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BACKGROUND: Since 2013, pediatric oncologists from Central and South America discuss neuro-oncology cases with experts from North America and Europe in a web-based "Latin American Tumor Board" (LATB). Here, we evaluate the feasibility of recommendations rendered by the Board. METHODS: An electronic questionnaire was distributed to physicians who had received recommendations between October 2017 and October 2018. Physicians were asked regarding the feasibility of each recommendation given during the LATB discussion. Baseline case characteristics of all presented cases were obtained from anonymized minutes. RESULTS: Of the 142 patients discussed, data on 103 patients from 15 countries were available, corresponding to 283 recommendations. Physicians followed 60% of diagnostic procedural recommendations and 69% of therapeutic recommendations. The most difficult recommendations to follow were genetic and molecular testing, pathology review, chemotherapy, surgery, and molecular targeted therapies. Histological diagnoses changed in eight of 18 cases in which a pathology review was undertaken. Fifty-four percent of the recommendations that could not be implemented were considered not feasible in the specific context of the patient, while 31% were not implemented due to a decision of the medical staff or the parents (15% not specified). However, 96% of respondents considered the recommendations useful. CONCLUSION: Recommendations were frequently perceived as useful, and were applicable in the participating institutions. Nevertheless, limitations in availability of diagnostic procedures and treatment modalities affected the feasibility of some recommendations. Tele-oncology tumor boards offer physicians from low- and middle-income countries access to real-time, high-level subspecialist expertise and provide a valuable platform for worldwide information exchange.

Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare recently described entity. Fourteen CNS HGNET-MN1 patients were identified using genome-wide methylation arrays/RT-PCR across seven institutions. All patients had surgery (gross total resection: 10; subtotal resection: four) as initial management followed by observation alone in three patients, followed by radiotherapy in eight patients (focal: five; craniospinal: two; CyberKnife: one) and systemic chemotherapy in three patients. Seven patients relapsed; five local and two metastatic, despite adjuvant radiotherapy, of which three died. Treatment of CNS HGNET-MN1 remains a major treatment challenge despite aggressive surgical resections and upfront radiotherapy, warranting new approaches to this rare malignancy.

Introduction: Whole genome analysis of non-WNT/non-SHH medulloblastomas (MB) was performed to compare chromosomal aberrations between MB without metastases (M0) and metastatic MB (M+). Objectives: Detection of whole chromosomal aberrations (WCA) as prognostic markers in distinct MB cohorts.[for full text, please go to the a.m. URL], Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS)

The identification of desmoplastic/nodular histology as an independent favourable prognostic marker in medulloblastoma (MB) of infancy has allowed the reduction of therapy in these patients to decrease longterm side-effects. Although we were able to demonstrate different origins and pathway activation[for full text, please go to the a.m. URL], 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Purpose: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. © 2014 by American Society of Clinical Oncology.

Objective: Rhabdoid tumors mainly affect infants and young children and may be found throughout the body. Within the CNS the term AT/RT, atypical teratoid rhabdoid tumor has been applied. Newer registry data suggest that in children below 6 months of age rhabdoid tumors may be the most common intracranial[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Summary Background Enteroaggregative Escherichia coli (EAggEC or EAEC) can spread and cause disease in developing countries, but it is not presently known whether it spreads disease in industrialised countries. Therefore, we did a prospective study to assess the incidence and the clinical manifestations of infections due to EAEC in children in Germany. Methods 798 children with diarrhoea, admitted to hospital within a defined geographical area during a 24-month period, were included in the trial. EAEC were cultured from stool specimens, screened by PCR, and identified by colony hybridisation from DNA sequences found on the virulence plasmid. The findings were confirmed by aggregative adherence to HEp-2 cells. Stool samples from 580 children admitted to hospital without diarrhoea were also studied as controls. Findings EAEC were found in the stools of 16 (2%) of 798 children with diarrhoea, but in none of 580 children without diarrhoea. Only four of the EAEC-infected children had travelled to developing countries. Most EAEC infections were acquired in the summer months. Infection with EAEC was associated with acute, watery diarrhoea in 12 children, and with chronic diarrhoea of up to 5 months' duration in four. Five children had abdominal colic that lasted for 2–4 weeks as their main symptom. The incidence of EAEC infection was 7·7 patients admitted to hospital per 100 000 children in the general population aged younger than 16 years. Interpretation EAEC infection is associated with acute, watery diarrhoea and may be acquired in industrialised countries. Chronic diarrhoea or abdominal colic of unknown aetiology in young children may also be caused by EAEC infection.

