Preoperative relative cerebral blood volume analysis in gliomas predicts survival and mitigates risk of biopsy sampling error.

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II-IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan-Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p < 0.0001) and the hazard ratio for each increase in 1.0 rCBV units was 1.12 (p < 0.002). Additionally, 3 of 13 (23%) patients initially diagnosed by biopsy were upgraded on subsequent resection. Preoperative rCBV was elevated at least one standard deviation above the mean in the 3 upgraded patients, suggestive of undergrading, but not in the ten concordant diagnoses. In conclusion, rCBV can predict overall survival similarly to pathologically determined WHO grade in patients with gliomas. Discordant rCBV analysis and histopathology may help identify patients at higher risk for undergrading.

A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels.

BACKGROUND: IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. PURPOSE AND METHODS: We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. RESULTS: All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke's cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. CONCLUSIONS: Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels.

Dynamic susceptibility contrast and dynamic contrast-enhanced MRI characteristics to distinguish microcystic meningiomas from traditional Grade I meningiomas and high-grade gliomas.

OBJECTIVE Microcystic meningioma (MM) is a meningioma variant with a multicystic appearance that may mimic intrinsic primary brain tumors and other nonmeningiomatous tumor types. Dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI techniques provide imaging parameters that can differentiate these tumors according to hemodynamic and permeability characteristics with the potential to aid in preoperative identification of tumor type. METHODS The medical data of 18 patients with a histopathological diagnosis of MM were identified through a retrospective review of procedures performed between 2008 and 2012; DSC imaging data were available for 12 patients and DCE imaging data for 6. A subcohort of 12 patients with Grade I meningiomas (i.e., of meningoepithelial subtype) and 54 patients with Grade IV primary gliomas (i.e., astrocytomas) was also included, and all preoperative imaging sequences were analyzed. Clinical variables including patient sex, age, and surgical blood loss were also included in the analysis. Images were acquired at both 1.5 and 3.0 T. The DSC images were acquired at a temporal resolution of either 1500 msec (3.0 T) or 2000 msec (1.5 T). In all cases, parameters including normalized cerebral blood volume (CBV) and transfer coefficient (kTrans) were calculated with region-of-interest analysis of enhancing tumor volume. The normalized CBV and kTrans data from the patient groups were analyzed with 1-way ANOVA, and post hoc statistical comparisons among groups were conducted with the Bonferroni adjustment. RESULTS Preoperative DSC imaging indicated mean (± SD) normalized CBVs of 5.7 ± 2.2 ml for WHO Grade I meningiomas of the meningoepithelial subtype (n = 12), 4.8 ± 1.8 ml for Grade IV astrocytomas (n = 54), and 12.3 ± 3.8 ml for Grade I meningiomas of the MM subtype (n = 12). The normalized CBV measured within the enhancing portion of the tumor was significantly higher in the MM subtype than in typical meningiomas and Grade IV astrocytomas (p < 0.001 for both). Preoperative DCE imaging indicated mean kTrans values of 0.49 ± 0.20 min-1 in Grade I meningiomas of the meningoepithelial subtype (n = 12), 0.27 ± 0.12 min-1 for Grade IV astrocytomas (n = 54), and 1.35 ± 0.74 min-1 for Grade I meningiomas of the MM subtype (n = 6). The kTrans was significantly higher in the MM variants than in the corresponding nonmicrocystic Grade 1 meningiomas and Grade IV astrocytomas (p < 0.001 for both). Intraoperative blood loss tended to increase with increased normalized CBV (R = 0.45, p = 0.085). CONCLUSIONS An enhancing cystic lesion with a normalized CBV greater than 10.3 ml or a kTrans greater than 0.88 min-1 should prompt radiologists and surgeons to consider the diagnosis of MM rather than traditional Grade I meningioma or high-grade glioma in planning surgical care. Higher normalized CBVs tend to be associated with increased intraoperative blood loss.

Genetic investigation of multicentric glioblastoma multiforme: case report.

The authors report a case of multicentric glioblastoma multiforme (GBM) in which all 4 tumor foci were resected and evaluated using both comparative genomic hybridization array and RNA sequencing. Genetic analysis showed that the tumors shared a common origin, although each had its own unique set of genetic aberrations. The authors note that the genetic heterogeneity of multicentric GBM likely contributes to the failures of current treatments. The case underscores the necessity of increased genetic investigation.

