tbuckley/cabot-search huggingface dataset:
Clinical features and outcome of follicular lymphoma: 17 years experience from All-India Institute of Medical Sciences (AIIMS), New Delhi, India.
Authors: Ajay Gogia, Vinod Raina, Atul Sharma, Lalit Kumar, Mehar C Sharma, Ritu Gupta, Prasenjit Das
Journal: Journal of Clinical Oncology (2013)

e19524 Background: Follicular lymphoma (FL) is second most common lymphoma in adult, constituted 20% of all lymphoma cases in the west. There is limited information is available on FL from India. Methods: The clinic-pathological profile, treatment outcome and prognostic factors for survival were assessed in 181 patients of FL seen at AIIMS, New Delhi, a large tertiary referral centre, over a period of 17 years (1996-2012). Results: There were 120 males and 61 females. The median age was 51 years (24-80 years). The common presenting features were lymphadenopathy 71%, fatigue 23% and fever 20%. Ann Arbor Rai stage distribution was: stage I - 9%, stage II - 11%, stage III -22 % and stage IV - 58%. Thirty six patients (20%) had ECOG performance status III/IV. Extra nodal involvement and bulky disease were present in 40 (22%) and 31 (19%) patients respectively. Follicular Lymphoma International Prognostic Index (FLIPI) 1 score : Low -25%, Intermediate-45% and high risk in 30% of cases. FL grade 1, 2 and 3 were seen in 63 ( 35%), 63 (35%) and 55 (30%) patients respectively. One forty five patients (80%) received treatment at presentation. Chemotherapeutic regimen used were: CHOP-45 , CVP-51, chlorambuil and prednisolone -7 , BR ( bendamustine and rituximab)-12, RCHOP- 14 and RCVP in 7 cases. The overall response (ORR) and complete remission (CR) rates were 70% and 35% respectively. Relapse occurred in 54 patients, 50 patients died and progression was observed in 63(35%) patients. Median overall survival (OS) and event free survival (EFS) was 5.5 years and 3.5 years respectively, with median follow up period of 3 years. Grade 3 histology, failure to attain CR, low serum albumin, PS III/IV, bulky disease and high risk FLIPI were significantly associated with lower event free survival. High risk FLIPI (HR 1.46, 95% CI 1.03-2.10, p=0.003) and failure to attain CR (HR 2.64, CI 1.10-4.30, p=0.001) were predictors of poor OS. Conclusions: FL represents 9 % of all lymphoma in adult. This is the largest data from single institute from India. Eighty percentage of patients presented in stage III/IV disease. High risk FLIPI and failure to attain CR were important prognostic variables for OS.
Reconciling estimates of the global influenza burden
Authors: Sheena G Sullivan, Benjamin J Cowling
Journal: The Lancet Respiratory Medicine (2018)

Influenza remains an important cause of morbidity and mortality, even in high-income countries. Yet quantification of its burden is contentious. Although influenza virus infections are commonly associated with respiratory symptoms, some infections can cause more severe disease, resulting in hospitalisation or death. Influenza can also trigger other health outcomes—eg, acute myocardial infarction1 which probably arises because infection stimulates inflammation, atherosclerosis, and coronary lesions.
Abstract 21155: Outcomes of Transcatheter Aortic Valve Replacement in High or Extreme Risk Patients With Severe Bicuspid Aortic Valve Stenosis
Authors: Andres M Pineda, Jennifer Rymer, Alice Wang, Lynne H Koweek, Ryan Plichta, Adam Williams, Todd L Kiefer, Andrew Wang, Jeffrey Gaca, Chad Hughes, John K Harrison
Journal: Circulation (2017)

