tbuckley/cabot-search huggingface dataset:
PS959 MVP COMBINED WITH FC AS LYMPHOCYTE‐DEPLETING CHEMOTHERAPY BEFORE CAR‐T TREATMENT CAN REDUCE THE INCIDENCE OF SEVERE CYTOKINE RELEASE SYNDROME FOR R/R ALL PATIENTS WITH HIGH TUMOUR BURDEN
Authors: X. Tang, Q. Liu, Z. Li, H. Dai, J. Yin, X. Tian, S. Xue, Y. Xu, X. Zhu, D. Wu
Journal: HemaSphere (2019)

Background: CAR‐T immunotherapy have shown remarkable promising results for relapsed/ refractory (R/R) acute lymphoblastic leukemia(ALL). However, the most common toxicity associated with CD19 CAR‐T treatment is Cytokine Release Syndrome(CRS) which can be a life threatening complication especially for high tumour burden ALL patients. How to reduce the incidence of severe CRS can be a great challenge for advanced high tumour patients. Aims: In order to evaluate the efficacy and safety of MVP+FC as lymphocyte‐depleting chemotherapy to reduce tumour burden before CAR‐T therapy. Methods: If patients’ blasts in bone marrow was more than 28%, the chemotherapy MVP(Mitoxantrone 10 mg/w once(d1)+ Vindesine 4 mg/w once(d1) + Dexamethasone 10 mg/d × 7d(d1‐d7) followed by FC(Fludarabine 30 mg/m 2 × 3d (d8‐ d10)+ cyclophosphamide 300 mg/m 2 × 3d(d8‐d10)) were performed. CD19 CAR‐T, CD22CAR‐T and CD19CD22 tandem CAR‐T were infused with dose escalation schedule: 10%&gt;‐ 40%&gt;‐ 60% (d13, d14, d15). Total dose of CAR‐T for infusion was 5–10 × 10 6 /kg. Results: 16 patients were enrolled in this study with median age of 24 (6–56) years old. 11 patients were relapse post multiple chemotherapies. Another 5 patients were relapse post allo‐HSCT including T315I and TP53 mutation patients. The median blasts in BM before and after MVP treatment were 56% (28–89%) and 34%(0–85%). Furthermore, the median blasts in BM after MVP+FC treatment were 6%(0–60.5%). Overall response of CAR‐T were 93.75% with hematological remission 93.75% and molecular remission 63.75%. Only 4 patients experienced 3 grade CRS and other patients just had 1–2 grade of CRS. Only one presented sepsis. No one experienced neurotoxicity. Treatment related mortality was 0. With the median follow up of 9(1–26)months, 6 and 12 months leukemia free survival were 56.9% and 40.6% respectively. Summary/Conclusion: MVP combined with FC was an effective and safety conditionning regimen before CAR‐T treatment with low incidence of severe CRS especially for high tumour burden ALL patients.
Time to put GPs first by investing in general practice
Authors: Michael Craig Watson, John Lloyd
Journal: BMJ (2019)

Iacobucci paints a bleak picture of working in general practice, particularly in deprived areas.1 But his assessment is supported by research and reports over several years emphasising the crisis.234 We know the GP workforce faces major challenges, but we disagree that these are insurmountable—urgent action is required. …
PB1945 EXPERIENCE OF THE ANDALUSIAN CHRONIC MYELOID LEUKEMIA GROUP (GALMC) IN THE DISCONTINUATION OF THE TYROSINE KINASE INHIBITOR TREATMENT OUTSIDE OF CLINICAL TRIALS
Authors: C. Alarcón‐Payer, J.M. Puerta Puerta, A. Jiménez Morales, M.J. Ramírez Sánchez, M.I. Montero Cuadrado, M.I. Mata Vázquez, C. Ferrer Chaves, M. Anguita Arance, J.A. Vera Goñi, M.J. García Pérez, Á. Mellado Gázquez, Y. Moatassim de la Torre, L. Hermosín Ramos, M. Jurado Chacón, P. López Garrido
Journal: HemaSphere (2019)

Background: Currently one of the most burning issues regarding the specific treatment of Chronic Myeloid Leukemia (CML) with Interleukin‐2‐inducible T‐cell kinases (ITKs) is whether in a percentage of patients who meet specific requirements treatment interruption could be attempted and maintain molecular relapse‐free survival without treatment restarting with the consequent reduction of side effects related to medication and the progressive increase in the quality of life of patients. Aims: To analyse molecular relapse‐free survival after suspension of Imatinib, Nilotinib or Dasatinib, which achieved and maintained a Molecular Response ≥ 4.5 log for at least 36 months. Methods: Multicenter prospective observational post‐authorization follow‐up study of patients with Chronic Phase Ph+ CML (CP‐CML). Inclusion criteria: minimum ITK treatment time of 5 years, no resistance to a previous ITK, no accelerated phase diagnosis or blast crisis and those who have achieved and maintained the Molecular Response ≥ 4.5 log for at least 36 months prior to treatment interruption. These patients were candidates for discontinuation of ITKs. Molecular monitoring of bcr‐abl oncogene levels was performed using the Real‐Time Reverse Polymerase Chain (RT‐PCR) technique with the GeneXpert automated system with a sensitivity of 5 log. Results: 71 patients with CP‐CML were discontinued. 