Five Key Articles on Curriculum Development for Graduate Medical Educators.

Background Curriculum development is an essential domain for medical educators, yet specific training in this area is inconsistent. With competing demands for educators' time, a succinct resource for best practice is needed. Objective To create a curated list of the most essential articles on curriculum development to guide education scholars in graduate medical education. Methods We used a modified Delphi method, a systematic consensus strategy to increase content validity, to achieve consensus on the most essential curriculum development articles. We convened a panel of 8 experts from the United States in curricular development, with diverse career stages, institutions, gender, and specialty. We conducted a literature search across PubMed and Google Scholar with keywords, such as "curriculum development" and "curricular design," to identify relevant articles focusing on a general overview or approach to curriculum development. Articles were reviewed across 3 iterative Delphi rounds to narrow down those that should be included in a list of the most essential articles on curriculum development. Results Our literature search yielded 1708 articles, 90 of which were selected for full-text review, and 26 of which were identified as appropriate for the modified Delphi process. We had a 100% response rate for each Delphi round. The panelists narrowed the articles to a final list of 5 articles, with 4 focusing on the development of new curriculum and 1 on curriculum renewal. Conclusions We developed a curated list of 5 essential articles on curriculum development that is broadly applicable to graduate medical educators.

Development of a single mobile phase for LC-IM-MS-based discovery lipidomics and metabolic phenotyping: Application to methapyrilene hepatotoxicity in the rat.

The untargeted global profiling of endogenous metabolites and lipids has the potential to increase knowledge and understanding in many areas of biology. LC-MS/MS is a key technology for such analyses however, several different LC methodologies, using different mobile phase compositions, are required to cover the diversity in polarity and analyte structure encountered in biological samples. Most notably many lipid screening methods make use of isopropanol (IPA) as a major component of mobile phases employed for comprehensive lipidomic profiling. In order to increase laboratory efficiency, and minimize opportunities for errors, a suite of methods, based on a single acetonitrile (ACN)-aqueous buffer mobile phase combination, has been developed. This mobile phase can be used for hydrophobic interaction liquid chromatography on an amide stationary phase (for polar analytes), reversed-phase (RP) LC analysis on a C8 stationary phase (for moderately polar-non-polar compounds) and RPLC using a CSH phenyl-hexyl bonded column (for lipids). All of these sub 10 minute separations had good throughput and reproducibility with CV's of analyte response <25 % whilst eliminating the need for complex mobile phase preparation and the use of IPA as an organic modifier for lipidomics. Advantages of removing IPA and replacing it with the ACN-based method were a 58 % increase in peak capacity for lipids, with improved resolution for the di- and triglycerides and cholesterol esters compared to current methods. Compared to the IPA-containing solvent system the ACN-based mobile phase also resulted in a 61 % increase in lipid feature detection. The utility of this "universal" mobile phase approach was demonstrated by its application to a rat toxicology study investigating the consequences of methapyrilene administration through on the endogenous metabolite profiles of plasma and urine. Methapyrilene and its metabolites were also profiled in these samples.

Hypertensive Disorders of Pregnancy.

Hypertensive disorders in pregnancy are a leading cause of global maternal and fetal morbidity. The four hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and chronic hypertension with superimposed preeclampsia. A careful history, review of systems, physical examination, and laboratory analysis can help differentiate these disorders and quantify the severity of the disease, which holds important implications for disease management. This article reviews the different types of disorders of hypertension in pregnancy and how to diagnose and manage these patients, with special attention paid to any recent changes made to this management algorithm.

Leptomeningeal Carcinomatosis: A Rare Complication of Metastatic Gastric Cancer.

Leptomeningeal disease, also known as leptomeningeal carcinomatosis, occurs when cancer metastasizes to the meninges. This rare complication is associated with a poor prognosis. It is most commonly seen in patients with metastatic breast cancer, lung cancer, and melanoma. However, it is extremely rare in patients with metastatic gastric cancer. A 64-year-old female with poorly differentiated gastric adenocarcinoma metastatic to the peritoneum developed new neurological symptoms twelve months after initiating palliative chemotherapy. Her uptrending tumor markers, brain magnetic resonance imaging (MRI) findings, and lumbar puncture results were consistent with leptomeningeal disease. The patient was started on treatment with intrathecal methotrexate (IT MTX), which resulted in significant improvement in her neurological symptoms. Leptomeningeal disease in gastric cancer has limited treatment options due to poor blood-brain barrier penetration. IT MTX is a potentially effective treatment for patients with leptomeningeal disease from gastric cancer.

