tbuckley/cabot-search huggingface dataset:
How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a multiple propensity score to adjust for confounding by indication in observational studies
Authors: Sytske Anne Bergstra, Lai-Ling Winchow, Elizabeth Murphy, Arvind Chopra, Karen Salomon-Escoto, João Eurico Fonseca, Cornelia F Allaart, Robert B M Landewé
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication. Methods Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS. Results After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95% CI) of −2.00 (−2.65 to −1.36) if patients received a bDMARD; of −0.96 (−1.33 to −0.59) if patients received csDMARD(s)+glucocorticoids and of −0.73 (−1.21 to −0.25) if patients received csDMARDs only. These changes were −0.91 (−1.23 to −0.60); −0.43 (−0.62 to −0.23) and −0.39 (−0.66 to −0.13), respectively after 1 year of follow-up. Conclusions In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.
The prognostic value of DNA damage level in peripheral blood lymphocytes in germ cell cancer patients
Authors: M. Mego, Z. Sestakova, K. Kalavska, L. Hurbanova, D. Jurkovicova, J. Gursky, M. Chovanec, D. Svetlovska, V. Miskovska, J. Obertova, P. Palacka, K. Rejlekova, Z. Sycova-Mila, J. Mardiak, M. Chovanec
Journal: Annals of Oncology (2018)
Abstract 14295: Increasing QRS Duration Over Time Is Associated With Mortality and Morbidity in an Outpatient Heart Failure Population
Authors: Hassan Alfraidi, William F McIntyre, Lindsay Torbiak, Shelley Zieroth, Colette M Seifer
Journal: Circulation (2015)

Introduction: Heart failure is a leading cause of morbidity and mortality. Prolonged QRS duration (QRSd), a marker of intra-ventricular conduction delay, has been shown to be associated with worse left ventricular (LV) systolic function, LV dilation and mitral regurgitation as well as with mortality. There are minimal data in the literature on the progression of QRSd over time, and the association with clinical outcomes. Hypothesis: We hypothesized that the progression of QRSd over time would be associated with mortality and hospitalizations in an outpatient heart failure population. Methods: Retrospective study of consecutive new adult referrals to a tertiary heart failure clinic over a 1 year period (2012). All patients with a narrow QRSd (defined as &lt;130 ms) were included. Data were collected on demographics, ejection fraction (EF), clinical course and major clinical events. Primary endpoint was mortality and secondary endpoint was heart failure hospitalization. Results: A total of 147 patients were included, 90 were males (61%). Mean age was 66 years (+/-15), mean EF was 33% (+/- 15) and mean NYHA class 2.2 (+/- 0.9) at baseline. An ischemic aetiology accounted for 50% of the patients. Mean QRSd was 100 ms (+/- 13) at baseline and 119 ms (+/- 25) at last follow-up, which was a mean of 2.5 years from baseline. Death occurred in 27 patients (18%) and there were 114 hospitalizations in 54 patients. Results of univariate regression analysis are presented in the table. Conclusion: An increase in QRSd over time is associated with increased heart failure hospitalizations and all cause mortality in a tertiary care outpatient heart failure population.
Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis
Authors: Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Junsheng Ma, Roland L Bassett, Noha Abdel-Wahab, Jaime Anderson, Jennifer E Davis, Jocelyn Joseph, Marc Uemura, Ali Noman, Hamzah Abu-Sbeih, Cassian Yee, Rodabe Amaria, Sapna Patel, Hussein Tawbi, Isabella C Glitza, Michael A Davies, Michael K Wong, Scott Woodman, Wen-Jen Hwu, Patrick Hwu, Yinghong Wang, Adi Diab
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have significant side effects and prolonged therapy may reduce CPI-anti-tumor activity. Early addition of TNF-α inhibitors such as infliximab (IFX) may expedite symptom resolution and shorten CS duration. Thus, we conducted the first retrospective study, to our knowledge, evaluating symptom resolution in patients with irEC treated with and without IFX. <h3>Methods</h3> Data were collected from the medical records of patients diagnosed with irEC. The primary endpoint was time to symptom resolution for irEC for cases managed with IFX plus CS (IFX group) versus CS alone (CS group). Duration of CS, overall survival (OS), and time to treatment failure (TTF) were secondary endpoints. <h3>Results</h3> Among 75 patients with irEC, 52% received CS alone, and 48% received IFX. Despite higher grade colitis in the IFX group (grade 3/4: 86% vs. 34%; <i>p</i> &lt; 0.001), median times to diarrhea resolution (3 vs. 9&nbsp;days; <i>p</i> &lt; 0.001) and to steroid titration (4 vs. 13&nbsp;days; <i>p</i> &lt; 0.001) were shorter in the IFX group than in the CS group without a negative impact on TTF or OS. Total steroid duration (median 35 vs. 51&nbsp;days; <i>p</i> = 0.150) was numerically lower in the IFX group. <h3>Conclusions</h3> Despite higher incidence of grade 3/4 colitis, IFX added to CS for the treatment of patients with irEC was associated with a significantly shorter time to symptom resolution. The data suggest that early introduction of IFX should be considered for patients with irEC until definitive prospective clinical trials are conducted.
Role of TP53 mutations in relation to response to anti-ALK agents in EML4-ALK-translocated NSCLC patients
Authors: M. Canale, A. Delmonte, C. Dazzi, A. Gamboni, C. Casanova, M. Papi, M. Mariotti, N. De Luigi, M.A. Burgio, G. Minuti, D. Calistri, M. Bonafè, L. Crinò, P. Ulivi
Journal: Annals of Oncology (2018)
In myocardial injury after noncardiac surgery, dabigatran reduced vascular events without increasing major bleeding
Authors: Eric R. Bates
Journal: Annals of Internal Medicine (2018)

