tbuckley/cabot-search huggingface dataset:
PF547 FACTORS ASSOCIATED WITH THE NEED FOR TRANSFUSIONS IN PATIENTS WITH LOWER RISK MYELODYSPLASTIC SYNDROME (MDS). DATA FROM THE REGULAR CARE MDS‐REGISTRY IN GERMANY
Authors: H.T. Steinmetz, J. Toczek‐Thiel, M. Hellmich, J. Lipke, R. Liersch, A. Sauer, H. Tesch, J. Hessling, S. Schmitz
Journal: HemaSphere (2019)

Background: In 2009 we started a registry to evaluate the course of MDS in routine care in Germany. Aims: The aim of the current evaluation was to analyze factors associated with the need for red blood cell transfusions in patients (pts) with IPSS low and intermediate‐1 (int‐1) risk at diagnosis and in the course of the disease. Methods: 2,447 patients (pts) with MDS were included in the regular care MDS‐registry from July 2009 till December 2016, provided that the diagnosis was confirmed by bone marrow biopsy and the pts had given their written informed consent. Baseline parameters at diagnosis and the clinical course were quarterly documented in an online database (IoStudy by Iomedico) by 90 centers all over Germany. image Results: At the data‐cut in April 2017 1,240 of 2,428 evaluable pts (50.7%) had a low‐ (612 pts/49,4%) or an int‐1 ‐risk MDS (628 pts. /50.6%). The median age of the lower risk pts was 74 years (range 26–94), 484 (39%) were women and the median time of observation was 25 months (mo, range 0–97, mean 30,62mo). At diagnosis 114 (18.6%) low‐ and 169 (26.9%) int‐1‐ risk pts were transfusion‐dependent (TD). The median time to become TD was significantly different (log rank (Mantel‐Cox) p = &lt;0.01) between low‐ (28mo, SD 4.030, 95% CI 20.1 – 35.9) and int‐1‐ risk pts (9mo, SD 1.380, 95% CI 6.295 – 11.705). Survival (OS) was estimated by Kaplan‐Meier curves for pts without TD mean 82,661mo (SD 1,813mo, 95%&gt;CI 79,108 ‐ 86,214) and pts with TD mean 51,261mo (SD 1,453mo, 95%&gt;CI 48,413 ‐ 54,109)(fig. 1A). Furthermore, OS after becoming TD was estimated by a time‐to‐TD stratified Kaplan‐Meyer curve (fig. 1B), that shows a significant difference (0.00 Log Rank, Mantel‐Cox). In an univariate analysis the following baseline parameters were significantly associated with a shorter duration to become TD: age ≥80years, hemoglobin (hb), count of reticulocytes, LDH, endogenous erythropoietin level (epo), ferritin, and fibrosis in bone marrow histology. The following parameters were not associated: sex, thrombocyte‐, leucocyte‐ and granulocyte‐count, folic‐acid‐, vitamin B12 level, and CRP. Del‐5q and trisomy 8 were the only cytogenetic abnormalities significantly associated with a shorter duration to become TD. In a cox regression analysis (table 1) hb and epo were significant only. image Summary/Conclusion: The sooner pts becomes TD in the course of MDS, the poorer is the prognosis. It should be tested if a therapy that respites TD can prolong OS. Supported by an unrestricted grand from Celgene, Munich, Germany
PB1797 DEATHS IN PEDIATRIC BURKITT LYMPHOMA PATIENTS. WHAT COULD BE IMPROVED?
Authors: H. Abdelrahman, A. Hamoda, N. El Kenaai, S. Salem, I. Zaki, G. Taha, O. Ahmed
Journal: HemaSphere (2019)

