tbuckley/cabot-search huggingface dataset:
QLIF-17. ASSESSING DEPRESSION IN GLIOMA PATIENTS
Authors: Alvina A Acquaye, Nancy Garren, Elizabeth Vera, Boris Lisa, Christine Siegel, Deric M Park, Jing Wu, Sonja Crandon, Brett J Theeler, Joo-Hee Sul, Mark R Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2017)

A recent Cochrane review revealed only 5 studies exploring depression in glioma patients with variable incidence of 17% to as high as 49%; and even fewer studies using instruments designed to measure depression severity and therapeutic approaches. Patients enrolled in the Neuro-Oncology Branch Natural History study were assessed for depression using the Patient Health Questionnaire (PHQ-9). Validated cut-off scores (≥ 5=mild; ≥ 10=moderate-severe with 88% sensitivity and specificity for major depression) were used to account for depression severity. Presence of one of 2 cardinal symptoms (anhedonia, feeling depressed) was also described. Independent sample t-tests and chi-square tests were used to evaluate group characteristics and differences. 124 patients (male=61%) with median age of 48 (21-75) participated, with Glioblastoma (31%) common and recurrence at 27%. KPS was ≥ 90 in 72%. The average PHQ-9 score was 4.9 (SD=4.4; range 0-19) with 50% scoring ≤ 4.0 and 15% scoring ≥10, indicating possible depression. Patients taking psychotropic medications scored 4.9 points higher than those not (t (118) = -3.0, p=0.003, n=120). Patients with poor KPS (£ 80) scored 2.2 points higher than patients with KPS 3 90 (t (105) = -2.4, p=0.019, n=107). A score of ≥ 10 was associated with psychotropic use (X2(1) = 9.5, P=0.002, n=120), while a score of ≥ 5 was associated with performance status (X2(1) =5.2, 0.023, n=107). Further review revealed that 18 patients (15%) reported at least one of the two cardinal symptoms and of these, only 6 (5%) also reported 5 total items required to diagnose depression. High PHQ-9 scores were associated with psychotropic use and lower KPS. Cardinal symptoms of depression were uncommon and scores suggestive of clinical depression were rare (4%). Our findings support the use of standardized scales of depression, paving the way for future studies exploring depression severity over the disease trajectory.
P1.12-009 Experience with Fully Covered Metallic Stents in Patients with Malignant Airway Obstruction
Authors: R.M. Ortiz Comino, A. Morales, E. Minchole, M. Diez-Ferrer, R. Lopez-Lisbona, N. Cubero, J. Dorca, A. Rosell
Journal: Journal of Thoracic Oncology (2017)
PerTe: efficacy and safety of pertuzumab in “real life setting” for the neoadjuvant treatment of HER2-positive breast cancer patients
Authors: D. Cianniello, A. Prudente, R. Caputo, M. Piezzo, M. Riemma, B. Savastano, S. Cocco, M. Licenziato, B. De Stefano, G. Di Gioia, G. Fusco, G. Buonfanti, A. Gravina, G. Landi, F. Di Rella, C. Pacilio, F. Nuzzo, G. Iodice, M. De Laurentiis, S. Del Prete
Journal: Annals of Oncology (2017)
Abstract 16403: Trajectories of Depression and Anxiety Symptoms are Predictive of Physical Health-related Quality of Life, Mortality, and Hospital Admission at 1-Year Among Patients With Heart Failure
Authors: Lynn P Roser, Abdullah S Alhurani, Terry A Lennie, Christopher S Lee, Martha Biddle, Susan Frazier, Stephen Fleming, Debra K Moser
Journal: Circulation (2015)