Source Citation Devereaux PJ, Duceppe E, Guyatt G, et al; MANAGE Investigators. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet. 2018;391:2325-34. 29900874
What treatments are effective for common cold in adults and children?
Authors: Mieke L van Driel, Sophie Scheire, Laura Deckx, Philippe Gevaert, An De Sutter
Journal: BMJ (2018)

What you need to know• Quality evidence to say whether over-the-counter treatments work for nasal symptoms of the common cold is limited.• For adults, consider a trial of decongestants alone, or with antihistamines or analgesics to alleviate bothersome nasal symptoms.• Do not prescribe decongestants to children under 12, as evidence of their effectiveness is limited and associated risks may exist.The common cold is usually caused by viruses and is mostly self limiting, 1 but it can have a substantial impact on work, school, 2 use of health services, and money spent on medications.Children have around 6-8 colds per year and adults have 2-4. 3 4Many over-the-counter (OTC) treatments for the common cold claim to alleviate nasal symptoms, such as congestion, rhinorrhoea (runny nose), and sneezing.Table 1 lists commonly used drugs.Evidence for the effectiveness of these treatments is limited and of low quality, and clear guidance is lacking. 5Long term use of nasal decongestants is known to lead to chronic nasal congestion.
Soft tissue sarcomas (STS) in elder patients: No impact of age on overall survival (OS) in an unselected cohort
Authors: J.A. Perez Fidalgo, A. Lopez, V. Gambardella, S. Navarro, A. Iranzo, N. Diaz Fernandez, P. Tolosa, A. Silvestre, E. Iriarte Moncho, M.C. Garcia Mora, A. De la Paz, J.J. Soler, A. Cervantes
Journal: Annals of Oncology (2018)
GW29-e0731 Effects of Different Intensity Exercise Preconditioning on Cardiac Inflammation in Rats after Exhaustive Exercise by Regulation of TXNIP/TRX/NF-κBp65/NLRP3 Inflammatory Pathway
Authors: Yuemin Li, Peng Xu, Junshi Zhang, Xuebin Cao
Journal: Journal of the American College of Cardiology (2018)
P3.16-10 Radiomic Features on CT are Prognostic of Recurrence as well as Predictive of Added Benefit of Adjuvant Chemotherapy in ES-NSCLC
Authors: P. Vaidya, K. Bera, P. Fu, S. Ganesan, A. Khunger, P. Patil, V. Velcheti, A. Madabhushi
Journal: Journal of Thoracic Oncology (2018)
Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension
Authors: Juan G. Abraldes, Jonel Trebicka, Naga Chalasani, Gennaro D’Amico, Don C. Rockey, Vijay H. Shah, Jaime Bosch, Guadalupe Garcia‐Tsao
Journal: Hepatology (2018)

