tbuckley/cabot-search huggingface dataset:
Hepatitis C and human immunodeficiency virus coinfection in the era of direct‐acting antiviral agents: No longer a difficult‐to‐treat population
Authors: Cameron Sikavi, Phillip H. Chen, Alex D. Lee, Elena G. Saab, Gina Choi, Sammy Saab
Journal: Hepatology (2017)

The treatment of chronic hepatitis C (HCV) in human immunodeficiency virus 1 (HIV)–infected individuals has been historically marked by low sustained virologic response (SVR) rates in comparison to those without HIV infection, resulting in the Food and Drug Administration labeling those coinfected as a “special population with an unmet medical need.” We systematically reviewed the treatment of chronic HCV infection in those infected with HIV. We propose that with the advent of direct‐acting antiviral (DAA) agents, patients coinfected with HCV and HIV have similar SVR rates as HCV‐monoinfected persons and that DAAs address an unmet medical need in this population. A review was performed using Medical Subject Heading terms within the PubMed, EMBASE, and Cochrane Library databases to search for studies dated between January 2004 and July 2017. Keywords used in the study included “hepatitis C,” “HIV,” “coinfection,” and “direct‐acting antiviral.” SVR rates for those with HCV and HIV coinfection treated with interferon‐based therapies were substantially lower that SVR rates of HCV‐monoinfected individuals. The advent of DAA agents has resulted in similar SVR rates between monoinfected and coinfected individuals, with SVR &gt;93%. These medications have been demonstrated to have improved safety, efficacy, and tolerability in comparison to interferon‐based regimens. Conclusion : The designation of a “special population” for those with coinfection requires reconsideration; DAA therapies have resulted in similarly high rates of SVR for HCV infection in those with and without HIV infection; despite these improvements, however, clinicians must be cognizant of negative predictors of SVR and barriers to treatment that may be more common in the coinfected population. (H epatology 2018;67:847–857)
A young man with palpitations and pre-syncope
Authors: Debjit Chatterjee
Journal: BMJ (2017)

A 20 year old man presented to the emergency department with palpitations lasting half an hour. He was also feeling dizzy and felt close to fainting. He denied any chest pain. He had no known cardiac history.

Examination revealed blood pressure of 70/50 mm Hg. Oxygen saturation was 91% on room air. There was no murmur on auscultation of the chest. The man underwent electrocardiography (ECG) (fig 1⇓). What rhythm does the ECG show?



Fig 1  Electrocardiography (ECG) on presentation to the emergency department



Atrial fibrillation with very fast ventricular response as a result of antegrade conduction through an accessory pathway (pre-excited atrial …
NIMG-37. CORRELATION OF VASARI-BASED MRI PHENOTYPES WITH MGMT AND IDH STATUS ACROSS GLIOMA GRADES: A STATISTICAL ANALYSIS IN 372 PATIENTS
Authors: Devsmita Das, Byung Yoon, Louis Golden, Peyman Samghabadi, Hannes Vogel, Kristen Yeom, Michael Iv, Tarik Massoud
Journal: Neuro-Oncology (2017)

