tbuckley/cabot-search huggingface dataset:
Concerns about the operational definition of remission in 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus
Authors: Íñigo Rua Figueroa, Celia Erausquin
Journal: Annals of the Rheumatic Diseases (2019)

Concerns about the operational definition of remission in 2019 update of the EULAR recommendations for the management of systemic lupus erythematosusWe have read the recently published update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) recommendations 1 with great interest.While we greatly appreciate the effort made by the panel of experts, we would like to add our own comments with regards treatment objectives and the definition of remission.Remission as suggested in figure 1 1 would be defined as systemic lupus erythematosus disease activity index (SLEDAI)=0 with no use of corticosteroids at all.However, although we are aware of the lack a universal definition for remission for SLE, 2 we believe this view of remission is too stringent, given that it should include remission of both a clinical and serological nature.Working within of this definition poses doubts as to the amount of effort that would have to be made in order to achieve remission in our SLE patients.For example, in the scenario of patients with no active clinical lupus but with hypocomplementemia of positive native DNA (serologically active, SLEDAI=4), a common occurrence in daily clinical practice, should we even use belimumab, to get a 'complete remission' as defined in the 2009 update of EULAR expert's panel recommendations?Several groups have proposed a diverse set of remission criteria for SLE and the creation of an international task force has led to the DORIS group proposal, 3 in which for two levels of remission, namely, clinical remission on-therapy and remission off-therapy, no treatment other than antimalarial agents should be permitted.Given the international consensus that no changes in the treatment should be implemented for patients who present only serological activity without clinical activity, we believe that it would be more realistic to define remission as 'clinical' SLEDAI-2K=0.Perhaps, a dose of prednisone no more than 5 mg/day for patients with/without stable immunosuppressants and antimalarials.According to data from several authors, this subgroup of patients does not accrue damage during follow-up. 4 5Furthermore, in a study from the Hopkins Lupus Cohort has shown that corticosteroid doses of under 7.5 mg/day are also associated with a very low degree of damage progression, as measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. 6 summary, we suggest that in order to avoid confusion, the definition 'SLEDAI=0' in figure 1 of the document should be changed for 'clinical SLEDAI=0'.
Frontline flumatinib versus imatinib in patients with chronic myeloid leukemia in chronic phase: Results from the China randomized phase III study.
Authors: Zhang Li, Li Meng, Yanli Zhang, Huanling Zhu, Jiuwei Cui, Aining Sun, Yu Hu, Jie Jin, Hao Jiang, Xi Zhang, Yan Li, Qifa Liu, Li Liu, Wanggang Zhang, Jian Gu, Jian-Hui Qiao, Bingcheng Liu, Fengkui Zhang, Yong Guo, Jianxiang Wang
Journal: Journal of Clinical Oncology (2019)

