14 results on '"immunomodulatory therapy"'
Search Results
2. Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.
- Author
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Reddy, Amit K, Reddy, Amit K, Miller, D Claire, Sura, Amol A, Rathinam, SR, Gonzales, John A, Thundikandy, Radhika, Kanakath, Anuradha, Murugan, Bala, Vedhanayaki, Rajesh, Lim, Lyndell L, Suhler, Eric B, Doan, Thuy, Al-Dhibi, Hassan A, Goldstein, Debra A, Arellanes-Garcia, Lourdes, Acharya, Nisha R, Reddy, Amit K, Reddy, Amit K, Miller, D Claire, Sura, Amol A, Rathinam, SR, Gonzales, John A, Thundikandy, Radhika, Kanakath, Anuradha, Murugan, Bala, Vedhanayaki, Rajesh, Lim, Lyndell L, Suhler, Eric B, Doan, Thuy, Al-Dhibi, Hassan A, Goldstein, Debra A, Arellanes-Garcia, Lourdes, and Acharya, Nisha R more...
- Abstract
BackgroundThe antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis.Main bodyThis is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF.ConclusionRetinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics. more...
- Published
- 2023
Catalog
3. Vesículas extracelulares (EVs) derivadas de células estromales mesenquimales (MSCs): un nuevo enfoque terapéutico para la Covid-19
- Author
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García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, Pons Alonso, Omar, García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, and Pons Alonso, Omar more...
- Abstract
[ES] La COVID-19 es la enfermedad causada por el coronavirus descubierto recientemente, el SARS-CoV-2. Actualmente se trata de una pandemia que afecta a numerosos países de todo el mundo y que está causando un elevado número de muertes. La virulencia del SARS-CoV-2 se debe principalmente a su capacidad para producir una reacción exacerbada de la respuesta inmune, provocando una liberación aguda de citoquinas proinflamatorias en el pulmón, lo que se conoce como tormenta de citoquinas. La lesión pulmonar inducida por inflamación provoca disfunción del intercambio gaseoso, síndrome de dificultad respiratoria aguda y disfunción multiorgánica, conduciendo a la muerte del paciente. En este aspecto, resulta de gran interés encontrar una terapia que regule la respuesta inmune de manera eficaz. Las células estromales mesenquimales (MSCs) han despertado un fuerte interés en la comunidad científica en los últimos años debido a sus propiedades inmunorreguladoras y a su capacidad para regenerar tejidos dañados. Por este motivo, el tratamiento de la COVD-19 basado en MSCs se ha propuesto como un enfoque terapéutico adecuado y ya se han comenzado varios ensayos clínicos. Las MSCs podrían proteger las células epiteliales alveolares, regenerar el microambiente pulmonar, prevenir la fibrosis y evitar la tormenta de citoquinas gracias a su capacidad inmunomoduladora. Las propiedades de las MSCs se deben a un mecanismo paracrino. Secretan factores solubles que regulan la respuesta inmune y promueven la supervivencia celular. Entre estos factores destacan las vesículas extracelulares (EVs). Una terapia basada en EVs evita los efectos adversos asociados a la terapia basada en células, como la obstrucción de la microvasculatura, la tumorigenicidad y el riesgo de infección. Los ensayos clínicos en los que se han utilizado las MSCs como tratamiento de patologías en las que hay una desregulación del sistema inmune han mostrado resultados inconsistentes, probablemente debido al uso de diferen, [EN] COVID-19, the disease caused by the new coronavirus SARS-CoV-2, has become a global pandemic that is causing countless deaths. It has been declared by the WHO as a health and social emergency that requires immediate and effective action. In the most severe cases of COVID-19, an acute inflammatory response known as a cytokine storm occurs. Inflammation-induced lung injury causes gas exchange dysfunction, acute respiratory distress syndrome, and multi-organ dysfunction, leading to the death of the patient. For this reason, it is vitally important to find an effective immunomodulatory therapy. Mesenchymal stromal cells (MSCs) -based therapy has been proposed as a suitable therapeutic approach due to its ability to regulate the immune system and regenerate damaged tissues. The properties of MSCs are due to a paracrine mechanism, they secrete soluble factors that regulate the immune response and promote cell survival. These factors include extracellular vesicles (EVs), which participate in intercellular communication transporting bioactive molecules. A therapy based on EVs would avoid the adverse effects associated with cell-based therapy, such as obstruction of the microvasculature, tumorigenicity and the risk of infection. Clinical trials that have used MSCs to treat pathologies related to dysregulation of the immune system have shown inconsistent and variable results. This is due to the use of different sources of MSCs and different culture conditions that can alter their therapeutic properties, which is why it is necessary to establish the population of MSCs with the greatest therapeutic potential and the culture conditions that allow improving the properties of MSCs. In the context of COVID-19, patients treated with MSCs show clear clinical improvement, a decrease in inflammation markers and a recovery of normal leukocyte levels. These data suggest that the mechanisms underlying this clinical improvement are due to the immunomodulatory capacity of MSCs. more...
