bluuebunny/crossref_metadata_2025_split huggingface dataset:
An unusual case of phytobezoar-induced small bowel obstruction
Authors: Taha Yasser , Salman Khaled , Alrayyes Fahad , Alrayyes Saad 
Published: September 2019

AbstractBezoars, and to lesser extent phytobezoars, are among the rare causes of small bowel obstruction. A bezoar generally describes retained concretions of indigestible foreign material that accumulate and conglomerate in the gastrointestinal tract, most commonly in the stomach. We present an unusual case of phytobezoar-induced sub-acute small bowel obstruction originating from unfamiliar plant material in a 74-year-old woman. The past history was insignificant regarding comorbidities other than depression. Presenting complaints were history of abdominal pain and vomiting. Imaging studies and physical examination suggested small bowel obstruction. The patient underwent exploratory laparotomy after 1 day of conservative treatment. We found a 4.5 cm obstructing phytobezoar intraoperatively. The undigested plant material caused the obstruction. Postoperatively, the plant was identified as Scorzonera papposa. The patient was discharged uneventfully. The elderly patients should avoid semi-cooked vegetables, plants of unknown origin and high-fibre diet.
A carbohydrate-binding protein, B-GRANULE CONTENT 1, influences starch granule size distribution in a dose-dependent manner in polyploid wheat
Authors: Chia Tansy , Chirico Marcella , King Rob , Ramirez-Gonzalez Ricardo , Saccomanno Benedetta , Seung David , Simmonds James , Trick Martin , Uauy Cristobal , Verhoeven Tamara , Trafford Kay 
Published: September 2019

Abstract
In Triticeae endosperm (e.g. wheat and barley), starch granules have a bimodal size distribution (with A- and B-type granules) whereas in other grasses the endosperm contains starch granules with a unimodal size distribution. Here, we identify the gene, BGC1 (B-GRANULE CONTENT 1), responsible for B-type starch granule content in Aegilops and wheat. Orthologues of this gene are known to influence starch synthesis in diploids such as rice, Arabidopsis, and barley. However, using polyploid Triticeae species, we uncovered a more complex biological role for BGC1 in starch granule initiation: BGC1 represses the initiation of A-granules in early grain development but promotes the initiation of B-granules in mid grain development. We provide evidence that the influence of BGC1 on starch synthesis is dose dependent and show that three very different starch phenotypes are conditioned by the gene dose of BGC1 in polyploid wheat: normal bimodal starch granule morphology; A-granules with few or no B-granules; or polymorphous starch with few normal A- or B-granules. We conclude from this work that BGC1 participates in controlling B-type starch granule initiation in Triticeae endosperm and that its precise effect on granule size and number varies with gene dose and stage of development.
Coccidioides (spherulin) skin testing in patients with pulmonary coccidioidomycosis in an endemic region†
Authors: Mafi Neema , Murphy C Brian , Girardo Marlene E , Blair Janis E 
Published: September 2019

Abstract
Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States. Intact cellular immunity is critical to the control of this infection. A recently released reformulated spherulin antigen (Spherusol; Nielsen BioSciences, Inc.) was approved to detect delayed-type hypersensitivity, which implies the presence of cellular immunity, to Coccidioides species. We aimed to summarize our experience with this test in patients with primary pulmonary coccidioidomycosis. We retrospectively reviewed clinical data for all patients with primary pulmonary coccidioidomycosis who had a Coccidioides (spherulin) skin test (CST) placed at our institution between January 1, 2015, and August 31, 2017. During the study period, 172 patients had a CST placed, and 122 met our inclusion criteria for proven or probable pulmonary coccidioidomycosis. Of these 122, 88 (72.1%) had a positive CST result and 34 (27.9%) had a negative result. In the positive CST group, 74 of the 79 treated patients (93.7%) had antifungal treatment stopped, 1 of whom (1.4%) had relapsed infection. In contrast, 27 of the 33 treated patients in the negative CST group (81.8%) had their antifungal treatment stopped, and none had a relapse. Seven patients overall (5.7%), all of whom had a positive CST, experienced mild local adverse reactions to the CST. Although previous controlled studies of CST showed sensitivity and specificity greater than 98%, our real-world experience with the CST showed lower rates of positivity. Negative CST results did not predict relapse with antifungal agent withdrawal.
PL1.1 CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDHmutant gliomas
Authors: Appay R , Dehais C , Colin C , Alentorn A , Carpentier C , Ducray F , Ibdaih A , Kamoun A , Mokhtari K , Tabouret E , Uro-Coste E , Delattre J , Figarella-Branger D 
Published: September 2019

