreasing cost. The poster highlights some of the Improvement Science processes, forms, and roles of the team as well as some of the projects and successes.
Kristin Jensen, Nicole Roehrig, Caroline Truong, and Jacklyn Wallace
Bridging the Gap: An Innovative Web-Based Approach for Evaluating EBP Readiness in Direct Care Nurses
JoAnn D. Long, Stacey L. Spradling, Karen Baggerly, Nikki L. Galaviz, and Jamie Roney
The provision of universal and equitable access to safe and effective healthcare emphasized in The 2012 World Health Report, 'no health without research': The endpoint needs to go beyond publication outputs, has forwarded the global evidence-based practice (EBP) movement (Zachariah et al., 2011). Notably, Lindeman (1975) identified research utilization and quality improvement as nursing priorities over forty years ago. Yet, current literature suggests research findings may take seventeen years to reach practice integration (Morris et al., 2011). Notably another dilemma added to the challenge is approximately 80% of current nursing practice does not reflect evidence-based nursing decisions (Conner, Dwyer, and Oliveria, 2016). Peer reviewed literature report direct care nurses self-identify lack of resources, time, and critical appraisal skills to navigate current literature (Yoder et al., 2014). Proficient skills of direct care nurses to acquire and appraise existing studies can be the catalyst translating scientific knowledge to the bedside; however, an understanding of the baseline knowledge and readiness of front-line providers is limited. Organizations worldwide are challenged to overcome these self-reported barriers to implementing and adopting research findings into clinical nursing practice. The purpose of this research study was to determine the self-perceived online research and critical appraisal skills and the EBP readiness and knowledge of front-line nurses from three care facilities in the southwest United States.
Methods: A cross-sectional exploratory descriptive design was used in this study. The Stevens EBP Readiness Inventory and EBP Knowledge Assessment questionnaires were used to assess direct care nurses’ self-reported evidenced-based readiness and baseline EBP knowledge. Research skill was measured using four questions adapted from the Research Readiness Self-Assessment tool. Informed consent was obtained from (N=49) Registered Nurses volunteering to participate. The survey questionnaires were administered online to nurses volunteering to participate from 22 nursing units during a 3-week period in May 2017.
Results: Demographic, descriptive, and frequency distributions were examined.Front-line nurses expressed the highest level of self-confidence in four questions pertaining to the area of use and implementation of clinical practice guidelines. The study data were analyzed using SPSS version 25. The highest area of perceived evidence-based practice readiness was ability to “deliver care using evidence-based clinical practice guidelines” with a mean 4.5, SD, 1.55; “use of agency-adopted clinical practice guidelines”, mean, 4.29, SD, 1.60; “choose evidence-based approaches over routine as a base for own clinical decision making”, mean 4.2, SD, 1.60; and “participate in evidence-based quality improvement processes to evaluate outcomes of practice changes”, mean, 4.02, SD, 1.49. In comparison, the lowest areas of self-confidence for evidence-based practice centered on a range of topics reflected in three questions reflecting the ability to assess the “major facets to be assessed when using clinical practice guidelines”, mean, 2.77, SD, 1.18; “ability to identify statistics commonly used in evidence summaries”, mean, 2.96, SD, 1.18; and “ability to conduct expert search strategies using pre-constructed strategies in major databases”, mean, 2.67, SD, 1.21. The remaining 14 questions assessing evidence-based practice readiness ranged from a low mean score of 3.02 – 3.69, reflecting scores falling approximately half-way between having “very little” to having a “great deal” of evidence-based readiness.
Conclusion: While front-line nurses reported high levels of self-confidence for using EBP to implement and deliver care using clinical practice guidelines, they also expressed lower knowledge and self-efficacy with use of more advanced EBP skills. Strengthening nurse online search skills was identified as the most important learning deficit in this sample of Registered Nurses. Limitations of this study included a voluntary and relatively small sample size and cross-sectional design. Findings from this study helped identify objective data to guide focused organizational education efforts to improve direct care nurses’ use of EBP and research concepts necessary to integrate research into clinical practice.
Roxanne McGray, Mary Waldo, and Catherine Van Son
Purpose: This quality improvement, doctorate of nursing practice (DNP) project assesses the need for and evaluates the impact of an engagement intervention focused on improving nurse, physician, and emergency department technician (EDT) engagement within an emergency department.
