tbuckley/cabot-search huggingface dataset:
Association of Hypertrophic Obstructive Cardiomyopathy With Outcomes Following Transcatheter Aortic Valve Replacement
Authors: Dhrubajyoti Bandyopadhyay, Sandipan Chakraborty, Birendra Amgai, Samir R. Kapadia, Eugene Braunwald, Srihari S. Naidu, Ankur Kalra
Journal: JAMA Network Open (2020)

Patients with HCM had greater incidence of in-hospital mortality (18
Increased risk of cognitive impairment in patients with diabetes is associated with metformin (vol 36, pg 2981, 2013)
Authors: EM Moore, AG Mander, D Ames, MA Kotowicz, RP Carne, H Brodaty, M Woodward, K Boundy, KA Ellis, A Bush, NG Faux, R Martins, C Szoeke, C Rowe, DA Watters
Journal: Diabetes Care (2013)
Weight loss pill praised as “holy grail” is withdrawn from US market over cancer link
Authors: Elisabeth Mahase
Journal: BMJ (2020)

A weight loss pill, which was heralded as the holy grail in the battle against obesity, is being withdrawn from the US market after a safety trial found that it was associated with an increased prevalence of cancer.1

The US Food and Drug Administration requested on 13 February that Eisai, the manufacturer of Belviq (lorcaserin), voluntarily withdraw the appetite suppressant from the market. The company has since submitted a request to do just that.

The move comes after the regulator told the public that it was reviewing a possible risk of cancer associated with lorcaserin, on the …
Predictive Biomarkers in NSCLC Patients Treated with Erlotinib after Chemotherapy: EGFR Expression or Mutations?
Authors: A. Inno, E. Maci, M. Martini, V. Arena, V.P. Di Noia, G. Schinzari, L.M. Larocca, A. Cassano, C. Pozzo, C. Barone
Journal: Annals of Oncology (2012)
A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis
Authors: Murielle Roussel, Giampaolo Merlini, Sylvie Chevret, Bertrand Arnulf, Anne Marie Stoppa, Aurore Perrot, Giovanni Palladini, Lionel Karlin, Bruno Royer, Antoine Huart, Margaret Macro, Pierre Morel, Laurent Frenzel, Cyrille Touzeau, Eileen Boyle, Véronique Dorvaux, Fabien Le Bras, David Lavergne, Frank Bridoux, Arnaud Jaccard
Journal: Blood (2020)
A Randomized Controlled Trial of Electronic Medication Monitoring (EMM), Patient Mobile App and Health Care Provider Feedback compared to EMM alone on Inhaled Corticosteroids (ICS) and Short Acting Beta2 Agonists (SABA) Utilization and Asthma Control in Adult Patients with Uncontrolled Asthma
Authors: Giselle Mosnaim, Candy Gonzalez, Brittney Adams, Linda Zhu, PRISCILLIA QUAN, Naomi BenIsrael Olive, Madeleine Shalowitz, Rahul Gondalia, Leanne Kaye, David Stempel
Journal: Journal of Allergy and Clinical Immunology (2020)
Avelumab as single agent for patients with metastatic or locally advanced urothelial cancer PD-L1+ unfit for cisplatin: The ARIES study.
Authors: Roberto Iacovelli, Sebastiano Buti, Consuelo Buttigliero, Rocco De Vivo, Claudia Caserta, Francesco Ferraú, Luca Galli, Valentino Martelli, Cristina Masini, Rodolfo Mattioli, Sara Merler, Laura Milesi, Emanuele Naglieri, Riccardo Ricotta, Mimma Rizzo, Cosimo Sacco, Daniele Santini, Rosa Tambaro, Elena Verri, Matteo Santoni
Journal: Journal of Clinical Oncology (2020)

