Electronic Consultations in a Community Neurology Practice: A Retrospective Study Informing Best Practice.

Objective: To describe our practice of electronic consultations (e-consults) and assess safety and risk factors for subsequent face-to-face consultations. Patients and Methods: A retrospective cohort study of all e-consults completed in a community neurology practice between May 5, 2018, and June 31, 2019, was completed. Clinical and demographic variables were compared between the successful and unsuccessful (defined by presence of subsequent face-to-face consultation) cohorts. Hazard ratios (HR) were calculated using Cox regression model. Kaplan-Meier probability analysis (with 95% CIs) of subsequent face-to-face consultation was performed. Case examples highlighting potential harm were summarized. Results: In total, 302 e-consults were reviewed. The most frequent referrals were for headache (n=125, 41.4%), dysesthesia (n=40, 13.2%), and abnormal imaging finding (n=27, 8.9%). The most common e-consult questions were for treatment (57.6%) and diagnostic evaluation (48.0%) recommendations. Moreover, 24.8% (n=75) of e-consults were followed by face-to-face consultations, with primary risk factors including female sex (HR, 1.9), referral for headache (HR, 1.7), and final diagnosis of migraine (HR, 2.0) or long-term migraine (HR, 5.0). Potential harm related to delayed diagnosis/treatment was identified in 6 (2.0%) patients with migraine and 4 (1.3%) without migraine presenting to emergency department. Conclusion: Utilization of e-consults may safely improve access to neurologic expertise and prevent the need for some visits, which may have required a face-to-face visit. In patients with chronic migraine, e-consults should be considered short-term and followed by face-to-face consultation as soon as access allows. Neurologists performing e-consults should be able to triage patients to face-to-face consultation, particularly when diagnosis is uncertain or the neurologic examination may help guide appropriate testing.

Feasibility and Usability of a Mobile App-Based Interactive Care Plan for Migraine in a Community Neurology Practice: Development and Pilot Implementation Study.

BACKGROUND: Migraine is a common and major cause of disability, poor quality of life, and high health care use. Access to evidence-based migraine care is limited and projected to worsen. Novel mobile health app-based tools may effectively deliver migraine patient education to support self-management, facilitate remote monitoring and treatment, and improve access to care. The risk that such an intervention may increase the care team workload is a potential implementation barrier. OBJECTIVE: This study aims to describe a novel electronic health record-integrated mobile app-based Migraine Interactive Care Plan (MICP) and evaluate its feasibility, usability, and impact on care teams in a community neurology practice. METHODS: Consecutive enrollees between September 1, 2020, and February 16, 2022, were assessed in a single-arm observational study of usability, defined by 74.3% (127/171) completing ≥1 assigned task. Task response rates, rate and type of care team escalations, and patient-reported outcomes were summarized. Patients were prospectively recruited and randomly assigned to routine care with or without the MICP from September 1, 2020, to September 1, 2021. Feasibility was defined by equal to or fewer downstream face-to-face visits, telephone contacts, and electronic messages in the MICP cohort. The Wilcoxon rank-sum test was used to compare continuous variables, and the chi-square test was used for categorical variables for those with at least 3 months of follow-up. RESULTS: A total of 171 patients were enrolled, and of these, 127 (74.3%) patients completed ≥1 MICP-assigned task. Mean escalations per patient per month was 0.9 (SD 0.37; range 0-1.7). Patient-confirmed understanding of the educational materials ranged from 26.6% (45/169) to 56.2% (95/169). Initial mean headache days per week was 4.54 (SD 2.06) days and declined to 2.86 (SD 1.87) days at week 26. The percentage of patients reporting favorable satisfaction increased from a baseline of 35% (20/57) to 83% (15/18; response rate of 42/136, 30.9% to 28/68, 41%) over the first 6 months. A total of 121 patients with MICP were compared with 62 patients in the control group. No differences were observed in the rate of telephone contacts or electronic messages. Fewer face-to-face visits were observed in the MICP cohort (13/121, 10.7%) compared with controls (26/62, 42%; P<.001). CONCLUSIONS: We describe the successful implementation of an electronic health record-integrated mobile app-based care plan for migraine in a community neurology practice. We observed fewer downstream face-to-face visits without increasing telephone calls, medication refills, or electronic messages. Our findings suggest that the MICP has the potential to improve patient access without increasing care team workload and the need for patient input from diverse populations to improve and sustain patient engagement. Additional studies are needed to assess its impact in primary care.

