Search

Meningiomas are associated with several gonadal steroid hormone-related risk factors and demonstrate a predominance in females. These associations led to investigations of the role that hormones may have on meningioma growth and development. While it is now accepted that most meningiomas express progesterone and somatostatin receptors, the conclusion for other receptors has been less definitive.We performed a review of what is known regarding the relationship between hormones and meningiomas in the published literature. Furthermore, we reviewed clinical trials related to hormonal agents in meningiomas using MEDLINE PubMed, Scopus, and the NIH clinical trials database.We identify that all steroid-hormone trials lacked receptor identification or positive receptor status in the majority of patients. In contrast, four out of five studies involving somatostatin analogs used positive receptor status as part of the inclusion criteria.Several clinical trials have recently been completed or are now underway using somatostatin analogs in combination with other therapies that appear promising, but a reevaluation of hormone-based monotherapy is warranted. Synthesizing this evidence, we clarify the remaining questions and present future directions for the study of the biological role and therapeutic potential of hormones in meningioma and discuss how the stratification of patients using features such as grade, receptor status, and somatic mutations, might be used for future trials to select patients most likely to benefit from specific therapies.

This study's objective was to determine if student participation in a co-curricular drug information journal would increase interprofessional education (IPE) competency as measured by a validated survey tool.To encourage interprofessional collaboration, students from diverse professional backgrounds were split into groups to conduct a literature review, draft an article on a topic of their choice, obtain revisions through formal review, and publish their article in a student-led journal, The ARxCH (The Annual Review of Changes in Healthcare). To measure IPE competency, students completed the validated Interprofessional Collaborative Competencies Attainment Survey (ICCAS) at the beginning and end of the study to measure changes in IPE competency scores.Results of the ICCAS survey found that 15 of the 17 IPE competency questions showed significant positive changes from the pre-survey to the post-survey. These findings suggest that The ARxCH publishing process increased IPE competencies when incorporating students from a variety of healthcare backgrounds and leveraging this novel IPE approach of formal manuscript preparation and group discussion.This student-led journal could serve as a prototype for future longitudinal activities designed to enhance student IPE competence through co-curricular activities.

PDF file, 102K, Linkage locations suggested by Loki on chromosome 17 by batches of 100K iterations and over all 500K iterations.

PDF file, 212K, Genome-wide multipoint model-based linkage under the three trait locus segregation models. Multipoint LOD scores have been truncated at -3. Some scores are below -3, such as for the whole of chromosome 15.

PDF file, 302K, Scatter plot of the visits at possible linked QTL locations on chromosome 17 vs. iteration.

PDF file, 133K, Additional methods describing the segregation-linkage analysis approach with variable age at onset.

PDF file, 89K, L-scores for three prior settings, after discarding the beginning 5K iterations

PDF file, 34K, Typical assumptions in model-based vs. model-free multipoint linkage analysis.

World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) isocitrate dehydrogenase (IDH) wildtype glioblastoma (~43%). The latter had an unusually low-frequency of epidermal growth factor receptor (EGFR) and high-frequency of platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the mitogen-activated protein kinases (MAPK) pathway and PDGFRA, oncolytic virotherapy, and immunotherapy. HGGs of the cerebellum exhibit biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment.

Introduction: Parent experience is a core component of the quality of pediatric care and an increasingly common focus of quality improvement initiatives. However, the parent experience of communication in the pediatric surgical setting remains unexplored. Methods: We conducted semi-structured interviews with 20 parents of children undergoing surgery. Interviews were analyzed using directed qualitative content analysis. Results: Content analysis revealed 3 overarching themes. The theme of “provider–parent communication” included interpersonal behaviors and communication-originating skills of the surgeon. Parents valued surgeons incorporating multimodal information-sharing techniques, recognizing children’s psychological needs, providing reassurance, engaging in teamwork, and including parents. The theme of “parental emotional experiences” included domains of parent worry, intimidation, offense, self-doubt, mistrust, and strength surrounding their child’s surgery. Parents felt simultaneously responsible for their child’s welfare and for understanding medical information. The theme of “process improvement” included preparation for surgery, efficiency, managing delays, anesthesia induction, emergence from anesthesia, privacy, and preparation for recovery. Conclusions: Themes identified through these parental narratives and proposed solutions inform quality improvement efforts related to surgeon communication strategies and facilitate family-centered surgical care for children. Parents often provided solutions after they described concerns, which attests to the utility of parent perspectives.

INTRODUCTION AND OBJECTIVE:Metastatic recurrence (MR) of upper tract urothelial carcinoma (UTUC) occurs in over 25% of patients treated with radical nephroureterectomy (RNU). While MR suggests poor...