Radiology Education Among Emergency Medicine Residencies: A National Needs Assessment.

INTRODUCTION: Radiology training is an important component of emergency medicine (EM) education, but its delivery has been variable. Program directors have reported a lack of radiology skills in incoming interns. A needs assessment is a crucial first step toward improving radiology education among EM residencies. Our objective was to explore the current state of radiology education in EM residency programs. METHODS: This was a cross-sectional survey study of all Accreditation Council for Graduate Medical Education-accredited EM programs in the United States. Program leadership completed an online survey consisting of multiple choice, Likert scale, and free-response items. We calculated and reported descriptive statistics. RESULTS: Of eligible EM programs, 142/252 (56%) completed the survey including 105 postgraduate year (PGY) 1-3 and 36 PGY 1-4 programs. One respondent opted out of answering demographic questions. 23/141 (16%) were from the Western region, 29/141 (21%) were from the North Central region, 14/141 (10%) were from the South-Central region, 28/141 (20%) were from the Southeast region, and 47/141 (33%) were from the Northeast region. A total of 88/142 (62%) of responding programs did not have formal radiology instruction. Of the education that is provided, 127/142 (89%) provide it via didactics/lectures and 115/142 (81%) rely on instruction during clinical shifts. Only 51/142 (36%) provide asynchronous opportunities, and 23/142 (16%) have a dedicated radiology rotation. The majority of respondents reported spending 0-2 hours per month on radiology instruction (108/142; 76%); 95/141 (67%) reported that EM faculty "often" or "always" provide radiology instruction; 134/142 (95%), felt that it was "extremely" or "very important" for ED providers to be able to independently interpret radiograph results; and 129/142 (90.84%) either "sometimes" or "always" rely on their independent radiograph interpretations to make clinical decisions. The radiology studies identified as most important to be able to independently interpret were radiographs obtained for lines/tubes, chest radiographs, and radiographs obtained for musculoskeletal-related complaints. CONCLUSION: A minority of EM residency programs have formal instruction in radiology despite the majority of responding program leadership believing that these are important skills. The most important curricular areas were identified. These results may inform the development of formal radiology curricula in EM graduate medical education.

Emergency Medicine Residents With Higher Levels of Debt Are Less Likely to Choose Academic Jobs, but There Is a Difference by Gender.

OBJECTIVES: We sought to answer the following question: Does educational debt burden affect decisions by emergency medicine residents about whether to pursue academic versus community medicine jobs directly after residency? METHODS: In this observational study, graduating residents across eight emergency medicine residencies were surveyed concurrent with their in-training examinations over 2 years to assess levels of educational debt and demographic information. Job types chosen by residents upon graduation were obtained from their respective program directors. The impact of debt on type of job chosen was assessed through multivariate logistic regression with demographic controls and program fixed effects, with additional analysis of observed differences by gender. RESULTS: Information was collected on 159 residents from 14 graduating classes across eight programs representing six different states. Residents with higher levels of debt had lower odds of choosing an academic fellowship or faculty position upon graduation (odds ratio [OR] = 0.77, confidence interval [CI] = 0.60 to 0.98). On further analysis, higher debt predicted lower odds of choosing an academic position for men (OR = 0.59, CI = 0.41 to 0.82), but not for women (OR = 1.05, CI = 0.63 to 1.76). CONCLUSIONS: When male emergency medicine residents have higher levels of debt, they are significantly less likely to pursue an academic fellowship or faculty position after residency. This may not be the case for female residents. Results may reflect differences in the factors that affect men and women's decisions about jobs after residency, which merits further study.

A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry: Application to the characterisation of metabolites in rat urine.

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.

Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4.