Background: Little is known about the symptom trajectories of depression and anxiety in heart failure (HF) patients and how these symptoms influence health outcomes over time. Objective: The goal of this study was to describe unique trajectories of depression and anxiety symptoms in HF patients over 12 months and determine whether changes in these symptoms predict subsequent physical health-related quality of life (P-HRQOL) and event-free survival. Method: The study sample consisted of 597 patients with HF enrolled as part of a larger longitudinal study at 8 sites from across the United States. The Patient Health Questionnaire-9, the Brief Symptom Inventory Anxiety subscale, and the Minnesota Living with Heart Failure Questionnaire Physical Subscale were used to assess depression, anxiety, and P-HRQOL, respectively. Latent growth mixture modeling was used to identify distinct trajectories of change in depression and anxiety. Results: Three trajectories of depression and three trajectories of anxiety were identified (entropy = 0.919). Trajectory changes in depressive symptoms were labeled as getting better (81.1%), bad and getting slightly worse (13.9%), and bad and getting much worse (5.0%). Trajectory changes in anxiety were labeled as getting better (66.7%), stable with slight improvement (22.1%), and getting much worse (11.2%). The trajectories of depression labeled as bad and getting slightly worse and bad and getting much worse were predictive of a poorer P-HRQOL at one-year than the trajectory which showed improvement (β 11.6, p&lt;0.001 and β 15.6, p&lt;0.001, respectively). Changes in depressive symptoms labeled as bad and getting slightly worse was also a significant predictor of event-free survival (HR = 2.17, p&lt;0.001). The two anxiety trajectories which showed stable, slight improvement and much worse anxiety symptoms over 12-months were significant predictors of worse P-HRQOL (β 12.0, p&lt;0.001 and β 18.7, p&lt;0.001, respectively). The trajectory of anxiety symptoms labeled getting much worse was a significant predictor of event-free survival (HR = 2.18, p&lt;0.001). Conclusion: We identified three distinct trajectories for both depression and anxiety symptoms, some of which were predictive of P-HRQOL and event-free survival at one year.
NIMG-49. PRESENCE AND PATTERN OF CALCIFICATION ON CT STRONGLY PREDICT GLIOMA SUBTYPE
Authors: Derek Johnson, Caterina Giannini, Alissa Caron, Daniel Lachance, Timothy Kaufmann
Journal: Neuro-Oncology (2017)

Macroscopic tumor calcification visible on computed tomography (CT) imaging is recognized as a frequent finding in oligodendroglial tumors, but can also occur in astrocytoma and glioblastoma, which are far more common overall. Given the recent 2016 revision to the World Health Organization (WHO) diagnostic criteria for gliomas, which incorporated genetic markers into the definitions of infiltrating glioma for the first time, the current predictive value of calcification for different glioma subtypes is unknown. We conducted a retrospective review of adult patients in whom pretreatment CT images and subsequent WHO 2016 diagnoses of infiltrating glioma were available. Presence and pattern of tumor calcification were determined by consensus. A total of 492 patients met inclusion criteria. Median age was 59 years and 61.8% were male. Tumor types included glioblastoma IDH wild-type (IDHwt) in 272/492 patients (55%), glioblastoma IDH mutant (IDHmut) in 18/492 (4%), WHO grade II/III astrocytoma IDHwt (71/492; 14%), WHO grade II/III astrocytoma IDHmut (56/492; 11%), and WHO grade II/III oligodendroglioma (69/492; 14%). The remaining six tumors (1%) could not be full characterized. Tumor calcification was present in 47/492 patients (10%). The majority of patients with calcification (27/47; 57%) were diagnosed with WHO grade II or III oligodendroglioma, followed by glioblastoma IDHwt (8/47, 17%). The presence of calcification was significantly associated with IDH mutation and 1p/19q codeletion (each p<0.001). A pattern of calcification we termed “classic varicoid” was observed in 18 patients (16 oligodendroglioma, one IDHmut GBM, and one IDHmut astrocytoma). Only 14/343 (4%) of patients with IDHwt WHO grade II/III astrocytoma or IDHwt glioblastoma demonstrated calcification and none showed the “classic varicoid” pattern. Tumor calcification at CT strongly predicts oligodendroglial pathology, despite the far greater frequency of astrocytoma/glioblastoma. The “classic varicoid” pattern of calcification is highly specific for IDH mutant gliomas.
PALL-02. PERAMPANEL FOR TREATMENT OF REFRACTORY SEIZURES IN PATIENTS WITH GLIOMAS
Authors: Anastasie Dunn-Pirio, Sarah Woodring, Sujata Panta, Eric S Lipp, Patrick Healy, James E Herndon, Eric Fountain, Annick Desjardins, Dina Randazzo, Henry S Friedman, Katherine B Peters
Journal: Neuro-Oncology (2017)