Abstract
The 2016 WHO classification of the central nervous system tumors stratifies diffuse adult gliomas into three major groups depending on the presence or absence of two main genetic alterations: IDH mutation and 1p/19q-codeletion. However, the grading system initially based on histological criteria remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification. Therefore, in a large cohort of 911 high grade IDH-mutant gliomas from the French national POLA network, we investigated the prognostic value of pathological criteria (mitoses, microvascular proliferation and necrosis) as well as CDKN2A gene homozygous deletion, with the aim to highlight a new grading approach for these tumors. We analyzed 212 anaplastic astrocytoma (AA), IDH-mutant, 216 glioblastoma (GB), IDH-mutant and 483 anaplastic oligodendroglioma (AO), IDH-mutant and 1p/19q-codeleted. In this series, the 2016 WHO integrated diagnosis was of prognostic value for progression free survival (PFS) and overall survival (OS) (p<0.0001 for both). CDKN2A homozygous deletion was associated with worse outcome among gliomas lacking 1p/19q-codeletion (p<0.0001 for PFS and p=0.004 for OS) as well as among AO, IDH-mutant and 1p/19q-codeleted (p=0.002 for PFS and p<0.0001 for OS). In both groups, the presence of microvascular proliferation and/or necrosis remained of prognostic value only in cases lacking CDKN2A homozygous deletion, whereas its prognostic value was lost in the subgroup of gliomas presenting with CDKN2A homozygous deletion. Thereby, our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the two broad categories of IDH-mutant gliomas stratified on 1p/19q-codeletion as well as the prognostic relevance of microvascular proliferation (associated or not to necrosis) among tumors lacking this alteration. We believe that these prognostic factors could be of great interest for a future grading approach of IDH-mutant gliomas.
PL1.2 Multiparametric assessment of factors influencing 2 HG accumulation in diffuse brain gliomas
Authors: Nichelli L , Branzoli F , Valabregue R , Capelle L , Ottolenghi C , Bielle F , Lerond J , Giry M , Villa C , Galanaud D , Lehéricy S , Marjańska M , Sanson M , Di Stefano A 
Published: September 2019

Abstract

BACKGROUND
2-hydroxyglutarate (2HG) can be detected non-invasively in IDH-mutant gliomas by in vivo magnetic resonance spectroscopy (MRS). We investigated factors affecting 2 HG accumulation and explored the prognostic value of 2 HG detection in IDH mutant gliomas and 2 HG variations during anti-cancer therapies.

MATERIAL AND METHODS
We prospectively scanned by MEGA-PRESS 70 glioma patients (24 before surgery and 46 IDH mutant operated glioma) and measured 2HG. CRLB cut-off was 50%. We followed up 9 IDH mutant patients during radiotherapy and chemotherapy.We analyzed radiological parameters (tumor and cystic/necrotic volumes, fractions of VOI filled with tumor, spectroscopic profile, “infiltrative” versus “expansive” morphology, contrast-enhancement) and genetic profile (IDH1, IDH2, 1p19q codeletion). 2HG concentrations in plasma, urine, and surgical obtained samples were measured by gas chromatography-mass spectrometry (GC-MS).

