tbuckley/cabot-search huggingface dataset:
Photopenic defects on O-(2-[18F]-fluoroethyl)-L-tyrosine PET: clinical relevance in glioma patients
Authors: Norbert Galldiks, Marcus Unterrainer, Natalie Judov, Gabriele Stoffels, Marion Rapp, Philipp Lohmann, Franziska Vettermann, Veronika Dunkl, Bogdana Suchorska, Jörg C Tonn, Friedrich-Wilhem Kreth, Gereon R Fink, Peter Bartenstein, Karl-Josef Langen, Nathalie L Albert
Journal: Neuro-Oncology (2019)

O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET has a sensitivity of more than 90% to detect gliomas. In the remaining small fraction of gliomas without increased tracer uptake, some tumors even show photopenic defects whose clinical significance is unclear.Glioma patients with a negative FET PET scan prior to neuropathological confirmation were identified retrospectively. Gliomas were rated visually as (i) having indifferent FET uptake or (ii) photopenic, if FET uptake was below background activity. FET uptake in the area of signal hyperintensity on the T2/fluid attenuated inversion recovery-weighted MRI was evaluated by mean standardized uptake value (SUV) and mean tumor-to-brain ratio (TBR). The progression-free survival (PFS) of photopenic gliomas was compared with that of gliomas with indifferent FET uptake.Of 100 FET-negative gliomas, 40 cases with photopenic defects were identified. Fifteen of these 40 cases (38%) had World Health Organization (WHO) grades III and IV gliomas. FET uptake in photopenic gliomas was significantly decreased compared with both the healthy-appearing brain tissue (SUV, 0.89 ± 0.26 vs 1.08 ± 0.23; P < 0.001) and gliomas with indifferent FET uptake (TBR, 0.82 ± 0.09 vs 0.96 ± 0.13; P < 0.001). Irrespective of the applied treatment, isocitrate dehydrogenase (IDH)-mutated WHO grade II diffuse astrocytoma patients with indifferent FET uptake (n = 25) had a significantly longer PFS than patients with IDH-mutated diffuse astrocytomas (WHO grade II) with photopenic defects (n = 11) (51 vs 24 mo; P = 0.027). The multivariate survival analysis indicated that photopenic defects predict an unfavorable PFS (P = 0.009).Photopenic gliomas in negative FET PET scans should be managed more actively, as they seem to have a higher risk of harboring a higher-grade glioma and an unfavorable outcome.
Contamination par Salmonella Enteritidis lysotype 13a : étude de cas-témoins à Hertsmere, Royaume-Uni
Authors: O Morgan, L Milne, S Kumar, D Murray, W Man, M Georgiou, N Q Verlander, E de Pinna, M McEvoy
Journal: Eurosurveillance (2007)

Des cas de contamination ont ete signales a Hertsmere parmi les personnes ayant participe a une fete de charite organisee en juin 2006. Les premieres analyses de laboratoire ont identifie Salmonella Enteritidis lysotype 13a comme etant probablement a l’origine de l’epidemie.
RTHP-35. LOCAL RECURRENCE PATTERN OF PATIENTS ENROLLED ON A RANDOMIZED STUDY OF POST-OPERATIVE STEREOTACTIC RADIOSURGERY VS OBSERVATION FOR COMPLETELY RESECTED BRAIN METASTASIS
Authors: Anita Mahajan, Xin Wang, Salmaan Ahmed, Mary Fran Mcaleer, Jeffrey S Weinberg, Jing Li, Paul D Brown, Sujit S Prabhu, Frederick F Lang, Susan L McGovern, Ian Mccutcheon, Erik Sulman, Amy Heimberger, Sherise Ferguson, Amol Ghia, Nandita Guha-Thakurta, Raymond Sawaya, Ganesh Rao
Journal: Neuro-Oncology (2017)

To evaluate the difference in patterns of local recurrence (LR) on a prospective randomized trial of stereotactic radiosurgery (SRS) or observation (OBS) after complete resection of a brain metastasis. All patients who experienced LR within or adjacent to the surgical cavity were identified and the failure pattern was evaluated. Failures were categorized as completely In-Field, Out-Field or Both based on the prescription isodose for the SRS arm or potential target volume if OBS. Characteristics including time to failure, initial size, histology, radiation dose are evaluated. Of the 128 eligible patients enrolled on study, 46 (15 SRS, 31 OBS) experienced LR (p=0.005). Six patients (5 SRS, 1 OBS) had LR before SRS or by post-op day 30 and were not included in this analysis. The median time to LR in the remaining group was 250d vs 115d (range: 126-488d vs 39-424d) in the SRS vs OBS arms, respectively (p=0.02). The median initial tumor diameter was 3.4cm vs 2.7cm for the LR vs non-LR, respectively, in both SRS and OBS. There was no statistically significant difference in recurrence rates between histologies, but, LR incidence after SRS was 0/3 and 0/12 in patients with renal and lung cancer vs 4/9 and 4/9 patients in breast and GI cancers (p=0.07). Recurrence pattern in the SRS patients was noted to be In-Field, Out-Field and Both in 40%, 30% and 30%, respectively. Similarly, for the OBS patients, these rates were 31%, 21% and 48%, respectively. Post-operative SRS for brain metastasis decreases and delays LR. It should be noted that 6/128 (4.6%) patients had LR by post-op day 30. Based on the outcomes of the remaining patients, improvements in dose and target volume delineation may be possible for higher risk patient cohorts based on tumor size and histology.