Migraine Patient Care Model Preferences in a Community Practice.

Background and Objectives: Developing high-value care models with limited resources for large populations of individuals with migraine requires advanced understanding of patient preferences for care delivery methods. In this study, we aimed to inform the development of migraine care models by assessing patient preferences for types of care delivery and determining differences based on migraine frequency and disability. Methods: We analyzed unpublished data from a cross-sectional survey of 516 randomly selected individuals with migraine within a community practice associated with Mayo Clinic, Rochester, MN. Results: Individuals with chronic migraine, compared with those with episodic migraine, were more likely to prefer a visit with a neurologist (p = 0.0005), synchronous telephone conference with primary care provider (PCP) and neurologist (p = 0.0102), and a written migraine action plan in the medical record (p = 0.0343). Compared with those with mild/no disability, individuals with moderate-to-severe disability were more likely to prefer a visit with a neurologist (p < 0.0001), synchronous video or telephone conference with PCP and neurologist (p < 0.0001), PCP communication with neurologist (p = 0.0099), electronic message to primary care team with access to neurologist (p = 0.0216), and written action plan in the medical record (p = 0.0011). Collectively, individuals most preferred telephone follow-up and least preferred communications with a nurse or pharmacist or generalized education (all p < 0.001). Discussion: We observed differences in migraine care delivery preferences between migraine frequency and level of migraine disability. Observations support development of care pathways that include a written migraine action plan, primary care-neurology collaboration including nontraditional interactions, and prioritization of traditional neurology consultation for the most disabled patients.

Posttraumatic Ruptured Axillary Mononeuropathy Without Shoulder Dislocation in an American Football Player: A Case Report and Review of the Literature.

ABSTRACT: A high school-aged right-handed adolescent boy presented with a 5-mo history of persistent proximal right arm weakness and numbness after an American football stinger injury without a documented history of a shoulder dislocation or humeral fracture. He developed diffuse deltoid muscle atrophy, persistent shoulder abduction weakness, and reduced pinprick sensation confined to the axillary distribution over 5 mos. Needle electromyography demonstrated dense fibrillation potentials and no voluntary activation in all three deltoid muscle heads, indicating a severe posttraumatic ruptured axillary mononeuropathy. The patient then underwent a complex three-cable sural nerve graft repair for attempted reinnervation of the axillary-innervated muscles. Isolated axillary nerve injuries are usually associated with anterior shoulder dislocations; however, a severe isolated persistent axillary mononeuropathy from a ruptured axillary nerve may occur in trauma patients without a clear history of shoulder dislocation. These patients may present with only mild persistent weakness of shoulder abduction. Electrodiagnostic testing to fully assess axillary nerve function should still be considered to identify patients with high-grade nerve injuries that may benefit from sural nerve grafting. The rapid recovery of our patient's initial symptoms with persistent severe axillary injury suggests a unique vulnerability of the nerve due to the neuroanatomy and possibly other factors.

Human Induced Pluripotent Stem Cell Encapsulation Geometry Impacts Three-Dimensional Developing Human Engineered Cardiac Tissue Functionality.