Poster-Abstract

Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Objective The aim of this systematic review with meta-analysis was to evaluate the effectiveness of RMT in internal and central nervous system disorders, on pulmonary function, exercise capacity and quality of life. Methods The inclusion criteria were (1) publications designed as Randomized Controlled Trial (RCT), with (2) participants being adults with pulmonary dysfunction caused by an internal disease or central nervous system disorder, (3) an intervention defined as RMT (either IMT or EMT) and (4) with the assessment of exercise capacity, respiratory function and quality of life. For the methodological quality assessment of risk of bias, likewise statistical analysis and meta-analysis the RevMan version 5.3 software and the Cochrane Risk of Bias Tool were used. Two authors independently analysed the following databases for relevant research articles: PubMed, Scopus, Cochrane Library, Web of Science, and Embase. Results From a total of 2200 records, the systematic review includes 29 RCT with an overall sample size of 1155 patients. Results suggest that patients with internal and central nervous system disorders who underwent RMT had better quality of life and improved significantly their performance in exercise capacity and in respiratory function assessed with FVC and MIP when compared to control conditions (i.e. no intervention, sham training, placebo or conventional treatments). Conclusion Respiratory muscle training seems to be more effective than control conditions (i.e. no intervention, sham training, placebo or conventional treatment), in patients with pulmonary dysfunction due to internal and central nervous system disorders, for quality of life, exercise capacity and respiratory function assessed with MIP and FVC, but not with FEV1.

It is estimated that over 400 million people worldwide experience some form of urinary incontinence (UI). Pelvic floor muscle training (PFMT) is commonly used in cases of urine loss. Game therapy (GT) has been suggested as a new conservative modality for UI treatments. GT represents a form of virtual reality (VR) that allows users to interact with elements of a simulated scenario. The purpose of this review was to assess the potential of using VR-based PFMT in the treatment of UI with a particular focus on the impact of this form of therapy on the patients’ muscle function, symptoms of UI and quality of life (QoL). The following electronic databases were searched: PubMed, Embase, Cochrane Library, Scopus and Web of Science. Systematic review methods were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Electronic medical databases were searched from inception to 28 January 2021. From a total of 38 articles, 26 were analyzed after removing duplicates, then 22 records were excluded according to inclusion criteria and 4 were assessed as full texts. Finally, 2 randomized controlled trials (RCT) with 79 patients were included. For the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the meta-analysis showed a significant difference in favor of the control condition (MD = 2.22; 95% CI 0.42, 4.01; I2 = 0%). Despite the popularity of the use of VR in rehabilitation, we found a scarcity of literature evaluating the application of VR in the field of UI therapy. Only one study matched all of the criteria established. The effects of VR training improved PFM function and QoL; however, these changes were comparable to those of traditional PFMT. It is not possible to reach final conclusions from one study; thus, further development of VR interventions in the field of UI treatments are needed.

