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Background: Lesion network mapping (LNM) is a popular framework to assess clinical syndromes following brain injury. The classical approach involves embedding lesions from patients into a normative functional connectome and using the corresponding functional maps as proxies for disconnections. However, previous studies indicated limited predictive power of this approach in behavioral deficits. We hypothesized similarly low predictiveness for overall survival (OS) in glioblastoma (GBM). Methods: A retrospective dataset of patients with GBM was included (n = 99). Lesion masks were registered in the normative space to compute disconnectivity maps. The brain functional normative connectome consisted in data from 173 healthy subjects obtained from the Human Connectome Project. A modified version of the LNM was then applied to core regions of GBM masks. Linear regression, classification, and principal component (PCA) analyses were conducted to explore the relationship between disconnectivity and OS. OS was considered both as continuous and categorical (low, intermediate, and high survival) variable. Results: The results revealed no significant associations between OS and network disconnection strength when analyzed at both voxel-wise and classification levels. Moreover, patients stratified into different OS groups did not exhibit significant differences in network connectivity patterns. The spatial similarity among the first PCA of network maps for each OS group suggested a lack of distinctive network patterns associated with survival duration. Conclusions: Compared with indirect structural measures, functional indirect mapping does not provide significant predictive power for OS in patients with GBM. These findings are consistent with previous research that demonstrated the limitations of indirect functional measures in predicting clinical outcomes, underscoring the need for more comprehensive methodologies and a deeper understanding of the factors influencing clinical outcomes in this challenging disease.

Denne artikel skærper indsigterne fra bogen Racism in Danish Welfare Work with Refugees – Troubled by Difference, Docility and Dignity (2022) ved at stille skarpt på bogens teoretiske bidrag med omdrejningspunkt i begrebet velfærdsracisme. Med udgangspunkt i korte beskrivelser af bogens teoretisk-analytiske tilgang, empiriske materiale og analytiske arbejde, udfolder artiklen, hvordan velfærdsracisme kan forstås som næret af en integrationistisk epistemologi i velfærdsarbejdet i form af de racialt kodede grundkategorier udvikling, menneske, samfund og professionalisme; som historisk rekursivitet i kraft af de moderne spøgelser forskel, føjelighed og værdighed, der til stadighed dukker op i velfærdsarbejdet med flygtninge; og som udtrykt i velfærdsarbejdets standardfortællinger om farveblindhed, potentialisering og medfølelse, som velfærdsarbejderne igennem deres arbejde kontinuerligt investerer i, hvorved sociale grænser for menneske og samfund patruljeres og den integrationistiske epistemologi institutionaliseres. På denne baggrund konkluderer vi, at velfærdsracismen forhindrer velfærdsarbejdets universelle realisering.

Abstract Meningiomas are the most prevalent tumors of the central nervous system. Their standard treatment is surgery, which can be curative. Adjuvant radiotherapy treatment is reserved for newly diagnosed cases of grade II and grade III meningiomas in cases of recurrent disease or when surgery is not radical or feasible. However, around 20% of these patients cannot undergo further surgical and/or radiotherapy treatment. Systemic oncological therapy can find its place in this setting. Several tyrosine kinase inhibitors have been tested (gefitinib, erlotinib, sunitinib) with unsatisfactory or negative results. Bevacizumab has shown encouraging results in these settings of patients. Immunotherapy with immune checkpoint inhibitors has reported interesting results with modest objective response rates. Several ongoing studies are assessing different target therapies and multimodal therapies; the results are to be disclosed. Not only a better understanding of the molecular characteristics in meningiomas has allowed the gathering of more information regarding pathogenesis and prognosis, but in addition, the availability of new target therapy, immunotherapy, and biological drugs has widened the scope of potentially effective treatments in this patient population. The aim of this review was to explore the radiotherapy and systemic treatments of meningioma with an analysis of ongoing trials and future therapeutic perspectives.

IntroductionDrug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter.MethodsThis was a multicenter phase II single-arm clinical trial. The experimental procedure involved the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol in newly-diagnosed GBM patients carrying an unmethylated MGMT gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity.ResultsForty-one patients were evaluated. Twenty patients (48.7%) completed 6 cycles of treatment with TMZ+CPZ. At 6 months, 27 patients (65.8%) were without progression, achieving the primary endpoint. Median PFS was 8.0 months (95% CI: 7.0-9.0). Median OS was 15.0 months (95% CI: 13.1-16.9). Adverse events led to reduction or interruption of CPZ dosage in 4 patients (9.7%).DiscussionThe addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated MGMT gene promoter was safe and led to a longer PFS than expected in this population of patients. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.