51 discontinued Imatinib treatment, 7 discontinued dasatinib treatment and 12 discontinued Nilotinib treatment. The preliminary rates of Molecular Relapse Free Survival (MRFS) and Treatment Free Remission (TFR) are consistent with those obtained in the different clinical trials, and no progression to advanced stages of the disease has been reported. With a median follow‐up of 9 months, 78% remain without specific treatment with ITK for not having lost the major molecular response, (BCR ABL ≤ 0.1%) cut‐off point established in the study as a criterion for reintroduction of ITK treatment. Relapse occurred before 6 months of discontinued treatment with a median of 3 months. Summary/Conclusion: Discontinuation of treatment with ITKs translates into clinical benefit for patients with CP‐CML, as it would reduce treatment‐related side effects and improve quality of life.
Abstract 10229: Increase the Predictive Capacity of Coronary Risk With a Genetic Score
Authors: Andreia Pereira, Isabel Mendonca, Susana Gomes, Ricardo Rodrigues, Micaela Neto, Ana C Sousa, Rui Ferreira, Ana I Freitas, Sonia Freitas, Roberto Palma dos Reis
Journal: Circulation (2015)

Introduction: Genes associated with coronary artery disease (CAD) and traditional cardiovascular risk factors (TCRF) present a limited individual predictive value. It is expected that the inclusion in global scores may increase the predictive ability. In genetic terms, there are no validated risk scores to predict the occurrence of cardiovascular disease or its complications. Hypothesis: Evaluate the ability of a multifactorial genetic risk score (GRS) be able to add predictive power, for the development of CAD, to the model developed only with TCRF. Methods: A case-control study was performed with 1321 consecutive coronary patients (mean age 53.4±8.1 years, 78.8% male) and 1148 controls selected to be similar to cases in terms of gender and age. TCRF were evaluated according to the International criteria. The genetic variants were analyzed with specific primers and the GRS was determined in the entire population, based on 29 genetic polymorphisms previously associated with atherosclerotic disease in general and, in particular, with CAD. A multiplicative model was then used based on risk multiplication (odds ratio - OR) of each genotype of the 29 studied genes. Subsequently, a multivariate analysis was done with the TCRF only or the TCRF with the GRS and a ROC curve was constructed for both situations. Pairwise comparison of the two ROC Curve was done by the DeLong test. Results: After multivariate analysis, the GRS was found to be an independent predictor for CAD (OR=2.1; CI: 1.7-2.5; p&lt;0.0001). The AUC increased from 0.71 to 0.74 after the inclusion of GRS to the TCRF in the multivariate analysis and this increase was highly significant (p&lt;0.0001) (Fig.). Conclusions: In our population, the multiplicative GRS was an independent predictor for CAD. When analyzed together with TCRF, it adds predictive value. Its usefulness, in clinical practice, may be directed to the intermediate risk group, in which a possible risk reclassification can have different therapeutic measures.
Abstract 17542: Novel Role of AMP-Activated Protein Kinase (AMPK) in Regulating Atrial Transcription Factors and Coordinating Channel Expression
Authors: Kevin N Su, Fadi Akar, Joseph G Akar, Lawrence H Young
Journal: Circulation (2017)

Introduction: Alterations in metabolic signaling may impact atrial remodeling and predispose to atrial fibrillation (AF). AMPK activation is altered in human AF, and global cardiac deletion of AMPK...
