tbuckley/cabot-search huggingface dataset:
Bone marrow plasma cells 20% or greater discriminate presentation, response, and survival in AL amyloidosis
Authors: Eli Muchtar, Morie A. Gertz, Taxiarchis V. Kourelis, Surbhi Sidana, Ronald S. Go, Martha Q. Lacy, Francis K. Buadi, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Wilson Gonsalves, Rahma Warsame, Stephen Russell, John A. Lust, Yi Lin, Steven Zeldenrust, S. Vincent Rajkumar, Robert A. Kyle, Shaji K. Kumar, Angela Dispenzieri
Journal: Leukemia (2019)
Abstract 13: Adenosine Receptor Activation During Extracorporeal Cardiopulmonary Resuscitation Improves Survival After Cardiac Arrest in Swine
Authors: William Z Chancellor, Dustin Money, Jared P Beller, Matthew R Byler, Aimee Zhang, Jennifer R Charlton, Daniel E Levin, Nadia Lunardi, Zequan Yang, Victor Laubach, James Mehaffey, Irving Kron, Mark E Roeser
Journal: Circulation (2019)

Introduction: Despite advances in resuscitation protocols, including the addition of Extracorporeal Cardiopulmonary Resuscitation (ECPR), survival after cardiac arrest remains less than 40% and novel methods are needed to attenuate global injury and improve outcomes. ATL1223, an adenosine 2A receptor (A2AR) agonist has been shown to attenuate organ specific reperfusion injury by modulating the interaction of inflammatory cells. Hypothesis: A2AR activation during ECPR will improve survival and decrease the burden of injury in a large animal model of cardiac arrest. Methods: Adult swine underwent 20 minutes of circulatory arrest followed by defibrillation and 6 hours of ECPR. Animals were randomized to receive saline control (n=5) or the A2AR agonist Regadenoson (0.144 and 14.4mcg/kg/hr, n=5/group). Animals were subsequently weaned from ECPR and monitored for 24 hours. Clinical and biochemical endpoints were compared between groups. Results: The administration of Regadenoson increased survival after cardiac arrest compared to saline controls (10/10, 100% vs 2/5, 40%, p=0.02, Figure 1). Anesthetic administration (p=0.41), fluid resuscitation (p=0.54), and epinephrine required to maintain target arterial pressure (p=0.08) were similar for all subjects. Biochemical markers of organ damage, including creatinine (p=0.87), aspartate aminotransferase (p=0.89), and troponin I (p=0.38), were similar among groups (Figure 2). Conclusions: In a clinically relevant model of cardiac arrest treated with ECPR, selective A2AR agonism increased survival from 40% to 100% at 24 hours. These results suggest A2AR activation is a promising therapeutic target after cardiac arrest.
Re: 18F-Fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in Patients with Early Biochemical Recurrence After Prostatectomy: A Prospective, Single-centre, Single-arm, Comparative Imaging Trial
Authors: Samantha Koschel, Jada Kapoosr, James Buteau, Declan G. Murphy
Journal: European Urology (2019)
Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis
Authors: Victor Llorenç, Miguel Cordero-Coma, Ana Blanco-Esteban, Henar Heras-Mulero, María-José Losada-Castillo, Vega Jovani-Casano, Elia Valls-Pascual, Margarita Jodar-Marquez, Ángel García-Aparicio, Alejandro Fonollosa, Juan Jacobo González-Guijarro, Luís Rodriguez-Melian, Manuel Fernández-Prada, María Jerez-Fidalgo, Marisa Hernandez-Garfella, Cristina Esquinas, Maite Sainz-de-la-Maza, Alfredo Adán
Journal: Ophthalmology (2019)
A divergent transcriptional landscape underpins the development and functional branching of MAIT cells
Authors: H.-F. Koay, S. Su, D. Amann-Zalcenstein, S. R. Daley, I. Comerford, L. Miosge, C. E. Whyte, I. E. Konstantinov, Y. d’Udekem, T. Baldwin, P. F. Hickey, S. P. Berzins, J. Y. W. Mak, Y. Sontani, C. M. Roots, T. Sidwell, A. Kallies, Z. Chen, S. Nüssing, K. Kedzierska, L. K. Mackay, S. R. McColl, E. K. Deenick, D. P. Fairlie, J. McCluskey, C. C. Goodnow, M. E. Ritchie, G. T. Belz, S. H. Naik, D. G. Pellicci, D. I. Godfrey
Journal: Science Immunology (2019)

