tbuckley/cabot-search huggingface dataset:
PB1938 PERSPECTIVE OF THE PATIENT WITH CML AND FAILURE TO TREATMENT WITH IMATINIB AT AN ENVIROMENT OF LIMITED RESOURCES.
Authors: K.L. Osorno‐Rodríguez, O.G. Cantú‐Rodriguez, J.P. Gómez‐Villarreal, M.R. Ríos‐Rodelo, B. Lafarga‐Amao, J.Á. Hawing‐Zárate, L.E. Villalobos‐Gutiérrez, D. Gómez‐Almaguer
Journal: HemaSphere (2019)

Background: Chronic myeloid leukemia (CML) is a haematological malignancy caused by translocation t(9;22). The advent of imatinib meant a substantial improvement in the survival of patients compared to older therapeutic options such as busulfan, hidroxyurea and alfa interferon. The presence of resistance or failure to treatment to imatinib requires second‐line drugs such as dasatinib or nilotinib, however its correct access to the population with limited resources is restricted mainly by their costs. Aims: Evaluate the behavior and outcome of patients with a loss of response to imatinib who do not have access opportunately to a second of third line tyrosine kinase inhibitor (TKI). Methods: It's a retrospective, observational, longitudinal study of two medical centers. We collected all the demographic data and the laboratory values of the patients older than 18 years with a diagnosis of CML with failure to imatinib as well as its clinical evolution and the therapeutic measures taken. Results: We obtained the data from 139 patients attended between 2007 and 2018. The median age was 48 years (38‐59) in which 51.8% were males. 64.7% (90) has access to second‐line TKI in a timely manner with a median time between the loss of response and the start of the second‐line therapy of 3 months. In the group without timely manner access, in 57.1% of the patients, the imatinib dose was increased, 14.3% continued imatinib at the same dose due to preservation of hematological response, 22.4% had Ara‐C and/or alfa interferon added to them therapeutic scheme and 18.3% entered to a clinical trial after which 81.2% continued in molecular failure. Of these patients, 44.9% had late access to a second‐line TKI with a median time of 29 months (15‐53), 10.8% developed blastic crises, and 10.2% underwent an allogeneic bone marrowa transplantion, of this subgroup currently 6.1% are in hematological failure and 26.5% are in molecular failure. Of the group with timely access, 39% went to a third‐line TKI due to los of response to treatment, 6.7% developed blastic crises and 4.4% underwent allogeneic bone marrow transplantation, of this group currently 2.2% are in hematological failure and 10% are in molecular failure. Summary/Conclusion: In a population of limited resources such as ours, due to the lack of timely access to second‐line TKI as estabished by international guidelines, other options such as haematopoietic cell transplantation should be considered, in order to limit the risks that delaying the access to a second‐line TKI can cause.
Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis
Authors: Christina Morse, Tracy Tabib, John Sembrat, Kristina L. Buschur, Humberto Trejo Bittar, Eleanor Valenzi, Yale Jiang, Daniel J. Kass, Kevin Gibson, Wei Chen, Ana Mora, Panayiotis V. Benos, Mauricio Rojas, Robert Lafyatis
Journal: European Respiratory Journal (2019)

A comprehensive understanding of the changes in gene expression in cell types involved in idiopathic pulmonary fibrosis (IPF) will shed light on the mechanisms underlying the loss of alveolar epithelial cells and development of honeycomb cysts and fibroblastic foci. We sought to understand changes in IPF lung cell transcriptomes and gain insight into innate immune aspects of pathogenesis. We investigated IPF pathogenesis using single-cell RNA-sequencing of fresh lung explants, comparing human IPF fibrotic lower lobes reflecting late disease, upper lobes reflecting early disease and normal lungs. IPF lower lobes showed increased fibroblasts, and basal, ciliated, goblet and club cells, but decreased alveolar epithelial cells, and marked alterations in inflammatory cells. We found three discrete macrophage subpopulations in normal and fibrotic lungs, one expressing monocyte markers, one highly expressing FABP4 and INHBA (FABP4 hi ), and one highly expressing SPP1 and MERTK (SPP1 hi ). SPP1 hi macrophages in fibrotic lower lobes showed highly upregulated SPP1 and MERTK expression. Low-level local proliferation of SPP1 hi macrophages in normal lungs was strikingly increased in IPF lungs. Co-localisation and causal modelling supported the role for these highly proliferative SPP1 hi macrophages in activation of IPF myofibroblasts in lung fibrosis. These data suggest that SPP1 hi macrophages contribute importantly to lung fibrosis in IPF, and that therapeutic strategies targeting MERTK and macrophage proliferation may show promise for treatment of this disease.
