tbuckley/cabot-search huggingface dataset:
Treat-to-target study for improved outcome in polyarticular juvenile idiopathic arthritis
Authors: Ariane Klein, Kirsten Minden, Anton Hospach, Ivan Foeldvari, Frank Weller-Heinemann, Ralf Trauzeddel, Hans-Iko Huppertz, Gerd Horneff
Journal: Annals of the Rheumatic Diseases (2020)

Background Juvenile idiopathic arthritis is one of the most prevalent chronic inflammatory diseases in children. Evidence suggests that early effective treatment minimises the burden of disease during childhood and in further life. We hypothesise that a guided treat-to-target (T2T) approach is superior to routine care in polyarticular juvenile idiopathic arthritis (pJIA) in terms of reaching a clinical remission after 12 months of treatment. Methods Patients with early and active pJIA were enrolled. Targets for treatment were the following: Recognisable Juvenile Arthritis Disease Activity Score (JADAS) improvement after 3 months, acceptable disease at 6 months, minimal disease activity at 9 months and as primary endpoint remission after 12 months. Initially, patients received methotrexate. Failure to meet a defined target required treatment modification at the specified intervals. The choice of biologics was not influenced by the protocol. Finally, T2T patients were compared with a cohort of matched controls of patients with pJIA with unguided therapy documented by BIKER. Results Sixty-three patients were enrolled. Treatment targets after 3/6/9 and 12 months were reached by 73%/75%/77% and 48% of patients. Fifty-four patients completed the protocol. Compared with matched controls, on T2T guidance significantly more patients reached JADAS remission (48% vs 32%; OR 1.96 (1.1–3.7); p=0.033) and JADAS minimal disease activity (JADAS-MDA) (76% vs 59%; OR 2.2 (1.1–4.4); p=0.028). Patients from the T2T cohort received a biologic significantly more frequent (50% vs 9% after 12 months; OR 9.8 (4.6–20.8); p&lt;0.0001). Conclusion The T2T concept was feasible and superior to unguided treatment. High rates of patients reached JADAS-MDA and JADA remission after 12 months. Approximately half of the patients achieved their therapy goals without a biologic.
PD-1 <sup>hi</sup> CD8 <sup>+</sup> resident memory T cells balance immunity and fibrotic sequelae
Authors: Zheng Wang, Shaohua Wang, Nick P. Goplen, Chaofan Li, In Su Cheon, Qigang Dai, Su Huang, Jinjun Shan, Chaoyu Ma, Zhenqing Ye, Min Xiang, Andrew H. Limper, Eva-Carmona Porquera, Jacob E. Kohlmeier, Mark H. Kaplan, Nu Zhang, Aaron J. Johnson, Robert Vassallo, Jie Sun
Journal: Science Immunology (2019)

Exhausted-like CD8 + resident memory T cells in the lung limit immune activation–driven fibrosis.
Association between ankylosing spondylitis and venous thromboembolism
Authors: Shih-Wei Lai
Journal: Annals of the Rheumatic Diseases (2019)

Association between ankylosing spondylitis and venous thromboembolismAnkylosing spondylitis is a type of arthritis that commonly affects the joints of the spine.The relationship between ankylosing spondylitis and other diseases has been extensively explored. 1 2Recently, a cohort study in Canada conducted by Aviña-Zubieta et al published in Annals of Rheumatic Diseases disclosed that people with ankylosing spondylitis were at higher risk of venous thromboembolism compared with people without ankylosing spondylitis (HR 1.53, 95% CI 1.16 to 2.01). 3Aviña-Zubieta et al's study is well performed and is informative to the researchers.Some of my views are shared with the readers as follows.First, the overall incidence of venous thromboembolism was 2.03-fold higher in people with ankylosing spondylitis than in those people without ankylosing spondylitis in Aviña-Zubieta et al's study (1.56 vs 0.77 per 1000 person-years). 3 The attributable risk associated with ankylosing spondylitis was 0.79 per 1000 person-years; that is, removal of ankylosing spondylitis can diminish approximately eight cases of venous thromboembolism per 10 000 person-years of follow-up.Second, another cohort study in the Republic of Korea disclosed that the overall incidence of new onset of atrial fibrillation was 1.54-fold higher in people with ankylosing spondylitis than in those without ankylosing spondylitis (2.32 vs 1.51 per 1000 person-years). 