Background: Engagement is defined as an energetic state of involvement with personally fulfilling activities that enhance one’s sense of professional efficacy and is characterized by vigor, dedication, and absorption. While a significant amount of research exists that correlates the relationship between low nurse engagement levels with high turnover rates, there is little known about the effectiveness of interventions aimed at improving nurse engagement. Therefore, a project evaluating the impact of an engagement intervention on increasing engagement levels for all staff was piloted in an emergency department.
Methods: In September 2017 staff (physicians, nurses and EDTs) who work in the emergency department (N=69) completed a pre-intervention survey to assess baseline engagement levels, using the Utrecht Work Engagement Scale (UWES). The preintervention survey included open-ended questions developed by the project team to solicit qualitative information regarding engagement, as well as demographic questions. The preintervention data revealed overall low engagement levels of participants (m = 2.10, sd = 1.63, n=40). The dedication subscale had the lowest mean (m = 1.30, sd = 1.49), while the absorption subscale had the highest mean (m = 2.53, sd = 1.78); the vigor subscale fell between these two means (m = 2.33, sd = 1.59). The open-ended pre-intervention survey results, along with recommendations from the literature and guided by the six areas of worklife framework, were used to guide the design of the unit-based engagement intervention. Some of the interventions will include enhanced staff recognition, activities to improve the sense of community within the department, increased accountability of staff members, augmented shared governance structures, and improved follow-through by the leadership team when staff suggestions are presented. The post-intervention survey will be administered in March 2018 following the intervention phase of the project. Pre- and postintervention survey results and the intervention will be presented.
Outcomes: The level of staff engagement is the primary outcome of this quality improvement project. Pre- and post-intervention survey data will be compared to understand the effectiveness of the intervention designed to increase engagement in the emergency department. The outcomes of this project will help to inform future interventions focused on supporting and maintaining high levels of staff engagement.
Conclusion: Staff engagement is integral to the vitality of the healthcare workforce. A onesize- fits-all approach is not enough to keep staff engaged, excited to come to work, and able to provide the best care for their patients. Listening to staff suggestions and creating an individualized approach for each unit is essential to keep the workforce engaged.
From the publisher:
Written by leading experts in the field and designed for dermatologists and residents, this book includes evidence-based medicine that underscores the clinical data, as well as practical tips on how to use both biologic and systemic agents in the field of dermatology. In the past decade, there have been several groundbreaking advances in medical dermatology. Novel biologic and systemic agents have been developed to treat inflammatory disorders, including psoriasis and atopic dermatitis, as well as skin malignancies such as melanoma.
Biologic and Systemic Agents in Dermatology encompasses these developments by describing the mechanism of action of these various agents and the clinical efficacy and safety to treating these respective disorders. The utilization of biologic and systemic agents in other dermatologic conditions, pharmacoeconomics, pharmacovigilance, and clinical trials outcomes are discussed as well as topics including tumor necrosis, conventional systemic agents for psoriatic disease, and oral agents for atopic dermatitis.
Philip Mease and Muhammad Asim Khan
From the publisher:
Focusing on the key essentials you need to know, Axial Spondyloarthritis provides a quick, expert overview of axSpA from a clinical perspective. This concise resource by Drs. Philip Mease and Muhammad Khan presents practical recommendations and guidelines for the diagnosis, management, and treatment of spondyloarthritis impacting the axial skeleton alongside an overview of epidemiology, special populations, and patient education.
- Discusses key information on genetic factors and disease biomarkers.
- Presents an overview of clinical features, classification criteria, and imaging to aid in diagnosis.
- Covers management and treatment guidelines, including non-pharmacologic management and the use of biologics.
- Consolidates essential information on this timely topic into a single, convenient resource.
