bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.39.B An unusual case of astroblastoma in adult: a case report and review of the literature
Authors: Bernardes L d , José Santos A , Novaes de Rezende Batistella G , Silva Catito M , Martini Pazini A , Neri Andrade T , Gutierres Gambirasio B , Silva Fernandes N , Henriques Coronatto L , Caroline Freitas Barboza I 
Published: September 2022

Abstract

Background
Astroblastoma is an uncommon glial neoplasm of controversial histogenesis, clinical behavior and response to treatment yet to be understood. It usually appears in the cerebral hemisphere of young patients, preferably in the frontal and parietal lobes. Histologically, its characteristics overlap with high-grade gliomas, making the differential diagnosis between these entities complex. Clinical, radiological, histopathological correlations and, if necessary, genetic tests (MN1 Rearrangement) are essential for an accurate diagnosis.

Material and Methods
We present a case report based on data collected retrospectively from electronic medical records.

Results
A 63-year-old male with a 3-month history of headache and one episode of mental confusion. In the neurological exam, language alteration was noted and the other systemic exams were normal. Magnetic resonance imaging of the brain revealed an intra-axial expansive formation involving the insula, superior and middle temporal gyrus, left portion of brainstem, with lobulated contours and heterogeneous, solid-cystic appearance with intermingled hematic foci. The solid portion had heterogeneous contrast enhancement and foci of gross calcification. The lesion was resected and the postoperative MRI showed no residual tumor lesion. Histopathological evaluation showed an extensive pattern of perivascular pseudorosettes of astrocytic cells with broad processes radiating to central vessels, in addition to frequent foci of hyalinization. Immunohistochemistry showed positive staining with antibodies to glial fibrillary acidic protein (GFAP), vimentin and S100 protein, in addition to membranous positivity for epithelial membrane antigen (EMA). The Ki-67 index was 20%. Based on these data, the diagnosis of NOS astroblastoma was established. Four months after resection, imaging follow-up displayed enhancement of the surgical cavity, suggestive of local recurrence. The patient underwent three-dimensional conformal radiotherapy with a total dose of 6000cGy in 30 sessions, followed by adjuvant chemotherapy with temozolomide.The patient did not have tumor recurrence until the last follow-up made 16 months after surgery.

Conclusion
This is an atypical case of an extremely rare glial tumor of the central nervous system, since most patients with astroblastoma range from 3 months to 40 years (median: 15 years), which makes the diagnosis challenging.
P11.48.A Primary CNS lymphoma after CLIPPERS: a case series
Authors: Doubrovinskaia S , Sahm F , Thier M C , Bendszus M , Wick W , Seliger C , Kaulen L D 
Published: September 2022

Abstract

Background
Few cases of primary CNS lymphoma(PCNSL) following a diagnosis of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) are reported in the literature. Here we explore implications of this sequel for CLIPPERS follow-up and PCNSL outcome.

Material and Methods
A systematic review and meta-analysis of previously described cases in the MEDLINE database was performed in compliance with PRISMA guidelines. Clinical, radiological and pathological characteristics were summarized. Overall survival was estimated using the Kaplan-Meier method.

Results
In addition to a case from our institution, nine cases were previously described in the literature. Eight patients fulfilled diagnostic criteria for ‘definite’ CLIPPERS whereas two cases were diagnosed with ‘probable’ CLIPPERS. Male-to-female ratio was 9:1. Median interval from CLIPPERS to PCNSL diagnosis was 4.5 months. All patients had received immunosuppressive therapy including methylprednisone in all and azathioprine or cyclophosphamide in most cases. On MRI, appearance of a larger lesion (&gt;3mm) with peripheral contrast enhancement was noted in the most cases upon PCNSLdiagnosis. Whereas Epstein-Barr virus was not detected in biopsy specimen upon CLIPPERS diagnosis, it was identified in the majority of samples upon PCNSL diagnosis. Treatmentfor PCNSL included high-dose methotrexate basedchemotherapy in most cases, however median overall survival was poor (5.5 months).

