tbuckley/cabot-search huggingface dataset:
PF603 FASTER &amp; SUSTAINED IMPROVEMENT IN HEALTH‐RELATED QUALITY OF LIFE IN TRANSPLANT‐INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA PTS TREATED WITH DARATUMUMAB, LENALIDOMIDE &amp; DEXAMETHASONE (D‐RD) VS RD: MAIA
Authors: A. Perrot, T. Facon, T. Plesner, S.Z. Usmani, S. Kumar, R.Z. Orlowski, N.J. Bahlis, H. Nahi, P. Mollee, K. Ramasamy, M. Roussel, C. Chaleteix, C. Araujo, A. Jaccard, M. Delforge, L. Karlin, B. Arnulf, A. Chari, J. Wang, R. Kobos, C. McKay, K.S. Gries, J. Trudeau, C. Hulin, K. Weisel
Journal: HemaSphere (2019)

Background: MAIA, an ongoing phase 3 trial of transplant‐ineligible patients with NDMM, demonstrated significant improvement in progression‐free survival with D‐Rd vs Rd alone. Assessment of patient‐reported outcomes (PRO) alongside efficacy endpoints provides patient perspective on their quality of survival and overall value of health‐related quality of life (HRQoL) while on treatments. Aims: To utilize PRO assessments as a tool in capturing the patient perspective on quality of survival and HRQoL changes in MAIA. Methods: The EORTC QLQ‐C30 and EQ‐5D‐5L questionnaires were completed by patients using an electronic device at baseline and every 3 months during treatment; interim results are presented for first 12 months. Treatment effects were assessed using repeated measures, mixed effects models and thresholds for clinically meaningful benefit were based on established criterion from the literature. Results: Compliance rates in completing the assessment tools were high and comparable at baseline (&gt;90%) and through month 12 (&gt;80%) for both groups (D‐Rd [n = 368]; Rd [n = 369]). Improvement in Global Health Status (GHS) occurred in both groups; however, for D‐Rd, significantly greater improvement was observed at cycle 3 (LS mean change; D‐Rd: 4.5 [95% CI: 2.4, 6.6], Rd: 1.5 [95% CI: −0.7, 3.7]; [p = 0.0454]) and increasing improvement occurred across all time points. Significant improvement and clinically meaningful benefit in HRQoL for D‐Rd was also observed in EQ‐5D‐5L Visual Analog Scale (VAS) scores (LS mean change; D‐Rd: 10.1 [95% CI: 8.1, 12.1], Rd: 4.9 [95% CI: 2.8, 7.0]; [p = 0.0002]). The VAS median time to worsening was 10 mo longer for D‐Rd. Of note, meaningful differences were observed between the treatment groups in two subscale scores, pain symptoms and cognitive functioning. Statistically significant less pain was reported early with D‐Rd (LS mean change at cycle 3; D‐Rd: −17.9 [95% CI: −20.7, −15.0], Rd: −11.0 [95% CI: −14.0, −8.1]; [p = 0.0007]); clinically meaningful reduction in pain symptoms was sustained with D‐Rd. There was a decline in cognitive functioning through Cycle 12 in both treatment arms with the peak difference occurring at Cycle 9, but mean differences between groups were not statistically significant. Summary/Conclusion: Faster and sustained improvement in patients treated with D‐Rd was observed using HRQoL assessments compared with Rd, with similar findings reflected across the pain subscale.
Abstract 13654: Gemcabene Monotherapy and in Combination With Atorvastatin Lowers High Sensitivity C-Reactive Protein (hsCRP) in a Phase 2 Clinical Trial
Authors: Evan A Stein, Rebecca Bakker-Arkenma, Margaret M McShane, Mina P Sooch, Charles L Bisgaier
Journal: Circulation (2015)

