tbuckley/cabot-search huggingface dataset:
Improvements in Fatigue Lag Behind Disease Remission in Early Rheumatoid Arthritis: Results From the Canadian Early Arthritis Cohort
Authors: Melissa Holdren, Orit Schieir, Susan J. Bartlett, Louis Bessette, Gilles Boire, Glen Hazlewood, Carol A. Hitchon, Edward Keystone, Diane Tin, Carter Thorne, Vivian P. Bykerk, Janet E. Pope
Journal: Arthritis & Rheumatology (2020)

To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA).Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11-point numerical rating scale (NRS) for up to 5 years of follow-up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3-months of cohort entry were compared.Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56-0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C-reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow-up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow-up. Maximal improvements in fatigue lagged behind remission by 6 months.Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3-months was associated with short-term and long-term benefits in fatigue over time.
THU0137 Lethal medium-vessel arteritis mimicking deep sepsis following etanercept and minocycline therapy in a patient with ra
Authors: JM Berthelot, J Glemarec, Y Maugars, A Prost
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To report the onset of a severe and lethal medium-vessel panarteritis mimicking deep sepsis three weeks after etanercept withdrawal and minocycline therapy in a patient with RA. <h3>Methods</h3> <h3>Results</h3> A 50-year-old man with RA (7/7 1987 ACR criteria) had poorly responded to all DMARDs and low-dose steroids for 12 years. In September 1999, DAS-28 score of 6.8 led to a treatment by etanercept (25 mg twice a week) for 4 months who remained poorly effective too (DAS-28 after 3 months: 6.05). Although no side-effects occurred, the patient wished to stop etanercept. A short cure by minocycline was administered. Ten days after, the patient's general condition worsened with fever (from 38°C to 39°C), hyperleukocytosis (24.109/ml), confusion, pleural effusion, hypoalbuminemia (17.2 g/l), epigastric pain, and CRP levels up to 295 mg/l. ANA and APL were negative, and ANCA only slightly positive (1/20, without anti-MPO antibodies). RF were 40 times the upper normal value. Extensive search for sepsis was unsuccessful. Highly false positive tests for myoglobin with ELISA kits using rodent antibodies were suggestive of anti-chimeric antibodies. The patient died in March 2000, three months after discontinuance of etanercept. An autopsy confirmed severe plurivisceral vasculitis typical of granulomatous, necrotising panarteritis, with both old and recent lesions involving mainly the medium-vessels in heart, muscles and gall-bladder. <h3>Conclusion</h3> Although the relation of the patient's death to treatments is uncertain, a flare of rheumatoid vasculitis could have been involved. This severe vasculitis occurring soon after etanercept withdrawal and presenting first as unexplained fever mimicked deep sepsis for several weeks and misled the treatment strategy.
PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection
Authors: Zheng-Zheng Tang, Gregory R. Sliwoski, Guanhua Chen, Bowen Jin, William S. Bush, Bingshan Li, John A. Capra
Journal: Genome biology (2020)

Abstract Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN’s performance on synthetic data and two real data sets for lipid traits and Alzheimer’s disease. Our results demonstrate that PSCAN performs competitively with existing gene-level tests while increasing power and identifying more specific signal variant sets. Furthermore, PSCAN enables generation of hypotheses about the molecular basis for the associations in the context of protein structures and functional domains.
Role of sodium bicarbonate in the management of acute upper gastrointestinal bleeding
Authors: Jonathan Wong, Susan Taylor, Diana Lerner
Journal: Endoscopy (2020)

Sodium bicarbonate has previously been reported to have effects on blood clot formation both in vitro and in vivo. It is thought that sodium bicarbonate interferes with fibrin clot formation [1] [2]. We describe our experience with two patients with upper gastrointestinal (GI) bleeding in whom sodium bicarbonate was used to improve visualization, thus allowing definitive control of the bleeding.
Internet Searches for Acute Anxiety During the Early Stages of the COVID-19 Pandemic
Authors: John W. Ayers, Eric C. Leas, Derek C. Johnson, Adam Poliak, Benjamin M. Althouse, Mark Dredze, Alicia L. Nobles
Journal: JAMA Internal Medicine (2020)

Internet Searches for Acute Anxiety During the Early Stages of the COVID-19 PandemicThere is widespread concern that the coronavirus disease 2019 (COVID-19) pandemic may harm population mental health, chiefly owing to anxiety about the disease and its societal fallout. 1 But traditional population mental health surveillance (eg, telephone surveys, medical records) is time consuming, expensive, and may miss persons who do not participate or seek care.To evaluate the association of COVID-19 with anxiety on a population basis, we examined internet searches 2 indicative of acute anxiety during the early stages of the COVID-19 pandemic.
Abstract 16849: Mortality Associated With Mitral Regurgitation and Impact of Intervention Among 76,402 Subjects Referred for Echocardiography Over 17 Years
Authors: Jared Breyley, Gautam Rangavajla, Thomas G Stewart, Eric Farber-Eger, Marcia A Blair, Evan L Brittain, Quinn S Wells
Journal: Circulation (2018)

