Rituximab en el tratamiento de esclerosis múltiple. Experiencia de un hospital de tercer nivel en México / Rituximab in the treatment of multiple sclerosis. Experience of a tertiary care hospital in Mexico

Resumen Antecedentes: La esclerosis múltiple es una enfermedad crónica, autoinmune y degenerativa. Las terapias blanco contra los linfocitos B han probado ser efectivas en su tratamiento; sin embargo, existen pocos estudios que evalúen su eficacia en población mexicana. Objetivo: Evaluar el impacto clínico del rituximab en pacientes con esclerosis múltiple remitente recurrente (EMRR) de reciente diagnóstico. Material y métodos: Estudio de vida real, descriptivo, en el que se evalúa rituximab como tratamiento de EMRR durante un periodo de 24 meses. Se analizaron variables clínicas pre y postratamiento; se realizó la comparación entre pacientes naïve y no naïve. Resultados: Se incluyeron 28 pacientes con EMRR. La edad media al diagnóstico fue de 30.7 años y 22 pacientes fueron naïve (78.5 %). Después de 24 meses, se observó una reducción media de 1.8 puntos en EDSS y en el número de lesiones activas por resonancia magnética. Aunque se logró establecer una diferencia significativa en ambas variables con p < 0.05, el modelo de regresión logística no mostró una relación entre las variables para alcanzar un NEDA-3. No se observaron eventos adversos graves. Conclusiones: El tratamiento con rituximab resultó en mejoría significativa clínica y radiológica en pacientes mexicanos con EMRR naïve y no-naïve.

Abstract Background: Multiple sclerosis is a chronic, autoimmune, degenerative disease. Therapies targeting B-cells have been shown to be effective in its treatment; however, there are few studies evaluating their efficacy in the Mexican population. Objective: To evaluate the clinical impact of rituximab in patients with newly-diagnosed relapsing-remitting multiple sclerosis (RRMS). Material and methods: Real life, descriptive study, in which rituximab was evaluated as treatment for RRMS over a 24-month period. Pre- and post-treatment clinical variables were analyzed; a comparison was made between treatment-naïve and non-treatment-naïve patients. Results: Twenty-eight patients with RRMS were included. Mean age at diagnosis was 30.7 years, and 22 patients were treatment-naïve (78.5 %). After 24 months, there was a mean reduction of 1.8 points in the EDSS scale and a decrease in the number of active lesions on magnetic resonance imaging; a significant difference in both variables could be established (p < 0.05). However, the logistic regression model did not show a relationship between the variables for achieving NEDA-3 criteria. No serious adverse events were observed. Conclusions: Treatment with rituximab resulted in significant clinical and radiological improvement in treatment-naïve and non-treatment-naïve Mexican patients with RRMS.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Postural Control in Relapsing-Remitting Multiple Sclerosis

Abstract Introduction Postural instability is considered one of the most disabling symptoms of relapsing-remitting multiple sclerosis (RRMS). Objective To evaluate postural control in patients with RRMS. Method A total of 79 individuals between 18 and 65 years old, of both genders, were distributed into an experimental group composed of patients with RRMS (n = 51) and in a control group composed by healthy individuals (n = 28). The evaluation consisted of anamnesis, Dizziness Handicap Inventory (DHI), visual vertigo analog scale (WAS), and static posturography (Tetrax IBS). Results Patients with RRMS presented mild degree in the DHI and in the VVAS; in Tetrax IBS, they presented higher or lower values of the indices of general stability, weight distribution, synchronization of postural oscillation, fall risk, and frequency bands of postural oscillation in two, five or all eight sensory conditions, in relation to the control group. Vestibular, visual and/or somatosensory dysfunction of peripheral type (51.0%) prevailed over the central type. The RRMS group, with an expanded scale of disability status > 3 points, presented a higher fall risk than with a score ≤ 3 points (p = 0.003). There was a positive correlation of the Fall Risk Index with the total DHI Score (s = 0.380; p = 0.006) and with the VVAS score (s = 0.348; p = 0.012). Conclusion Patients with RRMS may present with inability to maintain postural control due to general instability, desynchronization and increased postural oscillation at frequencies that suggest deficiencies in the vestibular, visual, and somatosensory systems; as well as fall risk related to the state and intensity of functional disability and self-perception of the influence of dizziness on quality of life.

Respuesta al tratamiento con Interferón beta-1a en pacientes con esclerosis múltiple remitente-recurrente / Response to treatment with Interferon beta-1a in patients with relapsing-remitting multiple sclerosis

