tbuckley/cabot-search huggingface dataset:
S890 NEW WHOLE GENOME ASSOCIATION SCANNING APPROACH FOR THE DISCOVERY OF HLA CLASS I‐RESTRICTED MINOR HISTOCOMPATIBILITY ANTIGENS
Authors: K. Fuchs, A. Adriaans, W. Honders, D. van der Lee, E. van der Meijden, M. Pont, R. Monajemi, S. Kielbasa, P. ’t Hoen, C. van Bergen, F. Falkenburg, M. Griffioen
Journal: HemaSphere (2019)

Background: Patients that undergo allogeneic stem cell transplantation (SCT) as treatment for hematological diseases face the risk of relapse as well as Graft‐versus‐Host Disease (GvHD). GvHD as well as the favorable Graft‐versus‐Leukemia effect are mediated by donor T cells. These T cells recognize minor histocompatibility antigens: polymorphic peptides, which are presented on the cell surface by HLA molecules and are caused by genetic differences in single nucleotide polymorphisms (SNPs) between patient and donor. Knowledge about mismatched minor histocompatibility antigens may enable a more directed donor search as well as better prediction and measurement of the Graft‐versus‐Leukemia effect and GvHD for personalized treatment after transplantation, thereby contributing to a better outcome for patients treated with allogeneic SCT. Aims: Identification of minor histocompatibility antigens has been a laborious process in the past. Therefore, whole genome association scanning was developed in our laboratory. However, this method was restricted to two HLAs and screening of one million SNPs. The aim of this study is to develop and use an optimized method to identify the dominant repertoire of minor histocompatibility antigens in common HLA class I alleles. Methods: Donor T‐cells isolated from patients after allogeneic SCT are tested for recognition of a new panel of 191 selected B‐cell lines, which are sequenced in the 1000 Genome Project. This panel enables the inclusion of seven common HLAs and increases SNP coverage to 12 million (MAF &gt; 0.01). SNPs that strongly associate with T‐cell recognition are subsequently validated to encode minor histocompatibility antigens. Results: A total of 19 novel minor histocompatibility antigens have been identified that are presented in seven common HLA class I alleles, showing the potential of this optimized approach. Besides conventional antigens, cryptic peptides were found as well as peptides restricted to HLAs that were not primarily targeted. Summary/Conclusion: This improved approach for whole genome association scanning has been successfully applied in rapidly discovering new minor histocompatibility antigens. The new method surpasses previous methods in its rapidness and coverage of HLAs and SNPs across the human genome, which additionally allows for identification of cryptic peptides. With the increasing number of patients that are analyzed in this study, T‐cells recognizing known minor histocompatibility antigens are more often isolated, indicating that the repertoire of minor histocompatibility antigens is limited. Our optimized method is expected to discover the majority of unknown antigens in this repertoire, thereby contributing essential knowledge for new strategies to improve clinical outcome after allogeneic SCT.
PS1284 GLOBAL GUIDELINE FOR THE DIAGNOSIS AND MANAGEMENT OF MUCORMYCOSIS: AN INITIATIVE OF THE ECMM IN COOPERATION WITH THE MSG ERC
Authors: O. Cornely, A. Chakrabarti
Journal: HemaSphere (2019)

Please indicate where the abstract has been published before: The Lancet Infectious Diseases Background: Mucormycosis is a rare disease that may progress rapidly. Although urgent surgical and medical intervention is lifesaving, diagnosis is often delayed and mortality rates are high. Guidance on the complex multidisciplinary management has the potential to improve prognosis. Management pathways depend on recognising disease patterns and availability of diagnostic and therapeutic options. Aims: To address differences between the regions of the world, authors from 33 countries analysed published evidence on mucormycosis management and provide recommendations as part of the “One World One Guideline” initiative. Methods: Consensus process involving experts from all UN regions, comprising physicians and scientists involved in various aspects of mucormycosis management, representing the fields of microbiology, pathology, radiology, infectious diseases, surgery, paediatrics, haematology, intensive care, dermatology, and pharmacology. Results: This guidance document provides practical help in clinical decision making and identifies areas of uncertainty and future research direction. Summary/Conclusion: Mucormycosis requires different tailored approaches in different regions of the world‐ This guidance document is the first in a series from One World One Guideline initiative.
