Effect of Perceived Level of Interaction on Faculty Evaluations of 3rd Year Medical Students.

INTRODUCTION: Several factors are known to affect the way clinical performance evaluations (CPEs) of medical students are completed by supervising physicians. We sought to explore the effect of faculty perceived "level of interaction" (LOI) on these evaluations. METHODS: Our third-year CPE requires evaluators to identify perceived LOI with each student as low, moderate, or high. We examined CPEs completed during the academic year 2018-2019 for differences in (1) clinical and professionalism ratings, (2) quality of narrative comments, (3) quantity of narrative comments, and (4) percentage of evaluation questions left unrated. RESULTS: A total of 3682 CPEs were included in the analysis. ANOVA revealed statistically significant differences between LOI and clinical ratings (p ≤ .001), with mean ratings from faculty with a high LOI significantly higher than from faculty with a moderate or low LOI (p ≤ .001). Chi-squared analysis demonstrated differences based on faculty LOI and whether questions were left unrated (p ≤ .001), quantity of narrative comments (p ≤ .001), and specificity of narrative comments (p ≤ .001). CONCLUSIONS: Faculty who perceive higher LOI were more likely to assign that student higher ratings, complete more of the clinical evaluation and were more likely to provide narrative feedback with more specific, higher-quality comments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01307-w.

The HEART Pathway Randomized Controlled Trial One-year Outcomes.

OBJECTIVE: The objective was to determine the impact of the HEART Pathway on health care utilization and safety outcomes at 1 year in patients with acute chest pain. METHODS: Adult emergency department (ED) patients with chest pain (N = 282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, ED providers used the HEART score and troponin measures (0 and 3 hours) to risk stratify patients. Usual care was based on American College of Cardiology/American Heart Association guidelines. Major adverse cardiac events (MACE-cardiac death, myocardial infarction [MI], or coronary revascularization), objective testing (stress testing or coronary angiography), and cardiac hospitalizations and ED visits were assessed at 1 year. Randomization arm outcomes were compared using Fisher's exact tests. RESULTS: A total of 282 patients were enrolled, with 141 randomized to each arm. MACE at 1 year occurred in 10.6% (30/282): 9.9% in the HEART Pathway arm (14/141; 10 MIs, four revascularizations without MI) versus 11.3% in usual care (16/141; one cardiac death, 13 MIs, two revascularizations without MI; p = 0.85). Among low-risk HEART Pathway patients, 0% (0/66) had MACE, with a negative predictive value (NPV) of 100% (95% confidence interval = 93%-100%). Objective testing through 1 year occurred in 63.1% (89/141) of HEART Pathway patients compared to 71.6% (101/141) in usual care (p = 0.16). Nonindex cardiac-related hospitalizations and ED visits occurred in 14.9% (21/141) and 21.3% (30/141) of patients in the HEART Pathway versus 10.6% (15/141) and 16.3% (23/141) in usual care (p = 0.37, p = 0.36). CONCLUSIONS: The HEART Pathway had a 100% NPV for 1-year safety outcomes (MACE) without increasing downstream hospitalizations or ED visits. Reduction in 1-year objective testing was not significant.

ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy.

Generalized arterial calcification of infancy (GACI) is a rare, life-threatening disorder caused by loss-of-function mutations in the gene encoding ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), which normally hydrolyzes extracellular ATP into AMP and pyrophosphate (PPi). The disease is characterized by extensive arterial calcification and stenosis of large- and medium-sized vessels, leading to vascular-related complications of hypertension and heart failure. There is currently no effective treatment available, but bisphosphonates - nonhydrolyzable PPi analogs - are being used off-label to reduce arterial calcification, although this has no reported impact on the hypertension and cardiac dysfunction features of GACI. In this study, the efficacy of a recombinant human ENPP1 protein therapeutic (rhENPP1) was tested in Enpp1asj-2J homozygous mice (Asj-2J or Asj-2J hom), a model previously described to show extensive mineralization in the arterial vasculature, similar to GACI patients. In a disease prevention study, Asj-2J mice treated with rhENPP1 for 3 weeks showed >95% reduction in aorta calcification. Terminal hemodynamics and echocardiography imaging of Asj-2J mice also revealed that a 6-week rhENPP1 treatment normalized elevated arterial and left ventricular pressure, which translated into significant improvements in myocardial compliance, contractility, heart workload and global cardiovascular efficiency. This study suggests that ENPP1 enzyme replacement therapy could be a more effective GACI therapeutic than bisphosphonates, treating not just the vascular calcification, but also the hypertension that eventually leads to cardiac failure in GACI patients.

RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory.

RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests. While T1- and T2-weighted images of RNaseT2 knockout rats exhibited no evidence of cystic lesions, the prefrontal cortex and hippocampal complex were enlarged in knockout animals. Diffusion-weighted imaging showed altered anisotropy and putative gray matter changes in the hippocampal complex of the RNaseT2 knockout rats. Immunohistochemistry for glial fibrillary acidic protein (GFAP) showed the presence of hippocampal neuroinflammation. Decreased levels of lysosome-associated membrane protein 2 (LAMP2) and elevated acid phosphatase and ß-N-acetylglucosaminidase (NAG) activities indicated that the RNASET2 knockout rats likely had altered lysosomal function and potential defects in autophagy. Object recognition tests confirmed that RNaseT2 knockout rats exhibited memory deficits. However, the Barnes maze, and balance beam and rotarod tests indicated there were no differences in spatial memory or motor impairments, respectively. Overall, patients with RNASET2 deficiency exhibited a more severe neurodegeneration phenotype than was observed in the RNaseT2 knockout rats. However, the vulnerability of the knockout rat hippocampus as evidenced by neuroinflammation, altered lysosomal function and cognitive defects indicates that this is still a useful in vivo model to study RNASET2 function.

Validation of the No Objective Testing Rule and Comparison to the HEART Pathway.

BACKGROUND: The no objective testing rule (NOTR) is a decision aid designed to safely identify emergency department (ED) patients with chest pain who do not require objective testing for coronary artery disease. OBJECTIVES: The objective was to validate the NOTR in a cohort of U.S. ED patients with acute chest pain and compare its performance to the HEART Pathway. METHODS: A secondary analysis of 282 participants enrolled in the HEART Pathway randomized controlled trial was conducted. Each patient was classified as low risk or at risk by the NOTR. Sensitivity for major adverse cardiac events (MACE) at 30 days was calculated in the entire study population. NOTR and HEART Pathways were compared among patients randomized to the HEART Pathway in the parent trial using McNemar's test and the net reclassification improvement (NRI). RESULTS: Major adverse cardiac events occurred in 22/282 (7.8%) participants, including no deaths, 16/282 (5.6%) with myocardial infarction (MI), and 6/282 (2.1%) with coronary revascularization without MI. NOTR was 100% (95% confidence interval [CI] = 84.6%-100%) sensitive for MACE and identified 78/282 patients (27.7%, 95% = CI 22.5-33.3%) as low risk. In the HEART Pathway arm (n = 141), both NOTR and HEART Pathway identified all patients with MACE as at risk. Compared to NOTR, the HEART Pathway was able to correctly reclassify 27 patients without MACE as low risk, yielding a NRI of 20.8% (95% CI = 11.3%-30.2%). CONCLUSIONS: Within a U.S. cohort of ED patients with chest pain, the NOTR and HEART Pathway were 100% sensitive for MACE at 30 days. However, the HEART Pathway identified more patients suitable for early discharge than the NOTR.

Erratum: This Article Corrects: "Trends in NRMP Data from 2007-2014 for U.S. Seniors Matching into Emergency Medicine".

[This corrects the article on p. 105 in vol. 18, PMID: 28116018.].

Trends in NRMP Data from 2007-2014 for U.S. Seniors Matching into Emergency Medicine.