RESUMEN Fundamento: los fármacos modificadores, en la esclerosis múltiple, tienen la finalidad de reducir la frecuencia de recaídas, retardar la progresión de la discapacidad, así como la aparición de nuevas lesiones en el Sistema Nervioso Central. Objetivo determinar los indicadores precoces de respuesta al tratamiento con IFNb-1ª en pacientes con esclerosis múltiple remitente-recurrente. Métodos: estudio observacional, analítico de cohorte con prospectiva longitudinal en los pacientes con diagnóstico de esclerosis múltiple. Se conformaron dos cohortes de estudio, cada una con 39 pacientes. Resultados: la media y desviación estándar de la escala ampliada del estado de discapacidad a los 36 meses fue de 2.37 ± 1.86 en el grupo estudio y en el control de 3.15 ± 2.1. En los brotes de .13 ± .33 en el grupo estudio y en el grupo control de .41 ± .59. Las lesiones nuevas en T2 tras los 12 primeros meses de tratamiento fue de 0.90 ± 1.16 para el grupo estudio y para el control de 1 ± 1.10. La progresión por escala ampliada del estado de discapacidad, la tasa anualizada de brotes antes del tratamiento, la edad de inicio de la enfermedad, tiempo de evolución de la enfermedad y lesiones que realzan gadolinio se asociaron de forma significativa con la razón de ventaja de mayor probabilidad de no progresión para el grupo estudio con respecto al grupo control por la variable combinada progresión por escala ampliada del estado de discapacidad y brotes. Conclusiones: se identificaron indicadores precoces de respuesta al tratamiento con el interferón beta-1a, que ayudan a valorar la respuesta al tratamiento de forma precoz, lo que repercute de forma positiva en la evolución de la enfermedad.

ABSTRACT Background: multiple sclerosis modifying drugs are intended to reduce the frequency of relapses, delay the progression of disability, as well as the appearance of new lesions in the Central Nervous System. Objective: to determine the early indicators of response to treatment with IFNb-1a. Methods: Observational, analytical longitudinal prospective cohort study in patients diagnosed with multiple sclerosis. Two study cohorts were formed, each with 39 patients. Results the mean and standard deviation of the expanded disability status scale at 36 months was 2.37 ± 1.86 in the study group and 3.15 ± 2.1 in the control group. In the outbreaks of .13 ± .33 in the study group and in the control group of .41 ± .59. New lesions in T2 after the first 12 months of treatment was 0.90 ± 1.16 for the study group and 1 ± 1.10 for the control. Extended-scale progression of disability status, pretreatment annualized relapse rate, age of disease onset, time since disease progression, and gadolinium-enhancing lesions were significantly associated with the odds ratio of older Probability of non-progression for the study group with respect to the control group for the combined variable progression by extended disability status scale and relapses. Conclusions: early indicators of response to treatment with interferon beta-1a were identified; that help assess the response to treatment early, which has a positive impact on the evolution of the disease.

Neurorrestauración integral en pacientes con esclerosis múltiple remitente-recurrente: estudio piloto / Comprehensive neurorestoration in patients with relapsing-remitting multiple sclerosis: a pilot study

Introducción: La neurorrestauración integral en la esclerosis múltiple mejora los déficits funcionales. Dentro de la atención de las personas con la enfermedad, se ha incluido la valoración de la calidad de vida relacionada con la salud, que es un elemento clave para la evaluación subjetiva de las influencias del estado de salud actual. Objetivo: Determinar la influencia de la neurorrestauración integral en la calidad de vida relacionada con la salud de los pacientes con esclerosis múltiple remitente-recurrente. Material y Métodos: Se realizó un estudio cuasi-experimental en 78 pacientes con esclerosis múltiple remitente-recurrente, tratados en el Hospital Universitario Clínico-quirúrgico Arnaldo Milián Castro de Santa Clara, en el periodo comprendido entre enero de 2014 a diciembre de 2020. Los pacientes se distribuyeron aleatoriamente en un grupo estudio y un grupo control, asignados por sorteo. Resultados: En cuanto a las actividades de la vida diaria mostró una media al final de la intervención de 95,89 para el grupo estudio; y para el grupo control de 81,28. Posterior a la intervención se evidenció una mejoría del funcionamiento de la calidad de vida relacionada con la salud del grupo estudio en los componentes de la escala en comparación con los controles. Conclusiones: se determinó como el desarrollo de intervenciones promueven el mayor bienestar posible de los pacientes con esclerosis múltiple remitente-recurrente a través de la neurorrestauración integral(AU)

Introduction: Comprehensive neurorestoration in Multiple Sclerosis improves functional deficits. The assessment of health-related quality of life, which is a key element for the subjective evaluation of the influences of the current state of health, has been included in the care of people with the disease. Objective: To determine the influence of comprehensive neurorestoration on the health-related quality of life of patients with relapsing-remitting multiple sclerosis. Material and Methods: A quasi-experimental study was carried out in 78 patients with relapsing-remitting multiple sclerosis treated at the "Arnaldo Milián Castro" Clinical-Surgical University Hospital in Santa Clara, in the period between January 2014 and December 2020. The patients were randomly assigned to a study group and a control group. Results: Regarding activities of daily living, the study group showed a mean of 95.89 at the end of the intervention, while the control group showed a mean of 81.28. After the intervention, an improvement in the functioning of the health-related quality of life of the study group was evidenced in the components of the scale, compared with the controls. Conclusions: It was determined that the development of interventions through comprehensive neurorestoration promote the best possible well-being of patients with relapsing-remitting multiple sclerosis(AU)

Efectividad del tratamiento neurorrehabilitador integral en la función cognitiva de los pacientes con esclerosis múltiple remitente recurrente

