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Background Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pathways within the tumour microenvironment for various cancers. In this study, the authors explore the involvement of cerebrospinal fluid (CSF) cytokines in Group 3 and 4 MB patients with disseminated disease. Methods This is an ethics approved, retrospective study of prospectively collected data based at a single institution. Patient clinicpathological data and corresponding bio-materials are collected after informed consent. All CSF samples are interrogated using a proteomic array. Resultant expression data of selected cytokines are correlated with each individual’s clinical information. Statistical analysis is employed to determine the significance of the expression of CSF cytokines in Group 3 and 4 patients with metastatic MB versus non-metastatic MB. Results A total of 10 patients are recruited for this study. Median age of the cohort is 6.6 years old. Based on Nanostring gene expression analysis, 5 patients have Group 3 as their molecular subtype and the remaining 5 are Group 4. There are 2 non-metastatic versus 3 metastatic patients within each molecular subtype. Proteomic CSF analysis of all patients for both subtypes show higher expression of CCL2 in the metastatic group versus the non-metastatic group. Within the Group 3 subtype, the MYC-amplified Group 3 MB patients with existing and delayed metastases express higher levels of CXCL1, IL6 and IL8 in their CSF specimens at initial presentation. Furthermore, a longitudinal study of metastatic Group 3 MB observes that selected cytokines are differentially expressed in MYC-amplified metastatic Group 3 MB, in comparison to the non-MYC amplified metastatic Group 3 MB patient. Conclusion This study demonstrates higher expression of selected CSF cytokines, in particular CCL2, in metastatic Group 3 and 4 MB patients. Although our results are preliminary, they establish a proof-of-concept basis for continued work in a larger cohort of patients affected by this devastating disease.

Leptomeningeal disease is a feared sequelae of malignant paediatric brain tumours. Current methods for its detection is the combined use of cranio-spinal MRI, and CSF cytology from a post-operative lumbar puncture. In this study, the authors hypothesize that CSF taken at the start of surgery, either from an external ventricular drain or neuroendoscope will have equal sensitivity for positive tumour cells, in comparison to lumbar puncture. Secondary hypotheses include positive correlation between CSF cytology and MRI findings of LMD. From a clinical perspective, the key aim of the study was for affected paediatric patients to avoid an additional procedure of a lumbar puncture, often performed under anaesthesia after neurosurgical intervention. This is single-institution, retrospective study of paediatric patients diagnosed with malignant brain tumours. Its main aim was to compare cytological data from CSF collected at the time of surgery versus data from an interval lumbar puncture. In addition, MRI imaging of the same cohort of patients was examined for leptomeningeal disease and corroborated against CSF tumour cytology findings. Thirty patients are recruited for this study. Data analysis demonstrates a statistically significant association between our intra-operative CSF and LP sampling. Furthermore, our results also show for significant correlation between evidence of leptomeningeal disease on MRI findings versus intra-operative CSF positivity for tumour cells. Although this is a retrospective study with a limited population, our data concurs with potential to avoid an additional procedure for the paediatric patient diagnosed with a malignant brain tumour.

Background Primary paediatric epidural sarcomas are extremely rare. Overall, there remains a paucity of knowledge in paediatric epidural sarcomas owing to the infrequent number of cases. The Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) is a next-generation sequencing assay that has been reported to be a useful technique to detect recurrent fusion in sarcomas. We report the molecular exploration of 3 primary paediatric epidural sarcomas—one in the cranium (mesenchymal chondrosarcoma) and 2 in the spine (mesenchymal chondrosarcoma and Ewing sarcoma respectively). Case presentation This is a study approved by the hospital ethics board. Clinico-pathological information from 3 consenting patients with primary epidural sarcomas was collected. These selected tumours are interrogated via Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) for genomic aberrations. Results were validated with RT-PCR and Sanger sequencing. All findings are corroborated and discussed in concordance with current literature. Our findings show 2 variants of the HEY1-NCOA2 gene fusion: HEY1 (exon 4)-NCOA2 (exon 13) and HEY1 (exon 4)-NCOA2 (exon 14), in both mesenchymal chondrosarcoma patients. Next, the Ewing sarcoma tumour is found to have EWSR1 (exon 10)-FLI1 (exon 8) translocation based on NGS. This result is not detected via conventional fluorescence in situ testing. Conclusions This is a molecularly-centered study based on 3 unique primary paediatric epidural sarcomas. Our findings to add to the growing body of literature for these exceptionally rare and malignant neoplasms. The authors advocate global collaborative efforts and in-depth studies for targeted therapy to benefit affected children.

