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.
Impact and Predictors of Paravalvular Regurgitation Following Implantation of the Fully Repostionable and Retrievable Lotus Transcatheter Aortic Valve: Results From the Reprise III Randomized Controlled Trial
Daniel O'Hair, Vivek Rajagopal, Axel Linke, Dean Kereiakes, Ron Waksman, Vinod H. Thourani, Nicolas Dumonteil, Robert W. Hodson, Jeffrey Southard, John Harrison, Samir Kapadia, Dominic Allocco, Ian Meredith, Michael Reardon, and Ted Feldman
Paravalvular leak (PVL) following TAVR has been associated with worse long-term outcomes including an increased risk of mortality. REPRISE III was a large randomized trial comparing 2 contemporary TAVR devices: Lotus and CoreValve (CV). Lotus incorporates an adaptive seal designed to minimize PVL. In this analysis, we evaluated the predictors of PVL and its impact on clinical outcomes.
Patients with high/extreme surgical risk and severe, symptomatic aortic stenosis underwent randomization to Lotus or CV. Multivariate modeling to assess predictors of PVL and outcomes stratified by PVL at 30 days were evaluated.
We randomized 912 patients (2 Lotus:1 CV), age 83±7 years, 51% female, and Society of Thoracic Surgeons predicted risk of mortality 6.8%±4.0%. Lotus was superior to CV for the secondary endpoint of ≥moderate PVL at 1 year (Lotus 0.9%, CV 6.9%; p
Rates of PVL with the Lotus valve were lower than with CV. Calcium was a strong predictor of PVL. Overall, outcomes were similar between groups at 1 year though longer-term follow-up is needed.
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.
Oral anticoagulant use in patients with atrial fibrillation managed by primary care and cardiology providers with or without use of a structured note for PINNACLE Registry reporting
J Petersen, Tyler J Gluckman, S Ingale, L Zhao, J Westcott, D Wells, J Buckler, and C Dale
Rates of Oral Anticoagulant Use in Patients With Atrial Fibrillation Managed By Primary Care and Cardiology Providers With or Without Use of a Structured Note For Pinnacle Registry Reporting
John Petersen, Tyler J Gluckman, Christopher Dale, Joshua Buckler, Darryl Wells, Lisa Zhao, Sahana Ingale, and R Jeffrey Westcott
Oral anticoagulant (OAC) therapy is underutilized in patients with atrial fibrillation (AF) and a CHA2DS2-VASc score ≥2. However, the patterns of OAC selection, adherence with recommendations, and impact of structured note reporting among different specialties has not been well described.
As a part of an internal Quality Improvement initiative, records at Swedish Medical Center (Seattle, WA) from 2016 were reviewed. 10,928 patients had a diagnosis of AF. 3362 were seen by a Primary Care Provider (PCP) and not cardiology, 4439 were seen by cardiology and not a PCP, and 3127 seen by both PCP and cardiology. Rates of discrete reporting of the CHA2DS2-VASc score were noted and for those with a CHA2DS2-VASc score >2, overall use, and specific use of Direct Oral Anticoagulant (DOAC), warfarin, antiplatelet alone, or no therapy was tabulated. Individual provider data for the 8 cardiology providers routinely using the PINNACLE Note were tabulated, and also adjusted for why not given codes.
Of the overall PCP patients (N=6489), 1862 (29%) had a CHA2DS2-VASc score, and 1552 (24%) had a CHA2DS2-VASc score ≥2. Of the overall cardiology patients (N= 7566), 4261 (56%) had a CHA2DS2-Vasc score documented, and of those, 3517 (46%) had a CHA2DS2-Vasc score ≥2. Of the PCP patients with a CHA2DS2-Vasc of ≥2, 35% were treated with warfarin, 36% were treated with a DOAC, 29% with an antiplatelet, and 19% were not treated. Of the cardiology patients, 31% were treated with warfarin, 38% with DOAC, 27% with an antiplatelet, and 23% were not treated. Among the PINNACLE note providers, overall adherence with recommendations was 75%, but after adjusting for why not given codes, adherence was 95% (p <0.05).
