PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

Paraganglioma of the Recurrent Laryngeal Nerve.

Background/Objective: Paragangliomas are rare neuroendocrine tumors that primarily arise in the adrenal gland. Head and neck paragangliomas comprise approximately 3% of all extra-adrenal paragangliomas, with a majority of those being found in the carotid body. Recurrent laryngeal nerve paragangliomas are exceedingly rare, with only 2 reported cases found in literature review. Here, we will present the third. Case Report: The patient is a 46-year-old woman with a history of a right thyroid nodule that had been previously biopsied benign with "paucity of diagnostic material." Neck ultrasonography revealed a 7.4 cm nodule that demonstrated interval growth over a 2-year period, so it was recommended to proceed with right thyroid lobectomy and isthmusectomy. During resection, the recurrent laryngeal nerve appeared to "disappear" into the nodule, and it was resected along with the nodule to ensure proper margins. The nerve was reconstructed with an ansa cervicalis interposition graft, and the nodule was sent to pathology. Pathology revealed that the nodule was a 4.8 cm paraganglioma of the recurrent laryngeal nerve. Discussion: Paragangliomas of the head and neck are exceedingly rare. In patients who present with symptoms of dysphagia or dysphonia, further workup, including laryngoscopy and magnetic resonance imaging, could potentially identify and allow for appropriate planning for surgical resection. Conclusion: In rare cases, consideration of paraganglioma as part of the differential for thyroid nodules may assist with planning of surgery but will unlikely alter treatment.

Emergency Department Pediatric Readiness: A Trauma Center Quality Improvement Initiative.

BACKGROUND: Most pediatric patients present to general emergency departments, yet maintaining pediatric equipment, skilled staff, and resources remains a challenge for many hospitals. Pediatric readiness assessment is now a requirement for trauma center verification. OBJECTIVE: This study aims to assess the impact of a quality improvement initiative to improve emergency department pediatric readiness. METHODS: A pre- and poststudy design was used to evaluate a quality improvement initiative to improve the National Pediatric Readiness assessment survey results conducted at a Southwestern United States adult Level I trauma center from September 2022 to April 2023. The multicomponent initiative included implementing a pediatric emergency care coordinator, pediatric-specific policies and procedures, identifying pediatric-specific quality and performance indicators, and educating pediatric-specific staff. Study inclusion criteria were all patients younger than 18 years who presented to the emergency department. The primary outcome measure was the improvement in the weighted Pediatric Readiness Score. Secondary outcomes were throughput, nursing documentation of vital signs, and pain scores. RESULTS: A total of N = 2,356 patients met inclusion, of which n = 1,158 (49.2%) were in the preintervention group and n = 1,198 (50.8%) postintervention group. The weighted Pediatric Readiness Score improved by 45.4%. Transfers to a pediatric hospital increased from 4.1% to 8.6% (p = .016). Blood pressure documentation improved slightly from 88.3% to 88.6%. Pain score documentation decreased from 83.9% to 63.1% (p = .008). Pain medication and administration improved from 19.8% to 26.7% (p = .046). CONCLUSION: We found that participation in the quality improvement initiative was associated with emergency department pediatric readiness improvements.

Burn and Trauma Burden and Screening for Interpersonal Violence During the COVID-19 Pandemic.

INTRODUCTION: Nationwide shelter-in-place (SIP) orders during the pandemic have had long-lasting effects, including increased rates of domestic violence and interpersonal violence. Screening for violence varies by institution, which tool is used, and when. Given increases in burn and trauma admissions over the course of the pandemic, we sought to examine trends at our institution during this time period to better guide care and anticipate system-level effects. METHODS: We performed a retrospective cohort study of pediatric burn and adult burn and trauma patients at our level 1 trauma/burn center between March-May 2019 and March-May 2020. Home safety screening was performed by nursing staff using a 1-part screening questionnaire. Patients presenting before March 15, 2020, were defined as "pre-SIP; " between March 16-May 19, 2020, were "during SIP; " and those after May 19, 2020, were designated as "post-SIP." Descriptive and chi-square statistics were used. Demographic, injury patterns, and screening information were collected. RESULTS: Blunt trauma comprised 60% of injuries, followed by burns (30%) then penetrating injury (7%). Over the entire time period analyzed, 1822 patients had documented home safety screening; ∼2% of patients screened reported a safety concern pre-SIP, compared to 3% of patients during SIP. There were higher rates of burns and penetrating injury during SIP compared to other periods (P ≤ 0.0001). Home safety screening rates were 94%-95% pre- and during SIP, but dropped to 85% post-SIP (P < 0.0001). Home safety concerns were reported almost 2% of the time pre-SIP and 3% during SIP (P = 0.016). CONCLUSIONS: We noted an increase in trauma and burns during and after SIP orders, consistent with the experiences of other institutions. Implementation of a nurse-driven screening process demonstrated high compliance with appropriate referrals. The burden of burn and traumatic injury remains significant, highlighting a need for continued psychosocial screening and the provision of psychosocial support resources in the acute trauma setting.

