Tratamiento del lupus eritematoso sistémico: nuevas opciones terapéuticas / Treatment of systemic lupus erythematosus: New therapeutic options

El lupus eritematoso sistémico (LES) es una enfermedad inflamatoria autoinmune sistémica de causa desconocida, con heterogeneidad en su presentación clínica, así como una variabilidad en su curso clínico y pronóstico. El objetivo actual del tratamiento es conseguir la remisión de la enfermedad o al menos un estado de baja actividad, y por consiguiente mejorar la calidad de vida del paciente. La terapia biológica en el lupus, a diferencia de otras entidades, si bien no ha conseguido instaurarse plenamente, ha irrumpido en los últimos años con novedades terapéuticas importantes. En esta revisión se pretende actualizar las herramientas terapéuticas del tratamiento del LES enfocado a las nuevas moléculas que han conseguido superar los objetivos de sus ensayos clínicos (AU)

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials (AU)

[Therapeutic Strategies and Disease-Modifying Therapies for Multiple Sclerosis].

Multiple sclerosis is an inflammatory demyelinating disease of unknown cause that affects the central nervous system. Although it was once deemed "incurable," many disease-modifying therapies have been introduced since the beginning of the 20th century; eight of these are now available in Japan. Treatment for multiple sclerosis is undergoing a significant shift from the safety-oriented "escalation strategy," in which the patient is initially administered medications with low risks of side effects but moderate efficacy, to a "personalized approach" based on individual prognostic factors followed by an "early top-down strategy" in which higher efficacy treatments are initiated first. Disease-modifying drugs for multiple sclerosis can be high- (fingolimod, ofatumumab, natalizumab) or moderate-efficacy (interferon beta, glatiramer acetate, dimethyl fumarate), and there are also disease-modifying therapies for secondary progressive multiple sclerosis (siponimod and ofatumumab). Approximately 20,000 Japanese patients have multiple sclerosis, and this number continues to increase. Many neurologists are expected to prescribe high-efficacy drugs in the future. The risk management of adverse events, particularly progressive multifocal leukoencephalopathy, is required to ensure that the importance of safety never be underestimated, even though treatment efficacy is the main focus.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience / Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro

Background Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. Objectives To study whether low-dose rituximab is also effective for bullous pemphigoid. Methods Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. Results Six patients, five males and a female, with a mean age of 78.6 years (range 65–89) and a mean history of BP of 6.7 months (range 2–16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1–3), and 4 weeks (range 3–5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13–20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. Conclusions Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP (AU)

Antecedentes La administración de dosis bajas de rituximab es un protocolo utilizado en diversas enfermedades autoinmunes, que ha demostrado también su eficacia y seguridad para el pénfigo vulgar. Objetivos Determinar si rituximab a dosis bajas es efectivo para el penfigoide ampolloso (PA). Métodos Se trató a los pacientes con PA con un ciclo único de 2 infusiones de rituximab 500 mg con un intervalo de 2 semanas. Se monitorizaron los puntos temprano y final tardío. Resultados Se incluyeron en el estudio 6 pacientes, 5 varones y una mujer, con una edad media de 78,6 años (rango: 65.89) e historia media de PA de 6,7 meses (rango: 2-16). Se observó una respuesta rápida y acusada tras un ciclo único de tratamiento, con un tiempo medio hasta el control de la enfermedad y el final de la fase de consolidación de 1,9 (rango: 1-3) y 4 semanas (rango: 3-5), respectivamente. Cuatro pacientes lograron un punto final tardío a una media de 15,75 semanas (rango: 13-20). Tres de ellos lograron una remisión parcial sin terapia (2 pacientes) o con terapia mínima (un paciente), logrando uno de ellos la remisión completa sin terapia. A un paciente se le realizó un seguimiento de 6 semanas tras la administración de rituximab. El paciente restante sufrió una recaída transcurridas 4 semanas del tratamiento de rituximab, permaneciendo en remisión completa con terapia mínima. Un paciente manifestó gingivoestomatitis herpética relacionada con rituximab. Conclusiones La administración de dosis bajas de rituximab para PA logró tasas de remisión aceptables y reducción de esteroides, con un mejor perfil de seguridad y un menor coste, en comparación con las dosis estándar. Este estudio piloto sugiere que la administración de bajas dosis de rituximab podría ser una opción terapéutica para el PA (AU)

[Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro / Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience

Antecedentes La administración de dosis bajas de rituximab es un protocolo utilizado en diversas enfermedades autoinmunes, que ha demostrado también su eficacia y seguridad para el pénfigo vulgar. Objetivos Determinar si rituximab a dosis bajas es efectivo para el penfigoide ampolloso (PA). Métodos Se trató a los pacientes con PA con un ciclo único de 2 infusiones de rituximab 500 mg con un intervalo de 2 semanas. Se monitorizaron los puntos temprano y final tardío. Resultados Se incluyeron en el estudio 6 pacientes, 5 varones y una mujer, con una edad media de 78,6 años (rango: 65.89) e historia media de PA de 6,7 meses (rango: 2-16). Se observó una respuesta rápida y acusada tras un ciclo único de tratamiento, con un tiempo medio hasta el control de la enfermedad y el final de la fase de consolidación de 1,9 (rango: 1-3) y 4 semanas (rango: 3-5), respectivamente. Cuatro pacientes lograron un punto final tardío a una media de 15,75 semanas (rango: 13-20). Tres de ellos lograron una remisión parcial sin terapia (2 pacientes) o con terapia mínima (un paciente), logrando uno de ellos la remisión completa sin terapia. A un paciente se le realizó un seguimiento de 6 semanas tras la administración de rituximab. El paciente restante sufrió una recaída transcurridas 4 semanas del tratamiento de rituximab, permaneciendo en remisión completa con terapia mínima. Un paciente manifestó gingivoestomatitis herpética relacionada con rituximab. Conclusiones La administración de dosis bajas de rituximab para PA logró tasas de remisión aceptables y reducción de esteroides, con un mejor perfil de seguridad y un menor coste, en comparación con las dosis estándar. Este estudio piloto sugiere que la administración de bajas dosis de rituximab podría ser una opción terapéutica para el PA (AU)

Background Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. Objectives To study whether low-dose rituximab is also effective for bullous pemphigoid. Methods Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. Results Six patients, five males and a female, with a mean age of 78.6 years (range 65–89) and a mean history of BP of 6.7 months (range 2–16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1–3), and 4 weeks (range 3–5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13–20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. Conclusions Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP (AU)

Compromiso cardíaco en el síndrome inflamatorio multisistémico post SARS-CoV-2 en niños / Cardiac involvement in post-SARS-CoV-2 multisystem inflammatory syndrome in children / Envolvimento cardíaco na síndrome inflamatória multissistêmica pós-SARS-CoV-2 em crianças

Objetivo: describir las características de ocho pacientes pediátricos que se presentaron con síndrome inflamatorio multisistémico (MIS-C) asociado a SARS-CoV-2 y compromiso cardíaco. Material y métodos: estudio descriptivo, retrospectivo de ocho pacientes con edades entre 1 y 13 años, con diagnóstico de MIS-C y compromiso cardíaco, asistidos en el CHPR. Se analiza su historia clínica, evolución y tratamiento. Resultados: los pacientes presentaron fiebre en el 100%, exantema e hiperemia conjuntival en el 88%, síntomas digestivos en el 50%, insuficiencia respiratoria en el 25% y shock en el 50%. Todos requirieron ingreso a cuidados intensivos. La alteración de la contractilidad cardíaca estuvo presente en el 63% de los pacientes, fue leve y segmentaria en el 80%, el 60% requirió soporte inotrópico por 3 días, recuperando una función normal en 7 días. La insuficiencia mitral se presentó en el 25% y el derrame pericárdico en el 38%, ambos de grado leve. Un paciente presentó dilatación de arterias coronarias con Z score < 2. El 85% de los pacientes presentó alteraciones del ECG, en el 29% se trató de alteración en la repolarización, en el 29% intervalo QTc prolongado, en el 15% bloqueo atrioventricular de 1er grado y bloqueo incompleto de rama derecha. Un paciente tuvo fibrilación auricular por 3 días con remisión espontánea a ritmo sinusal. Las troponinas estuvieron altas en el 57% de los pacientes y el ProBNP elevado en el 100%. Todos recibieron inmunoglobulinas, metilprednisolona y aspirina. Conclusiones: se presentaron ocho pacientes pediátricos con MIS-C y compromiso cardíaco, el 50% se presentó en shock, todos requirieron ingreso a cuidados intensivos. El 85% presento alteraciones en el ECG. El 63% presentó compromiso de la contractilidad sectorial y leve, se normalizó en 7 días. El 60% requirió soporte inotrópico por una media de 3 días.

