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https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#1
Peter M Anderson
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28320914/two-strikes-and-you-re-out-the-pathogenic-interplay-of-coinhibitor-deficiency-and-lymphopenia-induced-proliferation
#2
REVIEW
Kristofor K Ellestad, Colin C Anderson
Lymphopenia-induced proliferation (LIP) occurs when resources for T cell survival in a host are in excess. LIP has been associated with the development of inflammatory disease in situations where an additional disease-predisposing cofactor is present during LIP. This has led to the view of LIP-driven autoimmunity as a two hit model; however, not all cofactors have equal ability to precipitate autoimmunity and we have recently shown that in some circumstances, such as the absence of the coinhibitory molecule PD-1, additional hits are required...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28319634/late-onset-bexarotene-induced-cd4-lymphopenia-in-a-cutaneous-t-cell-lymphoma-patient
#3
Karin Eshagh, Laura S Romero, Jessica K So, Xianfeng Frank Zhao
Various infections, autoimmune diseases, medications, and total-body irradiation are known factors associated with CD4 lymphopenia, defined as a CD4 T-cell count below 300 cells/mL or less than 20% of total lymphocytes. We report a rare case of a patient with cutaneous T-cell lymphoma (CTCL) who developed profound CD4 lymphopenia in the setting of long-term bexarotene therapy. Bexarotene is a third-generation retinoid that inhibits epithelial cell proliferation and is approved for treatment of advanced CTCL (stages IIB-IVB) in adult patients who have failed at least 1 prior systemic therapy...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28316407/theileria-annulata-induced-brisket-oedema-in-a-bull-and-its-successful-treatment
#4
B Sudhakara Reddy, S Sivajothi
In the present case, jugular vein engorgement and oedema of the brisket region which mimic the signs of pseudopericarditis due to theileriosis in a bull was reported. An adult Ongole crossbred bull with history of weakness, anorexia and oedema at brisket region was referred to Teaching Veterinary Clinical Complex, College of Veterinary Science, Proddatur. Physical examination revealed the presence of ticks over the body, right and left prescapular lymphadenopathy and oedema at brisket region. Blood examination revealed the presence of piroplasms in erythrocytes, schizont in lymphocytes, anaemia and lymphopenia...
March 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28314788/the-parp-inhibitor-veliparib-can-be-safely-added-to-bendamustine-and-rituximab-and-has-preliminary-evidence-of-activity-in-b-cell-lymphoma
#5
Jacob D Soumerai, Andrew D Zelenetz, Craig Moskowitz, M Lia Palomba, Paul A Hamlin, Ariela Noy, David J Straus, Alison J Moskowitz, Anas Younes, Matthew J Matasar, Steven Horwitz, Carol Portlock, Jason Konner, Mrinal M Gounder, David M Hyman, Martin H Voss, Matthew G Fury, Devika Gajria, Richard D Carvajal, Alan L Ho, Jan H Beumer, Brian Kiesel, Zhigang Zhang, Alice Chen, Richard F Little, Christine Jarjies, Thu O Dang, Fallon France, Nishant Mishra, John F Gerecitano
PURPOSE: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase 1 study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. EXPERIMENTAL DESIGN: This dose-escalation study evaluated safety, pharmacokinetics and preliminary efficacy of veliparib (20-400 mg BID, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 IV, days 1 and 2)...