Cardiac tissue engineering has been working to alleviate the immense burden of cardiovascular disease for several decades. To improve cardiac tissue homogeneity and cardiomyocyte (CM) maturation, in this study, we investigated altering initial encapsulation geometry in a three-dimensional (3D) direct cardiac differentiation platform. Traditional engineered cardiac tissue production utilizes predifferentiated CMs to produce 3D cardiac tissue and often involves various cell selection and exogenous stimulation methods to promote CM maturation. Starting tissue formation directly with human induced pluripotent stem cells (hiPSCs), rather than predifferentiated CMs, simplifies the engineered cardiac tissue formation process, making it more applicable for widespread implementation and scale-up. In this study, hiPSCs were encapsulated in poly (ethylene glycol)-fibrinogen in three tissue geometries (disc-shaped microislands, squares, and rectangles) and subjected to established cardiac differentiation protocols. Resulting 3D engineered cardiac tissues (3D-ECTs) from each geometry displayed similar CM populations (∼65%) and gene expression over time. Notably, rectangular tissues displayed less tissue heterogeneity and suggested more advanced features of maturing CMs, including myofibrillar alignment and Z-line formation. In addition, rectangular tissue showed significantly higher anisotropic contractile properties compared to square and microisland tissues (MI 0.28 ± 0.03, SQ 0.35 ± 0.05, RT 0.79 ± 0.04). This study demonstrates a straightforward method for simplifying and improving 3D-ECT production without the use of exogenous mechanical or electrical pacing and has the potential to be utilized in bioprinting and drug testing applications. Impact statement Current methods for improving cardiac maturation postdifferentiation remain tedious and complex. In this study, we examined the impact of initial encapsulation geometry on improvement of three-dimensional engineered cardiac tissue (3D-ECT) production and postdifferentiation maturation for three tissue geometries, including disc-shaped microislands, squares, and rectangles. Notably, rectangular 3D-ECTs displayed less tissue heterogeneity and more advanced features of maturing cardiomyocytes, including myofibrillar alignment, Z-line formation, and anisotropic contractile properties, compared to microisland and square tissues. This study demonstrates an initial human induced pluripotent stem cell-encapsulated rectangular tissue geometry can improve cardiac maturation, rather than implementing cell selection or tedious postdifferentiation manipulation, including exogenous mechanical and/or electrical pacing.

Zotatifin, an eIF4A-Selective Inhibitor, Blocks Tumor Growth in Receptor Tyrosine Kinase Driven Tumors.

Oncoprotein expression is controlled at the level of mRNA translation and is regulated by the eukaryotic translation initiation factor 4F (eIF4F) complex. eIF4A, a component of eIF4F, catalyzes the unwinding of secondary structure in the 5'-untranslated region (5'-UTR) of mRNA to facilitate ribosome scanning and translation initiation. Zotatifin (eFT226) is a selective eIF4A inhibitor that increases the affinity between eIF4A and specific polypurine sequence motifs and has been reported to inhibit translation of driver oncogenes in models of lymphoma. Here we report the identification of zotatifin binding motifs in the 5'-UTRs of HER2 and FGFR1/2 Receptor Tyrosine Kinases (RTKs). Dysregulation of HER2 or FGFR1/2 in human cancers leads to activation of the PI3K/AKT and RAS/ERK signaling pathways, thus enhancing eIF4A activity and promoting the translation of select oncogenes that are required for tumor cell growth and survival. In solid tumor models driven by alterations in HER2 or FGFR1/2, downregulation of oncoprotein expression by zotatifin induces sustained pathway-dependent anti-tumor activity resulting in potent inhibition of cell proliferation, induction of apoptosis, and significant in vivo tumor growth inhibition or regression. Sensitivity of RTK-driven tumor models to zotatifin correlated with high basal levels of mTOR activity and elevated translational capacity highlighting the unique circuitry generated by the RTK-driven signaling pathway. This dependency identifies the potential for rational combination strategies aimed at vertical inhibition of the PI3K/AKT/eIF4F pathway. Combination of zotatifin with PI3K or AKT inhibitors was beneficial across RTK-driven cancer models by blocking RTK-driven resistance mechanisms demonstrating the clinical potential of these combination strategies.

Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A.