4 The attributable risk associated with ankylosing spondylitis was 0.81 per 1000 person-years; that is, removal of ankylosing spondylitis can diminish approximately eight cases of new onset of atrial fibrillation per 10 000 person-years of follow-up.According to the above measurement, ankylosing spondylitis seems to have a similar impact on the risks of venous thromboembolism and new onset of atrial fibrillation.Third, the evidence disclosed that people with ankylosing spondylitis who underwent tumour necrosis factor inhibitor therapy had a higher risk of new onset of atrial fibrillation (HR 1.60, 95% CI 1.02 to 2.39), 4 but Aviña-Zubieta et al's study did not disclose such data.I agree with Aviña-Zubieta et al's comments that future investigation is needed to clarify the effects of ankylosing spondylitis treatment on the risk of venous thromboembolism.Fourth, ankylosing spondylitis cannot be prevented and is less likely to be eradicated.Currently, the guidelines for stroke prevention in people with atrial fibrillation have been established. 5In addition, it is important to recognise people who have risk factors for venous thromboembolism, including those having cancer, major surgery, major trauma-like fractures and long-term immobilisation. 6Clinicians who participate in the long-time care of people with ankylosing spondylitis should take into consideration the above risk factors when considering the risk of venous thromboembolism.If necessary, pharmacological prophylaxis for venous thromboembolism should be initiated in these highrisk people.
PB1999 SECOND MALIGNANCIES IN LYMPHOMA SURVIVORS: A SINGLE CENTER EXPERIENCE
Authors: M.P. Simula, S. Massidda, A.M. Mamusa, G. La Nasa
Journal: HemaSphere (2019)

Background: Advances in the treatment of both Hodgkin's (HL) and non Hodgkin's Lymphomas (NHL) have resulted in an increasing number of long term survivors free of disease. However this patient's population is at high risk of developing late therapy related complications that can negatively affect long term survival and quality of life. Aims: Methods: In our institution the HL and aggressive NHL long term survivors are followed up in a dedicated clinic since September 2014. Here we report an update of data on second malignancies diagnosed after lymphoma resolution. We have collected retrospective data on second tumours in 587 consecutive lymphoma survivors. Results: We have analyzed data regarding 587 patients coming in our clinic from 15 September 2014 to 21 February 2019, 284 have been successfully treated for HL and 303 for NHL. Two hundred eighty six were females, 301 males; median of age at lymphoma diagnosis was 28 years for HL (range 7-84) and 46 years for NHL (range 14-83). Ninety six patients (16%) experienced a second cancer, 12 and 1 of them had respectively 2 and 3 neoplasms so we documented 110 second tumours. They were: 35 skin (32%) and 75 non cutaneous cancers (68%). Four of the cutaneous neoplasm were melanomas. The non skin neoplasm were: 21 breast, 12 gastroenteric, 10 thyroid, 8 prostatic, 2 lung, 9 bladder, 1 renal, 1 tongue, 1 testis, 2 ovarian,2 uterine, 1 laringeal, 1 meningioma, 1 myelodysplastic syndrome (MDS) with excess blasts, 1 melanoma urinary tract, 1 cutaneous marginal NHL and 1 cutaneous appendages malignant cancers. Fourteen of these tumours (3 colon, 6 breast, 2 thyroid,1 prostatic, 1 MDS and 1 ovarian) have been suspected during our annual visit or diagnosed with our program of early diagnosis of second cancers and thyroid dysfunctions. The median of time between the end of lymphoma therapy and diagnosis of second malignancy was 18 years (range 4-47), the median age of second cancer was 58 years (range 24-83). Regarding the previous therapies: 32 patients had received radiotherapies in the site of secondary tumours (33%) and 21 had more than 1 line of therapy (22%). Moreover we have documented relapse of their original lymphoma in 6 patients (1 HL and 5 NHL). Summary/Conclusion: In our Department we described a significant number of cases of second neoplasms in the lymphoma survivors population: some of these were detected by tests done for early diagnosis of late complications. These results outline the importance of continuous follow up and risk adapted plan for early diagnosis of cancers in this setting of patients that would be encouraged by both hematologist and general practitioners.