Updated efficacy of first or second-line pembrolizumab plus in metastatic triple negative breast cancer and correlations with baseline lymphocyte and naïve CD4+ T-cell count
David Page, Joanna Pucilowska, Laura Bennetts, I Kim, Katherine Sanchez, Maritza Martel, Alison Conlin, Nikki Moxon, Staci Mellinger, Anupama Acheson, K Kemmer, Z Mitri, J Vuky, J Ahn, C Abaya, T Manigault, R Basho, Walter Urba, and HL McArthur
Background: In mTNBC, anti-PD-1/L1 monotherapy is most effective when administered early in the course of disease, with recent trials demonstrating overall response rates (ORR) of 23-26% in the first-line setting and 5-6% in later lines. This may reflect iatrogenic lymphopenia from preceding cytotoxic chemotherapy. Furthermore, curative-intent chemotherapy is associated with prolonged suppression of naïve CD4+ cells, a T-cell subset that may play a critical role in the generation of de novo anti-tumor immune responses. We present the final clinical results of a pilot study evaluating the safety and efficacy of combining pembrolizumab plus standard-of-care capecitabine in the first/second-line mTNBC setting. We also explore potential associations between clinical benefit and lymphopenia, preceding chemotherapy, and absolute naïve CD4+ counts.
Methods: In a pilot study, we evaluated the tolerability and preliminary efficacy of concurrent pembro (200mg IV q21 day) plus investigator-selected 1st/2nd line paclitaxel (80mg/m2 IV weekly) or oral cape (2,000mg BID, weekly 1 on/1 off). The primary endpoint was tolerability, defined as the proportion of subjects receiving >6 weeks concurrent therapy without dose discontinuation with toxicities reported per CTCAE v4.0. The secondary endpoint was 12-week objective response rate (ORR) by RECIST1.1. Exploratory endpoints included peripheral blood cell enumeration by real-time flow cytometry and routine clinical laboratory. Naïve CD4+ cells were defined as CD45+ CD3+ TCRab+ CD4+ CD45RA+ CCR7+. Here, we report the results of the pilot phase of the cape cohort (NCT02734290).
Results: Twelve of 14 subjects were treated in the first-line setting. All subjects (14/14, 100%) tolerated cape+pembro for >6 weeks, with toxicities consistent with monotherapy cape experience (diarrhea: grade I-II 50%, grade III 7%; hand-foot: grade I-II 71%) that improved with dose-reduction as needed. At 12 weeks, the ORR was 6/14 (42.9%), and the clinical benefit rate (ORR + stable disease) was 8/14 (57.1%). Depressed absolute lymphocyte count at baseline (ALC<1.0/uL: 33% CBR; ALC≥1.0/uL: 75% CBR) and recent exposure to cytotoxic chemotherapy (6 months: 75% CBR) were associated with reduced clinical benefit. By flow cytometry, subjects experiencing clinical benefit had higher baseline absolute naïve CD4+ counts (average 283 cells/uL v. 93 cells/uL, p=.069).
Conclusions: This study met the primary endpoint of safety for cape plus pembro in mTNBC, with encouraging clinical activity. These data are supportive of further studies evaluating combination chemotherapy plus anti-PD-1/L1 mTNBC. We observed greater clinical benefit in subjects with non-suppressed ALC, less exposure to recent chemo, and higher baseline naïve CD4+ counts, suggesting that iatrogenic immunosuppression can impair response to immune checkpoint therapy in mTNBC. These findings should be confirmed in ongoing randomized trials of immune checkpoint +/- chemotherapy in mTNBC, and should be considered in the design of future clinical trials.
Femoral Nerve Injury after Primary Total Hip Arthroplasty is More Common in Patients with Prior Femoral Artery Catheterization
James W. Pritchett
INTRODUCTION: Nerve injury following total hip arthroplasty (THA) is a possible complication that is included in informed consent. Ninety-five percent of femoral artery catheterizations (FACs) utilize a right-side approach and can cause scar around the femoral nerve. The effect of FAC on femoral nerve injury during THA has not been investigated previously.
METHODS: The joint implant database was searched for patients who had primary THA after prior FAC from 2005-2015 (study group). Patients who underwent bilateral THA without prior FAC served as the control group. Proprietary software was used to query the database according to the International Classification of Diseases procedural codes for primary THA and FAC. Chi-square testing was used to determine significant differences between groups (p < 0.05).
RESULTS: There were 62,016 patients in the study group and 441,013 patients in the control group. The left femoral nerve injury rate in the control group was 0.53% and 0.55% in the study group. The right femoral nerve injury rate in the control group was 0.51% and 1.53% in the study group (p < 0.0001). A total of 91% were missed at the time of surgery but 69% of the femoral nerve injuries were identified within 90 days of THA.