Nearly one-third of patients with primary brain tumors experience a seizure as the presenting symptom and another 30-50% develop seizures during the disease course. Despite a wide availability of anti-seizure medications, some brain tumor patients have treatment refractory seizures. Perampanel is a highly selective non-competitive-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptor antagonist that is approved as an adjunct for partial-onset and primary generalized tonic-clonic seizures. We conducted a single-arm study to assess the safety, tolerability and efficacy of perampanel as an adjunctive anti-epileptic drug in patients with gliomas who have refractory partial-onset seizures. Participants were treated with a dose escalation of perampanel: 2 mg/day for two weeks, followed by 2mg-weekly increments up to a maximal dose of 8mg/day and then continued at this dose for 12 weeks. After 16 weeks of therapy, perampanel was tapered down by 2mg/week until the patients were no longer taking perampanel. Assessments included evaluations of Karnofsky Performance Status, seizure history, patient-reported outcomes of quality of life, and computer-based neurocognitive testing. Eight subjects were treated on study. Glioma subtypes represented: glioblastoma (n=1), anaplastic astrocytoma (n=3), anaplastic oligodendroglioma (n=1), oligodendroglioma (n=2) and diffuse astrocytoma (n=1). Seizure frequency varied widely between subjects. Three participants had clear reductions in seizure frequency after treatment initiation. The most common adverse events related to perampanel were fatigue (n=5) and dizziness (n=2). One participant died 8 weeks after study enrollment secondary to Pneumocystis jiroveci pneumonia and was deemed to be unrelated to perampanel. Of note, the study was stopped due to poor accrual. Adjunctive perampanel for patients with glial brain tumors and refractory partial-onset seizures is safe. Overall, this study suggests that perampanel is effective for refractory epilepsy in the brain tumor population but a larger study is needed to address definitively this question.
Une épidémie de psittacose chez des douaniers en Belgique
Authors: K De Schrijver
Journal: Eurosurveillance (1995)

En Mars 1994, l'inspection d'hygiene d'Anvers, Belgique, a pris acte d'un cas de psittacose survenu chez un douanier membre d'une equipe de 15 inspecteurs. Ce douanier a du etre hospitalise pour une pneumonie contractee une dizaine de jours auparavant, au contact de perruches confisquees a un marin indien, pour importation illicite.
ACTR-39. APPLICATION OF RTOG-RPA SCORES IN A PHASE 3 TRIAL OF TUMOR TREATING FIELDS WITH TEMOZOLOMIDE (TTFIELDS/TMZ) VERSUS TEMOZOLOMIDE (TMZ) ALONE IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Kevin Choe, Ahmed Idbaih, Sophie Taillibert, Jordi Bruna Escuder, Jan Sroubek, Andrew Kanner
Journal: Neuro-Oncology (2017)

A simplified model on prognostic factor recursive partitioning analysis (RPA) for survival of glioblastoma patients was previously published by the radiation therapy oncology group (RTOG) (Li et al. Int J Radiat Oncol Biol Phys. 2011). In this RPA model, patients are divided into three prognostic groups based on four variables: age, performance status (KPS), extent of resection, and neurologic function. The EF-14 phase 3 trial of TTFields/TMZ compared to TMZ alone showed that adding TTFields to TMZ increased the annual survival of newly diagnosed glioblastoma patients significantly out to 5 years. We applied the RTOG-RPA classes on the EF-14 population. The 1, 3 and 5 year survival rates of both arms of the EF-14 trial patient cohort were compared to that of the original validation cohort used to develop the simplified RTOG-RPA model. The annual survival rates for the TMZ alone arm were in line with the RTOG validation dataset in all three RPA classes at years 1, 3 and 5. However, the annual survival rates in the TTFields/TMZ arm were greater than both the TMZ alone arm and the RTOG validation cohort in all three RPA classes at years 1, 3 and 5. For the 3-year survival rates for the RTOG, EF-14 TMZ and EF-14 TMA/TTFields cohorts were as follows: RPA class III – 20%, 25% and 39%; RPA class IV: 7%, 15% and 23%; RPA class V+VI: 1%, 9% and 20%, respectively. This analysis validates the consistency of the EF-14 trial with historical control data when analyzed using the simplified RTOG-RPA model and strengthens the conclusion that TTFields/TMZ compared to TMZ alone increases annual survival rates out to 5 years regardless of patient prognostic factors.
An unstable knee
Authors: Fidel Peat, Michael Barrett, Stephen M McDonnell
Journal: BMJ (2017)

A 28 year old man was brought to hospital after a road traffic incident. He described hearing a “pop” as his right knee impacted against the dashboard at the time of collision, and he subsequently experienced extreme pain. On examination in the emergency department, his knee was swollen and tender, and range of movement was severely limited. After initial management in the emergency department, he was admitted under the orthopaedic team. Once the swelling was resolved, his knee was re-examined, and was found to be grossly unstable (fig 1⇓).