Background: Many patients with Burkitt lymphoma has rapid tumor regression following administration of chemotherapeutic drugs. However, while the patients are making “good progress” clinically, some of them suddenly collapse and die. Aims: The aim of this work is to analyze causes of death among pediatric mature B cell NHL, to identify adverse prognostic factors that might put those patients at high risk of mortality at different phases of treatment. And finally, to set a series of recommendation to ameliorate the OS and avoid unexpected treatment related mortality Methods: We conducted a retrospective analysis that included all Burkitt Lymphoma (BL) patients who were diagnosed and treated at CCHE during the period from 06/2012 till end of 12/2018 and died. All patients were treated according to LMB96 protocol, and were stratified as low, intermediate or high risk group. Analysis included epidemiologic data, initial presentation, laboratory and radiologic investigations, tumor stage, risk stratification, direct cause of death, associated co‐morbidity and phase of treatment where death occurred. Results: Out of 570 patients recorded during the study period, 84 (14.7%) died. Majority (69%) were males with mean age 7.6 years. Most of them (94%) had advanced stage (III and IV) disease. Forty eight patients from intermediate (12.2%), and 36 from high risk group (28.3%) died. Majority of patients (78.6%) died in active disease, while 21.4% died in CR/PR. Main causes of death were septic shock (34.5%), disease progression in (31%), tumor lysis syndrome (TLS) (11.9%). Other reported causes of death were sever chest infection (6%), multi‐organ failure associated with sepsis (6%), pulmonary hemorrhage (2.4%), neutropenic enterocolitis, GVHD, and gut perforation (1.2%) each. Three patients (3.6%) died upon arrival to the hospital without receiving any kind of chemotherapy, 17 (20.4%) during prephase, 24 (28.5%) during induction, 8 (9.5%) during consolidation, 2 (6.1%) during maintenance phase. For relapsing patients, 18 (21.4%) died from chemotherapy toxicity of second line, while 6 (7.1%) were on palliative care when they died. Summary/Conclusion: Despite being a well‐equipped tertiary care hospital dedicated to the management of pediatric malignancies, we report a very high mortality rate in our hospital. Late presentation, TLS and sever sepsis are main causes of death throughout different phases of treatment. For relapsed patient, toxicity of 2 nd line chemotherapy and tumor progression are the main causes of death. We need intensify supportive care measures, and to better identify patients at high risk for mortality to avoid unnecessary patients’ death.
Abstract 17: Prehospital Intubation Results in Increases in Pulmonary Infection in Traumatically Injured Patients
Authors: Douglas L Andrusiek, Daniel Szydlo, Martin Schrieber, Karen Brasel, Joseph Minei, Rardi van Heest, Susanne May
Journal: Circulation (2012)

Introduction: Infection is a major cause of morbidity and mortality in multisystem trauma. Sources of infection in trauma are not well understood. The impact of invasive prehospital procedures, inc...
PB2040 EMERGENT INFECTIONS ASSOCIATED TO THE TREATMENT WITH NEW MOLECULES IN CHRONIC LYMPHOCYTIC LEUKEMIA ‐ SINGLE CENTER EXPERIENCE
Authors: A.A. Tomescu, A. Enache, R. Dragan, M. Vasilica, D. Coriu, I. Ursuleac
Journal: HemaSphere (2019)