Background: It is well established that inflammation plays a key role the progression of atherosclerosis and that serum high sensitivity c-reactive protein (hsCRP), may be a good marker of the degree of underlying vascular inflammation. Thus hsCRP has been recognized as a predictor of cardiovascular risk and lipid lowering drugs, such as statins, which also result in a reduction of hsCRP may be more likely to reduce cardiovascular events. Gemcabene is an inhibitor of hepatic cholesterol, triglyceride, and apoC-III synthesis resulting in decreased assembly of VLDL and enhances the systemic clearance of VLDL and its subsequently production of remodeled lipoproteins including LDL. Study Design and Results: In an 8-week double blind randomized, placebo-controlled, dose-ranging, efficacy and safety Phase 2 study, gemcabene 300, 600 and 900 mg/day administered as monotherapy or in combination with atorvastatin 10, 20 and 80 mg/day resulted in a significant and dose dependent reduction of LDL-C (Study 4141001). A secondary objective of this study was to evaluate the modulation of hsCRP by gemcabene. Of 277 patients randomized, 250 (90%) completed the study. Baseline mean LDL-C was 174.7mg/dL, and median hsCRP = 2.5 mg/L. The median % reduction in hsCRP with Gemcabene 300, 600 and 900 mg monotherapy was 25.8%, 41.5% and 35.3% respectively compared with 9.4% for placebo. The rank-transformed data showed significant difference favoring gemcabene over placebo in the 600 and 900 mg groups (p=0.0070 and p =0.0018, respectively). Co-administration of 300, 600, and 900 mg gemcabene with atorvastatin aggregated over the dose range showed decreases in hsCRP beyond atorvastatin monotherapy (which ranged from 27-41%) by an additional 16% (p=0.0237), 23% (p=0.0017) and 28% (p=0.0001), respectively. Conclusions: Gemcabene significantly lowered hsCRP alone and on top of statins in hypercholesterolemic patients.
Loss of ARID1A in Tumor Cells Renders Selective Vulnerability to Combined Ionizing Radiation and PARP Inhibitor Therapy
Authors: Youngran Park, M. Herman Chui, Yohan Suryo Rahmanto, Zheng-Cheng Yu, Raghavendra A. Shamanna, Marina A. Bellani, Stephanie Gaillard, Ayse Ayhan, Akila Viswanathan, Michael M. Seidman, Sonia Franco, Anthony K.L. Leung, Vilhelm A. Bohr, Ie-Ming Shih, Tian-Li Wang
Journal: Clinical Cancer Research (2019)

Somatic inactivating mutations in ARID1A, a component of the SWI/SNF chromatin remodeling complex, are detected in various types of human malignancies. Loss of ARID1A compromises DNA damage repair. The induced DNA damage burden may increase reliance on PARP-dependent DNA repair of cancer cells to maintain genome integrity and render susceptibility to PARP inhibitor therapy.Experimental Design: Isogenic ARID1A-/- and wild-type cell lines were used for assessing DNA damage response, DNA compactness, and profiling global serine/threonine phosphoproteomic in vivo. A panel of inhibitors targeting DNA repair pathways was screened for a synergistic antitumor effect with irradiation in ARID1A-/- tumors.ARID1A-deficient endometrial cells exhibit sustained levels in DNA damage response, a result further supported by in vivo phosphoproteomic analysis. Our results show that ARID1A is essential for establishing an open chromatin state upon DNA damage, a process required for recruitment of 53BP1 and RIF1, key mediators of non-homologous end-joining (NHEJ) machinery, to DNA lesions. The inability of ARID1A-/- cells to mount NHEJ repair results in a partial cytotoxic response to radiation. Small-molecule compound screens revealed that PARP inhibitors act synergistically with radiation to potentiate cytotoxicity in ARID1A-/- cells. Combination treatment with low-dose radiation and olaparib greatly improved antitumor efficacy, resulting in long-term remission in mice bearing ARID1A-deficient tumors.ARID1A-deficient cells acquire high sensitivity to PARP inhibition after exposure to exogenously induced DNA breaks such as ionizing radiation. Our findings suggest a novel biologically informed strategy for treating ARID1A-deficient malignancies.
Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial
Authors: Willem D F Venter, Michelle Moorhouse, Simiso Sokhela, Celicia Serenata, Godspower Akpomiemie, Ambar Qavi, Nonkululeko Mashabane, Natasha Arulappan, Joel W Sim, Phumla Z Sinxadi, Lubbe Wiesner, Ellisha Maharaj, Carole Wallis, Tom Boyles, David Ripin, Sarah Stacey, Gila Chitauri, Andrew Hill
Journal: The Lancet HIV (2019)
Accurate Detection of Convergent Amino-Acid Evolution with PCOC
Authors: Carine Rey, Laurent Guéguen, Marie Sémon, Bastien Boussau
Journal: Molecular Biology and Evolution (2018)