March 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28303547/persistent-lymphopenia-is-a-risk-factor-for-icu-acquired-infections-and-for-death-in-icu-patients-with-sustained-hypotension-at-admission
#6
Christophe Adrie, Maxime Lugosi, Romain Sonneville, Bertrand Souweine, Stéphane Ruckly, Jean-Charles Cartier, Maité Garrouste-Orgeas, Carole Schwebel, Jean-François Timsit
BACKGROUND: Severely ill patients might develop an alteration of their immune system called post-aggressive immunosuppression. We sought to assess the risk of ICU-acquired infection and of mortality according to the absolute lymphocyte count at ICU admission and its changes over 3 days. METHODS: Adults in ICU for at least 3 days with a shock or persistent low blood pressure were extracted from a French ICU database and included. We evaluated the impact of the absolute lymphocyte count at baseline and its change at day 3 on the incidence of ICU-acquired infection and on the 28-day mortality rate...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28296810/activation-associated-accelerated-apoptosis-of-memory-b-cells-in-critically-ill-patients-with-sepsis
#7
Manu Shankar-Hari, David Fear, Paul Lavender, Tracey Mare, Richard Beale, Chad Swanson, Mervyn Singer, Jo Spencer
OBJECTIVE: Sepsis is life-threatening organ dysfunction due to dysregulated host responses to infection. Current knowledge of human B-cell alterations in sepsis is sparse. We tested the hypothesis that B-cell loss in sepsis involves distinct subpopulations of B cells and investigated mechanisms of B-cell depletion. DESIGN: Prospective cohort study. SETTING: Critical care units. PATIENTS: Adult sepsis patients without any documented immune comorbidity...
March 14, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28291723/cardiac-surgery-in-systemic-lupus-erythematosus-patients-clinical-characteristics-and-outcomes
#8
Javier Tejeda-Maldonado, Lauro Quintanilla-González, Jaime Galindo-Uribe, Andrea Hinojosa-Azaola
OBJECTIVES: To study the clinical characteristics and outcomes in systemic lupus erythematosus (SLE) patients who underwent cardiac surgery. METHODS: Retrospective analysis of 30 SLE patients who underwent cardiac surgery at a single center. Demographics, comorbidities, clinical and serologic characteristics, cardiovascular risk scores and treatment were recorded. Type of surgery, postoperative complications, mortality and histology were analyzed. RESULTS: Disease duration at surgery was 2 years...
March 11, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/28287491/natural-killer-cell-assessment-in-peripheral-circulation-and-bronchoalveolar-lavage-fluid-of-patients-with-severe-sepsis-a-case-control-study
#9
Paulo Souza-Fonseca-Guimaraes, Fernando Guimaraes, Caroline Natânia De Souza-Araujo, Lidiane Maria Boldrini Leite, Alexandra Cristina Senegaglia, Anita Nishiyama, Fernando Souza-Fonseca-Guimaraes
Sepsis is a complex systemic inflammatory syndrome, the most common cause of which is attributed to systemic underlying bacterial infection. The complete mechanisms of the dynamic pro- and anti-inflammatory processes underlying the pathophysiology of sepsis remain poorly understood. Natural killer (NK) cells play a crucial role in the pathophysiology of sepsis, leading to exaggerated inflammation due their rapid response and production of pro-inflammatory cytokines such as interferon gamma (IFN-γ). Several studies have already shown that NK cells undergo lymphopenia in the peripheral blood of patients with sepsis...
March 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28281183/a-phase-1b-dose-expansion-study-of-the-pan-class-i-pi3k-inhibitor-buparlisib-bkm120-plus-carboplatin-and-paclitaxel-in-pten-deficient-tumors-and-with-dose-intensified-carboplatin-and-paclitaxel
#10
Lillian M Smyth, Kelsey R Monson, Komal Jhaveri, Alexander Drilon, Bob T Li, Wassim Abida, Gopa Iyer, John F Gerecitano, Mrinal Gounder, James J Harding, Martin H Voss, Vicky Makker, Alan L Ho, Pedram Razavi, Alexia Iasonos, Philip Bialer, Mario E Lacouture, Jerrold B Teitcher, Joseph P Erinjeri, Nora Katabi, Matthew G Fury, David M Hyman
Purpose We previously reported the phase I dose escalation study of buparlisib, a pan-class 1A PI3K inhibitor, combined with platinum/taxane-based chemotherapy in patients with advanced solid tumors. The combination was well tolerated and promising preliminary efficacy was observed in PTEN deficient tumors. This phase I dose expansion study now evaluates buparlisib plus high dose carboplatin and paclitaxel in unselected patients with advanced solid tumors and buparlisib plus standard dose carboplatin and paclitaxel in patients with PTEN deficient tumors (ClinicalTrials...
