Glioblastomas are deadly neoplasms resistant to current treatment modalities. Fibroblast activation protein (FAP) is a protease which is not expressed in most of the normal adult tissues but is characteristically present in the stroma of extracranial malignancies. FAP is considered a potential therapeutic target and is associated with a worse patient outcome in some cancers. The FAP localization in the glioma microenvironment and its relation to patient survival are unknown. By analyzing 56 gliomas and 15 non-tumorous brain samples, we demonstrate increased FAP expression in a subgroup of high-grade gliomas, in particular on the protein level. FAP expression was most elevated in the mesenchymal subtype of glioblastoma. It was neither associated with glioblastoma patient survival in our patient cohort nor in publicly available datasets. FAP was expressed in both transformed and stromal cells; the latter were frequently localized around dysplastic blood vessels and commonly expressed mesenchymal markers. In a mouse xenotransplantation model, FAP was expressed in glioma cells in a subgroup of tumors that typically did not express the astrocytic marker GFAP. Endogenous FAP was frequently upregulated and part of the FAP host cells coexpressed the CXCR4 chemokine receptor. In summary, FAP is expressed by several constituents of the glioblastoma microenvironment, including stromal non-malignant mesenchymal cells recruited to and/or activated in response to glioma growth. The limited expression of FAP in healthy tissues together with its presence in both transformed and stromal cells suggests that FAP may be a candidate target for specific delivery of therapeutic agents in glioblastoma.

End-to-side neurorrhaphy offers an advantage over classic neurotization in not requiring sacrifice of any of the surrounding nerves or the fascicles of the ulnar nerve. Typical synkinesis of muscle contraction innervated by the recipient nerve with contraction of muscles innervated by the donor was observed in patients after end-to-side neurorrhaphy.

Object. To date, reports on the clinical efficacy of intraventricularly and intrathecally administered antibiotics for the treatment of neurosurgical ventriculitis and meningitis in adults are limited. The authors aimed to evaluate the efficacy and safety of the intraventricular (IVT) and lumbar intrathecal (IT) administration of antibiotics in critically ill neurosurgical patients.Methods. Thirty-four postneurosurgical patients with meningitis and ventriculitis were studied. Intraventricular/ lumbar intrathecal antibiotics were administered due to positive CSF cultures persisting despite the use of intravenous antibiotics. The time period until CSF sterilization, changes in clinical state, and efficacy of different routes of antibiotic administration were evaluated.Results. The mean time necessary to obtain CSF sterilization was 2.9 ± 2.7 days (range 1-12 days). The CSF cultures became negative within 24 hours after the administration of IVT/IT antibiotics in 17 patients (50%) and up to 48 hours in a further 6 patients (18%). The clinical outcome of patients assessed by the modified Rankin Scale improved in 17 patients (50%), stayed unchanged in 10 patients (29%), and was impaired in 1 patient (3%). Six patients (18%) died; however, 2 of them died due to reasons not directly related to meningitis or ventriculitis, so the overall mortality rate for meningitis and/or ventriculitis was 11.8% in this group of patients. All patients with ventriculitis (n = 4) were treated by antibiotics administered via the IVT route. The average time to CSF sterilization was 6.5 days in the patients with ventriculitis. Thirty patients had clinical signs of meningitis without ventriculitis. Despite the higher ratio of unfavorable Gram-negative meningitis in the subgroup of patients treated via lumbar drainage, the mean duration of CSF sterilization was 2.2 days compared with 2.6 days in the subgroup treated via external ventricular drainage, a difference that was not statistically significant (p = 0.3). Adverse effects of IVT/IT antibiotics appeared in 3 of 34 patients and were of low clinical significance.Conclusions. Intraventricular/lumbar intrathecal antibiotics can lead to very quick CSF sterilization in postneurosurgical patients with meningitis and ventriculitis. The relapse rate of meningitis and/or ventriculitis is also very low among patients treated by IVT/IT antibiotics. Intraventricular/lumbar intrathecal administration of antibiotics appears to be an effective and safe treatment for infections of the CNS caused by multidrug-resistant organisms. In patients with signs of ventriculitis, the authors prefer the IVT route of antibiotics. This study did not prove a lower efficacy of administration of antibiotics via lumbar drainage compared with the ventricular route in patients with meningitis. (http://thejns.org/doi/abs/10.3171/2013.6.JNS122126) key WorDs • antibiotic • intraventricular • intrathecal • meningitis • ventriculitis • brain abscess • infectionAbbreviations used in this paper: EVD = external ventricular dra...