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.
Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non–Small-Cell Lung Cancer
Authors: Julien Mazieres, Dariusz Kowalski, Alexander Luft, David Vicente, Ali Tafreshi, Mahmut Gümüş, Konstantin Laktionov, Barbara Hermes, Irfan Cicin, Jerónimo Rodríguez-Cid, Jonathan Wilson, Terufumi Kato, Rodryg Ramlau, Silvia Novello, Sreekanth Reddy, Hans-Georg Kopp, Bilal Piperdi, Xiaodong Li, Thomas Burke, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2019)

In the phase 3 KEYNOTE-407 study, the addition of pembrolizumab to carboplatin-paclitaxel/nab-paclitaxel significantly improved overall survival, progression-free survival, and objective response rate in patients with previously untreated metastatic squamous non-small-cell lung cancer (NSCLC), with little impact on severe toxicity. We present patient-reported outcomes (PROs) from KEYNOTE-407.Patients were randomly assigned to receive 4 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus carboplatin plus paclitaxel or nab-paclitaxel, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life (HRQoL) was evaluated using the European Organisation for Research and Treatment of Cancer Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Lung Cancer Module 13 (QLQ-LC13). Key PRO endpoints were change from baseline to weeks 9 and 18 (during and after platinum therapy) in the QLQ-C30 global health status/quality of life (GHS/QoL) score and time to deterioration in the composite endpoint of cough, chest pain, or dyspnea from the QLQ-C30 and QLQ-LC13. Two-sided, nominal P values are provided.A total of 554 and 553 patients completed ≥ 1 QLQ-C30 or ≥ 1 QLQ-LC13 assessment, respectively. GHS/QoL score improved for the pembrolizumab-combination group (least squares [LS] mean [95% CI] change from baseline: week 9, 1.8 [-0.9 to 4.4]; week 18, 4.3 [1.7 to 6.9]) and deteriorated in the placebo-combination group (week 9, -1.8 [-4.4 to 0.7]; week 18, -0.57 [-3.3 to 2.2]). Between-group differences were improved for the pembrolizumab-combination group (difference in LS mean scores: week 9, 3.6 [95% CI, 0.3 to 6.9], nominal P = .0337; week 18, 4.9 [1.4 to 8.3], nominal P = .0060). Median time to deterioration in cough, chest pain, or dyspnea was not reached in either group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06]; nominal P = .125).Addition of pembrolizumab to chemotherapy maintained or improved HRQoL measurements relative to baseline and improved HRQoL versus chemotherapy alone at weeks 9 and 18. These results support use of pembrolizumab plus chemotherapy as first-line therapy for metastatic squamous NSCLC.
Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma
Authors: Bruno Paiva, Noemi Puig, Maria-Teresa Cedena, Laura Rosiñol, Lourdes Cordón, María-Belén Vidriales, Leire Burgos, Juan Flores-Montero, Luzalba Sanoja-Flores, Lucia Lopez-Anglada, Roberto Maldonado, Javier de la Cruz, Norma C. Gutierrez, Maria-Jose Calasanz, Maria-Luisa Martin-Ramos, Ramón Garcia-Sanz, Joaquin Martinez-Lopez, Albert Oriol, María-Jesús Blanchard, Rafael Rios, Jesus Martin, Rafael Martinez-Martinez, Anna Sureda, Miguel-Teodoro Hernandez, Javier de la Rubia, Isabel Krsnik, Jose-Maria Moraleda, Luis Palomera, Joan Bargay, Jacques J.M. Van Dongen, Alberto Orfao, Maria-Victoria Mateos, Joan Blade, Jesús F. San-Miguel, Juan-José Lahuerta
Journal: Journal of Clinical Oncology (2019)

Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG).In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial.Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%.The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.
<i>Aspergillus</i> Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis
Authors: Oded Breuer, Andre Schultz, Luke W. Garratt, Lidija Turkovic, Tim Rosenow, Conor P. Murray, Yuliya V. Karpievitch, Lauren Akesson, Samuel Dalton, Peter D. Sly, Sarath Ranganathan, Stephen M. Stick, Daan Caudri
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Recent data show that Aspergillus species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown.Objectives: We aimed to evaluate longitudinal associations between Aspergillus infections and lung disease in young children with CF.Methods: Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000 and 2018 who underwent annual chest computed tomography (CT) imaging and BAL were used to determine the association between Aspergillus infections and the progression of structural lung disease. Results were adjusted for the effects of other common infections, associated variables, and repeated visits. Secondary outcomes included inflammatory markers in BAL, respiratory symptoms, and admissions for exacerbations.Measurements and Main Results:Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus infections were all associated with worse CT scores in the same year (Poverall < 0.05). Only P. aeruginosa and Aspergillus were associated with progression in CT scores in the year after an infection and worse CT scores at the end of the observation period. P. aeruginosa was most significantly associated with development of bronchiectasis (difference, 0.9; 95% confidence interval, 0.3-1.6; P = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 1.0-5.4; P = 0.004). Aspergillus infections were also associated with markers of neutrophilic inflammation (P < 0.001) and respiratory admissions risk (P = 0.008).Conclusions: Lower respiratory Aspergillus infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early Aspergillus species infections and the feasibility, risk, and benefit of eradication regimens.
Cost-Related Medication Nonadherence in Adults With Atherosclerotic Cardiovascular Disease in the United States, 2013 to 2017
Authors: Rohan Khera, Javier Valero-Elizondo, Sandeep R. Das, Salim S. Virani, Bita A. Kash, James A. de Lemos, Harlan M. Krumholz, Khurram Nasir
Journal: Circulation (2019)