INTRODUCTION: Since 1978, the National Residency Matching Program (NRMP) has published data demonstrating characteristics of applicants who have matched into their preferred specialty in the NRMP main residency match. These data have been published approximately every two years. There is limited information about trends within these published data for students matching into emergency medicine (EM). Our objective was to investigate and describe trends in NRMP data to include the following: the ratio of applicants to available EM positions; United State Medical Licensing Examination (USMLE) Step 1 and Step 2 scores (compared to the national means); number of programs ranked; and Alpha Omega Alpha Honor Medical Society (AOA) membership among U.S. seniors matching into EM. METHODS: This was a retrospective observational review of NRMP data published between 2007 and 2016. We analyzed the data using analysis of variance (ANOVA) or Kruskal-Wallis testing, and Fischer's exact or chi-squared testing, as appropriate to determine statistical significance. RESULTS: The ratio of applicants to available EM positions remained essentially stable from 2007 to 2014 but did increase slightly in 2016. We observed a net upward trend in overall Step 1 and Step 2 scores for EM applicants. However, this did not outpace the national trend increase in Step 1 and 2 scores overall. There was an increase in the mean number of programs ranked by EM applicants over the years studied from 7.8 (SD4.2) to 9.2 (SD5.0, p<0.001), driven predominantly by the cohort of U.S. students successful in the match. Among time intervals, there was a difference in the number of EM applicants with AOA membership (p=0.043) due to a drop in the number of AOA students in 2011. No sustained statistical trend in AOA membership was identified over the seven-year period studied. CONCLUSION: NRMP data demonstrate trends among EM applicants that are similar to national trends in other specialties for USMLE board scores, and a modest increase in number of programs ranked. AOA membership was largely stable. EM does not appear to have become more competitive relative to other specialties or previous years in these categories.

Use of the HEART Pathway with high sensitivity cardiac troponins: A secondary analysis.

OBJECTIVES: The HEART Pathway combines a decision aid and serial contemporary cardiac troponin I (cTnI) measures to achieve >99% sensitivity for major adverse cardiac events (MACE) at 30days and early discharge rates >20%. However, the impact of integrating high-sensitivity troponin (hs-cTn) measures into the HEART Pathway has yet to be determined. In this analysis we compare test characteristics of the HEART Pathway using hs-cTnI, hs-cTnT, or cTnI. DESIGN & METHODS: A secondary analysis of participants enrolled in the HEART Pathway RCT was conducted. Each patient was risk stratified by the cTn-HEART Pathway (Siemens TnI-Ultra at 0- and 3-h) and a hs-cTn-HEART Pathway using hs-cTnI (Abbott) or hs-cTnT (Roche) at 3-h. The early discharge rate, sensitivity, specificity, and negative predictive value (NPV) for MACE (death, myocardial infarction, or coronary revascularization) at 30days were calculated. RESULTS: hs-cTnI measures were available on 133 patients. MACE occurred in 11/133 (8%) of these patients. Test characteristics for the HEART Pathway using serial cTnI vs 3hour hs-cTnI were the same: sensitivity (100%, 95%CI: 72-100%), specificity (49%, 95%CI: 40-58%), NPV (100%, 95%CI: 94-100%), and early discharge rate (45%, 95%CI: 37-54%). The HEART Pathway using hs-cTnT missed one MACE event (myocardial infarction): sensitivity (91%, 95%CI: 59-100%), specificity (48%, 95%CI: 39-57%), NPV (98%, 95%CI: 91-100%), and early discharge rate (45%, 95%CI: 37-54%). CONCLUSIONS: There was no difference in the test characteristics of the HEART Pathway whether using cTnI or hs-cTnI, with both achieving 100% sensitivity and NPV. Use of hs-cTnT with the HEART Pathway was associated with one missed MACE.

Cost analysis of the History, ECG, Age, Risk factors, and initial Troponin (HEART) Pathway randomized control trial.