Conclusion
Interval from CLIPPERS to PCNSL diagnosis was short and may mandate close clinical and radiological follow-up, specifically within the first two years after CLIPPERS diagnosis. Characteristics of PCNSL following CLIPPERS resemble other immunodeficiency-related PCNSL. Outcome was inferior and may reflect late diagnosis or brainstem localization.
P12.15.B Astrocyte immunometabolic regulation of the glioblastoma microenvironment drives tumor pathogenicity
Authors: Perelroizen R , Philosof B , Budick-Harmelin N , Chernobylsky T , Rotem K , Ron A , Shimon D , Tessler A , Adir O , Gaoni-Yogev A , Meyer T , Madi A , Ruppin E , Mayo L 
Published: September 2022

Abstract

Background
Malignant brain tumors are the cause of a disproportionate level of morbidity and mortality among cancer patients, an unfortunate statistic that has remained constant for decades. Despite considerable advances in the molecular characterization of these tumors, targeting the cancer cells has yet to produce significant advances in treatment. An alternative strategy is to target cells in the glioblastoma microenvironment, such as tumor associated astrocytes. Astrocytes control multiple processes in health and disease, ranging from maintaining the brain's metabolic homeostasis, to modulating neuroinflammation. However, their role in glioblastoma pathogenicity is not well understood.

Material and Methods
Immunocompetent mice were implanted with murine glioma cell lines and the role of astrocyte in the tumor pathogenicity was analyzed, and further investigated using in-vitro co-cultures.

Results
Here we report that depletion of reactive astrocytes regresses glioblastoma and prolongs mouse survival. Analysis of the tumor-associated astrocyte translatome, revealed that astrocytes initiate transcriptional programs that shape the immune and metabolic compartments in the glioma microenvironment. Specifically, their expression of CCL2 and CSF1 governs the recruitment of tumor-associated macrophages and promotes a pro-tumorigenic macrophage phenotype. Concomitantly, we demonstrate that astrocyte-derived cholesterol is key to glioma cell survival, and that targeting astrocytic cholesterol efflux, via ABCA1, halts tumor progression. In summary, astrocytes control glioblastoma pathogenicity by reprogramming the immunological properties of the tumor microenvironment and supporting the non-oncogenic metabolic dependency of glioblastoma on cholesterol.

Conclusion
These findings suggest that targeting astrocyte immunometabolic signaling may help treat this uniformly lethal brain tumor.
P13.02.B Fully automated segmentation and volumetric measurement of intracranial meningioma using deep learning
Authors: Kang H , Witanto J N , Pratama K , Lee D , Choi K , Choi S , Kim K , Kim M , Kim J , Kim Y , Park S , Park C 
Published: September 2022

Abstract

Background
Most intracranial meningiomas are small, asymptomatic, and incidentally found tumors. Since the growth of meningioma is the principal indication of treatment, accurate and rapid measurement of the volume of intracranial meningiomas is essential in clinical practice to determine the growth rate of the tumor. It could be useful for the management of meningiomas given their increasing incidence and the wait-and-see policy currently in use for asymptomatic meningiomas. The aim of this study was to develop and validate a computational model for fully automated meningioma segmentation and volume measurement on contrast-enhanced MR scans using deep learning.

Material and Methods
The retrospectively collected axial contrast-enhanced T1-weighted section images from patients diagnosed with meningioma were manually segmented and used to construct automatic segmentation models with six U-Net- and nnU-Net-based architectures. The performance of each model was evaluated with the Sørensen-Dice similarity coefficient (DSC) with internal (IVS) and external validation sets (EVS), each consisting of 100 independent MRI examinations.

Results
A total of 12,909 section images from 459 patients were applied for the training (median age 58 [52-66] [IQR]; 385 women [83.9%]). The median tumor volume of the training set was 2.36 cm3. A 2D nnU-Net showed the highest median DSCs of 0.922 and 0.893 for the IVS and EVS, respectively. The nnU-Nets achieved superior performance in meningioma segmentation than the U-Nets. The DSCs of the 2D nnU-Net for small meningiomas less than 1 cm3 were 0.769 and 0.780 with the IVS and EVS, respectively.

Conclusion
We successfully developed a fully automated and accurate volumetric measurement tool for meningioma using nnU-Net. The volumetry performance for small meningioma was significantly better than that achieved in previous studies. The results of this study are clinically applicable and are expected to be of great use in the management of monitored meningioma patients.
P13.04.B Dissecting high-grade glioma immune infiltration in samples from fluorescence-guided surgery: digital pathology with automated image analysis
Authors: Lang A , Jeron R L , Kiesel B , Mischkulnig M , Bergmeister-Berghoff A S , Ricken G , Wöhrer A , Rössler K , Lötsch-Gojo D , Rötzer-Pejrimovsky T , Hainfellner J A , Höftberger R , Widhalm G , Erhart F 
Published: September 2022