Medication nonadherence is associated with worse outcomes in patients with atherosclerotic cardiovascular disease (ASCVD), a group who requires long-term therapy for secondary prevention. It is important to understand to what extent drug costs, which are potentially actionable factors, contribute to medication nonadherence.In a nationally representative survey of US adults in the National Health Interview Survey (2013-2017), we identified individuals ≥18 years with a reported history of ASCVD. Participants were considered to have experienced cost-related nonadherence (CRN) if in the preceding 12 months they reported skipping doses to save money, taking less medication to save money, or delaying filling a prescription to save money. We used survey analysis to obtain national estimates.Of the 14 279 surveyed individuals with ASCVD, a weighted 12.6% (or 2.2 million [95% CI, 2.1-2.4]) experienced CRN, including 8.6% or 1.5 million missing doses, 8.8% or 1.6 million taking lower than prescribed doses, and 10.5% or 1.9 million intentionally delaying a medication fill to save costs. Age <65 years, female sex, low family income, lack of health insurance, and high comorbidity burden were independently associated with CRN, with >1 in 5 reporting CRN in these subgroups. Survey respondents with CRN compared with those without CRN had 10.8-fold higher odds of requesting low-cost medications and 8.9-fold higher odds of using alternative, nonprescription, therapies.One in 8 patients with ASCVD reports nonadherence to medications because of cost. The removal of financial barriers to accessing medications, particularly among vulnerable patient groups, may help improve adherence to essential therapy to reduce ASCVD morbidity and mortality.
Mendelian randomisation analysis of red cell distribution width in pulmonary arterial hypertension
Authors: Anna Ulrich, John Wharton, Timothy E. Thayer, Emilia M. Swietlik, Tufik R. Assad, Ankit A. Desai, Stefan Gräf, Lars Harbaum, Marc Humbert, Nicholas W. Morrell, William C. Nichols, Florent Soubrier, Laura Southgate, David-Alexandre Trégouët, Richard C. Trembath, Evan L. Brittain, Martin R. Wilkins, Inga Prokopenko, Christopher J. Rhodes
Journal: European Respiratory Journal (2019)

Pulmonary arterial hypertension (PAH) is a rare disease that leads to premature death from right heart failure. It is strongly associated with elevated red cell distribution width (RDW), a correlate of several iron status biomarkers. High RDW values can signal early-stage iron deficiency or iron deficiency anaemia. This study investigated whether elevated RDW is causally associated with PAH. A two-sample Mendelian randomisation (MR) approach was applied to investigate whether genetic predisposition to higher levels of RDW increases the odds of developing PAH. Primary and secondary MR analyses were performed using all available genome-wide significant RDW variants (n=179) and five genome-wide significant RDW variants that act via systemic iron status, respectively. We confirmed the observed association between RDW and PAH (OR 1.90, 95% CI 1.80–2.01) in a multicentre case–control study (cases n=642, disease controls n=15 889). The primary MR analysis was adequately powered to detect a causal effect (odds ratio) between 1.25 and 1.52 or greater based on estimates reported in the RDW genome-wide association study or from our own data. There was no evidence for a causal association between RDW and PAH in either the primary (OR causal 1.07, 95% CI 0.92–1.24) or the secondary (OR causal 1.09, 95% CI 0.77–1.54) MR analysis. The results suggest that at least some of the observed association of RDW with PAH is secondary to disease progression. Results of iron therapeutic trials in PAH should be interpreted with caution, as any improvements observed may not be mechanistically linked to the development of PAH.
Characteristics of caregiving: A prospective, observational study of lung cancer patients and their informal caregivers.
Authors: Charlotte T. Lee, Clarelle L. Gonsalves, Jenny Gao-Kang, Brittney Jayne McKay, Wyatt G. Pickrell, Tara Sabzvari, Sandra Yalda, Ruth F. Barker
Journal: Journal of Clinical Oncology (2019)