How can clinician-educator training programs be optimized to match clinician motivations and concerns?

BACKGROUND: Several medical schools have implemented programs aimed at supporting clinician-educators with formal mentoring, training, and experience in undergraduate medical teaching. However, consensus program design has yet to be established, and the effectiveness of these programs in terms of producing quality clinician-educator teaching remains unclear. The goal of this study was to review the literature to identify motivations and perceived barriers to clinician-educators, which in turn will improve clinician-educator training programs to better align with clinician-educator needs and concerns. METHODS: Review of medical education literature using the terms "attitudes", "motivations", "physicians", "teaching", and "undergraduate medical education" resulted in identification of key themes revealing the primary motivations and barriers involved in physicians teaching undergraduate medical students. RESULTS: A synthesis of articles revealed that physicians are primarily motivated to teach undergraduate students for intrinsic reasons. To a lesser extent, physicians are motivated to teach for extrinsic reasons, such as rewards or recognition. The key barriers deterring physicians from teaching medical students included: decreased productivity, lack of compensation, increased length of the working day, patient concerns/ethical issues, and lack of confidence in their own ability. CONCLUSION: Our findings suggest that optimization of clinician-educator training programs should address, amongst other factors, time management concerns, appropriate academic recognition for teaching service, and confidence in teaching ability. Addressing these issues may increase the retention of clinicians who are active and proficient in medical education.

A review of teaching skills development programmes for medical students.

CONTEXT: The CanMEDS role of Scholar requires that medical trainees develop their skills as medical educators. The development of teaching skills in undergraduate medical students is therefore desirable, especially in view of the teaching obligations in residency programmes. OBJECTIVES: The goal of this review was to identify the characteristics and outcomes of programmes designed to develop the teaching skills of undergraduate medical students. METHODS: The authors searched medical literature databases using combinations of the search terms 'medical student', 'teacher', 'teaching skills', 'peer teaching', 'near-peer teaching' and 'student as teacher'. Twenty papers fit the predetermined search criteria, which included original characterisations of specific programmes involving undergraduate medical students. RESULTS: Three types of initiative were identified in the reviewed articles: peer teaching programmes; teaching workshops, and community outreach programmes. The majority of study participants were students in Years 3 and 4. Subjective self-evaluation by participants using Likert scale-based surveys was by far the most commonly used method of measuring project outcomes. Objective, quantitative teaching-related outcomes were rarely noted in the reports reviewed. Self-perceived improvements in teaching skills were noted by participants in most of the reports. Other perceived benefits included increases in organisational skills, knowledge and confidence in giving feedback. CONCLUSIONS: Although several types of programmes have been shown to subjectively improve the teaching skills of undergraduate medical students, characterisation of the objective outcomes of these initiatives is lacking and requires further study.

Enhancement of the pulmonary arteries and thoracic aorta: comparison of a biphasic contrast injection and fixed delay protocol with a monophasic injection and a timing bolus protocol.

The definitive diagnosis of pulmonary embolism, a significant cause of morbidity and mortality, relies on imaging. In this study, we compare the conventional computed tomography pulmonary angiogram (CTPA) protocol to a double-rule out CT angiogram (DRO CTA) protocol in terms of vascular enhancement, radiation dose, and contrast volume delivered. The CTPA protocol involves injection of a timing bolus for localization of the pulmonary artery, whereas the DRO CTA protocol involves a biphasic contrast. We analyzed 248 consecutive CTPA studies and 242 consecutive DRO CTA studies. Vessel enhancement using region of interest (ROI) measurements, radiation dose delivered, and total contrast volume administered was recorded. The enhancement of all vessels measured was statistically significantly higher with the biphasic DRO CTA protocol than the CTPA protocol. The difference in mean vascular enhancement for the two protocols was greatest in the descending aorta (DA, P < 0.001) and least in the main pulmonary artery (MPA, P = 0.001). The percent of studies with vascular enhancement ≥250 Hounsfield units (HU) was significantly greater in all vascular beds except the MPA when the DRO CTA protocol was used. Studies performed with the DRO CTA protocol led to less radiation exposure and used less contrast than those performed with the CTPA protocol (P < 0.001 for both). According to the final radiology report, 35.08 % of studies in the CTPA group and 22.31 % of studies in the DRO CTA group were considered indeterminate (P = 0.001). In conclusion, the biphasic DRO CTA protocol leads to statistically significantly higher opacification of all pulmonary arterial and aortic vessels studied, with no greater delivery of radiation or contrast, than the monophasic CTPA protocol.