- Published
- 2021
4. Vesículas extracelulares (EVs) derivadas de células estromales mesenquimales (MSCs): un nuevo enfoque terapéutico para la Covid-19
- Author
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García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, Pons Alonso, Omar, García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, and Pons Alonso, Omar more...
- Abstract
[ES] La COVID-19 es la enfermedad causada por el coronavirus descubierto recientemente, el SARS-CoV-2. Actualmente se trata de una pandemia que afecta a numerosos países de todo el mundo y que está causando un elevado número de muertes. La virulencia del SARS-CoV-2 se debe principalmente a su capacidad para producir una reacción exacerbada de la respuesta inmune, provocando una liberación aguda de citoquinas proinflamatorias en el pulmón, lo que se conoce como tormenta de citoquinas. La lesión pulmonar inducida por inflamación provoca disfunción del intercambio gaseoso, síndrome de dificultad respiratoria aguda y disfunción multiorgánica, conduciendo a la muerte del paciente. En este aspecto, resulta de gran interés encontrar una terapia que regule la respuesta inmune de manera eficaz. Las células estromales mesenquimales (MSCs) han despertado un fuerte interés en la comunidad científica en los últimos años debido a sus propiedades inmunorreguladoras y a su capacidad para regenerar tejidos dañados. Por este motivo, el tratamiento de la COVD-19 basado en MSCs se ha propuesto como un enfoque terapéutico adecuado y ya se han comenzado varios ensayos clínicos. Las MSCs podrían proteger las células epiteliales alveolares, regenerar el microambiente pulmonar, prevenir la fibrosis y evitar la tormenta de citoquinas gracias a su capacidad inmunomoduladora. Las propiedades de las MSCs se deben a un mecanismo paracrino. Secretan factores solubles que regulan la respuesta inmune y promueven la supervivencia celular. Entre estos factores destacan las vesículas extracelulares (EVs). Una terapia basada en EVs evita los efectos adversos asociados a la terapia basada en células, como la obstrucción de la microvasculatura, la tumorigenicidad y el riesgo de infección. Los ensayos clínicos en los que se han utilizado las MSCs como tratamiento de patologías en las que hay una desregulación del sistema inmune han mostrado resultados inconsistentes, probablemente debido al uso de diferen, [EN] COVID-19, the disease caused by the new coronavirus SARS-CoV-2, has become a global pandemic that is causing countless deaths. It has been declared by the WHO as a health and social emergency that requires immediate and effective action. In the most severe cases of COVID-19, an acute inflammatory response known as a cytokine storm occurs. Inflammation-induced lung injury causes gas exchange dysfunction, acute respiratory distress syndrome, and multi-organ dysfunction, leading to the death of the patient. For this reason, it is vitally important to find an effective immunomodulatory therapy. Mesenchymal stromal cells (MSCs) -based therapy has been proposed as a suitable therapeutic approach due to its ability to regulate the immune system and regenerate damaged tissues. The properties of MSCs are due to a paracrine mechanism, they secrete soluble factors that regulate the immune response and promote cell survival. These factors include extracellular vesicles (EVs), which participate in intercellular communication transporting bioactive molecules. A therapy based on EVs would avoid the adverse effects associated with cell-based therapy, such as obstruction of the microvasculature, tumorigenicity and the risk of infection. Clinical trials that have used MSCs to treat pathologies related to dysregulation of the immune system have shown inconsistent and variable results. This is due to the use of different sources of MSCs and different culture conditions that can alter their therapeutic properties, which is why it is necessary to establish the population of MSCs with the greatest therapeutic potential and the culture conditions that allow improving the properties of MSCs. In the context of COVID-19, patients treated with MSCs show clear clinical improvement, a decrease in inflammation markers and a recovery of normal leukocyte levels. These data suggest that the mechanisms underlying this clinical improvement are due to the immunomodulatory capacity of MSCs. more...