TPS596 Background: Urothelial cancer (UC) is the ninth most common cancer worldwide, this tumour has a poor prognosis when in advanced stage. Cisplatin-based chemotherapy is considered the most effective treatment but more than 50% of patients are considered not eligible ( cis-unfit) for this regimen and have a median survival of only 6-9 months. In the past years, the most used chemotherapy regimen for cis-unfit patients was the combination of carboplatin and gemcitabine. Two single arm studies tested the anti-PD-L1/PD1 monoclonal antibodies atezolizumab and pembrolizumab and reported a response rate of 25% with good safety profile in an unselected population for PD-L1 expression. Recently, atezolizumab alone showed longer OS compared to carboplatin-gemcitabine regimen. Avelumab is another fully human anti-PD-L1 IgG1 antibody already tested in urothelial and in other cancers with a promising safety and efficacy profile. Methods: The single arm, phase II ARIES trial (NCT03891238), aims to evaluate the activity and efficacy of avelumab in patients with metastatic or locally advanced UC considered cis-unfit with PD-L1 expression ≥5%. Overall survival is the primary endpoint. Cis-unfit definition includes at least one of the following characteristics (i) ECOG-Performance status=2; (ii) creatinine clearance &lt;60 ml/min; (iii) grade ≥2 peripheral neuropathy or hearing loss; (iv) disease progression within six months after a previous adjuvant/neoadjuvant treatment with cisplatin-based therapy. Avelumab will be administered at standard dose of 10 mg/kg in 1-hour intravenous infusion every 2 weeks (Q2W). Sixty-seven patients will be enrolled, and supportive care is allowed during the study. Avelumab may be continued after radiological progression of disease at physician’s discretion if an improvement of symptoms or not new symptoms will be reported. The study is currently ongoing in twenty centres in Italy. Clinical trial information: NCT03891238.
Grass pollination in different cities of Argentina and Paraguay in 2018: a comparative study
Authors: German Ramon, Laura Barrionuevo, Maria Reyes, Solange Gaviot, Perla Alcaraz Duarte, Cinthia Perez Ortiz, Pedro Piraino, Rosmary Stanley De Ramos, Adrian Kahn
Journal: Journal of Allergy and Clinical Immunology (2020)
Efficacy of neoadjuvant chemotherapy followed by resection in primary and secondary muscle-invasive bladder cancer (MIBC).
Authors: Josiah An, Kevin Sanchez, Sarah L. Mott, Rohan Garje
Journal: Journal of Clinical Oncology (2020)

497 Background: Neoadjuvant chemotherapy followed by cystectomy in MIBC is associated with improved survival compared to cystectomy alone. Recent retrospective studies indicated that secondary MIBC (non-MIBC progressed to MIBC) had worse outcome with cisplatin based neoadjuvant chemotherapy when compared to primary MIBC. To further evaluate this observation, we queried our database to assess the differential response and determine if prior use of intravesical therapy diminishes the effect of cisplatin based neoadjuvant chemotherapy. Methods: A total of 387 patients diagnosed with T 2-4 or N 0-3 and M 0 from 2000-2018 and underwent cystectomy were retrospectively chart reviewed for demographics, treatment and outcomes at University of Iowa Holden Comprehensive Cancer Center. Cox regression models were utilized to assess differences in recurrence-free survival (RFS) and overall survival (OS). Time was calculated from cystectomy to recurrence or death due to any cause for RFS and OS, respectively. Results: Of the 387 patients, 324 patients had primary MIBC and 63 had secondary MIBC. Median follow up was 25.8 months. Intravesical therapy was administered to 98% (62/63) of secondary MIBC patients. Neoadjuvant chemotherapy was administered to 38% (122/324) of primary MIBC patients and 21% (13/63) of secondary MIBC patients. NAC had no difference in response rates (CR and PR) for primary vs secondary MIBC (p=0.73). Additionally, there was no difference between the primary and secondary MIBC with regards to RFS (p=0.54) and OS (p=0.12) on univariate analysis. The effect of neoadjuvant chemotherapy did not differ based on prior use of intravesical therapy in terms of RFS (p=0.61) or OS (p=0.40). Additionally, neoadjuvant chemotherapy irrespective of prior use of intravesical therapy was not associated with RFS (p=0.66) or OS (p=0.15). Conclusions: Prior intravesical therapy was not associated with differential efficacy of neoadjuvant chemotherapy in secondary MIBC when compared to primary MIBC.
Molecular underpinnings of RB status as a biomarker of poor outcome in advanced prostate cancer.
Authors: Amy C. Mandigo, Christopher McNair, Kexin Ku, Angel Pang, Yi Fang Guan, Jeff Holst, Myles Brown, William Kevin Kelly, Karen E. Knudsen
Journal: Journal of Clinical Oncology (2020)