Race, Healthcare, and Health Disparities: A Critical Review and Recommendations for Advancing Health Equity.

An overwhelming body of evidence points to an inextricable link between race and health disparities in the United States. Although race is best understood as a social construct, its role in health outcomes has historically been attributed to increasingly debunked theories of underlying biological and genetic differences across races. Recently, growing calls for health equity and social justice have raised awareness of the impact of implicit bias and structural racism on social determinants of health, healthcare quality, and ultimately, health outcomes. This more nuanced recognition of the role of race in health disparities has, in turn, facilitated introspective racial disparities research, root cause analyses, and changes in practice within the medical community. Examining the complex interplay between race, social determinants of health, and health outcomes allows systems of health to create mechanisms for checks and balances that mitigate unfair and avoidable health inequalities. As one of the specialties most intertwined with social medicine, emergency medicine (EM) is ideally positioned to address racism in medicine, develop health equity metrics, monitor disparities in clinical performance data, identify research gaps, implement processes and policies to eliminate racial health inequities, and promote anti-racist ideals as advocates for structural change. In this critical review our aim was to (a) provide a synopsis of racial disparities across a broad scope of clinical pathology interests addressed in emergency departments-communicable diseases, non-communicable conditions, and injuries-and (b) through a race-conscious analysis, develop EM practice recommendations for advancing a culture of equity with the potential for measurable impact on healthcare quality and health outcomes.

Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in pancreatic beta cells.

In pancreatic islet beta cells, molecular motors use cytoskeletal polymers microtubules as tracks for intracellular transport of insulin secretory granules. Beta-cell microtubule network has a complex architecture and is non-directional, which provide insulin granules at the cell periphery for rapid secretion response, yet to avoid over-secretion and subsequent hypoglycemia. We have previously characterized a peripheral sub-membrane microtubule array, which is critical for withdrawal of excessive insulin granules from the secretion sites. Microtubules in beta cells originate at the Golgi in the cell interior, and how the peripheral array is formed is unknown. Using real-time imaging and photo-kinetics approaches in clonal mouse pancreatic beta cells MIN6, we now demonstrate that kinesin KIF5B, a motor protein with a capacity to transport microtubules as cargos, slides existing microtubules to the cell periphery and aligns them to each other along the plasma membrane. Moreover, like many physiological beta-cell features, microtubule sliding is facilitated by a high glucose stimulus. These new data, together with our previous report that in high glucose sub-membrane MT array is destabilized to allow for robust secretion, indicate that MT sliding is another integral part of glucose-triggered microtubule remodeling, likely replacing destabilized peripheral microtubules to prevent their loss over time and beta-cell malfunction.

Under the Lens: Team Perception of Trauma Video Review.

BACKGROUND: Video-based assessment and review are becoming increasingly common, and trauma video review (TVR) has been shown to be an effective educational, quality improvement, and research tool. Yet, trauma team perception of TVR remains incompletely understood. OBJECTIVE: We evaluated positive and negative perceptions of TVR across multiple team member groups. We hypothesized that members of the trauma team would find TVR educational and that anxiety would be low across all groups. METHODS: An anonymous electronic survey was provided to nurses, trainees, and faculty during weekly multidisciplinary trauma performance improvement conference following each TVR activity. Surveys assessed perception of performance improvement and anxiety or apprehension (Likert scale: 1 "strongly disagree" to 5 "strongly agree"). We report individual and normalized cumulative scores (average of responses for each positive [n = 6] and negative [n = 4] question stem). RESULTS: We analyzed 146 surveys over 8 months, with 100% completion rate. Respondents were trainees (58%), faculty (29%), and nurses (13%). Of the trainees, 73% were postgraduate year (PGY) 1-3 and 27% were PGY 4-9. Of all respondents, 84% had participated previously in a TVR conference. Respondents reported an improved perception of resuscitation education quality and personal leadership skills development. Participants found TVR to be more educational than punitive overall. Analysis of team member types showed lower scores for faculty for all positive stemmed questions. Trainees were more likely to agree with negative stemmed questions if they were a lower PGY, and nurses were least likely to agree with negative stemmed questions. CONCLUSIONS: TVR improves trauma resuscitation education in a conference setting, with trainees and nurses reporting the greatest benefit. Nurses were noted to be the least apprehensive about TVR.