Abstract

Background
Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) is a widely used technique to conduct maximum safe resection of high-grade gliomas (HGG). 5-ALA accumulates in malignant tumor tissue where it is metabolized to Protoporphyrin IX (PpIX), an agent with fluorescence properties. It helps neurosurgeons to distinguish between tumor-infiltrated tissue and healthy brain parenchyma. Even though fluorescence-guided surgery is clinically well established, the biological properties of different fluorescence levels are not comprehensively studied yet. A relevant current gap in that respect is the pattern of immune cell infiltration in fluorescent versus non-fluorescent tissue samples. In light of future research, reliable, standardized histopathology methods that allow high-throughput analysis are desirable and digital pathology with automated image analysis is an attractive option to explore.

Material and Methods
128 formalin-fixed paraffin-embedded (FFPE) tissue blocks of 39 patients who underwent fluorescence-guided surgery of a HGG were included. Samples were selected based on their documented 5-ALA fluorescence intensity status (strong, vague, negative). Microtome-cut sections of the tissue were stained with antibodies against CD8, CD68, CD163 and FOX P3, representing immune cell populations of specific interest (cytotoxic T cells, glioma-associated macrophages, regulatory T cells). A total of 512 stained slides were then available for assessment. In addition to a classical, semi-quantitative analysis by two independent human reviewers, the immune infiltration intensity was measured via automated image analysis with the digital pathology software QuPath Version 0.3.2.

Results
Across all stained FFPE samples CD68 showed the overall highest intensity, followed by CD163. CD8 and FoxP3 showed generally lower average intensities. In 5-ALA negative and positive high-grade glioma samples the immune cell infiltration pattern was the same. Quantitative automatic digital pathology correlated well with the classical human histopathological analysis for the majority of markers evaluated.

Conclusion
We successfully explored and established novel digital pathology technologies for the study of immune cell infiltration patterns in neurooncology, specifically in the context of fluorescence-guided resection. Leveraging this platform could allow parallelized and high-throughput analysis of immune cell infiltration also in other contexts.
P14.02.A Serum neurofilaments correlate with axonal loss in paclitaxel-induced peripheral neurotoxicity
Authors: Velasco R , Marco C , Mariotto S , Stradella A , Hernández J , Argyriou A A , Ferrari S , Bruna J 
Published: September 2022

Abstract

Background
Paclitaxel-induced peripheral neuropathy (PIPN) is a dose-limiting axonal polyneuropathy. Nerve conduction studies (NCS) are unique for the assessment of axonal impairment in PIPN. Neurofilaments (NFs), constituent of the neuronal cytoskeleton, are emerging as axonal damage biomarker. To date, the association between changes in NCS and NfL quantification across paclitaxel treatment in breast cancer patients has not been specifically addressed.
MATERIAL AND METHODS: Prospective longitudinal measurement of sNfL levels and NCS in 27 chemotherapy-naïve breast cancer patients before (V0) and after completion (V1) of 12 cycles of weekly paclitaxel-based therapy.

Results
Serum NfL levels (in pg/mL) increased over the course of treatment in the whole of patients (T0: 18,509 +/- 12,886 vs T1:255,805 +/- 194,165, p&lt;0.001). The increase in sNfL levels at T1 showed a significant moderate correlation with the percentage of decrease in the amplitude of the sural (ρ = 0.6205 (p=0.0035), radial (r=0.6134, p=0.005)), ulnar (ρ = 0.6298 (p=0.005)) and peroneal motor (ρ = 0.5676, p=0.024)) nerve in NCS across treatment.

Conclusion
sNfL levels increase proportionally to the degree of paclitaxel-induced neuroaxonal damage, revealing being a promising blood biomarker able to detect the severity of large nerve fiber degeneration and, therefore, improving the diagnostic accuracy in PIPN.
P15.14.B Radionecrosis versus progression in brain tumors: results of a promising MRI tools
Authors: Bellu L , Navarria P , Clerici E , Pessina F , Politi L , Savini G , Lillo S , Marzo M , Scorsetti M 
Published: September 2022

Abstract

Background
Distinguish between radiation necrosis (RN) and tumor progression, in patients with irradiated primary or metastatic brain tumors, is a diagnostic challenge. Also the use of new MRI sequences, like diffusion, perfusion-weighted and spectroscopy, or PET with new amino acid tracers, is not always able to differentiate these two entities.To overcome this crucial problem, encouraging results have been obtained using the analysis of delayed contrast extravasation MRI to calculate high resolution maps, called “treatment response assessment maps” (TRAMs). Aim of this exploratory analysis is to assess TRAM ability in differentiate between radiation effect and tumor progression in a small cohort of brain tumor patients treated with radiation therapy (RT).