Introduction: Although TAVR has been performed in patients with bicuspid aortic valves (BAV), these patients were excluded from all the US pivotal trials and therefore their postoperative outcomes are not clearly defined. Hypothesis: Patients with BAV undergoing TAVR may achieve similar outcomes when compared with trileaflet aortic valve (TAV) stenosis. Methods: We retrospectively evaluated the outcomes of high or extreme risk patients with BAV stenosis at our institution between April 2011 and November 2016, and compared them with those of patients with TAV stenosis. Chi-square and the Mann-Whitney U tests were used to compared the groups, and a Kaplan-Meier analysis was performed to estimate long-term survival. The study was approved by the Duke University Hospital Institutional Review Board. Results: TAVR was performed in a total of 567 eligible patients, from which 50 (8.8%) had BAV and 517 (91.2%) TAV disease. Patients with BAV were younger (median age 70 years [64-74] vs. 81 [75-86], p&lt;0.001), had higher prevalence of COPD (52.0% vs. 30.8, p=0.002), lower prevalence of coronary artery disease (64.0% vs 76.8, p=0.036), higher BMI (median 28 kg/m 2 [25-35] vs. 27 [24-31], p=0.046) and lower STS PROM score (median 4.6% [3.0-7.7] vs. 6.7 [4.4-9.9], p=0.004) when compared with those with TAV. Overall, self-expanding and balloon-expandable TAVR devices were used in 58.4% and 41.3% of the cases, and transfemoral access was used in 86.8%. Patients with BAV had a higher mean aortic valve gradient postoperatively (median 12 mmHg [10-15] vs. 10 [7-13], p&lt;0.001). There were no differences in the procedural characteristics or in the incidence of any of the postoperative adverse outcomes between the groups, including moderate to severe paravalvular regurgitation (4.0% vs. 3.5, p=0.541), stroke (2.0% vs. 1.5, p=0.567), and 30-day all-cause mortality (6.0% vs. 1.5, p=0.064). The 2-year survival (82.0% vs. 83.4, p=0.476) was similar between the groups. Conclusions: This initial experience suggests that TAVR can be performed in patients with severe BAV stenosis at high or extreme risk for traditional surgical aortic valve replacement achieving similar short-term clinical outcomes and mid-term survival compared with patients with TAV.
Abstract 19301: Treatment of Obstructive Hypertrophic Cardiomyopathy by Ultrasound-guided Percutaneous Radiofrequency Ablation of Interventricular Septum
Authors: Liwen Liu, Lei Zuo, Chao Sun, Jing Li, Jinzhou Zhang, Mengyao Zhou, Ruiqi Guo, Bo Xu, Rui Hu, Lize Xiong
Journal: Circulation (2017)

Introduction: The failure of medications and the unsuitability of myectomy and alchol septal ablation for some hypertrophic obstructive cardiomyopathy (HOCM) patients call for a novel treatment. A ...
Abstract 20770: A Novel Mini-Pig Genetic Model of Hypertrophic Cardiomyopathy: Altered Myofilament Dynamics, Hyper-Contractility, and Impaired Systolic/Diastolic Functional Reserve in vivo
Authors: Carlos L del Rio, Marcus P Henze, Fiona L Wong, Marc J Evanchik, Abhay Divekar, Lindsey M Gifford, Ahmad Ferhaan, Eric M Green
Journal: Circulation (2017)

Introduction: Hypertrophic cardiomyopathy (HCM) is a heritable cardiac disease characterized by hyper-contractility, impaired filling, and exertional intolerance. The molecular basis for this patho...
Abstract 14374: Characteristics of Plaque Disruption by IVUS in Women Presenting with MI without Obstructive CAD
Authors: Sohah N Iqbal, G.B. John Mancini, David Wood, James N Slater, Frederick Feit, Michael Attubato, Ivan Pena-Sing, Leonid Yatskar, Judith S Hochman, Harmony R Reynolds
Journal: Circulation (2012)

Background: In a prospective study, we recently demonstrated plaque disruption (PD; rupture and ulceration) in 38% of women with MI without angiographically obstructive CAD. Baseline clinical chara...
The Genomic Landscape of Multiple Myeloma Complex Structural Variations
Authors: Francesco Maura, Niccolò Bolli, Kevin J Dawson, Nicos Angelopoulos, Stephane Minvielle, Inigo Martincorena, Thomas J Mitchell, Anthony Fullam, Santiago Gonzalez, Dominik Glodzik, Raphael Szalat, Mehmet Kemal Samur, Mariateresa Fulciniti, Yu-Tzu Tai, Florence Magrangeas, Philippe Moreau, Paolo Corradini, Kenneth C Anderson, David Wedge, Moritz Gerstung, Hervé Avet-Loiseau, Nikhil Munshi, Peter J Campbell
Journal: Blood (2017)
Cardiovascular Health and Cognitive Decline—Reply
Authors: Cécilia Samieri, Jean-Philippe Empana
Journal: JAMA (2018)

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Notice of Retraction and Replacement. Snook et al. Change in percentages of adults with overweight or obesity trying to lose weight, 1988-2014. JAMA. 2017;317(9):971-973
Authors: Kassandra R. Snook, Andrew R. Hansen, Carmen H. Duke, Amy A. Hackney, Jian Zhang
Journal: JAMA (2018)