Abstract 11615: Influence of Age and Gender on Marfan Phenotype: The NHLBI GenTAC Registry
Authors: Mary J Roman, Richard B Devereux, Liliana Preiss, Federico M Asch, Joseph E Bavaria, Kim A Eagle, Kathryn Holmes, Cheryl Maslen, Dianna M Milewicz, Shaine A Morris, Siddharth Prakash, Reed Pyeritz, William J Ravekes, Ralph V Shohet, Howard Song, Jonathan W Weinsaft
Journal: Circulation (2016)

Background: The influence of gender and age on phenotypic features of individuals with Marfan syndrome has not been systematically examined in a large cohort of both children and adults. Methods: We evaluated 789 Marfan patients enrolled in the NHLBI GenTAC Registry (53% male; mean age 31 [range: 1-86 years]). Females aged≥15 and males aged≥16 years were considered adults based on average age of skeletal maturity. Results: Children (n=183) and adults (n=606) (see Table) were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalences of aortic root dilatation and mitral prolapse. However, adults were more likely to have spontaneous pneumothorax, scoliosis, dural ectasia and striae. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood vs. adulthood (2 vs. 35% and 1 vs. 9%, respectively, both p&lt;0.0001). There was only one childhood aortic dissection (type B in 15 year old male). Overall females were more likely than males to have arachnodactyly (54 vs. 40%), scoliosis (60 vs. 49%), and dural ectasia (16 vs. 10%), all p&lt;0.01. Adult males were more likely to have aortic root dilatation (92 vs. 84%), aortic regurgitation (55 vs. 36%) and to have undergone prophylactic aortic root replacement (47 vs. 24%), all p&lt;0.001. Prevalence of prior aortic dissection was higher in males than females (25 vs. 18%, p=0.06), 44% of which were type B. Mean age at dissection (35 vs. 38 years), age at prophylactic surgery (32 vs. 35 years), and need for mitral valve surgery (9.5 vs. 10.0%) were similar between men and women, respectively. Conclusions: Pulmonary, skeletal and aortic complications, but not other phenotypic features, increase with aging in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. In the era of current surgical and medical treatment, aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially among men.
Synergistic triple-combination therapy with hyaluronic acid-shelled PPy/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer
Authors: Wei Sun, Yang Du, Xiaolong Liang, Chunyao Yu, Junjie Fang, Wei Lu, Xiuyu Guo, Jie Tian, Yinhua Jin, Jianjun Zheng
Journal: Biomaterials (2019)

Breast cancer is characterized by high aggression, poor prognosis, and high recurrence rate. Early detection and specific targeted treatment with less toxicity are the ultimate goals for breast cancer therapy. To improve antitumor therapeutic effects, we developed a novel polypyrrole nanoparticle using the near infrared dye IRDye800CW with camptothecin (CPT)-conjugated hyaluronic acid (HA) shell (PPy@CPT-HA-IRDye800CW) and performed a photothermal therapy (PTT), along with chemotherapy, guided by fluorescence and photoacoustic dual-modality imaging, in combination with immunotherapy. Irradiation with near infrared (NIR) light offered a strong PTT effect and promoted CPT drug release in tumors. Moreover, we found that chemo-photothermal therapy with PPy@CPT-HA-IRDye800CW NPs, in combination with immune checkpoint inhibitor anti-PD-L1 immunotherapy, synergistically enhanced the anti-tumor immune response, thereby eliminating primary breast cancer and preventing tumor metastases and recurrences in 4T1 tumor-bearing mice. This approach may provide important clues for the clinical management of breast cancer and other malignant tumors.