Background: During the last years, the overall response to the treatment of patients with chronic lymphocytic leukemia (CLL) has improved due to the introduction in the therapeutical armentarium of the new molecules ‐ Bruton kinase (BTK) inhibitors (Ibrutinib) and Phosphoinositide 3‐kinases (PI3Ks) inhibitors ‐ Idelalisib. The main late adverse reaction of the treatment with these 2 products is immunosupression with high infectious risk, including viral reactivations and opportunistic de novo infections (bacterial, mycotic or viral). Aims: To find the risk factors associated to the risk of infections in CLL patients treated with new molecules Methods: A retrospective, clinico‐epidemiological study including 12 CLL patients diagnosed in our centre with various infections during therapy with Idelalisib or Ibrutinib. Results: 12 CLL patients (6 men, 6 women) have been observed: 2 treated with Idelalisib 150 mg BID and 10 treated with Ibrutinib 420 mg QD; median age ‐ 56 years (35 – 75). There have been studied: the number of anterior therapeutic lines (2 – 5 patients, 3 – 5 patients, 4 – 2 patients), treatment‐free period before new molecules have been introduced (medium 15 months), therapy duration before the onset of the infection (19 months medium); additional risk factors ‐ previous hypogammaglobulinemia (observed in all the studied patients). We have identified viral reactivations (CMV, VZV, HSV), fungal (Aspergillus sp.) and bacterial (Klebsiella sp., E. coli, Corynebacterium bovis, MRSA) infections. The localizations were: cerebral (2 cases of aspergillosis and CMV), pulmonary (3 cases of aspergillosis), genito‐urinary (3 cases of multiresistent E. coli and HSV) and cutaneous (2 cases of HSV and MRSA). 5 deaths occurred due to uncontrolled disease and infection. Summary/Conclusion: Treatment with new molecules is associated with high infectious risk. We have identified multiple causes: advanced stage of disease, heavily treated patiens, hypogammaglobulinemia and comorbidities (diabetes). These patients should be closely monitored for infectious risk during treatment with new molecules.
SP0041 TACKLING TRANSITION: THE CURRENT LANDSCAPE, AND WHERE WE ARE HEADING
Authors: Stephen Ball
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The transition from childhood to adulthood is a key life stage. While the time course of the bio-psycho-social development of young people is continuous, many of the health and social care services with which they may be involved have relatively fixed, rigid structures. This can be challenging for young adults: leading to a sense of marginalisation and alienation. Young people with long term health or social care needs and who require on-going support as they exit childhood are often further challenged by the requirement to move from a children"s service (with which they are familiar) to an adult service: one requiring new relationships and with differing expectations. Evidence supports the view that young people may be lost in the gap between children"s and adult services, with a negative impact on longer-term health. Good practice in 'transitional" care (<i>'a multi-faceted, active process that attends to the medical, psychological and educational/vocational needs of adolescents as they move from child to adult-centred care"</i>, Blum 1993) can improve engagement and result in positive longer-term outcomes. Developmentally appropriate services recognise young people as a distinct group, subject to constantly changing circumstances. This model considers the young person as a whole: addressing their biological, psychological and social development in the broadest terms. Critically, the approach supports the young person to take an active role in the processes with which they are involved. While developmentally appropriate care and 'transition" are not equivalent, a developmentally appropriate approach to transition has clear benefits: seeing the process as being outcome and skills-based, rather than time-based. Adolescence and early adulthood are times when life-long health behaviours are set in place; good health for young people is a foundation for good health in later life. There is a need to invest in age appropriate health promotion and youth-friendly health services if we are truly committed to improving young people"s health outcomes and the health of the adult population they will go on to form. There is an opportunity to develop and sustain a generational shift in health literacy and health-related behaviours: a real legacy; and an investment in the future. <h3>Reference:</h3> [1] Farre, A, Wood V, Radley T, et al. 2015. Developmentally appropriate healthcare for young people: a scoping study. Arch Dis Child 100: 144-151 <h3>Disclosure of Interests:</h3> None declared
AB0922 UPDATES ON THE EVIDENCE BASED INTERDISCIPLINARY GUIDELINES FOR HENOCH-SCHöNLEIN PURPURA
Authors: Mohammed Hassan Abu-Zaid, Yasser El Miedany, Waleed Hassan, Yomna Farag, Hala Lotfy, Mervat Eissa, Mohammed A. Mortada, Samah Ismail Nasef, Dalia Mekkawy, Ghada El Deriny, Maha El Gaafary, Yossra Atef, Nadia El Aroussy
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Henoch-Schönlein purpura (HSP) is the most common childhood vasculitis, it is characterized by inflammation of small vessels leading to non-thrombocytopenic purpura, arthritis/arthralgia, GI hemorrhage and glomerulonephritis<sup>1</sup>. There is a very poor evidence base to guide the management of HSP, particularly for those with the severe forms of HSP nephritis, Up till now there are no EULAR or ACR recommendations for management of HSP. <h3>Objectives</h3> To set an updated interdisciplinary recommendations for the management of HSP <h3>Methods</h3> Interdisciplinary guidelines were developed with representative from PRINTO Egypt for pediatric rheumatology as well as patients' group. A systemic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for treatment and final statements were discussed in a consensus meeting (Nominal Group Technique). A preliminary draft was fine tuned and discussed thereafter by all participants (Delphi Procedure). <h3>Results</h3> Consensus was reached on recommendations, including a standardized treatment strategy according to the HSP severity state in the individual patient. In this updated interdisciplinary guideline for HSP; treatment was tailored to the patient's pathology and its severity (figure 1). Criteria for admission were identified as: severe arthritis or arthralgia limiting ability to weight bearing and mobilization, severe abdominal pain, GI hemorrhage, evidence of nephritis/nephritic syndrome or renal impairment, evidence of neurological symptoms. Criteria for early referral to pediatric nephrologist were also identified including: hypertension, abnormal renal function, macroscopic hematuria for 5-days, nephrotic syndrome, acute nephritic syndrome, as well as persistent proteinuria. <h3>Conclusion</h3> A total of seven evidence based interdisciplinary recommendations for management of HSP have been formulated, that provide an up-to-date guidance of HSP management. <h3>Reference</h3> [1] Hetland LE, Susrud KS, Lindahl KH, Bygum A. Henoch-Schönlein Purpura: A Literature Review. Acta Derm Venereol. 2017Nov15;97(10):1160-1166. doi: 10.2340/00015555-2733. <h3>Disclosure of Interests</h3> None declared
Detection of <i>NRG1</i> Fusions in Solid Tumors: Rare Gold?
Authors: Anastasios Dimou, D. Ross Camidge
Journal: Clinical Cancer Research (2019)