RESUMEN Fundamento: las alternativas terapéuticas en pacientes con esclerosis múltiple no deben centrar sus esfuerzos en la rehabilitación de dominios cognitivos específicos, sino valorar el empleo de estrategias de intervención multimodal, con el propósito de minimizar los factores negativos que intervienen en la salud cognitiva de estos. Objetivo: determinar la efectividad del tratamiento neurorrehabilitador integral en la función cognitiva de los pacientes con esclerosis múltiple remitente recurrente. Métodos: se realizó un estudio cuasiexperimental con dos grupos (un grupo estudio y un grupo control) en pacientes con diagnóstico de esclerosis múltiple remitente recurrente. Cada grupo quedó conformado por 39 pacientes. Los métodos estadísticos exigieron la utilización de un estudio de pruebas repetidas, variante de ANOVA. Para las pruebas de dos momentos se utilizó el concepto de ANOVA de un factor. Resultados: después de la intervención se obtuvo en el grupo de estudio, un aumento de las puntuaciones en las pruebas de velocidad de procesamiento, memoria de trabajo-flexibilidad cognitiva, fluidez verbal y el control inhibitorio; así como disminución en los niveles de fatiga. Se comprobó una mejoría significativa en el estado emocional del grupo de estudio, pues hubo disminución del estado de ansiedad y depresión. Conclusiones: el proceso de neurorrehabilitación integral resultó efectivo al disminuir en los pacientes los niveles de depresión y ansiedad, además de mejorar el funcionamiento cognitivo en el grupo de pacientes que completó el proceso, lo que muestra la viabilidad de un enfoque de neurorrehabilitación integral y su utilidad para mejorar la calidad de vida en adultos con esclerosis múltiple.

ABSTRACT Background: Therapeutic alternatives should not focus their efforts on the rehabilitation of specific cognitive domains, but value the use of multimodal intervention strategies, with the purpose of minimizing the negative factors that intervene in the cognitive health of patients with multiple sclerosis. Objective: to determine the effectiveness of comprehensive neurorehabilitation treatment on the cognitive function of patients with relapsing-remitting multiple sclerosis. Methods: a quasi-experimental study was carried out with two groups (a study group and a control group) in patients diagnosed with relapsing-remitting multiple sclerosis. Each group was made up of 39 patients. Statistical methods required the use of a repeated test study, variant of ANOVA. For the two-moment tests, the one-way ANOVA concept was used. Results: after the intervention, in the study group, an increase in the scores in the tests of processing speed, working memory-cognitive flexibility, verbal fluency and inhibitory control was obtained; as well as decreased levels of fatigue. A significant improvement in the emotional state of the study group was verified, showing a decrease in the state of anxiety and depression. Conclusions: the comprehensive neurorehabilitation process was effective in reducing depression and anxiety levels in patients, in addition to improving cognitive functioning in the group of patients who completed the process, which shows the viability of a comprehensive neurorehabilitation approach and its effectiveness utility to improve quality of life in adults with multiple sclerosis.

Evolución clínica de pacientes con esclerosis múltiple remitente- recurrente tratados con interferón beta-1a / Clinical evolution of patients with relapsing-remitting multiple sclerosis treated with interferon beta-1a

RESUMEN Introducción: El inicio de la terapia con interferón ha sido y es el primer paso en el tratamiento de muchos pacientes con esclerosis múltiple, con el propósito de retrasar la progresión de la enfermedad. Objetivo: Identificar los marcadores clínicos de respuesta al tratamiento con interferón beta-1a de pacientes con esclerosis múltiple remitente-recurrente. Métodos: Se realizó un estudio observacional, descriptivo, longitudinal, prospectivo, de una serie de casos de pacientes con diagnóstico de esclerosis múltiple remitente-recurrente, que recibían tratamiento con interferón beta-1a, en el periodo comprendido entre enero del 2014 a diciembre del 2020. Se incluyeron los 39 pacientes. Resultados: La media de edad fue de 34,54 años. La media del nivel de discapacidad en la línea base, 12, 24 y a los 36 meses fue de 1,76; 1,91; 2,1 y 2,37 respectivamente. La media de los brotes en la línea base, 12, 24 y a los 36 meses fue de 1,13; 0,26; 0,38 y 0,13 respectivamente. Se muestra la cifra de progresiones inferior en un 51 % a los 36 meses. La razón de ventajas (odds ratio) para la no presencia de brotes se muestra entre 2 y 4 veces en estos pacientes. Conclusiones: Se identifican marcadores clínicos de respuesta al tratamiento con interferón beta-1a que ayudan a valorar la respuesta al tratamiento, lo cual repercute de forma positiva en la evolución de la enfermedad.

ABSTRACT Introduction: The initiation of interferon therapy has been and is the first step in the treatment of many patients with multiple sclerosis, with the aim of delaying the progression of the disease. Objective: To identify the clinical markers of response to treatment with Interferon beta-1a in patients with relapsing-remitting multiple sclerosis. Methods: An observational, descriptive, longitudinal, prospective study was carried out of a series of cases of patients diagnosed with relapsing-remitting multiple sclerosis, who received treatment with interferon beta-1a, in the period between January 2014 and December 2020. All 39 patients were included. Results: The mean age was 34.54 years. The mean disability level at baseline, 12, 24, and 36 months was 1.76; 1.91; 2.1 and 2.37 respectively. The mean number of flares at baseline, 12, 24, and 36 months was 1.13; 0.26; 0.38 and 0.13 respectively. The number of progressions lower by 51% at 36 months is shown. The odds ratio for the absence of relapses is between 2 and 4 times in these patients. Conclusions: Clinical markers of response to treatment with Interferon beta-1a are identified that help assess the response to treatment, which has a positive impact on the evolution of the disease.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome in children: a brief literature review / Síndrome da febre periódica, estomatite aftosa, faringite e adenite em crianças: uma breve revisão de literatura