- Published
- 2021
5. Vesículas extracelulares (EVs) derivadas de células estromales mesenquimales (MSCs): un nuevo enfoque terapéutico para la Covid-19
- Author
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García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, Pons Alonso, Omar, García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, and Pons Alonso, Omar more...
- Abstract
[ES] La COVID-19 es la enfermedad causada por el coronavirus descubierto recientemente, el SARS-CoV-2. Actualmente se trata de una pandemia que afecta a numerosos países de todo el mundo y que está causando un elevado número de muertes. La virulencia del SARS-CoV-2 se debe principalmente a su capacidad para producir una reacción exacerbada de la respuesta inmune, provocando una liberación aguda de citoquinas proinflamatorias en el pulmón, lo que se conoce como tormenta de citoquinas. La lesión pulmonar inducida por inflamación provoca disfunción del intercambio gaseoso, síndrome de dificultad respiratoria aguda y disfunción multiorgánica, conduciendo a la muerte del paciente. En este aspecto, resulta de gran interés encontrar una terapia que regule la respuesta inmune de manera eficaz. Las células estromales mesenquimales (MSCs) han despertado un fuerte interés en la comunidad científica en los últimos años debido a sus propiedades inmunorreguladoras y a su capacidad para regenerar tejidos dañados. Por este motivo, el tratamiento de la COVD-19 basado en MSCs se ha propuesto como un enfoque terapéutico adecuado y ya se han comenzado varios ensayos clínicos. Las MSCs podrían proteger las células epiteliales alveolares, regenerar el microambiente pulmonar, prevenir la fibrosis y evitar la tormenta de citoquinas gracias a su capacidad inmunomoduladora. Las propiedades de las MSCs se deben a un mecanismo paracrino. Secretan factores solubles que regulan la respuesta inmune y promueven la supervivencia celular. Entre estos factores destacan las vesículas extracelulares (EVs). Una terapia basada en EVs evita los efectos adversos asociados a la terapia basada en células, como la obstrucción de la microvasculatura, la tumorigenicidad y el riesgo de infección. Los ensayos clínicos en los que se han utilizado las MSCs como tratamiento de patologías en las que hay una desregulación del sistema inmune han mostrado resultados inconsistentes, probablemente debido al uso de diferen, [EN] COVID-19, the disease caused by the new coronavirus SARS-CoV-2, has become a global pandemic that is causing countless deaths. It has been declared by the WHO as a health and social emergency that requires immediate and effective action. In the most severe cases of COVID-19, an acute inflammatory response known as a cytokine storm occurs. Inflammation-induced lung injury causes gas exchange dysfunction, acute respiratory distress syndrome, and multi-organ dysfunction, leading to the death of the patient. For this reason, it is vitally important to find an effective immunomodulatory therapy. Mesenchymal stromal cells (MSCs) -based therapy has been proposed as a suitable therapeutic approach due to its ability to regulate the immune system and regenerate damaged tissues. The properties of MSCs are due to a paracrine mechanism, they secrete soluble factors that regulate the immune response and promote cell survival. These factors include extracellular vesicles (EVs), which participate in intercellular communication transporting bioactive molecules. A therapy based on EVs would avoid the adverse effects associated with cell-based therapy, such as obstruction of the microvasculature, tumorigenicity and the risk of infection. Clinical trials that have used MSCs to treat pathologies related to dysregulation of the immune system have shown inconsistent and variable results. This is due to the use of different sources of MSCs and different culture conditions that can alter their therapeutic properties, which is why it is necessary to establish the population of MSCs with the greatest therapeutic potential and the culture conditions that allow improving the properties of MSCs. In the context of COVID-19, patients treated with MSCs show clear clinical improvement, a decrease in inflammation markers and a recovery of normal leukocyte levels. These data suggest that the mechanisms underlying this clinical improvement are due to the immunomodulatory capacity of MSCs. more...