Material and Methods
Thirty-four patients irradiated for primary and metastatic brain tumors were evaluated. 12 patients have primary brain tumors, 22 patients have brain metastases from different solid tumors. Distinguish by histological subtypes and type of treatment, the 12 patients with primary brain tumors were: 8 glioblastoma, 2 anaplastic astrocitoma, 1 pleomorphic xanthoastrocytoma WHO grade II, and 1 anaplastic xanthoastrocytoma WHO grade III, treated with surgery followed by RT and concomitant and\or adjuvant chemotherapy with temozolomide. Among brain metastatic patients, primary tumor was: 18 non-small cell lung cancer, 2 malignant melanoma, 1 breast cancer and 1 renal cell carcinoma. All of them were treated with stereotactic radiosurgery at the dose of 20-24Gy in 1fraction, or with hypofractionated stereotactic radiotherapy at the dose of 27-30Gy in 3fractions. All images were uploaded and elaborate into the image workstation ([Brainlab AG, Olof-Palme-Straße 9, 81829 Munich]). TRAMs were calculated by subtracting T1 MRI images acquired 5 minutes after contrast injection from the T1 MRI images acquired 60-105 minutes later. On TRAMs, radiation effects appeared as red areas whereas persistent tumoral lesion appeared as blue areas.

Results
From February 2021, 34 patients have been evaluated, in a prospective study, with this novel MRI modality. During their follow-up, 13patients (38%) showed a clinicoradiologic suspicion of a persistent tumoral lesion or progressive disease, and 21 (62%) a suspicion of RN. For 14patients a brain MET-PET has been performed. TRAMs analysis have shown a fair agreement with clinicoradiologic diagnosis, perfusion-weighted MRI, and PET imaging. Moreover, 7 patients underwent surgical resection, with histopathological confirm of persistent disease in 4 and radionecrosis in 3.

Conclusion
These preliminary results show the ability of TRAMs evaluation in distinguish between RN and progressive disease. The recruitment of new patients continues, and further evaluations are ongoing to evaluate sensitivity and positive predictive value of TRAMs analysis.
P17.09.A Regorafenib and Re-irradiation: analysis of clinical outcomes and toxicities in patients with recurrent glioblastomas
Authors: Fiorelli S , Campisi G , Angelicone I , De Giacomo F , Ricciardi C , De Sanctis V , Ascolese A , Osti M 
Published: September 2022

Abstract

Background
Glioblastoma is the most common and aggressive primary brain tumor in adults.The aggressiveness and poor prognosis related to this disease join to the limited available treatment options. The current standard of care involves surgical resection followed by concomitant radiotherapy and chemotherapy. At recurrence, no standard treatment exists and there are no guidelines to facilitate decisions in the recurrent setting. Available options include re-operation, re-irradiation, systemic therapy, alone or in combination. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. Regorafenib (Stivarga) is an inhibitor of several kinases involved in the mechanisms that regulate neoangiogenesis processes, through the inhibition vascular endothelial growth factor (VEGF) receptors and the modifications of the tumor microenvironment; specifically, Regorafenib binds and stabilizes PSAT1 (phosphoserine aminotransferase 1). The dual regulatory mechanism underlying PSAT1-induced autophagy arrest accounts for the superior anti-GBM effect of Regorafenib compared with Temozolomide.

Material and Methods
15 patients with documented disease progression after surgery followed by RT and TMZ were assigned to receive regorafenib (REG) 160 mg once daily for the first 3 weeks of each 4-week cycle. All patients received prior radiation therapy (RT) to a median dose of 60 Gy (range 40.05 -60). Median time to retreatment after prior RT was 16 months (range 14-33). Tumor volumes ranged from 81.7 cm3 to 422.4 cm3 (CTV) and from 112.7 cm3 to 422.4 cm3 (PTV).3 patients (20%) received concomitant reirradiation with a radiation dose of 37.5 Gy in 15 fractions of 2.5 Gy.