SAT0064 EXPANSION OF CD16+ MONOCYTE SUBSETS AND ACE EXPRESSION ARE ASSOCIATED WITH ARTERIAL THICKENING AND VASCULAR FUNCTION IN VERY EARLY RHEUMATOID ARTHRITIS
Authors: Javier Rodríguez-Carrio, Mercedes Alperi-López, Patricia López, Ángel Pérez-Álvarez, Lorena Benavente, Francisco Javier Ballina-García, Ana Suárez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> monocytes are largely recognized as drivers of the atherosclerosis development, the leading determinant of cardiovascular (CV) morbidity in rheumatoid arthritis (RA). Far from being a unique population, functionally and phenotypically subpopulations can be distinguished, although their relevance to CV disease is uncertain. Recently, the expression of angiotensin-converting enzyme (ACE) expression has been described, with some heterogeneity being observed across monocyte subsets. However, although previously linked to blood pressure control, the significance of ACE expression on monocytes remains obscure. <h3>Objectives</h3> to evaluate whether monocyte subsets and ACE expression were associated with surrogates of CV subclinical disease in very early RA patients. <h3>Methods</h3> patients were recruited upon early referral to the rheumatology department. All patients were untreated at the time of sampling. The frequency of classical (CD14+CD16-), intermediate (CD14+CD16+) and non-classical (CD14lowCD16+) monocyte subpopulations and ACE expression were assessed by flow cytometry in peripheral blood. Plaque occurrence, cIMT and stiffness parameters were analyzed by Doppler ultrasound in internal carotid, middle cerebral and basilar arteries. <h3>Results</h3> 53 patients were recruited, 47 fulfilling 2010 ACR/EULAR classification criteria for RA (36 women, 26 FR+ and 26 ACPA+) and 6 fulfilling criteria for Clinically Suspect Arthralgia (CSA) (6 women, 3 RF+ and 2 ACPA+). Non-classical and intermediate monocytes were positively associated with cIMT (r=0.413, p=0.005 and r=0.353, p=0.018, respectively), as well as with pulsatility (r=0.332, p=0.026 and r=0.323, p=0.030) and resistivity indices (r=0.286, p=0.050 and r=0.277, p=0.045) at the left internal carotid artery. Expansion of CD16+ monocytes was not associated with disease activity, measured as DAS28 or SDAI (all p&gt;0.050), but frequency of intermediate monocytes paralleled duration of the symptoms (r=0.324, p=0.020). ACE expression was higher in CD16+ monocyte subsets than in their classical counterparts. ACE expression was not associated with blood pressure, individual traditional CV risk factors, body mass index nor with mSCORE (all p&gt;0.050). ACE expression on intermediate and classical monocytes was correlated with cIMT (r=0.382, p=0.010 and r=0.349, p=0.019, respectively). Moreover, ACE expression in all monocyte subsets was strongly associated with resistivity and pulsatility indices at the internal carotid artery (all p&lt;0.010). <h3>Conclusion</h3> the expansion of CD16+ monocyte subsets and the ACE expression are associated with arterial wall thickening and vascular functionality in treatment-naïve RA patients, hence suggesting a very early role for monocyte traits in this scenario. None declared
SP0088 HOW YOU KNOW IT IS SMART NOT TO SMOKE LIKE A CHIMNEY
Authors: Antonio Naranjo
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Smoking is associated with a higher prevalence of many diseases. When a health professional is well informed of the risks of smoking in rheumatic diseases, the advice given to the patient about quitting smoking could be more effective. It is known that smokers in the general population have an increased frequency of elevated rheumatoid factor (RF). Since 1987, we have known that cigarette smoking is a risk factor for rheumatoid arthritis (RA), especially in men with RF-positive who are heavy smokers. Later, it could be verified that cigarette smoking is implicated in the pathogenesis of RA particularly when associated with antibodies, cyclic citrullinated peptides (ACPA) and the shared epitope. Smoking increases the risk of both subsets of RA with a more pronounced influence on the risk of ACPA positive RA. The polyclonal immune response against modified antigens in patients with RA is not exclusively citrulline-specific, carbamylation of antigens like vimentin could be involved in the pathogenesis of the disease. Thus, smoking is a risk factor for breaking tolerance to multiple autoantigens in RA. In RA patients, cigarette smoking correlated with an increased risk of joint erosions, extra-articular manifestations and cardiovascular