Knowledge of MGMT promoter methylation and IDH mutation status carries prognostic significance for glioma patients. How MRI features may predict the presence or absence of these molecular markers has not been explored across all glioma subtypes. We retrospectively studied 372 glioma patients with known MGMT methylation and IDH mutation status. Mean age was 53 ± 18yr. There were 294 high-grade and 78 low-grade glioma patients. For each patient we analyzed associations of 30 VASARI MRI features with IDH and MGMT status, alone or in combination. We assessed these correlations with categorical MRI variables using Chi-square test, and ordinal MRI variables using Wilcoxon two-sample test. MGMT methylation significantly correlated with gender (p=0.004), tumor grade (p=0.018), IDH status (p=0.003), proportion of enhancing and non-enhancing tumor (p<0.0001), amount of restricted diffusion (p<0.0001), and proportion of edema (<0.0001). Negative-IDH significantly correlated with patient age (19-40yr, p<0.0001), tumor grade (p<0.0001), proportion of enhancing and non-enhancing tumor (p<0.0001), extent of restricted diffusion (p<0.0001), necrosis (p=0.002), definition of enhancing and non-enhancing tumor margins (p<0.0001), proportion of edema (<0.0001), hemorrhage (p=0.004), dural contact (p=0.0002), cortical involvement (p=0.0002), and enhancing tumor crossing midline (p=0.002). Seventy-two percent of positive-IDH tumors were significantly associated with MGMT positivity, whereas 57% of negative-IDH negative tumors were associated with MGMT negativity (p=0.004). Combined methylated MGMT and negative-IDH was associated with patient age (41-64yr, p<0.0001), and proportion of enhancing tumor (p=0.002). Combined unmethylated MGMT and positive-IDH was associated with presence of restriction (p=0.009) and presence of well-defined enhanced margins (p<0.0001). Combined unmethylated MGMT and negative-IDH was associated with lowest amounts of restricted diffusion (<1/3rd, p=0.03), lowest proportions of peritumoral edema (<1/3rd, p=0.0007) and absence of hemorrhage (p=0.02). Specific MRI features can be used to predict MGMT and IDH status in low grade as well as high grade gliomas, with important prognostic implications.
La rubéole au Danemark
Authors: S Glismann
Journal: Eurosurveillance (2004)

Jusqu'en 1987, au Danemark le nombre moyen annuel de cas de rubeole etait de 20 000. En 1989, seuls 1006 cas ont ete declares et actuellement l'incidence de la rubeole au Danemark n'est pas connue avec exactitude, mais consideree comme tres faible, inferieure a 1 pour 100 000. Cette baisse significative de l'incidence re-flete le succes de la vaccination chez les femmes en âge de procreer et sero-negatives a la rubeole, mise en place au Danemark en 1980. Depuis 1982, le Pro-gramme national de securite sanitaire a instaure le remboursement des vaccinations chez les enfants et le vaccin ROR a ete introduit dans le calendrier vaccinal des en-fants en 1987. Ces mesures ont permis de maintenir l'incidence a un niveau bas, et depuis 1994, le syndrome de rubeole congenitale et la rubeole en cours de grossesse font partie des maladies a declaration obligatoire au Danemark. Neanmoins, pour parvenir a l'eradication de la rubeole dans la Region, objectif fixe par l'OMS, la declaration obligatoire de tous les cas de rubeole diagnostiques en laboratoire est egalement a l'etude.
Epidémie d’oreillons limitée à une communauté religieuse
Authors: C A van den Bosch, B J Cohen, T Walters, L Jin
Journal: Eurosurveillance (2000)

Entre juillet 1998 et avril 1999, 144 cas d’oreillons ont ete declares dans une communaute religieuse de Londres et l’infection a ete confirmee chez 82% (51/62) de ceux qui avaient eu un test salivaire. La moitie des cas cliniques et la moitie des cas confirmes avaient recu une dose de vaccin ROR. L’efficacite du vaccin est en cours d’etude.
ACTR-76. FINAL RESULTS FROM A PHASE I STUDY OF PLERIXAFOR AND BEVACIZUMAB IN RECURRENT HIGH-GRADE GLIOMA
Authors: Eudocia Lee, Alona Muzikansky, Elizabeth Gerstner, John Kuhn, David Reardon, Lakshmi Nayak, Andrew Norden, Lisa Doherty, Jennifer Stefanik, Julee Armitage, Debra LaFrankie, Sandra Ruland, Trupti Vardam, Deirdre Stokes, Katrina Smith, Christine McCluskey, Sarah Gaffey, Tracy Batchelor, Rakesh Jain, Dan Duda, Patrick Wen
Journal: Neuro-Oncology (2017)