Ependymomas are rare glial tumors with clinical and biological heterogeneity, categorized into supratentorial ependymoma, posterior fossa ependymoma, and spinal cord ependymoma, according to anatomical localization. Spinal ependymoma comprises four different types: spinal ependymoma, spinal ependymoma MYCN-amplified, myxopapillary ependymoma, and subependymoma. The clinical onset largely depends on the spinal location of the tumor. Both non-specific and specific sensory and/or motor symptoms can be present. Owing to diverse features and the low incidence of spinal ependymomas, most of the current clinical management is derived from small retrospective studies, particularly in adults. Treatment involves primarily surgical resection, aiming at maximal safe resection. The use of radiotherapy remains controversial and the optimal dose has not been established; it is usually considered after subtotal resection for WHO grade 2 ependymoma and for WHO grade 3 ependymoma regardless of the extent of resection. There are limited systemic treatments available, with limited durable results and modest improvement in progression-free survival. Thus, chemotherapy is usually reserved for recurrent cases where resection and/or radiation is not feasible. Recently, a combination of temozolomide and lapatinib has shown modest results with a median progression-free survival (PFS) of 7.8 months in recurrent spinal ependymomas. Other studies have explored the use of temozolomide, platinum compounds, etoposide, and bevacizumab, but standard treatment options have not yet been defined. New treatment options with targeted treatments and immunotherapy are being investigated. Neurological and supportive care are crucial, even in the early stages. Post-surgical rehabilitation can improve the consequences of surgery and maintain a good quality of life, especially in young patients with long life expectancy. Here, we focus on the diagnosis and treatment recommendations for adults with spinal ependymoma, and discuss recent molecular advances and new treatment perspectives.

BackgroundResting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain’s functional topological organization and glioblastoma (GBM) location. Furthermore, we assessed whether GBM distribution across these networks was associated with overall survival (OS).Materials and methodsWe included patients with histopathological diagnosis of IDH-wildtype GBM, presurgical MRI and survival data. For each patient, we recorded clinical-prognostic variables. GBM core and edema were segmented and normalized to a standard space. Pre-existing functional connectivity-based atlases were used to define network parcellations: 17 GMNs and 12 WMNs were considered in particular. We computed the percentage of lesion overlap with GMNs and WMNs, both for core and edema. Differences between overlap percentages were assessed through descriptive statistics, ANOVA, post-hoc tests, Pearson’s correlation tests and canonical correlations. Multiple linear and non-linear regression tests were employed to explore relationships with OS.Results99 patients were included (70 males, mean age 62 years). The most involved GMNs included ventral somatomotor, salient ventral attention and default-mode networks; the most involved WMNs were ventral frontoparietal tracts, deep frontal white matter, and superior longitudinal fasciculus system. Superior longitudinal fasciculus system and dorsal frontoparietal tracts were significantly more included in the edema (p

BackgroundAlthough gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome.MethodsPeripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters.ResultsChanges in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient’s outcome.ConclusionsThis work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use.

This study aimed to prospectively evaluate, on a long-term basis, corneal side effects secondary to compassionate administration of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in patients affected by EGFR-amplified recurrent glioblastoma. Fifteen patients with a median follow-up of 4.3 months after treatment discontinuation were enrolled. Each patient underwent full ophthalmologic examination including in vivo corneal confocal microscopy (CCM). No CTCAE grade 4 toxicity and four (27%) grade 3 toxicities were documented during treatment. Ocular symptoms (blurred vision, eye pain, photophobia) were experienced by all patients, reaching maximal severity after the second ABT-414 infusion, with persistence until treatment discontinuation. During treatment, CCM documented specific changes in the corneal epithelium and in the sub-basal nerve plexus layer fibers of all eyes. The median time of symptoms resolution after treatment discontinuation ranged from 38 days (eye pain) to 53 days (photophobia). The median time of signs resolution ranges from 14 days (corneal ulcer) to 38 days (superficial punctate epitheliopathy, corneal stroma edema and intraepithelial cysts). ABT-414 corneal side effects are detectable in all treated patients. Related symptoms are gradually experienced by all patients during treatment and although reversible, they are characterized by a relative prolonged persistence after treatment discontinuation.

Background: The aim of this study was to prospectively analyse, for the first time worldwide by in vivo clinical confocal microscopy (CCM), corneal side effects secondary to the use of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in a cohort of patients affected by EGFR-amplified recurrent glioblastoma. Methods: Each enrolled patient underwent full ophthalmologic examination including in vivo CCM of the cornea. Each patient was examined at baseline and every 2 weeks during treatment as long as patient conditions allowed it. Results: A total of 10 patients were consecutively enrolled. Median follow-up was 5 months. No Common Terminology Criteria for Adverse Events Version 4.0 grade 4 toxicity was documented. Two (20%) grade 3 toxicities were documented at week 8. CCM examination detected in all eyes multiple and diffuse hyperreflective white round spots in the corneal basal epithelial layers (100%), progressive subbasal nerve plexus layer fibres fragmentation followed by full disappearance (100%) and appearance of round cystic structures in the corneal epithelium (100%). All CCM documented side effects reached the peak of prevalence and severity after a median of 3 infusions. After treatment discontinuation, the reversibility of corneal side effects was documented at CCM after a median of 4 weeks. Conclusion: ABT-414 toxicity is not only directed to the corneal epithelium, but also to corneal nerves. Side effects are detectable in all treated patients and CCM documents early corneal epithelium and subbasal nerve plexus toxicity, with subsequent progressive restoration after treatment discontinuation. Ocular side effects due to ABT-414 can be manageable.

Education is abundant in practical texts regulating, reflecting, guiding, and documenting. Nevertheless, practical texts often pass unnoticed in educational studies. This article discusses how poststructural documentary analysis can use practical texts for problematizing naturalized problematizations in education. Hence, the article takes educational problematizations of immigrant pupils as an example and objectifies it as a social question shaped by and shaping education. Then, key characteristics of practical texts, and how a text corpus can be established, is developed. In conclusion, the article advances a non-evaluative critique of education deploying systematic yet insubordinate analytical experimentation through aesthetic-effective montaging and (re)problematizations.

Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.