tbuckley/cabot-search huggingface dataset:
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Authors: Shannon L. Maude, Theodore W. Laetsch, Jochen Buechner, Susana Rives, Michael Boyer, Henrique Bittencourt, Peter Bader, Michael R. Verneris, Heather E. Stefanski, Gary D. Myers, Muna Qayed, Barbara De Moerloose, Hidefumi Hiramatsu, Krysta Schlis, Kara L. Davis, Paul L. Martin, Eneida R. Nemecek, Gregory A. Yanik, Christina Peters, Andre Baruchel, Nicolas Boissel, Francoise Mechinaud, Adriana Balduzzi, Joerg Krueger, Carl H. June, Bruce L. Levine, Patricia Wood, Tetiana Taran, Mimi Leung, Karen T. Mueller, Yiyun Zhang, Kapildeb Sen, David Lebwohl, Michael A. Pulsipher, Stephan A. Grupp
Journal: New England Journal of Medicine (2018)

In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months.For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported.In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849 .).
Seroepidemiology of enterovirus D68 infection in infants and children in Jiangsu, China
Authors: Shi-Yang Sun, Fan Gao, Ya-Lin Hu, Lian-Lian Bian, Qun-Ying Mao, Xing Wu, Jing-Xin Li, Feng-Cai Zhu, Jian-Wei Wang, Zheng-Lun Liang
Journal: Journal of Infection (2018)
Defining the Scope and Improving the Quality of Clinical Research Ethics Consultation: Response to Open Peer Commentaries About the National Collaborative
Authors: Kathryn M. Porter, Marion Danis, Holly A. Taylor, Mildred K. Cho, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2018)

The Open Peer Commentaries on “The Emergence of Clinical Research Ethics Consultation: Insights from a National Collaborative201D highlight the many ways in which the practice of ethics consultation for clinical research can be further advanced. We respond here to a number of key considerations highlighted by commentators, including the role and scope of research ethics consultation (REC), relationships with other institutional services and programs, efforts to ensure the quality of consultations provided, and the feasibility of widespread REC services.
Predicting Visual Acuity by Using Machine Learning in Patients Treated for Neovascular Age-Related Macular Degeneration
Authors: Markus Rohm, Volker Tresp, Michael Müller, Christoph Kern, Ilja Manakov, Maximilian Weiss, Dawn A. Sim, Siegfried Priglinger, Pearse A. Keane, Karsten Kortuem
Journal: Ophthalmology (2018)
Association of the Affordable Care Act Medicaid Expansion With Access to and Quality of Care for Surgical Conditions
Authors: Andrew P. Loehrer, David C. Chang, John W. Scott, Matthew M. Hutter, Virendra I. Patel, Jeffrey E. Lee, Benjamin D. Sommers
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Lack of insurance coverage has been associated with delays in seeking care, more complicated diseases at the time of diagnosis, and decreased likelihood of receiving optimal surgical care. The Patient Protection and Affordable Care Act’s (ACA) Medicaid expansion has increased coverage among millions of low-income Americans, but its effect on care for common surgical conditions remains unknown. <h3>Objective</h3> To evaluate the association of the ACA’s Medicaid expansion with access to timely and recommended care for common and serious surgical conditions. <h3>Design, Setting, and Participants</h3> This quasi-experimental, difference-in-differences study used hospital administrative data to compare patient-level outcomes in expansion vs nonexpansion states before (2010-2013) vs after (2014-2015) expansion. A total of 293 529 patients aged 18 to 64 years with appendicitis, cholecystitis, diverticulitis, peripheral artery disease (PAD), or aortic aneurysm admitted to an academic medical center or affiliated hospital in 27 Medicaid expansion states and 15 nonexpansion states from January 1, 2010, through September 31, 2015, were included in the study. Data analysis was performed from November 1, 2016, to March 3, 2017. <h3>Exposures</h3> State adoption of Medicaid expansion. <h3>Main Outcomes and Measures</h3> Presentation with early uncomplicated disease (diverticulitis without abscess, fistula, or sepsis; nonruptured aortic aneurysm at time of repair; and PAD without ulcerations or gangrene) and receipt of optimal management (cholecystectomy for acute cholecystitis, laparoscopic approach for cholecystectomy or appendectomy, and limb salvage for PAD). <h3>Results</h3> Of the 293 529 study patients (128 392 [43.7%] female and 165 137 [56.3%] male), 225 572 had admissions in Medicaid expansion states and 67 957 had admissions in nonexpansion states. Medicaid expansion was associated with a 7.5–percentage point decreased probability of patients being uninsured (95% CI, −12.2 to −2.9;<i>P</i> = .002) and an 8.6–percentage point increased probability of having Medicaid (95% CI, 6.1-11.1;<i>P</i> &lt; .001). Medicaid expansion was associated with a 1.8–percentage point increase in the probability of early uncomplicated presentation (95% CI, 0.7-2.9;<i>P</i> = .001) and a 2.6–percentage point increase in the probability of receiving optimal management (95% CI, 0.8-4.4;<i>P</i> = .006). <h3>Conclusions and Relevance</h3> The ACA’s Medicaid expansion was associated with increased insurance coverage and improved receipt of timely care for 5 common surgical conditions. Health care systems and policymakers should be aware of the influence of insurance coverage expansion (or its repeal) on presentation with and management of surgical disease.
Guidelines do not discuss resistance to antibiotics among pneumococci
Authors: H P Lambert
Journal: BMJ (1996)