Although anti‐angiogenic therapy for high-grade glioma (HGG) is promising, responses are not durable. The SDF-1/CXCR4 axis may help mediate resistance to VEGFR inhibition. Plerixafor is a reversible CXCR4 inhibitor that has demonstrated growth inhibition in glioblastoma xenografts. We conducted a Phase I study to determine the safety and tolerability of plerixafor in combination with bevacizumab in recurrent HGG. Part 1 of the study enrolled 23 patients and was a 3 x 3 dose escalation design to a maximum planned dose level of plerixafor 320 µg/kg on Days 1–21 and bevacizumab 10 mg/kg on Days 1 and 15 of each 28 day cycle. Dose-limiting toxicities (DLTs) were determined during the initial 4 weeks of therapy. CSF and concomitant plasma samples were obtained to determine pharmacokinetic (PK) data. Part 2 of the study enrolled 3 patients and was a surgical study to determine if plerixafor penetrates tumor tissue. Patients were pre-treated with plerixafor 320 µg/kg for 5–9 days before surgery. For all 26 patients enrolled on study, the median age is 59 (23–72), median KPS 90 (70–100), 11 women (42.3%). In Part 1, no DLTs were seen at the maximum planned dose level of plerixafor + bevacizumb. Treatment was well tolerated with one grade 3 hypophosphatemia and one grade 3 rectal fistula. Serum PK data on plerixafor in this study compares well with historical PK data. At a plerixafor dose of 320 µg/kg, the average CSF concentration was 26.8 ng/mL (SD +/- 19.6). Circulating biomarker data suggests that plerixafor + bevacizumab induces rapid and persistent increases in plasma SDF1 and PlGF. Plerixafor concentration in resected tumor tissue from patients pre-treated with plerixafor was 1000–1200 ng/mL. Combination treatment with bevacizumab and plerixafor was well tolerated in HGG patients. Plerixafor distributes to both the CSF and brain tumor tissue.
Abstract 11619: Basal Septal Hypertrophy in Severe Aortic Stenosis is Associated With Worse Left Ventricular Diastolic Function but Has Not Impact on the Postoperative Transvalvular Pressure Gradients
Authors: Dragos Alexandru, Florentina Petillo, Simcha Pollack, Nathaniel Reichek, Eddy Barasch
Journal: Circulation (2015)

Background: Basal septal hypertrophy (BSH) is found in 1.5 %-18% of the general population associated with hypertension. Its significance in severe aortic stenosis (AS) is uncertain. Hypothesis: In AS, BSH may adversely affects LV diastolic function and increases transvalvular gradients after valve replacement (AVR). Methods: Between 2011-2014, 6012 pts with AS of some degree underwent echocardiography. Severe AS was present in 255 with a septal buldge and normal EF, of whom 30 had BSH (AS+/BSH+). 106 were AS+/BSH-. Controls included 119 AS-/BSH+ pts. 38 with AS+/BSH+ with any EF underwent AVR. BSH was defined as BS diastolic diameter ≥ 15 mm and BS &gt;2 mm thicker than mid septum in PSLAX view in multiple images. Inter and intraobserver reliability were calculated (ICC, n = 20). One-way ANCOVA, Fisher’s exact test and multivariate logistic regression controlled for age, sex and BSA were used as appropriate. Results: ICC = 0.99 for BS and 0.80 for mid septum. AS+/BSH+ pts were older than AS+/BSH-, more were females and their diastolic function was worse despite similar transvalvular gradients, AVAi, LV mass index (table), and similar medical histories. After controlling for prosthetic valve type and size and stroke volumes, BSH did not affect post AVR transvalvular gradients. In adjusted logistic regression models, BSH was associated with E/A (OR = 2.6, CL s:1.32 and 5.29, p =0.006, AUC = 0.85) and showed a trend toward association with LA area index ( OR = 1.14, CLs,1.14 and 0.99, p = 0.06, AUC = 0.77). Conclusions: 1. Using rigorous criteria,&lt; 4% of pts with severe AS have BSH. 2. AS+/BSH+ have Doppler evidence of higher LV filling pressures despite similar stenosis severity and LV mass than AS +/BSH- pts, so that BSH may be a marker of worse diastolic function. 3. BSH does not affect post AVR transvalvular pressure gradients. 4. Larger prospective studies are warranted to validate these findings and compare outcomes of AS pts with and without BSH.
RTHP-31. A 40-YEAR MULTI-INSTITUTIONAL REVIEW OF INTRACRANIAL GERM CELL TUMORS IN ADOLESCENTS AND YOUNG ADULT
Authors: Andrea Lo, Karen Goddard, David Hodgson, Jennifer Dang, Scott Tyldesley, Eric Bouffet, Ute Bartels, Sylvia Cheng, Juliette Hukin, Philippe Bedard, Jordan Tran, Normand Laperriere
Journal: Neuro-Oncology (2017)

