tbuckley/cabot-search huggingface dataset:
Quality of life of prostate cancer (PCa) patients aged 60 years and older: Changes in QLQ-ELD14 dimensions after a six-month gonadotropin-releasing hormone agonist (GnRHa) therapy, according to age groups–Primary analysis of PRISME study.
Authors: Francois Rozet, Christophe Hennequin, Pierre Mongiat-Artus, Nathalie Pello Leprince Ringuet, Anne-Sophie Grandoulier, Morgan Roupret
Journal: Journal of Clinical Oncology (2021)

55 Background: PCa mostly affects elderly men and impacts their health-related quality of life (HRQOL). Our purpose was to compare the evolution, between age groups, of HRQOL measured through EORTC QLQ-ELD14 instrument, specific to the elderly cancer patients, after a 6-month GnRHa therapy. Methods: Between March 2018 and February 2020, a prospective, multicenter, non-interventional study was conducted in France (PRISME, NCT03516110). Urologists, radiation oncologists and medical oncologists recruited patients aged 60 years and older, with PCa, initiating a GnRHa therapy. 1000 patients were planned to be included 1:2:1 in prespecified age groups ([60-70[, [70-75[, ≥ 75 years). They reported HRQOL using ELD14 (7 dimensions, each scored 0-100): “Maintaining purpose”, “Family support” (higher scores represent better functioning), “Mobility”, “Worries about others”, “Future worries”, “Burden of illness” and “Joint stiffness” (higher scores represent worse functioning). Analyses of covariance (ANCOVA) were performed to compare evolution of each of the 7 dimensions of ELD14 between subgroups of ages, adjusted on baseline scores. Level of significance was set to 0.002 because of the multiplicity testing on the 7 dimensions (Bonferroni). Results: After enrollment of 814 patients by 138 investigators, enrollment was stopped because of a slow recruitment in the [70-75[ group. The final analysis included 652 patients (full analysis set population). Mean (±SD) age was 72.5±6.2 years. There were 193, 269 and 190 patients, in the [60-70[, [70-75[ and ≥75y age groups, respectively. 71.6% had at least one comorbidity at baseline and 65.0% were receiving at least one concomitant systemic treatment. Main reasons for GnRHa initiation were high risk PCa in 65.3%, metastatic stage in 18.4%, biochemical recurrence in 13.3%. For each dimension, ANCOVA analyses showed that changes from baseline, adjusted on baseline values, were not significantly different between age groups. For example, least square (LS) means (SE) changes in “Mobility” scores from baseline were 3.01 (1.13), 3.14 (0.95) and 6.13 (1.15) in the [60-70[, [70-75[ and ≥75y age groups, indicating a worsening in all groups, but without significant differences between groups (Table). Conclusions: In this large observational cohort of PCa men with prespecified age groups, HRQOL changes after a 6-month GnRHa therapy didn’t depend on age group. Clinical trial information: NCT03516110. [Table: see text]
Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk
Authors: Martin B Leon, Michael J Mack, Rebecca T Hahn, Vinod H Thourani, Raj Makkar, Susheel K Kodali, Maria C Alu, Mahesh V Madhavan, Katherine H Chau, Mark Russo, Samir R Kapadia, S Chris Malaisrie, David J Cohen, Philipp Blanke, Jonathon A Leipsic, Mathew R Williams, James M McCabe, David L Brown, Vasilis Babaliaros, Scott Goldman, Howard C Herrmann, Wilson Y Szeto, Philippe Genereux, Ashish Pershad, Michael Lu, John G Webb, Craig R Smith, Philippe Pibarot
Journal: Journal of the American College of Cardiology (2021)
Factors influencing noncompletion of radiotherapy among men with localized prostate cancer.
Authors: Edward Christopher Dee, Vinayak Muralidhar, Melaku A Arega, Amar Upadhyaya Kishan, Daniel Eidelberg Spratt, Robert Timothy Dess, Martin T. King, Sybil Sha, Patricia Mae G Santos, Santino Butler, Nina Niu Sanford, Paul L. Nguyen, Brandon Arvin Virgil Mahal
Journal: Journal of Clinical Oncology (2021)