PB2134 THE IMPACT OF COMORBIDITY ON OVERALL SURVIVAL IN MULTIPLE MYELOMA
Authors: E. Mikhailov, G. Salogub, I. Osipov, A. Melikhova, S. Bessmeltsev, N. Shnalieva, V. Bezrukikh
Journal: HemaSphere (2019)

Background: The median age at diagnosis of multiple myeloma (MM) is 66 years. Comorbidity is registered in 40% cases. This can have an impact on overall survival, frequency of complications and duration of hospitalization Aims: The aim of this study was to analyze the impact of comorbidity on overall survival in patients with MM. Methods The study included 156 patients with newly diagnosed MM. For each patient a comorbidity score was calculated by using Charlson Comorbidity index (CCI), Cumulative Illness Rating Scale (CIRS), Freiburg Comorbidity index (FCI), Kaplan‐Feinstein index (KFI), Satariano Index (SI). The patients with CCI &gt; 2, CIRS &gt; 5, SI &gt; 0, FCI &gt; 1, KFI &gt; 2 score were defined as high risk group, others were considered as the group of standard risk. Primary endpoint was overall survival. The survival analysis including creation of the Kaplan‐Meier survival curves was performed with use of IBM SPSS Statistics 21 The hypothesis was verificated by log‐rank test. Results: CIRS, KFI and SI did not show statistically significant difference in all groups. OS was significantly lower in high risk group estimated by CCI (96 vs 65 months, log rank p &lt; 0.05). However, age is also included in calculating of this comorbidity index. Due to median age at diagnosis (more than 60 years) the majority of patients is classified as high risk group CCI based only on age. Karnofsky performance status, glomerular filtration rate &lt;30 ml/min and pulmonary diseases were used for estimation by FCI. OS in high risk group was 43 months in comparison to 86 months in group of standard risk (p &lt; 0.05). 2 patients with FCI = 3 had extremely low OS (less than 2 months). Summary/Conclusion: Comorbidity has an impact on OS in patients with MM. According to our analysis, the most valid prognostic instruments turned out to be FCI and CCI. These indices can be used to predict clinical outcomes. image
PF292 LOW‐DOSE CYTARABINE WITH OR WITHOUT GLASDEGIB IN NEWLY DIAGNOSED PATIENTS WITH ACUTE MYELOID LEUKEMIA: LONG‐TERM ANALYSIS OF A PHASE 2 RANDOMIZED TRIAL
Authors: C. Papayannidis, B.D. Smith, M. Heuser, P. Montesinos, M.A. Sekeres, A. Oriol, G. Schiller, A. Candoni, C. Jamieson, C. Hoang, W.W. Ma, M. Zeremski, A. O’Connell, G. Chan, J. Cortes
Journal: HemaSphere (2019)

Background: Glasdegib is a potent, selective, oral inhibitor of the Hedgehog signaling pathway, approved in the US – in combination with low‐dose cytarabine (LDAC) – for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients unable to receive intensive chemotherapy due to comorbidities or age (75 years or older). Aims: To evaluate long‐term efficacy and safety of LDAC with or without glasdegib in patients newly diagnosed with AML unable to receive intensive chemotherapy due to comorbidities or age. Methods: In this follow‐up analysis from the phase 2 BRIGHT AML trial (NCT01546038), newly diagnosed patients with AML ineligible for intensive chemotherapy were randomized 2:1 to glasdegib + LDAC or LDAC alone (study design was reported previously: Cortes et al., Leukemia 2018). This long‐term analysis evaluated efficacy and safety after approximately 20 months of additional follow‐up. Results: As of October 11, 2018, 116 patients were assigned to treatment with glasdegib + LDAC (n = 78) or LDAC alone (n = 38). The median follow‐up time for glasdegib + LDAC and LDAC alone was 43.4 and 42.0 months, respectively. The median overall survival was higher with glasdegib + LDAC vs LDAC alone (Table). Improvement in overall survival was consistent across the prespecified subgroups. The main cause of death in both arms was disease progression (both during study and follow‐up). The incidence of adverse events (AEs) and serious AEs on glasdegib was generally lower long term (after 90 days) than short term (during the first 90 days) (83.7% and 51.2% vs 98.7% and 65.3%, respectively). Summary/Conclusion: Addition of glasdegib to LDAC vs LDAC alone continued to demonstrate improved overall survival in patients with AML in this analysis; improvement was consistent across groups stratified by cytogenetic risk. Long‐term follow‐up confirmed that treatment with glasdegib was associated with an acceptable safety profile. image
Daily performance status-based target physical activity of early rehabilitation for hematologic malignancy patients after allogeneic hematopoietic stem cell transplantation.
