tbuckley/cabot-search huggingface dataset:
PB2410 DEPRESSION AMONG CAREGIVERS OF CHILDREN WITH THALASSEMIA MAJOR
Authors: S. Sen, S. Sen, S. Tulpule, K. Mullanfiroze, S. Gupta
Journal: HemaSphere (2019)

Background: Caregivers of patients with thalasemia devote a significant proportion of their time to meet their ongoing medical needs. This can adversely affect the time dedicated to their other children, and as carriers of the disease, they may be burdened significant feelings of guilt and inadequecy. We evaluated symptoms of depression among parents of these patients by PHQ‐9, a well validated screening tool for assessing depression. Aims: To determine the incidence of mental health issues among caregivers of children with thalassemia. Methods: Parents and caregivers of patients with thalassemia in a Haemoglobinopathy Clinic were screened over a 2‐month period using the Patient Health Questionnaire (PHQ‐9). Responses were tabulated and analysed and the responses from male and female caregivers were analysed and compared separately. Results: Parents of of 98 thalassemia patients were screened during the study. Responses were obtained from 75 fathers and 98 mothers of patients. Overall among all parents, 34% screened positive for minor or major symptoms of depression. Among the fathers, 34% had minor symptoms on screening, but none had any symptoms of major depression. Whereas, among the mothers, only 11% had minor symptoms with 24% had major symptoms. In fact, in this cohort 7% of mothers had severe major depression. No thoughts of self harm were voiced by any caregivers, but 80% of fathers voiced feelings of inadequacy and 34% mentioned anger issues. In contrast, feelings of inadequacy or anger issues were voiced by only 14% of mothers. Summary/Conclusion: Our study showed that almost a third of parents of children with thalassemia were suffering from depression and we recommend all parents should have access to proper counselling, with active screening and access to appropriate services. It was concerning to note that mothers were more liable to major depression requiring therapy. Though fathers were noted to have less severe symptoms of depression, more than 80% harboured feelings of guilt and inadequacy. As physicians, we need to be actively aware of the mental health issues of thalassemia parents and be vigilant to help them access appropriate services as required.
Assessment of Rates of Child Maltreatment in States With Medicaid Expansion vs States Without Medicaid Expansion
Authors: Emily C. B. Brown, Michelle M. Garrison, Hao Bao, Pingping Qu, Carole Jenny, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Physical abuse and neglect affect a significant number of children in the United States. The 2014 Medicaid expansion, in which several states opted to expand their Medicaid programs, is associated with parental financial stability and access to mental health care. <h3>Objective</h3> To determine whether Medicaid expansion is associated with changes in physical abuse and neglect rates. <h3>Design, Setting, and Participants</h3> This ecological study used state-level National Child Abuse and Neglect Data Systems (NCANDS) data from January 1, 2010, through December 31, 2016, to compare the change in physical abuse and neglect rates in states that chose to expand Medicaid vs those that did not. All cases of physical abuse and neglect of children younger than 6 years during the study period that were referred to state-level Child Protective Services and screened in for further intervention after having met a maltreatment risk threshold were included. Cases with only documented sexual or emotional abuse were excluded. A difference-in-difference analysis was conducted from April 12, 2018, through March 26, 2019. <h3>Exposures</h3> State-level Medicaid expansion status. <h3>Main Outcomes and Measures</h3> Incidence rate of screened-in referrals for physical abuse or neglect per 100 000 children younger than 6 years per year by state. <h3>Results</h3> Data were analyzed for 31 states and the District of Columbia that expanded Medicaid and 19 states that did not during the study period, with baseline neglect counts of 646 463 and 388 265, respectively. After Medicaid expansion, 422 fewer cases of neglect per 100 000 children younger than 6 years (95% CI, −753 to −91) were reported each year after adjusting for confounders for comparison of postexpansion and preexpansion rates in states that expanded Medicaid contrasting with the change during that time in nonexpansion states. From 2013 to 2016, Medicaid coverage for adults with dependent children increased a median 1.9% (interquartile range, 0.4% to 4.3%) in the states that did not expand Medicaid and 4.2% (interquartile range, 0.9% to 6.0%) in the states that did. No associations were found between Medicaid coverage or Medicaid eligibility criteria and physical abuse or neglect rates. <h3>Conclusions and Relevance</h3> Medicaid expansion was associated with a reduction in the reported child neglect rate, but not the physical abuse rate. These findings suggest that expanding Medicaid may help prevent child neglect.