Abstract Fusions between NRG1 and partner genes are rare, tumorigenic genomic events occurring in patients with lung and other cancers, associated with activation of ERBB2/ERBB3 heterodimers. Inhibition of ERBB2 and/or ERBB3 in this group of patients is a promising strategy in clinical trials. See related article by Jonna et al., p. 4966
Giant oversights in the human gut virome
Authors: Thomas D S Sutton, Adam G Clooney, Colin Hill
Journal: Gut (2019)

We read with interest the paper by Zuo  et al ,1 which used deep sequencing to identify gut mucosal virome alterations in individuals with UC. One of many interesting findings reported by the authors was the detection of giant viruses infecting algae and amoeba ( Mimivirus and Chrysochromulina ericina virus). The authors suggested an association with the geographical distribution of individuals and concluded that they were more abundant in patients with UC than controls. We reanalysed the data and propose that issues related to the virome analysis pipeline led to the incorrect identification of these viruses.

First, the DNA extraction method states that 0.22 µm filters were used to remove bacterial and eukaryotic cells, followed by chemical and enzymatic degradation of DNA unprotected by viral capsids. Mimivirus has a capsid with a diameter of 0.5 µm, surrounded by a 0.125 µm thick layer of closely packed fibres,2 …
Insights into Platypus Population Structure and History from Whole-Genome Sequencing
Authors: Hilary C Martin, Elizabeth M Batty, Julie Hussin, Portia Westall, Tasman Daish, Stephen Kolomyjec, Paolo Piazza, Rory Bowden, Margaret Hawkins, Tom Grant, Craig Moritz, Frank Grutzner, Jaime Gongora, Peter Donnelly
Journal: Molecular Biology and Evolution (2018)

The platypus is an egg-laying mammal which, alongside the echidna, occupies a unique place in the mammalian phylogenetic tree. Despite widespread interest in its unusual biology, little is known about its population structure or recent evolutionary history. To provide new insights into the dispersal and demographic history of this iconic species, we sequenced the genomes of 57 platypuses from across the whole species range in eastern mainland Australia and Tasmania. Using a highly improved reference genome, we called over 6.7 M SNPs, providing an informative genetic data set for population analyses. Our results show very strong population structure in the platypus, with our sampling locations corresponding to discrete groupings between which there is no evidence for recent gene flow. Genome-wide data allowed us to establish that 28 of the 57 sampled individuals had at least a third-degree relative among other samples from the same river, often taken at different times. Taking advantage of a sampled family quartet, we estimated the de novo mutation rate in the platypus at 7.0 × 10−9/bp/generation (95% CI 4.1 × 10−9–1.2 × 10−8/bp/generation). We estimated effective population sizes of ancestral populations and haplotype sharing between current groupings, and found evidence for bottlenecks and long-term population decline in multiple regions, and early divergence between populations in different regions. This study demonstrates the power of whole-genome sequencing for studying natural populations of an evolutionarily important species.
PS1415 SURVIVAL OF MULTIPLE MYELOMA PATIENTS DIAGNOSED 1970–2015: REAL-WORLD DATA FROM A SINGLE CENTER
Authors: L.G. Rodríguez-Lobato, A. Pereira, C. Fernández de Larrea, N. Tovar, M.T. Cibeira, J. Bladé, L. Rosiñol
Journal: HemaSphere (2019)