The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5'-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant in vivo efficacy against a panel of diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma models with ≤1 mg/kg/week intravenous administration. Evaluation of predictive markers of sensitivity or resistance has shown that activation of eIF4A, mediated by mTOR signaling, correlated with eFT226 sensitivity in in vivo xenograft models. Mutation of PTEN is associated with reduced apoptosis in vitro and diminished efficacy in vivo in response to eFT226. In models evaluated with PTEN loss, AKT was stimulated without a corresponding increase in mTOR activation. AKT activation leads to the degradation of PDCD4, which can alter eIF4F complex formation. The association of eFT226 activity with PTEN/PI3K/mTOR pathway regulation of mRNA translation provides a means to identify patient subsets during clinical development.

Synchronous neurology-primary care collaboration in a medical home.

BACKGROUND: Synchronous collaboration as defined by a simultaneous encounter between primary care providers (PCPs), patients, and neurologists may improve access to neurologic expertise, care value, and satisfaction of PCPs and patients. We examined a series of synchronous collaborations and report outcomes, PCP satisfaction, downstream utilization, and illustrative case examples. METHODS: Within an outpatient collaborative primary care-neurology care model, we implemented synchronous video consultations from a central hub to satellite clinics while increasing availability of synchronous telephone and face-to-face collaboration. PCP experience was assessed by a postcollaboration survey. Individual cases were summarized. Clinical and utilization outcomes were assessed by a neurologist immediately after and by follow-up chart review. RESULTS: A total of 58 total synchronous collaborations were performed: 30 by telephone (52%), 18 face to face (31%), and 10 by video (17%) over 27 clinic half-days. The most frequent outcomes as assessed by the neurologist were reassurance of the PCP (23/58; 40%) and patient (22/59; 38%), and the neurologist changed the treatment plan (23/58; 40%). A subsequent face-to-face consultation was completed in 15% (6/58) of patients initially assessed by telephone or video. Test utilization was avoided in 40% (23/58). Unintended utilization occurred 9% (5/58). Most PCPs were very satisfied with the ease of access, quality of care, and reported high likelihood of subsequent use. PCPs perceived similar or less time spent during synchronous vs asynchronous collaboration and neurologist usually altered the testing (87.8%) and treatment plan (95.2%). CONCLUSIONS: Synchronous collaboration between neurologists and PCPs may improve timely access to neurologic expertise, downstream utilization, and PCP satisfaction.

Expanded neuromuscular morbidity in Hodgkin lymphoma after radiotherapy.

Our study aims to quantitate neuromuscular morbidity from radiotherapy in Hodgkin lymphoma including: (i) frequency and (ii) time of onsets for neurological localizations; (iii) degree of disabilities and (iv) number of clinical visits compared to cardiopulmonary Hodgkin lymphoma-radiation complications. Medical records from Mayo Health systems were retrieved; identifying neuromuscular radiation treated Hodgkin lymphoma-complications from 1 January 1994 to 31 December 2016. Of an estimated 4100 post-radiotherapy Hodgkin lymphoma patients, 4.6% (189) were identified with complications. Mean latency to physician visit for symptoms was 23.7 years (range: 1-50). Most commonly identified complications included: head drop 10% (19) with or without myopathy, myopathy 39% (73), plexopathy 29% (54), myelopathy 27% (51) and polyradiculopathy 13% (24). Other findings included benign and malignant nerve sheath tumours 5% (9), phrenic and long thoracic mononeuropathies 7% (14) and compressive spinal meningioma 2% (4). Patients frequently had multiple coexisting complications (single = 76% [144], double = 17% [33], triple = 4% [8], quadruple = 2% [4]). Cardiac 28% (53) and pulmonary 15% (29) complications were also seen in these patients. History of Hodgkin lymphoma was initially overlooked by neurologists (14.3%, 48/336 clinical notes). Hospital and outpatient visits for complications were frequent: neuromuscular 19% (77/411) versus cardiopulmonary 30% (125/411). Testing was largely exclusionary, except when imaging identified secondary malignancy. Modified Rankin score at diagnosis varied: 0-1 (55.8%), 2-3 (5.8%) and 4-5 (38.3%). Neuromuscular complications among post-radiation Hodgkin lymphoma are diverse, occurring in ∼1 of 20 having markedly delayed onsets often eluding diagnosis. Frequent care visits and major morbidity are common. Survivorship recommendations should recognize the diverse neurological complications.

