Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

Una aproximación actualizada hacia el tratamiento de la Esclerosis Múltiple / AN UPDATED APPROACH TO THE TREATMENT OF MULTIPLE SCLEROSIS

La presente es una revisión bibliográfica actualizada sobre el manejo de la Esclerosis Múltiple (EM), enfermedad neurológica progresiva de tipo desmielinizante más frecuente a nivel mundial. En Chile, su presentación remitente-recurrente (RRMS) es patología GES, por lo que se vuelve relevante para el médico general y estudiantes del área de la salud reconocer e identificar las terapias disponibles para el control de esta patología. Si bien la EM no es un cuadro frecuente, su sintomatología es alarmante e incapacitante, por lo que, con frecuencia, el primer acercamiento del paciente es a los servicios de urgencia, tornándose necesario contar con nociones básicas sobre el tratamiento y manejo. La presente revisión recopiló artículos publicados entre 2019 y 2023 de distintos motores de búsqueda con énfasis en el tratamiento farmacológico y no farmacológico de esta enfermedad. Además de describir el tratamiento convencional como la inmunomodulación, las terapias biológicas, el soporte con glucocorticoides y los fármacos remielinizantes, se abordan nuevas líneas de investigación prometedoras, como el rol inmunogénico de la microbiota intestinal, la capacidad epigenética de la dieta, estrategias de rehabilitación cognitiva y el potencial uso de cannabinoides para el manejo paliativo del dolor. Se concluye que un tratamiento oportuno con fármacos modificadores de la enfermedad, tanto de primera línea como de segunda, son imprescindibles para el manejo de la EM, sin embargo, la calidad de vida puede verse significativamente acrecentada por la incorporación de estrategias que se encuentran al alcance del médico general y que no requieren de derivación a nivel secundario.

This is an updated bibliographical review on the management of Multiple Sclerosis (MS), the most common progressive neurological disease of demyelinating disorders worldwide. In Chile, its relapsing-remitting presentation (RRMS) is a state-covered illness pathology, so it becomes relevant for the general practitioner and med students to recognize and identify therapies available for the control of this desease. Although MS is not a frequent condition, its symptoms are alarming and disabling, which is why, frequently, the first approach of the patient is to the emergency services, making it necessary to have basic knowledge about treatment and management. The present review compiled articles published between 2019 and 2023 from different search engines with an emphasis on the pharmacological and non-pharmacological treatment of the MS. In addition to describing conventional treatment such as immunomodulation, biological therapies, glucocorticoid support and remyelinating drugs, new promising lines of research are addressed, such as the immunogenic role of the intestinal microbiota, the epigenetic capacity of the diet, strategies on cognition rehabilitation and the potential use of cannabinoids for the palliative management of pain. It is concluded that the classic treatment with disease-modifying drugs, both first-line and second-line, are essential for the management of MS; however, quality of life can be significantly increased by incorporating strategies found at the reach of the general practitioner and do not require referral at a greater complexity center.

Pidotimod: An Immunity Booster

Pidotimod is a synthetic dipeptide, which has immunomodulatory property. It is used in recurrent upper respiratory tract infections, where there is nonspecific immune deficiency, especially in children who are more prone to recurrent respiratory infections. This article discusses its structure, pharmacokinetics including mechanism of action and clinical uses. A brief review of literature has been carried out. Possible future application is suggested.

Symphony of nanomaterials and immunotherapy based on the cancer-immunity cycle

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.

Thymomodulin in association with antifungal drugs in the therapy of cats with disseminated cutaneous sporotrichosis: a prospective study / Associação de timomodulina na terapia de gatos com esporotricose cutânea disseminada: um estudo prospectivo

ABSTRACT: Feline sporotrichosis is a relevant mycose in veterinary medicine due to its severity and zoonotic potential and the fact that it can be difficult to treat. The immune status of the animal exerts influence on the prognosis of the disease and determines its clinical outcome. This study evaluated the efficacy of the immunomodulatory thymomodulin as an adjunct to antifungal therapy in cats with disseminated sporotrichosis; thymomodulin was used in association with itraconazole (ITL) and potassium iodide (KI) to treat this fungal disease in the feline patient. Thirty-one cats (n=31) diagnosed with disseminated cutaneous sporotrichosis were divided into two groups as follows: Group 1 (G1) (n=16), which included those animals that were treated with thymomodulin in association with ITL and KI, and Group 2 (G2) (n=15) which had pacientsthat received ITL and KI only. The response to different treatment modalities was assessed, considering the survival rate, time frame for the lesions to respond to therapy, and clinical improvement or deterioration according to a body condition score system. Animals from G1 had a survival rate of nearly 100% (93.6%) that was approximately twice higher than the survival rate of those animals from G2 (53%). Moreover, patients from G1 had a significantly better prognosis, improved body condition, and shorter time for remission of the extra cutaneous clinical signs (p<0.02). Our findings showed that the association of thymomodulin with ITL and KI improves the prognosis of cats with disseminated cutaneous sporotrichosis.