Reply
Authors: Filipe S. Cardoso, Michelle Gottfried, Shannan Tujios, Jody C. Olson, Constantine J. Karvellas
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. We appreciate Kalal et al.'s comments to our article "Continuous Renal Replacement Therapy Is Associated With Reduced Serum Ammonia Levels and Mortality in Acute Liver Failure."1 In acute liver failure, the lack of liver capacity to metabolize ammonia into urea and glutamine leads to its accumulation in the bloodstream. Uptake of part of this ammonia by the brain, muscle, and other tissues results in a gradient between arterial and venous ammonia levels.2 Therefore, the arterial ammonia level has been found to be a better surrogate for the risk of cerebral edema, intracranial hypertension, and mortality in acute liver failure.3 Nevertheless, venous ammonia has been shown to correlate well with arterial ammonia and to be associated with such clinical endpoints in acute liver failure.2 Taking this into account and to maximize sample size and the internal validity of our results, we decided to use both arterial and venous ammonia measurements. Furthermore, we were especially interested in the ammonia variation from days 1‐3 post–study inclusion with and without renal replacement therapy (RRT). Finally, in our cohort (n = 1,186), while the serum ammonia level (arterial or venous) at study inclusion was associated with 21‐day transplant‐free mortality (P < 0.001), the type of ammonia (arterial versus venous) at study inclusion was not associated with 21‐day transplant‐free mortality (P = 0.49). Moreover, median arterial and venous ammonia levels were similar for each of the continuous RRT, intermittent RRT, and no RRT subgroups on days 1, 2, and 3 (P ≥ 0.08 for all comparisons). Thus, we believe that our methodology was robust to extract our conclusions.
Results of an integrated multi-platforms analysis in squamous cell lung carcinoma (SqCLC) revealed PI3K/RICTOR-mTORC2 axis as a potential prognostic biomarker and druggable target
Authors: S. Pilotto, M. Simbolo, A. Gkountakos, A. Mafficini, C. Vicentini, I. Sperduti, V. Ludovini, R. Chiari, S. Novello, M. Milella, L. Carbognin, E. Caregnato, A. Santo, M. Infante, M. Brunelli, V. Corbo, A. Scarpa, G. Tortora, E. Bria
Journal: Annals of Oncology (2017)
PDTM-49. GLOBAL REDUCTION IN H3K27me3, SIMILAR TO H3K27M MUTANT GLIOMAS, IS A MOLECULAR SURROGATE FOR PEDIATRIC POSTERIOR FOSSA- GROUP A EPENDYMOMAS
Authors: Sriram Vennneti, Pooja Panwalkar, Jonathan Clark, Vijay Ramaswamy, Debra Hawes, Fusheng Yang, Christopher Dunham, Stephen Yip, Juliette Hukin, Yilun Sun, Matthew Schipper, Lukas Chavez, Ashley Margol, Melike Pekmezci, Chan Chung, Adam Banda, Jill Bayliss, Sarah Curry, Mariarita Santi, Fausto Rodriguez, Matija Snuderl, Matthias Karajannis, Amanda Saratsis, Craig M Horbinski, Marcel Kool, Stefan M Pfister, Michael Taylor, Cynthia Hawkins, Andrey Korshunov, Alexander Judkins
Journal: Neuro-Oncology (2017)

Ependymomas in children occur most commonly in the posterior fossa of the brain and cause significant morbidity and mortality. The pathogenesis of these tumors remains obscure as recent whole genome and whole exome sequencings have not yielded recurrent genetic alterations. These tumors are classified into PFA and PFB groups based on abnormal CpG island methylation suggesting that epigenetic alterations may be a significant driver. To gain insights into the epigenetics of childhood ependymomas, we performed mass spectroscopy for histone modifications to discover that H3K27me3 was globally reduced in PFA tumors, similar to that observed in H3K27M diffuse intrinsic pontine gliomas (DIPGs). Despite global reduction in H3K27me3, ChIP-sequencing for H3K27me3 revealed genomic enrichment at several loci important for neurodevelopment. Comparison of DNA methylation and genome-wide H3K27me3 enrichment from both H3K27M mutant DIPGs and PFAs showed many similarities and pointed to factors that regulate radial glial (neuronal stem cells) development. Moreover, radial