In Reply Dr Fleminger and Ms Fleminger suggest that both the TBI itself and also constitutional factors, such as prior deliberate self-harm, may be responsible for the high suicide rates after TBI found in our study. 1Our study showed that the incidence rate ratio of suicide was increased by 1.90 times after adjusting for relevant covariates, including fractures not involving the skull, chronic medical diseases, socioeconomic status, and preinjury factors such as prior mental illness and deliberate self-harm.We adjusted our estimates for confounding effects more rigorously than prior studies that have yielded higher risk estimates after TBI; thus, our estimates were more conservative.Moreover, the suicide rate associated with TBI was found to be 1.73 times higher than for other fractures not involving the skull, which was a way of taking accident proneness due to constitutional factors into account.Nevertheless, in an observational study, adjustment may not completely eliminate confounding.The fact that the group with TBI had higher rates of deliberate self-harm before the TBI than the group without TBI could still have influenced our results.Prior research has shown that mental illness and deliberate self-harm are the main risk factors for suicide.Although we adjusted for these factors, the risk of suicide after deliberate self-harm and after first psychiatric diagnosis continues to be high for many years. 2,3A prior meta-analysis estimated that in absolute numbers, "only" relatively few individuals (4.2%) died by suicide after engaging in deliberate self-harm over a 10-year follow-up, 4 although some die of other causes. 5Those who survive will consequently be at risk of TBI.As such, individuals engaging in deliberate self-harm carry a long-term suicide risk and, as pointed out by Fleminger and Fleminger, they are at higher risk of experiencing subsequent TBI.A secondary finding in our study was the paradoxical effect that individuals engaging in deliberate self-harm but not subsequently experiencing a TBI had a higher suicide risk than those engaging in deliberate self-harm and subsequently experiencing a TBI, as seen in the interaction analyses.We agree that it is possible that this result reflects a survivor effect-individuals engaging in deliberate self-harm had to survive the immediate period of higher yet relatively low absolute suicide risk to be at risk of TBI later-rather than being due only to differences in personality traits and accident proneness.
Evaluation of the safety and the tolerability of durvalumab plus tremelimumab combined with FOLFOX in metastatic colorectal cancer (MEDITREME)
Authors: J.-D. Fumet, N. Isambert, A. Hervieu, S. Zanetta, J.-F. Guion, A. Hennequin, E. Rederstorff, A. Bertaut, F. Ghiringhelli
Journal: Annals of Oncology (2018)

Background: 5-Fluorouracil plus irinotecan or oxaliplatin with target therapy are standard 1st line therapy for metastatic colorectal cancer (mCRC). 5-Fluorouracil plus oxaliplatin are known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that blocks programmed cell death ligand 1 (PD-L1) binding to its receptor (PD-1). Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to FOLFOX increases treatment efficacy. Methods: After a phase I with 9 patients, this phase II study (ClinicalTrials.gov NCT03202758) will assess the efficacy and safety of FOLFOX/D/T association in patients (pts) with good performance status pts (ECOG < 2) with untreated, RAS mutational status mCRC. Prior adjuvant therapy is allowed provided recurrence is > 6 months post-completion. Assuming no safety concerns the study will go on to include 39 additional pts. Pts will receive folinic acid/5-fluorouracil (400mg/m2 as bolus followed by 2400mg/m2 as a 46h infusion)/Oxaliplatin (85mg/m2) q14 days with D (750 mg) D1 q 14 days and T (75 mg) D1q 28 days. After 6 cycles of FOLFOX only, D/T will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is safety and efficacy according to PFS; secondary endpoints include overall response rate and quality of life. Results: 9 patients were enrolled in the phase I. Grade 3-4 treatment-related adverse events occurred in 3 of 9 patients. The most common treatment-related grade 3-4 adverse events were neutropenia and diarrhea. No patients discontinued due to a drug-related adverse event. First clinical outcomes have shown 4 patients with partial response, 3 patients with stable disease and 2 patients with progression disease. Ancillary analysis were performed. Conclusions: FOLFOX/D/T was tolerable with manageable toxicity. Preliminary results have shown encouraging clinical outcome. The results of this phase I study have led to phase II study which are ongoing. Clinical trial identification: NCT03202758. Legal entity responsible for the study: Nicolas Isambert. Funding: AstraZeneca. Disclosure: All authors have declared no conflicts of interest.
Radical Prostatectomy or Watchful Waiting in Prostate Cancer — 29-Year Follow-up
Authors: Anna Bill-Axelson, Lars Holmberg, Hans Garmo, Kimmo Taari, Christer Busch, Stig Nordling, Michael Häggman, Swen-Olof Andersson, Ove Andrén, Gunnar Steineck, Hans-Olov Adami, Jan-Erik Johansson
Journal: New England Journal of Medicine (2018)

Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse.
Abstract 2249: Effects of Mechanical Asynchrony on Mitral Regurgitation After Acute Myocardial Infarction: The VALIANT Echo Study
Authors: Sung-Hee Shin, Amira H Hassanein, Maria Amigoni, Alessandra Meris, Anil Verma, Chung-Lieh Hung, Mikhail Bourgoun, Eric J Velazquez, Lars Kober, John J McMurray, Marc A Pfeffer, Scott D Solomon
Journal: Circulation (2008)

Mitral regurgitation (MR), a common complication of myocardial infarction (MI), is associated with adverse outcomes. However, the association between mechanical asynchrony and MR following MI is no...
Novel CTLA4 antibodies demonstrate potent anti-tumor activity in humanized CTLA4 mouse model
Authors: C. Guo, Y. Yang, Y. Guo, Y. Shen, J. Ni
Journal: Annals of Oncology (2018)

Background: CTLA4 (cytotoxic T-lymphocyte-associated protein 4) is homologous to the co-stimulatory protein CD28, and both receptor binds to CD80 and CD86. Cancer cells can be recognized and destructed by the host's immune system. In this setting, CTLA4 functions as a brake to dampen anti-tumor T cell responses, which promote cancer progression. Antibodies targeting CTLA4 was expected to subvert T cell inhibition. Moreover, regulatory T cells residing in the tumor microenvironment can be killed by anti-CTLA4 antibody since these cells have higher expression level of CTLA4 comparing with the activated T cells. Yervoy, an anti-CTLA4 antibody, was the first FDA-approved antibody targeting the immune checkpoint family, and it protects a fraction of cancer patients when either used alone or in combination with other drugs. We asked whether the efficacy of anti-CTLA4 antibodies could be evaluated in humanized mouse models. And if so, whether we can use in vivo assay to guide the development of potent antibodies targeting CTLA4. Methods: Here, we generated humanized CTLA4 knock-in mouse (B-hCTLA4) with a chimeric PD-1 receptor and this mouse were validated by Yervoy. Then, we utilized humanized B-hCTLA mice and implanted syngeneic tumors subcutaneously, followed by treating mice with purified testing CTLA4 antibodies and Yervoy. Via this approach, we are able to discern several clones that have better efficacy than Yervoy. These clones were further selected for humanization. The cohort of recombinant humanized CTLA4 antibodies were screened in B-hCTLA4 mice. Results: We successfully generated B-hCTLA4 mouse for anti-human CTLA4 antibody in vivo efficacy evaluation. A cohort of CTLA4 specific antibodies were successfully generated and purified. The clones with better efficacy than Yervoy were screened using Biocytogen's humanized mouse platform. These clones were humanized and screened by using B-hCTLA4 mice. Both the Fv and Fc portion of the lead antibody were optimized using the B-hCTLA4 mice, leading to the humanized form of the antibodies. Conclusions: Using the platform established at Biocytogen, we successfully discovered two antibodies whose efficacy is equivalent or exceed that of Yervoy. The clinical evaluation of these new entities are wanted. Legal entity responsible for the study: Yi Yang. Funding: Beijing Biocytogen Co., Ltd. Disclosure: All authors have declared no conflicts of interest.
Coronary-Artery Occlusion from Kawasaki’s Disease
Authors: Hiroki Matsuura, Masanobu Ohya
Journal: New England Journal of Medicine (2018)

An 18-year-old man with a history of Kawasaki’s disease and known coronary-artery aneurysms presented with chest pain. Coronary angiography revealed occlusion of the left anterior descending artery.
Voices for Healthy Kids: a multisectoral collaboration to accelerate policy changes that promote healthy weight for all children and adolescents in the United States
Authors: Emily A Callahan,, Marla Hollander, Diana V McGhie, Sarah Simpson, Jill Birnbaum, Monica H Vinluan
Journal: BMJ (2018)

<b>Emily Callahan and colleagues</b> report how a multisectoral collaboration of more than 140 stakeholder organisations is advancing policy changes to improve food and physical environments in the United States to promote healthy weight for all children and adolescents
Preliminary pharmacokinetic results from a phase I study of GBR 1302 in patients with HER2 positive cancers
Authors: G. Gudi, V. Ca, S. Gn, C. von Gunten, E. Fluhler, J. Back
Journal: Annals of Oncology (2018)