RESUMO: A esporotricose é uma das micoses de maior relevância na medicina veterinária, tanto pela sua gravidade, seu potencial zoonótico e seu difícil tratamento. Sabe-se que o aspecto imunológico do gato representa um fator prognóstico determinante. O objetivo desse trabalho foi avaliar a eficácia do imunomodulador timomodulina como adjuvante a terapia antifúngica, itraconazol (ITL) com iodeto de potássio (KI), em gatos com esporotricose disseminada. Trinta e um gatos (n=31) com esporotricose cutânea disseminada foram segregados em dois grupos, o grupo 1 (G1) (n=16) tratado com ITL, KI associada à timomodulina e o grupo 2 (G2) (n=15) apenas ITL e KI. Foi avaliada a resposta clínica aos diferentes tratamentos, levando em consideração a taxa de sobrevivência, tempo de resposta das lesões e progressão do escore de condição corporal. O G1 apresentou taxa de sobrevivência de quase 100% (93,6%), aproximadamente o dobro do encontrado no G2 (53%). Mais que isso, o G1 demonstrou significativamente melhor prognóstico, aprimoramento do escore de condição corporal e menor tempo para remissão dos sinais clínicos extracutâneos (p<0,02). Sendo assim, a associação da timomodulina ao ITL e KI melhora o prognóstico de gatos com esporotricose cutânea disseminada.

Esclerosis múltiple: reacciones adversas a medicamentos en pacientes bajo ley 20850, Hospital Regional de Talca / Multiple sclerosis: adverse drug reactions in patients under law 20850, Hospital Regional de Talca

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, which occurs in up to 85% of cases as relapsing remitting (RR), with episodes of neurological dysfunction partially forwarded. Its treatment in Chile is financially protected by the Explicit Health Guarantees (GES) and Law 20,850 on high-cost diseases. The Regional Hospital of Talca (HRT) has 25 patients benefiting from Law 20,850 in treatment with second-line biologic therapy. Adverse reactions (RAM) to the use of these drugs have been described and to date there are no case reports or studies of significant adverse events in Chile. Objectives: To present the experience of the use of biologic therapy in EMRR in HRT, in relation to adverse events. METHODS: A review of the current guidelines in Chile for the treatment of relapsing-remitting multiple sclerosis and the protocol of law 20,850 was carried out, the clinical records of 25 patients benefiting from the law in the HRT were reviewed, with emphasis on the adverse events presented before First and second line therapies and the con sequences of these events on the continuity of therapy. RESULTS: Half of the patients who started their treatment with first-line drugs had adverse effects, of which 28% involved a change in therapy, the remaining changed from therapy due to failure to treatment. Of the 26 patients included in the sample, 24 are currently using second-line drugs. The profile of adverse effects should be a variable to consider when indicating a therapy for MS.

Análisis del cumplimiento del plan de consumo de los medicamentos de alto costo. Matanzas. 2012-2017 / Analysis of the fulfillment of the consumption plan of high cost medications. Matanzas. 2012 - 2017