glia in the developing human posterior fossa were negative for H3K27me3. To assess the clinical utility of this finding, H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner in a cohort (n=112) of previously defined childhood PFA (n=72) and PFB tumors (n=40). Next, H3K27me3 immunohistochemistry status in two independent, non-overlapping cohorts of childhood EPN (n=133 and n=98) was determined and risk stratification was assessed retrospectively using univariate and multivariate Cox proportional hazards analyses. H3K27me3 immunohistochemistry showed 99% sensitivity and 100% specificity in delineating PFA from PFB tumors and was sufficient to delineate patients with worse prognosis (P<0.0001) in both cohorts. Together these data suggest that reduction in H3K27me3 is central to the pathogenesis of PFA ependymomas and immunohistochemical evaluation of H3K27me3 is an economic, easily available and readily adaptable molecular surrogate for PFA tumors to accurately classify childhood ependymomas to inform prognosis, treatment and future clinical trials.
High Prevalence of Barrett’s Esophagus and Esophageal Squamous Cell Carcinoma After Repair of Esophageal Atresia
Authors: Floor W.T. Vergouwe, Hanneke IJsselstijn, Katharina Biermann, Nicole S. Erler, René M.H. Wijnen, Marco J. Bruno, Manon C.W. Spaander
Journal: Clinical Gastroenterology and Hepatology (2017)
HER2 negative metastatic gastric cancer (mGC): a retrospective analysis on the efficacy of doublet or triplet chemotherapy (CT) as a first-line therapy in the clinical practice
Authors: A. Petrillo, M.M. Laterza, J. Ventriglia, B. Savastano, G. Tirino, L. Pompella, A. Pappalardo, M. Orditura, F. Ciardello, F. De Vita
Journal: Annals of Oncology (2017)
QLIF-21. FEASIBILITY RANDOMIZED CONTROLLED TRIAL OF A DYADIC YOGA PROGRAM FOR PATIENTS WITH BRAIN TUMORS UNDERGOING RADIOTHERAPY AND THEIR FAMILY CAREGIVERS
Authors: Kathrin Milbury, Smitha Mallaiah, Anita Mahajan, Terri S Armstrong, Shiao-Pei Weathers, Jing Li, Lorenzo Cohen
Journal: Neuro-Oncology (2017)

The role of behavioral medicine in the symptom management of glioma patients is largely unknown. Moreover, despite the high physical and psychological burden among family caregivers, the needs of caregivers generally remain unaddressed. Thus, we aimed to establish the feasibility and acceptability of a Dyadic Yoga (DY) intervention in 20 glioma patients and their family caregivers. Adults with low and high grade glioma undergoing radiotherapy (RT) and their family caregivers were included. Dyads were randomized to a 12-session DY program focusing on breathing exercises, gentle movements and guided meditations or a usual care control group. Participants in the DY group completed detailed program evaluations using Liker-scale items in addition to open-ended questions. Both groups completed the MDASI to assess cancer-related symptoms at baseline and post-DY, which was at the end of RT. We approached 36 dyads of which 21 (58%) consented with one dyad withdrawing prior to randomization. Dyads completed a mean of 11.67 sessions (range: 10-12) and 100% of pre/post MDASI assessments. All patients (mean age: 46 yrs., 58% male, 68% KPS=90) and caregivers (mean age: 51 yrs., 68% female, 50% spouses) indicated that they perceived benefit from the program. On the 1-10 Borg Scale, patients rated the intervention between “really easy” and “sort of hard” (mean=2.60), and 70%-84% of participants indicated that the sessions “very much” improved their emotional, physical, cognitive, and social wellbeing. All patients would recommend the program to other patients undergoing radiotherapy. MDASI scores of patients in the DY group showed clinically significantly improvements (baseline mean: 3.37 vs T2 mean: 1.80) whereas those in the control group did not. The DY program appears to be safe, feasible, acceptable, and subjectively useful for glioma patients and their caregivers. Consequently, a larger trial with an attention control group is warranted to examine treatment efficacy.