Factors Associated With Risk of Recurrent Transient Global Amnesia.

Importance: Transient global amnesia (TGA) is usually considered a benign event with a low recurrence rate. However, recurrence rates vary considerably among studies and there are no known risk factors for TGA. Objective: To examine risk factors for the recurrence of TGA. Design, Setting, and Participants: This retrospective cohort study involved medical record review of patients with isolated or recurrent TGA presenting to the Mayo Clinic in Rochester, Minnesota, between August 1, 1992, and February 28, 2018. A total of 1491 cases were reviewed and 1044 met diagnostic inclusion criteria for TGA, with the remainder excluded owing to indeterminate or alternate diagnoses or limited information available in the medical record. Exposures: Single vs recurrent episodes of TGA. Main Outcomes and Measures: Demographics, precipitating factors, migraine history, imaging and electrodiagnostic findings, and family history of TGA were collected. The main outcome measure was TGA recurrence. Results: Of 1044 included patients, 575 (55.1%) were male, and the mean (SD) age at inclusion was 75.0 (11.5) years. A total of 901 patients (86.3%) had a single episode of TGA and 143 (13.7%) had recurrent episodes of TGA. The 2 groups were similar in age at inclusion, sex, identifiable triggers, and duration of anterograde amnesia. The number of recurrences ranged from 1 to 9, with 137 individuals (95.8%) having 3 or fewer recurrences. The mean (SD) age at first episode of TGA was 65.2 (10.0) years for individuals with a single episode vs 58.8 (10.3) years for those with recurrent episodes (P < .001). There was a personal history of migraine in 180 individuals (20.0%) with a single episode of TGA and 52 individuals (36.4%) with recurrent episodes of TGA (P < .001), and a family history of migraine in 167 individuals (18.5%) with a single episode of TGA and 44 individuals (30.8%) with recurrent episodes of TGA (P = .001). There were no electroencephalographic findings associated with increased risk of TGA recurrence. Acute and subacute temporal lobe abnormalities on results of magnetic resonance imaging were seen rarely and did not require intervention. A family history of TGA was identified in 12 individuals (1.3%) with a single episode of TGA and 4 individuals (2.8%) with recurrent episodes of TGA. Conclusions and Relevance: This study suggests that, in this large cohort of patients with TGA, recurrent TGA was associated with earlier age at the time of first TGA episode and higher prevalence of both personal and family history of migraine compared with isolated cases. These results can be used to counsel patients about risks of recurrence and may have implications for the understanding of TGA pathophysiology.

Loneliness and Migraine Self-Management: A Cross-Sectional Assessment.

Background: Chronic illness is often comorbid with the psychological state of loneliness. Models of care for patients who experience chronic migraines may often lack an understanding of psychosocial influences of the illness. Addressing the effects of loneliness on the health behaviors of chronic migraine patients may further elucidate gaps in care that exist beyond the biomedical approach to migraine treatment. The primary aim of this study was to assess the relationship between loneliness and behavioral health decisions in chronic migraine patients, specifically patient ability to self-manage, and effectiveness of treatments. Methods: We conducted a cross-sectional survey among patients (n = 500) with migraine and assessed for the experience of loneliness by using the University of California, Los Angeles-Revised (UCLA-R) Three-item Loneliness Scale and the extent of migraine-related disability via the Migraine Disability Assessment (MIDAS). Furthermore, we evaluated patients for their ability to self-manage their migraines, and perceived effectiveness of treatment. Results: Nearly half of our population reported at least one measure of loneliness (230/500, 46.0%). Patients experiencing chronic migraine were statistically more likely to report feeling lonely when compared to patients with episodic migraines (P < .001). Patients who report loneliness had lower odds of feeling 'very satisfied" with their ability to self-manage their migraine symptoms (aOR = 0.34, 95% CI 0.14-0.81) and had lower odds of feeling "very satisfied" with their ability to avoid conditions that cause their headache (aOR = 0.39, 95% CI 0.16-0.91). Conclusions: Loneliness has significant effects on the illness experience of patients with chronic migraines, including their ability to self-manage or be satisfied with their current state of care. Psychosocial models of care that address loneliness among patients with chronic migraine may help improve health outcomes and management.

Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase.

Dysregulation of protein translation is a key driver for the pathogenesis of many cancers. Eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase, is a critical component of the eIF4F complex, which regulates cap-dependent protein synthesis. The flavagline class of natural products (i.e., rocaglamide A) has been shown to inhibit protein synthesis by stabilizing a translation-incompetent complex for select messenger RNAs (mRNAs) with eIF4A. Despite showing promising anticancer phenotypes, the development of flavagline derivatives as therapeutic agents has been hampered because of poor drug-like properties as well as synthetic complexity. A focused effort was undertaken utilizing a ligand-based design strategy to identify a chemotype with optimized physicochemical properties. Also, detailed mechanistic studies were undertaken to further elucidate mRNA sequence selectivity, key regulated target genes, and the associated antitumor phenotype. This work led to the design of eFT226 (Zotatifin), a compound with excellent physicochemical properties and significant antitumor activity that supports clinical development.

Spontaneous Vertebral Arteriovenous Fistula Mimicking Brachial Radiculoplexopathy.

BACKGROUND: Vertebral arteriovenous fistulas (VAVFs) are uncommon high-flow communications between a vertebral artery and surrounding venous plexus that occur spontaneously or secondary to trauma. CASE DESCRIPTION: A woman aged 57 years presented with a multiday history of rapidly progressive numbness and weakness in the left C5-C6 dermomyotomes. Her physical examination findings and subsequent electrophysiological testing were suggestive of a brachial radiculoplexopathy. Noninvasive imaging demonstrated venous congestion with multilevel compromise of the left-sided cervical foramina, and subsequent vertebral angiography confirmed a VAVF, which was treated with trapping of the involved vertebral artery segment. Her numbness and weakness progressively improved with concurrent involution of the dilated veins. CONCLUSIONS: This is a rare case of VAVF manifesting as a brachial radiculoplexopathy. Although rare, VAVF may be considered as a potential cause in patients presenting with similar symptoms.

Episodic and Chronic Migraine in Primary Care.

OBJECTIVE: To inform migraine care model development by assessing differences between patients with chronic migraine (CM) and episodic migraine (EM) in the current state of treatment, disability, patient satisfaction, and quality improvement opportunities. BACKGROUND: Efficient and focused use of scarce resources will be needed to address challenges within large populations of migraine patients. METHODS: We deployed a cross-sectional survey study of randomly selected migraine patients within a community primary care practice. RESULTS: There were 516 survey respondents (516/1804 [30%] response rate). CM patients were more likely than EM patients to report care from a neurologist (76/110 [69%] vs 229/406 [56%]; P = .0026), and higher disability according to the Migraine Disability Assessment and Headache Impact Test - 6 questionnaires (P < .0001). CM patients were less likely than EM patients to report overall satisfaction with care (16/110 [38%] vs 156/406 [66%], P = .0002), satisfaction with access to care (17/110 [33%] vs 176/406 [68%], P < .0001), and advice they needed (16/110 [31%] vs 160/406 [62%], P < .0001). Most patients with migraine had been offered triptan medications 377/516 (78%). Overall, 156/516 (31%) of individuals were currently taking any medication for migraine prevention, and 208/516 (40%) including botulinum toxin injections. CM patients were more likely to be taking preventive medication (39/110 [36%] vs 117/406 [29%], P = .0191) and report familiarity with the diagnosis of medication-overuse headache than patients with EM (80/110 [81%] vs 256/406 [69%], P = .0178). CONCLUSIONS: We observed differences between patients with chronic and EM and expected care delivery improvement opportunities for migraine patients in primary care. CM patients report higher levels of disability and less satisfaction with access to perceived needed medical advice and care. These findings support the need to further develop and study novel care models to efficiently and effectively deliver high-quality care and expertise in limited supply to a diverse migraine population.