DISCUSSION AND CONCLUSION: Patients with a previous history of right femoral artery catheterization have a significantly higher rate of right femoral nerve injury when undergoing THA. Orthopaedic surgeons should be aware of this increased risk of femoral nerve injury
Perilymphatic IRX-2 cytokine therapy to enhance tumor infiltrating lymphocytes and PD-L1 expression preceding curative-intent therapy in early stage breast cancer
Joanna Pucilowska, Venkatesh Rajamanickam, Katherine Sanchez, Valerie Conrad, Alison Conlin, Shagheyegh Aliabadi-Wahle, Shu-Ching Chang, Gary Grunkemeier, Nikki Moxon, Staci Mellinger, Maritza Martel, James Egan, Monil Shah, and David B Page
Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells, facilitates antigen presentation, and enhances activity of anti-PD-1/L1 in a SCC7 model. In a preceding head/neck squamous cell carcinoma phase I trial, perilymphatic IRX-2 was safe and increased TILs. Here, we report the final clinical results of a phase Ib trial evaluating the feasibility and immunologic activity of IRX-2 in ESBC.
Methods: Beginning 21 days prior to surgical resection, enrolled operable patients with stage I-III ESBC (all subtypes) received the pre-operative IRX-2 regimen consisting of a single low-dose cyclophosphamide (300 mg/m2 to facilitate T-regulatory cell depletion), followed by 10 days of subcutaneous peri-areolar IRX-2 injections into the affected breast (1 mL × 2 at tumor axis and at 90°). Endpoints were feasibility (primary endpoint), stromal TIL (sTIL) count (pre-treatment versus post-treatment, blinded average of two pathologist reads using San Antonio H&E sTIL guidelines), PD-L1 expression (Nanostring) and enumeration of peripheral immune cells by flow cytometry.
Results: All patients (n=16/16) completed and tolerated the regimen with no surgical delays or treatment-attributed grade III/IV toxicities. Common adverse events (occurring in >15% subjects) attributed to IRX-2 injections were: injection site reaction (grade 1, n=8/16), bruising (grade 1, n=7/16), and pain (grade 1, n=3/16). Common adverse events attributed to low-dose cyclophosphamide were: fatigue (grade 1, n=5/16) and nausea (grade 1/2, n=3/16). Treatment was associated with an increase in sTIL score (Wilcoxon signed-rank p=.04), with 4/10 sTIL-low tumors (0-10% score) re-categorized to sTIL-moderate (11-50% score). Increases in PD-L1 RNA expression were observed (Wilcoxon signed-rank p=.04) in 12/16 tumors (median 57% increase, range: -53% to 185% increase), as well as increases in Nanostring NK and Th1 cell signatures. In blood, increases in CD4 and CD8 effector T-cell activation (ICOS, HLA-DR, and CD38) and T-reg depletion were observed.
Conclusions: IRX-2 was well tolerated with preliminary evidence of sTIL increase, PD-L1 upregulation, and peripheral lymphocyte activation. Based upon these data and preclinical evaluations demonstrating synergy with checkpoint inhibition, the IRX-2 regimen is being evaluated for clinical efficacy in conjunction with pembrolizumab and neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, paclitaxel) in patients with stage II-III triple negative breast cancer.
Jeanne Rhynsburger, Patty Palmer, and Michelle Hansen
Swedish Edmonds 3 year journey to optimize hospital flow by opening a Service Operations Center – flow management hub.
Notable improvements included:
- Patient visit times decreased 27 minutes per patient
- Emergency department (ED) admit times decreased 68 minutes per patient
- Boarding hours decreased 20%.
Deborah Satterfield, Kathleen Fraser, Mary McLaughlin-Davis, and Vanessa Casillas
Complex patients, challenging patients, costly patients, we all have them. With a team-based care model, caring for these patients can become gratifying, even fun. Led by a primary care physician, a psychologist, and case managers from three organizations, this session will explore an integrated case management approach that uses case managers, behavioral health, and PharmDs.
After this presentation you will be able to:
- 1. Discuss the value of an integrated case management approach in complex populations
- Describe the value and use of behavioral health providers and PharmDs in the care of complex patients
- Explain how to structure and lead complex case conferences and how to use risk stratification to determine which patients will benefit