To determine the outcomes and complications of intracranial germ cell tumors (IGCT) in adolescents and young adults (AYA) according to different therapeutic approaches. One-hundred twelve patients with IGCT aged 15-39 years were managed at either Princess Margaret Cancer Centre or British Columbia Cancer Agency from 1975-2015. The charts of these patients were retrospectively reviewed. Ten-year rates of outcomes and complication rates are reported. Median duration of follow-up was 8.3 years. Ninety-three patients had germinomas, and 19 had non-germinomatous germ cell tumors (NGGCT). Fourteen patients (13%) presented with spinal metastatic disease. Progression-free survival (PFS) was 82% and overall survival (OS) was 88%. For patients with germinoma, PFS was 91% after craniospinal radiation therapy (CSRT) plus chemotherapy (N=11), 100% after whole ventricular RT (WVRT) or tumor bed RT (TBRT) plus chemotherapy (N=20), 89% after CSRT alone (N=44) and 41% after WVRT, whole brain RT or TBRT alone (N=16) (P<0.0005); OS was 91%, 100%, 89%, and 72%, respectively (P=0.085). For patients with NGGCT, PFS was 58% after TBRT plus chemotherapy (N=8) vs. 91% for all others (N=11 [6 treated with CSRT plus chemotherapy, 2 with WVRT plus chemotherapy, 2 with CSRT alone, and 1 with WBRT plus chemotherapy]) (P=0.24); OS was 58% and 100%, respectively (P=0.085). Irradiation-induced complications included a 14% rate of hypopituitarism, 5% seizure disorder, 2% second neoplasms, and 1% visual deterioration. Treatment-induced hearing loss or tinnitus was 10% after RT alone, and 26% after both chemotherapy and RT (N=0.018). Neurocognitive impairment from either disease or treatment was 42% after CSRT or WBRT (N=69), 47% after WVRT (N=23), and 17% after TBRT (N=18). We demonstrate excellent overall outcomes in the largest study of IGCT in AYA to our knowledge. High relapse rates were observed after non-CSRT without chemotherapy in germinoma, and after TBRT plus chemotherapy in NGGCT.
P3.05-001 Breath Analysis for Early Detection of Lung Cancer: The LuCID Study
Authors: M. Van Der Schee, J. Dickson, M. Ruparel, S. Janes, S. Dragonieri, L. Fuller, S. Grundy, D. Baldwin, P. Crosbie, A. Prasad, M. Haris, A. Barlow, L. Calvert, A. Wight, J. Bennett, M. Gaga, S. Chee, V. Conteh, M. Ledson, C. Hodkinson, J. Boschmans, R. Smith, R. Parris, D. Apthorp, S. Kitchen, M. Allsworth, B. Boyle, R. Rintoul
Journal: Journal of Thoracic Oncology (2017)
STEM-03. FOCAL ENHANCED DELIVERY OF SYSTEMICALLY ADMINISTERED THERAPEUTIC HUMAN MESENCHYMAL STEM CELLS USING MRI-GUIDED DISRUPTION OF THE BBB WITH FOCUSED ULTRASOUND
Authors: Rawan Al-kharboosh, Nicholas Ellens, Katarina Cheng, Maarten Rotman, Jordan Green, Alfredo Quinones-Hinojosa
Journal: Neuro-Oncology (2017)