7004 Background: Flumatinib (FM), a derivative of imatinib (IM), is a novel BCR-ABL1 tyrosine kinase inhibitor (TKI). The aim of this open-label phase III study was to validate the efficacy and safety of FM in comparison with IM as frontline treatment in Chinese patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CML-CP). Methods: Randomization was stratified by Sokal score with a 1:1 allocation to each arm. Primary endpoints were major molecular response (MMR = BCR-ABL IS≤0.1%) rates at 6 and 12 months. Molecular responses were assessed at a central laboratory blinded to treatment allocations during the study. Efficacy endpoints were analyzed for the intention-to-treat populations. This study is registered with ClinicalTrials.gov, number NCT02204644. Results: 400 eligible patients were randomized and patient characteristics at baseline were similar in each arm. The full analysis set (FAS) consisted of 393 patients who received FM 600 mg (n = 196) or IM 400 mg (n = 197) tablets once daily. Compared with IM, FM resulted significantly higher induction of MMR rate (%; 95%CI) at 6 month (33.7; 27.06-40.29 vs 18.3; 12.88-23.67; P = 0.0005) and 12 month (48.5; 41.47-55.47 vs 33.0; 26.43-39.56; P = 0.0021) and also at 3 month (8.2; 4.33- 12.00 vs 2.0; 0.06-4.00; P = 0.0058). Significantly more patients in the FM than in the IM arm achieved a complete molecular response (BCR-ABL IS≤0.0032%) at 12 months. Early molecular response (BCR-ABL IS ≤ 10%) at 3 months and early CCyR at 6 months were also significantly higher with FM than IM (82.1; 76.78-87.50 vs 53.3; 46.33-60.27; P &lt; 0.0001 and 60.71; 53.88-67.55 vs 49.75, 42.76, 56.73; P = 0.0332). FM has a safety profile similar to IM. The rates of grade 3/4 TEAEs of FM were similar to IM, 56.57% (112 of 198) vs 41.38% (87 of 196). However, the frequencies of some nonhematological and hematological adverse events were significantly lower in the FM than in the IM arm, such as rash (4.59% vs 12.63%, P = 0.0064) and eyelid edema (0.51 vs 14.65, P &lt; 0.0001); leukopenia (30.61 vs 62.63, P &lt; 0.0001) and neutropenia (30.10 vs 59.60, P &lt; 0.0001). No specific TEAE was identified in each arm. Conclusions: This phase III study met its primary endpoints. Our study results suggest that FM is comparable to IM in its safety and superior in its efficacy profile at 3, 6 and 12 month time points. These results support FM as a frontline treatment option for patients with newly diagnosed CML-CP. Clinical trial information: NCT02204644.
Abstract MP27: Comparative Prognostic Performance of Different Definitions of Prediabetes in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bethany Warren, James S Pankow, Mark Woodward, Elizabeth Selvin
Journal: Circulation (2016)

Introduction: Discordance among definitions of prediabetes has been well documented, however less is known about which definitions are most indicative of long-term risk of clinical outcomes. Hypothesis: Prediabetes defined by Hemoglobin A1c (HbA1c) will be more strongly associated with risk of future outcomes than prediabetes defined by fasting glucose (FG) or 2-hour glucose. Methods: We included 10,692 ARIC participants who attended visit 2 (1990-92), when HbA1c and FG were measured, and 6,521 participants who attended visit 4 (1996-98), when FG and 2-hour glucose were measured, without prevalent diabetes, cardiovascular disease, heart failure, or chronic kidney disease at the relevant baseline. Participants were followed for up to 20 years for all-cause mortality and incident diabetes, cardiovascular disease/heart failure, and chronic kidney disease. Cox proportional hazards models were used to estimate adjusted hazard ratios of incident events for each prediabetes definition compared to normal glycemic levels. Seemingly unrelated regression was used to compare prediabetes definitions. Results: Prediabetes defined by FG and 2-hour glucose were similarly associated with risk of all-cause mortality, cardiovascular disease/heart failure, and chronic kidney disease (all p-values &gt; 0.1). Prediabetes defined by FG was more strongly associated with risk of diabetes than the 2-hour glucose definition (p &lt; 0.01). Prediabetes defined by HbA1c was more strongly associated with risk of all-cause mortality, diabetes, cardiovascular disease/heart failure, and chronic kidney disease than with prediabetes defined by FG (all p-values &lt; 0.001; Table). Conclusion: The HbA1c-based definition of prediabetes was more strongly associated with all-cause mortality, and incident cardiovascular disease/heart failure, and chronic kidney disease as compared to FG or 2-hour glucose-based definitions. Screening with HbA1c to identify persons with prediabetes identifies a group of persons at high risk for clinical outcomes.
Abstract 4469: Clinical outcomes among patients treated with abiraterone acetate for advanced prostate cancer with pre-existing cardiovascular conditions
Authors: Grace Lu-Yao, Nikita Nikita, Scott Keith, Krupa Gandhi, Timothy R. Rebbeck, Jennifer Cullen, Ginah Nightingale, Mark Mann, Andrew Chapman
Journal: Cancer Research (2019)