Fig 1  Clinical photograph of the patient’s right knee





### 1. What sign is shown in the clinical photograph?

#### Short answer

Posterior sag sign suggesting injury to the posterior cruciate ligament.

#### Discussion

The posterior cruciate ligament serves as the main restraint to posterior displacement of the tibia relative to the femur. Secondary functions include resisting excessive valgus, varus, and external rotation movements. Disruption of the posterior cruciate ligament can be seen via posterior draw testing or by assessing for posterior sag (fig 2⇓). Normally, the anterior surface of the tibia lies around 1 cm anterior to the femoral surface when the knee is held in 90° of flexion. Any …
IMMU-02. VALIDATION OF PD-L1 EXPRESSION IN HIGH GRADE GLIOMAS AS AN INDEPENDENT NEGATIVE PROGNOSTIC MARKER
Authors: Drew Pratt, Gifty Dominah, Graham Lobel, Arnold Obungu, Xiang Wang, Nancy A Edwards, Dragan Maric, Mark R Gilbert, Martha Quezado, Edjah K Nduom
Journal: Neuro-Oncology (2017)

Checkpoint inhibition is believed to be a promising method of immune modulation for cancer patients. PD-L1 expression has correlated with improved response to anti-PD-1 therapy in other tumors. However, evaluation of PD-L1 expression in high grade glioma (HGG) patients remains fragmented and controversial. We aimed to compare existing methods of PD-L1 assessment in HGG, validate the status PD-L1 expression as an independent prognostic marker and define the expression profile of PD-L1 in the HGG microenvironment. We tested widely used PD-L1 antibodies to determine the expression of PD-L1 both in tumor cells and within the HGG microenvironment on large core (4mm) tissue microarrays. Antibodies were validated using Western blots of HEK293 cells transfected with a PD-L1 expressing plasmid. RNAScope in situ hybridization was used to validate PD-L1 expression results, and multiplex immunohistochemistry (MP-IHC) was used to immunophenotype selected cases. SP263 and SP142 emerged as our most reliable PD-L1 antibodies. Among HGG samples, 23.5% tumors expressed PD-L1 on greater than 5% of their cells. 36% of IDH wild type glioblastomas expressed PD-L1 at this level, consistent with prior reports. HGG patients expressing PD-L1 on >5% of their cells had a median survival of 19.5 months versus 26 months for patients with <5% (p=0.0072, log-rank test) in our patient cohort, and this was an independent prognostic variable. These expression data are being validated using RNAScope in-situ hybridization. Finally, MP-IHC demonstrated cell-surface PD-L1 expression on T cells, microglia, macrophages and glial cells in the immune microenvironment of HGG patients, demonstrating the heterogeneity of the cellular expression of this marker. High PD-L1 expression by IHC is an independent negative prognostic marker in HGG, thus justifying PD-L1 as a stratification factor in clinical trials, particularly in immunotherapeutic protocols. Our results also underscore the heterogeneity of the tumor microenvironment.
Targeted delivery of microRNA‐199a‐3p using self‐assembled dipeptide nanoparticles efficiently reduces hepatocellular carcinoma in mice
Authors: Aditi Varshney, Jiban J. Panda, Avishek K. Singh, Nitin Yadav, Chhagan Bihari, Subhrajit Biswas, Shiv K. Sarin, Virander S. Chauhan
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) is an aggressive tumor with limited systemic and locoregional modalities of treatment. Although microRNA (miRNA) based therapies have significant potential, their targeted delivery remains a major challenge. miR‐199a‐3p functions as an important tumor suppressor in HCC, which regulates various cellular processes. Recently, peptide‐based nanoparticles (NPs) have been developed to deliver oligonucleotides including miRNA. Here, we describe the synthesis and characterization of arginine α,β‐dehydrophenylalanine (RΔF) nanoparticles for the selective delivery of miR‐199a‐3p to restore dysregulated gene expression in HCC. Targeted delivery was achieved by conjugating lactobionic acid (LA) with RΔF NPs (RΔF‐LA NPs), a ligand for the asialoglycoprotein receptor known to be overexpressed in HCC cell lines. RΔF‐LA NPs condensed miR‐199a‐3p had an average size of ∼60nm and a zeta potential of ∼+2.54 mV. RΔF‐LA/miR NPs were found to be stable in serum as well as against RNase attack. RΔF‐LA/miR NPs showed an enhanced cellular uptake and an efficient delivery of miR‐199a‐3p leading to a significant increase in miR‐199a‐3p levels (over 500 fold). The increased miR‐199a‐3p levels remarkably suppressed cell proliferation and migration as well as induced cellular apoptosis and downregulation of the specific target gene (mTOR) in vitro. RΔF‐LA/miR NPs showed high tumor/ low organ ratios after intravenous injection into HCC tumor bearing nude mice. RΔF‐LA/miR NPs treated mice demonstrated>50% decline in tumor growth, which also corresponded well with suppression of mTOR protein expression, tumor cell proliferation and increased survival rate (P < 0.05). Conclusion: RΔF‐LA/miR NPs showed significantly enhanced delivery of the miRNA which underscores their potential for further development as a therapeutic approach for HCC. (Hepatology 2018;67:1392‐1407)
Reaching global HIV/AIDS goals: What got us here, won't get us there
Authors: Wafaa M. El-Sadr, Katherine Harripersaud, Miriam Rabkin
Journal: PLoS Medicine (2017)