199 Background: Treatment non-completion may occur with radiotherapy (RT), especially with protracted treatment courses such as RT for prostate cancer, and may affect the efficacy of RT. For men with localized prostate cancer managed with primary RT, we evaluated associations between rates of treatment non-completion and RT fractionation schedules. Methods: The National Cancer Database identified men diagnosed from 2004-2014 treated with primary RT. Patients receiving 180cGy/fraction (conventional), 200cGy/fraction (conventional), 250cGy/fraction (moderate hypofractionation), and 300cGy/fraction (moderate hypofractionation) were defined as having completed radiotherapy if they received ≥40 fractions, ≥37 fractions, ≥28 fractions, and ≥19 fractions, respectively. Stereotactic body radiotherapy (SBRT) was defined as 5-8 fractions of 600-800cGy/fraction. Odds ratios compared rates of treatment noncompletion, adjusting for various sociodemographic covariates. Propensity-adjusted multivariable Cox regression assessed the association between treatment completion and overall survival. Results: Of 93,079 patients, 90.5% (N = 84,260) received conventional fractionation, 2.3% (N = 2,181) received moderate hypofractionation, and 7.1% (N = 6,638) received SBRT. Rates of non-completion were 10.0% (N = 8,406) among patients who received conventional fractionation, 7.5% (N = 163) among patients who received moderate hypofractionation, and 1.7% (N = 115) among patients who received SBRT (OR versus conventional: 0.214, 95%CI 0.177-0.258, P &lt; 0.001). The rate of non-completion among 15,417 African American patients was 11.8%, compared to 8.8% among 74,189 white patients (OR 1.39, 95%CI 1.31-1.47, P &lt; 0.001). On subgroup analysis, the disparity in non-completion persisted for conventional fractionation (12.4% vs. 9.4%, OR 1.36, 95%CI 1.29-1.44, P &lt; 0.001) and moderate hypofractionation (13.6% vs. 6.6%, OR 2.24, 95%CI 1.52-3.29, P &lt; 0.001), but not for SBRT (2.0% vs. 1.6%, OR 1.25, 95%CI 0.76-2.06, P = 0.384). Non-completion was associated with worse survival on propensity-adjusted multivariate analysis (HR 1.37, 95%CI 1.31-1.43, P &lt; 0.001). Conclusions: SBRT was associated with lower rates of RT non-completion among men with localized prostate cancer. African American race was associated with greater rates of treatment non-completion, although the disparity may be decreased among men receiving SBRT.
Decreased activity and stability of pyruvate kinase in sickle cell disease: a novel target for mitapivat therapy
Authors: Minke A. E. Rab, Jennifer Bos, Brigitte A. van Oirschot, Stephanie van Straaten, Penelope A. Kosinski, Victor Chubukov, Hyeryun Kim, Heidi Mangus, Roger E. G. Schutgens, Gerard Pasterkamp, Lenny Dang, Charles Kung, Eduard J. van Beers, Richard van Wijk
Journal: Blood (2021)
HHV-8 positive clinically advanced castrate-resistant prostate cancer (mCRPC): A potentially distinct molecular subset.
Authors: Petros Grivas, Gennady Bratslavsky, Joseph M Jacob, Andrea Necchi, Philippe E. Spiess, Natalie Danziger, Douglas I. Lin, Richard Huang, Douglas A Mata, Brennan James Decker, Ole Gjoerup, Ethan Sokol, Hanna Tukachinsky, Jeffrey Michael Venstrom, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2021)

163 Background: Herpesvirus HHV-8 has been detected in normal prostate tissue and has been linked to the acquisition of androgen-independent growth of prostate cancer cells in vitro, early development of anti-androgen therapy resistance, and more aggressive disease in a subset of patients with mCRPC. We used comprehensive genomic profiling (CGP) to test the hypothesis that HHV-8 associated mCRPC is a distinct molecular subset of mCRPC featuring altered AR signaling compared to HHV-8 negative mCRPC. Methods: Using a hybrid capture-based FDA-approved CGP assay, a series of 4,918 mCRPC were sequenced to evaluate all classes of genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). HHV-8 status was determined by CGP-based identification of unique viral reads. Results: Overall, 128 (2.6%) of the mCRPC cases harbored HHV-8 sequences (Table). The patient age distribution was similar in the HHV-8+ and HHV-8− groups. GAs in AR, predominantly amplifications, and RAD21 were slightly reduced in HHV-8+ mCRPC cases (P = .01 for both). The frequencies of GAs in genes associated with mCRPC including PTEN, BRCA2, ATM, CDK12, and the TMPRSS2: ERG fusion were similar in the two groups. HHV-8+ patients were less likely to be of European ancestry (P = 0.001). Putative biomarkers associated with immunotherapy response (MSI status, TMB, and PD-L1 expression) were also similar in the two groups. Conclusions: HHV-8+ mCRPC is a rare sub-type of mCRPC with lower frequency of AR GAs compared to HHV-8− mCRPC cases, suggesting a potential role of HHV-8 in inducing androgen-independent prostate cancer growth. Additional alterations associated with potentially enhanced PARP inhibitor response seen in HHV-8+ mCRPC (e.g., RAD21) suggest that early performance of CGP may inform precision treatment strategies to be tested in clinical trials. [Table: see text]
Rheumatology and COVID-19 at 1 year: facing the unknowns
Authors: Leonard Calabrese, Kevin L Winthrop
Journal: Annals of the Rheumatic Diseases (2021)