The availability of timely, accessible and well documented data plays a central role in the process of digital transformation in our societies and businesses. Considering this, the European Commission has established an ambitious agenda that aims to leverage on the favourable technological and political context and build a society that is empowered by data-driven innovation. Within this context, geospatial data remains critically important for many businesses and public services. The process of establishing Spatial Data Infrastructures (SDIs) in response to the legal provisions of the European Union INSPIRE Directive has a long history. While INSPIRE focuses mainly on ’unlocking’ data from the public sector, there is need to address emerging technological trends, and consider the role of other actors such as the private sector and citizen science initiatives. The objective of this paper, given those bounding conditions is twofold. Firstly, we position SDI-related developments in Europe within the broader context of the current political and technological scenery. In doing so, we pay particular attention to relevant technological developments and emerging trends that we see as enablers for the evolution of European SDIs. Secondly, we propose a high level concept of a pan-European (geo)data space with a 10-year horizon in mind. We do this by considering today’s technology while trying to adopt an evolutionary approach with developments that are incremental to contemporary SDIs.

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th–April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017–2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

The dorsal root entry zone (DREZ) thermocoagulation for intractable pain after brachial plexus avulsion was performed in 21 patients. Good results in pain relief (relief of more than 75% of preoperative pain) were achieved in 62% of patients, whereby fair results (relief of 25-75% of preoperative pain) in 38% of patients. There was no patient with poor result (relief of less than 25% of preoperative pain). Complication rate was 14%. The whole patient population was subdivided into two groups (Group 1 and Group 2). Direct spinal cord bipolar stimulation and registration with the goal to localize DREZ was performed in the Group 2 consisting of 12 patients (n=12). The point on the spinal cord surface where no response after stimulus of low intensity was obtained was the site (the posterolateral sulcus) we identified as the most suitable point for the placement of radiofrequency thermocoagulation electrode. Comparing with the Group 1 consisting of nine patients (n=9), where the localization of DREZ by evoked potentials was not performed, significantly better effect of pain relief was recorded (P<0.05, odds ratio 10). There was no statistically significant difference (P>0.7) in complication rate in Group 1 and Group 2. Described electrophysiological technique is very helpful in identifying of DREZ and, in combination with microsurgical technique, can create DREZ thermocoagulation more effective.

Fibroblast activation protein (FAP) is a membrane-bound protease that is upregulated in a wide range of tumours and viewed as a marker of tumour-promoting stroma. Previously, we demonstrated increased FAP expression in glioblastomas and described its localisation in cancer and stromal cells. In this study, we show that FAP+ stromal cells are mostly localised in the vicinity of activated CD105+ endothelial cells and their quantity positively correlates with glioblastoma vascularisation. FAP+ mesenchymal cells derived from human glioblastomas are non-tumorigenic and mostly lack the cytogenetic aberrations characteristic of glioblastomas. Conditioned media from these cells induce angiogenic sprouting and chemotaxis of endothelial cells and promote migration and growth of glioma cells. In a chorioallantoic membrane assay, co-application of FAP+ mesenchymal cells with glioma cells was associated with enhanced abnormal angiogenesis, as evidenced by an increased number of erythrocytes in vessel-like structures and higher occurrence of haemorrhages. FAP+ mesenchymal cells express proangiogenic factors, but in comparison to normal pericytes exhibit decreased levels of antiangiogenic molecules and an increased Angiopoietin 2/1 ratio. Our results show that FAP+ mesenchymal cells promote angiogenesis and glioma cell migration and growth by paracrine communication and in this manner, they may thus contribute to glioblastoma progression.

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