Portal hypertension (PH) is the main driver of cirrhosis decompensation, the main determinant of death in patients with cirrhosis. PH results initially from increased intrahepatic vascular resistance. Subsequently, increased inflow from splanchnic vasodilation and increased cardiac output lead to a further increase in portal pressure (PP). Reducing PP in cirrhosis results in better outcomes. Removing the cause of cirrhosis might improve PP. However, this is a slow process and patients may continue to be at risk of decompensation. Additionally, for some chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD), etiological treatments are not yet available. Therefore, there is a need to develop better therapies specifically aimed at reducing PP. For over 35 years, the mainstay of such therapy has been the use of nonselective beta-blockers (NSBBs) that act by reducing portal venous inflow. Recently, many drugs (mainly targeting intrahepatic mechanisms) have shown promise in preclinical and early clinical studies and may act alone or synergistically with NSBBs in reducing PP in cirrhosis. The objective of this position paper is to propose a novel framework for the design of clinical trials (phase 1, 2, and 3) in patients with cirrhosis and PH and to prioritize targets and pharmacological therapies in this setting. We have focused the discussion on patients with compensated cirrhosis. The paper summarizes discussions held at The American Association for the Study of Liver Diseases (AASLD) Industry Colloquium in January 2018, with the participation of clinical and translational investigators, regulatory professionals, and industry partners.
Abstract 14726: Performance of the Novel Biomarker-Based ABC-Stroke Risk Score Over Time in Patients With Atrial Fibrillation
Authors: Ziad Hijazi, Jonas Oldgren, Johan Lindbäck, John H Alexander, Michael Hanna, Elaine M Hylek, Renato D Lopes, Christopher B Granger, Agneta Siegbahn, Lars Wallentin
Journal: Circulation (2016)

Introduction: The ABC-stroke risk score (Age, Biomarkers [troponin and NT-proBNP], and Clinical history of prior stroke) is a novel biomarker-based model for patients with atrial fibrillation (AF)....
Atezolizumab Plus nab-Paclitaxel in the Treatment of Metastatic Triple-Negative Breast Cancer With 2-Year Survival Follow-up
Authors: Sylvia Adams, Jennifer R. Diamond, Erika Hamilton, Paula R. Pohlmann, Sara M. Tolaney, Ching-Wei Chang, Wei Zhang, Koho Iizuka, Paul G. Foster, Luciana Molinero, Roel Funke, John Powderly
Journal: JAMA Oncology (2018)

<h3>Importance</h3> The humanized monoclonal antibody atezolizumab targets programmed death-ligand 1 and has demonstrated durable single-agent activity in a subset of metastatic triple-negative breast cancers. To extend the observed activity, combinatorial approaches are being tested with standard cytotoxic chemotherapies known to induce immunogenic tumor cell death. <h3>Objective</h3> To examine the safety, tolerability, and preliminary clinical activity of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancers. <h3>Design, Setting, and Participants</h3> This phase 1b multicohort study enrolled 33 women with stage IV or locally recurrent triple-negative breast cancers and 0 to 2 lines of prior chemotherapy in the metastatic setting from December 8, 2014, to April 30, 2017, at 11 sites in the United States. The median follow-up was 24.4 months (95% CI, 22.1-28.8 months). <h3>Interventions</h3> Patients received concurrent intravenous atezolizumab and intravenous nab-paclitaxel (minimum 4 cycles). <h3>Main Outcomes and Measures</h3> The primary end point was safety and tolerability. Secondary end points included best overall response rate by Response Evaluation Criteria in Solid Tumors, version 1.1; objective response rate; duration of response; disease control rate; progression-free survival; overall survival; and biomarker analyses. <h3>Results</h3> The 33 women had a median age of 55 years (range, 32-84 years) and received 1 or more doses of atezolizumab. All patients (100%) experienced at least 1 treatment-related adverse event, 24 patients (73%) experienced grade 3/4 adverse events, and 7 patients (21%) had grade 3/4 adverse events of special interest. No deaths were related to study treatment. The objective response rate was 39.4% (95% CI, 22.9%-57.9%), and the median duration of response was 9.1 months (95% CI, 2.0-20.9 months). The disease control rate was 51.5% (95% CI, 33.5%-69.2%). Median progression-free survival and overall survival were 5.5 months (95% CI, 5.1-7.7 months) and 14.7 months (95% CI, 10.1-not estimable), respectively. Concurrent nab-paclitaxel neither significantly changed biomarkers of the tumor immune microenvironment (programmed death-ligand 1, tumor-infiltrating lymphocytes, CD8) nor impaired atezolizumab systemic immune activation (expansion of proliferating CD8+ T cells, increase of CXCL10 chemokine). <h3>Conclusions and Relevance</h3> In this phase 1b trial for metastatic triple-negative breast cancers, the combination of atezolizumab plus nab-paclitaxel had a manageable safety profile. Antitumor responses were observed, including in patients previously treated with a taxane. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01633970
Intratumoral Immunotherapy with XCL1 and sFlt3L Encoded in Recombinant Semliki Forest Virus–Derived Vectors Fosters Dendritic Cell–Mediated T-cell Cross-Priming
Authors: Alfonso R. Sánchez-Paulete, Álvaro Teijeira, José I. Quetglas, María E. Rodríguez-Ruiz, Álvaro Sánchez-Arráez, Sara Labiano, Iñaki Etxeberria, Arantza Azpilikueta, Elixabet Bolaños, María Cristina Ballesteros-Briones, Noelia Casares, Sergio A. Quezada, Pedro Berraondo, David Sancho, Cristian Smerdou, Ignacio Melero
Journal: Cancer Research (2018)

