tbuckley/cabot-search huggingface dataset:
A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma
Authors: Sara M. Federico, M. Beth McCarville, Barry L. Shulkin, Paul M. Sondel, Jacquelyn A. Hank, Paul Hutson, Michael Meagher, Aaron Shafer, Catherine Y. Ng, Wing Leung, William E. Janssen, Jianrong Wu, Shenghua Mao, Rachel C. Brennan, Victor M. Santana, Alberto S. Pappo, Wayne L. Furman
Journal: Clinical Cancer Research (2017)

Purpose: Anti-GD2 mAbs, acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines, and haploidentical natural killer (NK) cells.Experimental Design: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40 mg/m2/dose, days 2-5), GM-CSF, and IL2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4), and ifosfamide/carboplatin/etoposide (courses 5,6). Parentally derived NK cells were administered with courses 2, 4, and 6. Serum for pharmacokinetic studies of hu14.18K322A, soluble IL2 receptor alpha (sIL2Rα) levels, and human antihuman antibodies (HAHA) were obtained.Results: Thirteen heavily pretreated patients (9 with prior anti-GD2 therapy) completed 65 courses. One patient developed an unacceptable toxicity (grade 4 thrombocytopenia >35 days). Four patients discontinued treatment for adverse events (hu14.18K322A allergic reaction, viral infection, surgical death, second malignancy). Common toxicities included grade 3/4 myelosuppression (13/13 patients) and grade 1/2 pain (13/13 patients). Eleven patients received 29 NK-cell infusions. The response rate was 61.5% (4 complete responses, 1 very good partial response, 3 partial responses) and five had stable disease. The median time to progression was 274 days (range, 239-568 days); 10 of 13 patients (77%) survived 1 year. Hu14.18K322A pharmacokinetics was not affected by chemotherapy or HAHA. All patients had increased sIL2Rα levels, indicating immune activation.Conclusions: Chemotherapy plus hu14.18K322A, cytokines, and NK cells is feasible and resulted in clinically meaningful responses in patients with refractory/recurrent neuroblastoma. Further studies of this approach are warranted in patients with relapsed and newly diagnosed neuroblastoma. Clin Cancer Res; 23(21); 6441-9. ©2017 AACR.
Pembrolizumab (pembro) plus chemotherapy as front-line therapy for advanced NSCLC: KEYNOTE-021 cohorts A-C.
Authors: Shirish M. Gadgeel, James Stevenson, Corey J. Langer, Leena Gandhi, Hossein Borghaei, Amita Patnaik, Liza Cosca Villaruz, Matthew A. Gubens, Ralph J. Hauke, James Chih-Hsin Yang, Lecia V. Sequist, Robert D. Bachman, Joy Yang Ge, Harry Raftopoulos, Vassiliki Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2016)

9016 Background: The anti–PD-1 antibody pembro exhibits robust antitumor activity in patients (pts) with advanced NSCLC. In cohorts A-C of KEYNOTE-021 (NCT02039674), we evaluated the efficacy and safety of pembro + various chemotherapy combinations in advanced NSCLC. Methods: Chemotherapy-naive, advanced, EGFR/ALK (-) NSCLC pts, PS 0 or 1, were randomly assigned to pembro 2 or 10 mg/kg Q3W plus either carboplatin AUC 6 + paclitaxel 200 mg/m2 (A, any histology), carboplatin AUC 6 + paclitaxel 200 mg/m2 + bevacizumab (BEV) 15 mg/kg (B, nonsquamous), or carboplatin AUC 5 + pemetrexed (PEM) 500 mg/m2(C, nonsquamous) for 4 cycles followed by maintenance pembro (A), pembro + BEV (B), or pembro + PEM (C). Response was assessed every 6 wk by central imaging vendor. Results: As of Dec 16, 2015, 74 pts (25 in A, 25 in B, and 24 in C) had been treated; median follow-up duration was 12 mo (A = 13; B = 9; C = 16). 1 DLT occurred in cycle 1 (gr 3 rash, C). Gr 3-4 treatment-related AEs occurred in 36%, 46%, and 42% of pts, in cohorts A, B, and C, respectively, most commonly AST elevation (n = 3 in C), anemia (n = 2 each in A and C), neutropenia (n = 2 each in A and B), and febrile neutropenia (n = 2 each in A and B). 1 treatment-related death occurred (B, pericardial effusion). Efficacy is shown by cohort and by PD-L1 status and pembro dose with cohorts combined. At data cutoff, 24 pts remained on treatment. Conclusions: Pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in treatment-naive advanced NSCLC. Longitudinal follow-up is ongoing. A randomized phase 3 study evaluating pemetrexed/platinum +/- pembro is currently recruiting. Clinical trial information: NCT02039674. N ORR (confirmed) Survival, median (95% CI), mo n (%) 95% CI PFS OS Total 74 42 (57) 45-68 10 (6-NR) NR (17-NR) Cohort A 25 13 (52) 31-72 10 (4-NR) NR (11-NR) Cohort B 25 12 (48) 28-69 NR (4.1-NR) NR (NR-NR) Cohort C 24 17 (71) 49-87 10 (6-15) NR (14-NR) PD-L1 25 15 (60) 39-79 15 (6-15) 17 (15-NR) TPS ≥50% TPS ≥1%-49% 26 14 (54) 33-73 14 (6-NR) NR (14-NR) TPS <1% 22 12 (55) 32-76 6 (4-NR) 11 (7-NR) Pembro dose 2 mg/kg 37 23 (62) 45-78 NR (6-NR) NR (15-NR) 10 mg/kg 37 19 (51) 34-68 7 (4-10) NR (10-NR) NR = not reached; TPS = tumor proportion score.
Effect of Intensive Therapy on the Microvascular Complications of Type 1 Diabetes Mellitus
Authors: None The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
Journal: JAMA (2002)