RESUMEN Introducción: los medicamentos de alto costo son medicamentos nuevos, altamente específicos y utilizados en condiciones clínicas complejas, como el tratamiento de algunos tipos de cáncer; enfermedades que comprometen el sistema inmunológico, enfermedades inflamatorias o infecciosas. Objetivo: determinar cumplimiento del plan de consumo de los medicamentos de alto costo en la provincia de Matanzas, en el quinquenio 2012-2017. Materiales y métodos: estudio descriptivo, observacional de seguimiento sobre el cumplimiento del plan de consumo de los medicamentos de alto costo, en la población matancera del año 2012 al 2017. Se analizó el universo de medicamentos incluidos en esta categoría, a partir de la base de datos de suministro de medicamentos que emplea la Empresa Comercializadora de Medicamentos. Se identificaron las variables estudiadas. Resultados: en todo el período de estudio se observó un incremento creciente de los medicamentos de alto costo, en el 88,9 % de ellos el consumo ha estado por encima de la planificación realizada por la provincia. Los costos se incrementaron en un 233 % y además en las prescripciones realizadas de estos productos, se encontraron problemas como escaques vacíos, antibióticos sin impresión diagnóstica y omisión de la forma de presentación del medicamento y/o dosis indicada. Conclusiones: el consumo de muchos medicamentos de alto costo fue mayor que la planificación realizada en la provincia de Matanzas, durante el período analizado. Implicó un incremento significativo del presupuesto destinado a estos fines y se detectaron dificultades en el cumplimiento de lo establecido en las prescripciones de dichos medicamentos (AU).

ABSTRACT Introduction: high cost medications (HCM) are new highly specific medications and used in complex clinical conditions as in treatment of some types of cancer, diseases that compromise the immunological system, inflammatory or infections disorders. Objective: to determine the fulfillment of the consumption plan of high-cost medications in the province of Matanzas in the period 2012-2017. Materials and methods: a descriptive, observational, follow up study on the fulfillment of the consumption plan of high-cost medication by the population of Matanzas2012 year to 2017. The universe of drugs included in this category was analyzed on the bases of the drug-supplying database used by the Drug Commercializing Enterprise (ENCOMED in Spanish). The studied variables were identified. Results: it was observed a growing increase of high-cost drugs use during all the period; in 88.9 % of them the consumption has been above the planning made in the province. The costs increased in 233 %, and besides that in the prescriptions made of these drugs there were found problems like empty boxes, antibiotics without diagnostic impression and omissions of the drug presentation forms and/or the prescribed doses. Conclusions: the consumption of many high-cost drugs was higher than the planning made in the province of Matanzas for the analyzed period. It implied a significant increase of the budget destined for these aims and difficulties were found in the fulfillment of the terms for prescribing these drugs (AU).

Evaluación de formulaciones inmunoterapéuticas experimentales en el modelo hibrido murino de Reaccion del Injerto contra el Hospedador / Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)

Los reumatólogos en la pandemia COVID-19 / Rheumatologists in the COVID-19 pandemic

Desde fines del 2019 enfrentamos el brote de una nueva infección por coronavirus llamada COVID-19, que rápidamente se transformó en una pandemia y llegó a nuestro país a principios del 2020. Esto ha traído muchas preguntas y desafíos, específicamente en nuestros pacientes con enfermedades autoinmunes, que tienen tradicionalmente mayor riesgo de contraer infecciones y de complicarse por estas. Por otra parte, en el tratamiento actual del síndrome respiratorio agudo severo causado por el coronavirus SARS-CoV-2 se están usando e investigando varios medicamentos inmunosupresores e inmunomoduladores del arsenal reumatológico para controlar la respuesta inmune exagerada que se produce en el huésped en el COVID-19 grave. En esta revisión analizamos la literatura existente hasta el momento sobre pacientes reumatológicos y COVID-19, medicamentos reumatológicos en investigación y en uso para el manejo de la infección por SARS-CoV-2, y resumimos ciertas recomendaciones de manejo específicas para nuestros pacientes.

Since the end of 2019 we have been facing the outbreak of a new coronavirus infection called COVID-19, which quickly turned into a pandemic arriving in Chile in early 2020. This has brought with it many questions and challenges, specifically for our patients with autoimmune diseases, which have an increased risk of infections due to their disease and the use of immunosuppresant and corticosteroid drugs. On the other hand, in the current treatment of severe acute respiratory syndrome caused by the SARS-CoV-2 coronavirus, several immunosuppressive and immunomodulatory drugs in the rheumatologic arsenal are being used and investigated to control the exaggerated immune response that occurs in the host in serious COVID -19 cases. In this review we investigated the literature to date on rheumatology patients and COVID-19, rheumatology drugs under investigation and in use for the management of SARS-CoV-2 infection, and have summarized certain specific management recommendations for our patients