disease, in addition to the established effects of longstanding disease activity on the risk of myocardial infarction and stroke. Systemic lupus erythematosus (SLE) is also associated with smoking. A strong and specific connection of current smoking and &gt;10 pack-years of smoking with dsDNA+ SLE has been observed. In patients with SLE, smoking exposure has deleterious effects on lupus morbidity and is related to cumulative chronic damage. In mucocutaneous SLE, smoking have a negative impact on the efficacy of belimumab and a 2-fold decrease in the proportion of patients achieving cutaneous improvement with antimalarials. Published data indicate that smoking has a dose-dependent impact on structural damage progression in Ankylosing Spondylitis. In a large UK cohort, smoking was positively associated with the risk of psoriatic arthritis in the general population, but negatively associated among patients with psoriasis. In addition, smokers with psoriatic arthritis had a poorer response to TNFi"s compared to non-smokers. Regarding osteoporosis, smoking has been identified as a predictor of ten-year fracture risk in men and women, largely independent of the densitometric results. This finding has eventually lead to incorporation of this risk factor into FRAX®. The impact of smoking on bone status is mainly associated with the number of smoking years. In a few reports, it has been observed an association between smoking and carpal tunnel syndrome and inflammatory bowel disease. Finally, current smoking in patients with fibromyalgia is associated with greater pain, possibly as a function of depression. <h3>Disclosure of Interests:</h3> Antonio Naranjo Grant/research support from: Amgen, Consultant for: UCB, Speakers bureau: Amgen, UCB
A Woman With Multiparity Experiencing Chest Pain in Her Early 60s
Authors: Prakriti Gaba, Sahil A. Parikh, Michael B. Collins
Journal: JAMA Cardiology (2019)

A woman in her early 60s with a history of hypertension, dyslipidemia, multiparity, and coronary angiogram 1 year prior presents with sudden onset of severe chest pain not alleviated by changing position and radiating to the left arm with concomitant nausea and diaphoresis. What would you do next?
Abstract 19331: The Adrenal Vein Sampling International Study-2: Results in 1636 Primary Aldosteronism Patients
Authors: Gian P Rossi, Giacomo Rossitto, Paul E Vanderriele, Laurence Amar, Martin Reincke
Journal: Circulation (2015)

Background: Guidelines recommend Adrenal vein sampling (AVS) for the subtyping of primary aldosteronism (PA), the most common curable cause of arterial hypertension. How this recommendation is implemented in practice remains uncertain. Hence, in 2011 upon completion of the AVIS-1 Study we launched the AVIS-2 Study to determine: 1) the success rate of the AVS studies performed in major referral centers worldwide; 2) the impact of AVS results on the clinical decision making and on outcome of the patients at follow-up. Methods: All the AVIS-1 Study centers were invited to join the AVIS-2 by entering the individual PA patients AVS and clinical data in an ad hoc predefined web-based database. Data were analyzed according to use of cosyntropin unstimulated or -stimulated protocols. Results and Conclusions: Sixteen centers in Europe, North America and Asia recruited a total of 1656 PA patients (age 50 years ± 10; 39.5% females). The AVS success rate was examined as a function of the Selectivity Index (SI) cutoffs. Among unstimulated AVS (n = 1307), the rate of bilaterally selective tests fell from 86% to 53% and 45% with cut off values of 1.10, 2.00 and 3.00, respectively; for adrenalectomized patients (49% of total), the decision was based on bilateral selective AVS in 71%, 56% and 43% of cases, respectively. Among cosyntropin-stimulated AVS, 85%, 80%, 76% and 72% were bilaterally selective, with a cut-off of 2.00, 3.00, 4.00, and 5.00, respectively; the rate of adrenalectomy based on AVS data fell from 47% with a cut-off = 2.00 to 40% with a cut-off = 5.00. The lateralization index value did not improve by comparing those with SI bilaterally &gt; 2.0 (baseline) and &gt; 5.0 after cosyntropin (3.8 [median, 1.6-12.7 IQR] vs 3.7 [1.5-14.0]). Conclusions: Only a minority of PA submitted to AVS have bilaterally selective studies if high cutoffs for the SI are used. Moreover, in even less patients AVS eventually led to adrenalectomy. These intriguing results from the largest dataset of AVS studies provide compelling evidence for the need of further prospective studies in this field.
