tbuckley/cabot-search huggingface dataset:
Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs
Authors: Zhibin Chen, Martin J. Brodie, Danny Liew, Patrick Kwan
Journal: JAMA Neurology (2017)

<h3>Importance</h3> A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades. <h3>Objective</h3> To assess long-term treatment outcome in patients with newly diagnosed and treated epilepsy. <h3>Design, Setting, and Participants</h3> This longitudinal observational cohort study was conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016. <h3>Exposures</h3> Treatment with antiepileptic drugs for patients newly diagnosed with epilepsy. <h3>Main Outcomes and Measures</h3> Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics. <h3>Results</h3> Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.
Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms extending to the cervical esophagus
Authors: Ryusuke Ariyoshi, Takashi Toyonaga, Shinwa Tanaka, Hirofumi Abe, Yoshiko Ohara, Fumiaki Kawara, Tsukasa Ishida, Yoshinori Morita, Eiji Umegaki, Takeshi Azuma
Journal: Endoscopy (2017)

Abstract Background The feasibility and safety of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms extending to the cervical esophagus currently remain unknown because of the limited number of cases. We aimed to clarify the clinical outcomes of these cases. Methods This was a case series study conducted at a single institution that enrolled 26 consecutive patients with superficial esophageal neoplasms extending to the cervical esophagus who underwent ESD between July 2003 and December 2015. Results En bloc and complete resection rates were both 100 % and no major intraprocedural complications occurred. Thirteen patients were treated with prophylactic steroid therapy. The incidence of postoperative stricture in patients with a circumferential mucosal defect of more than three-quarters was 72.7 %. Four patients required entire circumferential resection, with perforation occurring after endoscopic balloon dilation (EBD) in two and EBD being required for more than 1 year in the other two. Conclusions ESD including the cervical esophagus is technically feasible. Circumferential resection may cause refractory postoperative stricture or post-EBD perforation, so needs to be avoided where possible.
Azithromycin and Survival After Hematopoietic Stem Cell Transplant—Reply
Authors: Anne Bergeron, Louise Bondeelle, Sylvie Chevret
Journal: JAMA (2017)

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Agonist anti-GITR antibody synergizes with cyclophosphamide (CTX) to induce tumor immunity
Authors: Adam Cohen, Daniel Hirschhorn-Cymmerman, Adi Diab, Miguel Perales, Taha Merghoub, Jedd Wolchok, Alan Houghton
Journal: Cancer Research (2008)

3791  Ligation of GITR (glucocorticoid-induced tumor necrosis factor receptor) can both co-stimulate effector CD4 and CD8 T cells (Teff) and abrogate suppression by CD4+foxp3+ regulatory T cells (Tregs), leading to enhanced vaccine-induced and naturally-arising tumor immunity in murine models (Cohen et al, Cancer Res 2006; Ramirez-Montagut et al,, J Immunol 2006). CTX is a cytotoxic chemotherapeutic that modulates immunity through several postulated mechanisms, including 1) lymphopenia-induced proliferation and activation of surviving T and NK cells; 2) enhanced Teff priming through tumor cell death and cross-presentation of tumor antigens; and 3) elimination of Tregs and other suppressive populations. In this study, we assessed the efficacy of combining the agonist anti-mouse GITR mAb DTA1 with CTX to treat established, poorly immunogenic tumors. C57BL/6 mice received B16 melanoma intradermally and were treated on day 6 with CTX 250 mg/kg intraperitoneally (ip), followed on day 7 by 1mg DTA1 or control rat IgG ip. In repeated experiments, 60-80% of CTX + DTA1-treated mice had long-term tumor-free survival, compared with 0-20% of mice treated with CTX + IgG, or DTA1 alone. Treating more advanced day 10 tumors with CTX + DTA1 led to 40% tumor-free survival, with no survivors seen with either treatment alone. Synergy was lost with lower doses of CTX, when CTX was given prior to tumor inoculation, or when sublethal irradiation was substituted for CTX (B16 is relatively radio-resistant), supporting a requirement for tumor cell death and a mechanism involving enhanced cross-presentation of tumor antigens. Consistent with this, naive gp100-specific pmel-1 CD8+ T cells showed increased proliferation and activation when transferred into B16-bearing mice treated 1 day earlier with CTX, compared with untreated mice or CTX-treated, non-B16-bearing mice. In addition, CTX treatment induced CD86 upregulation on CD11c+ dendritic cells, demonstrating APC activation, and increased GITR expression on proliferating (Ki67+) Teff and Tregs, providing a greater target for GITR ligation by DTA1. Finally, CTX + DTA1 significantly decreased the frequency of tumor-infiltrating Tregs (5-15% of tumor-infiltrating CD4+ cells were foxp3+ vs. 50-60% for CTX + IgG). This led to a dramatic increase in the intra-tumoral Teff:Treg ratio (40:1 vs. 5:1 for CTX + IgG), and was associated with increased CD8+ and CD4+ Teff function, as measured by granzyme B and IFNγ production. In sum, CTX + agonist anti-GITR mAb can induce rejection of an aggressive syngeneic tumor, at a stage when either agent alone is ineffective. This synergy likely involves enhanced cross-priming and activation of Teff, with concomitant decrease in tumor-infiltrating Tregs. This combination warrants further evaluation as an immunotherapeutic strategy for cancer.
18F-FDG PET/CT in Primary Hepatic Neuroendocrine Tumors
Authors: Guangyu Ma, Jie Li, Baixuan Xu, Liping Fu
Journal: Clinical Nuclear Medicine (2017)