Abstract Background: Advanced prostate cancer patients with pre-existing cardiovascular diseases (CVD) are often excluded from clinical trials of abiraterone acetate (AA). Therefore, the clinical outcomes of these patients are uncertain. This study was undertaken to examine their outcomes - changes in the rate of hospitalization and short-term mortality after AA initiation by pre-existing CVD conditions. Methods: This population-based study identified PCa patients from the linked Surveillance, Epidemiology and End Result (SEER)-Medicare files diagnosed between 1/1/1991 and 12/31/2013 and treated with AA in 2011-2014. The primary endpoints were 6-month overall mortality and changes in hospitalization rates following AA initiation. Major pre-existing conditions are listed in the Table 1. The changes in hospitalization rate were measured by the incidence rate ratios (IRR), post treatment rate divided by pre-treatment rate. Results: Among 2,845 patients treated with AA (median age 75 years), 1,924 (67.6%) of these patients had at least one pre-existing CVD condition. Compared to pre-treatment period, the hospitalization incidence post-AA increased by 58% to 88%. The crude risk of 6-month overall mortality was between 21.4% to 25.6%. Table 1:Risk of Hospital Visits and 6-month Overall Mortality among AA Patients by Pre-Existing CVD condition.Pre-existing CVD conditionNo. hospitalizations per 6-months prior to AAIRR for hospitalizations (95% CI)Crude 6-month post AA MortalityAcute Myocardial Infraction0.651.88 (1.48-2.40)25.6%Atrial Fibrillation0.561.58 (1.36-1.83)24.4%Congestive Heart Failure0.591.72 (1.54-1.92)23.4%Stroke0.521.67 (1.40-2.01)22.1%Ischemic Heart Disease0.471.78 (1.63-1.95)21.4%No CVD0.251.87 (1.59-2.20)15.8% Conclusion: All patients experienced significant increase in hospitalization after initiation of AA. Our study highlights the importance of carefully monitoring patients after prescribing AA. Citation Format: Grace Lu-Yao, Nikita Nikita, Scott Keith, Krupa Gandhi, Timothy R. Rebbeck, Jennifer Cullen, Ginah Nightingale, Mark Mann, Andrew Chapman. Clinical outcomes among patients treated with abiraterone acetate for advanced prostate cancer with pre-existing cardiovascular conditions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4469.
Abstract 20441: Combined Assessment of Autonomic Tone and Cardiac Repolarization Identifies Patients With Better-Preserved Left Ventricular Systolic Function at High Risk of Death Following a Myocardial Infarction
Authors: Derek V Exner, Katherine M Kavanagh, Tomasz W Hruczkowski, Ahmad S Hersi, Bernard Thibault, François Philippon, Raymond Yee, Marie-Claude Guertin, Jeffrey Healey, Anthony Tang, Heikki Huikuri
Journal: Circulation (2016)

Introduction: A left ventricular (LV) ejection fraction (EF) of ≤ 35% later after myocardial infarction (MI) is principally used to identify patients for implantable cardioverter defibrillator (ICD...
Abstract 2931: The compounding effects of coenzyme q10 and radiation treatment on glial fibrillary acidic protein network of glioma <i>in vitro</i>
Authors: Chong-Chun Liao, Megha Jhunjhunwala, Li-Han Chung, Chi-Shuo Chen
Journal: Cancer Research (2019)

