INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99–not applicable], compared with 117 days (95% CI, 106–143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases.
Significance:
The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes.
See related commentary by Eggermont et al., p. 2677.
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Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.
The Airtraq laryngoscope is easier to use but it does not have any significant advantages compared with the Macintosh laryngoscope for routine airway management. More studies are needed to evaluate its use in patients with a difficult airway, and in emergency procedures.
In this work, the effect of different treatments using selected combinations of chloride salts (NaCl, KCl, CaCl2, MgCl2) in fermentation brine to assess the safety, quality, and nutritional value of the Spanish style cv. Chalkidiki green table olives spontaneously fermented is studied. Examination of safety parameters (bacteria/yeasts, pH, acidity) and changes in olive color and texture characteristics in brines during fermentation, and in mineral content of olives upon storage up to 12 months, is conducted using appropriate methods. Sensory evaluation takes place in certain cases. Among the tested salt combinations, those of 4.08% NaCl, 2.8% KCl, 1% CaCl2, and 0.12% MgCl2 (w/v) are found to be the most effective regarding safety, color, texture, and taste. Findings support that Spanish style cv. Chalkidiki green olives can be spontaneously fermented in reduced NaCl content brine. The 50% lower NaCl content of the fermented olives compared with that in traditionally fermented ones suggests that reformulation of cv. Chalkidiki green table olives by safe intervention is feasible.
Practical Applications: cv. Chalkidiki green table olives are of high importance for the Greek economy. Traditionally they are spontaneously fermented in NaCl brine (8% w/v). Partial replacement of NaCl content with other salts in such a line results in a product acceptable in terms of safety and quality characteristics. The Greek table olive industry may profit from the findings in an attempt to remodel the traditional spontaneous fermentation in green olive processing according to international dietary guidelines.
The project aimed to improve productivity of psychiatric out patient clinic using quality improvement techniques through “Listening Into Action", a national programme designed to engage and support front-line clinicians to make improvements to patient care. We identified reasons as to why our patients missed appointments and then introduced a system to reduce “did not attend” (DNA) rates.Non-attendance at appointments results in a waste of resources and increases waiting times. It has been reported that DNA rates in mental health are higher compared to other settings. Therefore, reducing DNA rates are a priority for mental health care providers.We collected DNA rates over a period of months over May 2013 to September 2013. We conducted a patient survey to inquire why the patients missed their appointments. The aim of the project and results from the survey were presented and discussed at the multi-disciplinary team meeting to generate ideas for improvement and engage the team with the project. As the most frequent response from the survey was ‘forgetting the appointment’, we decided to introduce text messaging as an intervention to remind patients of their appointments. We also ensured that staff updated the mobile phone records for the patients at each appointment. We monitored the DNA rates after introducing this change on a monthly basis.Following our intervention, there was an overall reduction in DNA rates for all disciplines from 11.4% to 10.62% with the greatest change for medical DNA's from 17.7% to 11.8 %.Results from a patient survey showed that the reasons for non-attendance are multi-factorial and require a complex approach. Our intervention was a simple one but still it demonstrated some effectiveness. Reducing DNA rates requires interventions to be regularly monitored so that their effect is sustained over a period of time.
An intraparenchymal pericatheter cyst is a rare complication of ventriculoperitoneal shunt, which is not well described yet. Due to its rarity, lack of characteristic symptoms and radiological features that often mimic brain tumors or abscesses, especially in head computed tomography without contrast can be easily misdiagnosed. We report the case of a 9-year-old girl who was admitted to a peripheral hospital due to severe headaches and vomiting. The child had a history of craniotomy and ventriculoperitoneal shunt for posterior fossa tumor, performed in our department, 4 years earlier. The patient underwent a brain magnetic resonance imaging (MRI) scan and transmitted to our hospital with the diagnosis of brain tumor. However, a closer look at the MRI established the diagnosis of intraparenchymal pericatheter cerebrospinal fluid cyst; hence, the patient underwent shunt revision and cyst drainage. We researched the literature and described 20 reported cases, discussing the pathophysiological mechanisms, the radiological features, and the optimal treatment of this interesting, yet a challenging complication.
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