INTRODUCTION: The HEART Pathway is a diagnostic protocol designed to identify low-risk patients presenting to the emergency department with chest pain that are safe for early discharge. This protocol has been shown to significantly decrease health care resource utilization compared with usual care. However, the impact of the HEART Pathway on the cost of care has yet to be reported. METHODS AND RESULTS: We performed a cost analysis of patients enrolled in the HEART Pathway trial, which randomized participants to either usual care or the HEART Pathway protocol. For low-risk patients, the HEART Pathway recommended early discharge from the emergency department without further testing. We compared index visit cost, cost at 30 days, and cardiac-related health care cost at 30 days between the 2 treatment arms. Costs for each patient included facility and professional costs. Cost at 30 days included total inpatient and outpatient costs, including the index encounter, regardless of etiology. Cardiac-related health care cost at 30 days included the index encounter and costs adjudicated to be cardiac-related within that period. Two hundred seventy of the 282 patients enrolled in the trial had cost data available for analysis. There was a significant reduction in cost for the HEART Pathway group at 30 days (median cost savings of $216 per individual), which was most evident in low-risk (Thrombolysis In Myocardial Infarction score of 0-1) patients (median savings of $253 per patient) and driven primarily by lower cardiac diagnostic costs in the HEART Pathway group. CONCLUSIONS: Using the HEART Pathway as a decision aid for patients with undifferentiated chest pain resulted in significant cost savings.

Chest Pain Risk Stratification: A Comparison of the 2-Hour Accelerated Diagnostic Protocol (ADAPT) and the HEART Pathway.

BACKGROUND: The 2-hour accelerated diagnostic protocol (ADAPT) and the history electrocardiogram age risk factors troponin (HEART) Pathway are decision aids designed to identify Emergency Department (ED) patients with chest pain who are safe for early discharge. Both have demonstrated high sensitivity (>99%) for major adverse cardiac events (MACE) at 30 days and early discharge rates ≥20%. The objective of this study is to compare the sensitivity and early discharge rates of the ADAPT and HEART Pathway decision aids in a cohort of ED patients with acute chest pain. METHODS: A secondary analysis of participants enrolled and randomized to the HEART Pathway arm of the HEART pathway randomized controlled trial was conducted. Each patient was prospectively classified as low risk (suitable for early discharge) or high risk by ADAPT and the HEART Pathway. Sensitivity for MACE at 30 days and the number of patients identified as low-risk were calculated for each decision aid. Decision aid performance was compared using McNemar's test. RESULTS: MACE occurred in 8 of 141 (5.7%); there were no deaths, 7 patients had myocardial infarction, and 1 patient had coronary revascularization without myocardial infarction. ADAPT and the HEART pathway identified all patients with MACE as high risk; sensitivity for MACE of 100% [95% confidence interval (CI): 63-100%]. ADAPT identified 34 of 141 patients (24%; 95% CI: 17-32%) as low-risk, whereas the Heart pathway identified 66 of 141 patients (47%, 95% CI: 38-55%) as low risk (P < 0.001). CONCLUSIONS: Within a cohort of ED patients with acute chest pain, ADAPT and the HEART pathway had high sensitivity for MACE. The HEART pathway outperformed ADAPT by correctly identifying more patients as low risk and safe for early discharge.

Adherence to an Accelerated Diagnostic Protocol for Chest Pain: Secondary Analysis of the HEART Pathway Randomized Trial.

OBJECTIVES: Accelerated diagnostic protocols (ADPs), such as the HEART Pathway, are gaining popularity in emergency departments (EDs) as tools used to risk stratify patients with acute chest pain. However, provider nonadherence may threaten the safety and effectiveness of ADPs. The objective of this study was to determine the frequency and impact of ADP nonadherence. METHODS: A secondary analysis of participants enrolled in the HEART Pathway RCT was conducted. This trial enrolled 282 adult ED patients with symptoms concerning for acute coronary syndrome without ST-elevation on electrocardiogram. Patients randomized to the HEART Pathway (N = 141) were included in this analysis. Outcomes included index visit disposition, nonadherence, and major adverse cardiac events (MACEs) at 30 days. MACE was defined as death, myocardial infarction, or revascularization. Nonadherence was defined as: 1) undertesting-discharging a high-risk patient from the ED without objective testing (stress testing or coronary angiography) or 2) overtesting-admitting or obtaining objective testing on a low-risk patient. RESULTS: Nonadherence to the HEART Pathway occurred in 28 of 141 patients (20%, 95% confidence interval [CI] = 14% to 27%). Overtesting occurred in 19 of 141 patients (13.5%, 95% CI = 8% to 19%) and undertesting in nine of 141 patients (6%, 95% CI = 3% to 12%). None of these 28 patients suffered MACE. The net effect of nonadherence was 10 additional admissions among patients identified as low-risk and appropriate for early discharge (absolute decrease in discharge rate of 7%, 95% CI = 3% to 13%). CONCLUSIONS: Real-time use of the HEART Pathway resulted in a nonadherence rate of 20%, mostly due to overtesting. None of these patients had MACE within 30 days. Nonadherence decreased the discharge rate, attenuating the HEART Pathway's impact on health care use.

