tbuckley/cabot-search huggingface dataset:
PB1800 PROGNOSTIC RELEVANCE OF PROTEIN EXPRESSION, CLINICAL FACTORS, AND MYD88 MUTATION IN PRIMARY TESTICULAR DIFFUSE LARGE B‐CELL LYMPHOMA
Authors: Y. Xu, R. zhou, B. Chen
Journal: HemaSphere (2019)

Background: Primary testicular diffuse large B‐cell lymphoma (tDLBCL) is a rare, clinically aggressive form of extranodal lymphoma confined to the testis. It is known to have a poor prognosis, with an outcome inferior to nodal DLBCL. Only a few studies of tDLBCL have included immunohistochemical and molecular investigations, and little is known about the prognostic significance of the in situ tissue antigen expression profiles in tDLBCL. Aims: We performed a mutation analysis of the MYD88 L265P mutation in 17 tDLBCL patients and investigated the immunophenotypic biomarkers and clinicopathological factors associated with tDLBCL. Methods: Clinical date and paraffin‐embedded material from 17 patients presenting with tDLBCL were retrieved from the archives of the pathology department at the Nanjing Drum Tower Hospital.Immunohistochemistry was used to examine the expression of CD10, Bcl2, Bcl6, MUM1, C‐myc, P50, P65, P53, PSTAT3, OCT4, PIM1, CXCR4 and JAK2. MYD88 gene mutation analysis and complete clinical data evaluation were carried out and linked to overall survival time. Results: High expression of B‐cell lymphoma 2 was detected in 7/17 tDLBCL patients and was associated with a poor prognosis in a univariate model. Most of these patients (6/7) also expressed c‐myc. P50, JAK2, PSTAT3, PIM1 and CXCR4 were also upregulated in tDLBCLs. There were seventeen cases of tDLBCL; in total, 82.4% (14/17) of patients exhibited an activated B‐cell‐like phenotype (ABC), 56.3% (9/16) of patients harbored the MYD88 L265P mutation and showed a correlation between the MYD88 L265P mutation and the ABC phenotype ( p = 0.009). However, there was no association between the MYD88 mutation status and overall survival. Summary/Conclusion: We demonstrated that clinical factors such as age, IPI score, stage, lack of B symptoms and the over‐expression of Bcl‐2 are independent prognostic factors determining overall survival and that the over‐expression of P50, JAK2, PSTAT3, PIM1 and CXCR4 may promote the pathogenesis of tDLBCL. Moreover, we found a high prevalence of the MYD88 L265P mutation in tDLBCL, which may reflect a fairly consistent genetic feature in tDLBCL.
Abstract 18815: Ascending Aorta Size at Birth Predicts White Matter Microstructure in Adolescents Who Underwent Fontan Palliation
Authors: Abbas H Zaidi, Caitlin K Rollins, Christian Stopp, Christopher G Watson, Kevin G Friedman, David Wypij, Michael J Rivkin, Jane W Newburger
Journal: Circulation (2017)

Introduction: In neonates with single ventricle (SV), reduced cerebral white matter (WM) microstructural development at birth has been associated with smaller ascending aorta size, presumably indic...
PB1814 RESULTS OF TREATMENT BY REGIMEN R-M-NHL-BFM-90/R-EPOCH FOR PATIENTS WITH PRIMARY MEDIASTINAL LYMPHOMA
Authors: N. Gabeeva, D. Koroleva, A. Belyaeva, A. Smolyaninova, S. Tatarnikova, O. Shchetsova, V. Lapin, A. Kovrigina, E. Zvonkov, V. Savchenko
Journal: HemaSphere (2019)