Objective: describe the characteristics of 8 children who presented Multisystem Inflammatory Syndrome associated with SARS-CoV2 infections (MIS-C) and cardiac involvement. Material and methods: descriptive, retrospective study of 8 patients of between 1 and 13 years of age, diagnosed with MIS-C and cardiac involvement, assisted at the Pereira Rossell Children Hospital, analysis of their medical records, evolution and treatment. Results: the patients showed: fever in 100% of the cases, rash and conjunctival hyperemia in 88%, digestive symptoms in 50%, respiratory failure in 25% and shock in 50%. All required admission to Intensive Care. Cardiac contractility alteration was present in 63% of patients, the affectation was mild and segmental in 80%, 60% required inotropic support for 3 days and recovered normal functions in 7 days. Mitral regurgitation was present in 25% of the cases and pericardial effusion in 38%, mild in both cases. One patient had dilated coronary arteries with a Z score <2. 85% of the patients presented ECG abnormalities, 29% present alteration of repolarization, 29% prolonged QTc, 15% 1st degree atrioventricular block and incomplete right bundle branch block. One patient had atrial fibrillation for 3 days with spontaneous remission to sinus rhythm. Troponins were increased in 57% of the patients and ProBNP elevated in 100%. All patients received Immunoglobulins, Methylprednisolone and Aspirin. Conclusions: we present eight pediatric patients with MIS-C and cardiac involvement, 50% suffered shock, all required admission to Intensive Care. ECG abnormalities were found in 85% of the patients. Mild and segmental contractility compromise was found in 63% of the patients and normalized in 7 days. 60% required inotropic support for a mean of 3 days.

Objetivo: descrever as características de 8 pacientes pediátricos que apresentaram Síndrome Inflamatória Multissistêmica (MIS-C) associada ao SARS-CoV-2 e comprometimento cardíaco. Material e métodos: estudo descritivo, retrospectivo, de oito pacientes com idade entre 1 e 13 anos, com diagnóstico de MIS-C e comprometimento cardíaco, assistidos pelo CHPR. Seu prontuário médico, evolução e tratamento são analisados. Resultados: os pacientes apresentaram febre em 100%, erupção cutânea e hiperemia conjuntival em 88%, sintomas digestivos em 50%, insuficiência respiratória em 25% e choque em 50%. Todos necessitaram de internação nos cuidados intensivos. A alteração da contratilidade cardíaca esteve presente em 63% dos pacientes, foi leve e segmentar em 80%, 60% necessitaram de suporte inotrópico por 3 dias, recuperando a função normal em 7 dias. A regurgitação mitral ocorreu em 25% dos pacientes e o derrame pericárdico em 38%, ambos de grau leve. Um paciente apresentou dilatação da artéria coronária com escore Z < 2. 85% dos pacientes apresentaram anormalidades no ECG, 29% foram alterações de repolarização, 29% intervalo QTc prolongado em bloqueio atrioventricular de 1º grau a 15% e bloqueio incompleto do ramo direito. Um paciente apresentou fibrilação atrial por 3 dias com remissão espontânea ao ritmo sinusal. As troponinas foram elevadas em 57% dos doentes e ProBNP elevado em 100%. Todos receberam imunoglobulinas, Metilprednisolona e aspirina. Conclusões: houve oito pacientes pediátricos com SMIM-C e comprometimento cardíaco, 50% em choque, todos necessitaram de internação em terapia intensiva. 85% apresentaram elevações no ECG. 63% apresentaram comprometimento setorial e de contratilidade leve, normalizados em 7 dias. 60% necessitaram de suporte inotrópico por uma média de 3 dias.