- Published
- 2021
6. Vesículas extracelulares (EVs) derivadas de células estromales mesenquimales (MSCs): un nuevo enfoque terapéutico para la Covid-19
- Author
-
García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, Pons Alonso, Omar, García Gimeno, María Adelaida, Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia, and Pons Alonso, Omar more...
- Abstract
[ES] La COVID-19 es la enfermedad causada por el coronavirus descubierto recientemente, el SARS-CoV-2. Actualmente se trata de una pandemia que afecta a numerosos países de todo el mundo y que está causando un elevado número de muertes. La virulencia del SARS-CoV-2 se debe principalmente a su capacidad para producir una reacción exacerbada de la respuesta inmune, provocando una liberación aguda de citoquinas proinflamatorias en el pulmón, lo que se conoce como tormenta de citoquinas. La lesión pulmonar inducida por inflamación provoca disfunción del intercambio gaseoso, síndrome de dificultad respiratoria aguda y disfunción multiorgánica, conduciendo a la muerte del paciente. En este aspecto, resulta de gran interés encontrar una terapia que regule la respuesta inmune de manera eficaz. Las células estromales mesenquimales (MSCs) han despertado un fuerte interés en la comunidad científica en los últimos años debido a sus propiedades inmunorreguladoras y a su capacidad para regenerar tejidos dañados. Por este motivo, el tratamiento de la COVD-19 basado en MSCs se ha propuesto como un enfoque terapéutico adecuado y ya se han comenzado varios ensayos clínicos. Las MSCs podrían proteger las células epiteliales alveolares, regenerar el microambiente pulmonar, prevenir la fibrosis y evitar la tormenta de citoquinas gracias a su capacidad inmunomoduladora. Las propiedades de las MSCs se deben a un mecanismo paracrino. Secretan factores solubles que regulan la respuesta inmune y promueven la supervivencia celular. Entre estos factores destacan las vesículas extracelulares (EVs). Una terapia basada en EVs evita los efectos adversos asociados a la terapia basada en células, como la obstrucción de la microvasculatura, la tumorigenicidad y el riesgo de infección. Los ensayos clínicos en los que se han utilizado las MSCs como tratamiento de patologías en las que hay una desregulación del sistema inmune han mostrado resultados inconsistentes, probablemente debido al uso de diferen, [EN] COVID-19, the disease caused by the new coronavirus SARS-CoV-2, has become a global pandemic that is causing countless deaths. It has been declared by the WHO as a health and social emergency that requires immediate and effective action. In the most severe cases of COVID-19, an acute inflammatory response known as a cytokine storm occurs. Inflammation-induced lung injury causes gas exchange dysfunction, acute respiratory distress syndrome, and multi-organ dysfunction, leading to the death of the patient. For this reason, it is vitally important to find an effective immunomodulatory therapy. Mesenchymal stromal cells (MSCs) -based therapy has been proposed as a suitable therapeutic approach due to its ability to regulate the immune system and regenerate damaged tissues. The properties of MSCs are due to a paracrine mechanism, they secrete soluble factors that regulate the immune response and promote cell survival. These factors include extracellular vesicles (EVs), which participate in intercellular communication transporting bioactive molecules. A therapy based on EVs would avoid the adverse effects associated with cell-based therapy, such as obstruction of the microvasculature, tumorigenicity and the risk of infection. Clinical trials that have used MSCs to treat pathologies related to dysregulation of the immune system have shown inconsistent and variable results. This is due to the use of different sources of MSCs and different culture conditions that can alter their therapeutic properties, which is why it is necessary to establish the population of MSCs with the greatest therapeutic potential and the culture conditions that allow improving the properties of MSCs. In the context of COVID-19, patients treated with MSCs show clear clinical improvement, a decrease in inflammation markers and a recovery of normal leukocyte levels. These data suggest that the mechanisms underlying this clinical improvement are due to the immunomodulatory capacity of MSCs. more...