March 9, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28279837/relevance-of-diagnostic-investigations-in-patients-with-uveitis-retrospective-cohort-study-on-300-patients
#11
REVIEW
Jérôme Hadjadj, Agnès Dechartres, Thibaut Chapron, Manal Assala, Sawsen Salah, Bertrand Dunogué, Lucile Musset, Bruno Baudin, Matthieu Groh, Philippe Blanche, Luc Mouthon, Dominique Monnet, Claire Le Jeunne, Antoine Brézin, Benjamin Terrier
OBJECTIVE: The diagnostic workup of uveitis is a challenge due to the wide range of diagnoses and the lack of a well-codified diagnostic procedure. We aimed to evaluate the relevance of diagnostic investigations for the etiological diagnosis of uveitis. METHODS: Retrospective cohort study of patients referred for etiological diagnosis of uveitis. Uveitis related to ophthalmological diseases or occurring during the course of previously diagnosed diseases were not included...
March 7, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28273776/half-dose-fingolimod-for-treating-relapsing-remitting-multiple-sclerosis-observational-study
#12
Chiara Zecca, Arianna Merlini, Giulio Disanto, Mariaemma Rodegher, Letizia Panicari, Marzia Anita Lucia Romeo, Ursula Candrian, Maria Josè Messina, Emanuele Pravatà, Lucia Moiola, Catia Stefanin, Angelo Ghezzi, Patrizia Perrone, Francesco Patti, Giancarlo Comi, Claudio Gobbi, Vittorio Martinelli
OBJECTIVES: To investigate the efficacy and safety of fingolimod (FTY) 0.5 mg administered every other day (FTY-EOD) compared to every day (FTY-ED) in multiple sclerosis patients. METHODS: Multicentre retrospective observational study. Clinical, laboratory and neuroimaging data were consecutively collected from 60 FTY-EOD and 63 FTY-ED patients. Baseline characteristics were compared using logistic regression. Efficacy in preventing occurrence of relapses and demyelinating lesions was tested using propensity score-adjusted Cox and linear regressions...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28270365/treatment-of-infants-identified-as-having-severe-combined-immunodeficiency-by-means-of-newborn-screening
#13
Morna J Dorsey, Christopher C Dvorak, Morton J Cowan, Jennifer M Puck
Severe combined immunodeficiency (SCID) is characterized by severely impaired T-cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pretransplantation care, and transplantation protocols for NBS identified infants with SCID, as well as infants with other T-lymphopenic disorders detected by using NBS...
March 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28264674/epstein-barr-virus-and-cytomegalovirus-infections-and-their-clinical-relevance-in-egyptian-leukemic-pediatric-patients
#14
Samah Aly Loutfy, Maha A Abo-Shadi, Mohamed Fawzy, Mohamed El-Wakil, Shimaa A Metwally, Manar M Moneer, Nasra F Abdel Fattah, Sara Kassem, Ahmed Elgebaly
BACKGROUND: Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) infections are environmental risk factors affecting the outcome of cancer due to an impairment in the cell-mediated immunity. Therefore, this study aimed to detect the frequency of EBV and CMV DNA and their association with clinical characteristics and outcome of pediatric leukemic patients. METHODS: Samples of 50 immunocompromised pediatric leukemic patients and 30 apparently healthy children were subjected to the amplification of EBV DNA by one version of PCR targeting the Bam H1 W region of the genomic region of EBV, and the amplification of CMV DNA by targeting the CMV UL97 genomic region by a second round PCR...