Results
the median follow-up was 9.5 months (range 5-22). The overall survival and the progression-free survival rates were 53,8 %, and 46,6 % respectively at 2 years. In 53% the symptoms were stable. Only one patient developed late toxicity: acute pancreatitis (Grade I) regressed on interruption of Regorafenib. No other neurological deficits occurred during follow-up. At last follow up 60% of patients were alive.

Conclusion
we report our experience with Regorafenib, administered in patients with rapid progression after the end of postoperative radio chemotherapy treatment. Regorafenib might be a new potential treatment option for recurrent glioblastoma: it was well tolerated also in cases of combined treatment with reirradiation and appeared effective. Other studies will be necessary to evaluate and confirm the role of Regorafenib in glioblastoma patients and the potential effectiveness of the combined therapeutic strategy: Regorafenib-reirradiation.
Getting With the Times: A Review of Peripartum Infections and Proposed Modernized Treatment Regimens
Authors: Pek Zachary , Heil Emily , Wilson Eleanor 
Published: September 2022

Abstract
This article provides a review of peripartum infections, including intra-amniotic infection, postpartum endometritis, and postabortal infections. We present a case of postabortal infection to frame the review. The microbiology, pathogenesis, risk factors, diagnosis, and treatment of peripartum infections are reviewed, and a critical appraisal of the literature and available guidelines is provided. There is a focus on discussing optimal antimicrobial therapy for treating these infections.
Millimeter methanol emission in the high-mass young stellar object G24.33+0.14
Authors: Hirota Tomoya , Wolak Pawel , Hunter Todd R , Brogan Crystal L , Bartkiewicz Anna , Durjasz Michal , Kobak Agnieszka , Olech Mateusz , Szymczak Marian , Burns Ross A , Aberfelds Artis , Baek Giseon , Brand Jan , Breen Shari , Byun Do-Young , Caratti o Garatti Alessio , Chen Xi , Chibueze James O , Cyganowski Claudia , Eislöffel Jochen , Ellingsen Simon , Hirano Naomi , Hu Bo , Kang Ji-hyun , Kim Jeong-Sook , Kim Jungha , Kim Kee-Tae , Kim Mi Kyoung , Kramer Busaba , Lee Jeong-Eun , Linz Hendrik , Liu Tie , MacLeod Gordon , McCarthy Tiege P , Menten Karl , Motogi Kazuhito , Oh Chung-Sik , Orosz Gabor , Sobolev Andrey M , Stecklum Bringfried , Sugiyama Koichiro , Sunada Kazuyoshi , Uscanga Lucero , van den Heever Fanie , Volvach Alexandr E , Volvach Larisa N , Wu Yuan Wei , Yonekura Yoshinori 
Published: September 2022

Abstract
In 2019 September, a sudden flare of the 6.7 GHz methanol maser was observed toward the high-mass young stellar object (HMYSO) G24.33+0.14. This may represent the fourth detection of a transient mass accretion event in an HMYSO after S255IR NIRS3, NGC 6334I-MM1, and G358.93−0.03-MM1. G24.33+0.14 is unique among these sources as it clearly shows a repeating flare with an 8 yr interval. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we observed the millimeter continuum and molecular lines toward G24.33+0.14 in the pre-flare phase in 2016 August (ALMA Cycle 3) and the mid-flare phase in 2019 September (ALMA Cycle 6). We identified three continuum sources in G24.33+0.14, and the brightest source, C1, which is closely associated with the 6.7 GHz maser emission, shows only a marginal increase in flux density with a flux ratio (Cycle 6$/$Cycle 3) of 1.16 ± 0.01, considering an additional absolute flux calibration uncertainty of $10\%$. We identified 26 transitions from 13 molecular species other than methanol, and they exhibit similar levels of flux differences with an average flux ratio of 1.12 ± 0.15. In contrast, eight methanol lines observed in Cycle 6 are brighter than those in Cycle 3 with an average flux ratio of 1.23 ± 0.13, and the higher excitation lines tend to show a larger flux increase. If this systematic increasing trend is real, it would suggest radiative heating close to the central HMYSO due to an accretion event which could expand the size of the emission region and/or change the excitation conditions. Given the low brightness temperatures and small flux changes, most of the methanol emission is likely to be predominantly thermal, except for the 229.759 GHz (8−1–70 E) line known as a class I methanol maser. The flux change in the millimeter continuum of G24.33+0.14 is smaller than in S255IR NIRS3 and NGC 6334I-MM1 but is comparable with that in G358.93−0.03-MM1, suggesting different amounts of accreted mass in these events.