In the history of life, some phenotypes have been acquired several times independently, through convergent evolution. Recently, lots of genome-scale studies have been devoted to identify nucleotides or amino acids that changed in a convergent manner when the convergent phenotypes evolved. These efforts have had mixed results, probably because of differences in the detection methods, and because of conceptual differences about the definition of a convergent substitution. Some methods contend that substitutions are convergent only if they occur on all branches where the phenotype changed toward the exact same state at a given nucleotide or amino acid position. Others are much looser in their requirements and define a convergent substitution as one that leads the site at which they occur to prefer a phylogeny in which species with the convergent phenotype group together. Here, we suggest to look for convergent shifts in amino acid preferences instead of convergent substitutions to the exact same amino acid. We define as convergent shifts substitutions that occur on all branches where the phenotype changed and such that they correspond to a change in the type of amino acid preferred at this position. We implement the corresponding model into a method named PCOC. We show on simulations that PCOC better recovers convergent shifts than existing methods in terms of sensitivity and specificity. We test it on a plant protein alignment where convergent evolution has been studied in detail and find that our method recovers several previously identified convergent substitutions and proposes credible new candidates.
Long-Term Results of PET-Guided Radiation Therapy in Patients with Advanced-Stage Diffuse Large B-Cell Lymphoma Treated with R-CHOP in British Columbia
Authors: Ciara Louise Freeman, Kerry J Savage, Diego Villa, David W. Scott, Line Srour, Alina S Gerrie, Maura J Brown, Graham W Slack, Pedro Farinha, Brian Skinnider, Christina Aquino Parsons, Tom Pickles, Pete Tonseth, Don Wilson, Joseph M Connors, Laurie H. Sehn
Journal: Blood (2017)
Large B‐cell lymphomas
Authors: Umberto Vitolo
Journal: HemaSphere (2019)

Learning goals After attending this session, you will be able to: Recognize the molecular heterogeneity of large B-cell lymphomas and understand current molecular classifier. Learn how new treatment strategies can be developed based on identified target alterations. Learn which prognostic and predictive biomarkers are biologically meaningful, robust, reproducible, widely available and affordable to serve as companion diagnostics. Recognize the optimal treatment for your DLBCL patients, learn the most recent data on the integration of novel drugs to standard chemmoimmunotherapy and discuss how new combo strategies, based on molecular and biological DLBCL subsets, may improve the outcome of DLBCL. Introduction Diffuse Large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy. Despite its high curable rate, 60%, with Rituximab-CHOP, 40% of the patients did not respond or relapse. To improve their outcome, we need to learn more about the heterogeneity and complexity of DLBCL. This educational session is focused on molecular and pathological subtyping of aggressive lymphomas and how treatment can be driven accordingly. Dr Chapuy will review genetic analysis of DLBCL. Gene recurrent mutations, somatic copy number alterations and low frequency alterations has been studied leading to the identification of five distinct molecular DLBCL subsets and other similar models. These genetic features provide new insights in the DLBCL pathogenesis, predicting the outcome and may lead the pathway to novel combination treatment approaches. Cell of origin (COO) has been extensively studied in DLBCL with activated B-cell-like subgroup carries the worst prognosis. The underlying genetic differences have been shown to differ between COO subgroups although with considerable overlap. Double hit lymphomas with MYC, BCL2 and/or BCL6 have a dismal prognosis and their recognition is mandatory because of different treatment strategy. The expression of predictive biomarkers as MYC, BCL2, CD30 and other is also important with several uncertainties. Dr de Jong will review all these histopatological findings. Based on these premises, many expectations have been placed on clinical trials using novel compounds as Ibrutinib, Lenalidomide, Venetoclax and others with R-CHOP, based on COO classification or biomarker expression to improve the results. Positive and negative results have been reported. Dr Trneny will critically discuss these findings, providing new insights for a possible future molecular driven DLBCL therapy.
Development and application of hyaluronic acid in tumor targeting drug delivery
Authors: Zhijian Luo, Yan Dai, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2019)

Hyaluronic acid (HA) is a natural polysaccharide that has gained much attention due to its biocompatibility, enzyme degradation capacity and active tumor targeting capacity. Its receptor, CD44, is overexpressed in many kinds of cancers and is associated with tumor progress, infiltration and metastasis. Therefore, many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting. In this review, we systemically overview the basic theory of HA, its receptor and hyaluronidase, then we categorize the studies in HA-based drug delivery systems according to the functions of HA, including tumor-targeting materials, enzyme-sensitive biodegradable modality, pH-sensitive component, reduction-sensitive component, and the gel backbone. Finally, the perspective is discussed.
AB1140 ROLE OF ULTRASOUND IN ASSESSMENT OF JOINT PAIN AMONG HEMO DIALYSIS PATIENTS
Authors: Ahmed Fahmy
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Few studies including limited number of patients assessed the rheumatologic effects of hemodialysis (HD) on joints using ultrasonography. Joint ultrasound has been emerged as a cheap noninvasive tool for assessment of joint pain among HD patients. This was the aim of our study to make use of such tool in such life quality threatening complaints <h3>Objectives</h3> to determine the role of ultrasound in evaluation of joint pain and its causes among patients on regular HD <h3>Methods</h3> One hundred and four patients with end stage renal disease (ESRD) who were regular on HD three sessions per week four hours per session were subjected to history taking, complete physical examination stressing on musculoskeletal examination and ultrasonography of painful joints. <h3>Results</h3> Dialysis related arthropathy (DRA) was not the only cause of joint pain among HD patients but there were diverse causes in different joints. As regard affected joints, knee was the most affected one then came wrist, shoulder, ankle and elbow respectively. As regard causes of joint pain, DRA was the commonest one then came osteoarthritis, Nonspecific ultrasonographic findings and few cases showed normal ultrasonographic studies. <h3>Conclusion</h3> This study confirmed that joint pain in HD patients has diverse causes not DRA by necessity but other causes must be considered as well as multifactorial etiologies. <h3>Disclosure of Interests</h3> None declared
SP0167 US FOR ASSESSING LUNG INVOLVEMENT IN RHEUMATIC DISEASES – CLINICAL USE + DEMO
Authors: Andrea Delle Sedie
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Evaluation of interstitial lung disease (ILD) is always difficult (low sensitivity for X-ray and pulmonary function tests or high level of radiation for HRCT): ultrasound (US) has recently shown interesting results on truth, discrimination and feasibility. Due to the thickening of interlobular septa for edema or fibrosis, US beam can interact with those structure and produce artifacts on the screen: B-lines (BL) and pleural line irregularity (PLI). A positive correlation between BL and HRCT has been established both in systemic sclerosis patients and in other patients with ILD; more recently similar results have been published by using PLI as a finding for US assessment in patients. BL has been recently defined by the OMERACT as a vertical hyperechoic reverberation artifact that arise from the pleural line, extend to the bottom of the screen without fading, and move synchronously with lung sliding, while PLI has been defined as a loss of regularity that may be associated with an increase in thickness, focal, diffuse, or nodular. A low number of BLs has been described in healthy subjects but they are generally confined to the posterior and lower part of the thorax. Up to now, many different scanning protocols have been used to assess BL or PLI in patients, providing similar results. <h3>Conclusion:</h3> US lung evaluation is a usefull and feasible imaging technique. <h3>Disclosure of Interests:</h3> Andrea Delle Sedie Speakers bureau: Abbvie, UCB, Celgene, MSD
Immune Checkpoint and Poly(ADP–Ribose) Polymerase Inhibition for Recurrent Platinum-Resistant Ovarian and Metastatic Triple-Negative Breast Cancers
Authors: Kunle Odunsi, Tanja Pejovic
Journal: JAMA Oncology (2019)

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
One in five children in the UK affected by “persistent poverty,” figures show
Authors: Susan Mayor
Journal: BMJ (2019)

Persistent poverty affects one in five children in the UK and is associated with poor physical and mental health in early adolescence, latest figures from the country’s first study tracking childhood health over time have shown.1

“Ending child poverty should become a policy priority for UK children to achieve their full potential,” said the study authors led by Eric Lai from the University of Liverpool.

“Our analysis of a representative UK children’s cohort following up from 2000 to 2016 found that one in five children were in persistent poverty up to age 14 years,” they reported.