Major medical outcomes with spinal augmentation vs conservative therapy.

IMPORTANCE: The symptomatic benefits of spinal augmentation (vertebroplasty or kyphoplasty) for the treatment of osteoporotic vertebral compression fractures are controversial. Recent population-based studies using medical billing claims have reported significant reductions in mortality with spinal augmentation compared with conservative therapy, but in nonrandomized settings such as these, there is the potential for selection bias to influence results. OBJECTIVE: To compare major medical outcomes following treatment of osteoporotic vertebral fractures with spinal augmentation or conservative therapy. Additionally, we evaluate the role of selection bias using preprocedure outcomes and propensity score analysis. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of Medicare claims for the 2002-2006 period. We compared 30-day and 1-year outcomes in patients with newly diagnosed vertebral fractures treated with spinal augmentation (n = 10,541) or conservative therapy (control group, n = 115,851). Outcomes were compared using traditional multivariate analyses adjusted for patient demographics and comorbid conditions. We also used propensity score matching to select 9017 pairs from the initial groups to compare the same outcomes. EXPOSURES: Spinal augmentation (vertebroplasty or kyphoplasty) or conservative therapy. MAIN OUTCOMES AND MEASURES: Mortality, major complications, and health care utilization. RESULTS: Using traditional covariate adjustments, mortality was significantly lower in the augmented group than among controls (5.2% vs 6.7% at 1 year; hazard ratio, 0.83; 95% CI, 0.75-0.92). However, patients in the augmented group who had not yet undergone augmentation (preprocedure subgroup) had lower rates of medical complications 30 days post fracture than did controls (6.5% vs 9.5%; odds ratio, 0.66; 95% CI, 0.57-0.78), suggesting that the augmented group was less medically ill. After propensity score matching to better account for selection bias, 1-year mortality was not significantly different between the groups. Furthermore, 1-year major medical complications were also similar between the groups, and the augmented group had higher rates of health care utilization, including hospital and intensive care unit admissions and discharges to skilled nursing facilities. CONCLUSIONS AND RELEVANCE: After accounting for selection bias, spinal augmentation did not improve mortality or major medical outcomes and was associated with greater health care utilization than conservative therapy. Our results also highlight how analyses of claims-based data that do not adequately account for unrecognized confounding can arrive at misleading conclusions.

Ferumoxytol in clinical practice: implications for MRI.

Ferumoxytol is an iron-containing parenteral treatment for iron deficiency anemia that was recently approved by the Food and Drug Administration. The iron is in the form of a superparamagnetic iron oxide that causes T1, T2, and T2* shortening on magnetic resonance imaging (MRI). Furthermore, the drug has a long intravascular half-life of 14-15 hours; a standard dose can affect MRI for days to months. We describe a case in which a patient underwent contrast-enhanced MRI of the liver 2 days after receiving a dose of ferumoxytol, which was unknown to the radiology team. The blood pool and soft tissues were hyperintense on T1-weighted images, concealing enhancement from the gadolinium-based contrast agent that was administered during the exam and rendering the exam nondiagnostic. Radiologists must be aware of this potential effect in screening patients for MRI and interpreting exams.

Lumbar MR imaging and reporting epidemiology: do epidemiologic data in reports affect clinical management?

