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Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.

The questions in one survey might emphasize negative emotions and find that physicians are indeed an unhappy group, whereas the questions in another survey might lead to a less negative view. Because the questions are not available online, however, it is difficult to directly test this theory. While these features seem reasonable as signs of burnout, their recognition will be challenging for senior leaders who may have only rare interactions with individual physicians on the medical staff. [...]the identification of burnout should be a specific task assigned to physician leaders such as division heads or chief medical officers.

The call for physician leadership development is becoming more insistent in the face of increasing costs, demand for services, and the appearance of new payment models (Morrissey, 2015). Senior leaders are in an ideal position to help physicians succeed in leadership, in part by promoting the benefits of membership in national associations. Professional membership organizations enhance career advancement in numerous ways that factor into physician's successful transition to leadership roles. As the author has witnessed at Piedmont Healthcare in Atlanta, physicians in leadership are uniquely poised to support system-wide initiatives by engaging medical colleagues in planning and other meaningful activities. Physician engagement is increasingly recognized as critical to change implementation. Through associations, physicians can strengthen their ability to effectively lead both clinical and nonclinical healthcare colleagues and advance as leaders in the healthcare delivery system.

[...]of whether this assumption is a self-fulfilling prophecy promoted by those who seek to avoid disruption of the status quo, senior leaders who value the entrance of this new group of leaders must take great care in preparing them for success in interacting with unfamiliar constituencies, such as senior administrative leaders in nursing or finance, in the complex and continually evolving healthcare landscape. Prepare Physicians for Specific New Leadership Roles Rather Than an Undefined Future Role Physician leader candidates share responsibility with senior leaders for thoughtful promotion on the basis of their (1) natural potential for the intended role and (2) preparation in areas where technical knowledge or new leadership skills are required.

Diffuse astrocytomas of the adult cerebral hemispheres are unique among tumours in human beings in the extent to which their imaging features are related to histopathological characteristics and clinical behaviour. However, understanding is still restricted about the value of imaging features in the measurement of response and of progression in these tumours. The present approach used in clinical trials, which consists of an anatomical measurement of the enhancing tumour on MRI, has many problems, and might not be acceptable as a surrogate endpoint for survival in patients with glioblastoma who are enrolled in clinical trials. Dynamic imaging techniques, such as capillary permeability mapping, are being used in studies of new drugs that target specific molecular features of gliomas; however, the validity of these techniques has not been elucidated. Diffusion imaging can be valuable for fibre-tract mapping to assist surgical planning and might become useful in measuring early response to treatment in densely cellular tumours. Functional imaging techniques can be used to localise motor, sensory, and language-control areas before surgery. Intraoperative MRI has produced improvements in the extent of tumour resection, and molecular imaging is another technique on the horizon, which could come to have a role in clinical trials in the near future. Thus, as a rapidly expanding sphere of investigation, brain-tumour imaging is producing great excitement. The aim of these new techniques is to aid the identification of more effective treatments.

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.

An environmental scan (ES) is an efficient mixed-methods approach to collect and interpret relevant data for strategic planning and project design. To date, the ES has not been used nor evaluated in the clinical cancer genetics setting. We created and implemented an ES to inform the design of a quality improvement (QI) project to increase the rates of adherence to national guidelines for cancer genetic counseling and genetic testing at three unique oncology care settings (OCS). The ES collected qualitative and quantitative data from reviews of internal processes, past QI efforts, the literature, and each OCS. The ES used a data collection form and semi-structured interviews to aid in data collection. The ES was completed within 6 months, and sufficient data were captured to identify opportunities and threats to the QI project’s success, as well as potential barriers to, and facilitators of guideline-based cancer genetics services at each OCS. Previously unreported barriers were identified, including inefficient genetic counseling appointment scheduling processes and the inability to track referrals, genetics appointments, and genetic test results within electronic medical record systems. The ES was a valuable process for QI project planning at three OCS and may be used to evaluate genetics services in other settings.

Purpose Temozolomide (TMZ), given concurrently with radiotherapy (RT) and as adjuvant monotherapy afterwards, has led to improved survival in glioblastoma multiforme (GBM). However, it is unclear whether its primary mechanism of action is through enhancement of radiation response, independent cytotoxicity, or both. We sought to determine the relative contribution of concomitant temozolomide in patients treated by concurrent and adjuvant TMZ versus adjuvant TMZ alone in the setting of newly diagnosed GBM. Methods and Materials We identified patients diagnosed with GBM and treated with surgery, involved-field radiotherapy, and chemotherapy at MGH between 2002 and 2004. Eligible patients received either adjuvant temozolomide alone (group 1) or temozolomide concurrently with RT followed by adjuvant TMZ (group 2). The primary endpoint of this retrospective analysis was overall survival (OS). Results Forty-three patients (group 1, n  = 21; group 2, n  = 22) were included in this study. The median follow-up was 33.7 months for surviving patients. There were no significant differences in baseline characteristics between these two groups. On univariate analysis, patients who received concurrent and adjuvant temozolomide experienced a 2-year OS of 51% and median survival of 25.5 months, compared with a 2-year OS of 36% and median survival of 15.6 months for group 1 patients ( P  < 0.05). On multivariable analysis, the hazard ratio (HR) favoring concurrent TMZ trended towards significance (HR = 0.51, P  = 0.08) despite modest patient numbers. Conclusions Concurrent and adjuvant TMZ was associated with improved survival compared to adjuvant TMZ alone, highlighting the potentiation of radiation effect by temozolomide in the clinical setting.

A 48-year-old man came to the neurology clinic because of progressive weakness of his arms and legs and pain in the left leg. Enlargement of the sciatic nerve and multiple spinal nerve roots was seen on imaging studies. The patient's 29-year-old nephew had been given a diagnosis of neurofibromatosis; no other family members were known to be affected. A diagnostic procedure was performed. A 48-year-old man had progressive weakness of his limbs. Enlargement of the sciatic nerve and multiple spinal nerve roots was seen on imaging studies. Presentation of Case A 48-year-old, right-handed man was evaluated in the neurology clinic of this hospital because of weakness of his arms and legs. When the patient was 18 years of age, a mass on the right side of his neck developed; a biopsy was performed at another hospital, and he was told he had von Recklinghausen's neurofibromatosis. At 45 years of age, pain and weakness in his left leg developed. A radiograph of the left knee performed elsewhere showed what were described as tumors, and he was referred to an orthopedist at this hospital. Magnetic resonance imaging (MRI) showed . . .