Authors: Junichiro Inoue, Rei Ono, Atsuo Okamura, Naomi Kiyota, Daisuke Makiura, Miyuki Kashiwa, Yasushi Miura, Masahiro Kurosaka, Ryuichi Saura
Journal: Journal of Clinical Oncology (2012)

e17020 Background: For hematologic malignancy patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT), the maintenance and/or increase of physical activity (PA) after allo-SCT possibly lead to favorable outcomes. However, it remains to be clarified how much intensity of daily rehabilitation should be prescribed. The aim of this study was to evaluate target PA according to daily performance status (PS) in these patients. Methods: Twenty-seven allo-SCT patients were enrolled in this study (13 males, 14 females, the median age; 47 years). Written informed consent was obtained from all patients. Donor types were bone marrow (n = 12), peripheral blood stem cell (n = 6), and single-unit cord blood (n = 9). All patients received our established exercise program supervised by physical therapists just after neutrophil engraftment in a bioclean room. As an alternative value of PA, daily steps (DS) were measured by using a uniaxial pedometer (Lifecorder EX, Suzuken Co. Ltd., Nagoya, Japan), and Eastern Cooperative Oncology Group PS after allo-SCT were also assessed daily for each individual. The data were statistically analyzed by using ANOVA and Scheff 's tests. Results: A correlation between DS and PS was observed. After the early physical intervention, the mean DS of patients with PS 1, 2, or 3 in a bioclean room were 2,411 ± 1,068, 1,205 ± 572, and 597 ± 216 steps/day, respectively. DS significantly declined by about 50% according to one grade deterioration of PS. Conclusions: As the target PA correlated with PS seems to be existence, we should plan daily activity in a bioclean room to keep more than above-mentioned mean DS according to daily PS for allo-SCT patients.
OP0036 EROSIONS ARE THE MOST OFTEN REPORTED STRUCTURAL LESION ON MRI OF THE SACROILIAC JOINTS IN AXSPA PATIENTS WITH IBP
Authors: Manouk de Hooge, Ann-Sophie De Craemer, Thomas Renson, Philippe Carron, Liselotte Deroo, Dirk Elewaut, Filip van den Bosch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> HLA-B27 and sacroiliitis on MRI form the basis of the Assessment of SpondyloArthritis international Society (ASAS) axial spondyloarthritis (axSpA) classification criteria. In addition, while not an entry criterion of the classification criteria, inflammatory back pain (IBP) is fundamental in the axSpA diagnostic process and it is endorsed as referral parameter in primary care. Besides inflammation on MRI, which is the hallmark of axSpA, there is still debate on the value of structural MRI lesions in these patients. <h3>Objectives</h3> To report on MRI of the sacroiliac joints (MRI-SIJ) findings in newly diagnosed axSpA patients stratified for the presence of IBP and HLA-B27 positivity. <h3>Methods</h3> Newly diagnosed and anti-TNF naive axSpA patients of an ongoing Belgian (Be-Giant) cohort were included in this study. MRI-SIJ assessment was performed independently by 3 calibrated readers according to an adapted method of the Spondyloarthritis Research Consortium of Canada score, evaluating erosions, fatty lesions, sclerosis and ankylosis (T1-weighted and STIR images viewed simultaneously). Also, the ASAS definition of a positive MRI-SIJ was evaluated. MRI sum scores were calculated as 2 out of 3 (median) reader scores. <h3>Results</h3> In 138 axSpA patients MRI-SIJ data was available; 68 (49.3%) patients were male, 104 (75.4%) HLA-B27 positive and 131 (94.9%) patients fulfilled the IBP criteria according to ASAS. In the IBP+ patient groups, a large amount of structural MRI lesions were seen. In these groups, erosions are most frequently reported, with an average extent of 5 erosions. IBP- patients were rarely seen in this cohort and erosions and fatty lesions were the only structural lesions observed in these patients, with a much lower extent compared to the IBP+ patients (see table 1). There were no axSpA patients with negative MRI-SIJ, negative HLA-B27 and without IBP. <h3>Conclusion</h3> In this cohort of newly diagnosed anti-TNF naïve axSpA patients, structural lesions are frequently and with a high extent seen in IBP+ patients. Only in the IBP+ axSpA patients the previously reported threshold for axSpA patients of ≥3 erosions and ≥3 fatty lesions is maintained, as IBP- axSpA patients have far fewer lesions. IBP seems to be an indicator for the presence of structural MRI-SI lesions in newly diagnosed axSpA patients. <h3>Disclosure of Interests</h3> Manouk de Hooge: None declared, Ann-Sophie De Craemer: None declared, Thomas Renson: None declared, Philippe Carron: None declared, Liselotte Deroo: None declared, Dirk Elewaut: None declared, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB.