The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial, and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus. The DCCT proved that intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by 35% to 90% compared with conventional treatment. The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin (HbA1c) level over the follow-up period preceding each event. Intensive treatment was most effective when begun early, before complications were detectable. These risk reductions, achieved at a median HbA1c level difference of 9.1% for conventional treatment vs 7.3% for intensive treatment have been maintained through 7 years of EDIC, even though the difference in mean HbA1c levels of the 2 former randomized treatment groups was only 0.4% at 1 year (P&lt;.001) (8.3% in the former conventional treatment group vs 7.9% in the former intensive treatment group), continued to narrow, and became statistically nonsignificant by 5 years (8.1% vs 8.2%, P = .09). The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group. Thus, the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation. Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter, aiming for a practicable target HbA1c level of 7.0% or less.
Development and validation of the Frontal Fibrosing Alopecia Severity Score
Authors: David Saceda-Corralo, Óscar Muñoz Moreno-Arrones, Pablo Fonda-Pascual, Cristina Pindado-Ortega, Diego Buendía-Castaño, Adrián Alegre-Sánchez, Gonzalo Segurado-Miravalles, Ana Rita Rodrigues-Barata, Pedro Jaén-Olasolo, Sergio Vaño-Galván
Journal: Journal of the American Academy of Dermatology (2017)
John Martin Ellison
Authors: Andrew Ellison
Journal: BMJ (2017)

John Martin Ellison was born in Leeds. Like most of his family, his parents were doctors. He was educated at Repton School and the University of Leeds Medical School. He qualified as a physician and surgeon in 1964, specialising in obstetrics and gynaecology. In 1965 he met Anne (nee Eastwood), a nurse and midwife, at Hillingdon Hospital, London. They married on 23 April 1966 and had two sons, Andrew John (in 1967), and David Martin (in 1969).

After practising medicine in various communities throughout England for six years, Martin brought his family to …
Effect of Sex on Reverse Remodeling in Chronic Systolic Heart Failure
Authors: Alberto Aimo, Giuseppe Vergaro, Vincenzo Castiglione, Andrea Barison, Emilio Pasanisi, Christina Petersen, Vladyslav Chubuchny, Alberto Giannoni, Roberta Poletti, Silvia Maffei, James L. Januzzi, Claudio Passino, Michele Emdin
Journal: JACC Heart Failure (2017)
Hepatitis C virus testing for case identification in persons born during 1945‐1965: Results from three randomized controlled trials
Authors: Anthony K. Yartel, David B. Rein, Kimberly Ann Brown, Katherine Krauskopf, Omar I. Massoud, Cynthia Jordan, Natalie Kil, Alex D. Federman, David R. Nerenz, Joanne E. Brady, Danielle L. Kruger, Bryce D. Smith
Journal: Hepatology (2017)