Immunomodulatory and Antitumoral Activity of Gold Nanoparticles Synthesized by Red Algae Aqueous Extracts.

This study reports on the green and cost-efficient synthesis of gold nanoparticles from three different red algae extracts. The nanoparticles synthesized were fully characterized by UV-Vis spectroscopy, HRTEM, and Z-potential. Relevant components occurring in the extracts, such as polysaccharides or phenolic content, were assessed by analytical techniques such as spectrophotometric assays and liquid chromatography. Finally, the antioxidant, antitumoral, and anti-inflammatory potential of both the extracts and the gold nanoparticles synthesized were analyzed in order to determine a possible synergistic effect on the nanoparticles. The results obtained confirmed the obtainment of gold nanoparticles with significant potential as immunotherapeutic agents. The therapeutic potential of these nanoparticles could be higher than that of inert gold nanoparticles loaded with bioactive molecules since the former would allow for higher accumulation into the targeted tissue.

Tratamiento con inmunoglobulina intravenosa y esteroides sistémicos en pacientes con necrólisis epidérmica tóxica: Experiencia en un hospital en Ciudad de México / Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients with Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City

La necrólisis epidérmica tóxica es la reacción secundaria a medicamentos más grave dentro del espectro de las reacciones mucocutáneas. El tratamiento multidisciplinario es clave para disminuir la mortalidad de los pacientes, además de la suspensión del fármaco causal. Existen pocos estudios de tratamientos farmacológicos en pacientes con necrólisis epidérmica tóxica en Latinoamérica que combinen el uso de esteroides sistémicos e inmunoglobulina intravenosa (IgIV). Describimos 6 casos de pacientes con necrólisis epidérmica tóxica tratados con esteroides sistémicos e IgIV en un hospital de referencia dermatológica en Ciudad de México. Ningún paciente falleció ni presentó complicaciones a corto y mediano plazo de seguimiento. En la mayoría de los casos se empleó una dosis de IgIV de 1g/kg por 3-5 días y 1g de metilprednisolona por 3-5 días. El tiempo de ingreso hospitalario fue de 14,8 días. La combinación de esteroides sistémicos e IgIv parece ser una opción segura en pacientes con necrólisis epidérmica tóxica (AU)

Toxic epidermal necrolysis is the most serious mucocutaneous adverse drug reaction. Multidisciplinary treatment and withdrawal of the causative drug are key to reducing mortality. Few studies have analyzed the use of systemic corticosteroids and intravenous immunoglobulins (IVIG) in patients with toxic epidermal necrolysis in Latin America. We describe our experience with 6 cases treated at a dermatology referral hospital in Mexico City. None of the patients died or developed complications in the short or medium term. The most widely used regimen was a combination of IVIG 1 g/kg for 3 to 5 days and methylprednisolone 1 g for 3 to 5 days. Mean hospital stay was 14.8 days. The combined use of systemic corticosteroids and IVIG seems to be a safe treatment option for patients with toxic epidermal necrolysis (AU)

[Translated article] Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients With Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City / Tratamiento con inmunoglobulina intravenosa y esteroides sistémicos en pacientes con necrólisis epidérmica tóxica: experiencia en un hospital en Ciudad de México