18 Background: Cancer self-management involves active partnership between patients and their informal caregivers (ICs). There is a dearth of literature on ICs to lung cancer patients. Multi-modality treatment and profound challenges in symptom management and lifestyle adjustment are hallmarks of this population. This study aimed to describe the characteristics of, and resources utilized by ICs to lung cancer patients and examine the association between symptom severity and a) caregiver burden and b) perceived support. Methods: This study was conducted at a cancer centre north of Toronto, Canada. Dyads of lung cancer patients receiving outpatient treatment and their self-identified ICs (N = 39) were recruited. Upon consent, participants completed a one-time survey which assessed study variables employing previously validated instruments, including: patient’s functional status, caregiver burden, caregiver’s perceived social support and utilization of resources to enhance self-management. Descriptive analysis was used to describe our sample and frequency of resource utilization. Pearson’s correlation was used to examine the association between symptom severity and a) caregiver burden and b) perceived support. Results: The study sample consisted of middle-aged patients and caregivers (median 55-64 years). A majority of caregivers were female (76.2%), received education above college level (56.1%) and were immediate family members (80.9%). The most frequently utilized resources were the lung cancer patient handbook (48.8%), followed by personal support worker (29.3%). Caregiver support group was the least utilized (10%) resource. Patient’s symptom severity was negatively correlated with one aspect of caregiver burden, caregiver’s self-esteem (r = -0.36, p &lt; 0.05). Conclusions: Findings indicated similarities in caregiver demographics to carers of other patient populations. Informational support and material aid appeared to be the most important resources. Patients’ well-being had the greatest impact on caregivers’ self-esteem, indicating implications on person-centred care and collaborative patient-provider relationships to support patient self-management.
Ablation Therapy for Refractory Ventricular Arrhythmias
Authors: Pasquale Santangeli, Francis E. Marchlinski
Journal: Annual Review of Medicine (2019)

Recurrent ventricular arrhythmias (VAs) are a leading cause of cardiovascular morbidity and mortality. In the last three decades, important advancements have occurred in the understanding of the mechanisms of recurrent VAs, their prognostic implications in different clinical contexts, and their treatment options. VAs occur in structurally normal hearts as well as in patients with underlying heart disease, but the latter group has a particularly high risk of recurrent VAs. Catheter ablation offers the possibility of cure for a substantial proportion of patients. Research has focused on identifying optimal targets for ablation, correlating the underlying structural abnormalities with the site of origin of VAs, and determining the optimal procedural approach. Ablation therapy can be life-saving in select patients with high burden of repetitive VAs or advanced heart failure syndromes. This article focuses on clinical aspects of catheter ablation of VAs, particularly the selection and clinical management of patients undergoing catheter ablation procedures and expected outcomes.
Functional Interactions between Transcription Factors Involved in Myeloma Pathogenesis - Biological and Therapeutic Implications
Authors: Sondra L. Downey-Kopyscinski, Ricardo De Matos Simoes, Ryosuke Shirasaki, Huihui Tang, Brian Glassner, Olga Dashevsky, Minasri Borah, Megan Bariteau, Richard Groen, John G Doench, Constantine S. Mitsiades
Journal: Blood (2019)
Increased risk of HIV and other drug-related harms associated with injecting in public places among people who inject drugs in Scotland: a national bio-behavioural survey
Authors: Kirsten M A Trayner, Andrew McAuley, Norah E Palmateer, David J Goldberg, Samantha J Shepherd, Rory N Gunson, Emily J Tweed, Saket Priyadarshi, Catriona Milosevic, Sharon J Hutchinson
Journal: The Lancet (2019)
Cannabidiol Products Are Everywhere, but Should People Be Using Them?
Authors: Rita Rubin
Journal: JAMA (2019)

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The effect of radium-223 therapy in agent orange related veterans with metastatic castrate resistance prostate carcinoma (CRPC)
Authors: A.D. Liman, A.D. Liman, R. Shah, V.A. Passero, J.L. Tan, H. Rai, L. Harrold, A.K. Liman, J. Tokarsky
Journal: Annals of Oncology (2019)
Change in Prevalence of Disabilities and Accommodation Practices Among US Medical Schools, 2016 vs 2019
Authors: Lisa M. Meeks, Ben Case, Kurt Herzer, Melissa Plegue, Bonnielin K. Swenor
Journal: JAMA (2019)

This survey study assesses the prevalence of students with disabilities and types of accomodation provided at US allopathic medical schools in 2019, and compares the numbers with those of a 2016 survey to characterize 3-year changes.
Monitoring the health-related Sustainable Development Goals: lessons learned and recommendations for improved measurement
Authors: Samira Asma, Rafael Lozano, Somnath Chatterji, Soumya Swaminathan, Maria de Fátima Marinho, Naoko Yamamoto, Elena Varavikova, Awoke Misganaw, Michael Ryan, Lalit Dandona, Ren Minghui, Christopher J L Murray
Journal: The Lancet (2019)