As an uncommon cancer, clinical and translational studies of glioma rely on multi-center collaborations, confirmatory studies, and meta-analyses. Unfortunately, interpretation of results across studies is hampered by the absence of uniformly coded clinical data. Common Data Elements (CDE) represent a set of clinical features for which the language has been standardized for consistent data capture across studies, institutions and registries. We constructed CDE for the longitudinal study of adult malignant glioma. To identify the minimum set of CDE needed to describe the clinical course of glioma, we surveyed clinical standards, ongoing trials, published studies, and data repositories for frequently used data elements. We harmonized the identified clinical variables, filled in gaps, and structured them in a modular schema, defining CDE for patient demographics, medical history, diagnosis, surgery, chemotherapy, radiotherapy, other treatments, and outcomes. Multidisciplinary experts from the Glioma Longitudinal AnalySiS (GLASS) consortium, representing clinical, molecular, and data research perspectives, were consulted regarding CDE. The validity and capture feasibility of the CDE were assessed through harmonization across published studies, then validated with single institution retrospective chart abstraction. The refined CDE library is implemented in the Research Electronic Data Capture (REDCap) System, a secure web application for building and managing online surveys and databases. The work was motivated by the GLASS consortium, which supports the aggregation and analysis of complex genetic datasets used to define molecular trajectories for glioma. The goal is that modular REDCap implementation of CDE allows broad adoption in glioma research. To accommodate novel aspects, the CDE sets can be expanded through additional modules. In contrast, for efficient initiation of focused studies, subsets of CDE can be selected. Broad adoption of CDE will improve the ability to compare results and share data between studies, thereby maximizing the value of existing data sources and small patient populations.

Purpose Metastatic recurrence occurs in over 25% of upper tract urothelial carcinoma patients treated with radical nephroureterectomy. While metastatic recurrence suggests poor prognosis, the impact of the specific site of recurrence on prognosis is not well documented. Materials and methods We retrospectively analyzed 188 patients who underwent radical nephroureterectomy for high-grade, node-negative upper tract urothelial carcinoma at our institution from 2003 to 2018 without receiving neoadjuvant or adjuvant chemotherapy. Competing-risks survival analysis was performed to evaluate the cumulative incidence and predictors of metastatic recurrence. The Kaplan-Meier method and log-rank test were used to estimate and compare recurrence site-specific survival probabilities following metastatic recurrence. Cox regression analyses were performed to assess site-specific prognoses. Results Of the 188 patients, 47 (25%) developed metastatic recurrence over a median follow-up of 30 months (interquartile range: 10.5–58.5 months). The 1- and 2-year cumulative incidences of metastatic recurrence were 13.6% and 23.6%, respectively. On multivariable analysis, lymphovascular invasion was significantly predictive of metastatic recurrence (subhazard ratio: 2.6, P = 0.01). Of the 47 patients who developed recurrence, 38 (80.9%) died over a median follow-up of 10 months (interquartile range: 5–20 months). Metastatic recurrence was most common in the lungs (n= 13, 28%) and at multiple sites (n= 14, 30%). Median time to recurrence was shorter for recurrences at multiple sites (6.5 months) and those in the liver (13 months) and bone (18 months) compared to other sites. Patients who recurred in the liver (hazard ratio: 6.3, P = 0.007), bone (hazard ratio: 4.9, P = 0.02), and multiple sites (hazard ratio: 4.6, P = 0.01) had significantly worse prognosis compared to those who recurred in lymph nodes. Statistical significance persisted after adjusting for treatment with salvage therapy. Conclusions A significant proportion of high-grade upper tract urothelial carcinoma patients recur systemically after radical nephroureterectomy. Lymphovascular invasion is a predictor of metastatic recurrence and may inform decisions regarding perioperative chemotherapy. Hepatic and osseous recurrences have relatively quicker onset and less favorable prognosis compared to other sites. These findings may benefit future efforts to develop recurrence site-specific treatment plans and highlight the necessity of subsequent endeavors to explore the genetic associations of recurrence in upper tract urothelial carcinoma.

A comprehensive characterization of the somatic alterations and molecular subtypes of glioma at diagnosis has been established. However, gliomas undergo significant molecular changes over time, some of these causing malignant progression or associated with therapy. Understanding this molecular evolution may uncover therapeutic vulnerabilities and facilitate development of more effective systemic therapies. The Glioma Longitudinal Analysis (GLASS) Consortium is an international effort to systemically catalogue the longitudinal changes in gliomas through multi-platform characterization. GLASS has developed computational and clinical infrastructure to enable its mission of establishing a well annotated longitudinal molecular dataset of 1500 gliomas including 500 gliomas per each of the IDHwt/IDH-mut-non-codel/IDH-mut-codel subtypes. An initial dataset comprising 150 cases with exome sequencing at multiple timepoints has been constructed, including cases diagnosed as IDHwt (55%), IDH-mut-non-codel (38%) and IDH-mut-codel (6%). Treatment regimens followed the expected combinations of chemo- and radiation therapy while survival was more favorable than reported in literature, suggested a bias in our dataset towards better performing cases. This is possibly explained by the need for two consecutive surgical procedures to be included in the analysis. While more than half of mutations in IDHwt primary tumors were recovered in their matching recurrences, this fraction was less than 30% in the other two subtypes. The disparity in mutations between primary and recurrences may reflect intratumoral heterogeneity in both primary and recurrence, and clonal selection patterns. We observed temozolomide treatment-associated hypermutation in up to 13 of our cohort. A more detailed analysis of mutational and DNA copy number data is underway. A cohort of 75 additional patients with multi-timepoint exome data is being processed and, through several funded projects, multi-platform characterization of 250 gliomas is in progress. In summary, GLASS will provide a rich resource to the glioma community with the potential for paradigm shifting discoveries.