Combined Versus Detailed Evaluation Components in Medical Student Global Rating Indexes.

INTRODUCTION: To determine if there is any correlation between any of the 10 individual components of a global rating index on an emergency medicine (EM) student clerkship evaluation form. If there is correlation, to determine if a weighted average of highly correlated components loses predictive value for the final clerkship grade. METHODS: This study reviewed medical student evaluations collected over two years of a required fourth-year rotation in EM. Evaluation cards, comprised of a detailed 10-part evaluation, were completed after each shift. We used a correlation matrix between evaluation category average scores, using Spearman's rho, to determine if there was any correlation of the grades between any of the 10 items on the evaluation form. RESULTS: A total of 233 students completed the rotation over the two-year period of the study. There were strong correlations (>0.80) between assessment components of medical knowledge, history taking, physical exam, and differential diagnosis. There were also strong correlations between assessment components of team rapport, patient rapport, and motivation. When these highly correlated were combined to produce a four-component model, linear regression demonstrated similar predictive power in terms of final clerkship grade (R(2)=0.71, CI95=0.65-0.77 and R(2)=0.69, CI95=0.63-0.76 for the full and reduced models respectively). CONCLUSION: This study revealed that several components of the evaluation card had a high degree of correlation. Combining the correlated items, a reduced model containing four items (clinical skills, interpersonal skills, procedural skills, and documentation) was as predictive of the student's clinical grade as the full 10-item evaluation. Clerkship directors should be aware of the performance of their individual global rating scales when assessing medical student performance, especially if attempting to measure greater than four components.

Performance of the EDACS-accelerated Diagnostic Pathway in a Cohort of US Patients with Acute Chest Pain.

BACKGROUND: The Emergency Department Assessment of Chest pain Score-Accelerated Diagnostic Protocol (EDACS-ADP) is a decision aid designed to safely identify emergency department (ED) patients with chest pain for early discharge. Derivation and validation studies in Australasia have demonstrated high sensitivity (99%-100%) for major adverse cardiac events (MACE). OBJECTIVES: To validate the EDACS-ADP in a cohort of US ED patients with symptoms suspicious for acute coronary syndrome (ACS). METHODS: A secondary analysis of participants enrolled in the HEART Pathway Randomized Controlled Trial was conducted. This single-site trial enrolled 282 ED patients≥21 years old with symptoms concerning for ACS, inclusive of all cardiac risk levels. Each patient was classified as low risk or at risk by the EDACS-ADP based on EDACS, electrocardiogram, and serial troponins. Potential early discharge rate and sensitivity for MACE at 30 days, defined as cardiac death, myocardial infarction (MI), or coronary revascularization were calculated. RESULTS: MACE occurred in 17/282 (6.0%) participants, including no deaths, 16/282 (5.6%) with MI, and 1/282 (0.4%) with coronary revascularization without MI. The EDACS-ADP identified 188/282 patients [66.7%, 95% confidence interval (CI): 60.8%-72.1%] as low risk. Of these, 2/188 (1.1%, 95% CI: 0.1%-3.9%) had MACE at 30 days. EDACS-ADP was 88.2% (95% CI: 63.6%-98.5%) sensitive for MACE, identifying 15/17 patients. Of the 2 patients identified as low risk with MACE, 1 had MI and 1 had coronary revascularization without MI. CONCLUSIONS: Within a US cohort of ED patients with symptoms concerning for ACS, sensitivity for MACE was 88.2%. We are unable to validate the EDACS-ADP as sufficiently sensitive for clinical use.