Background: HER2 is dysregulated in a wide range of solid tumors, including breast cancer, and is an attractive target for tailored oncologic treatment. GBR 1302 is a HER2xCD3 bispecific antibody that redirects cytotoxic T-cells to kill HER2 overexpressing cancer cells. This unique mode of action is anticipated to result in superior antitumor activity in HER2-positive tumors by harnessing the cytotoxic capabilities of patients’ existing T-cells. Methods: This ongoing, phase 1, first-in-human, open-label, multicenter, dose-escalation study is evaluating GBR 1302 in adults with progressive HER2-positive solid tumors for which no standard or curative treatment is available. Subjects receive intravenous GBR 1302 on Day 1 and Day 15 in 28-day treatment cycles at escalating dose levels, starting at 1 ng/kg. The first 4 cohorts consisted of a single subject; subsequent cohorts are being enrolled using a 3 + 3 design. Blood samples were collected for pharmacokinetic (PK) and anti-drug antibody (ADA) analyses (secondary endpoints). Quantification of GBR 1302 serum concentrations (for PK) and detection/confirmation of anti GBR 1302 antibodies (for immunogenicity) were performed using validated LC/MS/MS and ELISA methods, respectively. PK parameters were evaluated using standard non-compartmental methods. Results: As of 21 August 2018, PK data were available from 31 subjects over dose range of 1 ng/kg to 750 ng/kg. Serum concentrations were less than the lower limit of quantification of 50 pg/mL at the first dose (1 ng/kg), and only transient concentrations were observed at 3 and 10 ng/kg dose levels. Evaluable PK profiles were observed from 30 ng/kg onwards. GBR 1302 showed maximum serum concentration (Cmax) around the end of infusion, after which serum concentrations declined bi-exponentially with a mean terminal half-life of around 4 to 7 days. Both Cmax and area under the curve (AUC0-t) showed a near dose-proportional increase up to 750 ng/kg (maximum evaluated dose). None of the samples collected from subjects up to cohort 5 showed positive ADA response. Conclusions: Per ongoing analysis, GBR 1302 showed a favorable, linear PK. None of the subjects evaluated so far showed positive ADA response. Editorial acknowledgement: Editorial assistance was provided by Jacqueline Benjamin, PhD of Prescott Medical Communications Group, Chicago, IL. Clinical trial identification: NCT02829372. Legal entity responsible for the study: Glenmark Pharmaceuticals SA. Funding: Glenmark Pharmaceuticals SA. Disclosure: G. Gudi, E. Fluhler: Employee of Glenmark Pharmaceuticals Inc., V. Ca, S. Gn: Employee of Glenmark Pharmaceuticals, Ltd., C. von Gunten, J. Back: Employee of Glenmark Pharmaceuticals SA.
Abstract P146: Parental Influences on Children’s Healthy Behaviors
Authors: Kayla Marcotte, Rachel Krallman, Jean DuRussel-Weston, Eva Kline-Rogers, Elizabeth A Jackson, Kim A Eagle
Journal: Circulation (2017)

Background: The effect of parental health behaviors on children has not been well studied. This study examined how sixth-grade students’ health behaviors were influenced by perceptions of their parents’ health behaviors. Methods: Sixth grade students from 60 schools in Michigan participating in Project Healthy Schools were eligible for this study. Data on children’s and parents’ dietary, physical activity, and sedentary habits were collected through a validated health behavior questionnaire. Health behaviors analyzed included physical activity, screen time, sugary beverage consumption, fast/fatty food consumption, and fruit/vegetable consumption. Logistic regressions were used to determine the effect of parents’ health behaviors on their children’s health behaviors. Results: 4065 students completed the health behavior questionnaire. Children were more likely to have healthy physical activity habits if their parents also had healthy physical activity habits. Children were more likely to have healthy screen time habits if their parents had healthy screen time, fast/fatty food, and sugary beverage habits. Children were more likely to have healthy sugary beverage habits if their parents had healthy sugary beverage, fruit/vegetable, and fast/fatty food habits. Children were more likely to have healthy fast/fatty food habits if their parents had healthy fast/fatty food, screen time, and sugary beverage habits. Children were more likely to have healthy fruit/vegetable habits if their parents had healthy fruit/vegetable, physical activity, and fast/fatty food habits. Conclusions: Parent behaviors were strong predictors of child behaviors in the same category (e.g. high parental physical activity predicted high child physical activity) for all health behaviors assessed. All behaviors except physical activity were influenced by a multiple parent behaviors, suggesting more complex relationships. Further investigation may provide insight into strategies to improve children’s health behaviors.