It remains unknown whether variation of scores on the Medical Research Council (MRC) scale for muscle strength is associated with operator-independent techniques: dynamometry and surface electromyography (sEMG). This study aimed to evaluate whether the scores of the MRC strength scale are associated with instrumented measures of torque and muscle activity in post-stroke survivors with severe hemiparesis both before and after an intervention. Patients affected by a first ischemic or hemorrhagic stroke within 6 months before enrollment and with complete paresis were included in the study. The pre- and post-treatment assessments included the MRC strength scale, sEMG, and dynamometry assessment of the triceps brachii (TB) and biceps brachii (BB) as measures of maximal elbow extension and flexion torque, respectively. Proprioceptive-based training was used as a treatment model, which consisted of multidirectional exercises with verbal feedback. Each treatment session lasted 1 h/day, 5 days a week for a total 15 sessions. Nineteen individuals with stroke participated in the study. A significant correlation between outcome measures for the BB (MRC and sEMG p = 0.0177, ρ = 0.601; MRC and torque p = 0.0001, ρ = 0.867) and TB (MRC and sEMG p = 0.0026, ρ = 0.717; MRC and torque p = 0.0001, ρ = 0.873) were observed post intervention. Regression models revealed a relationship between the MRC score and sEMG and torque measures for both the TB and BB. The results confirmed that variation on the MRC strength scale is associated with variation in sEMG and torque measures, especially post intervention. The regression model showed a causal relationship between MRC scale scores, sEMG, and torque assessments.

BACKGROUND: Studies demonstrated the efficacy of virtual reality (VR) as a method supporting the post-stroke neuro-rehabilitation process by activating motor learning processes. Nevertheless, stroke is frequently accompanied by serious psychological problems including depression, which is associated with an increased risk of mortality, lower post-stroke physical activity, and higher disability in stroke patients. OBJECTIVES: To explore the current use of VR as a method supporting the neuro-rehabilitation process, both in physical and psychological dimensions. METHODS: An exploratory review was conducted with a narrative synthesis. PubMed was used for literature search. Search includes the use of VR in physical rehabilitation, and as support therapy in psychiatric disorders. Both primary research and systematic reviews were included. RESULTS: In neurological disorders rehabilitation, out of 22 studies, 16 concerned stroke survivors. In psychiatric disorders, 44 literature reviews were included. CONCLUSION: The studies confirmed the effectiveness of various forms of VR treatment in the alleviation of psychological and behavioral problems and psychiatric disorders. There is a shortage of VR-based technological solutions that would, besides physical rehabilitation, offer stroke patients therapeutic tools to alleviate psychological disturbance and improve the patient’s mood and motivation. Such solutions will most likely become a field of intensive research in the coming years.

Sebastian Rutkowski, 1 Anna Rutkowska, 1 Paweł Kiper, 2 Dariusz Jastrzebski, 3 Henryk Racheniuk, 1 Andrea Turolla, 2 Jan Szczegielniak, 1 Richard Casaburi 4 1Institute of Physiotherapy, Department of Physical Education and Physiotherapy, Opole University of Technology, Opole, Poland; 2Laboratory of Neurorehabilitation Technologies, Fondazione Ospedale San Camillo IRCCS, Venice, Italy; 3School of Medicine with the Division of Dentistry, Department of Lung Diseases and Tuberculosis, Medical University of Silesia, Zabrze, Poland; 4Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USACorrespondence: Sebastian RutkowskiInstitute of Physiotherapy, Department of Physical Education and Physiotherapy, Opole University of Technology, Opole, PolandTel +48 507027792Fax +48 77 449 80 00Email s.rutkowski@po.opole.plPurpose: This study compared the effects of inpatient-based rehabilitation program of patients with chronic obstructive pulmonary disease (COPD) using non-immersive virtual reality (VR) training with a traditional pulmonary rehabilitation program. The aims of this study were to determine 1) whether rehabilitation featuring both VR as well as exercise training provides benefits over exercise training (ET) alone and 2) whether rehabilitation featuring VR training instead of exercise training provides equivalent benefits.Patients and Methods: The study recruited 106 patients with COPD to a 2-week high-intensity, five times a week intervention. Randomized into three groups, 34 patients participated in a traditional pulmonary rehabilitation program including endurance exercise training (ET), 38 patients participated in traditional pulmonary rehabilitation, including both endurance exercise training and virtual reality training (ET+VR) and 34 patients participated in pulmonary rehabilitation program including virtual reality training but no endurance exercise training (VR). The traditional pulmonary rehabilitation program consisted of fitness exercises, resistance respiratory muscle and relaxation training. Xbox 360® and Kinect® Adventures software were used for the VR training of lower and upper body strength, endurance, trunk control and dynamic balance. Comparison of the changes in the Senior Fitness Test was the primary outcome. Analysis was performed using linear mixed-effects models.Results: The comparison between ET and ET+VR groups showed that ET+VR group was superior to ET group in Arm Curl (p< 0.003), Chair stand (p< 0.008), Back scratch (p< 0.002), Chair sit and reach (p< 0.001), Up and go (p< 0.000), 6-min walk test (p< 0.011). Whereas, the comparison between ET and VR groups showed that VR group was superior to ET group in Arm Curl (p< 0.000), Chair stand (p< 0.001), 6-min walk test (p< 0.031).Conclusion: Results suggest that pulmonary rehabilitation program supplemented with VR training is beneficial intervention to improve physical fitness in patients with COPD.Keywords: virtual reality, COPD, pulmonary rehabilitation, physical activity, exercise &nbsp