THU0728-HPR "I AM GOOD ENOUGH AS I AM EVEN IF I AM NOT PERFECT" A QUALITATIVE STUDY OF FIBROMYALGIA PATIENTS' EXPERIENCES FROM PARTICIPATION IN A MINDFULNESS-BASED GROUP-PROGRAMME
Authors: Heidi A. Zangi, Gyda Singstad, Ingrid Ruud Knutsen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> People with fibromyalgia (FM) suffer from widespread pain, non-refreshing sleep, fatigue and reduced mental wellbeing. No curative pharmacological treatment exists. Vitality Training (VTP) is a mindfulness- and acceptance-based group-programme that aims at enhancing participants health promoting resources, strengthening their inner authority and ability to act according to own values. It combines mindfulness with creative methods and group counselling. Two RCTs have shown significant improvements in mental wellbeing, pain coping and fatigue in patients with chronic musculoskeletal pain and inflammatory arthritis. The VTP is currently being evaluated in an ongoing study for patients with newly diagnosed FM [1]. <h3>Objectives</h3> The aim of this qualitative study was to explore FM patients experiences from participating in the VTP, and if they perceived that it had any impact on their health and functioning. <h3>Methods</h3> Six qualitative in-depth interviews with participants from three VTP-courses were conducted following a semi-structured interview guide. Interviews were audio-recorded and transcribed. All three authors analysed the data by use of systematic text condensation. <h3>Results</h3> Three main themes were identified. Understanding oneself in light of the group: Mutual understanding and acknowledgement had altered participants self-understanding from a feeling that something was wrong with me towards perceiving themselves as a normal person with similar challenges as others. Learning to accept oneself: Participants had obtained a greater understanding and acceptance for their emotions and reactions and had become kinder towards themselves. I have realised how strict I have been towards myself I am indeed good enough as I am even if I am not perfect. Coping with everyday challenges: Becoming aware of what had provoked stress and learn how to face it had helped participants take more control. I can do small changesthat really makes it better the illness does not decide everything. Indeed I can decide something myself. <h3>Conclusion</h3> Participation in the VTP had contributed to new ways of relating to oneself and the illness. The support and acknowledgement participants experienced from the group had helped them alter their self-understanding from only being ill towards also being healthy and normal. They had learnt ways to better cope with stress and everyday challenges. Although this was a small study, the findings correspond with findings in previous studies. <h3>References</h3> [1] Haugmark T. et al. Effects of a community-based multicomponent rehabilitation programme for patients with fibromyalgia: protocol for a randomised controlled trial. BMJ open. 2018 Jun 4; 8(6):e021004. <h3>Disclosure of Interests</h3> None declared
PB2453 DISTRIBUTION OF BLOOD DONOR IN DIFFERENT AGE GROUP IN KATHMANDU NEPAL
Authors: B. Nepal
Journal: HemaSphere (2019)

Background: Voluntary non‐remunerated blood donor consists of 78% blood donor's population in Nepal. Therefore demographic about the distribution of blood donors according to the age group is important to achieve 100% Voluntary non‐remunerated blood donors in Nepal. Aims: To explore the demographic distribution of the blood donor in different age group in the Kathmandu Nepal. Methods: This is retrospective study conducted at Nepal Red Cross Society Central Blood Transfusion Service. Data from January 2013 to January 2017 were collected from donor management software. The data includes socio demographic data. Data has been process with SPSS version ‐17 Results: During 4 years study period, total of 276,290 Blood donation happened from both mobile blood collection and in‐house blood collection. Out of 276,290 Collection, 48351 (17.5%) are from 18‐24 age group; 106924 (38.7%) are from 25‐31 age group 53324 (19.3%) are from 32‐38 age group; 34536 (12.5%) are from group 39‐45 age group; 23761 (8.6%) are from age group 46‐52 and 9394 (3.4%) from age group above 53 respectively. Summary/Conclusion: The distribution of ABO blood group varies regionally and from one population to another. In Kathmandu, Nepal 18‐38 years age group is the most common age group encountered donating blood. The data generated in the present study and several other studies of different geographical region of India will be useful to health planners and future health challenges in the region
SAT0415 HIGH BODY FAT OF TRUNK IS POSITIVELY CORRELATED WITH SERUM URIC ACID IN MALE GOUT PATIENTS