Screening and intervention for intimate partner violence at trauma centers and emergency departments: an evidence-based systematic review from the Eastern Association for the Surgery of Trauma.

Background: Intimate partner violence (IPV) is a serious public health issue with a substantial burden on society. Screening and intervention practices vary widely and there are no standard guidelines. Our objective was to review research on current practices for IPV prevention in emergency departments and trauma centers in the USA and provide evidenced-based recommendations. Methods: An evidence-based systematic review of the literature was conducted to address screening and intervention for IPV in adult trauma and emergency department patients. The Grading of Recommendations, Assessment, Development and Evaluations methodology was used to determine the quality of evidence. Studies were included if they addressed our prespecified population, intervention, control, and outcomes questions. Case reports, editorials, and abstracts were excluded from review. Results: Seven studies met inclusion criteria. All seven were centered around screening for IPV; none addressed interventions when abuse was identified. Screening instruments varied across studies. Although it is unclear if one tool is more accurate than others, significantly more victims were identified when screening protocols were implemented compared with non-standardized approaches to identifying IPV victims. Conclusion: Overall, there were very limited data addressing the topic of IPV screening and intervention in emergency medical settings, and the quality of the evidence was low. With likely low risk and a significant potential benefit, we conditionally recommend implementation of a screening protocol to identify victims of IPV in adults treated in the emergency department and trauma centers. Although the purpose of screening would ultimately be to provide resources for victims, no studies that assessed distinct interventions met our inclusion criteria. Therefore, we cannot make specific recommendations related to IPV interventions. PROSPERO registration number: CRD42020219517.

Impact of COVID-19 on U.S. Hospital-Based Injury Prevention Professionals: A National Survey.

BACKGROUND: COVID-19 challenged U.S. trauma centers to grapple with demands for expanded services with finite resources while also experiencing a concurrent increase in violent injuries. OBJECTIVE: The purpose of this study was to describe the impact of COVID-19 on the roles and duties of U.S. hospital-based injury prevention professionals. METHODS: This descriptive cross-sectional survey study of hospital-based injury prevention professionals was conducted between June 2021 and August 2021. Participants were recruited from six organizational members of the national Trauma Prevention Coalition, including the American Trauma Society, Emergency Nurses Association, Injury Free Coalition for Kids, Safe States Alliance, Society for Trauma Nurses, and Trauma Center Association of America. Results were analyzed using descriptive and inferential statistics. RESULTS: A total of 216 participants affiliated with 227 trauma centers responded. The following changes were reported during 2020: change in injury prevention position (range = 31%-88%); change in duties (range = 92%-100%); and change to hospital-based injury prevention programs (range = 75%-100%). Sixty-one (43%) single-center participants with a registered nurse license were reassigned to clinical duties compared with six (10%) nonlicensed participants (OR = 5.6; 95% CI [1.96, 13.57]; p < .001). Injury prevention programs at adult-only and combined adult and pediatric trauma centers had higher odds of suspension than pediatric-only trauma centers (OR = 3.6; 95% CI [1.26, 10.65]; p < .017). CONCLUSION: The COVID-19 response exposed the persistent inequity and limited prioritization of injury prevention programming as a key deliverable for trauma centers.

Role and Training of Emergency Department Charge Nurses: A Mixed Methods Analysis of Processes, Needs, and Expectations.

INTRODUCTION: Charge nurses (CNs) are shift leaders who manage resources and facilitate patient care, yet CNs in EDs receive minimal training, with implications for patient safety and emergency nursing practice. The purpose of the study was to describe the experiences of emergency nurses related to training, preparation, and function of the CN role. METHODS: An explanatory sequential mixed methods design using survey data (n = 2579) and focus group data (n = 49) from both CN and staff nurse perspectives. RESULTS: Participants reported minimal training for the CN role, with divergent understandings of role, required education and experience, the need for situational awareness, and the acceptability of the CN taking on other duties. CONCLUSIONS: The ED CN is critical to the safety of both nursing environment and patient care. Nurses in this pivotal role do not receive adequate leadership orientation or formal training in the key areas of nurse patient assignment, communication, and situational awareness. Formal training in nurse-patient assignment, communication, and situational awareness are critical to appropriate patient care and maintenance of interprofessional trust necessary for successful execution of the CN role. ED nurse managers should advocate for this training.

