tbuckley/cabot-search huggingface dataset:
AB1012 HENOCH-SCHöNLEIN PURPURA AND UVEITIS, AN UNUSUAL ASSOCIATION
Authors: Ilaria Maccora, Francesca Tirelli, Gabriele Simonini, Teresa Giani, Rolando Cimaz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Henoch-Schönlein purpura (HSP) is the most common childhood vasculitis characterized by cutaneous palpable purpura predominantly located in the lower limbs, arthralgia/arthritis, renal and bowel involvement. To our knowledge only 4 cases of HSP with ocular involvement have been reported so far. <h3>Objectives</h3> We describe a 6-year-old female patient who presented HSP and panuveitis. <h3>Methods</h3> Describe a case report. <h3>Results</h3> A 6-year-old female, previously in good health, received the diagnosis of HSP for cutaneous palpable purpura on her lower limbs, bilateral ankle arthritis and haematuria. Two weeks later the girl was admitted to our Emergency Department due to monolateral ocular pain with red eye. At ophthalmological assessment there was evidence of anterior uveitis with and edema of the optic disc. Blood tests showed increased values of CRP (1.92 mg/dl) and ESR (69 mm/h) with normal values of complement levels and complete blood count. Urinalysis displayed mild hematuria and proteinuria. Immunoglobulin levels were slightly increased: IgG (1850 mg/dl, n.v. 540-1330 mg/dl), IgA 244 mg/dl (n.v. 50-240 mg/dl) and IgM 72 mg/dl (n. v. 50-180 mg/dl) An extensive infectious work-up for viral, bacterial and parasitic infections was negative. ANA, ANCA, ASCA, LAC, HLA B27 and B51 were all negative. Chest X ray, abdominal ultrasound and echocardiography were negative. A brain MRI with contrast revealed an iris inflammation and excluded CNS involvement. Systemic therapy was started with i.v. methylprednisolone (30mg/kg/d for three consecutive days) and continued with oral prednisone (2 mg/kg/day), with a progressive improvement of the ocular, skin, nephrological and articular involvement. Prednisone was then gradually tapered over 2 months without disease recurrence. <h3>Conclusion</h3> In our literature search we were able to find an association between HSP and uveitis only in two adults and in an 11-year-old child. All these patients showed cutaneous and articular involvement and 3/4 nephrological involvement. Uveitis was observed in the first week of vasculitis onset. Although rare, the presence of ocular involvement can occur during HSP. <h3>References</h3> [1] Ozen S, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010 May;69(5):798-806. [2] Kaur S. et al. Henoch–Schonlein purpura with uveitis: an unusual case and review of literature. Rheumatol Int (2012) 32:4057–4059 <h3>Disclosure of Interests</h3> Ilaria Maccora: None declared, Francesca Tirelli: None declared, Gabriele Simonini Grant/research support from: Abbvie, Speakers bureau: Abbvie, Teresa Giani: None declared, Rolando Cimaz: None declared
Nanotechnology is an important strategy for combinational innovative chemo-immunotherapies against colorectal cancer
Authors: Ana I. Matos, Barbara Carreira, Carina Peres, Liane I.F. Moura, João Conniot, Thibaut Fourniols, Anna Scomparin, Águeda Martínez-Barriocanal, Diego Arango, João P. Conde, Véronique Préat, Ronit Satchi-Fainaro, Helena F. Florindo
Journal: Journal of Controlled Release (2019)
PB1734 THE ROLE OF ROTEM IN PREDICTING HEMORRHAGE AND HEMORRHAGIC EARLY DEATH RISK IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA
Authors: N. Sabljic, M. Mitrovic, T. Kocica, M. Virijevic, Z. Pravdic, J. Rajic, V. Milosevic, A. Vidovic, N. Suvajdzic, D. Tomin
Journal: HemaSphere (2019)

Background: Hemorrhagic early death (HED), with reported rates between 5 and 26.52%, is a major impediment in the managing of acute promyelocytic leukemia (APL). It is well recognized that conventional coagulation parameters do not accurately predict the risk of major bleeding. There are limited data on the clinical utility of ROTEM and extended coagulation parameters for evaluation of coagulopathy in patients with APL. Aims: 1. To identify predictive value of ROTEM parameters for hemorrhage and HED. 2. To identify a correlation between ROTEM and conventional coagulation tests. Methods: We analyzed data in 19 newly diagnosed PML-RARA positive patients (median age 37 years, range 18-73; 11 female/8 male) managed in the Clinic of Hematology from 2016-2019, with all-trans retinoic acid combined with anthracyclines. HED was defined as death from hemorrhage from the first day of hospitalization up to the end of the induction treatment. The following parameters were evaluated as risk factors for bleeding and HED: WBC count, platelet count, fibrinogen