ABSTRACT Objective: To describe clinical, diagnostic and therapeutic characteristics of the periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. Data source: Literature review in the PubMed database by using specific descriptors to identify all articles published in the English language in the last three years; 38 articles were found. After performing selection of titles and abstract analysis, 13 out of the 38 articles were fully read. Relevant studies found in the references of the reviewed articles were also included. Data synthesis: The PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis and cervical Adenitis) is a medical condition grouped among the periodic fever syndromes. The etiology is uncertain, but possibly multifactorial, and its symptoms are accompanied by recurrent febrile episodes although weight and height development are preserved. It is a self-limiting disease of benign course with remission of two to three years without significant interference in the patient's overall development. Treatment consists of three pillars: interruption of febrile episodes, increase in the interval between episodes, and remission. Conclusions: Despite several attempts to establish more sensitive and specific criteria, the diagnosis of PFAPA syndrome is still clinical and reached by exclusion, based on the modified Marshall's criteria. The most common pharmacological options for treatment include prednisolone and betamethasone; colchicine may be used as prophylaxis, and surgical treatment with tonsillectomy can be considered in selected cases.

RESUMO Objetivo: Descrever as características clínicas, diagnósticas e de tratamento da síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA). Fontes de dados: Revisão de literatura na base de dados PubMed, feita por meio de descritores específicos para identificar todos os artigos publicados em língua inglesa nos últimos três anos. Dos 38 artigos encontrados, foram encaminhados para leitura integral 13 publicações após seleção de títulos e análise de abstract. Estudos relevantes encontrados nas referências dos artigos revisados também foram incluídos. Síntese dos dados: A PFAPA é traduzida do inglês periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Caracterizada por etiologia ainda incerta e possivelmente multifatorial, seus sintomas são acompanhados por episódios recorrentes de febre associados a um desenvolvimento pôndero-estatural preservado. É uma doença autolimitada de curso benigno, com remissão em dois a três anos, sem interferências significativas no desenvolvimento do paciente pediátrico. O tratamento consiste em três pilares: interrupção da crise febril, aumento do intervalo entre crises e remissão. Conclusões: Apesar de várias tentativas de estabelecer critérios atuais mais sensíveis e específicos, o diagnóstico da síndrome PFAPA ainda é clínico e de exclusão com base nos critérios de Marshall modificados. As opções farmacológicas mais utilizadas para o tratamento são a prednisolona e betametasona; colchicina pode ser utilizada como profilaxia e o tratamento cirúrgico com tonsilectomia pode ser considerado em casos selecionados.

Recommendations of diagnosis and treatment of relapsing polychondritis in China / 中华内科杂志

Relapsing polychondritis is an immune mediated systemic inflammatory disease, involving the cartilaginous and proteoglycan rich structures. The characteristic manifestations were inflammation and deformity of ear and nasal cartilage. Here, Chinese Rheumatology Association summarized manifestations, diagnosis and disease activity index evaluation of relapsing polychondritis, standardized treatment regimens, to improve disease prognosis.

Experiencia en la unidad de enfermedades desmielinizantes a 2 años / Experience in the demyelinating diseases unit after 2 years

La esclerosis múltiple es una enfermedad desmielinizante crónica que produce discapacidad progresiva, por lo que el tratamiento se centra en retrasar la progresión, prevenir recaídas y disminuir los síntomas de manera efectiva. Realizamos un estudio observacional, descriptivo, longitudinal, de un solo centro, con los pacientes admitidos en la unidad de enfermedades desmielinizantes, desde diciembre 2017 hasta febrero 2020. Del total de pacientes, 62.5% recibieron tratamiento con ocrelizumab y completaron seguimiento por 12 meses, sin progresión de la enfermedad. Con este estudio, resaltamos la importancia y la efectividad de los tratamientos modificadores de la enfermedad.

Multiple sclerosis is a chronic demyelinating disease that causes progressive disability, so treatment focuses on slowing progression, preventing relapses, and effectively reducing symptoms. We conducted an observational, descriptive, longitudinal, single-center study with patients admitted to the demyelinating diseases unit from December 2017 to February 2020. Of the total number of patients, 62.5% received treatment with ocrelizumab and completed 12-month follow-up, without disease progression. With this study, we highlight the importance and effectiveness of disease-modifying treatments

Serum YKL-40 levels in patients with multiple sclerosis / Níveis séricos de YKL-40 em pacientes com esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. The YKL-40 protein, which is secreted from various cells that contribute to inflammation and infection, plays a role in immune regulation. Objective: This study investigated the serum YKL-40 levels of patients with clinically isolated syndrome (CIS) and MS. Methods: The participants was divided into three groups: 1) patients with CIS (n = 20); 2) patients with relapsing-remitting MS (RRMS; n = 39); and 3) healthy individuals (n = 35). The YKL-40 levels in serum samples obtained from the participants were measured using enzyme-linked immunoassays. Results: The median serum YKL-40 level was 20.2 ng/mL (range 9.8-75.9 ng/mL) in the patients with CIS, 22.7 ng/mL (range 13.4-57.9 ng/mL) in the patients with RRMS and 11.0 ng/mL (range 10.0-17.3 ng/mL) in the control group (p < 0.001). The serum YKL-40 levels in the patients with RRMS were correlated with the patients' expanded disability status scale scores and ages (p < 0.05). No relationships were determined between the serum YKL-40 levels and the other variables (p > 0.05). The serum YKL-40 levels were higher in the CIS group than in the MS group. These findings show that the serum YKL-40 levels were high even at the beginning of the disease. The serum YKL-40 levels were also not involved in the progression to clinically definite MS. Conclusions: The findings from this study suggested that YKL-40 may be a useful marker for the inflammatory process of MS.