- Published
- 2021
7. Clinical Characteristics and Outcomes of Coronavirus Disease 2019 Patients Who Received Compassionate-Use Leronlimab.
- Author
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Yang, Bryant, Yang, Bryant, Fulcher, Jennifer A, Ahn, Jenny, Berro, Marlene, Goodman-Meza, David, Dhody, Kush, Sacha, Jonah B, Naeim, Arash, Yang, Otto O, Yang, Bryant, Yang, Bryant, Fulcher, Jennifer A, Ahn, Jenny, Berro, Marlene, Goodman-Meza, David, Dhody, Kush, Sacha, Jonah B, Naeim, Arash, and Yang, Otto O more...
- Abstract
BackgroundLeronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19).MethodsTwenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records.ResultsMean age was 69.5 ± 14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died.ConclusionsLeronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative. more...
- Published
- 2021
8. Clinical Characteristics and Outcomes of COVID-19 Patients Receiving Compassionate Use Leronlimab.
- Author
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Yang, Bryant, Yang, Bryant, Fulcher, Jennifer A, Ahn, Jenny, Berro, Marlene, Goodman-Meza, David, Dhody, Kush, Sacha, Jonah B, Naeim, Arash, Yang, Otto O, Yang, Bryant, Yang, Bryant, Fulcher, Jennifer A, Ahn, Jenny, Berro, Marlene, Goodman-Meza, David, Dhody, Kush, Sacha, Jonah B, Naeim, Arash, and Yang, Otto O more...
- Abstract
BackgroundLeronlimab, a monoclonal antibody blocker of CCR5 originally developed to treat HIV-1 infection, was administered as an open label compassionate use therapeutic for COVID-19.Methods23 hospitalized severe/critical COVID-19 patients received 700mg leronlimab subcutaneously, repeated after seven days in 17/23 patients still hospitalized. 18/23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. 5/23 received leronlimab after blinded placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records.ResultsMean age was 69.5±14.9 years. 20/23 had significant co-morbidities. At baseline, 22/23 were receiving supplemental oxygen (3/23 high flow, 7/23 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and elevated neutrophil:lymphocyte ratio. By day 30 after initial dosing, 17/23 were recovered, 2/23 were still hospitalized, and 4/23 had died. Of the 7 intubated at baseline, 4/7 were fully recovered off oxygen, 2/7 were still hospitalized, and 1/7 had died.ConclusionsLeronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some but not all patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although IL-6 tended to fall. In some persons C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative. more...
- Published
- 2020
9. Central Nervous System Infections Associated with Immunosuppressive Therapy for Rheumatic Disease.
- Author
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Bradshaw, Michael J, Bradshaw, Michael J, Cho, Tracey A, Chow, Felicia C, Bradshaw, Michael J, Bradshaw, Michael J, Cho, Tracey A, and Chow, Felicia C
- Abstract
Patients on immunosuppressive therapy for rheumatic diseases are at increased risk of infection. Although infections of the central nervous system (CNS) are less common compared with other sites, patients on broadly immunosuppressive and biologic immunomodulatory agents may be susceptible to more severe, disseminated forms of infection, including of the CNS. Certain key principles regarding infection risk apply across immunosuppressive therapies, including increased risk with higher doses and longer duration of therapy and with combination therapy. Providers should be aware of the CNS infection risk related to immunosuppressant use to help guide best practices for screening and prophylaxis. more...
- Published
- 2017
10. Multiple Sclerosis in Pediatrics: Current Concepts and Treatment Options
- Author
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Jancic, J. (Jasna), Nikolic, B. (Blazo), Ivancevic, N. (Nikola), Djuric, V. (Vesna), Zaletel, I. (Ivan), Stevanovic, D. (Dejan), Peric, S. (Sasa), Anker, J.N. (John) van den, Samardzic, J. (Janko), Jancic, J. (Jasna), Nikolic, B. (Blazo), Ivancevic, N. (Nikola), Djuric, V. (Vesna), Zaletel, I. (Ivan), Stevanovic, D. (Dejan), Peric, S. (Sasa), Anker, J.N. (John) van den, and Samardzic, J. (Janko) more...