Pre-clinical interventions to the CNS require direct cranial administration of drugs for relevant therapeutic concentrations since the efficacy of systemic administration is hindered by the blood-brain barrier (BBB). We used MR-guided Focused Ultrasound (MRgFUS) to deliver primary-patient derived mesenchymal stem cells (hMSCs) for the first time, with sub-millimeter precision, in preselected areas. This method is a revolutionary way to deliver cellular therapy to delicate or inoperable regions obviating the need for invasive surgical intervention. MRgFUS mediates BBB opening when low intensity FUS is applied to brain vasculature containing circulating microbubbles. This causes high intensity oscillation leading to a pore formation in BBB. hMSCs were injected intracardially in mice as a proof-of-principal delivery system. Under guidance of MRI, 0.4-1MPa in situpressures at 1 MHz, 1ms bursts and 1Hz pulse repetition frequency for 120 seconds were administered on the left hemisphere. Each animal’s contralateral brain served as its own control We demonstrate that MRgFUS augments permeability of BBB. Each animal (n=3) received 3 cavitation parameters ranging from .4-1MPa in situ pressures at time points 2, 6 and 24hrs. Immunohistochemistry identified hMSC localization on sonicated points. Further analysis showed blood cell extravasation and capillary damage due to higher pressures and increased shear force from microbubble stream. The consequence is a cavitation pore larger than intended, necessitating further optimization. There were no observed behavioral complications after sonication and no hMSCs localization in non-pulsed regions demonstrating precise localization and no off-target delivery. The global hurdle of systemic therapy due to the BBB makes access of cellular therapy to the brain parenchyma, nearly impossible. This study investigates for the first time the utility of FUS to non-destructively permeabilize the BBB by creating a transient pore big enough for hMSC access.
Molecular characterization and pharmacological profile of myxofibrosarcoma primary cultures
Authors: A. De Vita, F. Recine, L. Mercatali, G. Miserocchi, C. Liverani, C. Spadazzi, R. Casadei, A. Bongiovanni, F. Pieri, N. Riva, V. Fausti, D. Amadori, T. Ibrahim
Journal: Annals of Oncology (2017)
Biological and clinical effects of abemaciclib in a phase 2 neoadjuvant study for postmenopausal patients with HR+/HER2- breast cancer
Authors: V. Guarneri, P.A. Fasching, M. Fernández Abad, J.A. García-Saenz, A. Schneeweiss, M. Colleoni, E. Petru, T.M. Costigan, C.W. Caldwell, S. Barriga, S. Hurvitz, D. Slamon
Journal: Annals of Oncology (2017)
Nuovi aspetti della rosolia in Spagna: evidenza di un'epidemia nella popolazione latino-americana a Madrid, dicembre 2002-marzo 2003
Authors: C Lemos, R Ramirez, M Ordobas, D H Guibert, J C Sanz, L Garcia, J. F. Martinez Navarro
Journal: Eurosurveillance (2004)