Authors: LI Qianhua, Lijuan Yang, Yan-Hui Xu, Chao Deng, Hui-Wen Lu, Xin-Yun Du, Jinjian Liang, Jianzi Lin, Yingqian Mo, Lie Dai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Obesity is an important risk factor of gout which is defined by body mass index (BMI). However, BMI has been challenged for the limitation of failure to differentiate comprising tissues of the body. More accurate body composition (BC) has been frequently recommended to assess metabolic status. <h3>Objectives:</h3> To investigate the characteristics of BC in gout patients and its clinical significance. <h3>Methods:</h3> Consecutive gout patients who fulfilled the 2016 ACR/EULAR classification criteria were recruited between June 2017 and December 2018. BC was assessed by bioelectric impedance analysis including body fat percentage (BF%), the mass and distribution of muscle and fat in trunk and appendicular extremities. Demographic information, clinical characteristics and comorbidities were collected. Overfat was defined by BF% ≥25% for male and ≥35% for female. <h3>Results:</h3> Among 362 recruited gout patients, 96.1% were male and the median age was 38 (30, 50) years, mean serum uric acid (sUA) was 9.2±2.2mg/dl, 18.0% presented tophi. The mean BF% was 25.8±6.4% with 53.6% overfat. Male gout patients with overfat (53.7%) showed more affecting joints, higher sUA and higher prevalence of comorbidities than those without overfat (<i>P</i>&lt;0.05, Figure 1). Their BF%, trunk BF% and limb BF% were positively correlated with count of affecting joints, sUA, hypertension, metabolic syndrome and fatty liver in Spearman correlation analysis, respectively (<i>r</i>=0.133∼0.424, all <i>P</i>&lt;0.05). The male patients with overfat also presented higher BMI and waist circumstance (WC), higher trunk/limb BF% ratio (<i>P</i>&lt;0.05, Figure 1). Their BF%, trunk BF% and limb BF% were also positively correlated with BMI and WC, respectively (<i>r</i>=0.604∼0.755, all <i>P</i>&lt;0.05). After adjustment for age, duration, family history, eGFR, hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, fatty liver, coronary heart diseases, urolithiasis, BMI and WC, multivariable linear regression showed that BF% (<i>β</i>=0.072, 95%<i>CI</i> 0.012∼0.132, P=0.018) and trunk BF% (<i>β</i>=0.152, 95%<i>CI</i> 0.043∼0.261, <i>P</i>=0.007), but not limb BF%, were positively correlated with sUA. <h3>Conclusion:</h3> The characteristics of fat distribution in male gout patients is more in trunk and trunk BF% is positively correlated with sUA. <h3>Disclosure of Interests:</h3> None declared
SAT0281 RELATIONSHIP BETWEEN AUTOANTIBODIES AND CYTOKINE PROFILES IN PATIENTS WITH MYOSITIS
Authors: Kazuhihiro Kurasawa, Satoko Arai, Yuta Takamura, Tomoyuki Miyao, Ayae Tanaka, Ryutaro Yamazaki, Takayoshi Owada, Reika Maezawa, Masafumi Arima
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> By autoantibodies, myositis is recently classified into subgroups with distinctive clinical features. Cytokines play critical roles in the development of the clinical features. However, it is not fully unknown whether myositis subgroups defined by autoantibodies have unique cytokine profiles. <h3>Objectives:</h3> To clarify the relationship between cytokine profiles and autoantibodies in myositis. <h3>Methods:</h3> Subjects were myositis patients who admitted Dokkyo Medical University and whose serum before starting therapy were available. Serum cytokine levels (IL-1a, 1b, 2, 4,5, 6, 10,12, 13,15,17, 23,IFN-g, TNF-a, IFN-a, b,IP-10 and MCP-1) in sera from the patients and controls were measured using Q-Plex™ Multiplex Arrays. Demographic and clinical data were obtained by reviewing medical record retrospectively. <h3>Results:</h3> Subjects were 45 myositis patients with male/female; 22/23 and 59.4 years of mean age. Amyopathic dermatomyositis (ADM), classical DM and polymyositis (PM) were 21, 11 and12 cases, respectively. Autoantibodies were anti-MDA5+ in 21, anti-ARS+ in18 and anti-TIF1g+ in 5 cases. ILD and malignancy was complicated in 39 and 5 cases, respectively. Serum cytokine levels were measured. As shown in Fig.1, IP-10 levels were increased in all types of myositis patients, but not in controls. In ant-MDA5 Ab + myositis, IL-6, IL-10, IL-15, TNF-a, IFN-a and MCP-1 levels were increased. In anti-ARS Ab+ cases, IFN-b levels were elevated as well as TNF-a and MCP-1. Through the correlation analysis between cytokine levels, cytokine groups were identified (Fig.2). In anti-MDA5 Ab+ cases, 2 cytokine groups were identified; one includes IFN-a, IL-15, TNF-a and IL-10, and the other involved IL-6, MCP-1. Both groups connected with IP-10. In In anti-ARS Ab+ cases, 2 groups were found; one included TNF-a, MCP-1and IP-10, and the other had IFN-b as a sole component. <h3>Conclusion:</h3> Cytokine profiles differ among subgroups in myositis. In anti-DDA5+ myositis, IL-15 and IFN-a with strong correlation and IL-6 were characteristic cytokines, while IFN-b was a unique one in anti-ARS+ myositis <h3>Disclosure of Interests:</h3> None declared
PF186 INTENSIVE CARE OF THE LIFE –THREATING COMPLICATION DE NOVO ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) PATIENTS (PTS)
Authors: A. Bazhenov, G. Galstyan, E. Parovichnikova, V. Troitskaya