Introduction: Mitral regurgitation (MR) guidelines are largely informed by registries that may not represent patients in current care. We hypothesized that assessing outcomes in a contemporary MR cohort curated from electronic health records (EHRs) would improve understanding of MR-related risk and the impact of interventions. Methods: Clinical and echocardiographic data were extracted at the time of first transthoracic echocardiogram (TTE) for all patients in Vanderbilt University Medical Center’s EHR between 1998-2015. Associations between all-cause mortality and MR severity were assessed by Kaplan-Meier (KM) curves and Cox proportional hazards regression model with time-varying covariates. Results: There were 76,402 subjects with trace MR. Subjects were median age 59 yrs (45, 70), 52% female, and 86% white. Moderate or greater MR was present in 5,260 (6.9%) subjects, of which 1,085 (1.4%) were severe. KM estimates of 10 year survival for severe vs trace MR were 0.45 (0.42, 0.49) vs 0.72 (0.71, 0.73) - relative 10 year risk 1.95 (1.82, 2.09); p&lt;0.001; Figure 1a. In an adjusted Cox model, features associated with mortality included MR severity, age, male sex, LV ejection fraction, LV systolic dimension, pulmonary artery pressure, heart failure, and atrial fibrillation (p&lt;0.001). In subjects with moderate MR and 1 year follow-up, mitral valve repair/replacement within 1 year of TTE significantly reduced 5 year mortality (0.38 (no intervention) vs 0.17 (repair/replace)) - relative 5 year risk 0.44 (0.01, 0.78); p&lt;0.001; Figure 1b. In KM analysis, the impact of intervention was attenuated at later time points. Conclusions: In a large cohort referred for TTE, MR is common and associated with significant mortality. Comorbidities and markers of cardiac remodeling are associated with increased mortality, while risk is attenuated by mitral valve intervention. Future analyses will evaluate predictors of treatment response and etiology-specific associations.
The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation
Authors: Susanna S. Ng, Fabian De Labastida Rivera, Juming Yan, Dillon Corvino, Indrajit Das, Ping Zhang, Rachel Kuns, Shashi Bhushan Chauhan, Jiajie Hou, Xian-Yang Li, Teija C. M. Frame, Benjamin A. McEnroe, Eilish Moore, Jinrui Na, Jessica A. Engel, Megan S. F. Soon, Bhawana Singh, Andrew J. Kueh, Marco J. Herold, Marcela Montes de Oca, Siddharth Sankar Singh, Patrick T. Bunn, Amy Roman Aguilera, Mika Casey, Matthias Braun, Nazanin Ghazanfari, Shivangi Wani, Yulin Wang, Fiona H. Amante, Chelsea L. Edwards, Ashraful Haque, William C. Dougall, Om Prakash Singh, Alan G. Baxter, Michele W. L. Teng, Alex Loukas, Norelle L. Daly, Nicole Cloonan, Mariapia A. Degli-Esposti, Jude Uzonna, William R. Heath, Tobias Bald, Siok-Keen Tey, Kyohei Nakamura, Geoffrey R. Hill, Rajiv Kumar, Shyam Sundar, Mark J. Smyth, Christian R. Engwerda
Journal: Nature Immunology (2020)
Reliability of Nailfold Capillary Density Measurement As a Possible Outcome Measure for Systemic Sclerosis-Related Microangiopathy
Authors: G Dinsdalel, T Moore, J Manning, A Murray, M Berks, P Tresadern, C Taylor, N O'Leary, C Roberts, J Allen, M Anderson, M Cutolo, R Hesselstrand, K Howell, P Pyrkotsch, F Ravera, Smith, A Sulli, M Wildt, A Herrick
Journal: Arthritis & Rheumatology (2014)
Phase I study of the IXO regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), as first-line therapy for metastatic colorectal cancer: Final survival results
Authors: J. Maroun, D. Jonker, C. Cripps, R. Goel, T. Asmis, H. Marginean, G. Chiritescu
Journal: Journal of Clinical Oncology (2009)