FRI0336 INCIDENCE OF IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM) IN ADULTS IN FIFE, SCOTLAND, UK
Authors: John McLaren, Paul Allcoat, Michael Hearst, Elizabeth Furrie, Sarah Hailwood
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> <h3>Objectives</h3> To determine the Adult incidence of IIM in the Kingdom of Fife, Scotland. The Fife population is 370,000 and constitutes 6.8% of the Scottish Population (5,425,000). 98% of the Fife population is Caucasian. We also sought to characterise the incident IIM cases in terms of subtype and autoantibody profile. <h3>Methods</h3> All newly diagnosed Adult cases (≥ 18 years) of IIM between 01.03.17 and 30.11.18 were recorded (11.75 year period). The cases were identified by a search of the Fife Rheumatic Diseases Unit Database using IIM-specific ICD-10 codes. These were cross-referenced with a prospective personal database of IIM cases established by the Lead Author (JMcL) on 26.02.17. In addition a search of all Fife patients enrolled in the UKMYONET study was also performed. All patients with 'definite' or 'probable' IIM by the Bohan &amp; Peter 1977 criteria; Clinically defined Inclusion Body Myositis (IBM) by the ENMC 2011 criteria; or other specific criteria in the case of Clinically Amyopathic Dermatomyositis (CADM) and Immune-mediated Necrotising myopathy (IMNM) were included. <h3>Results</h3> 53 newly diagnosed Adult IIM cases were identified. 11 Dermatomyositis (DM) (3 NXP2; 2 Jo-1; 2 TIF1-G; 1 Mi-2; 3 Myositis-specific antibody (MSA) not tested). 4 Polymositis (PM) (1 Jo-1; 1 MDA5; 1 MSA/Myosits-associated antibody (MAA) negative; 1 MSA not tested). 12 Anti-synthetase syndrome (8 Jo-1; 3 PL7; 1 PL12) and 3 patients with Jo-1 isolated Interstitial lung disease (ILD). 5 Overlap Connective tissue disease (CTD) : 2 Systemic Lupus Erythematosus; 2 Systemic sclerosis; 1 Mixed CTD. 5 Cancer-associated myositis (CAM) : 2 lung (1 NXP2 DM &amp; 1 SRP PM); 1 ovarian (DM, MSA not tested); 1 Breast (DM, TIF1-G); 1 Prostate (DM, Mi-2). 5 CADM (2 MDA5; 1 TIF1-G; 1 NXP2; 1 MSA not tested). 4 IMNM (2 HMGCR; 1 HMGCR overlap with IBM; 1 SRP overlap with IBM who developed bladder cancer &lt; 3 years after diagnosis). 4 sporadic IBM (2 cN-1A/Mup44 of which 1 overlap with Primary Sjogren's Syndrome; 2 MAA not tested). <h3>Conclusion</h3> The incidence of IIM in Fife, Scotland is 4.5 cases per year which equates to an annual incidence of 12.2 cases per million population. This is comparable with the incidence data published for Salford in the UK (17.6). However the IIM subtypes differed from Salford in that Fife has a much lower incidence of PM. 40/49 (82%) of Fife patients who were tested were found to be MSA positive. <h3>Disclosure of Interests</h3> None declared
Competition of charge-mediated and specific binding by peptide-tagged cationic liposome–DNA nanoparticles in vitro and in vivo
Authors: Emily Wonder, Lorena Simón-Gracia, Pablo Scodeller, Ramsey N. Majzoub, Venkata Ramana Kotamraju, Kai K. Ewert, Tambet Teesalu, Cyrus R. Safinya
Journal: Biomaterials (2018)
PF322 APPROACH TO DOUBLE HIT LYMPHOMA (DHL) DIAGNOSIS AND TREATMENT IN EUROPE – A CROSS‐SECTION STUDY OF EHA LYMPHOMA WORKING PARTY (EHA LYG)
Authors: I. Aurer, M.J. Kersten, M. Dreyling, M. Federico
Journal: HemaSphere (2019)

Background: DHL is a new lymphoma entity defined in the WHO 2018 classification. Diagnosis of DHL requires the use of FISH for MYC, BCL2 and BCL6, a technic that is not routinely used in the diagnostics of diffuse large‐B cell lymphomas (DLBCL). Treatment recommendations for DHL differ from those of DLBCL, but the level of evidence for them is low. Aims: EHA LYG performed this study to identify common practices in DHL diagnosis and treatment in different European countries. Methods: Lymphoma experts from different European countries were contacted and asked to fill out a questionnaire regarding recommendations and common practices in diagnosis and treatment of suspected DHL and DLBCL. Results: Almost