PURPOSE: Patients with human EGFR2-positive (HER2+) breast cancer have a high incidence of brain metastases, and trastuzumab emtansine (T-DM1) is often employed. Stereotactic radiosurgery (SRS) is frequently utilized, and case series report increased toxicity with combination SRS and T-DM1. We provide an update of our experience of T-DM1 and SRS evaluating risk of clinically significant radionecrosis (CSRN) and propose a mechanism for this toxicity. EXPERIMENTAL DESIGN: Patients with breast cancer who were ≤45 years regardless of HER2 status or had HER2+ disease regardless of age and underwent SRS for brain metastases were included. Rates of CSRN, SRS data, and details of T-DM1 administration were recorded. Proliferation and astrocytic swelling studies were performed to elucidate mechanisms of toxicity. RESULTS: A total of 45 patients were identified; 66.7% were HER2+, and 60.0% were ≤ 45 years old. Of the entire cohort, 10 patients (22.2%) developed CSRN, 9 of whom received T-DM1. CSRN was observed in 39.1% of patients who received T-DM1 versus 4.5% of patients who did not. Receipt of T-DM1 was associated with a 13.5-fold (P = 0.02) increase in CSRN. Mechanistically, T-DM1 targeted reactive astrocytes and increased radiation-induced cytotoxicity and astrocytic swelling via upregulation of Aquaporin-4 (Aqp4). CONCLUSIONS: The strong correlation between development of CSRN after SRS and T-DM1 warrants prospective studies controlling for variations in timing of T-DM1 and radiation dosing to further stratify risk of CSRN and mitigate toxicity. Until such studies are completed, we advise caution in the combination of SRS and T-DM1.

Simulation-based Remediation in Emergency Medicine Residency Training: A Consensus Study.

INTRODUCTION: Resident remediation is a pressing topic in emergency medicine (EM) training programs. Simulation has become a prominent educational tool in EM training and been recommended for identification of learning gaps and resident remediation. Despite the ubiquitous need for formalized remediation, there is a dearth of literature regarding best practices for simulation-based remediation (SBR). METHODS: We conducted a literature search on SBR practices using the terms "simulation," "remediation," and "simulation based remediation." We identified relevant themes and used them to develop an open-ended questionnaire that was distributed to EM programs with experience in SBR. Thematic analysis was performed on all subsequent responses and used to develop survey instruments, which were then used in a modified two-round Delphi panel to derive a set of consensus statements on the use of SBR from an aggregate of 41 experts in simulation and remediation in EM. RESULTS: Faculty representing 30 programs across North America composed the consensus group with 66% of participants identifying themselves as simulation faculty, 32% as program directors, and 2% as core faculty. The results from our study highlight a strong agreement across many areas of SBR in EM training. SBR is appropriate for a range of deficits, including procedural, medical knowledge application, clinical reasoning/decision-making, communication, teamwork, and crisis resource management. Simulation can be used both diagnostically and therapeutically in remediation, although SBR should be part of a larger remediation plan constructed by the residency leadership team or a faculty expert in remediation, and not the only component. Although summative assessment can have a role in SBR, it needs to be very clearly delineated and transparent to everyone involved. CONCLUSION: Simulation may be used for remediation purposes for certain specific kinds of competencies as long as it is carried out in a transparent manner to all those involved.

Are Hyoid Bone and Tongue the Risk Factors Contributing to Postoperative Relapse for Mandibular Prognathism?

OBJECTIVE: The purpose of this study was to investigate postoperative stability and the correlation between hyoid, tongue, and mandible position following surgery for mandibular prognathism. MATERIALS AND METHODS: Thirty-seven patients, treated for mandibular prognathism using intraoral vertical ramus osteotomy (IVRO), were evaluated cephalometrically. A set of four standardized lateral cephalograms were obtained from each subject preoperatively (T1), immediately postoperatively (T2), six weeks to three months postoperatively (T3), and more than one year postoperatively (T4). The Student t-tests, the Pearson correlation coefficient, and the multiple linear regression were used for statistical analysis. RESULTS: Immediately after surgery, menton (Me) setback was 12.8 mm, hyoid (H) setback was 4.9 mm, and vallecula epiglottica (V) setback was 5.8 mm. The postoperative stability significantly correlated (r = -0.512, p < 0.01) with the amount of setback. The hyoid bone and tongue did not have significant effects on postoperative stability. Multiple linear regression model (R(2) = 0.2658, p < 0.05) showed predictability: Horizontal Relapse Me (T4-T2) = -6.406 - 0.488Me (T2-T1) + 0.069H (T2-T1) - 0.0619V (T2-T1). CONCLUSION: Mandibular setback surgery may push the hyoid and tongue significantly backward, but this did not correlate with mandibular relapse. Postoperative stability significantly correlated with the amount of mandibular setback.

Unbiased Metabolomic Investigation of Alzheimer's Disease Brain Points to Dysregulation of Mitochondrial Aspartate Metabolism.