EDITOR,—The guidelines on preventing and treating infection in patients with an absent or dysfunctional spleen do not discuss the impact of current changes in patterns of resistance to antibiotics among pneumococci.1 The few and perfunctory phrases mentioning the problem are supported by a seven year old reference. Since then, resistance to penicillin and other antibiotics has steadily increased, with large variations among countries. The most recent figures for England and Wales (for 1994) from the Communicable …
Pazopanib (P) and bevacizumab (B) in patients with metastatic renal cell carcinoma (mRCC) or other advanced refractory tumors: Phase I combination study final analysis.
Authors: Sylvie Negrier, Diane Charlotte Imbs, David Pérol, Ratislav Bahleda, Antoine Hollebecque, Helen Jane Boyle, Celine Ferlay, Severine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard J. Escudier, Etienne Chatelut
Journal: Journal of Clinical Oncology (2013)

4574 Background: Since previous experiments of B with VEGFR tyrosine kinase inhibitors showed overlapping and limiting toxicities, a dose-finding study was designed to explore the safety and feasibility of the combination of a recent VEGFR inhibitor P with B in mRCC treatment-naive patients (pts) or in pts with other advanced refractory solid tumors. Methods: This double center trial was conducted with 3+3+3 escalation doses of P + B. The maximum tolerated dose (MTD) was the highest dosage not expected to cause a dose limiting toxicity (DLT) in more than 2/3, 3/6 or finally 3/9 pts, during the first 8 weeks of treatment. After preliminary DLT results, an approved by IDSMB extension cohort was enrolled and treated at MTD level.The effect of B on steady-state pharmacokinetic (PK) of P was also investigated by comparing PK at day 1 (D1) and D15 (day of B infusion). Results: 25 pts were enrolled with mRCC (n=7) or other advanced refractory solid tumors (n=18). Median age is 62 (41-79), 14 pts are male. At DL2 (n=10) 3 nephrectomized and 2 non-nephrectomized pts experienced DLT, as presented in the Table. In the 6-non-nephrectomized-pt extension cohort at DL1, 3 additional DLT were observed. Mean P AUC at D1 was higher than previously described in phase I P monotherapy (Clin Cancer Res 2009;15:4220). Mean P AUC at steady-state (D15) at both P dose levels was also significantly higher, though without being influenced by B infusion. Conclusions: The MTD of the P + B combination is respectively 400 mg/d and 7.5mg/kg (DL1) in all patients. Final PK analysis showed that there is no influence of B on P PK and that P AUC is higher than previously reported. Clinical trial information: NCT01202032. [Table: see text]
Priming Human Hematopoietic Stem and Progenitor Cells for Cas9/Sgrna and rAAV6-Mediated Homologous Recombination
Authors: Joab Camarena, Carsten T Charlesworth, Michael Kyle Cromer, Sriram Vaidyanathan, Rasmus O Bak, Jason Carte, Jason Potter, Daniel P. Dever, Matthew Porteus
Journal: Blood (2017)
Time May Be of the Essence in the Treatment of Pediatric Patients With Refractory Convulsive Status Epilepticus
Authors: Anup D. Patel
Journal: JAMA Neurology (2018)