half of European countries do not have national recommendations for DHL screening. Routine FISH screening is recommended in less than 20%, approximately 20% recommend screening all double‐expressors irrespective of cell of origin (COO), and 10% only GC‐type double‐expressors. COO is universally defined according to the Hans algorithm. MYC cut‐off values for defining double‐expressors are mostly 40% (but sometimes 70%), for BCL2 between 40% and 60% and for BCL6 60%. In one third of countries is screening recommended also in cases with clinical high‐risk features. FISH for DHL is routinely available to all DLBCL patients in approximately 40% of countries, in another 40% only to patients treated at referral hospitals, and not available at all in 20%. Only rarely is the availability of testing dependent on the type of insurance. Approximately a third of countries have nation‐wide recommendations for treating DHL. However, most patients with diagnosed DHL who are able to tolerate more aggressive therapies receive regimens different from R‐CHOP, mostly DA‐R‐EPOCH and Burkitt lymphoma‐type regimens, less frequently R‐CHOEP14. In approximately one third of the countries are alternative regimens used only in referral centers. Summary/Conclusion: The responses to our questionnaire suggest that current practices in recognizing DHL in Europe, even in relatively rich countries, result in missing of a substantial number of patients, especially in those treated outside of referral centers and with lower‐risk features. This fact must be taken into account when describing the natural history of DHL. Most patients diagnosed with DHL receive more aggressive treatment than those with DLBCL.
AB0159 SILENT CEREBRAL MRI FINDINGS IN LUPUS NEPHRITIS AND NON NEPHRITIS PATIENTS
Authors: Yumn Ahmed
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Lupus nephritis carries high morbidity and mortality and whenever added to neuropsychiatric manifestations lead to more unfavorable prognosis. The current work focused on LN patients comparing them to those without kidney affection, studying their cerebral MRI and its correlation with the histopathological classes of LN and disease activity. <h3>Objectives</h3> To study the effect of renal affection on the brain in SLE and their clinical significance with early detection and management of such lethal comorbidity <h3>Methods</h3> Cerebral MRI and MRA were studied in 40 SLE patients without neuropsychiatric manifestation; 20 LN patients with different histopathological classes and 20 patients without kidney affection. Disease activity was assessed for all patients using SLE disease activity index <h3>Results</h3> Abnormal MRI brain findings were more common in LN patients "though non significant" (P=0.9). The most common lesions were white matter hyperintense lesions. Number and size of such lesions were significantly higher in LN patients (1.8 fold that of non nephritis, P=0.003 and 0.03, respectively) and positively correlated with urea, creatinine, urinary albumin/creatinine ratio, SLEDAI, ESR, CRP, and grades of renal biopsy and negatively correlated with c3 and c4. cortical atrophy and prepontine space dilatation were also significantly higher in LN patients (P=0.01). <h3>Conclusion</h3> Asymptomatic MRI brain lesions in LN patients, they are usually clinically significant and correlate to laboratory parameters of LN, grades of renal biopsy, and disease activity independent to age, sex and hypertension. <h3>References</h3> [1] Pons_Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS. Understanding the epidemiology and progression of systemic lupus erythematous. Semin Arthritis Rheum2010;39:257-68. <h3>Disclosure of Interests</h3> None declared
Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma
Authors: Kathryn McCauley, Juliana Durack, Ricardo Valladares, Douglas W. Fadrosh, Din L. Lin, Agustin Calatroni, Petra K. LeBeau, Hoang T. Tran, Kei E. Fujimura, Brandon LaMere, Geil Merana, Kole Lynch, Robyn T. Cohen, Jacqueline Pongracic, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Michelle Gill, Andrew H. Liu, Haejin Kim, Meyer Kattan, Stephen J. Teach, Alkis Togias, Homer A. Boushey, James E. Gern, Daniel J. Jackson, Susan V. Lynch
Journal: Journal of Allergy and Clinical Immunology (2019)
TREM2 function impedes tau seeding in neuritic plaques
Authors: Cheryl E. G. Leyns, Maud Gratuze, Sneha Narasimhan, Nimansha Jain, Lauren J. Koscal, Hong Jiang, Melissa Manis, Marco Colonna, Virginia M. Y. Lee, Jason D. Ulrich, David M. Holtzman
Journal: Nature Neuroscience (2019)
In the Car With My Daughter
Authors: Lynette Lamp
Journal: Annals of Internal Medicine (2019)

Ad Libitum18 June 2019In the Car With My DaughterLynette Lamp, MDLynette Lamp, MDOlmsted Medical Center, St. Charles, Minnesota (L.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0238 Audio Reading - “In the Car With My Daughter” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “In the Car With My Daughter” by Lynette Lamp, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Sensitive SoulRegretting the lossOf bug livesOn the windshieldWondering if bug wivesAnd childrenGrieve for them.She retreats intoMelancholic silenceAs they continue toPing and splatSacrificing themselvesFor our mobility.I turn on the radioDrowning out the massacre.She shifts in her seatTo stare throughThe side windowAvoiding the carnageAnd asks me,Are we all waitingUnawareUntil stricken downLike the bugs?I tell her, yesBut it makes lifeNo less sweetTo savor the flightBefore the impact. Author, Article, and Disclosure InformationAffiliations: Olmsted Medical Center, St. Charles, Minnesota (L.L.)Current Author Address: Lynette Lamp, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “In the Car With My Daughter” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “In the Car With My Daughter” by Lynette Lamp, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 18 June 2019Volume 170, Issue 12Page: 900KeywordsChildren ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PF333 RISK OF BLEEDING COMPLICATIONS AND ATRIAL FIBRILLATION ASSOCIATED WITH IBRUTINIB TREATMENT: A SYSTEMATIC REVIEW AND META‐ANALYSIS
Authors: L. Pellegrini, U. Novak, M. Andres, M. Nagler
Journal: HemaSphere (2019)

Background: The use of ibrutinib is rapidly increasing because of its high potency to treat chronic lymphocytic leukaemia and other lymphoproliferative disorders. The application is however hampered by major adverse events such as bleeding complications and atrial fibrillation. The frequency and predictors of these adverse events are unknown. Aims: We aimed to study the frequency and predictors of bleeding complications and atrial fibrillation in patients treated with ibrutinib. Methods: Following a prespecified protocol, we systematically searched the literature for case series, cohort studies, as well as randomized controlled trials reporting on patients treated with ibrutinib using MEDLINE and EMBASE databases. We retrieved all relevant data in parallel. Methodological quality was observed using the Newcastle‐Ottawa Scale (NOS). Proportions of patients with bleeding events as well as atrial fibrillation were pooled in relevant subgroups using the binominal distribution and Freeman‐Tukey double arcsine transformation. Results: Among 1870 records screened, and 263 articles assessed in full‐text, 58 were finally included, comprising 4918 patients treated with ibrutinib. Methodological quality according to NOS was rated as poor to moderate. Bleeding events varied substantially with any bleedings reported between 2.8% and 78%, and major bleedings between 0% and 25% (Figure 1). New onset of atrial fibrillation was reported between 0% and 11%. Pooled estimates were 25% for any bleedings (95% confidence interval [CI] 19%, 32%); 3% for major bleedings (95% CI 2%, 4%), and 5% for atrial fibrillation (95% CI 4%, 6%). Predictors of adverse events were not apparent. Summary/Conclusion: Reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained suggests a relevant risk of bleeding events as well as atrial fibrillation in patients treated with ibrutinib. image