Review of 113 cases of autoimmune disorders in pregnancy

Background: Autoimmune disorders are chronic multisystem disorders affecting women of their reproductive age. Pregnancy among these women is complicated by the disease itself. Flaring up of disease, uteroplacental insufficiency due to vasculitis and drugs used for treatment are main reason for unfavourable pregnancy outcomes. The objective of this study was to analyze the pregnancy complications and outcome among 113 cases of autoimmune disorders.Methods: This study is a retrospective analysis of case records of pregnant women with autoimmune disorders. This study was conducted at PSG IMSR and Hospital, Coimbatore, and Tamil Nadu from July 2012 to June 2018. The case sheets were retrieved from medical record department and the details such as type of disease, maternal age, parity, status of disease at conception, treatment taken during pregnancy, maternal complications and fetal complications were collected and analyzed.Results: During 6-year period there were 113 pregnant women with autoimmune disorders, and they were studied of their previous and present pregnancy outcome. The disease incidence was 7.01% per 1000 deliveries. 40.7% were less than 25 years age group and 71.6% were multigravidae. We had forty-one patients (36%) who were positive for APLA syndrome which were the maximum number of patients with auto immune disorder in pregnancy and 37 patients (32.7) with SLE. We had significant numbers of maternal and fetal complications for common disorders. Most of the rare auto immune disorders were diagnosed before pregnancy and these pregnancies were managed by multi-disciplinary approach, and continued on immunomodulators throughout pregnancy, hence maternal and fetal complications were less for them.Conclusions: Adequate pre-conceptional counseling, vigilant monitoring during pregnancy and post-partum will avoid pregnancy related complications and have favorable outcomes.

Encefalitis por anticuerpos contra el receptor de NMDA. Reporte de un caso y revisión de la literatura / Anti-NMDA receptor encephalitis. Case Report and Literature Review / Encefalite causada por anticorpos contra o receptor NMDA. Relatório de caso e revisão da literatura

Resumen: La encefalitis por anticuerpos contra el receptor de NMDA es un desorden grave, tratable y potencialmente reversible, caracterizado por la presencia de alteraciones en el comportamiento, convulsiones y trastornos del movimiento. La presencia de anticuerpos contra el receptor del glutamato (anti-NMDA) en plasma o líquido cefalorraquídeo es específico para el diagnóstico de la enferme -dad. El reconocimiento temprano de la enfermedad es vital para el pronóstico del paciente, dado que el manejo precoz facilita la recuperación y reducción de la morbimortalidad. El tratamiento consiste en la utilización de corticoides, inmunoglobulina intravenosa o plasmaféresis como primera línea de terapia; además de otros inmunomoduladores, como ciclofosfamida o rituximab, como segunda línea. La recuperación es lenta, pero presenta mejoría en la medida en que los títulos de anticuerpos disminuyen y llega a una recuperación completa hasta en 75 % de los pacientes.

Abstract: Anti-NMDA receptor encephalitis is a severe, treatable, and potentially reversible disorder characterized by the presence of behavioral disturbances, seizures, and movement disorders. The presence of antibodies against the glutamate receptor (anti-NMDA) in plasma or cerebrospinal fluid is specific to the diagnosis of the disease. Early recognition of the disease is vital for the patient's prognosis since early management facilitates recovery and reduction of morbidity and mortality. Treatment consists of corticosteroids, intravenous immunoglobulin, or plasmapheresis as the first line of therapy, in addition to other immunomodulators, such as cyclophosphamide or rituximab, as the second line. Recovery is slow but improves as antibody titers decrease. Complete recovery occurs in up to 75 % of patients.

Resumo: A encefalite causada por anticorpos contra o receptor NMDA é um distúrbio grave, tratável e potencialmente reversível, caracterizado pela presença de alterações comportamentais, convulsões e transtornos de movimento. A presença de anticorpos contra o receptor de glutamato (anti-NMDA) no plasma ou no líquido cefalorraquidiano é específica para o diagnóstico da doença. O reconhecimento precoce da doença é vital para o prognóstico do paciente, visto que o tratamento precoce facilita a recuperação e a redução da morbimortalidade. O tratamento consiste no uso de corticoides, imunoglobulina intravenosa ou plasmaférese como primeira linha de terapia. Além de outros imunomoduladores, como ciclofosfamida ou rituximabe, como segunda linha. A recuperação é lenta, mas apresenta melhora à medida que os títulos de anticorpos diminuem e a recuperação completa ocorre em até 75% dos pacientes.