Alzheimer's disease (AD) is the most common cause of adult dementia. Yet the complete set of molecular changes accompanying this inexorable, neurodegenerative disease remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) and age-matched controls (n = 19), revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, we incorporated the novel molecular information into the known biochemical pathways and compared it with the results of a metabolomics meta-analysis of previously published AD research. We found six metabolic pathways of the central metabolism as well as glycerophospholipid metabolism predominantly altered in AD brains. Using targeted metabolomics approaches and MS imaging, we confirmed a marked dysregulation of mitochondrial aspartate metabolism. The altered metabolic pathways were further integrated with clinical data, showing various degrees of correlation with parameters of dementia and AD pathology. Our study highlights specific, altered biochemical pathways in the brains of individuals with AD compared with those of control subjects, emphasizing dysregulation of mitochondrial aspartate metabolism and supporting future venues of investigation.

Intraoperative Hemorrhage and Postoperative Sequelae after Intraoral Vertical Ramus Osteotomy to Treat Mandibular Prognathism.

Objective. To investigate the factors affecting intraoperative hemorrhage and postoperative sequelae after orthognathic surgery. Materials and Methods. Eighty patients with mandibular prognathism underwent surgical mandibular setback with intraoral vertical ramus osteotomy (IVRO). The correlation between the blood loss volume and postoperative VAS with the gender, age, and operating time was assessed using the t-test and Spearman rank correlation coefficient. The correlation between the magnitude of mandibular setback with the presence of TMJ clicking symptoms and lip sensation was also assessed. Results. The mean operating time and blood loss volume for men and women were 249.52 min and 229.39 min, and 104.03 mL and 86.12 mL, respectively. The mean VAS in men and women was 3.21 and 2.93, and 1.79 and 1.32 on the first and second postoperative days. There is no gender difference in the operating time, blood loss, VAS, TMJ symptoms, and lip numbness. The magnitude of mandibular setback was not correlated with immediate and long-term postoperative lip numbness. Conclusion. There are no gender differences in the intraoperative hemorrhage and postoperative sequelae (pain, lip numbness, and TMJ symptoms). In addition, neither symptom was significantly correlated with the amount of mandibular setback.

Correlation Between Blood Loss and Patient-Related Factors in the Bilateral Parasymphyseal Osteotomy.

The aim of this study was to determine the correlation between pre- and postsurgical loss of blood and blood components among patients undergoing treatment of facial deformities by bilateral parasymphyseal osteotomy (BPsO).The pre- and postoperative values of blood components were determined in 30 facial deformity patients who underwent orthognathic surgery by hypotensive anesthesia. Correlations among the blood loss, sex, age, operation time, and reduced values of blood components were assessed by a correlation matrix. The mean blood loss and operation time were 437.5 (± 52.5) mL and 355.8 (± 209.42) minutes, respectively. Two patients included in this study had required blood transfusion. The mean reduced red blood cell (× 10/µL), hemoglobin (g/dL), and hematocrit (%) were -1.02, -2.98, and -9.18, respectively. There was no significant correlation between blood loss and other related factors (eg, age, operation time, and reduced blood components). All patients, however, showed significantly lower values of blood components after surgery. In conclusion, no significant factor was associated with blood loss and reduced blood components among patients undergoing BPsO. Furthermore, hypotensive anesthesia is a well-accepted method to reduce blood loss during orthognathic surgery.

Correction of precursor and product ion relative abundances in order to standardize CID spectra and improve Ecom50 accuracy for non-targeted metabolomics.

Quantitative biases in the abundance of precursor and product ions due to mass discrimination in RF-only ion guides results in inaccurate collision induced dissociation (CID) spectra. We evaluated the effects of collision cell RF voltage and collision energy on CID spectra using ten singly protonated compounds (46-854 Da) in an orthogonal acceleration time-of-flight mass spectrometer. The relative ion transfer efficiency, i.e. the relative amount of ions transferred through the ion guide at any particular RF voltage was shown to be dependent on the ion's m/z. We developed an algorithm to correct for the mass discriminating effects of RF voltage on CID spectra. The algorithm was tested for both precursor and product ions at multiple RF voltages and collision energies in order to ensure reliability. Our results suggest that compounds that generate major product ions with m/z values <150 have peak intensities that deviate substantially from their actual abundance. This has implications for small molecule metabolomics research, particularly for studies that rely on CID spectra matching methods for structure identification.

Correlation between the Pharyngeal Airway Space and Head Posture after Surgery for Mandibular Prognathism.