The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born during 1945-1965 (birth cohort). However, few studies estimate the effect of birth cohort (BC) testing implementation on HCV diagnoses in primary care settings. We aimed to determine the probability of identifying HCV infections in primary care using targeted BC testing compared with usual care at three academic medical centers. From December 2012 to March 2014, each center compared one of three distinct interventions with usual care using an independently designed randomized controlled trial. Across centers, BC patients with no clinical documentation of previous HCV testing or diagnosis were randomly assigned to receive a one-time offering of HCV antibody (anti-HCV) testing via one of three independent implementation strategies (repeated-mailing outreach, electronic medical record-integrated provider best practice alert [BPA], and direct patient solicitation) or assigned to receive usual care. We estimated model-adjusted risk ratios (aRR) of anti-HCV-positive (anti-HCV+) identification using BC testing versus usual care. In the repeated mailing trial, 8992 patients (intervention, n = 2993; control, n = 5999) were included in the analysis. The intervention was eight times as likely to identify anti-HCV+ patients compared with controls (aRR, 8.0; 95% confidence interval [CI], 2.8-23.0; adjusted probabilities: intervention, 0.27%; control, 0.03%). In the BPA trial, data from 14,475 patients (BC, n = 8928; control, n = 5,547) were analyzed. The intervention was 2.6 times as likely to identify anti-HCV+ patients versus controls (aRR, 2.6; 95% CI, 1.1-6.4; adjusted probabilities: intervention, 0.29%; control, 0.11%). In the patient-solicitation trial, 8873 patients (BC, n = 4307; control, n = 4566) were analyzed. The intervention was five times as likely to identify anti-HCV+ patients compared with controls (aRR, 5.3; 95% CI, 2.3-12.3; adjusted probabilities: intervention, 0.68%; control, 0.11%). Conclusion: BC testing was effective in identifying previously undiagnosed HCV infections in primary care settings. (Hepatology 2018;67:524-533).
Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart
Authors: Cristina E Molina, Eric Jacquet, Prishila Ponien, Christian Muñoz-Guijosa, Istvan Baczkó, Lars S Maier, Patrick Donzeau-Gouge, Dobromir Dobrev, Rodolphe Fischmeister, Anne Garnier
Journal: Cardiovascular Research (2017)

Abstract Aims Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases. Methods and results We assessed the expression of 16 reference genes (ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A, PPIA, RPLP0, TBP, TFRC, UBC, YWHAZ, 18S) in tissues from: right and left ventricles from healthy controls and heart failure (HF) patients; right-atrial tissue from patients in sinus rhythm with (SRd) or without (SRnd) atrial dilatation, patients with paroxysmal (pAF) or chronic (cAF) atrial fibrillation or with HF; and left-atrial tissue from patients in SR or cAF. Consensual analysis (by geNorm and Normfinder algorithms, BestKeeper software tool and comparative delta-Ct method) of the variability scores obtained for each reference gene expression shows that the most stably expressed genes are: GAPDH, GUSB, IPO8, POLR2A, and YWHAZ when comparing either right and left ventricle or ventricle from healthy controls and HF patients; GAPDH, IPO8, POLR2A, PPIA, and RPLP0 when comparing either right and left atrium or right atria from all pathological groups. ACTB, TBP, TFRC, and 18S genes were identified as the least stable. Conclusions The overall most stable reference genes across different heart cavities and disease conditions were GAPDH, IPO8, POLR2A and PPIA. YWHAZ or GUSB could be added to this set for some specific experiments. This study should provide useful guidelines for reference gene selection in RT-qPCR studies in human heart.
David Oliver: Junior doctors’ working conditions are an urgent priority
Authors: David Oliver
Journal: BMJ (2017)

BerkshireA health service is nothing without its clinical workforce.The biggest existential threat to the NHS is a failure to retain existing clinicians or attract enough new ones.This damages morale, burns out those who stay, and compromises care quality. 1 For junior doctors, the workforce crisis is becoming critical.We must act now to tackle it or reap the consequences for years.The length of training means that there's no reserve of ready replacements.Juniors are a precious human resource that we shouldn't casually alienate or squander.Their intellect, skills, and UK training are eminently exportable-right out of the NHS.Fewer trainees today means fewer GPs or consultants tomorrow, and we are already failing to fill many consultant posts in key specialties.Junior doctors' intellect, skills, and UK training are eminently exportable-right out of the NHS Junior doctors suffer from being a transient workforce-often only in one hospital or even town for a year at a time-and their concerns all too easy to brush aside.We need to wake up and take those concerns more seriously.
Hereditary angioedema with normal C1 inhibitor: prevalence, clinical features and treatment of patients in a University Hospital in Brazil
Authors: D. Firinu, V. Bafunno, M.P. Barca, R. Meleddu, M. Pisanu, A. Matolo, P. Serra, P.E. Manconi, M. Margaglione, S.R. Del Giacco
Journal: Allergy (2015)
The independent association of overweight and obesity with breathlessness in adults: a cross-sectional, population-based study
Authors: David C. Currow, Eleonora Dal Grande, Calvin Sidhu, Magnus Ekström, Miriam J. Johnson
Journal: European Respiratory Journal (2017)