HDAC inhibitors stimulate LIFR when it is repressed by hypoxia or PTHrP in breast cancer.

Breast cancer cells frequently disseminate to the bone marrow, where they either induce osteolysis or enter a dormant state. Downregulation of leukemia inhibitory factor receptor (LIFR), a known breast tumor suppressor, enables otherwise dormant MCF7 human breast cancer cells to become aggressively osteolytic. Hypoxia (low oxygen tensions), which may develop in tumors as a pathological response to the metabolic demands of the proliferating cells and as a physiological state in the bone, downregulates LIFR in breast cancer cells independent of hypoxia-inducible factor (HIF) signaling. However, the mechanism by which LIFR is repressed in hypoxia is unknown. Histone deacetylase (HDAC) inhibitors stimulate LIFR by increasing histone acetylation in the proximal promoter and induce a dormancy phenotype in breast cancer cells inoculated into the mammary fat pad. We therefore aimed to determine whether hypoxia alters histone acetylation in the LIFR promoter, and whether HDAC inhibitors effectively stimulate LIFR in breast cancer cells residing in hypoxic microenvironments. Herein, we confirmed that disseminated MCF7 cells became hypoxic in the bone and that hypoxia increased the epigenetic transcriptional repressor H3K9me3 in the distal LIFR promoter while H3K9ac, which promotes transcription, was significantly reduced. Furthermore, HDAC inhibitor treatment rescued hypoxic repression and dramatically increased expression of LIFR, p38ß, and p21, which regulate tumor dormancy. In a second model of LIFR repression, in which parathyroid hormone-related protein (PTHrP) suppresses LIFR expression, we found that PTHrP binds to the distal LIFR promoter, and that PTHrP suppression of LIFR protein is similarly reversed by HDAC inhibitor treatment. Together, these data suggest that HDAC inhibitors stimulate LIFR regardless of the way it is repressed by the microenvironment.

HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer.

Despite advances in breast cancer treatment, residual disease driven by dormant tumor cells continues to be a significant clinical problem. Leukemia inhibitory factor receptor (LIFR) promotes a dormancy phenotype in breast cancer cells and LIFR loss is correlated with poor patient survival. Herein, we demonstrate that histone deacetylase inhibitors (HDACi), which are in phase III clinical trials for breast cancer, epigenetically induced LIFR and activated a pro-dormancy program in breast cancer cells. HDACi slowed breast cancer cell proliferation and reduced primary tumor growth. Primary breast tumors from HDACi-treated patients had increased LIFR levels and reduced proliferation rates compared to pre-treatment levels. Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.

From Good to Bad: The Opposing Effects of PTHrP on Tumor Growth, Dormancy, and Metastasis Throughout Cancer Progression.

Parathyroid hormone related protein (PTHrP) is a multifaceted protein with several biologically active domains that regulate its many roles in normal physiology and human disease. PTHrP causes humoral hypercalcemia of malignancy (HHM) through its endocrine actions and tumor-induced bone destruction through its paracrine actions. PTHrP has more recently been investigated as a regulator of tumor dormancy owing to its roles in regulating tumor cell proliferation, apoptosis, and survival through autocrine/paracrine and intracrine signaling. Tumor expression of PTHrP in late stages of cancer progression has been shown to promote distant metastasis formation, especially in bone by promoting tumor-induced osteolysis and exit from dormancy. In contrast, PTHrP may protect against further tumor progression and improve patient survival in early disease stages. This review highlights current knowledge from preclinical and clinical studies examining the role of PTHrP in promoting tumor progression as well as skeletal and soft tissue metastasis, especially with regards to the protein as a regulator of tumor dormancy. The discussion will also provide perspectives on PTHrP as a prognostic factor and therapeutic target to inhibit tumor progression, prevent tumor recurrence, and improve patient survival.

Understanding Exception from Informed Consent in Planned Emergency Research.