level, PT, APTT, D dimer, ISTH DIC score, EXTEM (CT, CFT, alfa, A10, A20, ML), INTEM (CT, CFT, alfa, A10, A20, ML) and FIBTEM (CT, alfa, A10, A20, ML). Results: Hemorrhage and HED occurred in 15/19 (78.95%) and 2/19 (10.53%) patients, respectively. The median platelet count was 32 x 109/L (range 4-137 x 109/L), fibrinogen level 3.3 g/L (range 1.31-6.08 g/L), PT 64 % (range 39-96 %) and APTT 26 s (range 20.5-96 s). In our group of patients, EXTEM ML and INTEM ML, differ significantly from a normal range (P < 0.001). Predictors of hemorrhage were: EXTEM A10 (32 mm vs. 14 mm in patients without and with hemorrhage, P = 0.028), INTEM CFT (150 s vs. 1302 s, P = 0.05) and INTEM A10 (44 mm vs. 12.5 mm, P = 0.021). The parameters, significantly associated with HED, were: higher WBC (2.3 vs. 164.3 x 109/L, P = 0.024), Sanz high-risk APL (P = 0.045), EXTEM CT (114 s vs. 586.5 s, P = 0.024), EXTEM A10 (16 mm vs. 3.5 mm, P = 0.024), INTEM CT (191 s vs. 754 s, P = 0.027), INTEM A10 (15 mm vs. 6 mm, P = 0.027), FIBTEM CT (140 s vs. 723 s, P = 0.046) and FIBTEM A10 (6 mm vs. 1.5 mm, P = 0.023). Correlation between EXTEM A10 and platelet count (P = 0.033), INTEM ML and APTT (P = 0.024) was showen. There was no correlation between other parameters of INTEM and APTT, EXTEM and PT or any parameter of FIBTEM and fibrinogen. Summary/Conclusion: Our study showed that ROTEM parameters are predictive for both hemorrhage and HED in APL. No clear correlation between conventional tests and ROTEM was registered. Accordingly, new strategy that combines both, conventional test and ROTEM, would probably better evaluate hemostatic function in patients with APL, and would guide the transfusion support in prevention of HED.
PB1859 PROSPECTIVE COHORT STUDY OF KOREAN PATIENTS WITH BONE MARROW DISORDERS WITHOUT LARGE PNH CLONE TO DEFINE FACTORS ASSOCIATED WITH PNH CLONE EXPANSION
Authors: Y. Koh, S.‐S. Yoon, J.W. Lee, J.H. Jang, J.‐H. Lee, J.S. Kim, S.E. Choi, S.‐H. Kim
Journal: HemaSphere (2019)

Background: Factors associated with PNH clone evolution is not well described in the Asian population. Aims: In this prospective cohort study, we recruited Korean patients with bone marrow disorder to define factors associated with an increase in PNH clone size. Methods: We included patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) if PNH clone is not absent at the time of screening. We also included patients who have small PNH clones (&lt;10%) regardless of bone marrow pathology except for hematologic malignancies. Patients should be free of complement inhibitor treatment for at least 8 weeks before study enrollment. PNH clone size testing was performed using high‐resolution flow cytometry and FLARE. Results: We enrolled 227 patients (Male:Female 121:106, mean age 53 years) from 6 centers in Korea. PNH clone was ≥ 1% in 28 patients, 0Table1 Characteristics of 5 patients who experienced more than 10% of PNH clone expansion Summary/Conclusion: We constructed a prospective cohort of Korean patients with AA, MDS or small PNH clones. PNH clone distribution had a distinctive pattern according to underlying bone marrow pathology. We expect to construct a precise model for PNH clone expansion using this cohort. image
Junior doctors are embarrassing themselves by opposing medical associate professionals
Authors: Brendan Fletcher
Journal: BMJ (2019)

I read the news that junior doctors opposed medical associate professionals sitting postgraduate exams and becoming equal in terms of staffing with disquiet.1

The idea that upskilling medical associate professionals is harmful to the integrity of the medical profession is ridiculous. To “actively oppose” recognising their contribution, skill, and training by not allowing them to prepare for …
Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants
Authors: Kathyayini P. Gopalakrishna, Benjamin R. Macadangdang, Matthew B. Rogers, Justin T. Tometich, Brian A. Firek, Robyn Baker, Junyi Ji, Ansen H. P. Burr, Congrong Ma, Misty Good, Michael J. Morowitz, Timothy W. Hand
Journal: Nature Medicine (2019)
PB2441 DIRECT ORAL ANTICOAGULATION IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS: A SINGLE‐CENTER REAL‐LIFE EXPERIENCE
Authors: S. Raso, M. santoro, M. Napolitano, S. Mancuso, V. Accurso, M. Carlisi, G. Tarantino, S. Siragusa
Journal: HemaSphere (2019)