RESUMO Contexto: A Esclerose Múltipla (EM) é uma doença inflamatória crônica que afeta o sistema nervoso central. A proteína UKL-40, secretada de várias células que participam de processos inflamatórios e infecciosos, desempenha um importante papel na regulação imunológica. Objetivo: Este estudo investigou níveis séricos de YKL-40 em pacientes com Síndrome Clinicamente Isolada (SCI) e EM. Métodos: Os participantes foram divididos em três grupos: 1) pacientes com SCI (n = 20); 2) pacientes com EM recorrente-remitente (EMRR; n = 39); e 3) indivíduos saudáveis (n = 35). Os níveis de YKL-40 em amostras séricas obtidas dos participantes foram medidos usando-se imunoensaios ligados a enzimas. Resultados: O nível sérico médio de YKL-40 foi 20.2 ng/mL (range 9.8-75.9 ng/mL) em pacientes com CIS, 22.7 ng/mL (intervalo entre 13.4-57.9 ng/mL) em pacientes com EMRR e 11.0 ng/mL (intervalo entre 10.0-17.3 ng/mL) no grupo controle (p < 0.001). Os níveis séricos de YKL-40 em pacientes com EMRR estavam correlacionados às pontuações e idades dos pacientes na EDSS (p < 0.05). Não foram determinadas relações entre os níveis séricos de YKL-40 e outras variáveis (p > 0.05). Os níveis séricos de YKL-40 no grupo SCI estavam mais elevados do que no grupo EM. Estes resultados demonstram que os níveis séricos de YKL-40 estavam mais elevados até mesmo no início da doença. Os níveis séricos de YKL-40 também não estavam associados à progressão da EM clinicamente definida. Conclusões: A partir deste estudo, os resultados sugeriram que a proteína YKL-40 pode ser um indicador útil no processo inflamatório da EM.

Encefalopatía subaguda en una paciente con policondritis recidivante: caso clínico / Subacute encephalopathy associated with relapsing polychondritis: report of one case

Relapsing polychondritis (RP) is a rare multisystemic autoimmune disorder characterized by the inflammation and destruction of cartilages, with preference for auricular, nasal and laryngotracheal cartilages. RP may also affect proteoglycan-rich structures, such as, blood vessels, eyes, kidneys, and heart. The central nervous system (CNS) is involved in less than 3% of patients. We report a 32-year-old female with RP associated with a progressive subacute encephalopathy characterized by behavioral disturbances, auditory and visual hallucinations. The EEG showed generalized slow activity and a mononuclear pleocytosis with increased protein was found in the cerebrospinal fluid. The brain magnetic resonance imaging showed multiple supra and infratentorial nodular inflammatory lesions. After initiating treatment with corticosteroids and cyclophosphamide, a significant improvement in chondritis and neurological status was observed.

Cladribina oral para o tratamento da esclerose múltipla remitente-recorrente altamente ativa: análise de impacto orçamentário sob a perspectiva do sistema brasileiro de saúde suplementar / Cladribine tablets for the treatment of highly active recurrent multiple sclerosis: budget impact analysis from the perspective of the Brazilian supplementary health system

Objetivo: Avaliar o impacto orçamentário da inclusão da cladribina oral no tratamento de esclerose múltipla remitente-recorrente em alta atividade da doença (EMRR HDA) no Sistema de Saúde Suplementar (SSS). Métodos: Foi conduzida uma análise de impacto orçamentário, sob a perspectiva do SSS, com horizonte temporal de quatro anos, considerando a abordagem de coorte aberta na qual o número de pacientes elegíveis para tratamento varia em cada ano com a introdução de novos pacientes diagnosticados de EMRR HDA e a retirada de indivíduos prevalentes devido a morte ou progressão secundária. Foram considerados custos médicos diretos, incluindo a aquisição e administração de medicamentos, monitoramento, eventos adversos e surtos. Os comparadores utilizados na análise foram: alentuzumabe, fingolimode, natalizumabe e ocrelizumabe. Os custos foram apresentados em real brasileiro (BRL). Resultados: O custo incremental da inclusão da cladribina oral para o SSS foi estimado em 463.265 BRL, 739.691 BRL, -1.414.963 BRL, -3.719.007 BRL, nos anos 1, 2, 3 e 4, respectivamente. Isso resultou em um custo incremental total de -3.931.015 BRL no período analisado, representando 1,5% da redução orçamentária total no tratamento de EMRR HDA. Conclusão: A inclusão da cladribina oral para o tratamento de pacientes com diagnóstico de EMRR HDA poderia gerar uma economia substancial para o sistema brasileiro de saúde suplementar, atingindo um valor de cerca de 3,9 milhões de BRL em um período de quatro anos