Abstract Introduction: Astrocytoma is an aggressive primary malignant brain tumor in adults. Radiation therapy is an effective medical treatment, but one of its undesired side-effects is the induced genomic instability of surrounding astrocytes, which can lead abnormal distribution of GFAP and associates with severe brain injury (BI). Purpose: In order to cope with this serious difficulty, various antioxidants have been applied with radiation therapy. Among antioxidants, Coenzyme Q10 (Q10) is one of the few candidates without double-edged sword effect. However, the understand about Q10 therapeutic effect on radiological protection is limited. In this study, we aimed to investigate the potential therapeutic effects of Q10 on brain tumor radiation treatment. Materials and Methods: Astrocyte and glioma cell lines were cultivated with Q10 (10μM~ 50 μM) and exposed to 10 Gy single dose from Cobalt-60 (60Co). After the radiation exposure, cell viability was analyzed using MTT assay, GFAP responses was examined by immunofluorescence staining and qPCR, and other cell phenotype indexes, such as the morphology, migration, and invasion in vitro, were observed by microscopy. Results: Our results indicated that Q10 treatment was capable of maintaining GFAP network of astrocyte after radiation exposure. Besides, Q10 synergistically eliminated glioma proliferation after radiation treatment. By extending horizontally along the base of GFAP remodeling, we further investigated the ability of 3D tumor invasion in co-culture model which simulated the microenvironment composed of reactive astrocyte and glioma in clinical research. Results indicated that radiation therapy with Q10 can further suppress the invasive ability in vitro. Conclusions: In sum, our results demonstrated the potential radiological protection of Q10 on astrocyte and amplified the therapeutic effectiveness for brain tumor therapy. Citation Format: Chong-Chun Liao, Megha Jhunjhunwala, Li-Han Chung, Chi-Shuo Chen. The compounding effects of coenzyme q10 and radiation treatment on glial fibrillary acidic protein network of glioma in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2931.
Antitumor Effects of Anti-Semaphorin 4D Antibody Unravel a Novel Proinvasive Mechanism of Vascular-Targeting Agents
Authors: Iratxe Zuazo-Gaztelu, Marta Pàez-Ribes, Patricia Carrasco, Laura Martín, Adriana Soler, Mar Martínez-Lozano, Roser Pons, Judith Llena, Luis Palomero, Mariona Graupera, Oriol Casanovas
Journal: Cancer Research (2019)

One of the main consequences of inhibition of neovessel growth and vessel pruning produced by angiogenesis inhibitors is increased intratumor hypoxia. Growing evidence indicates that tumor cells escape from this hypoxic environment to better nourished locations, presenting hypoxia as a positive stimulus for invasion. In particular, anti-VEGF/R therapies produce hypoxia-induced invasion and metastasis in a spontaneous mouse model of pancreatic neuroendocrine cancer (PanNET), RIP1-Tag2. Here, a novel vascular-targeting agent targeting semaphorin 4D (Sema4D) demonstrated impaired tumor growth and extended survival in the RIP1-Tag2 model. Surprisingly, although there was no induction of intratumor hypoxia by anti-Sema4D therapy, the increase in local invasion and distant metastases was comparable with the one produced by VEGFR inhibition. Mechanistically, the antitumor effect was due to an alteration in vascular function by modification of pericyte coverage involving platelet-derived growth factor B. On the other hand, the aggressive phenotype involved a macrophage-derived Sema4D signaling engagement, which induced their recruitment to the tumor invasive fronts and secretion of stromal cell-derived factor 1 (SDF1) that triggered tumor cell invasive behavior via CXCR4. A comprehensive clinical validation of the targets in different stages of PanNETs demonstrated the implication of both Sema4D and CXCR4 in tumor progression. Taken together, we demonstrate beneficial antitumor and prosurvival effects of anti-Sema4D antibody but also unravel a novel mechanism of tumor aggressivity. This mechanism implicates recruitment of Sema4D-positive macrophages to invasive fronts and their secretion of proinvasive molecules that ultimately induce local tumor invasion and distant metastasis in PanNETs. SIGNIFICANCE: An anti-semaphorin-4D vascular targeting agent demonstrates antitumor and prosurvival effects but also unravels a novel promalignant effect involving macrophage-derived SDF1 that promotes tumor invasion and metastasis, both in animal models and patients.
Abstract 4874: Incidental gallbladder cancer: Best step forward
Authors: Saurabh Galodha, Puneet Mahajan
Journal: Cancer Research (2019)