: Multiple lines of evidence indicate a critical role of antigen cross-presentation by conventional BATF3-dependent type 1 classical dendritic cells (cDC1) in CD8-mediated antitumor immunity. Flt3L and XCL1, respectively, constitute a key growth/differentiation factor and a potent and specific chemoattractant for cDC1. To exploit their antitumor functions in local immunotherapy, we prepared Semliki Forest Virus (SFV)-based vectors encoding XCL1 and soluble Flt3L (sFlt3L). These vectors readily conferred transgene expression to the tumor cells in culture and when engrafted as subcutaneous mouse tumor models. In syngeneic mice, intratumoral injection of SFV-XCL1-sFlt3L (SFV-XF) delayed progression of MC38- and B16-derived tumors. Therapeutic activity was observed and exerted additive effects in combination with anti-PD-1, anti-CD137, or CTLA-4 immunostimulatory mAbs. Therapeutic effects were abolished by CD8β T-cell depletion and were enhanced by CD4 T-cell depletion, but not by T regulatory cell predepletion with anti-CD25 mAb. Antitumor effects were also abolished in BATF3- and IFNAR-deficient mice. In B16-OVA tumors, SFV-XF increased the number of infiltrating CD8 T cells, including those recognizing OVA. Consistently, following the intratumoral SFV-XF treatment courses, we observed increased BATF3-dependent cDC1 among B16-OVA tumor-infiltrating leukocytes. Such an intratumoral increase was not seen in MC38-derived tumors, but both resident and migratory cDC1 were boosted in SFV-XF-treated MC38 tumor-draining lymph nodes. In conclusion, viral gene transfer of sFlt3L and XCL1 is feasible, safe, and biologically active in mice, exerting antitumor effects that can be potentiated by CD4 T-cell depletion. SIGNIFICANCE: These findings demonstrate that transgenic expression of sFLT3L and XCL1 in tumor cells mediates cross-priming of, and elicits potent antitumor activity from, CD8 T lymphocytes, particularly in combination with CD4 T-cell depletion.
Efficacy and safety of axitinib in metastatic papillary renal carcinoma (mPRC): Results of a GETUG multicenter phase II trial (Axipap)
Authors: S. Negrier, N. Rioux-Leclercq, A. Ravaud, G. Gravis, L. Geoffrois, C.M. Chevreau, F. Rolland, E. Blanc, C. Segura-Ferlay, D. Perol, M. Gross Goupil, S. Dermeche, A. Flechon, L. Albiges, B. Escudier
Journal: Annals of Oncology (2018)
GW29-e0483 Hyperlipidemia and sustained statins therapy for the risk of major adverse cardiovascular events in patients with acute coronary syndrome: A observational cohort study
Authors: Ling Zhu, Yin Liu, Zhongwei Liu, Fuqiang Liu, Shuo Pan, Na Zhao, Yong Zhang, Xin Jiang, Gongchang Guan, Junkui Wang
Journal: Journal of the American College of Cardiology (2018)
CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma
Authors: Hiroko Nishida, Mutsumi Hayashi, Chikao Morimoto, Michiie Sakamoto, Taketo Yamada
Journal: Blood Cancer Journal (2018)