Primary hepatic neuroendocrine tumors are extremely rare and difficult to distinguish from other liver tumors such as hepatocellular carcinoma and cholangiocarcinoma. We present a case of primary hepatic neuroendocrine tumor in which F-FDG PET/CT imaging played an important role in the diagnosis.
Alteration of the Tumor Stroma Using a Consensus DNA Vaccine Targeting Fibroblast Activation Protein (FAP) Synergizes with Antitumor Vaccine Therapy in Mice
Authors: Elizabeth K. Duperret, Aspen Trautz, Dylan Ammons, Alfredo Perales-Puchalt, Megan C. Wise, Jian Yan, Charles Reed, David B. Weiner
Journal: Clinical Cancer Research (2017)

Purpose: Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to affect the tumor stroma. Our aim was to extend this earlier work through the development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines.Experimental Design: We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and antitumor activity of this novel FAP vaccine in preclinical studies, and correlated these findings to patient data.Results: This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8+ and CD4+ immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared with a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor antigen-specific DNA vaccines to enhance antitumor immunity. Evaluation of the tumor microenvironment showed increased CD8+ T-cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from The Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8+ T-cell infiltration.Conclusions: These results suggest that immune therapy targeting tumor antigens in combination with a microconsensus FAP vaccine provides two-fisted punch-inducing responses that target both the tumor microenvironment and tumor cells directly. Clin Cancer Res; 24(5); 1190-201. ©2018 AACR.
The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids
Authors: Wei Cao, Hisako Kayama, Mei Lan Chen, Amber Delmas, Amy Sun, Sang Yong Kim, Erumbi S. Rangarajan, Kelly McKevitt, Amanda P. Beck, Cody B. Jackson, Gogce Crynen, Angelos Oikonomopoulos, Precious N. Lacey, Gustavo J. Martinez, Tina Izard, Robin G. Lorenz, Alex Rodriguez-Palacios, Fabio Cominelli, Maria T. Abreu, Daniel W. Hommes, Sergei B. Koralov, Kiyoshi Takeda, Mark S. Sundrud
Journal: Immunity (2017)
The Added Value of Dynamic 18F-Florbetapir PET in the Assessment of Dementia With Lewy Bodies
Authors: Diego Alfonso López-Mora, Valle Camacho, Alberto Lleó, Alejandro Fernández, Ignasi Carrió
Journal: Clinical Nuclear Medicine (2017)