CHA2DS2-Vasc scores are inconsistently documented by both PCP and cardiology providers. Among patients with documented CHA2DS2-Vasc scores of ≥2, 19% of PCP patients and 23% of cardiology patients did not have documented anticoagulation. DOAC use was more prevalent among cardiologists. Of the providers using the PINNACLE Note, following adjustment for why not given codes, documentation of adherence with guideline recommended treatment was 95%.
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.
Incorporating Standardized Simulation into the Clinical Academy, a Transition into Practice (TIP) Program
- Describe evidence-based justification for incorporating simulation into Transition into Practice (TIP) programs
- Evaluate current simulation curriculum design and standardization process and compare with elements utilized by Providence St. Joseph Health
- Develop an outline for Transition into Practice simulation facilitator education and development
Rachelle Reid and Michelle Scortzaru
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
Using Knowledge Management and Data Literacy to enable caregivers to have ready access to Organizations’ documented base of facts, source of information and solutions.
Marietta Sperry and Kimberly Kohlieber
Background: Nurses have been noted to model unsafe sleep practices for the newborn in the hospital, despite having been extensively trained. Parents report they repeat this behavior at home. There is a reluctance of nurses to comply, notwithstanding implementation of Back to Sleep programs and documentation of parents being taught safe sleep practices, causing a plateau in the reduction sudden infant death syndrome (SIDS).
Methods: Systematic review of literature from CINHAL, Indiana State University Library, Google Scholar, and PubMed from last five years.
Results: Nurses were found to agree with many guidelines. Personal bias, or habit influenced poor implementation. Although provided with the knowledge, infants were continually placed in unsafe sleep positions, resulting in an inconsistency from knowledge to practice by nurses.
Discussion: Every nurse must model a consistent safe sleep message at every bedside interaction throughout the hospital stay. Interventions could include nurse re-education with mandatory declaration of education, and a Nurse Champion to follow up on unsafe sleep observations. Education should resolve the perceived risk of aspiration for supine positioning by nurses, the primary reason for non-compliance. Under educated parents use sleep positions modeled by nurses. Nurses must be educated that modeling unsafe sleep behaviors, such as using rolled blankets, bulb syringes to support side lying, or propping the bassinet up in the crib cannot be used in the hospital. Non-supine positioning should be utilized only when medically indicated, and with clear education for parents.
Krishnansu S Tewari, Richard T. Penson, and Bradley J. Monk
From the Publisher:
Now updated quarterly for the life of the edition, DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology, 11th Edition, carries on a tradition of excellence while keeping you continually up to date in this fast-changing field. Every quarter, your eBook will be updated with late-breaking developments in oncology, including new drugs, clinical trials, and more. These quarterly updates ensure that your purchase remains fresh and relevant to your practice—a unique, living reference to enhance and improve your patient care.
Meredith Roberts Tomasi, Katie Dobler, and Pamela Mariea-Nason
Learn how Oregon and other states and regions are addressing health care quality and affordability with multi-payer regional data, cost reporting, and community stakeholder collaborations. This session will create a common understanding of terminology and share reports in use today. Participants will draft an affordability roadmap, deepen their knowledge of how to identify meaningful partnerships, and understand how any organization fits into the conversation.
After this presentation you will be able to:
- 1. Discuss the terminology, data elements, and regional resources already working with quality and cost data across the country, and explain how Oregon uses regional data and multi-stakeholder partnerships to address barriers to affordability
- Identify key champions of effective multi-stakeholder collaborations, and develop an affordability asset map for a community
- Generate ideas to create a collaborative community approach to understanding and optimizing the use of data
A volume in the Translational Oncology series, Immunotherapy in Translational Cancer Research explores the recent developments in the role that immunotherapy plays in the treatment of a wide range of cancers. The editors present key concepts, illustrative examples, and suggest alternative strategies in order to achieve individualized targeted therapy. Comprehensive in scope, Immunotherapy in Translational Cancer Research reviews the relevant history, current state, and the future of burgeoning cancer-fighting therapies. The book also includes critical information on drug development, clinical trials, and governmental resources and regulatory issues.