- Abstract
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment. The treatment of children with MS has to be multidisciplinary and include pediatric neurologists, ophthalmologists, psychologists, physiotherapists, and if necessary, pediatric psychiatrists and pharmacologists. The basis of MS therapy should rely on drugs that are able to modify the course of the disease, i.e. immunomodulatory drugs. These drugs can be subdivided into two general categories: first-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, glatiramer acetate) and second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab). Treatment of relapses involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis. We summarize here the current available information related to the etiology and treatment options in MS. Early administration of immunomodulatory therapy is beneficial in adults, while more studies are needed to prove their effectiveness in pediatric populations. Therefore, pediatric MS still represents a great challenge for both, the early and correct diagnosis, as well as its treatment. more...
- Published
- 2016
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11. Досвід застосування імуномодулюючої терапії в комплексному лікуванні хронічного тонзиліту в дітей
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Marushko, Yu.V.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, Hyshchak, T.V.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, Lysovets, O.V.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, Marushko, Ye.Yu.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, Marushko, Yu.V.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, Hyshchak, T.V.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, Lysovets, O.V.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv, and Marushko, Ye.Yu.; National Medical University named after O.O. Bohomolets, Kyiv; Children’s Clinical Hospital № 5, Kyiv more...
- Abstract
Імуномодулююча терапія є важливою складовою лікування хворих на хронічний тонзиліт, викликаний β-гемолітичним стрептококом групи А, на фоні антибіотикотерапії вона дозволяє досягти більш ефективної елімінації збудника. Призначення препарату Імупрет у комплексному лікуванні загострення хронічного тонзиліту стрептококової етіології сприяє швидкому зникненню клінічних проявів захворювання, збільшує частоту елімінації збудника, зменшує частоту загострень хронічного тонзиліту., Иммуномодулирующая терапия является важной составляющей лечения больных хроническим тонзиллитом, вызванным β-гемолитическим стрептококком группы А, на фоне антибиотикотерапии она позволяет достичь более эффективной элиминации возбудителя. Назначение препарата Имупрет в комплексном лечении обострения хронического тонзиллита стрептококковой этиологии способствует быстрому исчезновению клинических проявлений заболевания, повышает частоту элиминации возбудителя, уменьшает частоту обострений хронического тонзиллита., Immunomodulatory therapy is an important part of treating patients with chronic tonsillitis caused by β-hemolytic streptococcus group A, on the background of antibiotic therapy it allows us to achieve a more effective elimination of the pathogen. Administration of Imupret in the comprehensive treatment for exacerbation of chronic tonsillitis of streptococcal origin leads to the rapid disappearance of clinical manifestations of the disease, high frequency of pathogen elimination, reduces the incidence of chronic tonsillitis exacerbations. more...
- Published
- 2016
12. Intravenous Immunoglobulins: Mechanism of Action and Limitations of Clinical Application in Pediatrics
- Author
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Mokiia-Serbina, S.O.; State Institution «Dnipropetrovsk Medical Academy of the Ministry of Healthcare of Ukraine», Dnipropetrovsk and Mokiia-Serbina, S.O.; State Institution «Dnipropetrovsk Medical Academy of the Ministry of Healthcare of Ukraine», Dnipropetrovsk more...