Obesity and overweight are significant health problems worldwide, with a rapidly rising prevalence [1]. Obesity and overweight have serious consequences, including higher rates of metabolic syndrome, diabetes, cardiovascular and cerebrovascular diseases, joint disorders and sleep problems. Obesity is an independent risk factor for chronic breathlessness and should be assessed in people with this symptom <http://ow.ly/W89K30e6NaL>
Addendum to “MicroRNA profiles in graft preservation solution are predictive of ischemic-type biliary lesions after liver transplantation” [J Hepatol 2013;59:1231–1238]
Authors: Cornelia J. Verhoeven, Jasmijn W. Selten, Henk P. Roest, Waqar R.R. Farid, Petra E. de Ruiter, Bettina E. Hansen, Jeroen de Jonge, Jaap Kwekkeboom, Herold J. Metselaar, Hugo W. Tilanus, Geert Kazemier, Jan N.M. IJzermans, Luc J.W. van der Laan
Journal: Journal of Hepatology (2017)
Abstract 18248: Development and Evaluation of a Novel Algorithm for Diagnosing Atrial Fibrillation Using Wristband Technology
Authors: Nino Isakadze, Oleksiy Levantsevych, Gari Clifford, Shamim Nemati, Amit Shah
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) increases the risk of ischemic stroke by 5-fold, yet is often asymptomatic and undiagnosed. Wristband technologies using photoplethysmography (PPG) for pulse ...
Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients
Authors: Antoni Bayés‐Genis, David E. Lanfear, Maurice W.J. de Ronde, Josep Lupón, Joost J. Leenders, Zhen Liu, Nicolaas P.A. Zuithoff, Marinus J.C. Eijkemans, Elisabet Zamora, Marta De Antonio, Aeilko H. Zwinderman, Sara‐Joan Pinto‐Sietsma, Yigal M. Pinto
Journal: European Journal of Heart Failure (2017)
Characteristics, treatments and 1‐year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long‐Term Registry
Authors: Marco Canepa, Ewa Straburzynska‐Migaj, Jaroslaw Drozdz, Carla Fernandez‐Vivancos, Jose Manuel Garcia Pinilla, Noemi Nyolczas, Pier Luigi Temporelli, Alexandre Mebazaa, Mitja Lainscak, Cécile Laroche, Aldo Pietro Maggioni, Massimo F. Piepoli, Andrew J.S. Coats, Roberto Ferrari, Luigi Tavazzi
Journal: European Journal of Heart Failure (2017)
Patient-reported outcomes from randomized, phase-3 study of trabectedin (T) vs. dacarbazine (D) in advanced leiomyosarcoma (LMS) or liposarcoma (LPS).
Authors: George D. Demetri, Margaret von Mehren, Robin Lewis Jones, Martee Leigh Hensley, Scott Schuetze, Anthony D. Elias, Renee F. Pierson, Roland Elmar Knoblauch, Youn C. Park, George C. Wang, Nushmia Z. Khokhar, Robert G Maki, Shreyaskumar Patel, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2016)