Objectives To analyse the effectiveness of virtual reality-based interventions within several fields of rehabilitation, and to investigate whether the outcomes of virtual reality-based interventions, in terms of upper or lower limb function, gait and balance, differ with respect to the virtual reality system used. Methods A search of PubMed database resulted in an initial total of 481 records. Of these, 27 articles were included in the study. A final total of 20 articles, with neurological, orthoapedic, geriatric or paediatric patients, published between 2012 and 2019, were included in the study. Two independent reviewers selected potentially relevant articles based on the inclusion criteria for full-text reading. They extracted data, and evaluated the methodological quality of each study. Results Seventeen studies were included in the meta¬ -analysis. Eight studies analysed upper limb function, with no significant evidence that specialized VR is superior to conventional treatment. Regarding FuglMeyer scale results, the effect of specialized virtual reality therapy was found to be significantly better than conventional treatment. No significant differences between specialized VR and conventional treatment were observed in effects on hand dexterity and gait. There was a significant difference in effects on balance in favour of specialized virtual reality as compared to conventional treatment. Gaming virtual reality was significantly better than conventional treatment for upper limb function, but not for hand dexterity, gait and balance. Conclusion Use of specialized virtual reality and gaming virtual reality can be advantageous for treatment of the upper extremity, but not for hand dexterity and gait in all pathologies considered. Specialized virtual reality can improve balance in neurological patients.

Background Virtual reality (VR) is being used more and more often as a therapeutic tool in psychology or psychiatry. In recent years, VR interventions appear more extensively also in disorders such as depression, anxiety and phobia. However, there has yet to be a comprehensive synthesis and critical review of the literature to identify future directions to advance the field in this area. Objectives To broadly characterize the literature to date on the application of VR in psychiatric disorders by conducting a systematic review of reviews, describe the limitations of existing research, suggest avenues for future research to address gaps in the current literature and provide practical recommendations for incorporating VR into various treatments for psychiatric disorders. Methods PubMed and Web of Science databases were searched for reviews on VR use in psychiatric disorders (e.g. various pain perceptions, post-traumatic stress disorder, phobias, attention deficit hyperactivity disorder, psychosis, depression). The methodological quality of each literature review was assessed using AMSTAR. Results The original search identified 848 reviews, of which 70 were included in the systematic review of reviews. Broadly, the literature indicates that various VR interventions could be useful in different psychiatric disorders. Conclusion This study provides evidence supporting the positive impact of VR therapy in psychiatric disorders. However, the impact is defined differently according to the studied area. Nevertheless, due to the continuous development of VR hardware and software, it is essential to conduct further research in the area of psychiatric disorders, especially as no review has concluded that VR does not work.

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.