Abstract CD26, a 110-kDa transmembrane glycoprotein that is expressed on several tumor cells including malignant lymphoma, has been implicated in tumorigenesis: however, little is known regarding its role in multiple myeloma (MM). Recently, we identified CD26 expression on human osteoclasts (OCs) and demonstrated that humanized IgG 1 monoclonal antibody targeting CD26, huCD26mAb, inhibits human OC differentiation. Herein, we show that CD26 expression was present on plasma cells in the bone marrow tissues of MM patients. In vitro immunostaining studies revealed that although CD26 expression was low or absent on MM cell lines cultured alone, it was intensely and uniformly expressed on MM cell lines co-cultured with OCs. The augmented CD26 expression in MM cells was exploited to enhance anti-MM efficacy of huCD26mAb via a substantial increase in antibody-dependent cytotoxicity (ADCC) but not complement-dependent cytotoxicity (CDC). Moreover, huCD26mAb in combination with novel agents synergistically enhanced huCD26mAb induced ADCC activity against CD26+ MM cells compared with each agent alone. huCD26mAb additionally reduced the ratio of the side population (SP) fraction in CD26+ MM cells by ADCC. Finally, huCD26mAb significantly reduced the MM tumor burden and OC formation in vivo. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent.
New insight into parrots’ mitogenomes indicates that their ancestor contained a duplicated region
Authors: Adam Dawid Urantowka, Aleksandra Kroczak, Tony Silva, Rafael Zamora Padrón, Nuhacet Fernández Gallardo, Julie Blanch, Barry Blanch, Paweł Mackiewicz
Journal: Molecular Biology and Evolution (2018)

Mitochondrial genomes of vertebrates are generally thought to evolve under strong selection for size reduction and gene order conservation. Therefore, a growing number of mitogenomes with duplicated regions changes our view on the genome evolution. Among Aves, order Psittaciformes (parrots) is especially noteworthy because of its large morphological, ecological, and taxonomical diversity, which offers an opportunity to study genome evolution in various aspects. Former analyses showed that tandem duplications comprising the control region with adjacent genes are restricted to several lineages in which the duplication occurred independently. However, using an appropriate polymerase chain reaction strategy, we demonstrate that early diverged parrot groups contain mitogenomes with the duplicated region. These findings together with mapping duplication data from other mitogenomes onto parrot phylogeny indicate that the duplication was an ancestral state for Psittaciformes. The state was inherited by main parrot groups and was lost several times in some lineages. The duplicated regions were subjected to concerted evolution with a frequency higher than the rate of speciation. The duplicated control regions may provide a selective advantage due to a more efficient initiation of replication or transcription and a larger number of replicating genomes per organelle, which may lead to a more effective energy production by mitochondria. The mitogenomic duplications were associated with phenotypic features and parrots with the duplicated region can live longer, show larger body mass as well as predispositions to a more active flight. The results have wider implications on the presence of duplications and their evolution in mitogenomes of other avian groups.
Abstract 19029: Gasping During Cardiopulmonary Resuscitation is Associated With a Higher Likelihood of One Year Survival After Cardiac Arrest
Authors: Guillaume Debaty, José Labarere, Ralph J Frascone, Marvin A Wayne, Robert Swor, Brian Mahoney, Robert Domeier, Michael Olinger, Brian O’Neil, Tom P Aufderheide, Demetris Yannopoulos
Journal: Circulation (2016)

Introduction: Gasping has been found to be common after cardiac arrest and associated with increased survival to discharge for out-of-hospital cardiac arrests (OHCA). Active compression decompression (ACD) plus an impedance threshold device (ITD) improves brain blood flow and survival to hospital discharge with favorable neurologic function after OHCA compared with standard CPR (S-CPR). Hypothesis: We assessed the association of gasping during CPR on 1-year survival. Methods: The ResQTrial data, which compared ACD+ITD versus S-CPR, was used for these analyses. Nearly all one-year survivors had normal brain function. We included all evaluable subjects in the run-in and pivotal phases of the trial. Beginning in January 2007, the original case report forms were modified to include whether or not spontaneous gasping or breathing was observed at anytime during CPR. A logistic regression analysis was performed. Odds ratios (OR) were adjusted for ResQTrial study intervention arm, pre-specified prognostic factors...