189 Background: There is emergent and compelling evidence to support RB status as a biomarker in advanced prostate cancer. RB loss is strongly associated with poor progression-free, disease-specific, and overall survival in prostate cancer (PCa). Preclinical studies in PCa have revealed RB positive tumors are more responsive to CDK4/6 inhibitors. An ongoing randomized Phase IB/II study of enzalutamide with and without ribociclib in patients with metastatic castration-resistant, chemotherapy naïve PCa has become a pioneer trial to include a positive RB status as inclusion criteria in a PCa study (NCT02555189). Beyond CDK4/6 inhibitors, therapeutic agents that target tumor metabolism have been introduced in the clinic. Current data suggests that RB status may be crucial to understand and predict therapeutic response to these agents within tumors. Methods: The biological significance of RB loss was studied utilizing isogenic model systems and human tumor xenografts of castration resistant prostate cancer (CRPC) with and without RB deletion. The mechanism that drives aggressive tumor phenotypes was identified through comprehensive transcriptomic, cistromic, and metabolomic analysis. Novel functions of RB were identified and the response to clinically-relevant therapeutics was examined. Results: Exclusively in CRPC, RB loss results in significant rewiring of cancer cell metabolism. Functional investigation revealed a causative link between RB loss and antioxidant production sufficient to alter responsiveness to genomic insult and selected chemotherapeutics. Observed changes in response to therapeutic intervention were attributed to RB-dependent modulation of intracellular reactive oxygen species. Conclusions: RB loss is strongly associated with poor outcome in advanced PCa. Molecular investigation identified RB-dependent rewiring of cancer cell metabolism as a significant consequence of RB loss, sufficient to alter response in model systems to therapeutic strategies of clinical relevance. These studies significantly advance understanding of the means by which RB loss enhances lethal tumor phenotypes, and are of relevance for development of RB status as a clinically actionable biomarker.
Hyperbranched poly(β-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer
Authors: Xueqin Gao, Zhuang Jin, Xiangyu Tan, Chong Zhang, Chenming Zou, Wei Zhang, Jiahui Ding, Bhudev C. Das, Konstantin Severinov, Inga Isabel Hitzeroth, Priya Ranjan Debata, Dan He, Xin Ma, Xun Tian, Qinglei Gao, Jun Wu, Rui Tian, Zifeng Cui, Weiwen Fan, Zhaoyue Huang, Chen Cao, Yuxian Bao, Songwei Tan, Zheng Hu
Journal: Journal of Controlled Release (2020)
First ever real-world safety analysis of preschool peanut oral immunotherapy
Authors: Lianne Soller, Stuart Carr, Sandeep Kapur, Sara Leo, Gregory A. Rex, Per G. Lidman, Joanne Yeung, Timothy K. Vander Leek, Tiffany Wong, Mary McHenry, Kyla Hildebrand, Victoria E. Cook, Elissa M. Abrams, Nicole J. Lee, Scott B. Cameron, Edmond S. Chan
Journal: Journal of Allergy and Clinical Immunology (2019)
Effect of E-B-FAHF-2 and 7,4'-Dihydroxiflavone (DHF) on TNF-α and IL-8 Production, Inflammatory Markers of a non-IgE-mediated food hypersensitivity
Authors: Zixi Wang, Monica Kim, Yara Marghani, Linda Zambrano, Kamal Srivastava, Nan Yang, Xiuhua Yu, Johnathan Neshiwat, Michal Krenz, Yujuan Chen, Yanmei Shi, David Dunkin, Anna Nowak-Wegrzyn, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2020)
Outcomes of Transcatheter Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Disease
Authors: Sharif A. Halim, Fred H. Edwards, David Dai, Zhuokai Li, Michael J. Mack, David R. Holmes, E. Murat Tuzcu, Vinod H. Thourani, J. Kevin Harrison, J. Matthew Brennan
Journal: Circulation (2020)