PB2288 BENDAMUSTINE‐BORTEZOMIB‐DEXAMETHASONE (BVD) IN HEAVILY PRETREATED MULTIPLE MYELOMA: OLD/NEW ARM IN NOVEL AGENTS’ WORLD
Authors: C. Cerchione, G. Martinelli, S. Rocco, S. Palmieri, D. Nappi, A. E. Pareto, F. Pane, L. Catalano, F. Ferrara
Journal: HemaSphere (2019)

Background: Bendamustine is a bifunctional alkylating agent, with low toxicity, proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Aims: In this retrospective study, It has been evaluated efficacy and tolerance of Bendamustine, in combination with bortezomib‐dexamethasone (BVD) in patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. A regional retrospective real‐life analysis of patients with rrMM who had been treated with BVD as salvage therapy has been performed. Methods: 56 patients (31 M/25 F), with rrMM, median age at diagnosis 57.3 years (r. 36‐82), median age at start of treatment 61.8 years (r.37‐83) treated with several lines of treatments (median 6, r. 2‐11), every refractory to all the drugs previously received (also Bortezomib), received BVD (Bendamustine 90 mg/sqm days 1,2; Bortezomib 1.3 mg/sqm days 1,4,8,11, Dexamethasone 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. ISS was equally distributed, and cytogenetic was evaluable in 12 patients, and in particular one del13q and one t (11;14). All the patients had previously been treated with schedule containing bortezomib and IMIDs, and 30% had also received radiotherapy. 67% of them had undergone at least to a single auSCT. All patients were relapsed and refractory to last therapies received before BVD. Results: Bendamustine was well tolerated, with grade 3 transfusion‐dependent anemia in 41% of patients, and 37% grade 3 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, after a median follow‐up of 14 months (r.2‐36), ORR was 64% (36/56: 4 CR, 7 VGPR, 16 PR, 9 MR) with 8 PD and 12 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Three patients have shown a notable PR after failure of novel agents (i.e. Carfilzomib and Pomalidomide). Median time to response was 1.2 months (r.1‐3), median OS from diagnosis was 62.7 months (range 6‐151), median OS from start of Bendamustine was 9.8 months (range 2‐36). Summary/Conclusion: The triplet Bendamustine‐Bortezomib‐Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT.
AB1342 TRANSLATION AND ADJUSTING THE PATIENT GUIDE FOR OSTEOARTHRITIS INTO DUTCH. LESSONS LEARNED FROM THE JIGSAW-E PROJECT
Authors: Maarten deWit, Wilfred Peter, Thea Vliet Vlieland, Ronald van Ingen, S.M.A. Bierma-Zeinstra, Astrid Dunweg, Hilda Buitelaar, Jorit Meesters, Krysia Dziedzic, Laura Campbell, Steven Blackburn, Dieuwke Schiphof
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In the UK a guidebook was co-developed with UK patients during a OA research study (1). Within the JIGSAW-E (Joint Implementation of Guidelines for Osteoarthritis in Western Europe) project the guidebook is disseminated and implemented in clinical practice in 5 countries: UK, The Netherlands, Norway, Denmark and Portugal. We translated and adapted the English guidebook for use in the Netherlands. <h3>Objectives</h3> To describe the process of translating and adjusting the guidebook into Dutch, and to summarize the key lessons learned. <h3>Methods</h3> Starting point was a paid translated version of the guidebook. The translation was reviewed by an interdisciplinary working group and distributed among stakeholder organizations. Data collections took place by reports of working group meetings, written feedback from stakeholder organizations and patients' interviews focusing on their information needs. Along the way a logbook of adaptations was kept. After triangulation of findings, adaptations were clustered in six preliminary categories and, together with lessons learned, agreed upon in a consensus meeting with the working group. <h3>Results</h3> The working group convened fifteen times. Ten patients were interviewed about the readability and usefulness of the OA guidebook. Eight out of thirteen stakeholder organizations provided feedback on the draft guidebook. Advice for adaptations related to the following