North Carolina College of Emergency Physicians' Guidance Document on Emergency Medical Services.

The North Carolina College of Emergency Physicians (NCCEP) Emergency Medical Services (EMS) Committee uses an evidence-based approach in writing its protocols and procedures. The most recent revision of the NCCEP document, which was started in late 2010, lasted for more than 1 year and utilized committee members from across the state. Four meetings were held at locations across North Carolina. In addition, 2 surveys were sent to get input from EMS providers. Since 2010, the document has been updated on an ongoing basis, aligning it with the latest evidence-based medicine.

The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge.

BACKGROUND: The HEART Pathway is a decision aid designed to identify emergency department patients with acute chest pain for early discharge. No randomized trials have compared the HEART Pathway with usual care. METHODS AND RESULTS: Adult emergency department patients with symptoms related to acute coronary syndrome without ST-elevation on ECG (n=282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, emergency department providers used the HEART score, a validated decision aid, and troponin measures at 0 and 3 hours to identify patients for early discharge. Usual care was based on American College of Cardiology/American Heart Association guidelines. The primary outcome, objective cardiac testing (stress testing or angiography), and secondary outcomes, index length of stay, early discharge, and major adverse cardiac events (death, myocardial infarction, or coronary revascularization), were assessed at 30 days by phone interview and record review. Participants had a mean age of 53 years, 16% had previous myocardial infarction, and 6% (95% confidence interval, 3.6%-9.5%) had major adverse cardiac events within 30 days of randomization. Compared with usual care, use of the HEART Pathway decreased objective cardiac testing at 30 days by 12.1% (68.8% versus 56.7%; P=0.048) and length of stay by 12 hours (9.9 versus 21.9 hours; P=0.013) and increased early discharges by 21.3% (39.7% versus 18.4%; P<0.001). No patients identified for early discharge had major adverse cardiac events within 30 days. CONCLUSIONS: The HEART Pathway reduces objective cardiac testing during 30 days, shortens length of stay, and increases early discharges. These important efficiency gains occurred without any patients identified for early discharge suffering MACE at 30 days. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01665521.

Consensus development of a pediatric emergency medicine clerkship curriculum.

INTRODUCTION: As emergency medicine (EM) has become a more prominent feature in the clinical years of medical school training, national EM clerkship curricula have been published to address the need to standardize students' experiences in the field. However, current national student curricula in EM do not include core pediatric emergency medicine (PEM) concepts. METHODS: A workgroup was formed by the Clerkship Directors in Emergency Medicine and the Pediatric Interest Group of the Society of Academic Emergency Medicine to develop a consensus on the content to be covered in EM and PEM student courses. RESULTS: The consensus is presented with the goal of outlining principles of pediatric emergency care and prioritizing students' exposure to the most common and life-threatening illnesses and injuries. CONCLUSION: This consensus curriculum can serve as a guide to directors of PEM and EM courses to optimize PEM knowledge and skills education.

NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans.

In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs) stabilize neuronal structure and restrict compensatory sprouting following injury. The Nogo receptor family members NgR1 and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of proteoglycans and participate in CSPG inhibition in cultured neurons. Nogo receptor triple mutants (Ngr1(-/-); Ngr2(-/-); Ngr3(-/-); which are also known as Rtn4r, Rtn4rl2 and Rtn4rl1, respectively), but not single mutants, showed enhanced axonal regeneration following retro-orbital optic nerve crush injury. The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2 (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by simultaneous ablation of Rptpσ (also known as Ptprs), a known CSPG receptor. Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that there is functional redundancy among CSPG receptors, and provide evidence for shared mechanisms of MAI and CSPG inhibition.