Abstract 21023: Population Attributable Risk for Cardiovascular Disease Associated With Hypertension and Prehypertension in African Americans: The Jackson Heart Study
Authors: Donald Clark, Yuan-I Min, Michael E Hall, Robert J Mentz, Yuichiro Yano, Dachi Shimbo, Lisandro D Colantonio, Gbenga Ogedegbe, Daniel W Jones, Adolfo Correa, Paul Muntner
Journal: Circulation (2017)

Introduction: African Americans are disproportionately affected by hypertension (HTN) and cardiovascular disease (CVD). Determining the population attributable risk (PAR) for CVD associated with HTN and prehypertension in African Americans can help inform policymakers and prioritize public health interventions. Methods: Among 3770 participants in the Jackson Heart Study without prevalent CVD, we used Cox-proportional hazard analysis adjusted for traditional CVD risk factors to determine the association of HTN and prehypertension with incident CVD and its components including coronary heart disease, heart failure, and stroke. The PAR was calculated as pd*(HR-1)/HR; where pd is the prevalence of the exposure and HR is the hazard ratio for the outcome associated with the exposure. HTN was defined as a systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or self-reported antihypertensive medication use and prehypertension as SBP of 120 to 139 mmHg or DBP of 80 to 89 mmHg. Results: At baseline, 52.4% of the cohort had HTN and 77.1% had prehypertension or HTN. Over a median of 9.9 years follow-up, 349 (9.3%) participants developed CVD. The HR for CVD and PAR associated with HTN was 2.17 (95% CI 1.63, 2.89) and 0.28 (95% CI 0.20, 0.35), respectively (Table). The HR for CVD and PAR associated with HTN and prehypertension pooled together was 2.21 (95% CI 1.41, 3.47) and 0.42 (95% CI 0.25, 0.56), respectively. In the pooled group there were significant associations with incident coronary heart disease, heart failure, and stroke. Sex-specific sensitivity analysis demonstrated PAR for CVD associated with HTN and prehypertension was 0.40 (95% CI 0.07, 0.62) in men and 0.43 (95% CI 0.19, 0.61) in women. Conclusions: Approximately 40% of incident CVD is attributable to HTN and prehypertension among African Americans in the southeastern United States. Preventing HTN and prehypertension in this population is a major public health priority.
PATH-47. CLINICAL SENSITIVITY AND SPECIFICITY OF ILLUMINA METHYLATION ARRAY FOR CLASSIFYING ADULT GLIOMAS INTO WHO GROUPS
Authors: Jeanette Eckel-Passow, Paul Decker, Edward Hughes, Thomas Kollmeyer, Matthew Kosel, Danielle Burgenske, Jann Sarkaria, Caterina Giannini, Benjamin Kipp, Daniel Lachance, Robert Jenkins
Journal: Neuro-Oncology (2017)

WHO criteria now classify adult glioma into groups using combination of tumor grade and two tumor markers: 1p/19q codeletion and IDH1/2 mutation. TERT promoter mutation has also been shown to further classify tumors into clinically-meaningful groups. The Cancer Genome Atlas (TCGA) recently identified six methylation subtypes of glioma. Thus, as part of a clinical transformation process, we evaluated sensitivity and specificity of the Illumina methylation array to classify adult gliomas into appropriate WHO groups. We molecularly profiled 86 specimens from our institution via Illumina EPIC methylation array: 76 adult gliomas, seven other brain tumors (anaplastic ependymoma, glial neoplasm, pilocytic astrocytoma) and three gliosis samples. The 76 adult gliomas also have Affymetrix OncoScan array, IDH1/2 and TERT promoter mutation sequencing data. Using only methylation data, the EPIC array correctly classified 70 (92%) of 76 gliomas into appropriate WHO groups. When EPIC array copy number data were used to verify codeletion status, 71 (93%) were correctly classified. Similarly, using only Illumina methylation data, 560 (90%) of 622 TCGA gliomas were correctly classified into WHO groups. When methylation array copy number data were used to verify codeletion status 611 (98%) were correctly classified. While the OncoScan and EPIC methylation array had 100% concordant codeletion status, there were discrepancies for other genomic regions; especially in gliomas that carry IDH1/2, ATRX and TP53 mutations. All seven (100%) of the other brain tumors were classified as LGm6. With respect to TERT mutation, of 44 TCGA IDH wildtype, TERT wild-type and non-codeleted gliomas, 64% were classified as LGm6; thus, supporting the importance of TERT for further classifying gliomas. Overall, when methylation and 1p/19q copy number data are used, the Illumina methylation array correctly classified most adult gliomas into appropriate WHO groups. However, caution should be used when evaluating genome-wide copy number alterations solely using the methylation array.