SAT0230 GIANT CELL ARTERITIS WITH INTRACRANIAL VASCULITIS: A CASE SERIES
Authors: Alexander Hawkins, Catalina Sanchez Alvarez, Matthew Koster, Cynthia S. Crowson, Kenneth J. Warrington
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Giant cell arteritis (GCA) is a large vessel vasculitis that primarily affects the aorta and its branches. Extracranial branches of the carotid artery are frequently affected; however, intracranial involvement in GCA is rare [1]. <h3>Objectives</h3> To determine the clinical features and outcome of patients with intracranial giant cell arteritis (IC-GCA). <h3>Methods</h3> A retrospective medical record review was performed to identify all patients with IC-GCA from 1/1996 through 5/2018. Demographic, clinical, laboratory, radiographic, and treatment data at baseline and subsequent follow-up visits were collected. Data was summarized using descriptive statistics. <h3>Results</h3> The study cohort included 9 patients with IC-GCA (78% male, mean [±SD] age 72.1 [±7.9] years). 8 of 9 patients had positive temporal artery biopsies. One patient with negative biopsy had evidence of large-vessel GCA on thoracic CT angiography. The mean time from onset of GCA to intracranial involvement was 17 months (±38). All patients had neurologic symptoms, 33% (n:3) had a stroke and 22% (n:2) had a transient ischemic attack. IC-GCA was diagnosed by cranial imaging in 8 patients and by autopsy in one. Cranial imaging modalities used included magnetic resonance angiography (n=8), CT angiography (n=2) and cerebral angiography (n=2). Intracranial vasculitis most commonly affected the internal carotid artery 78% (N=7) followed by the, vertebral artery 56% (n=5), posterior cerebral artery 56% (n=5), middle cerebral artery 44% (n=4), anterior cerebral artery 33% (n=3) and posterior inferior cerebral artery 11% (n=1). Stenosis was present in 89%, occlusion in 33%, dilatation in 11%, and wall thickening in 11%. All patients received glucocorticoids. For treatment of intracranial disease, additional agents included: cyclophosphamide (67%), Tocilizumab (22%). Despite treatment, outcomes for patients with IC-GCA were poor. Five of nine patients died during a mean length of follow-up of 2.4 months. <h3>Conclusion</h3> Although rare, IC-GCA is associated with significant morbidity and mortality. It occurs predominantly in men, presenting with ischemic cerebrovascular events. Current treatment strategies appear to be of limited efficacy for IC-GCA. <h3>Reference</h3> [1] Salvarani C, Giannini C, Miller DV, Hunder G. Giant cell arteritis: Involvement of intracranial arteries. Arthritis Rheum. 2006;55(6):985-9. <h3>Disclosure of Interests</h3> None declared
THU0461 IDENTIFICATION OF DEFINITIONS OF POOR OUTCOME AFTER TREATMENT OF KNEE OSTEOARTHRITIS: A LITERATURE REVIEW
Authors: Malou te Molder, J.M.H. Smolders, Petra Heesterbeek, Cornelia van den Ende
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Total knee replacement (TKR) is considered an effective intervention of the treatment of advanced knee osteoarthritis (OA) (Kellgren &amp; Lawrence &gt;2). However, a significant proportion of patients could be considered as a poor-responder to TKR (i.e. no or little improvement) in terms of chronic knee pain, functional disability, poor quality of life (QoL), and dissatisfaction after TKR. Both in research and in clinical practice it is challenging to identify those patients with an unfavourable course after TKR. It is difficult though to quantify the proportion of patients with poor response to TKR, as different definitions of, and perspectives (clinician's and patient's) on failure are being used. <h3>Objectives</h3> The aim of this study was to review the literature and summarize definitions of poor response to TKR. <h3>Methods</h3> A systematic search up to 2016 was performed to identify and review previously used definitions of poor response to primary TKR in the literature. Studies were included if dichotomous definitions of outcome after primary TKR were used, if a prospective design was used and in English full text available. The type, amount and combination of domains (i.e. pain and physical function), outcome measures, type of responses (absolute/relative, change/cut-off), values and moments of follow-up used in definitions were summarized. <h3>Results</h3> A total of 44 different dichotomous definitions of poor response to TKR, were extracted from 1849 initially identified studies. 34 definitions incorporated one domain, six definitions comprised two domains and four definitions comprised three domains. Eight different domains were used in identified definitions: pain, physical function (mobility), physical functioning (body), QoL, satisfaction, anxiety, depression and patient global assessment. Patient satisfaction was most commonly used (n=10) as single domain with a wide variation in wording of questions and answering categories. The absolute cut-off value was the most common type of response, with large variety in value and timing of follow-up. Table 1 shows one definition for each combination of domains. <h3>Conclusion</h3> Our review shows that definitions for poor response to TKR are ambiguous. Our findings stress the need for an unambiguous definition of poor response to draw conclusions about the prevalence of poor-responders to TKR across hospitals and countries, and to identify patients at risk. <h3><b>Disclosure of Interests:</b>&nbsp;</h3> None declared