Much accomplished, but much more neededA decade ago, today's progress towards confronting the global HIV epidemic would have been unimaginable.A remarkable global mobilization of resources through the United States President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund for AIDS, Tuberculosis and Malaria, combined with the commitment of affected countries and communities, has enabled 19.5 million persons living with HIV (PLHIV) to access life-saving antiretroviral therapy (ART) [1].This has resulted in decreasing HIV-related morbidity and mortality and contributed to a significant decline in the number of new infections [1].Despite earlier concerns about the feasibility of scaling up HIV services in resource-limited settings, the majority of PLHIV accessing ART are in sub-Saharan Africa, where many countries have austere health systems characterized by scarce healthcare providers and weak laboratory, infrastructure, drug procurement, monitoring, and governance systems [2].One of the critical enablers of this achievement was the adoption of the public health approach to HIV service delivery [2].This strategy used simple evidence-based algorithms for HIV testing, prevention, and treatment; employed a single first-line antiretroviral regimen, standardized laboratory tests, and testing schedules; and involved streamlined data monitoring systems [3].The simplicity and consistency of this approach enabled HIV services to be provided by nonphysician clinicians and facilitated the establishment of simplified laboratory and medication procurement systems, enabling the successful scale-up of treatment [3].By facilitating the successful scale-up of HIV services, the public health approach is arguably "what got us here," to a context in which more than half of all PLHIV are accessing treatment [1].However, in order to reach ambitious global targets and achieve epidemic control, much more must be done-and swiftly.Not only must the number of PLHIV accessing ART increase substantially to reach 30 million people by 2020, but the quality of HIV services must be enhanced and effective primary prevention interventions must be brought to scale [1].Challenges include reaching diverse patient populations, retaining them in either treatment or prevention programs, supporting adherence to ART and prevention methods, and addressing long wait times and health facility crowding, a problem for both recipients of care and health workers.In addition, concern over the plateauing of global resources highlights the vital importance of efficiency and cost-effectiveness as a possible way to address this enormous challenge [1]. Differentiated care for people living with HIVDifferentiated care may be an important step towards addressing health system and individual barriers to achieve HIV treatment goals [4].Whereas earlier efforts, anchored in the public health approach, often distinguished only 2 groups of adult patients-pregnant and
Are Cholesterol Treatment Targets a Deterrent to Optimal Lipid-Lowering Therapy?
Authors: David D. Waters
Journal: JAMA Cardiology (2017)

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