PB1862 WHOLE EXOME SEQUENCING REVEALS XRCC2 MUTATION CAUSING FANCONI ANEMIA
Authors: A. Alhashem, B. Alabbasi, H. Alfaridi
Journal: HemaSphere (2019)

Background: The XRCC2 gene is a member of the RAD51 gene family, which encode proteins involved in homologous recombination repair of DNA damage. The XRCC2 gene acts late in the Fanconi anemia (FA)‐BRCA pathway of DNA repair. Fanconi anemia (FA) is a group of inherited disorder characterized by bone marrow failure, pancytopenia with multiple craniofacial and skeletal involvement. Aims: 1‐To delinate the XRCC2 gene mutation,how it will present,and it is association with Fanocni anemia. 2‐To show the importance of extensive genetic testing in a high consanguinous population, where autosomal recessive disorders are common. Methods: We are reporting here an extremely rare gene, detected by Whole exome sequence(WES) for a 3 years old Saudi girl born at Prince Sultan Medical Military City, with multiple congenital anomalies, bilateral hypoplastic thumb, cafe au lait spots, strabismus, abnormal limb morphology, dysmorphic facial features, short stature. Results: Patients had chromosomal breakage study of 100%. Her WES reveled a rare XRCC2 gene, c.643C&gt;T p.(Arg215∗). which creates a premature stop codon. Summary/Conclusion: So far the detected variant is the second variant that was reported in the XRRC2 gene and has been associated with the Fanconi anemia of complementation group U (FANCU, OMIM: 617247). It was reported in a Saudi family on 2012. The importance of this communication is to emphasize on the open approach when dealing with a disease with wide possible genes like in FA. Moreover, to consider XRRC2 gene, especially in a Saudi population with high consanguinity and calls for further investigation of the potential contribution of XRCC2 mutations to the overall mutational load of FA.
SP0205 SCIENCE CARRIER AND MENTAL HEALTH
Authors: Annet van Royen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Clinician scientists are at the heart of the transitional medicine process. Over the last decades many reports and studies have showed that they risk becoming extinct, and that efficient career pathways are lacking. Recently more reports show that alarming numbers of clinicians and clinical scientists suffer from burn out and depression. To address this issue, next to thorough study of the root factors leading to mental problems it is important to develop career pathways for clinician scientists and educational programs to improve resilience. New educational programs such as those offered by the Eureka Institute help to build networks of translational scientists and help to strengthen resilience, needs to overcome the challenges they face while pursuing translational research. <h3>Disclosure of Interests:</h3> None declared
Sofosbuvir and Ribavirin Therapy for Children Aged 3 to &lt;12 Years With Hepatitis C Virus Genotype 2 or 3 Infection
Authors: Philip Rosenthal, Kathleen B. Schwarz, Regino P. Gonzalez‐Peralta, Chuan‐Hao Lin, Deidre A. Kelly, Scott Nightingale, William F. Balistreri, Sanjay Bansal, Maureen M. Jonas, Benedetta Massetto, Diana M. Brainard, Chia‐Hsiang Hsueh, Jiang Shao, Bandita Parhy, Suzanne Davison, Cornelia Feiterna‐Sperling, Lynette A. Gillis, Giuseppe Indolfi, Etienne M. Sokal, Karen F. Murray, Stefan Wirth
Journal: Hepatology (2019)

Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open-label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty-four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naïve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%-100%). The patient who did not achieve SVR12 was a 4-year-old who discontinued treatment after 3 days because of "abnormal drug taste." The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3-year-old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection.