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biologic therapy in children

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https://www.readbyqxmd.com/read/28632924/metabolomics-as-a-driver-in-advancing-precision-medicine-in-sepsis
#1
Michelle Eckerle, Lilliam Ambroggio, Michael Puskarich, Brent Winston, Alan E Jones, Theodore J Standiford, Kathleen A Stringer
OBJECTIVE: The objective of this review is to explain the science of metabolomics-a science of systems biology that measures and studies endogenous small molecules (metabolites) that are present in a single biological sample-and its application to the diagnosis and treatment of sepsis. In addition, we discuss how discovery through metabolomics can contribute to the development of precision medicine targets for this complex disease state and the potential avenues for those new discoveries to be applied in the clinical environment...
June 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28628351/sleep-in-adolescents-and-young-adults-in-the-year-after-cancer-treatment
#2
Lauren C Daniel, Richa Aggarwal, Lisa A Schwartz
PURPOSE: Adolescents and young adults (AYA) with cancer are a vulnerable group facing more intense treatments, higher symptom burden, and poorer treatment outcomes relative to younger children. Sleep disruption is common during cancer treatment and sleep problems persist into adulthood for some survivors of AYA cancer. The developmental period of adolescence/emerging adulthood confers greater biological and behavioral risk for insufficient sleep relative to older or younger ages. Thus, understanding AYA sleep disturbances shortly after completing treatment can inform interventions to manage cancer-related symptoms and improve quality of life...
June 19, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28627000/pencil-beam-scanned-protons-for-the-treatment-of-patients-with-ewing-sarcoma
#3
Damien C Weber, Fritz R Murray, Dora Correia, Alessandra Bolsi, Martina Frei-Welte, Alessia Pica, Antony J Lomax, Ralf Schneider, Barbara Bachtiary
BACKGROUND: Few data exist regarding the clinical outcome of patients with Ewing sarcoma (EWS) treated with pencil beam scanning proton therapy (PT). We report the outcome of children, adolescents and young adults (AYA) treated with PT at the Paul Scherrer Institute. MATERIALS: Thirty-eight patients (median age, 9.9 years) received a median dose of 54.9 Gy(RBE) (where RBE is relative biologic effectiveness). Size of the tumor ranged from 1.7 to 24 cm. Most common primary site was axial/pelvic (n = 27; 71%)...
June 19, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28620836/sox2-immunity-and-tissue-resident-memory-in-children-and-young-adults-with-glioma
#4
Juan C Vasquez, Anita Huttner, Lin Zhang, Asher Marks, Amy Chan, Joachim M Baehring, Kristopher T Kahle, Kavita M Dhodapkar
Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied...
June 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28618012/metabolomic-signature-of-brain-cancer
#5
Renu Pandey, Laura Caflisch, Alessia Lodi, Andrew J Brenner, Stefano Tiziani
Despite advances in surgery and adjuvant therapy, brain tumours represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumours, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which characterizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumour biology...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28617804/integrating-tenascin-c-protein-expression-and-1q25-copy-number-status-in-pediatric-intracranial-ependymoma-prognostication-a-new-model-for-risk-stratification
#6
Felipe Andreiuolo, Gwénaël Le Teuff, Mohamed Amine Bayar, John-Paul Kilday, Torsten Pietsch, André O von Bueren, Hendrik Witt, Andrey Korshunov, Piergiorgio Modena, Stefan M Pfister, Mélanie Pagès, David Castel, Felice Giangaspero, Leila Chimelli, Pascale Varlet, Stefan Rutkowski, Didier Frappaz, Maura Massimino, Richard Grundy, Jacques Grill
PURPOSE: Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. EXPERIMENTAL DESIGN: This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort...
2017: PloS One
https://www.readbyqxmd.com/read/28610606/biologic-therapies-for-refractory-juvenile-dermatomyositis-five-years-of-experience-of-the-childhood-arthritis-and-rheumatology-research-alliance-in-north-america
#7
C H Spencer, K Rouster-Stevens, H Gewanter, G Syverson, R Modica, K Schmidt, H Emery, C Wallace, S Grevich, K Nanda, Y D Zhao, S Shenoi, S Tarvin, S Hong, C Lindsley, J E Weiss, M Passo, K Ede, A Brown, K Ardalan, W Bernal, M L Stoll, B Lang, R Carrasco, C Agaiar, L Feller, H Bukulmez, R Vehe, H Kim, H Schmeling, D Gerstbacher, M Hoeltzel, B Eberhard, R Sundel, S Kim, A M Huber, A Patwardhan
BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA)...