Background: There is no consensus on the most optimal program for primary mediastinal lymphoma (PML) treatment. Recently a phase II study of R-DA-EPOCH regimen (Dunleavy K. et al) demonstrated high cure rate. But there were no randomized trials and according to different authors, about 10-30% of patients (pts) develop relapse/progression within 2 years from diagnose. We have previously demonstrated the high efficacy of the modified R-m-NHL-BFM-90 program for treating patients with aggressive lymphomas, including PML, but high toxicity of this protocol restricts it application. Positron emission tomography (PET/CT) is one of the most significant predictor of outcome in pts with aggressive lymphomas. Therefore, we have developed a hybrid PET/CT-guided protocol with intensive induction (blocks A and B) of R-m-NHL-BFM-90/4R-EPOCH (without escalation). Aims: To assess the efficacy and safety of R-m-NHL-BFM-90/R-EPOCH regimen for pts with untreated PML. Methods: A total 15 pts were enrolled in prospective study between 2015 and 2019 years. The median age was 34 (range 19-50); M:F = 3:12; Ann Arbor stage >I in 15 (100%); adverse factors (bulky mediastinal disease>10 cm in 10 pts, soft tissues involvement in 7 pts, breast in 4 pts, pleural effusion in 6 pts, elevated lactate dehydrogenase level in 7 pts). All pts underwent PET/CT before the start of therapy, after 2 courses of induction (available in 12 pts) and after the end of therapy. Results: Following 2 courses of induction 6 pts (40%) were in CR (D1-3) and 9 pts (60%) in PR (D4). All pts eventually received 1-4 courses R-EPOCH. After the end of therapy 14 pts (93%) were in CR (D1-3). (tab.1). Only 1 patient response was assessed as D4. She received autologous transplantation of hematopoietic stem cells and achieved CR (D3). With a median follow-up of 12 months (range 1-36) all pts (100%) are alive in complete remission.Summary/Conclusion: R-m-NHL-BFM-90/R-EPOCH protocol associated with high efficacy and favorable safety.
SP0083 MOLECULAR AND METABOLIC EVENTS WHICH UNDERWRITE T CELL PHENOTYPES IN AUTOIMMUNITY
Authors: George Tsokos
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The distribution and function of T cell subsets in patients with systemic lupus erythematosus (SLE) is aberrant. Distinct molecular and metabolic event dictate the numbers and function of T cells. Specifically, the transcriptional repressor cyclic AMP response element modulator alpha (CREMα), which is increased in cells from patients with SLE, accounts for the decreased expression of interleukin (IL)-2 and the increased expression of IL-17 through distinct epigenetic processes. CREMα promotes Th17 cell expansion by promoting the expression of Gls1, the first enzyme in glutaminolysis and by suppressing the expression of pyruvate dehydrogenase phosphatase catalytic subunit 2 that enables entry of pyruvate in to the Krebs cycle. In parallel, calcium calmodulin kinase 4 which is responsible for the increased binding of CREMα to cAMP response elements of the <i>IL-2</i>and <i>IL-17</i> loci, promotes the activity of pyruvate kinase M2 and promotes glycolysis and TH17 generation while suppressing the numbers of regulatory T cells. Understanding the exact molecular and metabolic processes that control T cell function in SLE enables therapeutic considerations. <h3>Disclosure of Interests:</h3> George Tsokos Grant/research support from: Janssen Research &amp; Development, LLC
PROPHYLAXIS OF OPHTHALMIA NEONATORUM
Authors: Alexander Russell Simpson
Journal: JAMA (1952)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage
Authors: Jinfang Zhang, Yu-Ru Lee, Fabin Dang, Wenjian Gan, Archita Venugopal Menon, Jesse M. Katon, Chih-Hung Hsu, John M. Asara, Priyanka Tibarewal, Nicholas R. Leslie, Yang Shi, Pier Paolo Pandolfi, Wenyi Wei
Journal: Cancer Discovery (2019)