Toxic epidermal necrolysis is the most serious mucocutaneous adverse drug reaction. Multidisciplinary treatment and withdrawal of the causative drug are key to reducing mortality. Few studies have analyzed the use of systemic corticosteroids and intravenous immunoglobulins (IVIG) in patients with toxic epidermal necrolysis in Latin America. We describe our experience with 6 cases treated at a dermatology referral hospital in Mexico City. None of the patients died or developed complications in the short or medium term. The most widely used regimen was a combination of IVIG 1g/kg for 3–5 days and methylprednisolone 1g for 3–5 days. Mean hospital stay was 14.8 days. The combined use of systemic corticosteroids and IVIG seems to be a safe treatment option for patients with toxic epidermal necrolysis (AU)

La necrólisis epidérmica tóxica es la reacción secundaria a medicamentos más grave dentro del espectro de las reacciones mucocutáneas. El tratamiento multidisciplinario es clave para disminuir la mortalidad de los pacientes, además de la suspensión del fármaco causal. Existen pocos estudios de tratamientos farmacológicos en pacientes con necrólisis epidérmica tóxica en Latinoamérica que combinen el uso de esteroides sistémicos e inmunoglobulina intravenosa (IgIV). Describimos 6 casos de pacientes con necrólisis epidérmica tóxica tratados con esteroides sistémicos e IgIV en un hospital de referencia dermatológica en Ciudad de México. Ningún paciente falleció ni presentó complicaciones a corto y mediano plazo de seguimiento. En la mayoría de los casos se empleó una dosis de IgIV de 1g/kg por 3-5 días y 1g de metilprednisolona por 3-5 días. El tiempo de ingreso hospitalario fue de 14,8 días. La combinación de esteroides sistémicos e IgIv parece ser una opción segura en pacientes con necrólisis epidérmica tóxica (AU)

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.

Characterization of Alpinia officinarum Hance polysaccharide and its immune modulatory activity in mice.

This study aimed to characterize the structural features of a novel water-soluble polysaccharide (AOHP) extracted from Alpinia officinarum Hance and to verify its regulating effect on mouse immunity. Cellulose DEAE-52 and Sephadex G-100 columns were used to obtain purified AOHP. Techniques including NMR, methylation, monosaccharide composition, FT-IR, and molecular weight determination were applied to investigate the physicochemical properties and structural characterization of AOHP. Then, the influence of AOHP on mice was studied. After oral administration of AOHP, organ indexes, serum biochemistry indexes, and cytokines in the spleens of the mice were analysed. The results showed that AOHP was composed of T-α-D-Glcp, (1,4)-α-D-Glcp and (1,4,6)-α-D-Glcp with a number-average molecular weight of 26.0 kDa and a weight-average molecular weight of 52.8 kDa. Additionally, the innate immune statuses of the mice were improved by treatment with AOHP, while no obvious damage was identified. To conclude, the immunomodulatory activity and biological safety make AOHP a viable candidate as an ingredient for healthcare drugs.

Oral administration of Lactobacillus delbrueckii enhances intestinal immunity through inducing dendritic cell activation in suckling piglets.

Lactobacillus delbrueckii (LAB) has been demonstrated to exert versatile beneficial effects on modulating intestinal immunity, increasing gut microbial diversity, promoting growth performance, and even preventing disease onset in pigs. However, the underlying mechanism of LAB-mediated gut immunity regulation in piglets remains unclear. In this study, we found that supplementation of LAB significantly increases serum TNF-α, ileum IL-4, and IL-10 levels compared with the control group. Meanwhile, oral supplementation of LAB-modified gut microbial communities was evidenced by the increased abundance of the Lactobacillus genus in the colon. Mechanistically, LAB induced dendritic cell (DC) maturation and activation, which may be relevant to the activation of NF-κB and MAPK signaling pathways. Moreover, we found that oral administration of LAB during the suckling period shows long-lasting immunomodulatory impacts on intestinal immunity after weaning. Collectively, this study uncovers the mechanism of LAB in regulating the intestinal immunity of piglets, suggesting that LAB can be developed as an immunoenhancing biological agent during the suckling period.

Preemptive Interferon-α Therapy Could Protect Against Relapse and Improve Survival of Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation: Long-Term Results of Two Registry Studies.