Allergic Conjunctivitis: A Practice Pattern Survey From North India

PURPOSE: The purpose of this survey was to establish the prevalence of AC and to know the practice pattern of managing ocular allergy in north India. METHODS: A descriptive cross sectional study done in the states of north India, involving registered practicing ophthalmologists (RP). The survey was conducted in the month of May 2019. 14 fourteen survey questionnaire prepared on significant clinical situations related to ocular allergy was sent via goggle form to 300 Ophthalmologists of north India. The response was recorded and analyzed. RESULTS: The survey was participated by 232 RP (77.33%) out of 300 whom the questionnaire was sent. The results analysis involved epidemiological, treatment and complication pattern. CONCLUSION:AC patients form a significant proportion of our clinical patients specially in summer season. The chronic nature of this disease specially VKC needs a judicious use of different pharmacological agents considering their adverse effects. Newer molecules like Alcaftadine, Bepotastine and various Immunomodulators need further study by randomized clinical trials for their relative efficacy as survey are not sufficient to give us a clear indication towards rationalized use.

Tratamiento de la miastenia gravis juvenil / Treatment of juvenile myasthenia gravis

La miastenia gravis juvenil es una enfermedad autoimmune poco frecuente, por lo que ha sido difícil recopilar datos de estudios controlados aleatorizados prospectivos para evaluar la eficacia y los resultados de distintos tratamientos. Si bien hay diferencias entre la miastenia gravis juvenil y la del adulto, se han utilizado los datos aportados por algunas investigaciones en adultos en el tratamiento de la miastenia gravis juvenil. Se evaluarán las distintas opciones terapéuticas, con las distintas evidencias que lo sostienen y se elaborará un algoritmo de tratamiento teniendo siempre presente que cada paciente nos ofrece distintos desafíos.

Juvenile myasthenia gravis is a rare autoimmune disease, which has made it difficult to collect data from prospective randomized controlled trials to evaluate the efficacy and results of different treatments. Although there are differences between the juvenile myasthenia gravis and that of the adult, the data provided by some researches in adults in the treatment of juvenile myasthenia gravis have been used. The different therapeutic options will be evaluated, with the different evidences that sustain it and a treatment algorithm will be elaborated keeping always in mind that each patient offers us different challenges.

A study on the safety and tolerability of mycophenolate mofetil in patients with connective tissue disease

Background: Connective tissue disorders (CTD) are mostly due to inflammatory and fibrotic tissue injury. Glucocorticoids and immunomodulators though useful but are toxic. Mycophenolate mofetil (MMF) is now being used successfully in many autoimmune diseases, but the safety of MMF in CTD patients is yet to be conclusively established.Methods: The study was a retrospective record based observational one in patients of CTD satisfying the predetermined inclusion criteria. Various safety parameters were noted down from the observed records and analysed accordingly.Results: The 120 case records of CTD patients were analysed for a specific set of safety parameters over the preceding one year. Diarrhoeal attacks were the most commonly encountered side effect (38.3%) of long term patients who were on mycophenolate therapy followed by infection.Conclusions: Mycophenolate was found to be generally well tolerated in CTD patients with few reports of adverse events, but larger clinical trials are needed to conclusively establish its safety.

Two-Round Mixed Lymphocyte Reaction for Evaluation of the Functional Activities of Anti-PD-1 and Immunomodulators

Immune checkpoint inhibitors (ICIs), such as anti-PD-1 and anti-PD-L1 Abs, have shown efficacy for the treatment of various cancers. Although research has actively sought to develop new ICIs and immunomodulators, no efficient in vitro assay system is available to evaluate their functional activities. In the present study, we established a two-round MLR with human PBMCs for evaluation of the T cell-activating capacity of anti-PD-1 and other immunomodulators. We initially performed conventional MLR for this purpose. However, anti-PD-1 blocking Abs could not increase the proliferation of allo-reactive T cells in conventional MLR because PD-L1+ and PD-L2+ cells disappeared gradually during MLR. Therefore, we re-applied the same stimulator PBMCs to the allo-stimulated responder cells as a second-round MLR on day 6 when anti-PD-1 or immunomodulators were also added. In this two-round MLR, the proliferation of allo-reactive T cells was enhanced by anti-PD-1 in a dose-dependent manner or by immunomodulators, such as lenalidomide and galunisertib, a TGF-β receptor-1 inhibitor. Proliferation was further increased by the combination of immunomodulators with anti-PD-1. Here, we established a modified two-round MLR method with human PBMCs for evaluation of the functional activities of anti-PD-1 and immunomodulators.