This issue of the Annals of the Rheumatic Diseases includes the freshly minted European Alliance of Associations for Rheumatology (EULAR) points to consider on the pathophysiology and use of immunomodulatory therapies in COVID-19.1 This publication adds to the formidable extant literature on COVID-19, which is of particular interest to rheumatology as the field has become an important stakeholder in the investigation of immune-based therapies targeting the inflammatory phase of SARS-CoV-2 infection. From the outset, we believe these authors recognised that their mission to provide real-time analysis in a timely and reflective manner was a Sisyphean task, as at the time of this writing, over 113 635 publications have been posted on PubMed and MedRxiv alone, largely in the past 12 months (search date 14 February 2021). To their credit, the systematic review process in the accompanying literature search2 even included a ‘hand search’ of the ever increasingly quoted ‘grey literature’ consisting of the torrent of press releases on new drugs and therapies. These types of sources in the COVID-19 field are of particular importance as they are often amplified by social media, creating what some may refer to as ‘epistemic chaos’, and posing an increasing threat to the iterative method of science (eg, the early embrace of hydroxychloroquine). Thus, these points to consider should be viewed as ephemeral and will need ongoing curation to maximise their value in the months ahead.

To poise ourselves to best meet this challenge, we thought it logical to not focus on what has already happened but rather to attempt to selectively gaze ahead and consider some key areas of interest to the field of rheumatology which will likely impact our profession and our patients.

We now have strong efficacy data reported for three different vaccine constructs: 90%–95% for mRNA vaccines from Pfizer3 …
Corrigendum to “van Bommel EJM, Muskiet MHA, van Baar MJB, et al. The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial.” Kidney Int. 2020;97:202–212
Journal: Kidney International (2020)
Safety and Efficacy of Virtual Prostatectomy With Single-Dose Radiotherapy in Patients With Intermediate-Risk Prostate Cancer
Authors: Carlo Greco, Oriol Pares, Nuno Pimentel, Vasco Louro, Inês Santiago, Sandra Vieira, Joep Stroom, Dalila Mateus, Ana Soares, João Marques, Elda Freitas, Graça Coelho, Manuela Seixas, Antonio Lopez-Beltran, Zvi Fuks
Journal: JAMA Oncology (2021)