Objective: To evaluate the budget impact of adopting cladribine tablets as a treatment strategy for relapsing remitting multiple sclerosis with high disease activity (RRMS HDA), from the Brazilian private healthcare system perspective. Methods: A budget impact analysis, under private healthcare system perspective, with a 4-years time horizon was conducted, considering the open cohort approach in which the number of patients eligible for treatment varies each year with the introduction of newly diagnosed RRMS HDA patients and the drop out of prevalent individuals due to death or secondary progression. Direct medical costs, including acquisition, drug administration, monitoring, adverse events and relapses were considered. Comparators used in the analysis were: alentuzumab, fingolimod, natalizumab and ocrelizumab. Costs were presented in Brazilian real (BRL). Results: The incremental cost of incorporating cladribine tablets into the private healthcare system was estimated at 463,265BRL, 739,961BRL, -1,414,963 BRL, -3,716,007 BRL, in years 1, 2, 3 and 4, respectively. This resulted in a total incremental cost of -3,931,015 BRL over the period analyzed, representing 1.5% of the total budget reduction in the treatment of RRMS HDA. Conclusion: Incorporation of cladribine tablets for the management of RRMS HDA could generate substantial savings for the private healthcare system, reaching a value of approximately 3.9 million BRL in a 4-years period

Cerebellar-cerebral resting-state functional connectivity alterations in relapsing-remitting multiple sclerosis / 中华放射学杂志

Objective:To investigate the alterations of cerebellar and cerebral functional connectivity (FC) in patients with relapsing-remitting multiple sclerosis (RRMS) and associations with clinical parameters.Methods:Eighteen acute RRMS patients, 25 remitting RRMS patients and 20 healthy controls (HC) who underwent 3.0 T brain MRI using resting-state functional protocols were collected retrospectively from September 2012 to June 2019 at the First Hospital of Nanchang University. After data preprocessing, the functional connectivity coefficients were calculated between each seed of the cerebellum and every other voxel in the cerebrum for comparison of the inter-groups difference and correlation analysis with clinical variables.Results:Compared with HC, the acute RRMS patients showed significant decreased FC of left cerebellar lobule Ⅵ, the right cerebellar lobule Ⅵ and the left vermis ( P<0.001, Gaussian Random Field theory correction at cluster level P<0.05), the remitting RRMS patients showed the decreased FC of the right cerebellar Crus I, the left cerebellar Crus Ⅰ, the left cerebellar lobule Ⅴ and right cerebellar lobule Ⅴ ( P<0.001, Gaussian Random Field theory correction at cluster level P<0.05). In the acute RRMS patients, FC between the left cerebellar lobule Ⅵ and the right precentral/postcentral gyrus was negatively correlated with illness duration ( r=-0.492, P=0.038). FC between the right cerebellar lobule Ⅵ and the right postcentral gyrus/right superior parietal gyrus was negatively correlated with the expanded disability status scale scores ( r=-0.611, P=0.007). FC between the left vermis and the left calcarine gyrus was negatively correlated with illness duration ( r=-0.534, P=0.02). In the remitting RRMS patients, FC between the right Crus Ⅰ and the left anterior insula was negatively correlated with normalized total white matter lesion load ( r=-0.453, P=0.023). FC between the right Crus Ⅰ and the right anterior insula was negatively correlated with modified fatigue impact scale ( r=-0.450, P=0.024). Conclusions:The cerebello-cerebral connection of cognitive related networks is decreased in both acute attack and remission stages of RRMS patients. In addition, the cerebello-cerebral connection in sensorimotor network can also be significantly impacted in acute attack stage, while the cerebello-cerebral connection of emotional network may be decreased in remission stage.

Clinical reasearch of bendamustine combination regimen in the treatment of relapsed/refractory multiple myeloma / 中国医师杂志

Objective:To investigate the clinical efficacy and safety of bendamustine combination regimen in the treatment of patients with relapsed or refractory multiple myeloma (RRMM).Methods:From March 2020 to December 2020, 16 patients with RRMM were treated with bendamustine combination regimen in Beijing Jishuitan Hospital. The efficacy and adverse events (AEs) of bendamustine combination regimen were retrospectively analyzed in the 16 patients.Results:The median treatment lines for 16 patients with RRMM who received bendamustine combination regimen was 4 lines, and the median course of treatment was 3 (1-8). The median follow-up time after bendamustine treatment started was 5.3(1.3-9.2)months. Among the 16 cases, the disease control rate (DCR), overall response rate(ORR), and ≥ very good partial remission (VGPR) rate were 13/16, 5/16, 4/16 respectively. The median PFS was 4.9 months. Among them, the ORR of bendamustine combined with immunomodulators was higher. AEs were anemia, leukopenia, neutropenia, thrombocytopenia and fatigue. No patients who stopped treatment and adjusted the dose due to AEs.Conclusions:Bendamustine combination regimen is an effective and safe regimen for relapsed/refractory multiple myeloma.