Journal: HemaSphere (2019)

Background: Treatment of ALL pts can be associated with the life‐threating complications requiring intensive care unit (ICU) admission. The long‐term outcomes of ALL pts after discharge from ICU is unknown. Aims: To compare the overall survival (OS) of de novo ALL pts who required and not required ICU admission during induction remission chemotherapy. Methods: All de novo ALL pts (median age 28 yo, 17–60 yo), treated from 2013 to 2017, were enrolled into the study. Pts were divided into 2 groups: pts required ICU admission (ICU group), and pts not required ICU admission (non‐ICU group). Landmark OS was assessed by the Kaplan – Meier method, log rank value p &lt; 0.05 was considered as significant. Landmark was the date of discharge from ICU, and median time of discharge from ICU. Univariate analysis was performed with χ 2 tests or Fisher's exact tests for categorical variables to find an independent ICU mortality predictor. Results: In total, 87 ALL pts were enrolled into the study, 18 (20.6%) of them pts required ICU admission and 69 pts were treated without ICU. Reasons for ICU admissions were: acute respiratory failure (44%), acute neurological events (28%), tumor lysis syndrome (17%), septic shock (SS) (11%). Mechanical ventilation (MV) was required in 28% of pts, vasopressor support ‐ in 28% of pts, and renal replacement therapy ‐ in 22% of pts. ICU survival rate was 89% (2 pts died in ICU due to the SS). Needs for MV and for vasopressors were independent predictors of ICU mortality ( p &lt; 0.05). No one pts died in non‐ICU group during induction chemotherapy. Five year OS was 44% and 76% in ICU and non‐ICU group, respectively, ( p &lt; 0.05) (figure 1). Summary/Conclusion: Despite high ICU survival rate (89%), 5– years OS was only 44%. I non‐ICU group OS was 76% (p &lt; 0.05). The long‐term prognosis of ALL pts discharged from ICU worse in comparison AML pts discharged from ICU [1,2]. This phenomenon it could be explained by negative selection of ALL pts in ICU. image Reference 1. The influence of ICU admission of the patients with de novo AML on the long‐term survival. Bazhenov A., Galstyan G., Parovichnikova E. et al. Intensive care medicine experimental. 2018 (6) supplement 2. P.4422. Prognostic factors for intensive care unit admission, intensive care outcome, and post‐intensive care survival in patients with de novo acute myeloid leukemia: a single center experience. Schellongowski P. Haematologica. 2011. № 2 (96).
Abstract 16766: Increased Clinical and Financial Burden of Heart Failure Hospitalizations in Patients With Systemic Lupus Erythematosus: Insights From the National Inpatient Sample 2012-2014
Authors: Aditya A Joshi, Aparna P Sajja, Amit K Dey, Joseph B Lerman, Tsion M Aberra, Maria M Patorroyo-Aponte, Srinivas Murali, Raymond L Benza, Amresh Raina
Journal: Circulation (2018)

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease associated with increased cardiovascular (CV) co-morbidities. Recent evidence suggests that (SLE) is associated with higher incidence of heart failure (HF) independent of traditional CV risk factors. Despite a known association with accelerated CV diseases, the association between burden of acute decompensated HF (ADHF) and SLE is not well-characterized. Therefore, we used a large national database to examine the clinical and financial burden of ADHF in SLE. Hypothesis: SLE would associate with increased hospitalization for ADHF along with a longer length of stay (LOS) and higher hospital charges. Methods: SLE patients (n=160,350) older than 18 years were identified in the Nationwide Inpatient Sample (NIS) 2012-2014 databases using the ICD-9 code 710.0. ADHF was classified using appropriate ICD-9 codes from 428.0-428.9. Demographics, traditional CV risk factors, and HF-related outcomes were defined in SLE patients and compared to the general population. Results: Patients in the general population and with SLE were middle-aged (median 56 and 59 years). Prevalence of hypertension and chronic kidney disease was higher in SLE patients, whereas diabetes, coronary artery disease, dyslipidemia was lower (Table 1). ADHF rate, LOS and total hospital charges were increased in SLE. Furthermore, LOS (standardized β=0.003, p&lt;0.001) and hospital charges (β=0.006, p&lt;0.001) were associated with SLE beyond CV risk factors. Finally, after adjustment for CV risk factors (age, sex, hypertension, diabetes, dyslipidemia, coronary artery disease, chronic kidney disease, smoking), dysrhythmias, thyroid disorders, alcohol use and median household income, SLE associated with ADHF (OR, 95% CI: 1.53 [1.51-1.55], p&lt;0.001), increased LOS (1.14 [1.11-1.17], p&lt;0.001) and increased hospital charges (1.12 [1.09-1.15], p&lt;0.001) (Table 1). Conclusion: SLE is associated with increased clinical and financial burden of ADHF beyond CVRF, underscoring the need for greater early clinical awareness of SLE in HF patients. Larger prospective studies are needed to confirm our findings.