Ultra-high single-dose radiotherapy (SDRT) represents a potential alternative to curative extreme hypofractionated stereotactic body radiotherapy (SBRT) in organ-confined prostate cancer.To compare toxic effect profiles, prostate-specific antigen (PSA) responses, and quality-of-life end points of SDRT vs extreme hypofractionated SBRT.The PROSINT single-institution phase 2 randomized clinical trial accrued, between September 2015 and January 2017, 30 participants with intermediate-risk prostate cancer to receive SDRT or extreme hypofractionated SBRT. Androgen deprivation therapy was not permitted. Data were analyzed from March to May 2020.Patients were randomized in a 1:1 ratio to receive 5 × 9 Gy SBRT (control arm) or 24 Gy SDRT (test arm).The primary end point was toxic effects; the secondary end points were PSA response, PSA relapse-free survival, and patient-reported quality of life measured with the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaires.A total of 30 men were randomized; median (interquartile range) age was 66.3 (61.2-69.9) and 73.6 (64.7-75.9) years for the SBRT and SDRT arms, respectively. Time to appearance and duration of acute and late toxic effects were similar in the 2 trial arms. Cumulative late actuarial urinary toxic effects did not differ for grade 1 (hazard ratio [HR], 0.41; 90% CI, 0.13-1.27) and grade 2 or greater (HR, 1.07; 90% CI, 0.21-5.57). Actuarial grade 1 late gastrointestinal (GI) toxic effects were comparable (HR, 0.37; 90% CI, 0.07-1.94) and there were no grade 2 or greater late GI toxic effects. Declines in PSA level to less than 0.5 ng/mL occurred by 36 months in both study arms. No PSA relapses occurred in favorable intermediate-risk disease, while in the unfavorable category, the actuarial 4-year PSA relapse-free survival values were 75.0% vs 64.0% (HR, 0.76; 90% CI, 0.17-3.31) for SBRT vs SDRT, respectively. The EPIC-26 median summary scores for the genitourinary and GI domains dropped transiently at 1 month and returned to pretreatment scores by 3 months in both arms. The IPSS-derived transient late urinary flare symptoms occurred at 9 to 18 months in 20% (90% CI, 3%-37%) of patients receiving SDRT.In this randomized clinical trial among patients with intermediate-risk prostate cancer, SDRT was safe and associated with low toxicity, and the tumor control and quality-of-life end points closely match the SBRT arm outcomes. Further studies are encouraged to explore indications for SDRT in the cure of prostate cancer.ClinicalTrials.gov Identifier: NCT02570919.
15P A pivotal multicenter translational research project on malignant pleural mesothelioma (MPM): Preliminary results
Authors: R. Di Liello, C.M. Della Corte, V. Ciaramella, A. Insa, D. Compañ-Quilis, G. Alonso, R. Borrás, G. Viscardi, N. Zanaletti, F. Sparano, I. Cozzolino, M. Montella, G. Vicidomini, I. Pastor-Escartín, M. Santini, R. Franco, F. Ciardiello, P. Martín-Martorell, F. Morgillo
Journal: Annals of Oncology (2021)
Single leg hop for distance symmetry masks lower limb biomechanics: time to discuss hop distance as decision criterion for return to sport after ACL reconstruction?
Authors: Argyro Kotsifaki, Rod Whiteley, Sam Van Rossom, Vasileios Korakakis, Roald Bahr, Vasileios Sideris, Philip Graham-Smith, Ilse Jonkers
Journal: British Journal of Sports Medicine (2021)

We evaluated the lower limb status of athletes after anterior cruciate ligament reconstruction (ACLR) during the propulsion and landing phases of a single leg hop for distance (SLHD) task after they had been cleared to return to sport. We wanted to evaluate the biomechanical components of the involved (operated) and uninvolved legs of athletes with ACLR and compare these legs with those of uninjured athletes (controls).We captured standard video-based three-dimensional motion and electromyography (EMG) in 26 athletes after ACLR and 23 healthy controls during SLHD and calculated lower limb and trunk kinematics. We calculated lower limb joint moments and work using inverse dynamics and computed lower limb muscle forces using an EMG-constrained musculoskeletal modelling approach. Between-limb (within ACLR athletes) and between-group differences (between ACLR athletes and controls) were evaluated using paired and independent sample t-tests, respectively.Significant differences in kinematics (effect sizes ranging from 0.42 to 1.56), moments (0.39 to 1.08), and joint work contribution (0.55 to 1.04) were seen between the involved and uninvolved legs, as well as between groups. Athletes after ACLR achieved a 97%±4% limb symmetry index in hop distance but the symmetry in work done by the knee during propulsion was only 69%. During landing, the involved knee absorbed less work than the uninvolved, while the uninvolved knee absorbed more work than the control group. Athletes after ACLR compensated for lower knee work with greater hip work contribution and by landing with more hip flexion, anterior pelvis tilt, and trunk flexion.Symmetry in performance on a SLHD test does not ensure symmetry in lower limb biomechanics. The distance hopped is a poor measure of knee function, and largely reflects hip and ankle function. Male athletes after ACLR selectively unload the involved limb but outperform controls on the uninvolved knee.
Abstract 19967: The Clinical Impact of In-hospital Heart Failure Exacerbation After Transfemoral Aortic Valve Implantation
Authors: Fumiaki Yashima, Masanori Yamamoto, Yusuke Watanabe, Toru Naganuma, Shinichi Shirai, Motoharu Araki, Norio Tada, Futoshi Yamanaka, Hideyuki Shimizu, Keiichi Fukuda, Kentaro Hayashida
Journal: Circulation (2017)