Background: The risk of developing a venous thromboembolic event (VTE) in Myeloproliferative Neoplasms (MPNs) accounts from 5 to 10‐fold the general population risk. According to recommendations of European Leukemia Net, patients affected by MPNs already diagnosed with VTE have to be considered at high risk for VTE recurrence. To date the standard treatment adopted for prevention and treatment of VTE in this setting of patients is represented by low molecular weight heparin (LMWH) and vitamin K antagonists (AVK). Recent data have demonstrated the noninferiority of direct oral anticoagulant (DOAC) drugs, when compared to LMWH, in preventing VTE recurrences in patients affected by cancer with an acceptable toxic profile. However, there are only scarce evidences on the safety and efficacy of DOACs in patients with hematological malignancies. Aims: Our aim is to collect real‐life data on the use, efficacy and safety of DOACs in patients with diagnosis of MPNs. Methods: Data from 51 patients affected by MPNs on anticoagulant therapies were collected. Of them, 27 were on treatment with AVK, 4 on LMWH and 20 on DOAC. Data from the 20 MPNs patients taking DOACs for treatment/prevention of VTE or atrial fibrillation (AF) were retrospectively collected in a specific database. Data were analyzed with descriptive statistic tools. Adverse events were graded according to the “Common Terminology Criteria – Adverse Events” (CTC‐AE) scale. Results: 14/20 (70%) of the patients on treatment with DOAC have the indication for prevention of VTE recurrences and 6/20 (30%) for AF. Of the 20 patients, 5 were taking dabigatran, 6 rivaroxaban, 3 apixaban and 4 edoxaban. Of the 14 patients on anticoagulation treatment for prevention of VTE, 2 (14.3%) patients failed prevention and showed VTE recurrence: in one case, because of drug failure a second line prophylaxis therapy with warfarin was started; in the second case, failure was due to inadequate cytoreduction for MPN and the DOAC was not dropped. Bleeding was registered in three cases: 2 graded as first and 1 as second grade as per CTC AE classification. Grade 2 bleeding was resolved with dose reduction of anticoagulation treatment. None of the patient was concomitantly under antiplatelet therapy. Summary/Conclusion: Real life data from a single center experience on the use of DOAC in patients with MPN suggest that also in these setting of patients DOACs are safe. More extensive data collection is needed to confirm these preliminary findings.
Liquid biopsy in ovarian cancer: recent advances in circulating extracellular vesicle detection for early diagnosis and monitoring progression
Authors: Lei Chang, Jie Ni, Ying Zhu, Bairen Pang, Peter Graham, Hao Zhang, Yong Li
Journal: Theranostics (2019)

The current biomarkers available in the clinic are not enough for early diagnosis or for monitoring disease progression of ovarian cancer.Liquid biopsy is a minimally invasive test and has the advantage of early diagnosis and real-time monitoring of treatment response.Although significant progress has been made in the usage of circulating tumor cells and cell-free DNA for ovarian cancer diagnosis, their potential for early detection or monitoring progression remains elusive.Extracellular vesicles (EVs) are a heterogeneous group of lipid membranous particles released from almost all cell types.EVs contain proteins, mRNA, DNA fragments, non-coding RNAs, and lipids and play a critical role in intercellular communication.Emerging evidence suggests that EVs have crucial roles in cancer development and metastasis, thus holding promise for liquid biopsy-based biomarker discovery for ovarian cancer diagnosis.In this review, we discuss the advantages of EV-based liquid biopsy, summarize the protein biomarkers identified from EVs in ovarian cancer, and highlight the utility of new technologies recently developed for EV detection with an emphasis on their use for diagnosing ovarian cancer, monitoring cancer progression, and developing personalized medicine.
Detection of<i>NTRK</i>Fusions: Merits and Limitations of Current Diagnostic Platforms
Authors: James P. Solomon, Jaclyn F. Hechtman
Journal: Cancer Research (2019)

Abstract Oncogenic fusions involving NTRK1, NTRK2, and NTRK3 with various partners are diagnostic of infantile fibrosarcoma and secretory carcinoma yet also occur in lower frequencies across many types of malignancies. Recently, targeted small molecular inhibitor therapy has been shown to induce a durable response in a high percentage of patients with NTRK fusion–positive cancers, which has made the detection of NTRK fusions critical. Several techniques for NTRK fusion diagnosis exist, including pan-Trk IHC, FISH, reverse transcription PCR, DNA-based next-generation sequencing (NGS), and RNA-based NGS. Each of these assays has unique features, advantages, and limitations, and familiarity with these assays is critical to appropriately screen for NTRK fusions. Here, we review the details of each existing methodology.
AB0323 CARDIOVASCULAR RISK ESTIMATION IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH BIOLOGICS OR C-DMARDS
Authors: Evangelia Mole, Sousana Gazi, Dimitra Moschou, Georgia Mpaili, Stavros Theodorakopoulos, Konstantina Zoupidou, Nikolaos Kontodimopoulos
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with Rheumatoid Arthritis (RA) are at increased risk of developing atherosclerotic cardiovascular (CV) disease. The impact of treatment with conventional or biological disease modifying drugs (c- or b-DMARDs) on inflammation of systemic circulation is an important question. <h3>Objectives</h3> The aim of this study is to determine the influence of therapy (c-DMARDs or b-DMARDs) on 10 year CV risk in patients with RA, over a period of 18 months. <h3>Methods</h3> A single center, observational study of 229 consecutive RA patients, who were treated with c-DMARDs or b-DMARDs mono/combination therapy for at least 18 months. The 10 year CV risk was calculated with Framingham risk score (FRS). <h3>Results</h3> A total of 229 patients were included, 111 received b-DMARDs and 194 c-DMARDs. The mean age was comparable between 2 groups (62.45±12.74 vs 64.56±12.48years, p: 0.1596) and 148 (64.63%) were female. Patients receiving b-DMARDs had longer disease duration compared to c-DMARDs group (14.34±9.89 vs 9.99±9.3 years respectively, p: 0.001) and comparable baseline FRS 10-year percent CV risk (10.74±8.88 vs 11.68±8.78 respectively, p: 0.3710). Baseline patient distribution across intermediate (9.6% vs 16.6%) and high (10.91% vs 16.16%) FRS 10-year CV risk categories was comparable between treatment groups (b-DMARDs vs c-DMARDs, p: 0.208), except low FRS category (27.51% vs 51.53% respectively, p&lt;0.001). At month 18, FRS 10-year CV risk category remained stable in b-DMARDs patients (low: 31.88%, intermediate: 10.92%, high: 5.24%, p: 0.47), whereas a significant shift in FRS 10-year CV risk category was observed in c-DMARDs patients (low: 58.1%, intermediate: 17.03%, high: 9.17%, p: 0.001). Within-group the mean (SD) change in FRS 10-year percent CV risk from baseline to month 18 was statistically significant for both b-DMARDs (Δ: 10.74-8.94= 1.8 (1.14), p&lt;0.001) and c-DMARDs (Δ: 11.68-8.73= 2.95 (0.91), p&lt;0.001). <h3>Conclusion</h3> Patients treated with b-DMARDs had lower baseline and month 18 10-year CV risk. However, both treatment arms induced significant improvement of 10-year CV risk at 18 months. <h3>References</h3> [1] Ann M. Chodara, MD, Aimée Wattiaux, BS, and Christie M. Bartels, MD, MS. Managing cardiovascular disease risk in rheumatoid arthritis: clinical updates and three strategic approaches. Curr Rheumatol Rep. 2017Apr; 19(4): 16. [2] Meyer PW1, Anderson R2, Ker JA3, Ally MT4. Rheumatoid arthritis and risk of cardiovascular disease. Cardiovasc J Afr. 2018 Sep/Oct 23;29(5):317-321. <h3>Disclosure of Interests</h3> None declared
THU0171 TOFACITINIB, AN ORAL JANUS KINASE INHIBITOR, IN THE TREATMENT OF RHEUMATOID ARTHRITIS – THE RESULTS OF RUSSIAN NATIONAL REGISTER OF PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH TOFACITINIB
Authors: Inna Gaydukova, V Mazurov, Evgeniy Zhilyaev, Iuliia Grabovetskaya, Irina Marusenko, Elizaveta Vasilenko, Diana Abdulganieva, Ilia Smitienko, Anna Misiyuk, Galina Lukina, Larisa Knyazeva, Elena Kalinina, Ruzana Samigullina, Irina Bondareva, Natalya Yudina, N Lapkina, Evgeny Nasonov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Tofacitinib (TF) is an oral Janus Kinase inhibitor for the treatment of rheumatoid arthritis (RA). <h3>Objectives:</h3> To evaluate the one-year effectiveness of tofacitinib as first-line therapy in RA conventional synthetic (cs) DMARDs non-responders. <h3>Methods:</h3> Data from 415 patients from Russian national register of patients with RA treated with TF were analyzed. 119 RA patients, who had complete clinical and laboratory data from 4 consecutive visits after baseline with an interval of 3 months between the visits and who used the TF as first-line therapy after failure of cs DMARDs, were included. Treatment with any biologics ever was an exclusion criteria. Demographical (age, sex) and RA activity data (DAS28, SDAI, number of tender and swollen joints (NTJ, NSJ), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP), and HAQ, EQ5D were collected, table 1. Statistical analysis performed in SPSS2017. p-value &lt;0.05 considered as significant. <h3>Results:</h3> At baseline 12 (10%) were treated with NSAIDs, 15 (12.6) with 5-10 mg/dayof prednisolone, 82 (68.9) – with methotrexate (10-25 mg/week), 8 (6.7%) – with sulfasalazine (2.0-3.0 g/day). Changes in the disease activity in patients with RA, treated with tofacitinib after csDMARD are presented in Table 2 At visit 3 DAS28 &lt;3.2 achieved 80 (67.22%) of the patients: 71 patients on 20 mg of TF (59.66%) and 9 patients on 10 mg of TF 11 (9.24%) patients at visit 3 had DAS28 ≥5.1. <h3>Conclusion:</h3> Treatment with TF may provide good response rates in RA patients, refractory previous cs DMARDs. <h3>Acknowledgement:</h3> Study sponsored by Pfizer <h3>Disclosure of Interests:</h3> Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: paiment from Pfizer, Novartis, Abbvie, Biocad, Selgene, MSD, Sanofy does not exceed 10 000 euros, V Mazurov Grant/research support from: JSC BIOCAD, Evgeniy Zhilyaev: None declared, Iuliia Grabovetskaya: None declared, Irina Marusenko: None declared, Elizaveta Vasilenko: None declared, Diana Abdulganieva: None declared, Ilia Smitienko: None declared, Anna Misiyuk: None declared, Galina Lukina: None declared, Larisa Knyazeva: None declared, Elena Kalinina: None declared, Ruzana Samigullina: None declared, Irina Bondareva: None declared, Natalya Yudina: None declared, N Lapkina: None declared, Evgeny Nasonov: None declared
PS980 GRIK5 DRIVES SELF RENEWAL PATHWAYS IN HUMAN ACUTE MYELOID LEUKEMIA CELLS
Authors: J. Xia, S. Garg, L. He, P. Jagdhane, M.‐T. Carsten, P. Caroline
Journal: HemaSphere (2019)

Background: Acute myeloid leukemia (AML) is characterized by a block in differentiation and uncontrolled proliferation of immature hematopoietic precursor cells. Self‐renewing leukemia stem cells (LSCs) are supposed to initiate and promote the disease. In our previous study, we had identified a set of genes associated with high LSC frequency in normal karyotype AML. Among these, we identified the Glutamate receptor ionotropic, kainate 5 (GRIK5) coding for a transmembrane protein, which is known to be expressed in the central nervous system as a ligand‐gated ion channel receptor. Aims: In this study, we aimed to understand the functional role of GRIK5 in normal HSPCs and AML cells. In particular, we investigated how GRIK5 drives self‐renewal pathways in AML and whether GRIK5 might represent a novel cell surface target for anti‐leukemic therapy. Methods: We performed knockdown (KD) experiments using small hairpin (sh) RNAs to determine whether GRIK5 was essential for proliferation, differentiation, and survival of primary human cord blood CD34+ HSPCs, leukemic cell lines, and primary human‐derived AML xenograft cells. Furthermore, lentivirally transduced HSPCs and leukemia cells were analyzed in vitro for proliferative output, viability, immunophenotype, and colony formation potential. RNA sequencing (RNA‐Seq) and whole cell mass spectrometry followed by enrichment analysis were used to identify key signaling pathways affected by GRIK5 KD. Results: We found that knockdown of GRIK5 expression strongly impaired leukemic cell proliferation and totally abrogated human leukemic engraftment in immunocompromised mice. In the healthy system, however, GRIK5 KD predominantly reduced the proliferative output of more committed progenitors, while more immature HSPCs were less affected. RNA‐Seq data points towards a major involvement in several key self‐renewal pathways. Summary/Conclusion: Here we found that the surface receptor GRIK5 is overexpressed in the majority of AML samples compared to healthy HSPCs. GRIK5 plays a pivotal role in proliferation, differentiation, and engraftment capacity of primary human leukemia cells in xenotransplantation assays and might, therefore, be used as a novel therapeutic target for anti‐leukemic therapies.