Getting to the Heart of the Matter: A Triage Model to Improve Utilization of Cardiology Consultative Services.

OBJECTIVE: To assess the impact of a triage system of emergency department (ED) referrals for outpatient cardiology appointments. PATIENT AND METHODS: We implemented a triage system of ED referrals for outpatient cardiology appointments among patients with a cardiovascular chief complaint deemed safe to leave the ED but needing outpatient follow-up. There were 303 and 267 unique patients in the pre-triage implementation and post-triage implementation cohorts, respectively. We collected retrospective billing data to assess ED return visits, hospitalizations, cardiology outpatient visits, and cardiovascular testing. The pre-triage implementation cohort included patients with an ED visit date between January 1, 2014, and December 31, 2014. The post-triage implementation cohort included patients with an ED visit date between July 1, 2015, and June 30, 2016. RESULTS: The triage model reduced the number of ED-referred cardiovascular service appointments by 73.0% (195 of 267 patients). Additionally, the "no-show" rate for appointments decreased from 17.8% (54 of 303 patients) to 7.9% (21 of 267 patients). There was no increase in ED return visits or unplanned hospitalizations in the posttriage cohort. Finally, the triage model was not associated with an increase in resource-intensive cardiovascular testing (eg, imaging stress tests or computed tomography). CONCLUSION: Triage of ED referrals for outpatient cardiovascular service appointments reduced cardiology appointment utilization with no impact on return ED visits, hospitalizations, or cardiovascular testing.

Genetic Analysis Reveals AMPK Is Required to Support Tumor Growth in Murine Kras-Dependent Lung Cancer Models.

AMPK, a conserved sensor of low cellular energy, can either repress or promote tumor growth depending on the context. However, no studies have examined AMPK function in autochthonous genetic mouse models of epithelial cancer. Here, we examine the role of AMPK in murine KrasG12D-mediated non-small-cell lung cancer (NSCLC), a cancer type in humans that harbors frequent inactivating mutations in the LKB1 tumor suppressor-the predominant upstream activating kinase of AMPK and 12 related kinases. Unlike LKB1 deletion, AMPK deletion in KrasG12D lung tumors did not accelerate lung tumor growth. Moreover, deletion of AMPK in KrasG12D p53f/f tumors reduced lung tumor burden. We identified a critical role for AMPK in regulating lysosomal gene expression through the Tfe3 transcription factor, which was required to support NSCLC growth. Thus, AMPK supports the growth of KrasG12D-dependent lung cancer through the induction of lysosomes, highlighting an unrecognized liability of NSCLC.

Neuroimaging utilization and findings in headache outpatients: Significance of red and yellow flags.

Background Neuroimaging for headache commonly exceeds published guideline recommendations and may be overutilized. Methods We conducted a retrospective cross-sectional study of all outpatient community patients at Mayo Clinic Rochester who underwent a neuroimaging study for a headache indication in 2015. We assessed the neuroimaging utilization pattern, clinical application of red flags, and concordance with neuroimaging guidelines. Results We identified 190 outpatients who underwent 304 neuroimaging studies for headache. The median age was 46.5 years (range 18-91 years), 65% were female, and most reported no prior history of headache (n = 97, 51%). A minority of patients had prior brain imaging studies (n = 44, 23%) and neurological consultations for headache (n = 29, 15%). Few studies were ordered after consultation with a neurologist (n = 14, 7%). Seventy-seven percent of patients were documented to have a "red flag" justifying the imaging study. Abnormal neuroimaging findings were found in 3.1% of patients with warning flags (5/161); carotid dissection (n = 3) and reversible cerebral vasoconstrictive syndrome (n = 2). An estimated 35% of patients were imaged against guidelines. Conclusions The prevalence of serious causes of headache in a community practice was low despite the presence of a documented red flag symptom. Inadequate understanding or application of red flags may be contributing to recommendations to image patients against current guidelines. Interventions to reduce unnecessary neuroimaging of patients with headache need to be designed and implemented.