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Somatic Mutations and Clonal Hematopoiesis
Authors: José J. Fuster, Kenneth Walsh
Journal: Circulation Research (2018)

Increasing evidence shows that conventional cardiovascular risk factors are incompletely predictive of cardiovascular disease, particularly in elderly individuals, suggesting that there may still be unidentified causal risk factors. Although the accumulation of somatic DNA mutations is a hallmark of aging, its relevance in cardiovascular disease or other age-related conditions has been, with the exception of cancer, largely unexplored. Here, we review recent clinical and preclinical studies that have identified acquired mutations in hematopoietic stem cells and subsequent clonal hematopoiesis as a new cardiovascular risk factor and a potential major driver of atherosclerosis. Understanding the mechanisms underlying the connection between somatic mutation-driven clonal hematopoiesis and cardiovascular disease will be highly relevant in the context of personalized medicine, as it may provide key information for the design of diagnostic, preventive, or therapeutic strategies tailored to the effects of specific somatic mutations.
Outcome of acute staphylococcal prosthetic joint infection treated with debridement, implant retention and antimicrobial treatment with short duration of rifampicin
Authors: Henk Scheper, Daphne van Hooven, Michiel van de Sande, Robert van der Wal, Martha van der Beek, Leo Visser, Mark de Boer, Rob Nelissen
Journal: Journal of Infection (2018)
CD4/CD8 T-Cell Selection Enhances CD22 CAR-T Cell Transduction and in-Vivo CAR-T Expansion: Updated Results on Phase I Anti-CD22 CAR Dose Expansion Cohort
Authors: Nirali N Shah, Steven L Highfill, Haneen Shalabi, Bonnie Yates, Eli Kane, Vicki Fellowes, Cynthia Delbrook, Jiaqiang Ren, Jianjian Jin, David Stroncek, Terry J. Fry
Journal: Blood (2017)
Abstract 13606: Platelet Activation is Less Enhanced in the New Balloon Expandable Edwards Sapien 3 Valve Compared to Its Predecessor Model (Edwards Sapien XT)
Authors: Suzanne Fateh-Moghadam, Sabrina Voesch, Tobias Geisler, Meinrad Gawaz, Wolfgang Bocksch
Journal: Circulation (2015)

Aim of the study: Stroke and thromboembolic events after transfemoral aortic valve replacement (TAVR) continue to be a problem. The aim of our study was to compare platelet aggregation (Agg) and platelet activation (PA) observed with two different catheter valves, the ESV-XT and the newer ESV-3 valve in patients (pts) undergoing TAVR on dual antiplatelet therapy (DAPT). Methods and results: 174 pts with severe aortic stenosis and high surgical risk underwent successfully TAVR (60 ESV-XT; 114 ESV-3). Platelet Agg and PA (CD62P expression) were evaluated before and for the following 3 days after TAVR under DAPT. Platelet Agg was inhibited to the same extent in both valve types and there was no significant difference in platelet drop between both valve types between day 0 and day 3 [ESV-XT versus ESV-3: median (25th-75th percentile): platelet count (x 1000 ): 55 (42-74) versus 61(42-93), p=0.280]. However there was an enhanced CD62P expression directly after TAVR with the ESV-XT compared to the ESV-3 [CD62P (MIF): 7.4 (6.8-8.6) versus 6.6 (6-7.9), p=0.014 ]. Surface expression of platelet CD62P was associated with the occurrence of residual aortic regurgitation (AR) and was significantly higher in pts with residual AR [ CD62P (Mild AR) versus CD 62 P (no or trace AR): 7.9 (7.3-9.1) versus 7.1 (6.4 -8.0), p &lt; 0.001)]. Conclusion: Although platelet inhibition was similar in both valve types, platelet activation was significantly enhanced in pts with the ESV-XT compared to the ESV-3 valve and was associated to the amount of residual AR which was significantly reduced by ESV-3, which may have implications for thromboischemic events following TAVR procedure.
Brief Report: The Genetic Profile of Rheumatoid Factor–Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis
Authors: Anne Hinks, Miranda C. Marion, Joanna Cobb, Mary E. Comeau, Marc Sudman, Hannah C. Ainsworth, John Bowes, Mara L. Becker, John F. Bohnsack, Johannes‐Peter Haas, Daniel J. Lovell, Elizabeth D. Mellins, J. Lee Nelson, Ellen Nordal, Marilynn Punaro, Ann M. Reed, Carlos D. Rose, Alan M. Rosenberg, Marite Rygg, Samantha L. Smith, Anne M. Stevens, Vibeke Videm, Carol A. Wallace, Lucy R. Wedderburn, Annie Yarwood, Rae S. M. Yeung, Carl D. Langefeld, Susan D. Thompson, Wendy Thomson, Sampath Prahalad
Journal: Arthritis & Rheumatology (2018)

Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies.Patients with RF-positive polyarticular JIA (n = 340) and controls (n = 14,412) were genotyped using the Immunochip array. Single-nucleotide polymorphisms were tested for association using a logistic regression model adjusting for admixture proportions. We calculated weighted genetic risk scores (wGRS) of reported RA and JIA risk loci, and we compared the ability of these wGRS to predict RF-positive polyarticular JIA.As expected, the HLA region was strongly associated with RF-positive polyarticular JIA (P = 5.51 × 10-31 ). Nineteen of 44 RA risk loci and 6 of 27 oligoarticular/RF-negative polyarticular JIA risk loci were associated with RF-positive polyarticular JIA (P < 0.05). The RA wGRS predicted RF-positive polyarticular JIA (area under the curve [AUC] 0.71) better than did the oligoarticular/RF-negative polyarticular JIA wGRS (AUC 0.59). The genetic profile of patients with RF-positive polyarticular JIA was more similar to that of RA patients with age at onset 16-29 years than to that of RA patients with age at onset ≥70 years.RF-positive polyarticular JIA is genetically more similar to adult RA than to the most common JIA categories and thus appears to be a childhood-onset presentation of autoantibody-positive RA. These findings suggest common disease mechanisms, which could lead to novel therapeutic targets and shared treatment strategies.
Concordance between Bone Marrow and Peripheral Blood Samples for Assessment of FLT3 Internal Tandem Duplication (ITD) Mutations: Data from Patients Screened for Participation in Quantum-R, a Global, Randomized, Open-Label, Phase 3 Study Examining the Effect of Quizartinib Monotherapy Vs Salvage Chemotherapy on Overall Survival in Patients with FLT3 - ITD - Mutated AML Who Are Refractory to or Have Relapsed after First-Line Therapy
Authors: Samer Khaled, Siddhartha Ganguly, Alexander E. Perl, Ken Kobayashi, Flora Berisha, Wei Ding, Jelveh Lameh, Giovanni Martinelli
Journal: Blood (2017)
Variability in the prescribing of intravenous fluids: A cross sectional multicentre analysis of clinical practice
Authors: G. Ramsay, A. Baggaley, P.G. Vaughan Shaw, E. Soltanmohammadi, N. Ventham, Ng Guat Shi, R. Pearson, S.R. Knight, C.T. Forde, N. Moore, J. Kilkenny, K.D. Clement, M. Kumar
Journal: International Journal of Surgery (2018)
Phase II trial of XL184 (cabozantinib) plus erlotinib in patients (pts) with advanced EGFR-mutant non-small cell lung cancer (NSCLC) with progressive disease (PD) on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy: A California Cancer Consortium phase II trial (NCI 9303).
Authors: Karen L. Reckamp, Paul Henry Frankel, Philip C Mack, Barbara Jennifer Gitlitz, Nora Ruel, Primo Lara, Tianhong Li, Marianna Koczywas, Shirish M. Gadgeel, Mihaela C. Cristea, Chandra Prakash Belani, Edward M. Newman, David R. Gandara
Journal: Journal of Clinical Oncology (2014)