Patients with bicuspid aortic valve (AV) stenosis were excluded from the pivotal evaluations of transcatheter AV replacement (TAVR) devices. We sought to evaluate the outcomes of TAVR in patients with bicuspid AV stenosis in comparison with those with tricuspid AV stenosis.We used data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (November 2011 through November 2018) to determine device success, procedural outcomes, post-TAVR valve performance, and in-hospital clinical outcomes (mortality, stroke, and major bleeding) according to valve morphology (bicuspid versus tricuspid). Results were stratified by older and current (Sapien 3 and Evolut R) generation valve prostheses. Medicare administrative claims were used to evaluate mortality and stroke to 1 year among eligible individuals (≥65 years).After exclusions, there were 170 959 eligible procedures at 593 sites during the specified interval. Of these, 5412 TAVR procedures (3.2%) were performed in patients with bicuspid AV, including 3705 with current-generation devices. In comparison with patients with tricuspid valves, patients with bicuspid AV were younger and had a lower Society of Thoracic Surgeons Predicted Risk of Operative Mortality score. When current-generation devices were used to treat patients with bicuspid AV, device success increased (93.5 versus 96.3; P=0.001) and the incidence of 2+ aortic insufficiency declined (14.0% versus 2.7%; P<0.001) in comparison with older-generation devices. With current-generation devices, device success was slightly lower in the bicuspid (versus tricuspid) AV group (96.3% in bicuspid versus 97.4% in tricuspid, P=0.07), with a slightly higher incidence of residual moderate or severe aortic insufficiency among patients with bicuspid AV (2.7% versus 2.1%; P<0.001). A lower 1-year adjusted risk of mortality (hazard ratio, 0.88 [95% CI, 0.78-0.99]) was observed for patients with bicuspid AV versus patients with tricuspid AV in the Medicare-linked cohort, whereas no difference was observed in the 1-year adjusted risk of stroke (hazard ratio, 1.14 [95% CI, 0.94-1.39]).Using current-generation devices, procedural, postprocedural, and 1-year outcomes were comparable following TAVR for bicuspid AV versus tricuspid AV disease. With newer-generation devices, TAVR is a viable treatment option for patients with bicuspid AV disease.
Randomized phase II study of docetaxel (D) + abiraterone acetate (AA) versus D after disease progression to first-line AA in metastatic castration-resistant prostate cancer (mCRPC): ABIDO-SOGUG Trial.
Authors: Miguel Angel Climent Duran, Albert Font, Ignacio Duran, Javier Puente, Daniel Castellano, M Isabel Sáez, Maria Jose José Mendez Vidal, Carmen Santander, Jose Angel Arranz Arija, Aranzazu Gonzalez del Alba, Alfredo Sanchez-Hernandez, Emilio Esteban, Teresa Alonso Gordoa, Pablo Maroto, Martín Emilio Lázaro Quintela, Javier Cassinello, Begona Perez Valderrama, María José Juan Fita, Begona Mellado
Journal: Journal of Clinical Oncology (2020)

95 Background: Abiraterone acetate (AA) improves OS and rPFS in first line mCRPC patients (pts). After AA progression D is commonly used as standard second line therapy. However, the value of maintaining AA in combination with D despite progression has not been tested beyond small exploratory studies (Tagawa ST, Eur Urol 2016) ABIDO is a randomized-phase II trial that evaluates efficacy and safety of D + AA vs D after first-line AA progression in mCRPC. Methods: Asymptomatic or minimally symptomatic mCRPC pts with no visceral metastases, ECOG PS 0-1, and adequate organ functions were included. The study has two stages: In stage I pts receive AA (1000 mg/d + prednisone (P) 10 mg qd) until radiological or unequivocal clinical progression. In stage II pts were randomized to D 75 mg/m2 q3wk in combination with AA 1000 mg/d (arm A) or without AA (arm B) The primary endpoint was rPFS and the secondary endpoints radiological response (RR), OS, PSA-response, PSA-PFS and safety. Results: 88 pts were randomized, (46 arm A, 42 Arm B). Median age was 69 y/o, 43% had ECOG 0 and 91%/11%/5% had bone, liver and lung metastases. Median rPFS was 11.4 months (m) in arm A vs 10.5 m in ARM B; 12-m rPFS was 43% vs 45%; Median PSA PFS was 6.2 vs 5.5 m and median OS was 17.3 vs 16.9 m. Twenty four pts (52%) in arm A and 19 (46%) in arm B achieve ≥50% PSA response. RR was achieved in 15% vs 7% of pts and disease control rate in 74% in both arms. No statistically significant differences were found in efficacy parameters. Half of pts received 10 cycles of D (median 7 and 8). D median dose intensity was 86% and 90% for each arm and 91% for AA. Eleven pts discontinued treatment due to non-hematological toxicity, 5 in arm A and 6 in arm B. Most frequent G3-4 toxicities per arm (A/B) were: neutropenia (57%/29%; P=0.027), febrile neutropenia (17%/10%), diarrhea (9%/7%), and asthenia (11%/10%). Conclusions: ABIDO trial was unable to demonstrate the significant clinical benefit of maintenance AA approach + D after AA first-line therapy. No differences were observed in RR, PSA PFS, rPFS and OS. In AA + D cohort, more frequent and severe hematological toxicity (neutropenia and febrile neutropenia) were reported. Clinical trial information: NCT02036060.
The role of 68Ga-DOTATATE for evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Mehmet Asim Bilen, Akinyemi A Akintayo, Olayinka A. Abiodun-Ojo, Omer Kucuk, Bradley Curtis Carthon, David M. Schuster, Ephraim E Parent
Journal: Journal of Clinical Oncology (2020)

217 Background: Neuroendocrine transformation (NE) of prostate cancer is difficult to diagnose and treat. 68 Ga-DOTATATE PET is useful to detect well-differentiated neuroendocrine tumors, but its application in prostate cancer is not well understood. We evaluated DOTATATE PET in patients with mCRPC and suspected or known NE. Methods: DOTATATE PET/CT were performed in 17 patients with mCRPC. Summed SUVmax of up to 5 bone and 5 soft tissue lesions in each patient were correlated with histologic presence of NE and response to standard of care treatment and clinical outcome (NCT03448458). Results: Mean age was 62.3±9.2 years. Median PSA was 39.0 ng/ml. 2/17 patients had biopsy proven NE. 1/17 was found to have squamous cell cancer and therefore excluded from analysis. 2 patients with NE had platinum-based chemotherapy. Of the 14 patients without NE, 7/14 received enzalutamide or abiraterone, and 7/14 received taxane based chemotherapy after DOTATATE PET. On PET, all patients had at least one lesion (median 7 [interquartile range 6-9]) with uptake. 11/16 patients had bone and visceral/nodal lesions, 4/16 had only bone lesions, and 1 had only nodal disease. Summed SUVmax was significantly higher in 2/16 patients with proven NE compared to the 14/16 non-NE patients (99.1± 16.5 ng/ml vs 48.4± 40.6 ng/ml; p=0.04). There was no correlation between summed SUVmax and PSA. Follow-up was available in 15/16 patients. SUVmax was higher in patients who did not respond to treatment, however, the trend was non-significant (69.5 ± 46.6 vs 39.3 ± 29.6; p=0.20). There was no significant association between survival and DOTATATE uptake. 6/16 patients had next generation sequencing. Of these, 1 patient without NE had BRCA2 mutation, and also had the highest summed uptake in this study. Conclusions: DOTATATE uptake is higher in mCRPC patients with NE or with BRCA mutation. Uptake was higher in patients who did not respond to standard of care treatment, though this was a nonsignificant trend, possibly due to small sample size. Larger studies are therefore recommended. Clinical trial information: NCT03448458.
Contemporary strategies to improve clinical trial design for critical care research: insights from the First Critical Care Clinical Trialists Workshop
Authors: Michael O. Harhay, Jonathan D. Casey, Marina Clement, Sean P. Collins, Étienne Gayat, Michelle Ng Gong, Samir Jaber, Pierre-François Laterre, John C. Marshall, Michael A. Matthay, Rhonda E. Monroe, Todd W. Rice, Eileen Rubin, Wesley H. Self, Alexandre Mebazaa
Journal: Intensive Care Medicine (2020)
Psychedelics and Psychedelic-Assisted Psychotherapy
Authors: Collin M. Reiff, Elon E. Richman, Charles B. Nemeroff, Linda L. Carpenter, Alik S. Widge, Carolyn I. Rodriguez, Ned H. Kalin, William M. McDonald
Journal: American Journal of Psychiatry (2020)

The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on "psilocybin," "lysergic acid diethylamide," "LSD," "ayahuasca," "3,4-methylenedioxymethamphetamine," and "MDMA," in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms "clinical trial," "therapy," or "imaging" in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care.The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as "breakthrough therapies" for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders.Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.