June 13, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28604107/accelerating-drug-development-for-neuroblastoma-new-drug-development-strategy-an-innovative-therapies-for-children-with-cancer-european-network-for-cancer-research-in-children-and-adolescents-and-international-society-of-paediatric-oncology-europe-neuroblastoma
#8
Lucas Moreno, Hubert Caron, Birgit Geoerger, Angelika Eggert, Gudrun Schleiermacher, Penelope Brock, Dominique Valteau-Couanet, Louis Chesler, Johannes H Schulte, Katleen De Preter, Jan Molenaar, Alexander Schramm, Martin Eilers, Tom Van Maerken, John Inge Johnsen, Michelle Garrett, Sally L George, Deborah A Tweddle, Per Kogner, Frank Berthold, Jan Koster, Giuseppe Barone, Elizabeth R Tucker, Lynley Marshall, Ralf Herold, Jaroslav Sterba, Koen Norga, Gilles Vassal, Andrew Dj Pearson
Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma...
June 12, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28600472/precision-medicine-in-pediatric-oncology-translating-genomic-discoveries-into-optimized-therapies
#9
Thai Hoa Tran, Avanthi Tayi Shah, Mignon L Loh
Survival of children with cancers has dramatically improved over the past several decades.  This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified "driver" genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28592748/epigenetic-targeted-therapy-for-diffuse-intrinsic-pontine-glioma
#10
Rintaro Hashizume
Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5-7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone...
June 7, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28590344/the-characteristics-and-long-term-outcomes-of-pediatric-crohn-s-disease-patients-with-perianal-disease
#11
Yonatan Herman, Firas Rinawi, Benjamin Rothschild, Osnat Nir, Raanan Shamir, Amit Assa
BACKGROUND: Data on the outcomes of children with perianal Crohn's disease are limited. We aimed to assess phenotypic features at diagnosis and long-term disease-specific outcomes of this phenotype. METHODS: The medical records of 296 pediatric onset patients with Crohn's disease, diagnosed from 2001 to 2015, were reviewed retrospectively. Baseline characteristics included age, sex, severity indices, laboratory data, endoscopic findings, and anthropometric measurements...
June 5, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28587051/evaluating-intensity-modulated-proton-therapy-relative-to-passive-scattering-proton-therapy-for-increased-vertebral-column-sparing-in-craniospinal-irradiation-in-growing-pediatric-patients
#12
Drosoula Giantsoudi, Joao Seco, Bree R Eaton, F Joseph Simeone, Hanne Kooy, Torunn I Yock, Nancy J Tarbell, Thomas F DeLaney, Judith Adams, Harald Paganetti, Shannon M MacDonald
PURPOSE: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. METHODS AND MATERIALS: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS)...
May 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28575919/zika-virus-infection-in-pregnant-women-and-microcephaly
#13
Geraldo Duarte, Antonio Fernandes Moron, Artur Timerman, César Eduardo Fernandes, Corintio Mariani Neto, Gutemberg Leão de Almeida Filho, Heron Werner Junior, Hilka Flavia Barra do Espírito Santo, João Alfredo Piffero Steibel, João Bortoletti Filho, Juvenal Barreto Borriello de Andrade, Marcelo Burlá, Marcos Felipe Silva de Sá, Newton Eduardo Busso, Paulo César Giraldo, Renato Augusto Moreira de Sá, Renato Passini Junior, Rosiane Mattar, Rossana Pulcineli Vieira Francisco
From the discovery of the Zika virus (ZIKV) in 1947 in Uganda (Africa), until its arrival in South America, it was not known that it would affect human reproductive life so severely. Today, damage to the central nervous system is known to be multiple, and microcephaly is considered the tip of the iceberg. Microcephaly actually represents the epilogue of this infection's devastating process on the central nervous system of embryos and fetuses. As a result of central nervous system aggression by the ZIKV, this infection brings the possibility of arthrogryposis, dysphagia, deafness and visual impairment...
May 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28570506/strategies-for-preventing-hiv-infection-among-hiv-uninfected-women-attempting-conception-with-hiv-infected-men-united-states
#14
REVIEW
Jennifer F Kawwass, Dawn K Smith, Dmitry M Kissin, Lisa B Haddad, Sheree L Boulet, Saswati Sunderam, Denise J Jamieson
By the end of 2014, a total of 955,081 persons in the United States (299.5 per 100,000 population) had received a diagnosis of human immunodeficiency virus type 1 (HIV-1) infection (1). The annual estimated number of HIV infections and incidence rate in the United States decreased from 2010 to 2014, and the survival rate has increased over time (1). Effective highly active antiretroviral therapy (HAART) is helping persons with HIV to live longer, healthier lives. Many of these persons, including an unknown percentage in discordant relationships (i...