Revisiting the Efficacy of Immunomodulatory Effect of Hydroxychloroquine in Oral Lichen Planus: A Case Series

Oral lichen planus (OLP) is a common inflammatory, autoimmune disorder that affects stratified squamous epithelium. The exact etiopathogenesis of this mucocutaneous disease is still uncertain. Although OLP has been associated with altered Quality of Life and considerable morbidity, with important note for erosive type of OLP, its treatment is often disappointing and controversial. Though corticosteroids remained the first line of treatment for OLP, the associated adverse effects of corticosteroids are not acceptable. Hence, there is a need of drugs with steroid sparing effect. Use of immunomodulators is systemic pathologies is widely encountered. However, their use in oral lesions is not frequently seen. Use of hydroxychloroquine (HCQ), an age-old disease-modifyinganti-rheumatic-drug, has been widely used in various autoimmune diseases; however, it received little attention in treatment of OLP. This article presents a case series of three patients with erosive OLP which were managed with HCQ. The results presented allow the authors to consider systemic HCQ as a newer therapy for atrophicerosive lichen planus.

Protective effect of ß-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C) / Efeito protetor do ß-glucano e glutamina em lesões intestinais e imunológicas induzidas por ciratabina (Ara-C) em camundongos

Recently, glutamine and ß-glucan have been demonstrated to play an important role in modulation of the immune system and in promoting intestinal health benefits. The aim of this study was to investigate the effect of this intervention on inflammatory responses and intestinal health in mice orally pretreated with soluble Saccharomyces cerevisiae derived 1,3/1,6-ß-glucan (80mg/kg) with or without glutamine (150mg/kg) and then challenged with cytarabine (Ara-C) (15mg/kg). Improvements in villi and crypts were not observed in the ß-glucan group. The intestinal morphometry in the glutamine group showed the best results. ß-glucan in combination with glutamine presented the highest values of IL-1ß and IL-10 and lowest values for leukocytes and INF-γ. Based on these results, combined ß-glucan and glutamine pretreatment reduced intestinal inflammation and improved the immune response after Ara-C challenge.(AU)

Recentemente, glutamina e ß-glucano têm demonstrado desempenhar um papel importante na modulação do sistema imune e na promoção de benefícios para a saúde intestinal. O objetivo deste estudo foi investigar o efeito dessa intervenção sobre as respostas inflamatórias e saúde intestinal de camundongos pré- tratados por via oral com 1,3/1,6-ß-glucano (80mg/kg) derivado de Saccharomyces cerevisiae com ou sem glutamina (150mg/kg) e posteriormente desafiados com citarabina (Ara-C) (15mg/kg). Melhoras em vilosidades e criptas não foram observadas no grupo de tratamento com ß-glucano. A morfometria intestinal no grupo de tratamento com glutamina apresentou os melhores resultados. O grupo em que foi utilizado ß-glucano em combinação com glutamina apresentou os maiores valores de IL-1ß e IL -10 e valores mais baixos para os leucócitos e INF-γ. Com base nestes resultados, o pré-tratamento de ß-glucano combinado com glutamina reduziu a inflamação intestinal e melhorou a resposta imune após o desafio com Ara-C.(AU)

Impacto de fórmulas enterais imunomoduladoras em pacientes com câncer do trato gastrointestinal enteral: uma revisão da literatura / Formulas immunomodulating impact of patients with cancer of the gastrointestinal tract a literature review

O estado nutricional de pacientes oncológicos é afetado pelos fatores tumorais e pela terapia instituída. Evidências científicas apontam que a imunonutrição é capaz de exercer efeitos benéficos em pacientes com câncer gastrointestinal. O objetivo desse trabalho foi averiguar, na literatura, o impacto de fórmulas enterais imunomoduladoras em pacientes com câncer do trato gastrointestinal. Os resultados mostram que a desnutrição é diagnosticada em 60% a 80% dos pacientes com câncer gastrointestinal e está diretamente relacionada à morbidade, tempo de hospitalização, resposta e tolerância ao tratamento. Estudos mostram que o suporte nutricional e o uso de imunomoduladores são capazes de exercer efeitos benéficos sobre o sistema imunológico e a recuperação de pacientes com câncer, promovendo o estado nutricional melhorado, reduzindo complicações, tempo de internação e mortalidade. Estudos adicionais são necessários para elucidar os mecanismos de ação e dose de imunonutrientes em vários tipos de câncer.