Dementia with Lewy bodies (DLB) is the most common cause of dementia after Alzheimer disease. It is often underdiagnosed because of the overlapping with Alzheimer disease symptoms. We report the F-FDG and F-florbetapir dynamic PET images (early and delay phases) of an 83-year-old woman with cognitive impairment associated with visual hallucinations and parkinsonism due to probable DLB. This image highlights that the early phases of F-florbetapir may reflect regional cerebral perfusion with a pattern very similar to that of regional glucose metabolism in DLB.
Progression-free survival (PFS) and health-related quality of life (HRQoL) in AVAglio, a phase III study of bevacizumab (Bv), temozolomide (T), and radiotherapy (RT) in newly diagnosed glioblastoma (GBM).
Authors: Roger Henriksson, Andrew Bottomley, Warren Mason, Frank Saran, Wolfgang Wick, Ryo Nishikawa, Timothy Francis Cloughesy, Antoine F Carpentier, Khe Hoang-Xuan, Petr Kavan, Dana Cernea, Alba Ariela Brandes, Magalie Hilton, Ana Maria Abajo Guijarro, Arliene Ravelo, Oliver L. Chinot
Journal: Journal of Clinical Oncology (2013)

2005^ Background: GBM has a high disease burden and poor prognosis, and impacts negatively on HRQoL. Symptomatic therapies for GBM, such as corticosteroids (CS), may impact patient status negatively Methods: AVAglio, a randomized, double-blind, placebo (P)-controlled trial in patients (pts) ≥18 yrs with newly diagnosed GBM, evaluated the addition of Bv or P (10mg/kg, q2w) to 6 wks of T (75mg/m 2 /d) + RT (2Gy, 5d/wk) followed by 28 treatment-free days, then 6 cycles of T (150–200 mg/m 2 /d, 5d q4w) with Bv or P (10 mg/kg, q2w), and then single-agent Bv or P (15 mg/kg, q3w) until disease progression (PD)/unacceptable toxicity. Co-primary endpoints were investigator-assessed PFS and overall survival. Secondary endpoints included HRQoL (EORTC QLQ-C30 and BN20, with 5 prespecified domains based on relevance in GBM). HRQoL time to definitive deterioration (TDD) was defined as time from randomization to ≥10 point deterioration from baseline with no subsequent improvement, PD, or death. Exploratory endpoints included KPS and CS use. Results: Baseline characteristics were well balanced. Bv significantly prolonged PFS (HR 0.64, 95% CI 0.55–0.74, p&lt;0.0001; median 10.6 vs 6.2 mo) and delayed TDD in HRQoL compared with P (p&lt;0.0001; Table). Functional independence (KPS ≥ 70%) was maintained during PFS in both arms (median Bv vs P: 9 vs 6 mo). Among pts on CS (≥ 2mg) at baseline, discontinuation (≥ 5 consecutive days) was more frequent with Bv than P (66% vs 47%). In pts off CS at baseline (&lt; 2mg), time to CS initiation was significantly longer with Bv than P (HR 0.71, 95% CI 0.57–0.88; median 12.3 vs 3.7 mo). Conclusions: Addition of Bv to RT/T provided a clinically meaningful and statistically significant PFS improvement associated with stable/improved HRQoL and KPS, and reduced CS requirement. Clinical trial information: NCT00943826. [Table: see text]
Do Less Harm: Evaluating HIV Programmatic Alternatives in Response to Cutbacks in Foreign Aid
Authors: Rochelle P. Walensky, Ethan D. Borre, Linda-Gail Bekker, Emily P. Hyle, Gregg S. Gonsalves, Robin Wood, Serge P. Eholié, Milton C. Weinstein, Xavier Anglaret, Kenneth A. Freedberg, A. David Paltiel
Journal: Annals of Internal Medicine (2017)