4082 Background: This study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of the IXO regimen when used as first-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients with ECOG PS 0–2, histologically proven, chemo-naïve, non-resectable mCRC were eligible. Phase I starting doses were as follows: I (180 mg/m 2 i.v.) d1, X (850 mg/m 2 bid orally) d2–15, O (85 mg/m 2 i.v.) d1; q3w. Dose escalation (3+3 design) was based on toxicity observed at previous dose levels (DL) until DLT and the MTD were reached. Results: 39 pts (31 male/8 female, median age 58 years, ECOG PS 0–1 in 37, 95%) received a median of 11 cycles (range 1–34) at 8 DLs. 39 pts were evaluable for toxicity. The most common grade 3/4 hematological adverse events (AEs) were granulocytopenia (60%) and fever/febrile neutropenia (18%). The most common grade 3 non-hematological AEs were diarrhea (15%), vomiting (10%), fatigue (8%). No grade 3/4 neuropathy was reported. DLTs: 1 DLT was observed at each of the first 4 DLs, no DLTs at DL5 &amp; 6, 1 at DL7 and 2 at DL8. MTD was reached at DL8. The recommended phase II dose (DL7) is as follows: I (160 mg/m 2 ), X (950 mg/m 2 ), O (100 mg/m 2 ). Efficacy: 38 pts are evaluable for efficacy. The RR is 74% (95% CI 60–89), including 4 CRs, 25 PRs and 6 SDs. The disease control rate is 90% (95% CI 80–100). 10 (26%) pts had subsequent liver surgery with curative intent; 1 had lung resection. Median progression-free survival was 12.3 months (95% CI, 8–17). Overall median survival was 26.4 months (95% CI, 13–36). Conclusions: Diarrhea is the main DLT. Severe neutropenia was of short duration and manageable. The IXO regimen is well tolerated and highly effective as first-line treatment for mCRC. It appears to be particularly effective in downsizing of initially unresectable colorectal cancer liver metastases. A phase II study to confirm the efficacy/safety of IXO in combination with bevacizumab (Avastin) is ongoing. Supported by: Hoffmann La-Roche, Sanofi-Aventis, Pfizer Canada. [Table: see text]
Assessment of Trends in the Design, Accrual, and Completion of Trials Registered in ClinicalTrials.gov by Sponsor Type, 2000-2019
Authors: Gillian Gresham, Jill L. Meinert, Arthur G. Gresham, Curtis L. Meinert
Journal: JAMA Network Open (2020)

<h3>Importance</h3> ClinicalTrials.gov is a valuable resource that can be used to trace the state and nature of trials. Since its launch in 2000, more than 345 000 trials have been registered. Little is known about the characteristics and trends in clinical trials over time and how they differ by sponsor type. <h3>Objective</h3> To assess trends in clinical trials registered in ClinicalTrials.gov over time and by sponsor type. <h3>Design, Setting, and Participants</h3> This cross-sectional study included clinical trials (interventional studies) registered in ClinicalTrials.gov from January 1, 2000, through December 31, 2019. The trials were grouped by lead sponsor: National Institutes of Health (NIH) and other US government agencies, industry, and other sources (foundations, universities, hospitals, clinics, and others). A static version of the Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database was downloaded on January 1, 2020, for analysis. <h3>Main Outcomes and Measures</h3> ClinicalTrials.gov registration fields, including overall status, phase, intervention, number of sites, use of masking and randomization, sample size, and time to study completion by start year and lead sponsor (organization that provided funding or support for a clinical study). <h3>Results</h3> A total of 245 999 clinical trials (interventional studies) were started between 2000 and 2019, of which 135 144 (54.9%) were completed. Among completed trials, 5113 (3.8%) were sponsored by the NIH or a US government agency, 48 668 (36.0%) by industry, and 81 363 (60.2%) by other sources. Most trials were single center (61.3%), randomized (65.6%), and phase 1 to 2 (35.5%) or did not have a US Food and Drug Administration–defined phase (38.4%), with fewer drug trials being conducted over time. Sample sizes were small (median, 60; interquartile range [IQR], 30-160) and diminished over time. Trial median completion times varied by lead sponsor: 3.4 years (IQR, 1.9-5.0 years) for NIH- and US government–sponsored trials, 1.2 years (IQR, 0.5-2.4 years) for industry trials, and 2.1 years (IQR, 1.1-3.7) for trials sponsored by other sources. <h3>Conclusions and Relevance</h3> The findings suggest that the composition and design of trials changed from 2000 to 2019 and differed substantially by sponsor type. Increased funding toward larger randomized clinical trials may be warranted to inform clinical decision-making and guide future research.
Cutaneous B‐cell lymphomas: 2021 update on diagnosis, risk‐stratification, and management
Authors: Alexandra C. Hristov, Trilokraj Tejasvi, Ryan A. Wilcox
Journal: American Journal of Hematology (2020)

Approximately one-fourth of primary cutaneous lymphomas are B-cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT).Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B-cell lymphomas from systemic B-cell lymphomas with secondary skin involvement.Disease histopathology remains the most important prognostic determinant in primary cutaneous B-cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5-year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.Both PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multi-agent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
Risk factors of cervical neoplasia in a low income sector under control program in a developing country
Authors: J. J. Zarba, S. Holgado, M. Sanchez Segura, A. Gonzalez, A. Gonzalez, V. M. Cano Busnelli, C. E. Lorente, A. Elias de Vacaflor
Journal: Journal of Clinical Oncology (2009)