The function of PTEN in the cytoplasm largely depends on its lipid-phosphatase activity, though which it antagonizes the PI3K-AKT oncogenic pathway. However, molecular mechanisms underlying the role of PTEN in the nucleus remain largely elusive. Here, we report that DNA double-strand breaks (DSB) promote PTEN interaction with MDC1 upon ATM-dependent phosphorylation of T/S398-PTEN. Importantly, DNA DSBs enhance NSD2 (MMSET/WHSC1)-mediated dimethylation of PTEN at K349, which is recognized by the tudor domain of 53BP1 to recruit PTEN to DNA-damage sites, governing efficient repair of DSBs partly through dephosphorylation of γH2AX. Of note, inhibiting NSD2-mediated methylation of PTEN, either through expressing methylation-deficient PTEN mutants or through inhibiting NSD2, sensitizes cancer cells to combinatorial treatment with a PI3K inhibitor and DNA-damaging agents in both cell culture and in vivo xenograft models. Therefore, our study provides a novel molecular mechanism for PTEN regulation of DSB repair in a methylation- and protein phosphatase-dependent manner. SIGNIFICANCE: NSD2-mediated dimethylation of PTEN is recognized by the 53BP1 tudor domain to facilitate PTEN recruitment into DNA-damage sites, governing efficient repair of DNA DSBs. Importantly, inhibiting PTEN methylation sensitizes cancer cells to combinatorial treatment with a PI3K inhibitor combined with DNA-damaging agents in both cell culture and in vivo xenograft models.This article is highlighted in the In This Issue feature, p. 1143.
SP0201 CATASTROPHIC APS TREATMENT GUIDELINES
Authors: Ricard Cervera
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The current recommendation for specific therapy of catastrophic antiphospholipid syndrome (CAPS) is the triple therapy with anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulins. Of note, only anticoagulation had a significant effect improving the vital prognosis of these patients. From the experimental point of view, there is only indirect evidence to advocate the use of these immunomodulatory therapies in CAPS. Recently, two monoclonal antibodies, rituximab and eculizumab, have been successfully used in some cases of severe or refractory CAPS. The first decreases the generation of pathogenic autoantibodies such as antiphospholipid. The second prevents the generation of C5b-C9 complex. The current presentation will describe the conventional and recent modalities of CAPS treatment, discussing the rationale for each one. <h3>References:</h3> [1] Cervera R, Rodríguez-Pintó I, Espinosa G. The diagnosis and clinical management of the catastrophic antiphospholipid syndrome: A comprehensive review. J Autoimmun2018; 92: 1-11. [2] Rodríguez-Pintó I, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: The current management approach. Best Pract Res Clin Rheumatol2016; 30: 239-249. [3] Rodriguez-Pintó I, Santacreu I, Cervera R, Espinosa G. What is the best strategy in treating catastrophic antiphospholipid syndrome?Int J Clin Rheumtol2015;10: 245–255. [4] Rodríguez-Pintó I, Espinosa G, Erkan D, Shoenfeld Y, Cervera R, for the CAPS Registry Project Group. The effect of triple therapy on the mortality of catastrophic antiphospholipid syndrome. Rheumatol 2018; 57: 1264-1270. <h3>Disclosure of Interests:</h3> None declared
Polymorphic assembly of virus-capsid proteins around DNA and the cellular uptake of the resulting particles
Authors: M.V. de Ruiter, R.M. van der Hee, A.J.M. Driessen, E.D. Keurhorst, M. Hamid, J.J.L.M. Cornelissen
Journal: Journal of Controlled Release (2019)

Virus-like particles (VLPs), i.e. molecular assemblies that resemble the geometry and organization of viruses, are promising platforms for therapeutics and imaging. Understanding the assembly and cellular uptake pathways of VLPs can contribute to the development of new antiviral drugs and new virus-based materials for the delivery of drugs or nucleic acid-based therapies. Here we report the assembly of capsid proteins of the cowpea chlorotic mottle virus (CCMV) around DNA into defined structures at neutral pH. Depending on the type of DNA used, we are able to create spherical structures of various diameters and rods of various lengths. In order to determine the shape dependency, the cellular uptake routes and intracellular positioning of these formed polymorphic VLPs in RAW264.7, HeLa and HEK 293 cells are evaluated using flow cytometry analysis with specific chemical inhibitors for different uptake routes. We observed particular uptake routes for the various CCMV-based nanostructures, but the experiments point to clathrin-mediated endocytosis as the major route for cell entry for the studied VLPs. Confocal microscopy reveals that the formed VLPs enter the cells, with clear colocalization in the endosomes. The obtained results provide insight in the cargo dependent VLP morphology and increase the understanding of shape dependent uptake into cells, which is relevant in the design of new virus-based structures with applications in drug and gene delivery.
Immunometabolism and atherosclerosis: perspectives and clinical significance: a position paper from the Working Group on Atherosclerosis and Vascular Biology of the European Society of Cardiology
Authors: Daniel F J Ketelhuth, Esther Lutgens, Magnus Bäck, Christoph J Binder, Jan Van den Bossche, Carolin Daniel, Ingrid E Dumitriu, Imo Hoefer, Peter Libby, Luke O’Neill, Christian Weber, Paul C Evans
Journal: Cardiovascular Research (2019)

Inflammation is an important driver of atherosclerosis, and the favourable outcomes of the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial revealed the large potential of anti-inflammatory drugs for the treatment of cardiovascular disease, especially in patients with a pro-inflammatory constitution. However, the complex immune reactions driving inflammation in the vascular wall in response to an atherosclerotic microenvironment are still being unravelled. Novel insights into the cellular processes driving immunity and inflammation revealed that alterations in intracellular metabolic pathways are strong drivers of survival, growth, and function of immune cells. Therefore, this position paper presents a brief overview of the recent developments in the immunometabolism field, focusing on its role in atherosclerosis. We will also highlight the potential impact of immunometabolic markers and targets in clinical cardiovascular medicine.
Anthracycline-based sequential adjuvant chemotherapy in operable breast cancer: Five-year results of a randomized study by the Michelangelo Foundation
Authors: A. Moliterni, M. Mansutti, D. Aldrighetti, L. Merlini, L. Zuccarino, M. Bari, A. Farris, P. Mariani, S. Fava, L. Gianni
Journal: Journal of Clinical Oncology (2007)