Introduction: Some patients with aortic stenosis (AS) who are treated using transcatheter aortic valve implantation (TAVI) procedures present in-hospital heart failure (HF) exacerbation after TAVI....
Abstract 9351: Are “All-Comer” Clinical Trials Representative of Contemporary Clinical Practice: A Linked Analysis of the Dual Antiplatelet Therapy (DAPT) Study and the National Cardiovascular Data Registry®
Authors: Robert W Yeh, Matthew J Czarny, Sunghee Kim, Matthew T Roe, David R Holmes, Ralph G Brindis, W D Weaver, Sharon-Lise T Normand, Dean Kereiakes, Laura Mauri
Journal: Circulation (2013)

Background: Randomized clinical trials are often criticized for not reflecting real-world practice. To understand the effect of site and patient selection on trial generalizability, we examined US patient and hospital participation within the Dual Antiplatelet Therapy (DAPT) Study, a broadly inclusive trial of PCI patients, using a linked analysis with the CathPCI Registry®. Methods: Within the CathPCI Registry, we identified patients undergoing PCI between September 1, 2009 and July 1, 2011 - the period of DAPT Study enrollment. We compared US patients enrolled in DAPT to CathPCI Registry patients meeting DAPT inclusion criteria. Characteristics of US DAPT sites were also compared to those of hospitals not participating in DAPT. Standardized differences (%) for all variables were estimated, with those greater than 10% considered significant. Results: Among 1,139,932 NCDR patients undergoing PCI, 748374 (65.7%) met the enrollment criteria for DAPT, and 23495 (2.1%) were enrolled. Enrolled patients were younger and had lower rates of prior stroke, CHF and peripheral vascular disease, but were similar with respect to race and gender compared with eligible patients (Table). Of the 1276 hospitals within the NCDR, 309 (24.2%) participated in DAPT. Hospital characteristics differed markedly, with DAPT-participating hospitals being larger (mean beds 468 vs. 311), more often located in urban settings (61.2% vs. 42.6%), more often affiliated with training programs (53.7% vs. 34.1%), and with higher annual PCI volumes (mean annual hospital volume 858 vs. 378 PCIs) compared with non-DAPT hospitals. Conclusions: While liberal inclusion criteria may allow randomized trials to better simulate “real-world” clinical practice, the process of site selection may encourage participation of higher volume, urban hospital settings. These findings are relevant to clinical trial interpretation and implementation of evidence-based practice throughout the healthcare system.
Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the <scp>MCRN</scp>‐003/<scp>MYX</scp>.1 single arm phase <scp>II</scp> trial
Authors: Christopher P. Venner, Richard LeBlanc, Irwindeep Sandhu, Darrell White, Andrew R. Belch, Donna E. Reece, Christine Chen, Sean Dolan, Marc Lalancette, Martha Louzada, Andrea Kew, Arleigh McCurdy, Bethany Monteith, Tony Reiman, Gail McDonald, Max Sherry, Engin Gul, Bingshu E. Chen, Annette E. Hay
Journal: American Journal of Hematology (2021)

Abstract The MCRN‐003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)‐free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m 2 ), dexamethasone 40 mg and cyclophosphamide 300 mg/m 2 was delivered over 28‐day cycles. The primary endpoint was overall response after four cycles. Secondary endpoints included toxicity, response depth, PFS and OS. Exploratory endpoints included the impact of cytogenetics, prior therapy exposure and serum free light chain (sFLC) escape; 76 patients were accrued. The ORR was 85% (68% ≥very good partial response [VGPR] and 29% ≥complete response [CR]). The median OS and PFS were 27 and 17 months respectively. High‐risk cytogenetics conferred a worse ORR (75% vs. 97%, p = .013) and median OS (18 months vs. NR, p = .002) with a trend toward a worse median PFS (14 vs. 22 months, p = .06). Prior proteasome inhibitor (PI) or lenalidomide did not influence OS or PFS. The sFLC was noted in 15% of patients with a median PFS of 17 months when included as a progression event. The most common ≥ grade 3 non‐hematologic adverse events were infectious (40%), vascular (17%) and cardiac (15%). The wKCD is a safe and effective regimen in relapse, especially for patients ineligible for lenalidomide‐based therapies.