THU0701-HPR “TO REGAIN ONE’S HEALTH” – PATIENTS’ PREFERENCES OF TREATMENT OUTCOMES IN EARLY RHEUMATOID ARTHRITIS – A QUALITATIVE STUDY
Authors: Ellen Landgren, Ann Bremander, Elisabet Lindqvist, Kristien Van der Elst, Ingrid Larsson
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatology care strives to identify and meet the needs of the patients, and to understand disease and treatment impact from the patients' perspective. A better understanding of patients' expectations from the treatment is needed to enable a patient centered approach in clinical practice and a shared-decision making as recommended in the EULAR treatment recommendations for rheumatoid arthritis (RA). Understanding of patients' expectations in the early stage of the RA disease may facilitate adherence to treatment, patient independence and prevent unmet needs in the future. <h3>Objectives</h3> To explore patients' preferred treatment outcomes in early rheumatoid arthritis (eRA). <h3>Methods</h3> A qualitative, explorative study. Individual interviews were conducted with 31 patients with eRA, defined as disease duration of ≤ 1 year and disease-modifying antirheumatic drugs (DMARDs) treatment for 3-6 months<sup>1</sup>. Interviews were analyzed using a constant comparison method according to the Qualitative Analysis Guide of Leuven (QUAGOL) and lasted in a core category and four related concepts. <h3>Results</h3> The patient-preferred treatment outcomes in eRA were described in the core category "to regain one's health" and the four related concepts: to experience external control of the disease, to experience independence, to regain identity and to experience joy in everyday life. The patients expected to experience external control of the disease by the given treatment to regain one's health. It was perceived as controlling the symptoms and as absence of disease. Independence was perceived as regaining former activity levels, experiencing autonomy and using active coping strategies. Patients wanted to regain identity through participation, empowerment and their self-image. Joy in everyday life was perceived as vitality and believing in the future. <h3>Conclusion</h3> Patients' preferred treatment outcomes in eRA were to regain one's health including both external and internal control. External control as disease control and independence as well as internal control as identity and joy in everyday life. The results from this study can assist healthcare professionals to better understand patients' preferred treatment outcomes early in the disease process and to tailor the interventions accordingly to improve long term treatment outcome. <h3>References</h3> [1] Van der Elst K, Bremander A, De Groef A, Larsson I, Mathijssen E, Vriezekolk J, Westhovens R, van Eijk-Hustings Y. (2019). European Qualitative research project on Patient-preferred outcomes in Early Rheumatoid Arthritis (EQPERA): rationale, design and methods of a multinational, multicenter, multilingual, longitudinal qualitative study. BMJ Open, accepted 181220 <h3>Disclosure of Interests</h3> None declared
Abstract 20080: Deletion Of B56α, a Regulatory Subunit of Protein Phosphatase 2A, is Associated With Improved Cardiac Performance
Authors: Dennis Glaser, Frank U Müller, Frank Stümpel, Peter Boknik, Uwe Kirchhefer
Journal: Circulation (2017)

Protein Phosphatase 2A (PP2A) is a major intracellular phosphatase that regulates myocardial excitation-contraction coupling. We have demonstrated that patients suffering from heart failure exhibit...