535 Background: Anthracycline-based sequential chemotherapy significantly improves efficacy outcomes compared to CMF alone. Methods: 806 eligible patients with operable breast cancer were enrolled into a randomized study (ratio 1:1:1:1) of sequential chemotherapy. In a 2×2-type design patients were allocated to first receive 4 cycles of AT (doxorubicin, A 60 mg/m 2 iv + paclitaxel, T 200 mg/m 2 as 3 h inf q 3wks) or EV (epirubicin, E 75 mg/m 2 iv + vinorelbine, V 25 mg/m 2 iv D1,8 q3wks) followed either by 4 monthly cycles of iv CMF or 6 cycles of q3w T alone (100 mg/m 2 as 1h inf D1,8). Tamoxifen was recommended for 5 yr after chemotherapy in patients with HR+ tumors. Patients with tumors &gt; 2 cm in diameter were allowed to start primary chemotherapy with 4 cycles of either AT or EV followed by surgery and postoperative systemic treatment as detailed above. Aim of the study was to test the role of T vs V when combined with an anthracycline during the first 4 cycles of the regimen as well as the role of CMF vs T during the last 4 cycles. Results: At a median follow-up of approximately 48 months, the 5 year freedom from progression (FFP) and overall survival (OS) for the main endpoints were as in the Table : The four treatment sequences were fairly well tolerated, with only 1 treatment-related death after EV. Type and severity of hematological toxicities were similar in all treatment arms. The incidence of reversible G2–3 neurotoxicity was 21.9% after AT, 5.3% after EV and 29.1% after sequential T. Chemical phlebitis was more frequent after EV (6.5%) then after AT (0.3). Conclusions: The results indicate that vinorelbine-epirubicin and classical CMF when appropriately used in a sequential modality for high-risk breast cancer are as valid and less neurotoxic an option of adjuvant therapy than the more widely used taxane-containing adjuvant regimens. Supported in part by Bristol-Myers Squibb, Pierre Fabre and Pharmacia. [Table: see text] [Table: see text]
PB1851 PREDICAMENT OF SHORTENED PRE‐OPERATIVE EVALUATION OF UNDIAGNOSED BLEEDING DISORDERS IN SURGICAL PATIENTS IN UNDER DEVELOPED COUNTRY.
Authors: T. Imran, H.N. Altaf
Journal: HemaSphere (2019)

Background: Von Willebrand Disease (VWD) is a prevalent genetic bleeding disorder in Pakistan. it is a leading congenital bleeding disorder followed by Haemophilia. the significance of bleeding pattern in undiagnosed patients as evident after haemostatic challanges leads to the importance of the need to confirm bleeding disorders in emergency surgical patients. Aims: the aim of this retrosepctive study is to document the pattern of mortality and morbidity in undiagnosed surgical patients with various congenital bledding disorders in Pakistan Methods: we analyzed the bleeding pattern of VWD and Haemophilia A and B in patients who were undiagnosed at the time of surgery. this retrospective study was done at Fauji Foundation Hospital from 2012 to 2016. patients’ charts were reviewed for primary diagnosis, surgical procedures and severity of bleeding by detailed history and laboratory workup. the study was carried out after approval of institutional ethical committee. Results: we received 14 VWD and 7 Haemophilia patients in emergency for surgical intervention. the median age was from 3 to 22 years. there were 16 male and 5 female patients. out of 21 patients 29% had laparotomy, 10% had head surgeries, 14% post trauma thoracic intervention, 10% had cholecystectomy, 19% had dental procedures and 14% had cesarean sections. collective mortality rate was 56% because of the obsecure condition added by delay in arranging appropriate treatment line for ongoing bleeding. Summary/Conclusion: congenital bleeding disorders are common in Pakistan. there is lack of diagnostic facilities and recognition by health care professionals. lack of awareness about these bleeding disorders before emergency surgeries results in fatal outcomes. awareness programes must be initiated in developing countries.
PS1059 DEFINING TRANSIENT ABNORMAL MYELOPOIESIS BY GATA1 MUTATION IN INFANTS WITH DOWN SYNDROME
Authors: M. Elalfy, I. Ragab, H. Abdel‐Khalek, M. Fayek, T. Kamal, N. Abdel‐Fattah
Journal: HemaSphere (2019)