preliminary categories: language; patients' needs; cross-cultural differences; health care system; scientific evidence; structure and layout (see Table 1 for examples). Lessons learned related to the low quality of the initial translation, selection of representative working group members, selection of stakeholder organizations, and required time for thorough deliberation during meetings. <h3>Conclusion</h3> Important ingredients for a successful translation and crosscultural adaption of a guidebook (or other patient material) are: time, a professional translation (sufficient budget), relevant stakeholders, and patients who can be critical. Patients who were interviewed about the guidebook added valuable patients' information needs, relevant to the cross-cultural adaptation. A draft framework of categories for cross-cultural adaptation is proposed. <h3>References</h3> [1] Traut, EF, et al, "Specific vascular changes in gout", JAMA, 1954,156(6):591-593 <h3>Acknowledgement:</h3> We thank all stakeholder organizations, patients and the JIGSAW-E team for their efforts. <h3>Disclosure of Interests:</h3> None declared
PS1017 MICRO RNA SIGNATURE OF ONCOGENIC MUSASHI RNA BINDING PROTEINS MSI1 AND MSI2
Authors: S. Duggimpudi, J. Höll, A. Borkhardt
Journal: HemaSphere (2019)

Background: MSI1 and MSI2 are two paralogous RNA binding proteins (RBPs) which are frequently dysregulated in multiple cancers ranging from breast cancer, gliomas, medullobalstoma to acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). RBPs along with MicroRNAs are key form of regulatory molecules working post‐transcriptionally. The interplay between miRNAs and Musashi proteins on target 3’UTRs can rapidly modulate their target mRNA expression. Therefore, identification of mRNA and miRNA interactome is essential for defining the roles of these proteins. We previously identified the mRNAs that are bound and regulated by MSI proteins, next we chose to identify the microRNAs that are regulated by MSI1/2 Aims: The overall objective of the study is to identify the microRNAs that are regulating and regulated by MSI1 and MSI2 to increase our understanding on the function of these oncogenic proteins. Methods: AGO2 PAR‐CLIP experiments aid in identifying the miRNAs that bind to the MSI1/2 mRNA sequence. We will also bioinformatically identify the seed sequence regions on mRNAs that are preferentially bound by miRNAs. Next, we silenced the expression of MSI1 and MSI2 and sequenced the resulting small RNAs using Truseq small RNA sequencing on Illumina platform to identify the miRNAs that are differentially expressed. We carried out functional validation of some of the most promising leukemic miRNA candidates of MSI1/2 using microRNA mimics which will help us uncover new biomarkers and potential therapeutic targets. Results: We have performed AGO2 PAR‐CLIPs on AML and CML cell lines THP‐1 and K562 along with a control and found several interesting oncogenic microRNAs binding MSI1/2. Additionally, we knocked down the expression of MSI1/2 using siRNA cocktail and isolated the microRNAs. We sequenced these microRNAs and are currently in the process of identifying the differentially regulated miRNAs. Also, miR‐143 was identified as top microRNA that bind to MSI2, therefore using miR143 mimics, we validated its binding and effect of its binding on MSI2 expression. We noted a decreased expression of MSI2 upon transfection of cells with miR143 mimics compared to controls. Other top microRNA targets like miR128, miR137, miR320 and miR181 as currently being validated. Summary/Conclusion: We identified transcriptome wide microRNAs that bind and regulate the expression of MSI1 and MSI2. We are also evaluating the miRNAs that are differentially regulated by MSI1/2. We validated the binding and regulation of miR143 on MSI2 expression. Combining the data from AGO‐CLIPs and TruSeq small RNA sequencing data, we will be able to establish the microRNA interactome of Musashi family of RBPs. Data from this study can help us to design therapeutic RNA‐decoys that can target the expression of oncogenic musashi proteins.
PS1058 NOVEL CIRCULATING TUMOR DNA (CTDNA) BASED DDPCR DROP-OFF ASSAYS FOR IMPROVED DISEASE MONITORING IN ACUTE MYELOID LEUKEMIA (AML) A “LIQUID BIOPSY” FOR A “LIQUID TUMOR”
Authors: C. Rausch, F. Ziemann, S. Schneider, M. Subklewe, S. Karsten, M. Rothenberg-Thurley, K.H. Metzeler
Journal: HemaSphere (2019)

Background: AML therapeutic options in recent years for patients over 65 years of age, who generally are not candidates for intensive chemotherapy, have been quite limited, mainly with low intensity chemotherapy, hypomethylating agents and supportive care. Aims: Since January 2014 we have followed the therapeutic protocol consisting in induction chemotherapy with FLUGA chemotherapy scheme according to the PETHEMA group, 2 cycles in the patients of ≤ 75 years and one cycle for the older age, followed by maintenance with decitabine (20 mg / m2 5 days every 4 weeks until progression). Methods: A total of 33 patients with AML with age ≥65 years have recieved the treatment, 17 men and 16 women, with a median age of 77 years (65–91), 19 with primary AML, 2 related to previous chemotherapy, 3 secondary Myeloproliferative Chronic Syndrome and 9 to Myelodysplastic Syndrome. Characteristics of the patients at diagnosis are shown in the Table 1. Table 1. Data at diagnosis∗Median (interval). Results: Twelve patients received 2 cycles of FLUGA scheme and 21 patients received only one cycle. Twenty-one patients went into the maintenance phase with decitabine with a median of administered cycles of 6.5 (range 1–31). 13 patients (39%) reached complete remission. Early mortality at 30 days was 13.3% (4 patients). During evolution, 10 patients (29%) required hospital admission due to infectious process. The median overall survival (OS) was 6 months (95% CI 1–11 months), with a probability of OS at 6 and 12 months of 51% and 29% respectively. There were no significant differences in OS between patients with primary AML versus secondary AML or treatment-related (median 6 versus 3 months, Log-Rank p = 0.73) neither between patients of less or more than 75 years (median of 6 and 5 months respectively: p = 0.93). OS was significantly higher in patients who reached complete remission compared to those who did not (median of 2 and 18 months respectively, p <0.001). Summary/Conclusion: The induction with FLUGA followed by Decitabine maintenance therapy until disease progression is a generally well tolerated treatment, with low initial mortality rate and low number of hospital admissions due to any infection. The percentage of complete responses is reached in a third of the patients and, as is usually observed in elderly subjects, survival is limited to only a third of patients after a year of diagnosis.
AB0584 JOINT PROFILE OF BEHÇET’S DISEASE
Authors: Amel Farhat, Khadija Baccouche, Mohamed Amine EL Achek, Nejla El Amri, Hela Zeglaoui, Elyes Bouajina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Joint manifestations during Behçet's disease (BD) are frequent and polymorphic. <h3>Objectives</h3> To analyze these manifestations through 41 cases. <h3>Methods</h3> A retrospective study of 41 patients, collected at the rheumatology department of Farhat Hached University Hospital over a period of 19 years, meeting the criteria of the international study group on BD. <h3>Results</h3> 41 patients with a mean age of 40.21 years [16-66] were collected. The sex ratio=2.41. The articular and mucocutaneous involvement were constant. Also were found ocular manifestations (5cas), neurological (1cas), cardiac (1cas), gastro-intestinal (1cas), venous thrombosis (5 cases), arterial thrombosis (1 case) and an aneurysm (2 cases). Joint involvement was revealing in 21 cases (51.2%) occurring during evolution in 20 cases with an average delay of 102 months [6-360]. The most frequent manifestations were arthralgia in 24 cases (58.5%) and arthritis in 17 cases. It was predominantly asymmetric (21 cases), mono articular (13 cases), oligoarticular (16 cases) and polyarticular (12 cases). The knees and ankles were the most affected joints in 32 cases and 25 cases respectively, followed by wrist involvement (12 cases), MCP (5 cases) and elbows and shoulders in 4 cases each. A knee flessum was found in 2 cases. X-rays were mostly normal (35 cases). They showed erosive involvement (1case), joint narrowing (1case), osteonecrosis (2cases) and sacroiliitis (2cases). The presence of a popliteal cyst was noted in 2 cases. <h3>Conclusion</h3> Joint manifestations during the BD can be inaugural and take on several clinical aspects. They usually heal without sequelae and do not engage functional prognosis with the exception of rare cases of destructive arthritis. <h3>Disclosure of Interests</h3> None declared
PB2377 SECONDARY HYPOGAMMAGLOBULINEMIA AFTER HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION FOR LYMPHOMA
Authors: A. Nakaya, K. Ishii, S. Fujita, A. Satake, T. Nakanishi, Y. Azuma, Y. Tsubokura, R. Saito, A. Konishi, M. Hotta, H. Yoshimura, T. Ito, S. Nomura
Journal: HemaSphere (2019)

Background: Secondary hypogammaglobulinemia is associated with hematological malignancy, particularly related to lymphoid malignancy. Other than malignancy itself, treatments induce iatrogenic hypogammaglobulinemia. In standard, eligible patients with advanced lymphoma receive high dose chemotherapy with autologous stem cell transplantation (HDT/ASCT). However, frequency and risk of hypogammaglobulinemia in auto‐setting is unknown. Aims: To clarify frequency and risk of hypogammaglobulinemia in auto‐setting. Methods: We retrospectively analyzed 101 patients with advanced lymphoma who received HDT/ASCT at Kansai Medical University Hospital and Kansai Medical University Medical Center from August 2006 to September 2018. All patients received MEAM regimen with/without rituximab as a conditioning. Results: Median age was 59(24‐71) y/o. Among 101 patients, 92% of patients(n = 93) was measured immunoglobulin levels routinely. 52% of patients(n = 53) had hypogammaglobulinemia(IgG &lt; 700 mg/dl) and 25%(n = 25) of patients remains hypogammaglobulinemia presently. 14 patients recovered from hypogammaglobulinemia. Median period to recovery was 28(0.7‐56.8)months. Among the patients developed hypogammaglobulinemia, 87% was with B cell lymphoma, 9% with T cell lymphoma and 4% with Hodgkin lymphoma. Severe infection(≥grade3) was seen in 16 patients. The most frequent infection was bacterial infection unknown species(n = 5), followed HBV reactivation(n = 3) and Herpes zoster(n = 3), and BKV(n = 2). Summary/Conclusion: 52% of patients had hypogammaglobulinemia after HDT/ASCT, which was not only with B cell lymphoma but also with T cell and Hodgkin lymphoma. Median period of immunoglobulin recover is over one year. Addition to common bacterial infections, we should be careful about virus infections.
Novel Drug Targets for Ischemic Stroke Identified Through Mendelian Randomization Analysis of the Blood Proteome
Authors: Michael Chong, Jennifer Sjaarda, Marie Pigeyre, Pedrum Mohammadi-Shemirani, Ricky Lali, Ashkan Shoamanesh, Hertzel Chaim Gerstein, Guillaume Paré
Journal: Circulation (2019)

Novel, effective, and safe drugs are warranted for treatment of ischemic stroke. Circulating protein biomarkers with causal genetic evidence represent promising drug targets, but no systematic screen of the proteome has been performed.First, using Mendelian randomization (MR) analyses, we assessed 653 circulating proteins as possible causal mediators for 3 different subtypes of ischemic stroke: large artery atherosclerosis, cardioembolic stroke, and small artery occlusion. Second, we used MR to assess whether identified biomarkers also affect risk for intracranial bleeding, specifically intracerebral and subarachnoid hemorrhages. Third, we expanded this analysis to 679 diseases to test a broad spectrum of side effects associated with hypothetical therapeutic agents for ischemic stroke that target the identified biomarkers. For all MR analyses, summary-level data from genome-wide association studies (GWAS) were used to ascertain genetic effects on circulating biomarker levels versus disease risk. Biomarker effects were derived by meta-analysis of 5 GWAS (N≤20 509). Disease effects were derived from large GWAS analyses, including MEGASTROKE (N≤322 150) and UK Biobank (N≤408 961) studies.Several biomarkers emerged as causal mediators for ischemic stroke. Causal mediators for cardioembolic stroke included histo-blood group ABO system transferase, coagulation factor XI, scavenger receptor class A5 (SCARA5), and tumor necrosis factor-like weak inducer of apoptosis (TNFSF12). Causal mediators for large artery atherosclerosis included ABO, cluster of differentiation 40, apolipoprotein(a), and matrix metalloproteinase-12. SCARA5 (odds ratio [OR]=0.78; 95% CI, 0.70-0.88; P=1.46×10-5) and TNFSF12 (OR=0.86; 95% CI, 0.81-0.91; P=7.69×10-7) represent novel protective mediators of cardioembolic stroke. TNFSF12 also increased the risk of subarachnoid (OR=1.53; 95% CI, 1.31-1.78; P=3.32×10-8) and intracerebral (OR=1.34; 95% CI, 1.14-1.58; P=4.05×10-4) hemorrhages, whereas SCARA5 decreased the risk of subarachnoid hemorrhage (OR=0.61; 95% CI, 0.47-0.81; P=5.20×10-4). Multiple side effects beyond stroke were identified for 6 of 7 biomarkers, most (75%) of which were beneficial. No adverse side effects were found for coagulation factor XI, apolipoprotein(a), and SCARA5.Through a systematic MR screen of the circulating proteome, causal roles for 5 established and 2 novel biomarkers for ischemic stroke were identified. Side-effect profiles were characterized to help inform drug target prioritization. In particular, SCARA5 represents a promising target for treatment of cardioembolic stroke, with no predicted adverse side effects.