Background: Resource-limited nations must consider their response to potential contractions in international support for HIV programs. Objective: To evaluate the clinical, epidemiologic, and budgetary consequences of alternative HIV program scale-back strategies in 2 recipient nations, the Republic of South Africa (RSA) and Côte d'Ivoire (CI). Design: Model-based comparison between current standard (CD4 count at presentation of 0.260 × 109 cells/L, universal antiretroviral therapy [ART] eligibility, and 5-year retention rate of 84%) and scale-back alternatives, including reduced HIV detection, no ART or delayed initiation (when CD4 count is <0.350 × 109 cells/L), reduced investment in retention, and no viral load monitoring or second-line ART. Data Sources: Published RSA- and CI-specific estimates of the HIV care continuum, ART efficacy, and HIV-related costs. Target Population: HIV-infected persons, including future incident cases. Time Horizon: 5 and 10 years. Perspective: Modified societal perspective, excluding time and productivity costs. Outcome Measures: HIV transmissions and deaths, years of life, and budgetary outlays (2015 U.S. dollars). Results of Base-Case Analysis: At 10 years, scale-back strategies increase projected HIV transmissions by 0.5% to 19.4% and deaths by 0.6% to 39.1%. Strategies can produce budgetary savings of up to 30% but no more. Compared with the current standard, nearly every scale-back strategy produces proportionally more HIV deaths (and transmissions, in RSA) than savings. When the least harmful and most efficient alternatives for achieving budget cuts of 10% to 20% are applied, every year of life lost will save roughly $900 in HIV-related outlays in RSA and $600 to $900 in CI. Results of Sensitivity Analysis: Scale-back programs, when combined, may result in clinical and budgetary synergies and offsets. Limitation: The magnitude and details of budget cuts are not yet known, nor is the degree to which other international partners might step in to restore budget shortfalls. Conclusion: Scaling back international aid to HIV programs will have severe adverse clinical consequences; for similar economic savings, certain programmatic scale-back choices result in less harm than others. Primary Funding Source: National Institutes of Health and Steve and Deborah Gorlin MGH Research Scholars Award.
THU0064 Clinical signification of anti-ku antibody
Authors: F Limbach, J Goetz, RM Javier, JL Kuntz, J Sibilia
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The Ku autoantigen is a DNA binding factor consisting of 70 and 80 kDa protein which form a heterodimer involved in repair of ds DNA breaks. Since the original description of anti-Ku antibody in patients with polymyositis-scleroderma overlap syndrome, this antibody has been showed to be associated with several autoimmune diseases. <h3>Objectives</h3> To describe clinical features of 8 patients with anti-KU antibody. <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3> anti-Ku antibody is not specific of a connective tissu disease and can also be observed in patients without any autoimmune disease (n°7). In addition to previous described association, anti-Ku antibody can also be present in Wegener granulomatosis and idiopathic Raynaud's phenomen. Two of our patients had an evaluative cancer (n°5 and 8) and one (n°7) presented a stomach neoplasm 3 years before the detection of anti-Ku antibody. This finding needs further investigations to assess if anti-Ku antibody can be associated with or predictive of a neoplasm.
Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells
Authors: Saurabh Dixit, Rajnish Sahu, Richa Verma, Skyla Duncan, Guillermo H. Giambartolomei, Shree R. Singh, Vida A. Dennis
Journal: Biomaterials (2017)
Design and characterization of monolaurin loaded electrospun shellac nanofibers with antimicrobial activity
Authors: Nawinda Chinatangkul, Chutima Limmatvapirat, Jurairat Nunthanid, Manee Luangtana-Anan, Pornsak Sriamornsak, Sontaya Limmatvapirat
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The aim of this study was to elucidate the optimized fabrication factors influencing the formation and properties of shellac (SHL) nanofibers loaded with an antimicrobial monolaurin (ML). The main and interaction effects of formulation and process parameters including SHL content (35%-40% w/w), ML content (1%-3% w/w), applied voltage (9-27 kV) and flow rate (0.4-1.2 ml/h) on the characteristic of nanofibers were investigated through a total of 19 experiments based on a full factorial design with three replicated center points. As a result, the SHL content was the major parameter affecting fiber diameter. Another response result revealed that the SHL content would be also the most significant negative impact on amount of beads. An increase in the concentration of SHL leaded to a reduction in the amount of beads. From the results of characterization study, it was proved that ML might be entrapped between the chains of SHL during the electrospinning process exhibiting an excellent encapsulation. According to the response surface area, small (~488 nm) and beadless (~0.48) fibers were obtained with the SHL and ML contents of 37.5% and 1.1% w/w respectively, at the applied voltage of 18 kV and the flow rate of 0.8 ml/h. In addition, the results of the kill-kinetic studies showed that SHL nanofibers loaded with ML exhibited an excellent antibacterial activity against Staphylococcus aureus, while Escherichia coli was less affected due to the hydrophilic structure of the its outer membrane. ML also exerted an antifungal activity by reducing the number of Candida albicans colonies. Based on their structural and antimicrobial properties, SHL nanofibers containing ML could be potentially used as a medicated dressing for wound treatment.
Розробка неінвазивної моделі для підвищення точності діагностики стадії фіброзу печінки при неалкогольній жировій хворобі печінки
Authors: Yu.M. Stepanov, N.V. Nedzvetskaya, V.B. Yagmur, I.A. Klenina, N.Yu. Oshmyanskaya
Journal: GASTROENTEROLOGY (2017)