Differentiation of relapsing-remitting and secondary progressive multiple sclerosis: a magnetic resonance spectroscopy study based on machine learning / Diferenciação de esclerose múltipla recorrente-remitente e progressiva secundária: um estudo de ressonância magnética com espectroscopia baseado em aprendizado de máquina

ABSTRACT Introduction: Magnetic resonance imaging (MRI) is the most important tool for diagnosis and follow-up in multiple sclerosis (MS). The discrimination of relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS) is clinically difficult, and developing the proposal presented in this study would contribute to the process. Objective: This study aimed to ensure the automatic classification of healthy controls, RRMS, and SPMS by using MR spectroscopy and machine learning methods. Methods: MR spectroscopy (MRS) was performed on a total of 91 participants, distributed into healthy controls (n=30), RRMS (n=36), and SPMS (n=25). Firstly, MRS metabolites were identified using signal processing techniques. Secondly, feature extraction was performed based on MRS Spectra. N-acetylaspartate (NAA) was the most significant metabolite in differentiating MS types. Lastly, binary classifications (healthy controls-RRMS and RRMS-SPMS) were carried out according to features obtained by the Support Vector Machine algorithm. Results: RRMS cases were differentiated from healthy controls with 85% accuracy, 90.91% sensitivity, and 77.78% specificity. RRMS and SPMS were classified with 83.33% accuracy, 81.81% sensitivity, and 85.71% specificity. Conclusions: A combined analysis of MRS and computer-aided diagnosis may be useful as a complementary imaging technique to determine MS types.

RESUMO Introdução: A ressonância magnética é a ferramenta mais importante para o diagnóstico e acompanhamento na EM. A transição da EM recorrente-remitente (EMRR) para a EM progressiva secundária (EMPS) é clinicamente difícil e seria importante desenvolver a proposta apresentada neste estudo a fim de contribuir com o processo. Objetivo: o objetivo deste estudo foi garantir a classificação automática de grupo controle saudável, EMRR e EMPS usando a RM com espectroscopia e métodos de aprendizado de máquina. Métodos: Os exames de RM com espectroscopia foram realizados em um total de 91 amostras com grupo controle saudável (n=30), EMRR (n=36) e EMPS (n=25). Em primeiro lugar, os metabólitos da RM com espectroscopia foram identificados usando técnicas de processamento de sinal. Em segundo lugar, a extração de recursos foi realizada a partir do MRS Spectra. O NAA foi determinado como o metabólito mais significativo na diferenciação dos tipos de MS. Por fim, as classificações binárias (Healthy Control Group-RRMS e RRMS-SPMS) foram realizadas de acordo com as características obtidas por meio do algoritmo Support Vector Machine. Resultados: Os casos de EMRR e do grupo de controle saudável foram diferenciados entre si com 85% de acerto, 90,91% de sensibilidade e 77,78% de especificidade, respectivamente. A EMRR e a EMPS foram classificadas com 83,33% de acurácia, 81,81% de sensibilidade e 85,71% de especificidade, respectivamente. Conclusões: Uma análise combinada de RM com espectroscopia e abordagem de diagnóstico auxiliado por computador pode ser útil como uma técnica de imagem complementar na determinação dos tipos de EM.

Retos terapéuticos en el síndrome nefrótico idiopático / Therapeutic challenges in the idiopathic nephrotic syndrome

El diagnóstico, evaluación y tratamiento del síndrome nefrótico en el niño data de los tiempos de Hipócrates. Sin embargo, en la actualidad algunos pacientes con la enfermedad siguen siendo un reto terapéutico para el médico. Nos proponemos examinar en la literatura reciente, distintas propuestas o protocolos de tratamiento y las nuevas drogas que pueden utilizarse en la atención al paciente con esta enfermedad. Los protocolos de tratamiento varían con relativa frecuencia y las drogas, tanto en los síndromes nefróticos recaedores frecuentes, corticodependientes o corticorresistentes, no garantizan en muchas ocasiones la curación del paciente. Cuando fracasan los esteroides se pueden utilizar agentes alquilantes, inhibidores de la calcineurina, antiproliferativos, anticuerpos monoclonales y otros fármacos, pero existen pacientes que no tienen remisión de la proteinuria con ninguno de estos tratamientos. Por sus características evolutivas, algunos pacientes con síndrome nefrótico idiopático siguen siendo un reto para el médico que trata de evitar su evolución hacia la pérdida de la función renal. A pesar de todos los avances en la atención del niño con síndrome nefrótico, desde el descubrimiento de los esteroides, antibióticos, diuréticos e inmunosupresores, en la actualidad no sabemos exactamente cuál es el mejor tratamiento en las formas resistentes del síndrome nefrótico idiopático en niños(AU)

Diagnosis, evaluation and treatment of nephrotic syndrome in children dates from Hypocrate times. However, nowadays some patients with this disease are still a therapeutic challenge for physicians. The aim of this work is to search in recent literature different proposals or treatment protocols, and new drugs that can be used in the care of patients with this disease. Treatment protocols vary with relative frequency and drugs, as well as in frequent relapsing nephrotic, corticodependent or corticoresistant syndromes, do not guarantee in many ocassions the cure of the patient. When steroids fail, alkylanting agents, calcineurin depressants, antispreading, monoclonal antibodies and other drugs can be ussed; but there are patients who do not have remission of proteinuria with any of these treatments. Due to their evolutive characteristics, some patients with idiopathic nephrotic syndrome are still a challenge for the physicians who try to avoid its evolution toward the loss of renal function. Although all the advances in the care of children with nephrotic syndrome due to the discover of steroids, antibiotics, diuretics and immunosupressive drugs, nowadays we do not exactly know which is the best treatment for the resistant types of idiopathic nephrotic syndrome in children(AU)

Medicamentos modificadores en esclerosis múltiple: esquemas terapéuticos actuales / Disease-Modifying drugs in multiple sclerosis: current therapeutic schemes