Background: The management of relapsed myeloma continues to evolve including the dose and schedule of carfilzomib (carfil) with increasing use of once weekly (QW) IV carfil as opposed to twice weekly (BIW) administration. Selinexor in combination with dexamethasone (dex) has demonstrated a 26.2% ORR in pts with triple-class refractory myeloma (defined as refractory to an immunomodulatory imide drug [IMiD], proteasome inhibitor [PI] and anti-CD-38 monoclonal antibody [mAb]) including deep responses with 6 very good partial response (VGPR) and 2 pts in a stringent complete response (sCR) (minimal residual disease negative). Jakubowiak et al.have previously demonstrated that BIW selinexor can be safely combined with BIW carfil with an ORR of 63% (ASH 2016). Given the increasing use of QW carfil, we have initiated a phase 1 study to determine the recommended phase 2 dose(RP2D) of QW selinexor in combination with carfil/dex. Aims: The primary objectives of the study were to determine the maximum tolerated dose (MTD), RP2D, and to assess the safety, tolerability, and preliminary efficacy of the combination of SKd in pts with RRMM. Methods: This is amulticenter, open-label study. Pts whose MM is relapsing, is not refractory to carfil, and may have had prior PI exposure were eligible. Selinexor was dosed QW at 80 or 100 mg. Carfil was dosed QW at 56 mg/m2or 70 mg/m2. Dex was given at 40 mg QW. Results: As of February 20th, 2019, 9 pts were enrolled in the study. Of these, 3 were male and 6 were female. The median age was 71 years (range 50 – 76) and the median number of prior treatments was of 4 (range 2 – 8) prior treatment regimens. All 9 pts were carfil naïve. Seven of 9 pts were refractory to prior treatment with bortezomib. Eight pts were refractory to prior lenalidomide (len) or pomalidomide (pom) treatment including 3 pts refractory to both len and pom. Five pts were refractory to prior dara treatment. Six dose limiting toxicities (DLTs) were observed, which can be seen in Table 1. Common treatment-related Grade 1/2 adverse events (AEs) included: nausea (6 pts), anemia (3 pts), fatigue (3 pts), and leukopenia (3 pts). Grade 3/4 AEs included: thrombocytopenia (5 pts), hyperglycemia (2 pts), and anemia (2 pts). Eight pts were evaluable for response and the ORR was 75% including (1 complete response, 4 VGPR, 1 unconfirmed VGPR); the patient with unconfirmed VGPR is still on study. Two pts had stable disease. One pt is pending response evaluation. As of February 20th, 6 pts remain on treatment.Summary/Conclusion: The combination of SKd has demonstrated encouraging preliminary activity with an ORR of 75%. No unexpected AEs were noted. Phase 1 dose escalation of the combination of SKd will define the optimal RP2D.
Abstract 18068: Trends in Proportionate Cardiovascular Mortality Among Adults With Human Immunodeficiency Virus in the United States: 1999-2013
Authors: Ehete M Bahiru, Matthew J Feinstein, Chad J Achenbach, Chris T Longenecker, Priscilla Y Hsue, Kaku So-Armah, Matthew S Freiberg, Donald M Lloyd-Jones
Journal: Circulation (2015)

Introduction: Due to the success of antiretroviral therapy, Human Immunodeficiency Virus (HIV)-infected individuals live longer and are at risk for cardiovascular disease (CVD). Whether the proportion of deaths due to CVD in the HIV-infected population has increased over time is unknown. Hypothesis: Our hypothesis was that proportionate mortality from CVD in the HIV-infected population has increased significantly since 1999. Methods: Using the publicly available CDC Wonder database of U.S. national mortality data, we assessed proportionate CVD mortality among adults aged ≥25 years with HIV. We compared these data to proportionate CVD mortality in two control groups: the general population and people with underlying inflammatory disease (i.e., inflammatory polyarthropathies (IPA)). For each group, we calculated proportionate CVD mortality by dividing deaths attributed to circulatory causes (based on ICD10 coding) by all causes of death for each year from 1999 to 2013. Results: Proportionate CVD mortality increased among HIV+ individuals from 1.9% of deaths in 1999 to 4.6% in 2013 (Figure 1); this pattern of increasing proportionate mortality was highly significant for men and women (P&lt;0.01) and consistent across race groups. Meanwhile, proportionate CVD mortality declined in the general population (41% in 1999 to 32% in 2013; P&lt;0.01) and IPA population (40% in 1999 to 29% in 2013; P&lt;0.01). A sensitivity analysis including only in-hospital deaths also revealed a highly significant increase in proportionate CVD mortality for HIV-infected individuals, from 2.1% in 1999 to 3.9% in 2013 (P&lt;0.01). Hypertensive and pulmonary heart diseases were 2-3 times more likely to be the cause of death in the HIV population than in the general population. Conclusions: Proportionate CVD mortality appears to have increased substantially in the HIV-infected population since 1999. Further studies are needed to guide risk assessment and prevention in this unique population.