- Abstract
This review deals with an analysis of the available clinical studies and reports concerning the evaluation of the effectiveness and safety of intravenous immunoglobulins (IVIG) in various diseases in children. Intravenous immunoglobulins are drugs with a strictly regulated indications and proven efficacy and safety. Most often they are used for the correction of hypogammaglobulinemia, which is the result of a primary or secondary immunodeficiency (ID).To date, a large, but heterogeneous evidence base on the effectiveness of the standard IVIG in sepsis in children of different age groups is accumulated.IVIG consumption is increasing due to the fact that in many cases the drugs are being used off-label. IVIG were more likely to be used in autoimmune and systemic inflammatory diseases. However, in randomized clinical trials, a good effect was achieved only in Kawasaki disease and immune thrombocytopenic purpura. Current clinical guidelines narrowed the indications for IVIG, limiting their use in sepsis. Immunoglobulin replacement therapy is recommended for children with physiological delay of immunoglobulin production only in repeated infections, which can not be controlled or prevented with antibiotics. In secondary ID, replacement therapy must be carried out if the cause of hypogammaglobulinemia can not be eliminated or elimination is contraindicated, as well as in association with β-cell cancers, in which severe infections caused by encapsulated bacteria persist despite preventive antibiotic therapy., Данный обзор посвящен анализу доступных клинических исследований и сообщений, касающихся оценки эффективности и безопасности применения внутривенных иммуноглобулинов (ВВИГ) при различных заболеваниях у детей. Внутривенные иммуноглобулины являются препаратами со строго регламентированными показаниями и доказанной эффективностью и безопасностью. Наиболее часто их применяют для коррекции гипогаммаглобулинемии, являющейся результатом первичного или вторичного иммунодефицитного состояния (ИДС).На сегодняшний день накоплена обширная, однако неоднородная доказательная база эффективности применения стандартных ВВИГ при сепсисе у детей различных возрастных групп.Потребление ВВИГ растет в связи с тем, что во многих случаях препараты назначают вне регламентированных показаний. ВВИГ стали чаще применяться при аутоиммунных и системных воспалительных заболеваниях. Однако в рандомизированных клинических исследованиях хороший эффект был достигнут только при болезни Кавасаки и иммунной тромбоцитопенической пурпуре. Современные клинические руководства сузили показания к назначению ВВИГ, ограничивают их применение при сепсисе. Заместительная терапия иммуноглобулинами рекомендуется детям с физиологической задержкой производства своего иммуноглобулина только при наличии повторных инфекций, которые нельзя проконтролировать или предотвратить с помощью антибиотиков. При вторичном ИДС заместительную терапию разрешается проводить, если причина гипогаммаглобулинемии не может быть устранена или устранение противопоказано, а также при ассоциации с β-клеточными онкозаболеваниями, при которых тяжелые инфекции, вызванные инкапсулированными бактериями, персистируют, несмотря на проведение профилактической антибиотикотерапии., Даний огляд присвячений аналізу доступних клінічних досліджень і повідомлень, що стосуються оцінки ефективності та безпеки застосування внутрішньовенних імуноглобулінів (ВВІГ) при різних захворюваннях у дітей. Внутрішньовенні імуноглобуліни є препаратами зі строго регламентованими показаннями і доведеною ефективністю і безпекою. Найбільш часто їх застосовують для корекції гіпогаммаглобулінемії, що є результатом первинного чи вторинного імунодефіцитного стану (ІДС).На сьогодні накопичена велика, однак неоднорідна доказова база ефективності застосування стандартних ВВІГ при сепсисі в дітей різних вікових груп.Споживання ВВІГ зростає у зв’язку з тим, що в багатьох випадках препарати призначають поза регламентованих показань. ВВІГ почали частіше застосовуватися при аутоімунних і системних запальних захворюваннях. Однак у рандомізованих клінічних дослідженнях хороший ефект був досягнутий тільки при хворобі Кавасакі та імунній тромбоцитопенічній пурпурі. Сучасні клінічні керівництва звузили показання до призначення ВВІГ, обмежують їх застосування при сепсисі. Замісна терапія імуноглобулінами рекомендується дітям із фізіологічною затримкою вироблення свого імуноглобуліну тільки при наявності повторних інфекцій, які не можна проконтролювати або запобігти їм за допомогою антибіотиків. При вторинному ІДС замісну терапію дозволяється проводити, якщо причина гіпогаммаглобулінемії не може бути усунена або усунення протипоказано, а також при асоціації з β-клітинними онкозахворюваннями, при яких тяжкі інфекції, викликані інкапсульованими бактеріями, персистують, незважаючи на проведення профілактичної антибіотикотерапії. more...
- Published
- 2016
13. Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares
- Author
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Christoffersen, Mette, Woodward, E. M., Bojesen, Anders Miki, Petersen, Morten Rønn, Squires, E. L., Lehn-Jensen, Henrik, Troedsson, M. H. T., Christoffersen, Mette, Woodward, E. M., Bojesen, Anders Miki, Petersen, Morten Rønn, Squires, E. L., Lehn-Jensen, Henrik, and Troedsson, M. H. T. more...
- Abstract
The objective of the present study was to evaluate the effect of immunomodulatory therapy (glucocorticoids (GC) and mycobacterium cell wall extract (MCWE)) on the endometrial gene expression of inflammatory cytokines in susceptible mares with induced infectious endometritis. Endometrial gene expression of pro- and anti-inflammatory cytokines; interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-a, IL-1 receptor antagonist (ra), acute phase protein (APP) serum amyloid A (SAA) and clinical parameters were evaluated. Five mares were classified as susceptible to persistent endometritis based on their endometrial histopathology and ability to clear an induced uterine inflammation. To investigate the effect of immunomodulatory therapy, the mares were inoculated with 10(5) colony forming units (CFU) Escherichia coli in three consecutive estrus cycles in a modified cross-over study design. Thus, each mare served as its own control and the treatment type was performed in randomized order. The effect of treatment with MCWE (1.5 mg Settle IV), dexamethasone (0.1 mg per kg IV) or no treatment was investigated. All mares were free from uterine inflammation before each E. coli inoculation. Endometrial biopsies were recovered 3, 24 and 72 h post inoculation. Relative gene-expression analyses were performed by quantitative reverse transcriptase PCR (qRT-PCR). Endometrial gene expression of inflammatory cytokines was modulated by administration of GC. Expression of proinflammatory cytokines (IL-1ß, IL-6, IL-8) and SAA was significantly lower in the GC treated group late in the study period (72 h) compared to "no treatment" and MCWE treatment. Increased expression of the anti-inflammatory cytokine IL-10 was observed 3 and 24 h after E. coli infusion and GC treatment. A significant decrease of SAA expression was observed after MCWE treatment compared to "no treatment". MCWE and GC treatment had a significant effect on the clearance of uterine pathogens and number of mar more...
- Published
- 2012
14. Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares
- Author
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Christoffersen, Mette, Woodward, E. M., Bojesen, Anders Miki, Petersen, Morten Rønn, Squires, E. L., Lehn-Jensen, Henrik, Troedsson, M. H. T., Christoffersen, Mette, Woodward, E. M., Bojesen, Anders Miki, Petersen, Morten Rønn, Squires, E. L., Lehn-Jensen, Henrik, and Troedsson, M. H. T. more...
- Abstract
The objective of the present study was to evaluate the effect of immunomodulatory therapy (glucocorticoids (GC) and mycobacterium cell wall extract (MCWE)) on the endometrial gene expression of inflammatory cytokines in susceptible mares with induced infectious endometritis. Endometrial gene expression of pro- and anti-inflammatory cytokines; interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-a, IL-1 receptor antagonist (ra), acute phase protein (APP) serum amyloid A (SAA) and clinical parameters were evaluated. Five mares were classified as susceptible to persistent endometritis based on their endometrial histopathology and ability to clear an induced uterine inflammation. To investigate the effect of immunomodulatory therapy, the mares were inoculated with 10(5) colony forming units (CFU) Escherichia coli in three consecutive estrus cycles in a modified cross-over study design. Thus, each mare served as its own control and the treatment type was performed in randomized order. The effect of treatment with MCWE (1.5 mg Settle IV), dexamethasone (0.1 mg per kg IV) or no treatment was investigated. All mares were free from uterine inflammation before each E. coli inoculation. Endometrial biopsies were recovered 3, 24 and 72 h post inoculation. Relative gene-expression analyses were performed by quantitative reverse transcriptase PCR (qRT-PCR). Endometrial gene expression of inflammatory cytokines was modulated by administration of GC. Expression of proinflammatory cytokines (IL-1ß, IL-6, IL-8) and SAA was significantly lower in the GC treated group late in the study period (72 h) compared to "no treatment" and MCWE treatment. Increased expression of the anti-inflammatory cytokine IL-10 was observed 3 and 24 h after E. coli infusion and GC treatment. A significant decrease of SAA expression was observed after MCWE treatment compared to "no treatment". MCWE and GC treatment had a significant effect on the clearance of uterine pathogens and number of mar more...
- Published
- 2012
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