“Any exposure to poverty was associated with worse physical and mental health in …
AB0401 SWITCH FROM ETANERCEPT ORIGINATOR TO ETANERCEPT BIOSIMILAR: DATA FROM REAL LIFE
Authors: Maria Chiara Ditto, Simone Parisi, Marta Priora, Angela Laganà, Clara Lisa Peroni, Enrico Fusaro
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Biosimilars of antiTNF-α are now available for the treatment of arthritis. There are a lot of data about maintenance of clinical efficacy after switching from originator to biosimilar but also reports about flares and adverse events (AE). Controversies still exist due to ethical and economic reasons. We describe the disease activity trend after switching from etanercept originator (oETA) to its biosimilar (bETA) in a population of Turin, Piedmont, Italy. In this region switch to biosimilar is mandatory by law except in case of patients with history of allergy, off-label, psycological reasons, active disease that required different treatment. <h3>Objectives:</h3> To evaluate the disease activity trend before and after switch from oETA to bETA. <h3>Methods:</h3> We switched 82 patients (M/F 33/49, mean age 59.65±11.5, duration of disease 17.56±10.3 years) in stable state of disease from oETA to bETA; 49 patients affected by RA, 24 by PsA, 10 by AS. The mean of duration of oETA and bETA treatment was respectively 129.2 and 6.2 months. We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, DAS28 for RA, DAPSA for PsA, HAQ and HAQ-S, BASDAI for AS patients. <h3>Results:</h3> Differences of variables between oETA and bETA are summarized in table1. We didn't find any significant difference between oETA and bETA in order to efficacy. However 8 patients, 5 RA and 4 PsA(9.75%) discontinued bETA because arthritis flare(7) or AE(1). <h3>Conclusion:</h3> Data about maintenance of efficacy and percentage of discontinuation were similar to the literature. We didn't find significant differences on efficacy after switching from originator to biosimilar. However, considering the rate of flares and AE, further strong studies are required. <h3>References</h3> [1] Jørgensen, K. K. et al. Lancet 2017 Jun 10;389(10086):2304-2316. [2] Kay J and KL Winthrop Nat Rev Rheumatol 2017 Jul;13(7):391-392. [3] Toussirot E, Marotte H. RMD Open 2017;3:e000492. <h3>Disclosure of Interests:</h3> None declared
PB2033 IMMUNOGLOBULIN REPLACEMENT THERAPY IN ADULT HEMATOLOGICAL PATIENTS: EFFECT ON THE INCIDENCE OF INFECTIOUS COMPLICATIONS
Authors: O. Gerasimovich, I. Stoma, I. Iskrov, N. Milanovich, I. Lendina, A. Uss
Journal: HemaSphere (2019)

Background: The problem of infectious complications in hematology is determined by their high frequency, severity and difficulty of diagnosis. The clinical effect of immunoglobulin replacement therapy in relation to the risk of infectious complications in adult hematological patients currently needs to be assessed and revised. Aims: The aim of this prospective study was to evaluate the independent effect of immunoglobulin replacement therapy on the risk of developing infectious complications in hematological patients. Methods: The study included 34 adult patients receiving chemotherapy for hematological disease. Intervention groups (immunoglobulin replacement therapy) and the control group were matched by clinical and demographic characteristics. The primary outcome in the analysis was taken as the infection‐free period in the 180‐days survival analysis performed by Kaplan‐Meier with log‐rank test, Cox regression and Cox regression. Results: The average age of patients was 57.8 years, with sex distribution: 19 female and 15 male. Hematological diseases were distributed as follows: chronic lymphocytic leukemia ‐ 18, multiple myeloma ‐ 8, acute myeloid leukemia ‐ 2, acute lymphocytic leukemia ‐ 4, myelodysplastic syndrome ‐ 2. Among the included ‐ 15 patients had profound hypogammaglobulinemia (less than 4 g/l). Statistically significant association of immunoglobulin replacement therapy and reduction of the risk of infectious episodes was shown in a 180‐days period (log‐rank test, p = 0.037), Fig 1. The average duration of the period without infectious complications in the replacement group was 164 days (95% CI 147‐180 days), while in the control group it was 148 days (95% CI 124‐171 days). No additional confounding factors, which could cause the differences in the groups were found in the regression analysis (p = 0.035). The number needed to treat (NNT) was 3 patients (p = 0.018). Summary/Conclusion: The obtained data show that the use of immunoglobulin replacement therapy is independently associated with a longer period of infection‐free survival in adult hematological patients, what substantially improves the quality of life of such patients. The clinical effect may be assessed within 6 months from the start of immunoglobulin replacement therapy. image