La esclerosis múltiple (EM) es una enfermedad crónica, autoinmune y neurodegenerativa; que tiene como principal característica la desmielinización de los axones en el sistema nervioso. Los medicamentos modificadores de la enfermedad (MME) logran retrasar la aparición de los síntomas y modificar parcialmente el progreso de la desmielinización y daño neuronal, resultando cada vez más complejo determinar un esquema terapéutico estandarizado según la condición particular de cada paciente. En este artículo se presenta una revisión actualizada de la evidencia clínica que ha llevado al uso de los esquemas terapéuticos en EM. La mayoría de los medicamentos aprobados actualmente son utilizados para la EM remitente-recurrente y se pueden dividir de acuerdo a la eficacia y seguridad. Los medicamentos de primera línea han mostrado una baja o moderada eficacia y alta seguridad; después de usar estos fármacos sin lograr una buena respuesta o ante una enfermedad avanzada se usan medicamentos de segunda y tercera línea que tienen una alta eficacia, pero son menos seguros, presentando mayores efectos secundarios y riesgos asociados para los pacientes. El ocrelizumab es el único fármaco aceptado para la EM primaria progresiva y el siponimod fue aprobado como una alternativa para la EM secundaria progresiva. El desarrollo de nuevos medicamentos y el seguimiento clínico de los ya aprobados permitirá establecer un mejor abordaje terapéutico logrando así mejorar la calidad de vida de cada paciente.

Multiple sclerosis (MS) is a chronic, autoimmune and neurodegenerative disease; whose main characteristic is the demyelination of axons in the nervous system. Disease-modifying drugs (DMD) can delay the onset of symptoms and partially modify the progression of demyelination and neuronal damage, making it increasingly complex to determine a standardized therapeutic scheme that is individualized to each patient. This article presents an updated review on the clinical evidence that has led to the use of current therapeutic schemes in MS with focus on DMD. Current medications in treating relapsing-remitting MS can be divided according to efficacy and safety. First-line drugs have shown low or moderate efficacy and high safety. Second- and third-line drugs are used after a poor response or in cases of advanced disease. These drugs are highly effective, but less safe, presenting greater side effects and associated risks for patients. Ocrelizumab is the only accepted drug for primary progressive MS and siponimod is accepted as an alternative for secondary progressive MS. The development of new medications and the clinical follow-up of those already approved will allow establishing a better therapeutic approach, thus improving the quality of life of each patient.

Relative safety of steroid sparing agents in frequently relapsing, steroid dependent and steroid resistant nephrotic syndrome in pediatric patients

Background: In patients with frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) and steroid resistant nephrotic syndrome (SRNS) steroids are either used for prolonged period of time or ineffective. To reduce the degree of steroid dependency and avoid steroid toxicity, several immunosuppressive steroid sparing agents (SPAs) have been proposed to treat these children. The present study tried to study the relative safety of most commonly steroid sparing agent in such children.Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.Results: A total 110 patients were screened, examined and enrolled. Levamisole, cyclophosphamide and MMF were commonly used SPAs. Of the two tertiary care hospitals, all the patients of FRNS and SDNS were started with levamisole and SRNS with cyclophosphamide in one set-up, while in the other hospital some SDNS patients were started with cyclophosphamide and SRNS with MMF but without clinically significant outcomes. In comparison with few minor adverse events in MMF group, some serious adverse events were documented in the both cyclophosphamide and levamisole groups.Conclusions: Levamisole being a very efficacious, safe and easily affordable drug, should be used as an initial first line SPA in treating FRNS and SDNS children. The side effect profiles of levamisole and MMF are much more patient friendly.

Policondritis recidivante: manifestaciones clínicas y tratamiento / Recurrent polychondritis. Clinical, diagnosis and treatment

La policondritis recidivante es una enfermedad rara caracterizada por la inflamación recurrente del cartílago y otros tejidos en todo el cuerpo. La afectación del oído es la característica más común, pero puede afectar otras áreas del cuerpo, incluidos el cartílago costal, los ojos, la nariz, las vías respiratorias, el corazón, el sistema vascular, la piel, las articulaciones, los riñones y el sistema nervioso. Los signos y síntomas varían de persona a persona según las partes del cuerpo afectadas. La causa subyacente exacta de la policondritis recidivante se desconoce, aunque los científicos sospechan que se trata de una enfermedad autoinmune. Las complicaciones respiratorias (colapso de la tráquea e infecciones) son la causa más común de muerte, seguidas de la afectación cardiovascular. Los objetivos principales del tratamiento son aliviar los síntomas actuales y preservar la estructura del cartílago afectado. Gracias a las mejoras en el tratamiento, en los últimos años las tasas de supervivencia han aumentado, incluso después de 10 años(AU)

Recurrent polychondritis is a rare condition characterized by recurrent inflammation of cartilage and other tissues throughout the body. Ear involvement is the most common feature, but a variety of other areas of the body may be compromised, including costal cartilage, eyes, nose, airways, heart, vascular system, skin, joints, kidneys and nervous system. The signs and symptoms vary from person to person depending on the body parts affected. The exact underlying cause of recurrent polychondritis is unknown; however, scientists suspect it is an autoimmune condition. The main goals of treatment for people with recurrent polychondritis are to alleviate current symptoms and preserve the structure of the affected cartilage(AU)