8014 Background: MET and VEGF are important in mediating NSCLC tumorigenesis and EGFR TKI resistance. We hypothesized that treatment with the dual MET-VEGF inhibitor cabozantinib plus erlotinib in EGFR mutation-positive NSCLC following PD on EGFR TKI therapy may allow for tumors to overcome this resistance or restore sensitivity to therapy. Methods: Eligible pts were required to have known EGFR mutation and PD on an EGFR TKI immediately prior to enrollment without intervening therapy. Pts received erlotinib 150 mg daily + cabozantinib 40 mg daily on a 28 day cycle. This was a single-arm study to distinguish between a promising response rate of 20% and a discouraging response rate of 5% (requiring at least 4/37 responders). There was a pre-planned analysis of the percent of patients with at least a 30% increase in the tumor doubling time (DT), reflecting a reduction in the tumor growth rate with the addition of cabozantinib using each patient’s tumor growth rate during prior TKI treatment as their own control. Secondary endpoints include the evaluation of specific EGFR mutations and MET amplification in pre-treatment tissue. Results: 37 patients were registered between 5/2013 and 1/2014 in 4 centers; 35 have been treated. Median age was 63 years, 63% female and 51% ECOG PS 0. 4 pts had a PR (2 confirmed, 2 unconfirmed), with 13 patients remaining on treatment. In addition, 20/23 demonstrated significant growth rate reduction corresponding to a greater than 30% increase in DT. Diarrhea (10/35, 29%) was the most common grade 3 AE; 2 patients (6%) had a grade 3 maculopapular rash. Grade 4 AE’s include vomiting (1), elevated lipase (2), elevated amylase (1). Ongoing correlative studies are to determine correlation of response with MET amplification and T790M mutation. Conclusions: Combination erlotinib and cabozantinib demonstrates anti-tumor activity in pts with EGFR mutation and PD on EGFR TKI. Supported by NCI N01CM2011-00038 and U01CA062505. Clinical trial information: NCT01866410.
Evaluation of the MD Anderson Tumor Score and Their Tumor Related Prognostic Variables in the Rituximab Era
Authors: Antonio Gutierrez, Leyre Bento, Carlos Montalban, Antonio Diaz-Lopez, Heidys Garrote, Julian Freue, Lourdes Lopez, Raquel Oña, Ana Maria Martin Moreno, Armando Lopez-Guillermo, Ivan Dlouhy, Jordina Rovira, Mario Rodriguez, Jose M. Sanchez, Monica Baile, Alejandro Martín, Silvana Novelli, Juan Manuel Sancho, Olga García, Antonio Salar, Mariana Bastos, Maria J. Rodriguez-Salazar, Ruben Fernandez, Juan F. Dominguez, Jose Antonio Queizan, Sonia González de Villambrosia, Raul Cordoba, Victor Abraira, Juan F. Garcia, Jose Rodriguez
Journal: Blood (2017)
Response to: ‘Smoking paradox in the development of psoriatic arthritis among patients with psoriasis’ by Lee and Song
Authors: Uyen-Sa D T Nguyen, Yuqing Zhang, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2018)

We thank Lee and Song1 for their interest in our extended report on the smoking paradox in the development of psoriatic arthritis among patients with psoriasis.2 Please note that the point of our paper was indeed to demonstrate how …
Ibrutinib: A Risk Factor for Invasive Fungal Infections?
Authors: Rosa Ruchlemer, Ronen Ben Ami, Maskit Bar-Meir, Jennifer R. Brown, Marion Malphettes, Rogier Mous, Sanne Tonino, Carole Soussain, Noelie Barzic, Julia A. Messina, Preetesh Jain, Regev Cohen, Brian T. Hill, Stephen Mulligan, Marcel Nijland, Yair Herishanu, Ohad Benjamini, Tamar Tadmor, Koh Okamoto, Benjamin Arthurs, Jacob M. Rowe, Tamar Lachish
Journal: Blood (2017)
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
Authors: Masatoshi Kudo, Richard S Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Fabio Piscaglia, Ari Baron, Joong-Won Park, Guohong Han, Jacek Jassem, Jean Frederic Blanc, Arndt Vogel, Dmitry Komov, T R Jeffry Evans, Carlos Lopez, Corina Dutcus, Matthew Guo, Kenichi Saito, Silvija Kraljevic, Toshiyuki Tamai, Min Ren, Ann-Lii Cheng
Journal: The Lancet (2018)