(1) Background: pediatric hydrocephalus is a challenging condition. Programmable shunt valves (PSV) have been increasingly used. This study is undertaken to firstly, to objectively evaluate the efficacy of PSV as a treatment modality for pediatric hydrocephalus; and next, review its associated patient outcomes at our institution. Secondary objectives include the assessment of our indications for PSV, and corroboration of our results with published literature. (2) Methods: this is an ethics-approved, retrospective study. Variables of interest include age, gender, hydrocephalus etiology, shunt failure rates and incidence of adjustments made per PSV. Data including shunt failure, implant survival, and utility comparisons between PSV types are subjected to statistical analyses. (3) Results: in this case, 51 patients with PSV are identified for this study, with 32 index and 19 revision shunts. There are 3 cases of shunt failure (6%). The mean number of adjustments per PSV is 1.82 times and the mean number of adjustments made per PSV is significantly lower for MEDTRONIC™ Strata PSVs compared with others (p = 0.031). Next, PSV patients that are adjusted more frequently include cases of shunt revisions, PSVs inserted due to CSF over-drainage and tumor-related hydrocephalus. (4) Conclusion: we describe our institutional experience of PSV use in pediatric hydrocephalus and its advantages in a subset of patients whose opening pressures are uncertain and evolving.

Background: Rosai-Dorfman disease (RDD) is a rare benign histioproliferative disease. It is typically characterized by benign histiocyte proliferation with lymphadenopathy, fever, and leukocytosis and was first described in 1969 by Rosai and Dorfman. Extranodal involvement has been reported in approximately up to 43% of the cases with isolated central nervous system (CNS) manifestations being even rarer. Case Description: We report our management of a 41-year-old female with extranodalpurely CNS RDD presenting as a benign scalp lump. Her lump progressed from an asymptomatic benign lesion to one causing localized cerebral edema. Treatment was surgical excision of both the cervical and CNS lesions achieving complete removal of the lesions and resolution of her symptoms. Conclusion: RDD is a rare condition and isolated CNS RDD is even less common. Benign scalp lumps have a myriad of differential diagnoses, but RDD should be a consideration in the presence of preexisting RDD lesions at other sites given its potential to progress and result in morbidity. It is imperative to be aware that symptoms may be especially deceiving as the absence of lymphadenopathy may point away from RDD as the diagnosis.

Issues of measurement and evidence of therapeutic effectiveness, and how these are exacerbated when data crosses cultural boundaries, are discussed. Widely used measures are reviewed, and two that have been more recently developed and employed in a wide variety of cultural contexts are selected for detailed consideration. The SCORE and the Outcome Rating Scale/Session Rating Scale are described with evaluation of their relevance for systemic family therapy, usability for routine outcome monitoring, and applicability across cultures. Experiences reported by users in widely different cultures and countries across the world are presented. Both sets of measures are shown to provide valid measurement of therapy progress and outcome, and both exist in carefully translated versions from across the world. In practice, therapists have found that in addition to measuring effectiveness, both types of measures can powerfully influence the therapeutic process when used interactively in the session with clients. The evidence of wide applicability and acceptability to clients is supplemented by examples of cultural variation. These extensive experiences demonstrate the potential of measures with a proven cross‐cultural applicability to enhance the cultural sensitivity of therapists, enable countries with limited resources and provision of family therapy to draw on strong empirical support, and ensure that linguistic minorities can be fully included in research.

Issues of measurement and evidence of therapeutic effectiveness, and how these are exacerbated when data crosses cultural boundaries, are discussed. Widely used measures are reviewed, and two that have been more recently developed and employed in a wide variety of cultural contexts are selected for detailed consideration. The SCORE and the Outcome Rating Scale/Session Rating Scale are described with evaluation of their relevance for systemic family therapy, usability for routine outcome monitoring, and applicability across cultures. Experiences reported by users in widely different cultures and countries across the world are presented. Both sets of measures are shown to provide valid measurement of therapy progress and outcome, and both exist in carefully translated versions from across the world. In practice, therapists have found that in addition to measuring effectiveness, both types of measures can powerfully influence the therapeutic process when used interactively in the session with clients. The evidence of wide applicability and acceptability to clients is supplemented by examples of cultural variation. These extensive experiences demonstrate the potential of measures with a proven cross‐cultural applicability to enhance the cultural sensitivity of therapists, enable countries with limited resources and provision of family therapy to draw on strong empirical support, and ensure that linguistic minorities can be fully included in research.

This paper studies the intermediation of auto loans through auto dealers using new and comprehensive administrative data. The arrangements between auto dealers and lenders incentivize dealers to increase loan prices. We leverage details of the corresponding contracts to demonstrate that many consumers are less responsive to finance charges than to vehicle charges. Taking this behavior into account, we estimate an equilibrium model of dealer price setting and lender competition. We explore counterfactuals where dealers have no discretion to price loans and final rates are set by lenders instead. We find large gains in consumer surplus from such a policy.

This paper studies the intermediation of auto loans through auto dealers using new and comprehensive administrative data. The arrangements between auto dealers and lenders incentivize dealers to increase loan prices. We leverage details of the corresponding contracts to demonstrate that many consumers are less responsive to finance charges than to vehicle charges. Taking this behavior into account, we estimate an equilibrium model of dealer price setting and lender competition. We explore counterfactuals where dealers have no discretion to price loans and final rates are set by lenders instead. We find large gains in consumer surplus from such a policy.

Over the past couple of decades, and especially since the financial crisis in 2008-09, real interest rates have collapsed. For much of the past two years they have been negative, but they have been trending down for some while. But how far have real rates fallen? This note computes a measure of the world real interest rate and, where possible, a measure of the implied future real rate. It also makes public our estimates of the world real interest rate so they can be used by other researchers.