11061 Background: T is recently approved in the US for treatment of advanced LMS or LPS after prior chemotherapy failure based on results from a randomized, phase-3 study (Demetri et al, 2015, J Clin Oncol; 62.4734). Here we describe patient-reported outcomes from this pivotal study, performed at the time of final progression-free survival and overall response rate analyses (interim overall survival analysis). Methods: Patients (pts) completed the M. D. Anderson Symptom Inventory (MDASI), a 19-item questionnaire that measures symptom severity (SS), and whether symptoms interfere with daily function (Symptom Interference-SI). Pts rated their experience (on 0-10 point scales, where lower scores mean fewer symptoms and less interference) across 13 different symptom measures (SS), and 6 measures of physical and mental function (SI), before treatment on day 1 of each treatment cycle (Cy). Results: Among 495 (T = 340; D = 155) pts randomized and treated, 329 (96.8%) from T group and 150 (96.8%) from D group completed baseline MDASI; compliance at each treatment Cy was high (91.4-100% [T] vs. 92.6-100% [D]). 72 pts on T and 14 on D received at least 8 Cy, and 71 (98.6%) pts (T) and 14 (100%) pts (D) completed questionnaires at Cy 8. Baseline MDASI scores for all measured symptoms were low and comparable across T and D groups (median range: 0-2.0). Pts' experience with 3 core MDASI items (pain, fatigue, nausea) were representative of other SS measures with comparable mean baselines scores for both groups. Mean changes from baseline to Cy 8 in SS measures were not clinically meaningful for either group. Severe symptoms ( ≥ 7 on 0-10 scale) at baseline were reported most frequently in the pain (T: 15.9%, D:17.3%) and fatigue (T:13.4%, D: 16.7%) scores. The only statistically significant between-group difference was observed for nausea, and only at Cy 2 (9.4% [T] vs. 3.3% [D], p = 0.0396). Conclusions: Pts enrolled on this study had a relatively low baseline symptom burden. Symptom burden, assessed by MDASI, was generally not affected by drug treatment. Comparable side effects between treatment groups coupled with an improvement in efficacy supports T over D. Clinical trial information: NCT01343277.
The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years)
Authors: Hans Flaatten, Dylan W. De Lange, Alessandro Morandi, Finn H. Andersen, Antonio Artigas, Guido Bertolini, Ariane Boumendil, Maurizio Cecconi, Steffen Christensen, Loredana Faraldi, Jesper Fjølner, Christian Jung, Brian Marsh, Rui Moreno, Sandra Oeyen, Christina Agwald Öhman, Bernardo Bollen Pinto, Ivo W. Soliman, Wojciech Szczeklik, Andreas Valentin, Ximena Watson, Tilemachos Zaferidis, Bertrand Guidet
Journal: Intensive Care Medicine (2017)
The Peguero-Lo Presti Electrocardiographic Criteria Predict All-Cause Mortality in Patients With Aortic Stenosis
Authors: Jay Ramchand, Thalys Sampaio Rodrigues, Leighton G. Kearney, Sheila K. Patel, Piyush M. Srivastava, Louise M. Burrell
Journal: Journal of the American College of Cardiology (2017)
Sclerotherapy for Reticular Veins in the Lower Limbs
Authors: Matheus Bertanha, Rodrigo Gibin Jaldin, Regina Moura, Rafael Elias Farres Pimenta, Jamil Victor de Oliveira Mariúba, Carlos Eduardo Pinheiro Lúcio Filho, Giovana Piteri Alcantara, Carlos Roberto Padovani, Winston Bonetti Yoshida, Marcone Lima Sobreira
Journal: JAMA Dermatology (2017)

Reticular veins are subdermal veins located in the lower limbs and are mainly associated with aesthetic complaints. Although sclerotherapy is the treatment of choice for reticular veins in the lower limbs, no consensus has been reached regarding to the optimal sclerosant.To compare the efficacy and safety of 2 sclerosants used to treat reticular veins: 0.2% polidocanol diluted in 70% hypertonic glucose (HG) (group 1) vs 75% HG alone (group 2).Prospective, randomized, triple-blind, controlled, parallel-group clinical trial with patients randomly assigned in a 1:1 ratio between the 2 treatment groups from March through December 2014, with 2 months' follow-up. The study was conducted in a single academic medical center. Eligible participants were all women, aged 18 to 69 years, who had at least 1 reticular vein with a minimum length of 10 cm in 1 of their lower limbs.The patients underwent sclerotherapy in a single intervention with either 0.2% polidocanol plus 70% HG or 75% HG alone to eliminate reticular veins.The primary efficacy end point was the disappearance of the reticular veins within 60 days after treatment with sclerotherapy. The reticular veins were measured on images obtained before treatment and after treatment using ImageJ software. Safety outcomes were analyzed immediately after treatment and 7 days and 60 days after treatment and included serious adverse events (eg, deep vein thrombosis and systemic complications) and minor adverse events (eg, pigmentation, edema, telangiectatic matting, and hematomas).Ninety-three women completed the study, median (interquartile range) age 43.0 (24.0-61.0) years for group 1 and 41.0 (27.0-62.0) years for group 2. Sclerotherapy with 0.2% polidocanol plus 70% HG was significantly more effective than with 75% HG alone in eliminating reticular veins from the treated area (95.17% vs 85.40%; P < .001). No serious adverse events occurred in either group. Pigmentation was the most common minor adverse event, with a 3.53% treated-vein pigmentation length for group 1 and 7.09% for group 2, with no significant difference between the groups (P = .09).Sclerotherapy with 0.2% polidocanol diluted in 70% HG was superior to 75% HG alone in sclerosing reticular veins, with no statistical difference for complications. Pigmentation occurred in both groups, with no statistical difference between them. No serious adverse events occurred in either group.clinicaltrials.gov Identifier: NCT02054325.