PURPOSE: The aim of this study was to determine the correlation between the pharyngeal airway space and head posture after mandibular setback surgery for mandibular prognathism. MATERIALS AND METHODS: Serial lateral cephalograms of 37 patients with mandibular prognathism who underwent intraoral vertical ramus osteotomy (IVRO) were evaluated before (T1) and immediately (T2), between 6 weeks and 3 months (T3), and more than 1 year (T4) after surgery. Paired t-tests and Pearson's correlation analysis were used to evaluate the postoperative changes in all cephalometric parameters, including the mandible, hyoid, head posture (craniocervical angle), and pharyngeal airway space. RESULTS: The mandible and hyoid were set back by 12.8 mm and 4.9 mm, respectively, at T2. Furthermore, the hyoid showed significant inferior movement of 10.7 mm, with an 8 mm increase in the tongue depth. The upper oropharyngeal airway (UOP) shortened by 4.1 mm, the lower oropharyngeal airway (LOP) by 1.7 mm, and the laryngopharyngeal airway by 2 mm. The craniocervical angle showed a significant increase of 2.8°. UOP and LOP showed a significant correlation with the craniocervical angle at T2 and T4. CONCLUSIONS: Our findings conclude that the oropharyngeal airway space is significantly decreased and correlated with a change in the head posture after mandibular setback surgery.

Tetrahydrobiopterin and alkylglycerol monooxygenase substantially alter the murine macrophage lipidome.

Tetrahydrobiopterin is a cofactor synthesized from GTP with well-known roles in enzymatic nitric oxide synthesis and aromatic amino acid hydroxylation. It is used to treat mild forms of phenylketonuria. Less is known about the role of tetrahydrobiopterin in lipid metabolism, although it is essential for irreversible ether lipid cleavage by alkylglycerol monooxygenase. Here we found intracellular alkylglycerol monooxygenase activity to be an important regulator of alkylglycerol metabolism in intact murine RAW264.7 macrophage-like cells. Alkylglycerol monooxygenase was expressed and active also in primary mouse bone marrow-derived monocytes and "alternatively activated" M2 macrophages obtained by interleukin 4 treatment, but almost missing in M1 macrophages obtained by IFN-γ and lipopolysaccharide treatment. The cellular lipidome of RAW264.7 was markedly changed in a parallel way by modulation of alkylglycerol monooxygenase expression and of tetrahydrobiopterin biosynthesis affecting not only various ether lipid species upstream of alkylglycerol monooxygenase but also other more complex lipids including glycosylated ceramides and cardiolipins, which have no direct connection to ether lipid pathways. Alkylglycerol monooxygenase activity manipulation modulated the IFN-γ/lipopolysaccharide-induced expression of inducible nitric oxide synthase, interleukin-1ß, and interleukin 1 receptor antagonist but not transforming growth factor ß1, suggesting that alkylglycerol monooxygenase activity affects IFN-γ/lipopolysaccharide signaling. Our results demonstrate a central role of tetrahydrobiopterin and alkylglycerol monooxygenase in ether lipid metabolism of murine macrophages and reveal that alteration of alkylglycerol monooxygenase activity has a profound impact on the lipidome also beyond the class of ether lipids.

Ion mobility-derived collision cross section as an additional measure for lipid fingerprinting and identification.

Despite recent advances in analytical and computational chemistry, lipid identification remains a significant challenge in lipidomics. Ion-mobility spectrometry provides an accurate measure of the molecules' rotationally averaged collision cross-section (CCS) in the gas phase and is thus related to ionic shape. Here, we investigate the use of CCS as a highly specific molecular descriptor for identifying lipids in biological samples. Using traveling wave ion mobility mass spectrometry (MS), we measured the CCS values of over 200 lipids within multiple chemical classes. CCS values derived from ion mobility were not affected by instrument settings or chromatographic conditions, and they were highly reproducible on instruments located in independent laboratories (interlaboratory RSD < 3% for 98% of molecules). CCS values were used as additional molecular descriptors to identify brain lipids using a variety of traditional lipidomic approaches. The addition of CCS improved the reproducibility of analysis in a liquid chromatography-MS workflow and maximized the separation of isobaric species and the signal-to-noise ratio in direct-MS analyses (e.g., "shotgun" lipidomics and MS imaging). These results indicate that adding CCS to databases and lipidomics workflows increases the specificity and selectivity of analysis, thus improving the confidence in lipid identification compared to traditional analytical approaches. The CCS/accurate-mass database described here is made publicly available.