PURPOSE: To retrospectively examine the association between the inclusion of epidemiologic information in lumbar spine magnetic resonance (MR) imaging reports regarding findings in asymptomatic individuals and the rates of subsequent cross-sectional imaging and treatments in patients with low back pain or radiculopathy referred for imaging by primary care providers. MATERIALS AND METHODS: Institutional review board approval was received for a retrospective chart review, with waiver of informed consent and HIPAA authorization. During 3 years, an epidemiologic statement was routinely but arbitrarily included in lumbar spine MR imaging reports. Two hundred thirty-seven reports documenting uncomplicated degenerative changes on initial lumbar spine MR images were identified, 71 (30%) of which included the statement (statement group) and 166 (70%) did not (nonstatement group). The rates of repeat cross-sectional imaging and treatments within 1 year were compared between groups by using logistic regression controlling for severity of MR imaging findings. RESULTS: Patients in the statement group were significantly less likely to receive a prescription for narcotics for their symptoms than patients in the nonstatement group (odds ratio = 0.29, P = .01). Repeat cross-sectional imaging and physical therapy referrals were also less common in the statement group than in the nonstatement group (odds ratio = 0.22 and 0.55, respectively), but these differences were not statistically significant (P = .14 and .06, respectively). Rates of steroid injections, surgical consultations, and surgeries were similar between groups. CONCLUSION: Patients were less likely to receive narcotics prescriptions from primary care providers when epidemiologic information was included in their lumbar spine MR imaging reports.

Diagnosis of concussion: the role of imaging now and in the future.

The primary role of neuroimaging in the clinical context of sports-related concussion is the exclusion of a more severe, unsuspected intracranial injury. Computed tomography remains the test of choice for this purpose. Magnetic resonance imaging is more commonly used as a secondary test for the investigation of persistent symptoms. New imaging techniques are currently being developed to detect the molecular and cellular changes underlying concussion that are invisible with standard structural imaging. In the future, these techniques may be used as tools for directing rehabilitation after concussion and aiding in the decision of when it is safe for an athlete to return to play.

3p-- syndrome defines a hearing loss locus in 3p25.3.

Deletions affecting the terminal end of chromosome 3p result in a characteristic set of clinical features termed 3p-- syndrome. Bilateral, sensorineural hearing loss (SNHL) has been found in some but not all cases, suggesting the possibility that it is due to loss of a critical gene in band 3p25. To date, no genetic locus in this region has been shown to cause human hearing loss. However, the ATP2B2 gene is located in 3p25.3, and haploinsufficiency of the mouse homolog results in SNHL with similar severity. We compared auditory test results with fine deletion mapping in seven previously unreported 3p-- syndrome patients and identified a 1.38Mb region in 3p25.3 in which deletions were associated with moderate to severe, bilateral SNHL. This novel hearing loss locus contains 18 genes, including ATP2B2. ATP2B2 encodes the plasma membrane calcium pump PMCA2. We used immunohistochemistry in human cochlear sections to show that PMCA2 is located in the stereocilia of hair cells, suggesting its function in the auditory system is conserved between humans and mice. Although other genes in this region remain candidates, we conclude that haploinsufficiency of ATP2B2 is the most likely cause of SNHL in 3p-- syndrome.

Haplo-insufficiency revealed in deafwaddler mice when tested for hearing loss and ataxia.

The auditory and vestibular systems rely on the plasma membrane calcium ATPase, isoform 2 (PMCA2) to extrude calcium that enters the stereocilia during transduction. Mutations in the gene encoding this protein result in recessive sensorineural deafness and ataxia in the deafwaddler mouse. In this study, we report the identification of a new allele of deafwaddler, dfw(3j). This allele contains a 4-nucleotide deletion resulting in a frame-shift and predicted truncation of PMCA2. No protein is detected in dfw(3j) homozygotes. To examine the dependence of auditory and vestibular function on PMCA2 activity, we compared dfw(3j) with another functional null allele, dfw(2j), and the partial loss-of-function allele, dfw. All mice studied were in the good-hearing CBA/CaJ background. Heterozygotes of either functional null allele displayed highly significant hearing loss by auditory-evoked brainstem responses relative to controls (P < 0.0001), particularly at high frequencies (> 24 kHz). Ataxia was also apparent in these mice on an accelerating rotarod (P < 0.05). In contrast, +/dfw mice were not measurably different from controls in either behavioral test. dfw/dfw mice were deaf, but showed less ataxia than dfw(2j)/dfw(2j) or dfw(3j)/dfw(3j) mice. These results demonstrate that hearing loss and ataxia are dependent on gene dosage and PMCA2 dysfunction.