Abstract Objective: There is a rising trend of Incidental Gall Bladder Cancer (IGBC) with increase in laparoscopic cholecystectomy. Objective of our study was to evaluate the efficacy of further management (completion surgery and adjuvant chemotherapy) in IGBC in terms of long-term survival (&amp;gt; 5 years). Material and Method: Clinic-pathological and survival data of 145 IGBC patients was analysed from a prospectively maintained database of GBC. Patients investigated with triple phase CT abdomen and if required PET-CT. Diagnostic laparoscopy with Completion extended cholecystectomy performed in patients amenable for resection. Adjuvant therapy consisted of gemcitabine and cisplatin. Patients followed up with OPD visits and telephonic enquiry. Results: 864 patients of GBC were treated during the period of January 1989 to December 2012. Out of these 145 patients were IGBC [113 women (77%), median age; 52 years)]. 96 patients were detected on histopathology while 49 were diagnosed intra-operatively. Open cholecystectomy was done in 88, laparoscopic in 45 while 12 underwent laparoscopic converted to open cholecystectomy. Commonest T stage was T3 (n=71). All patients were re-evaluated after diagnosis of IGBC. 80 patients (55%) were taken up for surgery of which, 50 (62.5%) underwent completion extended cholecystectomy (rest had metastases or locally advanced unresectable disease). Median time interval between index surgeries to re-exploration was 35 days (0-250). It was longer in patients who could not undergo completion extended cholecystectomy (70 days vs. 49 days). Overall 5-year survival in pT1b, pT2 and pT3 stage was 49.5%, 36.1% and 8.4% respectively, but was considerably better in patients who underwent completion extended cholecystectomy compared with those who did not undergo re-surgery [pT1; 62.5% vs. 29.1%, pT2; 52.2% vs. 15.9%, pT3; 22.6% vs. 7.2%, p&amp;lt;0.001]. Prognostic factors associated with poor prognosis were higher T stage, R1 resection, bile spillage during index surgery, no completion surgery and residual disease on re-exploration on univariate analysis. On multivariate analysis factors portending poor prognosis were higher T stage, R1 resection and residual disease. Conclusion: Early recognition, early completion radical surgery and adjuvant therapy lends considerable survival benefit to patients of incidental carcinoma gall bladder. Residual disease and R1 resection portends a poorer survival. High index of suspicion should be kept in patients with thick walled GB to avoid missing a malignancy at index surgery. Citation Format: Saurabh Galodha, Puneet Mahajan. Incidental gallbladder cancer: Best step forward [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4874.
High Blood Pressure in Young Adulthood and Risk of Premature Cardiovascular Disease
Authors: Ramachandran S. Vasan
Journal: JAMA (2018)

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Abstract 332: STI Assessment of Left Ventricular Function in Patients With Previous Myocardial Infarction and Recurrent Ventricular Arrhythmias
Authors: Bich Lien Nguyen, Lidia Capotosto, Gaetana D’Alessandro, Eli S Gang, Fiorella Caranci, Francesco Barillá, Robert J Siegel, Antonio Vitarelli
Journal: Circulation (2012)

Purpose. Our aim was to compare strain parameters of patients with structural heart disease with and without ventricular tachycardia (VT) in order to identify high-risk patients that could have been missed by left ventricular ejection fraction (LVEF) criteria. Methods. We studied 86 patients (pts) with previous myocardial infarction (age, 59±14 years) scheduled for cardioverter-defibrillator (ICD) implantation. Forty-three pts had documented VT and 43 pts presented with no VT. Left ventricular (LV) function and volumes and score index were determined by two-dimensional echocardiography. Longitudinal LV strain was defined as the average of negative longitudinal strains of 6 segments of the septal and lateral walls in the apical 4-chamber view. Average radial and circumferential strain of 6 mid-LV segments was determined in the mid-short-axis view. Global strain was obtained by averaging the maximum systolic shortening in a 16-segment model. The analysis of strain parameters was performed offline using customized computer software (EchoPAC BT09, GE Ultrasound). Results. There were no differences in LVEF, LV volumes, QRS and QTc duration between pts with or without VT occurring during follow-up. Multivariate analysis revealed that global (p=0.018) and posterior wall circumferential strain (p=0.007) were strong and independent predictors of the occurrence of arrhythmic events. The area under the curve (AUC) for posterior wall circumferential strain was 0.79 and the optimal cutoff value -6.2% for a sensitivity of 71% and a specificity of 89% in predicting arrhythmic events. AUC for QTc was 0.32 yielding a sensitivity and specificity of, respectively, 49% and 65% to predict arrhythmias and AUC for EF was 0.51 yielding a sensitivity and specificity of, respectively, 56% and 70%. Conclusions. Circumferential strain was the strongest predictor of spontaneous ventricular arrhythmias among other clinical and echocardiographic variables such as score index and LV function and volumes in patients with previous myocardial infarction scheduled for ICD therapy.