RESULTS
MEGA-PRESS sequence detected 2HG with a sensitivity of 95% in untreated patients, and of 69% in pre-treated patient. Positive predictive value was 100% in both groups. 2HG was lower in pre-treated IDH mutant gliomas (1.1 versus 2.3 mM, P=0.02) and decreased rapidly during radiotherapy and chemotherapy before any radiological change. 2HG detection was positively correlated with tumor volume (P=0.02), choline measurements (r=0.58 P<0.0001), cellular density (measured by restricted diffusivity, Pearson r -0.40 P=0.01), “expansive” presentation, mutated reads/total reads ratio by NGS and was inversely correlated with Myo-inositol (Pearson R -0.29 P=0.03) and cystic/necrotic areas (P=0.04). 2HG by MRS positively correlated with urine 2HG (r=0.80 P=0.003). 2 HG was higher in IDH2 mutant (4.7 versus 2.4 Mm, P=0.02) and lower in non R132H IDH1 mutant (1.12 mM P=0.004). Among IDH mutant glioma patients, 2 HG detection was associated with longer survival (HR 0.09; 95%CI 0.018–0.52).

CONCLUSION
Tumor volume, cellular density, previous radio- and chemotherapy and genetic features determine 2 HG detection in IDH mutant gliomas. 2 HG detection is associated with better outcome and can be reliably monitored during anti-cancer treatments.
OS1.5 Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers
Authors: Noushmehr H , Sabedot T , Malta T , Nelson K , Snyder J , Wells M , deCarvalho A , Mukherjee A , Chitale D , Mosella M , Asmaro K , Robin A , Rosenblum M , Mikkelsen T , Rock J , Poisson L , Walbert T , Kalkanis S , Castro A 
Published: September 2019

Abstract
BACKGROUND: Genome-wide DNA methylation profiling has shown that epigenetic abnormalities are biologically important in glioma and can be used to classify these tumors into distinct prognostic groups. Thus far, DNA profiling has required surgically resected glioma tissue; however, gliomas release tumoral material into biofluids providing an opportunity for a minimally invasive testing. While prior studies have shown that molecular markers can be detected in liquid biopsy (LB), there has been low sensitivity for tumor-specific markers. We hypothesize that the low sensitivity is due to the targeted assay methods. METHODS: Genome-wide CpG methylation levels in DNA of tumor tissue and cell-free DNA serum of glioma patients. RESULTS: We defined glioma-specific and IDH-specific epigenetic LB (eLB) signatures (Glioma-eLB and IDH-eLB, respectively) from serum cell-free DNA from patients diagnosed with glioma (N=15 IDH mutant and N=7 IDH wildtype) and with epilepsy (N=3). The epigenetic profiles of the matched tissue demonstrate that these eLB signatures reflected the signature of the tumor. Through cross-validation we show that Glioma-eLB can accurately predict a patient’s glioma from those with other neoplasias (N=6 Colon; N=14 Pituitary; N=3 Breast; N=4 Lung), non-neoplastic immunological conditions (N=22 sepsis; N=9 pancreatic islet transplantation), and from healthy individuals (sensitivity: 98%; specificity: 99%). Finally, IDH-eLB includes promoter methylated markers associated with genes known to be involved in glioma tumorigenesis (PVT1 and CXCR6). CONCLUSIONS: The application of the non-invasive eLB signature discovered in this study has the potential to complement the standard of care for patients harboring glioma.
This project is supported by the Henry Ford Health System, Department of Neurosurgery and the Hermelin Brain Tumor Center Foundation (A30935), United States National Institutes of Health (R01CA222146), and United States Department of Defense (CA170278)
OS2.1 Incidence patterns for primary spinal cord ependymomas in adults: a Surveillance, Epidemiology, and End Results study
Authors: Man W , Wang G 
Published: September 2019

Abstract

BACKGROUND
Ependymomas are the most common primary spinal cord tumors in adults. However, few population-based studies analyzed the epidemiological features for this tumor type. We explored Surveillance, Epidemiology, and End Results (SEER) database to evaluate the incidence patterns over time with regard to patient gender, race, age at diagnosis, and histological subtype for patients diagnosed with primary malignant spinal cord gliomas between 1973 and 2015.

METHODS
We queried SEER database to identify all adult patients (≥ 20 years of age) diagnosed with primary spinal cord ependymomas during 1973–2015. Variables of interest included gender, race, age at diagnosis, and histological subtype of tumor. The SEER*Stat 8.3.5 program was used to calculate frequencies, age-adjusted incidence rates (IR) with adjustment to the 2000 US Standard population and 95% confidence intervals (CI). An annual percentage change (APC) statistic with a 2-sided p-values was used to assess incidence patterns over time.

RESULTS
1224 adult patients with primary spinal cord ependymomas were diagnosed between 1973 and 2015. Of the total population, 55.7% were males (n = 682) and 44.3% were females (n=542). Myxopapillary ependymomas (ICD-O-3 code 9394), papillary ependymomas (9393), ependymomas (9391) and anaplastic ependymomas (9392) accounts for 28.7% (n = 351), 0.5% (n = 6), 69.4% (n = 849) and 1.5% (n = 18) respectively. The overall age-adjusted IR for all adult primary spinal cord ependymomas was 0.16 per 100,000 (95%CI 0.15–0.17). The IR in male was higher than that in female (males 0.19 per 100,000 [95% CI 0.17–0.20], females 0.14 per 100,000 [95% CI 0.13–0.14]. Caucasians experienced higher IR (0.18 per 100,000 [95% CI 0.17–0.19]) compared to African Americans (0.19 per 100,000 [95% CI 0.07–0.12]) and the others (0.10 per 100,000 [95% CI 0.08–0.13]). Patients of age between 40 and 49 years experienced the highest IR (0.25 per 100,000 [95% CI 0.22–0.29]) than patients in the other age ranges. The most common histological subtypes were ependymomas (0.11 per 100,000 [95% CI 0.11–0.12]) and myxopapillary ependymomas (0.047 per 100,000 [95% CI 0.042–0.052]. The overall age-adjusted IR for all adult primary spinal cord ependymomas showed a statistically significant increase over time between 1973 and 2015 (APC=5.15, p<0.01). The same increasing trend was found in Caucasians (APC=5.36, p<0.01) and in both males (APC=5.13, p<0.01) and females (APC=4.95, p<0.01).

CONCLUSION
This study demonstrates an increasing IR of adult primary spinal cord ependymomas over the past four decades. Males, Caucasians and age between 40 and 49 years experienced a higher IR.
OS3.4 Karnofsky and WHO performance scores of brain tumour patients may limit inclusion in protocols though they depend on clinician status
Authors: Frappaz D , Taillandier L , Bonneville Levard A , Sorre J , Ricard D , Carrie S , Schiffler C , Weller M 
Published: September 2019

Abstract

BACKGROUND
Inclusion criteria for oncological protocols often use the Karnofsky performance score (KPS) >=70 or the WHO performance score (PS) 0–2 as a cut-off value. Inclusion of neuro-oncology patients may be hampered, when general condition is preserved, while performance is decreased due to physical handicap. The goal of this study is to compare the KPS and PS assessments according to the status of the clinician.

MATERIAL AND METHODS
A cross-sectional survey was conducted through ANOCEF and EANO networks. Clinicians evaluated KPS and PS in 6 clinical situations concerning neuro oncology patients (from youngest and fittest to oldest, crippled with comorbidities).