Актуальність. Відмінність між м’яким (F1–2) і розвинутим фіброзом (F3–4), як і відсутність фіброзу у хворих на неалкогольну жирову хворобу печінки (НАЖХП), є важливим питанням для з’ясування прогнозу. Сироваткові маркери були запропоновані як альтернатива біопсії. Мета: розробити нову модель для визначення стадії фіброзу на основі більш ефективної комбінації серологічних маркерів та порівняння її з встановленими алгоритмами. Матеріали та методи. У дослідження включені 60 пацієнтів із НАЖХП, які проходили обстеження і лікування у відділенні захворювань печінки та підшлункової залози ДУ «Інститут гастроентерології НАМН України». Серед досліджених 26 (42,3 %) чоловіків та 34 (56,7 %) жінки, середній вік яких (37,1 ± 12,4) та (44,3 ± 7,3) року відповідно. Всім пацієнтам була проведена черезшкірна пункційна трепан-біопсія печінки з подальшим морфологічним дослідженням пунктату; виконано визначення вмісту гіалуронової кислоти, α2-макроглобуліну, аполіпопротеїну А1, фібронектину, гаптоглобіну в сироватці крові та був проведений розрахунок неінвазивних маркерів фіброзу печінки: AAR, APRI, FIB-4. Результати. Проведений ROC-аналіз показав, що найбільші показники площі під AUROC-кривою були для індексу FIB-4 для F2 — 0,72, F3 — 0,8, F4 — 0,82 при р &lt; 0,05. Результати індексу APRI були вірогідно високими для помірного та вираженого фіброзу (F2 — 0,74, F3 — 0,82, р &lt; 0,05). А показники AAR були вірогідними лише для цирозу печінки (площа під AUROC-кривою 0,89, р &lt; 0,05). Установлено сильний прямий зв’язок між стадією фіброзу та рівнем гіалуронової кислоти, α2-макроглобуліну і фібронектину (r = 0,72, 0,93 та 0,71 відповідно при р &lt; 0,05) та обернений зв’язок помірної сили між показниками аполіпопротеїну А1, гаптоглобіну (r = –0,61 і –0,35 при р &lt; 0,05). Визначено прямий зв’язок помірної сили між ступенем активності запального процесу і показниками гіалуронової кислоти, α2-макроглобуліну і фібронектину (r = 0,54, 0,67 та 0,55 при р &lt; 0,05) і обернений помірний зв’язок — аполіпопротеїну А1 та гаптоглобіну (r = –0,56 і –0,33 при р &lt; 0,05). Висновки. Установлено, що найбільшу діагностичну цінність із неінвазивних маркерів фіброзу мають показники α2-макроглобуліну, аполіпопротеїну А1, гіалуронової кислоти та фібронектину, для яких площа під AUROC-кривою для мінімального фіброзу не була нижчою ніж 0,75, а для помірного, вираженого фіброзу та цирозу становила більше 0,9.