March 6, 2017: Virology Journal
https://www.readbyqxmd.com/read/28260922/metronomic-treatment-of-advanced-non-small-cell-lung-cancer-with-daily-oral-vinorelbine-a-phase-i-trial
#15
Sylvia Guetz, Amanda Tufman, Joachim von Pawel, Achim Rittmeyer, Astrid Borgmeier, Pierre Ferré, Birgit Edlich, Rudolf Maria Huber
MICRO-ABSTRACT: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. INTRODUCTION: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine(®) Oral, NVBo) in advanced non-small-cell lung cancer (NSCLC)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28251801/origin-of-enriched-regulatory-t-cells-in-patients-receiving-combined-kidney-bone-marrow-transplantation-to-induce-transplantation-tolerance
#16
Ben Sprangers, Susan DeWolf, Thomas M Savage, Tatsuaki Morokata, Aleksandar Obradovic, Samuel A LoCascio, Brittany Shonts, Julien Zuber, Sai Ping Lau, Ravi Shah, Heather Morris, Valeria Steshenko, Emmanuel Zorn, Frederic I Preffer, Sven Olek, David M Dombkowski, Laurence A Turka, Robert Colvin, Robert Winchester, Tatsuo Kawai, Megan Sykes
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells (CD3(+) CD4(+) CD25(high) CD127(low) Foxp3(+) ) in blood that resulted from peripheral proliferation (Ki67(+) ), possibly new thymic emigration (CD31(+) ) and, in one tolerant subject, conversion from non-Tregs...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28243230/first-report-of-cd4-lymphopenia-and-defective-neutrophil-functions-in-a-patient-with-amebiasis-associated-with-cmv-reactivation-and-severe-bacterial-and-fungal-infections
#17
Etienne Ghrenassia, Amélie Guihot, Yuan Dong, Pauline Robinet, Thierry Fontaine, Karine Lacombe, Thomas Lescot, Marie-Caroline Meyohas, Carole Elbim
We report the case of a patient with acute necrotizing colitis due to invasive amebiasis associated with CD4 lymphopenia and impaired neutrophil responses. The course of the disease was characterized by CMV reactivation and severe and recurrent bacterial and fungal infections, which might be related to the decreased CD4 T cell count and the impaired functional capacities of neutrophils, respectively. The clinical outcome was positive with normalization of both CD4 cell count and neutrophil functions.
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28240600/the-antiviral-restriction-factor-ifn-induced-transmembrane-protein-3-prevents-cytokine-driven-cmv-pathogenesis
#18
Maria A Stacey, Simon Clare, Mathew Clement, Morgan Marsden, Juneid Abdul-Karim, Leanne Kane, Katherine Harcourt, Cordelia Brandt, Ceri A Fielding, Sarah E Smith, Rachael S Wash, Silvia Gimeno Brias, Gabrielle Stack, George Notley, Emma L Cambridge, Christopher Isherwood, Anneliese O Speak, Zoë Johnson, Walter Ferlin, Simon A Jones, Paul Kellam, Ian R Humphreys
The antiviral restriction factor IFN-induced transmembrane protein 3 (IFITM3) inhibits cell entry of a number of viruses, and genetic diversity within IFITM3 determines susceptibility to viral disease in humans. Here, we used the murine CMV (MCMV) model of infection to determine that IFITM3 limits herpesvirus-associated pathogenesis without directly preventing virus replication. Instead, IFITM3 promoted antiviral cellular immunity through the restriction of virus-induced lymphopenia, apoptosis-independent NK cell death, and loss of T cells...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28216187/recombinant-proteins-of-zaire-ebolavirus-induce-potent-humoral-and-cellular-immune-responses-and-protect-against-live-virus-infection-in-mice
#19
Axel T Lehrer, Teri-Ann S Wong, Michael M Lieberman, Tom Humphreys, David E Clements, Russell R Bakken, Mary Kate Hart, William D Pratt, John M Dye
Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death...
February 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28214184/-systemic-lupus-erythematosus-and-lymphopenia-clinical-and-pathophysiological-features
#20
M Martin, A Guffroy, X Argemi, T Martin
Lymphopenia is frequent in systemic lupus erythematosus (SLE) and profound (<500/mm(3)) in 10% of cases. T lymphocytes, especially CD4+, are more affected than B cells. The pathophysiological mechanisms are complex, involving lymphocytotoxic antibodies, excess of apoptosis, increased susceptibility of T cells to complement mediated cytolysis, as well as lymphopoiesis impairment and lymphocyte sequestration. Lymphopenia in SLE is independent from other cytopenia and immunosuppressive drug regiments, and associated with disease activity, risk of flare and damage scores...
February 14, 2017: La Revue de Médecine Interne
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