1545 Background: There are a high number of risk factors (RF) in cervical neoplasias, most of them related with human papilloma virus infection: women with history of multiple sex partners (MSP), with early onset of sexual intercourse (EOSI),and non-previous cervical Papanicolaou (Pap) smear (NPAP).Objective: To determine the presence of RF in the studied population, the frecuency and types of lesions found, and the correlation between non-previous pap smear and underlying pathology. Methods: The population included in the study were 14,021 patients from institutions of public (PU) (n = 7523) and private (PRI) (n = 6499) sectors in the province of Tucumán–the average age being 34 and 43 years old, respectively–studied between 2007 and 2008, in a routine screening for CC with Pap testing. Both sectors include mostly low income people with none or limited health insurance. All testings were performed under methodologic norms of a CC Detection Program. The RF analized were: NPAP, EOSI, and MSP. Cervical lesions were studied with Bethesda System 2001. The statistic applied was the exploratory analysis. Results: NPAP in PU n = 4562 (75.76%), PRI n = 3247 (81.66%). EOSI with mean age being in PU 17 years old (sD 3.55) and PRI 19 (sD 5.33).MSP above 4 partners PU n= 482 (6.55%) PRI n= 161 (2.75%).Frecuency of LSIL in PU n= 30 (0,40%) PRI n = 50 (0.80%).HSIL in PU n = 29 (0.39%) PRI n = 28 (0.45%).Ca INV in PU n = 6 (0.08%) PRI n = 3 (0.05%). ASCUS in PU n = 24 (0.32%) PRI n = 10 (0.16%). Asociation between NPAP and cervical pathology was found p = 0.024 &lt; 0.05 given that 100/142 (70.42%) patients with lesion had NPAP and 42/142 (29.57%) paitents had previous Pap. Conclusions: The results in this sample indicate low Pap coverture is mantained in PU and PRI sectors and the need to approach the population under 20 years old in Tucuman, Argentina, to prevent CC. No significant financial relationships to disclose.
Watery Diarrhea in a Patient With Metastatic Appendiceal Adenocarcinoma
Authors: Elijah J. Mun, Dennis J. Ahnen, Swati G. Patel
Journal: JAMA Oncology (2020)

A 72-year-old man with metastatic appendiceal adenocarcinoma undergoing chemotherapy with capecitabine plus oxaliplatin presents with lower abdominal pain and watery, large-volume diarrhea up to 15 times per day for the previous 3 weeks. What is your diagnosis?
Implementing Society of Surgical Oncology and the American Society for Radiation Oncology Margin Guidelines to Reduce Reoperations After Lumpectomy for Early Breast Cancer
Authors: Cheng-Har Yip
Journal: JAMA Surgery (2020)

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Revised 15-item MDS-specific frailty scale maintains prognostic potential
Authors: Bo A. Wan, Aziz Nazha, Rebecca Starkman, Shabbir Alibhai, Richard. A. Wells, Michelle Geddes, Nancy Zhu, Mary-Margaret Keating, Brian Leber, Lisa Chodirker, Mitchell Sabloff, Grace Christou, Heather A. Leitch, Eve St-Hilaire, Nicholas Finn, April Shamy, Karen W. L. Yee, John Storring, Thomas J. Nevill, Robert Delage, Mohamed Elemary, Versha Banerji, Anne Parmentier, Mohammad Siddiqui, Aksharh Kirubananthaan, Alexandre Mamedov, Liying Zhang, Rena Buckstein
Journal: Leukemia (2020)
Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
Authors: Constantin J. Thieme, Moritz Anft, Krystallenia Paniskaki, Arturo Blazquez-Navarro, Adrian Doevelaar, Felix S. Seibert, Bodo Hoelzer, Margarethe Justine Konik, Marc Moritz Berger, Thorsten Brenner, Clemens Tempfer, Carsten Watzl, Toni L. Meister, Stephanie Pfaender, Eike Steinmann, Sebastian Dolff, Ulf Dittmer, Timm H. Westhoff, Oliver Witzke, Ulrik Stervbo, Toralf Roch, Nina Babel
Journal: Cell Reports Medicine (2020)

T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.
Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Véronique Diéras, Hyo S Han, Bella Kaufman, Hans Wildiers, Michael Friedlander, Jean-Pierre Ayoub, Shannon L Puhalla, Igor Bondarenko, Mario Campone, Erik H Jakobsen, Mathilde Jalving, Cristina Oprean, Marketa Palácová, Yeon Hee Park, Yaroslav Shparyk, Eduardo Yañez, Nikhil Khandelwal, Madan G Kundu, Matthew Dudley, Christine K Ratajczak, David Maag, Banu K Arun
Journal: The Lancet Oncology (2020)