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5-30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4-20.6%) and 3.9% (95%CI, 0.0-17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2-91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4-95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5-77.0%) and 10.4% (95%CI, 3.6-17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.

Progressive, refractory macrophage activation syndrome as the initial presentation of anti-MDA5 antibody positive juvenile dermatomyositis: a case report and literature review.

BACKGROUND: Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis. CASE PRESENTATION: We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings. CONCLUSIONS: JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient's clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.

Recomendaciones para la administración de antineoplásicos e inmunomoduladores orales por sonda enteral en oncohematología / Recommendations for using oral antineoplastic and immunomodulating agents in oncohematology by enteral tube administration

Introducción y objetivo: en los últimos años, el número de fármacos antineoplásicos e inmunomoduladores orales (ANIOS) ha crecido enormemente. Con frecuencia, estos fármacos deben administrarse por sonda enteral (SE) o a pacientes con problemas de deglución, planteando un problema respecto a su manipulación (muchos pertenecen al grupo de medicamentos peligrosos). Además, también pueden presentar interacciones cuando se administran con la nutrición enteral (NE). El objetivo ha sido analizar y actualizar las recomendaciones de administración y manipulación de los ANIOS. Métodos: se creó un Grupo de Trabajo formado por farmacéuticos del Grupo de Farmacia de la Sociedad Española de Nutrición Clínica y Metabolismo (SENPE) y del Grupo de Nutrición Clínica de la Sociedad Española de Farmacia Hospitalaria (SEFH). Se realizó una revisión bibliográfica entre 2015 y 2020 de las condiciones de manipulación y administración de los ANIOS en oncohematología, elaborando una tabla que recoge especialidades farmacéuticas, dosis, presentación, nombre comercial, instrucciones para la administración oral y por SE, interacciones con la NE, precauciones y observaciones para su manipulación y administración. Resultados: se elaboró una tabla con 77 principios activos y 84 formas farmacéuticas, recogiendo recomendaciones e instrucciones para su administración por vía oral, sonda nasogástrica y gastrostomía, para la correcta manipulación y para la administración junto a la NE. Conclusiones: la información sobre cómo administrar y manipular los ANIOS en personas con accesos enterales o problemas de deglución es escasa. Consideramos importante incluir en los estudios poscomercialización una investigación dirigida a responder a estas cuestiones para garantizar una administración segura y eficaz de los medicamentos a estos pacientes (AU)

Introduction and objective: in recent years, the number of oral antineoplastic and immunomodulating drugs in oncohematology has increased enormously. Often, these drugs must be administered to patients with enteral tube feeding or swallowing disorders, which causes safety problems when handling these drugs (many of them are classified as hazardous drugs). In addition, it is important to note that the administration of these drugs can also interact with enteral nutrition (EN). The objective of this study was to review and update the recommendations for the administration and handling of oral antineoplastic and immunomodulating drugs. Methods: a Working Group made up of pharmacists from the Pharmacy Group of The Spanish Society of Clinical Nutrition and Metabolism (SENPE) and the Clinical Nutrition Group of The Spanish Society of Hospital Pharmacy (SEFH) was created. A bibliographic review was carried out between 2015 and 2020 on the administration and handling of oral antineoplastic and immunomodulating drugs in oncohematology. The information about pharmaceutical specialties, dosage, presentation, brand names, instructions for oral or enteral tube administration, interactions with EN, precautions, and remarks for handling and administration was analyzed. Results: a total of 77 active principles and 84 pharmaceutical forms were included. Recommendations and instructions for oral, nasogastric tube, and gastrostomy administration, handling of the antineoplastic and immunomodulating drugs, and interactions with EN were described. Conclusions: the handling and administration information about the oral antineoplastic and immunomodulating drugs currently used in oncohematology for people with enteral accesses or swallowing disorders is limited. It is important to perform post-marketing studies to ensure a safe and effective administration of these drugs (AU)

Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study.

OBJECTIVES: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). METHODS: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. RESULTS: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. INTERPRETATION: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.