The nutritional status of cancer patients is affected by tumor factors and therapy instituted. Scientific evidence suggests that immunonutrition can exert beneficial effects in patients with gastrointestinal cancer. The objective of this review is to ascertain, in the literature the impact of immunomodulating enteral formulas in patients with gastrointestinal cancer. The results show that malnutrition is diagnosed in 60 % -80 % of patients with gastrointestinal cancer and is directly related to morbidity, hospitalization time, response and tolerance to treatment. Studies show that nutritional support and the use of immunomodulators are able to exert beneficial effects on the immune system and the recovery of cancer patients, promoting improved nutritional status, reducing complications, hospitalization time and mortality. Further studies are needed to elucidate the mechanisms of action and dose of immunonutrients in various types of cancer.

Clinical study of modified amniotic membrane transplantation combined with corneal contact lens and immunemodulators in the treatment of recrudesced epithelial herpes simplex keratitis / 眼科新进展

Objective To observe the clinical effects of fresh amniotic membrane transplantation combined soft corneal contact lens and immunomodulatory therapy on epithelial herpes simplex keratitis (HSK),Methods Together 56 participants with recrudesced epithelial type HSK were incorporated from January of 2012 to January of 2014,and randomly divided into control group and treatment group according to random number table.The treatment group was performed complete removal of corneal lesions with microscope,and then the whole cornea was covered with double fresh amniotic membrane;after the whole limbus was fixed with continuous suturing,the soft contact lenses were worn at the end of the operation.After the operation,Chinese formula,including Yupingfeng particles,ganciclovir ophthalmic gel and oral valacyclovir hydrochloride tablets,was administrated.The control group was treated only with ganciclovir ophthalmic gel and oral valaciclovir hydrochloride tablets,Results In control group,15 patients (53.6％) were cured,6 (21.4％) were markedly improved,2 (7.1％) were effective,5 (17.9％) was invalid,and the overall effective rate was 82.1％,but 6 patients (21.4％) were recrudesced;while in the treatment group,22 patients (78.6％)were cured,6 (21.4％) were markedly improved,and the total effective rate was 100.0％,but 3 patients were recurred.Moreover,the visual acuity were improved about 0.43 visual lines in the control group,and about 2.14 lines in treatment group.Therefore,the curative rate,effective rate and visual improvement of the treatment group was significantly better than those of the control group (all P ＜ 0.05),but the recurrence rate was lower than that of the control group (P ＜ 0.05).Conclusion The comprehensive treatment including fresh anniotic membrane transplantation combined corneal contact lens with Chinese formula were effective for quickly and effectively controlling inflammation,promoting ulcer repair and shortening the course of disease as well as reducing the recurrence.

Vacunas en pacientes con terapia biológica / Vaccines in patients with biological therapy

Los pacientes portadores de enfermedades reumáticas inflamatorias autoinmunes (AIIRD) tienen mayor riesgo de contraer infecciones, secundario al efecto inmunosupresor de la enfermedad y también por el efecto de los inmunomoduladores utilizados en su tratamiento. Muchas veces los anti-TNF se usan en forma concomitante con metotrexato y corticoides, u otros DMARDs, lo que puede aumentar el riesgo de infección. Entre los efectos adversos graves que se han relacionado con los anti-TNF están las infecciones lo que ha hecho plantear la utilidad de las inmunizaciones para disminuir este riesgo asociado a la enfermedad y a la terapia. Se realizó una revisión de la literatura con el objetivo de analizar los factores que deben ser considerados en el momento de indicar vacunas en estos pacientes.

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at higher risk for infections secondary to the immunosuppressive effect of the disease and the effect of the immunomodulators used in their treatment. Anti-TNF are often used concomitantly with methotrexate and corticosteroids, or other DMARDs, which may increase the risk of infection. Among the serious adverse effects that have been associated with anti-TNF are infections that has raised the utility of immunizations to reduce this risk associated with disease and therapy.A review of the literature was carried out with the objective of analyzing the factors that should be considered at the time of indicating vaccines in these patients.