June 2, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28553077/spotlight-on-dupilumab-in-the-treatment-of-atopic-dermatitis-design-development-and-potential-place-in-therapy
#15
REVIEW
Angelo Massimiliano D'Erme, Marco Romanelli, Andrea Chiricozzi
Atopic dermatitis (AD) is among the most common inflammatory skin diseases in children and adults in industrialized countries. Up to one-third of adults (probably a smaller proportion in childhood) suffer from moderate-to-severe AD, whose recommended treatment is usually based on systemic therapies. The currently available therapeutics are limited, and AD management becomes challenging in most cases. Over the last few years, new advances in the understanding of AD pathogenic mechanisms and inflammatory pathways have led to the identification of specific therapeutic targets and new molecules have been tested...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28548702/p16-loss-and-e2f-cell-cycle-deregulation-in-infant-posterior-fossa-ependymoma
#16
Seth C Lummus, Andrew M Donson, Katherine Gowan, Kenneth L Jones, Rajeev Vibhakar, Nicholas K Foreman, B K Kleinschmidt-DeMasters
BACKGROUND: Posterior fossa (PF) ependymomas (EPNs) in infants less than 1 year of age (iEPN-PF) have a poorer clinical outcome than EPNs in older children. While radiation therapy is the standard of care for the latter, it is withheld in infants to avoid neurotoxicity to immature brain. It is unknown whether the adverse outcome in iEPN-PFs is due to treatment differences or aggressive biology. We examined this question using molecular profiling. METHODS: Six anaplastic iEPN-PFs were subjected to transcriptomic analysis and FISH for p16 loss and gains of 1q, and compared with anaplastic PF EPNs from older children...
May 26, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28545823/novel-molecular-subgroups-for-clinical-classification-and-outcome-prediction-in-childhood-medulloblastoma-a-cohort-study
#17
Edward C Schwalbe, Janet C Lindsey, Sirintra Nakjang, Stephen Crosier, Amanda J Smith, Debbie Hicks, Gholamreza Rafiee, Rebecca M Hill, Alice Iliasova, Thomas Stone, Barry Pizer, Antony Michalski, Abhijit Joshi, Stephen B Wharton, Thomas S Jacques, Simon Bailey, Daniel Williamson, Steven C Clifford
BACKGROUND: International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved...
May 22, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28542043/induction-therapy-with-biosimilar-infliximab-in-children-with-crohn-s-disease
#18
Joanna Sieczkowska-Golub, Monika Meglicka, Anna Plocek, Aleksandra Banaszkiewicz, Dorota Jarzębicka, Ewa Toporowska-Kowalska, Agnieszka Gawronska, Grzegorz Oracz, Jaroslaw Kierkus
INTRODUCTION: In most European countries, an infliximab biosimilar (CT-P13) is currently in common use. In vitro and in vivo studies have proved a high similarity between CT-P13 and the reference infliximab. CT-P13 was licensed for use in patients with Crohn's diseases (CD) based on the extrapolation of data from preclinical studies and clinical trials in rheumatology indications. The aim of this study was to assess the similarity between CT-P13 and the originator infliximab in induction therapy in CD paediatric patients...
May 24, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28540347/interdisciplinary-management-of-head-and-neck-vascular-anomalies-clinical-presentation-diagnostic-findings-and-minimalinvasive-therapies
#19
REVIEW
Maliha Sadick, Walter A Wohlgemuth, Roland Huelse, Bettina Lange, Thomas Henzler, Stefan O Schoenberg, Haneen Sadick
OBJECTIVES: Vascular anomalies are included in the 30 000 rare diseases worldwide affecting less than 5/10 000 people. Depending on their morphology and biological properties, they can cause varied disorders with organ involvement. Almost 60% of vascular anomalies have a predilection for the head and neck region in children. Clinical and scientific effort to establish interdisciplinary management concepts for vascular anomalies is increasing worldwide. METHODS: Especially in the head and neck region, clinical impairment and organ dysfunction is associated with cosmetic issues that may represent a physical and psychological issue for the patient...
2017: European Journal of Radiology Open
https://www.readbyqxmd.com/read/28538013/update-on-the-pathogenesis-and-treatment-of-juvenile-idiopathic-arthritis
#20
Gabriella Giancane, Alessandra Alongi, Angelo Ravelli
PURPOSE OF REVIEW: To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA). RECENT FINDINGS: In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process...
May 22, 2017: Current Opinion in Rheumatology
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