PI3Kδ Inhibition Elicits Anti-Leukemic Effects through Bim-Dependent Apoptosis
Authors: Matthew J Carter, Kerry L Cox, Stuart J Blakemore, Anna H Turaj, Robert J Oldham, Lekh N. Dahal, Stacey Tannheimer, Francesco Forconi, Graham Packham, Mark S Cragg
Journal: Blood (2016)
Meeting Summary: State and Local Implementation Strategies for Increasing Access to Contraception During Zika Preparedness and Response — United States, September 2016
Authors: Charlan D. Kroelinger, Lisa Romero, Eva Lathrop, Shanna Cox, Isabel Morgan, Meghan T. Frey, Lee Warner, Kathryn M. Curtis, Karen Pazol, Wanda D. Barfield, Dana Meaney-Delman, Denise J. Jamieson
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Zika virus infection during pregnancy is a cause of microcephaly and other serious brain abnormalities (1). To support state and territory response to the threat of Zika, CDC's Interim Zika Response Plan outlined activities for vector control; clinical management of exposed pregnant women and infants; targeted communication about Zika virus transmission among women and men of reproductive age; and primary prevention of Zika-related adverse pregnancy and birth outcomes by prevention of unintended pregnancies through increased access to contraception.* The most highly effective,† reversible contraception includes intrauterine devices and implants, known as long-acting reversible contraception (LARC). On September 28, 2016, the Association of Maternal and Child Health Programs (AMCHP) and CDC facilitated a meeting in Atlanta, Georgia, of representatives from 15 states to identify state-led efforts to implement seven CDC-published strategies aimed at increasing access to contraception in the context of Zika virus (2). Qualitative data were collected from participating jurisdictions. The number of states reporting implementation of each strategy ranged from four to 11. Participants identified numerous challenges, particularly for strategies implemented less frequently. Examples of barriers were discussed and presented with corresponding approaches to address each barrier. Addressing these barriers could facilitate increased access to contraception, which might decrease the number of unintended pregnancies affected by Zika virus.
Cell autonomous VEGF signaling is required for epithelial tumor cell proliferation
Authors: Beate Lichtenberger, Poi Kiang Tan, Maria Sibilia
Journal: Cancer Research (2008)

3423   The vascular endothelial growth factor (VEGF) is a key mediator for normal and abnormal angiogenesis and is implicated in the development of many epidermal tumors. K5-SOS transgenic mice expressing a constitutively active form of the Ras activator Son of Sevenless (SOS) in the basal layers of the epidermis develop skin papillomas at 100% penetrance in a wild-type epidermal growth factor receptor (EGFR) background, whereas in a hypomorphic (wa2) EGFR background tumor development is severely impaired and can be induced by wounding. While it could be shown that the EGFR provides an essential survival signal to the tumor cells, the mechanism by which SOS expression leads to strong proliferation was unclear (1).  Here we show that the vascular endothelial growth factor (VEGF) is upregulated in SOS expressing tumors and is responsible for autocrine tumor cell proliferation. Genetic deletion of VEGF with a K5-Cre transgenic line delays the onset of SOS-dependent skin tumor development in a wild-type EGFR background. Surprisingly, in a hypomorphic EGFR background the lack of VEGF expression in keratinocytes completely inhibits SOS-dependent papilloma formation and tumors can not even be induced by wounding. Interestingly, the VEGF-receptor Flt1 and its coreceptor Neuropilin 1 (Nrp1) are expressed on keratinocytes and are strongly upregulated by K5-SOS. However, Nrp1 upregulation is reduced in the absence of a functional EGFR. These results suggest that, besides controlling angiogenesis, VEGF might cooperate with the EGFR during SOS-dependent transformation in a cell-autonomous way thereby demonstrating a novel function of VEGF during tumor development.  Supported by a Boehringer Ingelheim Fonds (BIF) PhD Fellowship to B.M.L. and an EC FP5 grant to M.S.  (1) Sibilia et. al. Cell, 2000