Many of the current accepted treatment practices provided to patients in the first critical hour after a traumatic injury, stroke, or cardiac arrest have not been rigorously tested in clinical research trials. The inability to obtain informed consent is often a barrier to research in emergency, time-sensitive situations in which the patient is not able to provide informed consent nor is their family member immediately available to provide consent on behalf of the patient. Planned emergency research, often with exception from informed consent, is a type of research study that involves a patient with a life-threatening medical condition that requires urgent interventions, wherein the current treatments may be unproven or suboptimal, and who, because of their current condition, is unable to provide informed consent. This article summarizes the necessary components for using exception from informed consent in planned emergency research. Understanding the research design, particularly research processes specific to time-critical emergency situations, will ensure that the care provided by stretcher-side emergency nurses will result in optimal patient outcomes and is an integral aspect of emergency nursing practice.

Targeting Histone Modifications in Bone and Lung Metastatic Cancers.

PURPOSE OF REVIEW: Breast cancer frequently metastasizes to the bone and lung, but the ability to treat metastatic tumor cells remains a pressing clinical challenge. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) have emerged as promising targets since these enzymes are aberrantly expressed in numerous cancers and regulate the expression of genes that drive tumorigenesis and metastasis. This review focuses on the abnormal expression of histone-modifying enzymes in cancers that have a high tropism for the bone and lung and explores the clinical use of histone deacetylase inhibitors for the treatment and prevention of metastasis to these sites. RECENT FINDINGS: Preclinical studies have demonstrated that the role for HDACs is highly dependent on tumor type and stage of disease progression. HDAC inhibitors can induce apoptosis, senescence, cell differentiation, and tumor dormancy genes and inhibit angiogenesis, making these promising therapeutics for the treatment of metastatic disease. HDAC inhibitors are already FDA approved for hematologic malignancies and are in clinical trials with standard-of-care chemotherapies and targeted agents for several solid tumors, including cases of metastatic disease. However, these drugs can negatively impact bone homeostasis. Although HDAC inhibitors are not currently administered for the treatment of bone and lung metastatic disease, preclinical studies have shown that these drugs can reduce distant metastasis by targeting molecular factors and signaling pathways that drive tumor cell dissemination to these sites. Thus, HDAC inhibitors in combination with bone protective therapies may be beneficial in the treatment of bone metastatic cancers.

Traumatic stress in emergency nurses: Does your work environment feel like a war zone?

INTRODUCTION: Emergency nurses are exposed to both primary and secondary trauma with attendant sequelae in both work and personal spheres. The purpose of the study was to investigate the prevalence of traumatic stress, measured by the secondary traumatic stress scale (STSS) in a sample of emergency nurses and describe the impact of traumatic stress on nursing practice and workplace environment. METHODS: Mixed methods approach using survey instrument data from the Secondary Traumatic Stress Scale (STSS) (N = 125) and focus group data (N = 53). RESULTS: The average total score on the STSS was 51.83 for nurses who attended one of the focus groups 48.42 for nurses who did not attend (clinical cutoff for STS = 39). Focus group data aligned with elements of the STSS; thematic categories of cumulative trauma, mental health sequelae, bullying and organizational violence, coping mechanisms, relationship damage, and solutions were described. Although we measured only STS, participants often used the terms "PTSD" and "STS" interchangeably. CONCLUSIONS: The nurses in this study demonstrated high levels of STS and described in detail how chronic, cumulative trauma affected relational nursing care and social connections. Participants discussed high levels of suicidality in the profession, and the compounding trauma of relational and organizational violence. The pervasiveness of traumatic stress and the extent to which it affects all areas of nurses' lives is a cause for great concern.

Actionability and Usability of a Fever Management Tool for Pediatric Caregivers.

BACKGROUND: Effective fever management in children relies on caregivers having adequate general and numerical literacy. Nationally, nine of 10 adults have difficulty understanding health information. Lack of understanding basic information about fever management is a primary reason given for nonurgent pediatric emergency department visits. The Assess-Communicate-Treat (A.C.T.) tool was created by nurses 18 years ago to help parents better understand fever management. METHOD: This article describes a quality improvement project that used an expert health care provider panel and parents who attended focus groups to reevaluate the A.C.T. tool. The Simply Put manual, Simple Measure of Gobbledygook readability formula (SMOG) tool, Flesch-Kincaid Grade Level (FKGL) readability test, and Patient Education Materials Assessment Tool (PEMAT-P) were used to evaluate the A.C.T. tool. RESULTS: Following focus groups, 45 of 72 items on the A.C.T. tool were revised using a 4-point Likert scale. After revision, the tool rated 88% for understandability and 83% actionability using the PEMAT-P tool. CONCLUSION: Recognizing caregivers' health literacy needs is critical to optimizing health outcomes and reducing health care costs in the pediatric population. [J Contin Educ Nurs. 2020;51(7):338-344.].