Background: Infants with Down syndrome are more prone to transient abnormal myelopoiesis. A small percentage of this condition can be fatal, yet they are more prone to develop acute myeloid leukemia if harboring GATA1 mutation. Aims: Aim of the Work was to screen infants with Down syndrome for peripheral GATA1 mutation by sequencing of exon2 and to correlate it with clinical and laboratory parameters. Methods: The study included 79 patients with Down syndrome aged 1–90 days from the outpatient Genetics Clinic, Children's Hospital, Ain Shams University. Complete blood count with manual differential leukocytes count and blast cells count was assessed to all patients.By peripheral blast count patients were divided into three groups, Group A with peripheral blast count more than 10%, group B with blast count &gt;0–10% and group C with no detected blasts in peripheral blood. Mutation analysis of exon2 of GATA1 gene was performed by Sanger sequencing to 15 cases based on results of blast cells count. Results: The median age of patients was 23.5 days. Prematurity was detected in only 6.3% of patients. Eighteen percent of DS patients (15 of 78) had blasts on blood smears (range 1%&gt;60%). %). Group A included 4 patients, group B 11 patients and Group C 63 patients. The patients in group A were younger in age than patients in group B and C. Those 15 patients were divided into two groups: Mutation positive group: 4 patients, all of them had blast cells count &gt;10% and Mutation negative group: 11 patients. The peripheral blast cells% was significantly higher in the mutation positive than mutation negative group. The only patient presented with splenomegaly was positive for the mutation of exon 2 of GATA‐1 gene.There was higher leucocytic count in patients with positive mutations compared to negative ones.One patient with positive GATA1 mutation developed AMKL and died of disease, he had initial blast count more than 10% in peripheral blood. Summary/Conclusion: All patients with positive GATA1 mutations had blasts&gt;10% in their peripheral blood. One of the mutation positive patients developed acute myeloid leukemia. We conclude that blast cells count in peripheral blood combined with peripheral GATA1 mutation analysis can be used for close follow up of patients for early detection of acute megakaryocytic leukemia in infants with Down syndrome.
PB2408 MEASUREMENT OF SERUM KLOTHO AND ITS CORRELATION WITH BONE MINERAL DENSITY IN EGYPTIAN PATIENTS WITH β-THALASSEMIA
Authors: H. Abdelbary, M. Moussa, N. Nabil, R. El-Gamal, N. El Sayed
Journal: HemaSphere (2019)

Background: Growth retardation and pathological fractures are very common in thalassemic patients and a substantial proportion of those patients are affected with osteoporosis and osteopenia. The main sites of Klotho expression are the kidney and parathyroid glands. Klotho knock-out mice express an aging phenotype which includes reduced bone mineral density, growth retardation similar to BTM. Aims: The aim of this study was to compare Klotho levels in β-Thalssemia patients with healthy controls. Moreover, we analyzed possible correlations between Klotho level with osteoporosis and fractures. Methods: 50 patients were enrolled in this cross-sectional study, 27 had β -thalassemia major and 23 had B-thalassemia intermedia. We assessed Klotho level using ELISA assay for patients compared to healthy control group. Results: The mean Klotho level in thalassemic patients were significantly lower than controls (P-value <0.001) but no significant difference between thalassemia major and intermedia. Klotho levels were significantly lower in patients who had previous fragility fractures than those who had no fractures (P-value 0.033). Bone mineral density at the neck of femur showed that Klotho levels were significantly lower in patients who were osteopenic than those who were normal. Similarly, At lower spine, Klotho levels were lower in osteopenic and osteoporotic patients compared to controls (P-value <0.001). Lastly, significant positive correlations were found between Klotho levels in patients and BMD at the neck of femur and lower spine (P-value <0.001). Summary/Conclusion: Our data identify Klotho as a potential risk factor for osteopenia, osteoporosis and fragility fractures in Thalassemic patients.
Methylphenidate and the risk of psychosis in adolescents and young adults: a population-based cohort study
Authors: Chris Hollis, Qi Chen, Zheng Chang, Patrick D Quinn, Alexander Viktorin, Paul Lichtenstein, Brian D'Onofrio, Mikael Landén, Henrik Larsson
Journal: The Lancet Psychiatry (2019)

There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder.