Citations

PurposeTo investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls.Materials and MethodsA 1.5T spin‐echo, echo planar imaging MRE (SE‐EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls. Data were collected at residual volume (RV) and total lung capacity (TLC). Spirometry data were obtained immediately prior to scanning. To test for statistical significance between RV and TLC shear stiffness estimates a two‐sample t‐test was performed. To assess variability within individual subject shear stiffness estimates, the intraclass correlation coefficient (ICC) and Krippendorff's alpha were calculated.ResultsPatients with ILD exhibited an average (±1 standard deviation) shear stiffness of 2.74 (±0.896) kPa at TLC and 1.32 (±0.300) kPa at RV. The corresponding values for healthy individuals were 1.33 (±0.195) kPa and 0.849 (±0.250) kPa, respectively. The difference in shear stiffness between RV and TLC was statistically significant (P < 0.001). At TLC, the ICC and alpha values were 0.909 and 0.887, respectively. At RV, the ICC and alpha values were 0.852 and 0.862, respectively.ConclusionIn subjects with known fibrotic interstitial lung disease, parenchymal shear stiffness is increased when compared to normal controls at both RV and TLC, with TLC demonstrating the most significant difference. MRE‐derived parenchymal shear stiffness is a promising new noninvasive imaging‐based biomarker of interstitial lung disease.Level of Evidence: 1Technical Efficacy: Stage 2J. MAGN. RESON. IMAGING 2017;46:365–374

ABSTRACTIntroductionPolyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial.MethodsWe assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis) and its subscores and correlation with disability and health scores.ResultsThe mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests.ConclusionsSpecially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017

By the current WHO classification, benign notochordal cell tumor (BNCT) and chordoma comprise the entire spectrum of notochordal-derived tumors. They have defined radiologic and histologic criteria, and differ considerably in management and clinical outcome. Chordomas are malignant tumors; they show progressive, destructive growth and have the capacity for metastasis. In contrast, BNCT are benign and show limited intraosseous growth. Patients with BNCT can be managed with serial imaging or conservative excision, whereas patients with spinal/sacral chordomas typically undergo radical en bloc resection often with adjuvant therapy and significant morbidity. As such, the distinction between BNCT and chordoma is critically important. We have seen 4 unusual notochordal tumors with radiologic and/or histologic features that defy classification as either BNCT or chordoma. Cases occurred in 4 adults (53 to 83 y), and involved the lumbar spine (N=2) and sacrum (N=2). Three cases had subtle radiologic features of cortical permeation with minimal soft tissue extension. All 4 cases had the characteristic histologic features of BNCT; however, 2 cases also had focal myxoid change. Three patients were followed with serial imaging (follow-up range, 26 to 120 mo); 2 showed no disease progression and 1 had a 10-year cumulative interval growth of 3.7 mm. One patient underwent sacrectomy. The tumor was examined in toto and had the characteristic histologic features of BNCT, with the exception of minimal soft tissue extension. On the basis of these observations, we propose a provisional designation of atypical notochordal cell tumors (ANCT) be used for the subset of notochordal-derived tumors that fail to fulfill current diagnostic criteria for either BNCT or chordoma. We would argue that designating these atypical notochordal tumors as chordoma precipitates potentially overly aggressive surgical management. Patients with ANCT may be better managed by close observation and serial imaging. Additional studies with more cases and longer clinical follow-up should clarify the relationship of ANCT to BNCT and chordoma.

Purpose The flipped classroom (FC), in which instructional content is delivered before class with class time devoted to knowledge application, has the potential to engage residents. A Mayo Clinic Internal Medicine Residency Program study was conducted to validate an FC perception instrument (FCPI); determine whether participation improved FC perceptions; and determine associations between resident characteristics, change in quality improvement (QI) knowledge, and FC perception scores. Method All 143 internal medicine residents at Mayo Clinic, Rochester participated from 2014 to 2015; some experienced a flipped QI curriculum and others completed the traditional nonflipped course. The FCPI was developed, and factor analysis revealed an intuitive two-factor structure: preclass activity and in-class application. Residents were surveyed before and after the monthlong curriculum to measure changes in perception, and the QI Knowledge Assessment Tool was employed to measure knowledge improvement. Results Postcourse FCPI scores significantly increased for three of the eight items. QI knowledge increased significantly among residents who experienced the FC compared with residents who completed the non-FC curriculum. Those without prior FC exposure demonstrated a significant increase in QI knowledge compared with those with previous FC experience. The FCPI had compelling validity evidence with improved scores after curriculum exposure and associations with greater engagement in online modules. Conclusions Residents who participated in the FC demonstrated improved QI knowledge compared with the control group. Residents valued the in-class application sessions more than the online component. These findings have important implications for graduate medical education as residency training programs increasingly use FC models.

Krabbe's disease (KD) is a fatal neurodegenerative disorder, with the early‐infantile form (EIKD) defined by onset of symptoms before age 6 months. Early and highly accurate identification of EIKD is required to maximize benefits of hematopoietic stem cell transplantation treatment. This study investigates the potential for accurate prediction of EIKD based on a novel newborn screening (NBS) tool developed from two biomarkers, galactocerebrosidase (GALC) enzyme activity and galactosylsphingosine concentration (psychosine [PSY]). Normative information about PSY and GALC, derived from distinct samples of normal newborns, was used to develop the novel diagnostic tool. Bivariate normal limits (BVNL) were constructed, assuming a multivariate normal distribution of natural logarithms of GALC and PSY of normal newborns. The (lnGALC, lnPSY) points for newborns in various “abnormal groups,” including one group of infants who subsequently suffered EIKD, were plotted on a graph of BVNL. The points for all EIKD patients fell outside of BVNL (100% sensitivity). In a simulation study to compare the false‐positive rate of existing univariate methods of diagnosis with our new BVNL‐based method, we generated 100 million normal newborn data points. All fell within BVNL (i.e., zero false positives), whereas 5,682 false positives were observed when applying a two‐tiered univariate method of the type suggested in the literature. These results suggest that (lnGALC, lnPSY) BVNLs will allow highly accurate prediction of EIKD, whereas two‐tiered univariate approaches will not. Redevelopment of the BVNL based on GALCs and PSYs measured on a common large sample of normal newborns is required for NBS use. © 2016 Wiley Periodicals, Inc.

Purpose To learn the size, composition, and scholarly output of biostatistics, epidemiology, and research design (BERD) units in U.S. academic health centers (AHCs). Method Each year for four years, the authors surveyed all BERD units in U.S. AHCs that were members of the Clinical and Translational Science Award (CTSA) Consortium. In 2010, 46 BERD units were surveyed; in 2011, 55; in 2012, 60; and in 2013, 61. Results Response rates to the 2010, 2011, 2012, and 2013 surveys were 93.5%, 98.2%, 98.3%, and 86.9%, respectively. Overall, the size of BERD units ranged from 3 to 86 individuals. The median FTE in BERD units remained similar and ranged from 3.0 to 3.5 FTEs over the years. BERD units reported more availability of doctoral-level biostatisticians than doctoral-level epidemiologists. In 2011, 2012, and 2013, more than a third of BERD units provided consulting support on 101 to 200 projects. A majority of BERD units reported that between 25% and 75% (in 2011) and 31% to 70% (in 2012) of their consulting was to junior investigators. More than two-thirds of BERD units reported their contributions to the submission of 20 or more non-BERD grant or contract applications annually. Nearly half of BERD units reported 1 to 10 manuscripts submitted annually with a BERD practitioner as the first or corresponding author. Conclusions The findings regarding BERD units provide a benchmark against which to compare BERD resources and may be particularly useful for institutions planning to develop new units to support programs such as the CTSA.

It is well established that traumatic brain injury (TBI) is associated with the development of psychiatric disorders. However, the impact of psychiatric disorders on TBI outcome is less well understood. We examined the outcomes of patients who experienced a traumatic subdural hemorrhage and whether a comorbid psychiatric disorder was associated with a change in outcome. A retrospective observational study was performed in the California Office of Statewide Health Planning and Development (OSHPD) and the Nationwide Inpatient Sample (NIS). Patients hospitalized for acute subdural hemorrhage were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Patients with coexisting psychiatric diagnoses were identified. Outcomes studied included mortality and adverse discharge disposition. In OSPHD, diagnoses of depression (OR = 0.64, p < 0.001), bipolar disorder (OR = 0.45, p < 0.05), and anxiety (OR = 0.37, p < 0.001) were associated with reduced mortality during hospitalization for TBI, with a trend toward psychosis (OR = 0.56, p = 0.08). Schizophrenia had no effect. Diagnoses of psychosis (OR = 2.12, p < 0.001) and schizophrenia (OR = 2.60, p < 0.001) were associated with increased adverse discharge. Depression and bipolar disorder had no effect, and anxiety was associated with reduced adverse discharge (OR = 0.73, p = 0.01). Results were confirmed using the NIS. Analysis revealed novel associations between coexisting psychiatric diagnoses and TBI outcomes, with some subgroups having decreased mortality and increased adverse discharge. Potential mechanisms include pharmacological effects of frequently prescribed psychiatric medications, the pathophysiology of individual psychiatric disorders, or under-coding of psychiatric illness in the most severely injured patients. Because pharmacological mechanisms, if validated, might lead to improved outcome in TBI patients, further studies may provide significant public health benefit.