RESULTS
The rate of PS <70 or PS> 2 increased significantly from case 1 to 6.
Sex or nationality of the clinicians had no impact when adjusting on clinician characteristics. Conversely, speciality (residents/general practitioner vs neurosurgeons vs neurologists vs oncologists), impacted KPS or PS evaluations (p<.0001 and p=0.0046, respectively). Residents or general practitioner estimate KPS much lower than the others specialities. Neurosurgeons estimate PS more severely. Clinicians who were not used to including patients in clinical trials proposed lower KPS scores (p = 0.0008). This tendancy was not shown on PS. Eldest physicians significantly rated more severely than the youngest (p = 0.0459 and p <.0001 for KPS and PS, respectively).
In a multivariate analysis, age and speciality were correlated with KPS and PS rating even if adjusted on cases.
Discordant decision for protocol inclusion (i:e: (KPS) >=70 vs PS 0–2) showed little discrepancy in case 1 (2.3%), while discrepancy increased to respectively 16, 46, 39, 33 and 43% for cases 2 to 6: in nearly all cases, the KPS would have denied access to a trial, while WHO Ps would have allowed

CONCLUSION
Rating of KP and PS is subjective in neuro oncology patients: influenced by speciality, age and inclusion habit (for KPS) of clinicians, PS 0–2 allows usually more inclusion than KPS>=70 in more severely disabled patients. A Neuro oncology specific KPS and/or PS definition is warranted to allow more widely inclusion of patients with exclusive neurologic handicap.
OS4.3 Feasibility and benefit of Molecular Profiling to Guide Enrollment of Patients with Recurrent Gliomas in Early Phase Trials
Authors: Baldini C , Younan N , Castanon Alvarez E , Bahleda R , Hollebecque A , Dhermain F , Ammari S , Alentorn A , Dumont S , Frenel J , Di Stefano A , Bielle F , Hoang-Xuan K , Delattre J , Soria J , Sanson M , Idbaih A , Massard C , Touat M 
Published: September 2019

Abstract

BACKGROUND
Participation of glioma patients in early phase clinical trials has recently shown to be safe, although clinical benefits reported in this population were marginal. We aimed to evaluate whether an enrichment strategy based on molecular profiling associates with improved outcome in gliomas patients participating in early phase trials.

MATERIAL AND METHODS
Records of patients enrolled in early phase trials of cytotoxic therapies, small molecule inhibitors or monoclonal antibodies from 2008 to 2017 were analyzed for clinicopathological characteristics, toxicity, response, median progression-free survival (PFS) and overall survival (OS). The primary objective was to evaluate the feasibility and benefit of using molecular profiling to guide enrollment.

RESULTS
Ninety-one patients were enrolled, of whom 47/91 (51.6%) were molecularly oriented. Molecular targets included IDH1/2 (n=15) and BRAF (11) mutations, FGFR1-3 fusions (n= 10) and mutations (n = 4), mismatch repair deficiency (8), and MDM2 amplification (1). Grade 3/4 adverse events were reported in 9/91 (9.9%) patients. In patients with IDH1/2-wild-type high-grade glioma (n=45), the overall response rate (24.0% [95% CI 11.5–43.4] vs 0.0% [95% CI 0.0–16.1], P=0.027) was significantly higher in molecularly-oriented vs non-molecularly-oriented patients. Updated outcome results, and clinical and molecular factors associated with response, PFS and OS in multivariate analyses will be presented at the conference.

CONCLUSION
Using molecular profiling to guide enrollment in early phase trials is feasible and offers potential benefit to gliomas patients. Further studies are warranted to identify the population most likely to benefit from this approach.
OS6.3 The complex role of lactate dehydrogenases in glioblastoma development
Authors: Daubon T , Guyon J , Chouleur T , Espedal H , Leon C , Bjerkvig R , Bikfalvi A 
Published: September 2019

Abstract

BACKGROUND
Glioblastomas are among the most malignant primary brain tumors. GBMs are highly angiogenic, exhibit invasive growth, and elevated glycolysis. Under glycolytic conditions, glucose from the blood is metabolized in astrocytes into lactate by LDHA, and exported by MCT4 into the extracellular compartment, inducing a concomitant acidification of the microenvironment. LDHB, generally expressed in oligodendrocytes or neurons, metabolizes lactate into pyruvate for generating ATP in mitochondria. LDH expression was reported to be linked to phenotypic modifications in vitro in GBMs but the mechanisms and the precise role in vivo have not yet been investigated.

MATERIAL AND METHODS
We designed LDHA and LDHB Crispr-Cas9 constructs for infecting glioblastoma stem-like cells. Results: In vitro tumor cell invasion was not significantly impaired in sgLDHA glioblastoma cells, even under extreme hypoxic conditions. Tumor development was moderately impacted in terms of invasion or vascular density. We then explored the role of LDHB in these processes. LDHB knock-out cells had decreased invasive properties in vitro but surprisingly tumors were highly hemorrhagic and angiogenic, supporting a role of tumor-derived LDHB in blood vessel development. We furthermore evaluated the consequences of a double LDHA and LDHB knock-out in the glioma cells. Under hypoxic conditions, sgLDHA/B cell invasion was dramatically decreased in comparison to control cells, and apoptosis was also increased. Tumor development was dramatically impaired for LDHA/LDHB knockout tumors.

CONCLUSION
These results indicate the complex role of LDH enzymes in glioblastoma development. It constitutes the basis for further mechanistical studies linking lactate metabolism to brain tumor development and perturbation of the neuro-vascular microenvironment.
OS7.1 Impact of the addition of Rituximab to standard therapy with high dose methotrexate on health-related quality of life in primary central nervous system lymphoma patients
Authors: van der Meulen M , Dirven L , Bakunina K , Taphoorn M J B , van den Bent M J , Issa S , Doorduijn J K , Bromberg J E C 
Published: September 2019

Abstract

BACKGROUND
Data on the impact of treatment with Rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma (PCNSL) patients are scarce. To determine the net clinical benefit of a new treatment, analyzing the effect on HRQoL is warranted.

MATERIAL AND METHODS
Patients from a phase III trial (HOVON 105/ ALLG NHL 24), randomized to standard chemotherapy with or without Rituximab, were asked to fill in the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 2 years follow-up or progression. Five predetermined scales were selected for primary analyses: global health status (GH), role (RF) and social functioning (SF), fatigue (FA), and motor dysfunction (MD). A difference ≥10 points was defined as clinically relevant. Cross-sectional analyses were performed comparing changes in HRQoL scores from baseline between the two arms at 12 and 24 months after treatment. Effect of whole brain radiotherapy (WBRT) was analyzed in irradiated patients only. Differences in HRQoL over time between the treatment arms, i.e. the primary outcome, were assessed using linear mixed models (LMM).

RESULTS
175/199 patients completed at least one HRQoL questionnaire, and compliance was >60% at all evaluation points. Median age was 61 (IQR 55–66), 74% had a WHO performance score <2, and 38% received WBRT, similar to the total trial population. HRQoL scores on all five scales were significantly and to a clinically relevant extent improved at 12 and 24 months follow-up when compared to baseline in both arms (range: 11.6–42.4), except for FA and MD at 12 months (both -7.2). Differences in HRQoL changes from baseline to 12 and 24 months between the two arms were not statistically significant (range: 3.6–10.9). In the irradiated patients (n=52), HRQoL scores remained stable up to 24 months compared to shortly after WBRT for GH, SF, FA and MD (range -8.1 - 7.6). A clinically relevant and statically significant improvement was seen in RF for both arms at 12 and 24 months compared to ‘after WBRT’(range: +16.7 - +22.2). After correction for multiple testing, LMM analyses showed no statistically significant and clinically relevant differences between the arms for any of the scales over time (range: -3.8 to +4.0).

CONCLUSION
Treatment resulted in improved HRQoL, but the addition of Rituximab to standard chemotherapy did not further impact HRQoL over time. WBRT did not result in deterioration of HRQoL up to 2 years of follow-up.