STATISTICAL COMPARISON OF AFIRMA GSC AND AFIRMA GEC OUTCOMES IN A COMMUNITY ENDOCRINE SURGICAL PRACTICE: EARLY FINDINGS.

OBJECTIVE: The Veracyte Afirma Gene Expression Classifier (GEC) has been the most widely used negative predictive value molecular classifier for indeterminate cytology thyroid nodules since January 2011. To improve the specificity and further reduce unnecessary thyroid surgeries, a second-generation assay (Afirma Genetic Sequence Classifier [GSC]) was released for clinical use in August 2017. We report 11 months of clinical outcomes experience with the GSC and compare them to our 6.5-year experience with the GEC. METHODS: We searched our practice registry for FNAB nodules with Afirma results from January 2011through June 2018. GEC versus GSC results were compared overall, in oncocytic and nononcocytic aspirates and by pathologic outcomes. RESULTS: GSC identified less indeterminate cytology nodules as suspicious (38.8%; 54/139) when compared to GEC (58.4%; 281/481). There was a decrease of in the percentage of oncocytic fine-needle aspiration thyroid biopsy (FNAB) subjects classified as suspicious in the GSC group, with 86 of 104 oncocytic indeterminates (82.7%) classified as suspicious by GEC and 12 of 34 (35.3%) classified as suspicious by GSC. The surgery rate in patients with oncocytic aspirates fell from 56% in the GEC group to 31% in the GSC-evaluated group (45%). Pathology analysis demonstrated a false-negative percentage for an incomplete surgical group of 9.5% for GEC and 1.2% for GSC. CONCLUSION: Our GSC data suggest that the GSC further reduces surgery in indeterminate thyroid nodules by improving the specificity of Afirma technology without compromising sensitivity. A primary determinant for this change is a significant improvement in the specificity of the Afirma GSC test in oncocytic FNAB aspirates. ABBREVIATIONS: FNAB = fine-needle aspiration biopsy; GEC = Gene Expression Classifier; GSC = Genetic Sequence Classifier.

COMMUNITY ENDOCRINE SURGICAL EXPERIENCE WITH FALSE-NEGATIVE AFIRMA GEC® RESULTS: 2011-2017.

OBJECTIVE: Afirma Gene Expression Classifier® (Afirma GEC) molecular analysis (Veracyte, Inc, San Francisco, CA) is a negative predictive value test developed to reduce the number of thyroidectomies in thyroid nodule patients with indeterminate cytology. GEC technology has reportedly reduced unnecessary thyroid surgery, but few studies have examined Afirma GEC false-negative rates, since usually patients with GEC benign nodules do not undergo surgery for definitive diagnosis. Occasionally, Afirma GEC benign patients require removal of their thyroid nodules for other reasons; this work describes the incidence of malignancy and noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) in this population. METHODS: We reviewed our community endocrine surgical practice database for patients who had undergone thyroid surgery from January 2011 through April 2017 despite benign Afirma GEC results. RESULTS: Afirma GEC testing was completed for 475 patients during the study period. Surgery was clinically indicated for other reasons in 42 of the 193 patients (22%) with Afirma GEC benign results. Malignancy or NIFTP in the targeted nodule was found in the final histologic evaluation of 14 of the 42 Afirma GEC benign surgical patients. The Afirma GEC false-negative percentage for our incomplete surgical group (FNP-ISG), defined as the surgically proven false negatives divided by the total Afirma GEC benign patients, was 7.3%. CONCLUSION: Our high surgical rate in Afirma GEC benign nodules reveals an FNP-ISG of 7.3% in our community endocrine surgical patient population; this value exceeds the 5.7% reported in the multicenter 2012 Afirma GEC validation study. ABBREVIATIONS: Afirma GEC = Afirma Gene Expression Classifier; FNA = fine-needle aspiration; FNP = false-negative percentage; FNP-ISG = false-negative percentage for an incomplete surgical group; NIFTP = noninvasive follicular thyroid neoplasms with papillary-like nuclear features.