Nella maggior parte dell'Europa occidentale la copertura vaccinale contro la rosolia e alta. Tuttavia, prima dell'introduzione del vaccino in America Latina, la suscettibilita alla rosolia nelle donne in eta fertile era del 10-25%. Nel 2002 in America Latina 41 paesi (93%) hanno adottato il vaccino contro la rosolia. La popolazione immigrata adulta in Spagna costituisce un gruppo di suscettibili.
In febbraio 2003, il piano di eliminazione del morbillo dalla comunita ha rilevato un aumento di notifiche di rosolia in donne di origine latino-americana a Madrid. E' stato fatto uno studio descrittivo per caratterizzare l'epidemia, basandosi sui risultati di laboratorio e sul modo di trasmissione. La definizione di caso confermato era una persona che tra il 1 dicembre 2002 e il 31 marzo 2003 aveva presentato febbre o rash con IgM positivo, e che viveva a Madrid. E' stato calcolato il tasso di attacco secondario (TAS) per famiglia. In totale sono stati identificati 19 casi di rosolia, dei quali 15 sono stati confermati e 4 sono stati classificati come casi probabili. Quattordici casi (73,7%) erano donne in eta fertile. L'eta media era di 25,1 anni. Un caso e stato diagnosticato in una donna incinta, che ha poi interrotto la gravidanza volontariamente. Undici casi provenivano dall'Ecuador. Il tempo medio di residenza in Spagna era di 41 mesi. Nessun caso ne i 54 contatti familiari (78,3%) era stato vaccinato contro la rosolia. Il TAS era del 9,1%. 
Lo studio ha messo in evidenza la diffusione della rosolia nella comunita latino-americana suscettibile, residente a Madrid. Gli interventi proposti sono stati un programma di vaccinazione rivolto alle immigrate, una campagna di educazione sanitaria per prevenire la rosolia congenita, e un programma di formazione professionale per gestire i casi.
P2.01-039 Erythropoiesis-Stimulating Agents for Chemotherapy-Induced Anaemia in Lung Cancer: Efficacy, Toxicity and Effect on Survival
Authors: V. Xirou, I. Gkiozos, D. Grapsa, I. Dimitroulis, K. Syrigos
Journal: Journal of Thoracic Oncology (2017)
MA 13.08 Long Term Follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): a Randomized Phase II Study of 2 SBRT Schedules for Lung Cancer
Authors: G. Videtic, R. Paulus, A. Singh, J. Chang, W. Parker, K. Olivier, R. Timmerman, R. Komaki, J. Urbanic, K. Stephans, S. Yom, C. Robinson, C. Belani, P. Iyengar, M. Ajlouni, D. Gopaul, S. Lele, R. Mcgarry, H. Choy, J. Bradley
Journal: Journal of Thoracic Oncology (2017)
P1.07-027 PD-L1 Expression Analysis in African American (AA) and Hispanic Lung Cancer Patients at a Minority-Based Academic Cancer Center
Authors: E. Shum, C. Su, C. Zhu, R. Gucalp, M. Haigentz, S. Packer, R. Perez-Soler, B. Halmos, H. Cheng
Journal: Journal of Thoracic Oncology (2017)
Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy
Authors: Barbara Seitz-Polski, Hanna Debiec, Alexandra Rousseau, Karine Dahan, Christelle Zaghrini, Christine Payré, Vincent L.M. Esnault, Gérard Lambeau, Pierre Ronco
Journal: Journal of the American Society of Nephrology (2017)

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). At baseline, the epitope profile (CysR, CysRC1, CysRC7, or CysRC1C7) did not correlate with age, sex, time from diagnosis, proteinuria, or serum albumin, but epitope spreading strongly correlated with PLA2R1-Ab titer (P<0.001). Ten (58.8%) of the 17 patients who had epitope spreading at baseline and were treated with rituximab showed reversal of epitope spreading at month 6. In adjusted analysis, epitope spreading at baseline was associated with a decreased remission rate at month 6 (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.72; P=0.02) and last follow-up (median, 23 months; odds ratio, 0.14; 95% confidence interval, 0.03 to 0.64; P=0.01), independently from age, sex, baseline PLA2R1-Ab level, and treatment group. We propose that epitope spreading at baseline be considered in the decision for early therapeutic intervention in patients with primary membranous nephropathy.
A Young Man With Disseminated Intra-abdominal Masses
Authors: Aung Myint Tun, Philip Xiao, Elizabeth Guevara
Journal: JAMA Oncology (2017)

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