Each chapter is created to feature: development of the immunotherapy; challenges that have been overcome in order to scale up and undertake clinical trials; and clinical experience and application of research. This authoritative volume is edited by a team of noted experts from MD Anderson Cancer Center, the world’s foremost cancer research and care center and:
- Offers a comprehensive presentation of state-of-the-art cancer immunotherapy research that accelerates the pace of clinical cancer care
- Filled with the concepts, examples, and approaches for developing individualized therapy
- Explores the breath of treatments that reflect the complexity of the immune system itself
- Includes contributions from a panel international experts in the field of immunotherapy
Designed for physicians, medical students, scientists, pharmaceutical executives, public health and public policy government leaders and community oncologists, this essential resource offers a guide to the bidirectional interaction between laboratory and clinic immunotherapy cancer research.
Patrick Triplett and Amy Nist
Medical/Surgical units often lack behavioral health specialty resources to identify and support individuals with mental health and substance misuse conditions. Not addressing these issues increases costs, imposes undue burdens on staff, intensifies patient agitation, and impairs the care experience for individuals and their families. Our behavioral health teams proactively identify, assess and intervene on patients in our medical/surgical units while supporting and teaching medical/surgical staff how to more effectively interact with these populations.
Objectives for Johns Hopkins:
- Describe some of the considerations that go into formation of a pro-active psychiatric consultation service
- Review metrics and purported quality measures used to assess psychiatric consultation programs
- Discuss the cultural and qualitative impacts of a successful pro-active psychiatric consultation program
Objectives for Providence St. Joseph Health:
- Discuss an actionable roadmap to implementing a proactive Behavioral Health Intervention Team in an inpatient setting
- Identify how proactively identifying and intervening in behavioral health issues (mental health and substance misuse) on medical units improves care for patients while improving employee satisfaction
- Define measurable outcomes to monitor program evaluation, development, and improvement in support of a sustainable Behavioral Health Intervention Team
Left atrial pressure elevation limits exercise capacity in LVAD patients: Insights from left pressure sensor monitoring in a Heartmate II patient
Jacob Abraham, L Wang, and Kateri Spinelli
R. Bryan Bell, Peter E. Andersen, and Rui P. Fernandes
From the Publisher:
Oral, Head and Neck Oncology and Reconstructive Surgery is the first multidisciplinary text to provide readers with a system for managing adult head and neck cancers based upon stage. Using an evidence-based approach to the management and treatment of a wide variety of clinical conditions, the extensive experience of the author and contributors in head and neck surgery and oncology are highlighted throughout the text. This includes computer aided surgical simulation, intraoperative navigation, robotic surgery, endoscopic surgery, microvascular reconstructive surgery, molecular science, and tumor immunology. In addition, high quality photos and illustrations are included, which are easily accessible on mobile devices.
Xiaoyan Huang, Lesley Jones Larson, and Meredeth Rosenthal
Rebecca Lewis, Lian Wang, Kateri Spinelli, Joshua Remick, Jeff Paulson, Jay Chappell, and Jacob Abraham
Systematic review of patient teaching outcomes to form a concept requiring validation of patient’s understanding of information disseminated. Concept map illustrating defining attributes, antecedents, consequences, empirical referents, and model case.
Aortic root thrombus and myocardial infarction after LVAD treated with intra-aortic thrombolysis and systemic anticoagulation
Yan Xu, Laura Holton, and Jacob Abraham
Background and new guidelines vs. old guidelines. Systematic review of obstacles, recommendations, and conclusions.